3rd WORLD PARKINSON
ABSTRACTS
Pre-Congress Oral Presentations
PCO01
Fundamentals of PD - Introduction
Tom Isaacs
The Cure
Parkinson’s Trust, London, UK
Objectives: To welcome everyone to the World
Parkinson Congress 2013
To provide
an overview of the history of WPC and the increasing involvement of people with
Parkinson’s
To look
back at the legacies of previous WPC’s and to suggest possible initiatives
going forward
To set the
tone of the meeting – the importance of having PwP’s at the Congress and our
role in making the conference a success
“Do’s and
Don’ts” for WPC 2013
PCO02
Pathology of Parkinson’s disease
Dennis W. Dickson
Mayo
Clinic, Jacksonville, FL, USA
Objective:
To describe pathologic changes in the brain in PD.
Methods:
Illustrate pathology in PD from a personal review of over 250 PD brains, as
well as a set of over 1000 dementia brains with Lewy body pathology.
Results: The most common pathologic
substrate of PD is Lewy body disease. Lewy bodies (LBs) are intraneuronal
inclusions composed of α-synuclein. In addition to LBs, abnormal
α-synuclein is also found within neuronal processes as Lewy neurites (LNs)
and in oligodendroglial inclusions. LNs are widely distributed and are most
abundant lesion in most regions. They may also be the earliest alteration in
affected neurons and may precede LB formation in perikarya. The vulnerability
of select populations of neurons to LBs has been known for many years and
includes not only monoaminergic neurons of the substantia nigra, locus ceruleus
and raphe nuclei, but also cholinergic neurons of the basal forebrain, as well
as neurons in the dorsal motor nucleus of the vagus and the medullary and
pontine reticular formation. The hypothalamus and pedunculopontine nuclei are
often affected. Spinal cord neurons of the intermediolateral cell column are
vulnerable. LBs and LNs are also found in the autonomic ganglia of the
gastrointestinal and cardiovascular systems. Neurons in the anterior olfactory
nucleus are also vulnerable. Cortical neurons are less often affected in PD,
with neurons in the limbic cortices most vulnerable. Braak and co-workers
proposed a pathologic staging system for PD that takes these observations into
account. In the most advanced stages, LBs are widespread in the cerebral cortex
similar to dementia with Lewy bodies (DLB). In contrast to DLB, Alzheimer type
pathology is less frequent in PD and PD with dementia (PDD).
PCO03
What causes PD?
Marie-Francoise Chesselet
Department
of Neurology, UCLA, Los Angeles, CA USA
Objective: Our understanding of the causes
of Parkinson’s disease has progressed very much in the last decade. This
presentation will review the current information.
Methods: Both genetic and environmental
(epidemiological) studies have contributed to elucidating some of the causes
and risk factors of PD.
Results: In most cases, the cause of PD
is not known but studies have revealed important factors both from exposure to
the environment and from individual genetic make up, that can combine to
increase or decrease the risk of developing PD. In addition, in some cases, PD
runs into families and many of the genetic factors involved in these familial
cases have now been elucidated. Importantly, these have illuminated some
general mechanisms of the disease that apply to everyone and may help develop
new treatments.
PCO04
Non-motor Features of PD
Ronald F. Pfeiffer
University
of Tennessee Health Science Center, USA
Objective: In recent years,
recognition has grown that Parkinson’s disease (PD) encompasses much more than
difficulty with movement. A whole host of features that have little or nothing
to do with movement are important, and sometimes dominant, features of PD.
Changes in mood, loss of motivation, increased anxiety, difficulty with
thinking and memory, excessive fatigue, sleep disturbances, problems with
bowel, bladder, and sexual function, excessive sweating, impairment of sense of
smell and therefore also taste, changes in some aspects of vision, and a variety
of types of pain all are examples of these “nonmotor” features of PD. Although
some nonmotor features characteristically appear later in the course of PD,
others may occur very early, even before the classic motor features of PD
develop and sometimes before PD is even diagnosed. Recognition of the nonmotor
aspects of PD is important because they do not always respond to traditional PD
treatment measures that typically target dopamine, but may respond to other
treatment approaches. The fact that nonmotor features of PD often cause more
distress - both for persons with PD and for their family members – makes it
especially important that these features are recognized and addressed. In this
session, an overview of the nonmotor features of PD will be provided.
PCO05
Medical Therapy
Christopher G. Goetz
Rush
University Medical Center, Chicago, IL USA
Parkinson’s
disease (PD) can be considered as a cellular disease and a biochemical disease.
One the one hand, circumscribed cells in the central nervous system begin to
die and this process is an ongoing degenerative process; on the other hand,
these cells primarily produce the chemical, dopamine, causing a progressing
deficit of this chemical and, to a lesser extent, other naturally occurring
chemicals, termed neurotransmitters. Existing and evolving medical therapies
for PD target both of these processes. To date, no therapy has been documented
to preserve brain cells in PD, although many new programs are on-going and are
aimed at restoring (neuro-restorative) or preventing (neuroprotection)
continued cell degeneration. If successful, these treatments could potentially
halt the disease at a very early phase in newly diagnosed patients, stabilize
patients in the mid-stage of disease, and potentially prevent the disease from
emerging if it can be diagnosed before the typical signs that define the
disease emerge (tremor, bradykinesia and rigidity). Most available medical
treatments used for treating PD enhance dopamine function and therefore target
the biochemical deficit that results from cell loss. The Movement Disorder
Society (MDS) sponsors an Evidence Based Medical Review (EBMR) program to apply
a set of standard criteria to compare treatments in different drug categories
across four distinct patient applications: use as monotherapy to treat
parkinsonism; use as an adjunct to levodopa, the precursor to dopamine and the
most widely used drug to treat PD; use in the prevention of motor complications
that include involuntary movements, termed dyskinesia and an irregular response
to medication, termed motor fluctuations; use in the treatment of dyskinesias
and motor fluctuations. A review of the 2011 MDS EBMR document for these four
categories of treatment emphasizes the utility of different agents for
different problems and allows a focus on those treatments that have been
designated as EFFICACIOUS for a given clinical problem. Agents include
monoamine oxidase B inhibitors, amantadine, dopamine agonists (pramipexole,
ropinirole, rotigotine), and levodopa, prescribed with carbidopa and sometimes
with a catechol-O-methyl transferase inhibitor (entacapone or tolcapone). With
scientific advances, a number of new agents are being tested to face the
challenges of PD and new formulations of older drugs are being developed. These
advances are aimed at refining the existing treatments to enhance benefit,
reduce side effects, and ultimately improve the quality of life of PD patients
and their families.
PCO06
What you can do after
you are diagnosed to stay involved
Peter Davison
Person
with Young Onset Parkinson’s, Bedford, NS, Canada
Objective: This presentation highlights the options and benefits of getting
involved and helping at the local and national level with opportunities and
needs such as: advocacy, education, fundraising, clinical trials and support
groups. Webinars, teleconferences and other community empowering technology
will also be showcased as effective tools to keep people informed, encouraged
and involved in living well with Parkinson's.
PCO07
Therapeutic options to
stay active and involved: Speech and Parkinson’s
Bonnie Bereskin
Speech-Language
Pathology Clinic, Toronto, ON, Canada
Objective: Speech therapy in
Parkinson’s is both an art and a science. Communication is one of the most
challenging of human behaviors, requiring rapid functioning and coordination of
many systems. This talk will review the current understanding of all aspects of
communication and its changes throughout the Parkinson journey. Communication
includes motor-speech, language, pragmatic and social skills. Parkinson’s
affects all of these functions. Speech may be quiet and monotonous with
indistinct articulation and occasionally, stuttering. Some individuals
experience difficulty finding words or following a complicated conversation, in
later stages. Others may find a social situation challenging, as a result of
slowness in formulating a message and “getting into” a conversation. Current
knowledge of all of these changes will be discussed, as they impact the success
of therapy and transfer of skills to social settings. The targets of
intervention have broadened and include not only the speaker with Parkinson’s
but the listener, as speech is not a solitary activity. LSVT has proven
effectiveness in improving speech and voice loudness in all stages of
Parkinson’s. With progression of the illness, cognitive and mood changes may
make it challenging for some to practice voice exercises and transfer the
louder voice to social settings. As a result, it has been found helpful to involve
family members and/or volunteers to support communication. Therapeutic
approaches, in addition to LSVT, are beneficial for those with more severe
dysarthria.
Discussion: There will be
discussion of the resource challenge of providing effective intervention in a
neuro-degenerative disorder that spans many years and affects the motor and
cognitive systems. A number of creative models of on-going and cost effective
approaches will be discussed, such as on-line therapy, cycling of intervention
and group treatment.
PCO08
Therapeutic options to
stay active and involved: Physical Therapy and Parkinson’s
Terry Ellis
Boston
University, Boston, USA
In this session, participants will become more
informed regarding the benefits of physical therapy and exercise. In addition,
participants will gain an appreciation of the role that physical therapy can
play in the management of Parkinson’s over the course of the disease. The
evidence demonstrating the benefits of physical therapy and exercise for
persons with Parkinson disease will be summarized and the impact on reducing
disability, improving physical function and enhancing quality of life will be
reviewed. In addition, the key elements of an exercise program will be
explored. The importance of long-term adherence to exercise and adopting an
active lifestyle to optimize outcome will also be emphasized. Practical tips to
reduce sedentary behaviors and become more active will be shared.
PCO09
Therapeutic options to stay active and involved: Occupational Therapy
and Parkinson’s
Margarita Makoutonina
ParkiLife Australia Pty Ltd,
Melbourne, Victoria, Australia
Objective: Despite the benefits of
medical and surgical interventions for people with Parkinson’s (PwP), patients
still develop disability in both the motor and non-motor domains that lead to
the likelihood of hospitalisation, a loss of independent living and serious
social and economic consequences (Chaudhuri, 2011). Many Occupational
Therapists (OTs) lack understanding of the symptoms of Parkinson’s disease (PD)
and the latest assessment and treatment techniques due to a lack of description
of evidence and consensus Occupational Therapy in PD. This presentation will
review the OT’s vital role within multidisciplinary team (MDT) (Iansek et.al.,
1995) addressing motor and non-motor symptoms (NMS).
Methods: In this short presentation we will provide a summary of
importance of specialist training in PD for OTs and interdisciplinary team work
in assisting PwP to stay active and involved; specific guidelines for OT
intervention and their relationship with disease severity and duration;
implementation of PD specific assessments to address holistic evaluation
(Chaudhuri, 2010) thus assisting the OTs in designing of targeted
rehabilitation and provision of the best practice in OT for PwP. We will
emphasise the importance of: clients to be referred to OT services; self
management of the disease by the clients; empowering the patients and families
to control and to minimise impairment through taking an active role in the
process of both comprehensive assessments and establishing rehabilitation
program, considering the functional ability during ON and OFF phenomenon.
Results: Through
this presentation we hope to increase awareness and promote OTs as Health
Professionals that have expertise in optimising PwP functional performance and
engagement in meaningful activities (Bloem et al., 2010) thus delaying the
earlier development of disability.
PCO10
Future therapies: Drug
treatments
Olivier Rascol
Departments
of Clinical Pharmacology and Neurosciences, CIC-9302/INSERM UMR825, Faculty of
Medicine Purpan, University UPS of Toulouse III, Toulouse, France
Available antiparkinsonian
medications improve the motor symptoms of patients with Parkinson’s disease
(PD). However, overtime, disability progresses despite the combinations of such
medications and three current therapeutic limitations deserve new approaches:
Managing “dopa-resistant” motor and non-motor symptoms (speech impairment,
abnormal posture, gait and balance problems, autonomic dysfunction, mood and
cognitive impairment, sleep problems, pain…), Managing drug-related
dopaminergic side effects (psychosis, motor fluctuations, dyskinesias,
somnolence, ICD…), Halting or slowing the progression of the disease.
Efficacious “disease modifying” medications should prevent the patients from
reaching the stages when patients are facing most problems resisting to current
therapies. Many candidates are developed. A definite demonstration of such a
disease-modifying effect proves difficult, although some pilot encouraging
results have been obtained with drugs like rasagiline. Novel symptomatic
medications are on development, acting via dopaminergic (new L-dopa
formulations, novel COMT inhibitors) or non dopaminergic mechanisms (including
agents acting on adenosine A2, glutamate NMDA and mGluR5, serotoninergic,
noradrenergic alpha-2, histaminergic, cannabinoïds receptors). New delivery
systems are also explored such as peripheral transdermal patches, subcutaneous
and intraduodenal pumps or direct drug delivery within the brain (pumps, cell-
or gene-therapy). Such innovative strategies raise numerous challenges
including the refinement of new pathophysiological concepts, the development of
more predictive animal models and the improvement of clinical trials designs.
PCO11
What do we face?
Bastiaan R. Bloem
Department
of Neurology, Parkinson Centre Nijmegen, Radboud University Nijmegen Medical
Centre, Nijmegen, The Netherlands
Parkinson’s
disease (PD) is a complex disorder with a diverse set of motor and non-motor
symptoms (NMS) that are progressively debilitating. Patients may also develop
co-morbidities, such as cerebrovascular disease. Traditionally, Parkinson
patients are managed by a single medical specialty (neurologist or
geriatrician) and are prescribed dopaminergic medication. The drugs can improve
some, but not all, motor symptoms, and are generally not effective against NMS.
Moreover, efficacy is lost over time, because motor complications limit drug
dosage, and psychiatric complications develop. Patient adherence is poor,
perhaps because of adverse side effects, difficult drug regimens or perceived
lack of efficacy. Non-pharmacological therapies should therefore be considered,
in particular multidisciplinary rehabilitation to ensure that patients receive
the right treatment at the right time. The rehabilitation team should include
medical specialists, Parkinson nurses, allied healthcare specialists,
psychologists and dieticians. Additionally, patients and their caregivers
should be included as full team members. Treatment plans should be
patient-centered and tailored to the individual’s needs, addressing not just
disease severity and symptoms but also the associated problems in everyday
activities, relationships, employment and independence. Patients should be
involved in shared decision making, and prioritize the treatment goals. One
example that includes these elements of care is the Dutch ParkinsonNet concept,
which consists of a series of regional networks of dedicated professionals
specialized in the treatment of PD. A clinical trial involving 700 patients
showed that the ParkinsonNet markedly improves the quality of care and allows
for considerable cost savings. While the clinical experience with a
multidisciplinary rehabilitation approach to managing PD patients has been
excellent worldwide, the data to support this approach remains limited. More
studies are needed to demonstrate the cost-effectiveness of integrated multidisciplinary
care and to find the best organization of care to improve the quality of life
for patients, their families and caregivers.
PCO12
How is it addressed?
& Overview of available delivery options
Ruth Hagestuen
National
Parkinson Foundation
Struthers
Parkinson’s Center, MN, USA
Objective: Present an overview of care delivery for Parkinson’s
disease as a dynamic, evolving process. Discuss models and rationale for
multidisciplinary / interdisciplinary and / or inter professional patient centered
care for person’s whose lives are affected by Parkinson’s disease throughout
the continuum of care. Describe the chronic care model and propose a framework
for action based on recommendation of the World Health Organization.
Methods: This presentation will
·
lay the groundwork for discussion throughout the day with an
overview of how care models for PD have evolved in the recent decade
·
include description of currently available PD care delivery
options in a variety of settings
·
build the case the importance of establishing a PD care
environment that offers access to the right information, care and support /
wellness options at the right time throughout the continuum of care
·
this will be done in the context of acknowledging barriers:
educational; financial and healthcare systems.
·
examples of successful initiatives and programs which have been
established to meet the care needs for Parkinson’s will be presented and
available evidence for coordinated team and inter professional care will be
presented
·
outline the framework for action put forth by the World Health
Organization as a prototype for delivery of care for chronic illness
Results: Participants will be able to
·
Discuss
the importance and advantages of patient centered care
o
Identify
at least three barriers to accessing optimum care which are often encountered
by persons with Parkinson’s
o
Describe
the core components of an effective inter professional care model
o
Identify
two key processes involved in the WHO framework for action
PCO13
What this all means for people with Parkinson’s
Alice Templin
Parkinson Society Ottawa, Ottawa,
ON, Canada
At the heart of the
discussion about a service delivery model that engages many team members is a
unique individual living with Parkinson’s. This presentation will explore the
perspective of the PwP - the importance of his individuality, his expectations
and his role - along with his reaction to a multidisciplinary team, in the
development of an effective service delivery model.
First and foremost, the
care plan for the PwP must be rooted in a person-centered philosophy of care,
one which is sensitive towards the individual expression of the person he is.
All clinical interactions and interventions must respect his feelings, needs,
values and beliefs. Secondly, each PwP will have his own understandings and
expectations regarding his future with PD. The service delivery model faces the
challenge of ensuring the alignment of that perspective with facts, realistic
hope and the rights of the PwP. Furthermore, the expectation to receive the
best treatment possible requires the model to be flexible enough to incorporate
new best practices based on the ever-growing body of PD knowledge and the
continually changing reality of the world we live in. Finally, the multidisciplinary
team approach involves many people. The constant and central role of the PwP
needs to work with the changing roles of the other team members. The PwP has a
right and a responsibility to be a key member of the team but may not always be
able and willing to fulfill that role. The service delivery model should
incorporate and foster the leadership role of the PwP while engaging the other
team members in a timely, sensitive, effective and efficient manner. The
integration of these factors into a service delivery model will ensure that the
PwP is receiving the best care possible
PCO14
General practitioner’s role
Christiane Lepage
Montreal University,
Montréal, QC, Canada
With the increase prevalence of
Parkinson disease, the general practioner (GP) will be asked to play a
important role in PD patients care. Although the current medical literature
shows better outcomes for the patient when followed by a neurologist, what is
the place for the GP? Would the best model care not be an interdisciplinary
team ? A team composed by the GP, the neurologist and other healthcare
professionals. The GP is often the first one to suspect the diagnosis. He can
make the initial assesment and begin a treatment if indicated. He can play an
important role in medication's adjustment in association with the neurologist,
especially for the patients of remote regions. Besides, the GP is the best
placed to make the management of the non-motor symptoms wich are quite similar
to geriatric problems. He is also well placed to be the conductor of the
interdisciplinary team when the patient begins to present a loss of autonomy.
However, several difficulties can be raised: in opposition to chronic diseases
as diabetes or HBP, the GP often does not feel confortable with the diagnosis
and the management of Parkinson disease. The neurologists sometimes have to
substitute themselves for the first line, even to solve problems which do not
normaly concern them. The difficult access to specialized services and the
misunderstanding of specific services for this clientele can limit their use.
Suggested solutions: Better training during primary care program and continuing
medical education in the management of Parkinson disease. Better communication
between GP and neurologists and use of videoconsultation. Diffusion of the
available services through the Parkinson societies. Finally, research has to be
made on the impact of services provided by an interdisciplinary team on
patients' quality of life.
PCO15
Nurse’s role
Lucie Lachance
McGill University Health Centre,
Montreal, QC, Canada
Background: The Canadian guideline
for Parkinson Disease recommends that People with suspected PD and untreated
should be referred “quickly” to a specialist with expertise in the differential
diagnosis of this condition- “quickly’ means within 6 weeks, but new referrals
in later disease with more complex problems require an appointment in 2 weeks.
Objective: Our goal was to reduce the waiting list
from 6 months down to a maximum of 6-8 weeks and. We believe that a rapid
access clinic staffed by expert health professionals allow patients seamless
care throughout the continuum of their disease. The Rapid Access Parkinson
clinic offer each patient the services of a nurse clinician, a highly-trained
professional who “coaches” individuals, and their families through the health
care system.
Method: This extra clinic day consist of 2
nurses clinicians and one the neurologist. Patients with suspected Parkinson’s
disease are seen in a timely fashion and have immediate access to the nurse
clinician who guide and counsel patients ensuring continuity of care. If need
be the nurses clinicians see patients in follow-up in between the MD visits to
address emerging and urgent needs. If a patient is admitted to ER, the nurse
clinician ensure seamless communication with respect to medication schedules
and personalized care.
Results: Already the Rapid Access PD clinic
proved to be a better way to function, better triage of our waiting list and
the addition of the nurse clinician has already positive feedback in terms of
returning telephone calls for anxious patients of caregivers in a timely
manner. We are collecting stats and we anticipate other benefits like fewer
emergency room visits and more support when in-patient hospital care is
required. This program also provide the much needed communication to home care
staffs and long-term care facilities.
PCO16
PANEL-
Multidisciplinary teams
Ruth A Hagestuen
Struthers Parkinson’s Center, Minneapolis, MN
National Parkinson Foundation
Objective: Introduce the individual presenters, and
outline theme and logistics of the session.
Methods: Brief speak to the value of joint learning in sessions such as
this where we are introduced to service delivery models of care that have developed
and are continually evolving in different countries and varying healthcare
systems.
Results: Panel will
present their care delivery programs and systems. Following the presentation
there will be an opportunity for discussion. Participants will be able to
identify core themes of all care delivery models and identify unique aspects of
each.
PCO17
Israeli Model- Tel Aviv
Nir Giladi
Department of Neurology, Tel Aviv
Medical Center, Israel
Sackler School of Medicine, Tel
Aviv University, Israel
Sagol School of Neuroscience,
Tel-Aviv University Israel
In
1996 we have established the first Parkinson Center in Israel working according
to the Interdisciplinary team approach methods. The concept of the Center is
that the team members see the patients and the families with Parkinson in the
Parkinson Center – the Movement Disorders Unit. Besides 4 neurologists we
always have 1-3 specialized Parkinson nurses, a social worker as well as a
speech and language pathologist, physiotherapists and sexologist. In addition
to the main Parkinson clinic we have opened a special clinic for care givers, a
special fall prevention clinic as well as a special clinic for atypical
parkinsonism as well as a special service for autonomic dysfunction. In the
past year we have realized the importance of the psychiatric aspects involved
in PD as well as the results of DBS which justifying a psychiatrist in the
team. The addition of a psychiatrist to our team has added a whole new
dimension to our center and we are only now realizing the significance and the
added value of such a specialized person in our team. Since the recent
development in the role of genetics in PD and the fact than in Israel up to a
1/3 of the Ashkenazi patients are genetic cases of PD we have developed over the
recent years a genetic counseling service for Families with PD as well as
clinical counseling to first degree relatives of PD patients with known
mutation, recommending behavioral modification as well as specific
interventions to reduce the risk for PD. The Parkinson Center is actively
involved in multiple clinical studies as well as more basic research. All
researchers as well as the students are participating in a weekly meeting with
the clinicians, where exchanges of information as well as new research ideas
are brought up. Such weekly meeting is essential for the success of the Center.
Since 2005 our center is recognized as a Center of Excellence by the National
Parkinson Foundation of Miami USA.
PCO18
Netherlands Model-
ParkinsonNet
Marten Munneke1,2,
Bastiaan Bloem1,2
1ParkinsonNet,
Nijmegen, The Netherlands
2Parkinson Centre
(PARC), Radboud University Nijmegen Medical Centre, The Netherlands
The Dutch model to deliver optimal care to all Dutch
patients with Parkinson’s Disease consists of regional networks of health care
professionals (e.g. neurologist, Parkinson nurse, physical therapist, speech
therapist, occupational therapist, social worker, etc) who are specialised in
the treatment of Parkinson patients, and who work effectively together in a
patient-centred approach. We started with this concept in 2004 in our own
region (Nijmegen) and other regions followed soon. Currently a ParkinsonNet has
been implemented in all of the Netherlands (in total 66 regions, including more
than 2.500 specialised healthcare providers who have become members of
ParkinsonNet). ParkinsonNet is characterized by adequate and continuous
training (to work according to current clinical guidelines) and by
certification of all members. In addition, we stimulate collaboration between
healthcare providers within regions and provide patients with background
information about our members, allowing them to make an informed decision about
the treatment that best suits their individual needs. Moreover, we provide
feedback to patients about the actual quality of care delivered by our members,
both as a service to patients and as a benchmark for professionals (so they can
improve their services). More information is presented on our website www.parkinsonnet.info
PCO19
US Model – Struthers
Parkinson’s Center
Ruth Hagestuen
Struthers
Parkinson’s Center, Golden Valley, MN
National
Parkinson Foundation
Objective: This presentation will provide an overview
of the Struthers Parkinson’s Center’s integrated approach to clinical,
educational, research, support, outreach and wellness programs. The Center,
established over 30 years ago, is a free-standing facility which is part of the
Park Nicollet Health System.
Methods: The SPC integrated system of care is designed to provide access
to the right care, information, and support at the right time, over time. The
majority of programs which will be presented are team based. The full day
assessment clinic, for example, includes physician, nurse, social worker,
physical therapy, occupational therapy, speech therapy. Different combinations
of the team members are part of the FOCUS program for persons newly diagnosed,
the Caregiver Skills-building series, and the DBS educational sessions for
patients and families considering Deep Brain Stimulation. The same is true of
the regularly scheduled professional education days for nurses, rehabilitation
therapists and social workers. Two other unique programs of this Center are (1)
the CREATE (Center for Research Education Artistic and Therapeutic Endeavors)
program which includes a therapeutic day program, an arts café, and a variety
of exercise based wellness and support programs and (2) The Struthers
Parkinson’s Care Network (SPCN), working with senior residential communities to
improve PD awareness, staff education and support services.
Results: Attendees at this session will (1) be able to list at least two unique
program initiatives from Struthers Parkinson’s Center that can be replicated in
other locations, (2) Discuss the role of a Parkinson’s Center as a regional hub
of specialized care in the U.S. (3) Identify times during the course of living
with Parkinson’s disease where access to specialized services is most critical.
PCO20
Australian Model- Melbourne
Meg E Morris
La Trobe University, Victoria,
Australia
Objective: Parkinson’s disease
is a chronic and progressive condition that can affect movement, balance, mobility,
the ability to perform daily activities, autonomic function, cognition, and
psycho-social function. It affects individuals as well as families and
care-givers. Each person living with Parkinson’s disease is unique and services
need to be comprehensive and tailed to individual needs.
Methods: In Melbourne Australia
we have led comprehensive inter-professional rehabilitation services to assist
people with Parkinson’s disease and the significant others in their lives to
live well with this condition. Rehabilitation interventions are research led
and based on current scientific findings on responses to movement
rehabilitation strategies, strength training, cognitive training, and physical
activities such as walking, dancing and hydrotherapy. Services are provided in
home, community and hospital settings. As well as adopting science informed
clinical guidelines, emphasis is placed on teaching health professional how to
work effectively and efficiently within a team and how to ensure client centred
and family focussed outcomes.
Results: In both young adults
and older people with PD, a comprehensive inter-professional team based model
of rehabilitation has been found to be effective, feasible and safe. As well as
optimising mobility, functional task performance and physical activity, it is
argued to reduce care-giver burden by empowering people to be more independent.
The aim is to optimise quality and life and well-being through targeted and
effective services provided at the right time by the right person in the right
environment.
PCO21
Canadian Model- McGill
Movement Disorders Clinic
Anne-Louise Lafontaine
McGill
Movement Disorder Clinic, Montreal, QC, Canada
Objective: This presentation will
describe a new model for care. The rapid access clinic was established for the
diagnosis and early intervention in patients with suspected Parkinson disease.
Our goal in establishing this clinic was to reduce the current waiting list
from 6-12 months down to a maximum of 6-8 weeks. The clinic would also provide
patients access to care in between the scheduled MD visits to deal with
important issues as they emerge. The McGill Movement Disorder clinic was
established in 2001. The clinic currently follows close to 1000 patients.
Because of space and manpower issues, our wait list is 6-12 months for the
initial visit and follow up visits are routinely scheduled at 4-6 month
intervals. The waiting time to first visit is well outside the window
recommended by a recently developed Canadian guideline for Parkinson Disease. The
guidelines recommend that People with suspected PD should be referred quickly*
and untreated to a specialist with expertise in the differential diagnosis of
this condition. (*..should be seen within 6 weeks, but new referrals in later
disease with more complex problems require an appointment in 2 weeks).
Method: The Rapid Access
Parkinson clinic offers each patient the services of pivot nurses,
highly-trained professionals who “coaches” individuals, and their families
through the health care system. This model of care has the pivot nurse as the
first line contact with patients from first visit and throughout the continuum.
Patients will be provided with a telephone number that links them with a pivot
nurse for concerns in between visits or for telephone feedback. This program will reduce delays in
diagnosis and treatment of Parkinson’s disease and will alleviate the anxiety
of navigating complex symptoms. Other anticipated benefits include easier
access to follow- up care, fewer emergency room visits and more support when
in-patient hospital care is required. This program will also provide the much
needed communication to CLSCs and long-term care facilities. Pivot nurses and the social worker
will see patients in follow-up in between the MD visits to address emerging and
urgent needs. When Parkinson patients are admitted to the emergency room or
hospital ward, the pivot nurse will ensure seamless communication with respect
to medication schedules and personalized care.
Oral Sessions
O1
Propagation of the
neurodegenerative process in PD and the Prion-like hypothesis
Virginia Lee
University
of Pennsylvania, Philadelphia, PA, USA
The
accumulation of misfolded proteins is a fundamental pathogenic process in
neurodegenerative diseases. These hallmark proteinaceous lesions include
extracellular senile plaques comprised of the Aβ peptide and intracellular
neurofibrillary tangles consisted of tau proteins in Alzheimer’s disease as
well as α-synuclein (α-syn) containing Lewy bodies and Lewy neurites
in Parkinson’s disease. We hypothesized that templated recruitment of
endogenous proteins by misfolded conformers follow by cell-to-cell spreading of
the pathology are a common disease mechanism that account for the progression
of these age-related disorders. In both tauopathies and synucleinopathies, we
demonstrate that pre-formed fibrils (pffs) generated from recombinant tau or
α-syn enters cultured primary neurons as well as transgenic and wildtype
mice, promoted recruitment of soluble endogenous proteins into insoluble
protein aggregates resembling the pathology in their human counterparts.
Pathologic misfolded aggregates propagated along major central nervous system
(CNS) pathways to regions far beyond injection sites and appear to follow
neuroanatomical interconnectomes. Thus, synthetic α-Syn or tau pffs are
wholly sufficient to initiate neurodegenerative disease pathology and transmit
disease in primary neurons in vitro
and in mice in vivo. Thus, these data
support a prion-like cascade in neurodegenerative disease protein spreading
whereby cell-to-cell transmission and propagation of misfolded proteins
underlie the CNS proliferation of disease pathology. These findings open up new
avenues for understanding the progression of neurodegenerative diseases and for
developing novel therapeutics.
O2
Can the interaction
between genetics, environment, and behavior be a key determinant of PD
expression?
Christine Klein
University
of Luebeck, Luebeck, Germany
The
current consensus on the pathogenesis of Parkinson disease (PD) suggests that
PD is an etiologically heterogeneous disorder developing from multiple
causative/risk factors including genetic predisposition, aging, and
environmental exposure. Accordingly, this has led to a multiple-hit model of PD
pathogenesis, ultimately resulting in a ‘disease map’. Although collectively
only explaining about 5% of all cases, causative PD genes are the currently
best-studied etiology of the condition and monogenic PD can serve as a human
disease model. Among the six unequivocally identified forms causing a clinical
picture closely resembling idiopathic PD, three (SNCA, LRRK2, VPS35) follow an
autosomal dominant mode of inheritance, whereas three are recessively inherited
(Parkin, PINK1, DJ-1). Risk variants in some of these, as well as in other
genes - most notably GBA -, can act as susceptibility factors and disease
modifiers of ‘idiopathic’ PD. Importantly, monogenic and ‘idiopathic’ PD share
common pathophysiological mechanisms converging on oxidative modification,
impaired protein degradation, and mitochondrial dysfunction. Epigenetics, i.e.
heritable changes in gene expression that do not involve coding sequence
modifications, is commonly considered the missing link between the genome and
the environment. Environmental agents, often present in the context of specific
behaviors, such as smoking, have the potential to not only directly
damage/protect the developing and mature nervous system but to also impact on
genes involved in neurodegeneration by epigenetic means, leading to altered
gene expression. Instead of studying individual components of PD pathogenesis,
recent attention has increasingly been focused on the interaction and dynamics
of these different etiological factors. This has led to the discovery of first
significant gene-environment interactions, such as SNCA risk variants and head
injury. These observations collectively suggest that a network analysis may be
required to disentangle the complex puzzle of genetic, environmental, and
behavioral factors in the etiology and expression of PD.
O3
What epidemiological
and preclinical studies teach us about inflammation and PD
Etienne C. Hirsch
Centre de recherche de l’Institut
du cerveau et de la moelle épinière, INSERM UMR975, CNRS UMR 7225, UPMC,
Hôpital de la Salpêtrière, Paris, France
Both
epidemiological and genetic studies support a role of neuroinflammation in the
pathophysiology of Parkinson’s disease (PD). Indeed, both prospective and
retrospective epidemiological studies indicate that the long term use of
anti-inflammatory drugs and especially ibuprofen reduces the risk od developing
Parkinson’s disease. On the other hand genome wide analysis also indicate that
one haplotype the immune related gene HLRdr is associated with a higher risk to
develop the disease. Furthermore, post mortem studies confirm the involvement
of innate as well as adaptive immunity in the affected brain regions in
patients with PD. Indeed, activated microglial cells and T lymphocytes have
been detected in the substantia nigra of patients concomitantly with an
increased expression of pro-inflammatory mediators. Preclinical investigations
inflammatory processes are instrumental in neuronal cell death even though they
are unlikely to be a primary cause for neuronal loss. Neuroinflammatory
processes in PD are rather involved in self-perpetuating deleterious events
that lead to protracted neuronal degeneration. In line with this, recent data
indicate that glucocorticoid receptors are important in curtailing microglial
reactivity, and deregulation in their activity in PD could lead to sustained
inflammation-mediated degeneration. Altogether, neuroinflammatory processes
might represent a target for neuroprotection in PD.
O4
Developing new
treatments founded on the basic science of Parkinson’s disease
Patrik Brundin
Laboratory
for Translational Parkinson's Disease Research, Center for Neurodegenerative
Science, 1Van Andel Institute, Grand Rapids, MI, USA, and Neuronal
Survival Unit, Wallenberg Neuroscience Center, Lund University, Lund, Sweden
This
presentation highlights some challenges facing the translation of findings in
the basic science laboratories to clinical therapies for Parkinson's disease
(PD). The past three decades have seen a tremendous development of
animal-models of PD, primarily along two lines: First, researchers have used neurotoxins that are relatively
specific for dopamine neurons and/or have mechanisms of action resembling
putative pathogenic mechanisms of PD. In animals, these toxins can result in
excellent modeling of the transmitter changes occurring in the nigrostriatal
pathway, and in motor impairments akin to those observed in PD. The development
of new pharmacological treatments to "replace" dopamine has
benefitted from toxin-based models. Neurodegeneration in toxin-based animal
models, however, is often very rapid lacking the slow, progressive features
that are typical of PD. Moreover, these models rarely encompass the non-motor
symptoms (e.g. depression, cognitive decline, constipation) that are important
sources of morbidity in patients. Second,
several genetic models have been created based on the numerous mutations that
are coupled to rare inherited forms of PD. These models do not always result in
neuronal death, but instead recapitulate other neuropathological features of PD
(e.g. protein aggregation). Furthermore, these models might not be relevant to
the more common sporadic PD.
The main
challenge today is the need for a therapy that slows PD progression. Such a
disease-modifying therapy would revolutionize the PD treatment. Several
experimental treatments have been found to "modify disease", in the
toxin-based and genetic PD models. Yet when tested clinically, they have
failed. The reasons for failure could be manifold. Possibly, some drugs have a
poorer bioavailability or less favorable pharmacokinetics in humans, or simply
do not effectively engage the crucial molecular targets in the brain. Another
more compelling option is that the animal PD models simply are not relevant to
the true disease process in humans, for the reasons briefly mentioned above. It
is imperative that better animal models mimicking the slow neurodegeneration
seen in PD, with the relevant associated molecular changes, are developed.
The
development and testing of new PD therapies cost huge sums of money. Another
attractive option for development of novel PD therapies is drug repositioning,
i.e. testing drugs that have been proven safe and effective for other
disorders. As one of several organizations thinking along these lines, the Cure
Parkinson's Trust UK The Linked Clinical Trials Initiative is promoting this
approach (1). The advantages are that cost and time delays are reduced
dramatically, and issues regarding bioavailability have usually already been
addressed. Frequently these drugs are tested with a more open-ended hypothesis
as to how they might work in the brain, and not only target the dopamine
system. Therefore they might also be found to be effective at treating the
important non-motor symptoms.
O5
The Life and Times of
James Parkinson
Gerald Stern
University
College Hospitals, Queen Square, London, UK
“English
born and bred, an English physician and scientist, forgotten by the English and
by the world at large – such is the fate of James Parkinson”. LG Rowntree 1912.
Thus wrote Parkinson’s first biographer. Today, as a consequence of his famous
and original essay, ironically, the name of Parkinson is now recognised
throughout the world. He was a remarkable man. We remember him not only for his
seminal contribution to neurology but also for his benevolent concern for the
physical, social and moral welfare of his patients and for his love of honest
controversy and freedom of speech. Despite living in dangerous times, he
vigorously attacked what appeared to him to be wrong in the society in which he
lived and proved himself to be a courageous radical reformer. He had a deep
interest in many branches of science, which he pursued with energy and
insatiable curiosity. He was a modest, scholarly, astute and original clinician
who gained - alas posthumous - fame and global recognition. His story will be
briefly recapitulated.
O6
New PD genes and rare
variants
Matthew Farrer
Vancouver,
BC, Canada
Parkinson disease (PD) is a
multifactorial neurodegenerative disease that was long considered
environmental. However, in the past fifteen years a genetic etiology for PD has
begun to emerge. This seminar will review results from linkage and
next-generation sequencing studies of familial parkinsonism as well as
candidate gene and genome-wide association studies of sporadic PD. Many of the
genetic findings in these different study designs overlap, providing
unequivocal proof. While the altruism of patients, families and their DNA, and
the help of their neurologists, made the discoveries possible, seldom are
individual pathogenic mutations in specific genes useful for a differential
diagnosis or for a patient’s prognosis. Nevertheless the results have enabled
the creation of a new generation of genetically-engineered mouse models that
are currently providing physiologically-relevant insights into disease
pathogenesis. Molecular neuroscience, with these novel targets and tools, now
has an opportunity to develop intervention strategies aimed at disease modification
(neuroprotection). In parallel, genetic analysis can reciprocally inform
patient recruitment into neuroimaging studies and future clinical trials. The
genetic revolution has started, not in diagnosis nor personalized medicine, but
in our knowledge of the neuronal biology gone awry. In PD, based on only a few
years of discovery, a temporal ecology has become apparent whereby deficits in
synaptic exo- and endocytosis, endosomal trafficking, lysosomal-autophagy and
mitochondrial maintenance increase individual susceptibility. However, most the
phenotypic variance in PD has yet to be explained; for example genetic
modifiers are as likely to contribute to age of onset, motor and non-motor
symptoms, disease progression and/or a patient’s response to medication (trait
components) as susceptibility. Knowing an individual’s genetic background, the
contribution of the environment, epistatic interactions and epigenetic
inheritance might also be more readily defined.
O7
Generic Risk factors of sporadic PD
Andrew Singleton
Laboratory
of Neurogenetics, National Institute on Aging, National Institutes of Health,
Bethesda, MD, USA
There has been considerable
progress in our understanding of the genetic basis of monogenic, familial forms
of Parkinson’s disease over the last 15 years. Based on the foundation of this
knowledge, and with the use of second generation genetic methods now available,
a great deal of progress has also been made in understanding the genetic
architecture of the common apparently sporadic forms of Parkinson’s disease.
Here I will describe the progress that has been made in this regard, starting
with a discussion of how candidate gene based analysis initially implicated
genetic variability at the gene encoding alpha-synuclein. This will be expanded
upon to include lessons learned from deep sequencing of LRRK2 and from the discovery that GBA2 mutations are a risk factor
for disease. Next I will discuss the application of genome wide association
studies, and how these have lead to the identification of ~30 genetic risk loci
for disease, and more accurate estimates of the heritability of Parkinson’s
disease. Lastly I will discuss future directions for the genetic dissection of
apparently sporadic, genetically complex Parkinson’s disease.
O8
Genetics and gene environment interactions
Haydeh Payami
New York State Department of
Health Wadsworth Center, Albany, NY, USA
Objective: During the 20th
century, PD was thought to be purely environmental with no genetic component.
The turn of the century brought an awakening, and the 21st century
unleashed unprecedented progress in the genetics of PD. With more than 20
PD-related gene in hand, it is now time to go full circle, take what we know
about environmental factors, and begin building an understanding of which genes
interact with which environmental factors. Through the efforts of many
scientists we now understand that PD involves interactions between genetic
make-up and environmental exposures. Not everyone who is exposed to a
neurotoxin will develop neurodegenerative disease. Not everyone treated with
the same drug will experience the same benefit. Our objective is to understand
the genetic basis for the individual differences in response to environmental
exposures and drugs.
Methods: Gene-environment
studies require that several thousands of persons with PD and an equal number
without PD are enrolled. They are asked to provide a source of DNA (usually
blood) and environmental exposure history (pesticides, smoking, coffee, etc.).
DNA is used to determine the genetic make-up of the individuals which can then
be correlated with their previous environmental exposures and current disease
state. Early studies could only test one or two genes at a time; now, with new
technologies, we cast the search across the entire genome.
Results: Our lab is especially
interested in environmental factors that can be used for prevention and
treatment. To that end, we have conducted genome-wide searches for genes that
underlie the population variability in the response to protective effects of
nicotine, caffeine, and non-steroidal anti-inflammatory drugs. In this
presentation, I will discuss the genes that we have uncovered so far, and the
relevance of this knowledge to moving the field forward with regard to
development of therapeutics and disease prevention.
O9
Alpha-synuclein conformation and neurodegeneration
Maria Xilouri1, Oystein Brekk1, Natalie
Landeck2, Deniz Kirik2, Leonidas Stefanis1,3
1Laboratory
of Biology of Neurodegenerative Diseases, Biomedical Research Foundation of the
Academy of Athens (BRFAA), Athens, Greece
2Lund
Univeristy, Lund, Sweden
3Second
Department of Neurology, University of Athens Medical School
Aberrant alpha-synuclein (AS) is
linked to the pathogenesis of Parkinson’s Disease and other synucleinopathies.
Oligomerization of AS into soluble protofibrils and eventually insoluble
fibrils, comprising the building blocks of Lewy Body and Lewy neurites, is
thought to underlie its neurotoxic potential. One of the critical factors that
determine the propensity of AS to follow this pathway of aggregation is its
levels. Excess of AS leads to PD in humans and to abnormal protein deposition
and neurodegeneration in experimental animals. Levels of AS are in part
regulated by mechanisms of protein degradation. We and others have provided
evidence that Wild Type (WT) AS is degraded in part by the lysosomal process of
Chaperone-Mediated Autophagy (CMA). PD-associated mutant forms of AS are not
degraded by this process, and in fact impede degradation of other CMA
substrates. We reasoned that a possible therapeutic avenue against the toxic
effects of AS would be induction of CMA, so as to, on the one hand, accelerate
AS clearance, and, on the other, attenuate its toxic effects on lysosomes.
To this end, we have expressed
the lysosomal transmembrane protein Lamp-2a, the rate-limiting step in the CMA
pathway, in SH-SY5Y neuroblastoma cell lines and in cortical neurons. This
approach led to significant induction of CMA activity, accelerated clearance of
AS and protection against WT AS-mediated neurotoxicity. To extend this approach
to the in vivo level, we have examined the impact of Lamp-2a overexpression in
the Adeno Associated Virus (rAAV) model of nigral WT AS overexpression. We
achieved robust expression of Lamp-2a via nigral stereotaxic injection of the
rAAV without any observable toxicity. Significantly, Lamp-2a rAAV co-injection
with AS rAAV curtailed nigrostriatal degeneration and attenuated the
accumulation of detergent-insoluble and oligomeric AS species. Thus, CMA
induction may provide a therapeutic avenue against abnormal AS accumulation and
neurotoxicity in synucleinopathies.
O10
Protein misfolding in neurodegenerative disease
Leonard Petrucelli
Mayo Clinic, Jacksonville, FL,
USA
Objective: Recent genome wide association studies
(GWAS) provide compelling evidence that variants in the tau gene (MAPT) are a
major risk factor, second only to risk variants in the gene for
α-synuclein (SNCA), for Parkinson’s disease (PD). Given that tau and
α-synuclein (α-syn) have been shown to promote the fibrillization of
one another in vitro and in vivo, the conversion of soluble tau
into oligomeric and fibrillar species may not only cause toxic tau dysfunction,
it may also promote the aggregation of α-syn and the formation of
pathological α-syn inclusions. As such, blocking filamentous or
phosphorylated tau production may have a two-fold benefit: preventing
aggregation of tau and α-syn.
Methods: We have previously demonstrated that levels of the enzyme
cytosolic histone deacetylase 6 (HDAC6) positively correlate with tau burden,
while a decrease in HDAC6 activity or expression promotes tau clearance. Using a variety of approaches, including the
generation of a novel tau acetylated antibody as well as in vitro and in vivo
assays, we now know how this may occur. Our new preliminary data reveal loss of HDAC6
activity increases the ratio of tau acetylation to tau phosphorylation, thereby
favoring tau clearance and preventing filament formation associated with
disease progression.
Results: We have
obtained a novel brain penetrant and highly specific HDAC6 inhibitor that we
demonstrate simultaneously decreases phosphorylation and increases acetylation at
crucial sites on tau, thereby preventing tau aggregation and promoting abnormal
tau clearance in vivo. These data and future approaches will be discussed in this
session.
O11
Link between lysosomal function and neurodegeneration in PD
Dimitri Krainc
Massachusetts General Hospital
and Harvard Medical School, Boston, MA, USA
The recurrent observation of
accumulation and aggregation of mutant proteins such alpha-synuclein, tau,
a-beta in different neurodegenerative disorders indicates the possibility of a
shared pathogenic mechanism. Recent data suggest that elimination of mutant
protein accumulation can halt the symptomatic progression and also lead to
regression of the disease. The evidence in Parkinson’s disease (PD) is most
compelling since the clinical and genetic studies point to a clear dosage
relationship between alpha-synuclein and disease and subtle alterations in
expression level of alpha-synuclein are sufficient to cause a wide spectrum of
disease. These findings indicate that if alpha-synuclein can somehow be
cleared, the disease can be prevented or even reversed. The clearance of
aggregation-prone proteins is largely achieved through the autophagy-lysosomal
system. However, one of the main challenges is to identify specific mechanisms
and targets involved in the clearance of these proteins in order to develop
specific therapeutics. To tackle this challenge, we examined rare disorders
caused by mutations in genes involved in lysosomal function that result in
neurodegeneration. To this end, we examined a linkage between Gaucher’s that is
caused by mutations in lysosomal glucocerebrosidase and Parkinson’s disease. We
found that inactive glucocerebrosidase leads to accumulation of the
sphingolipid glucosylceramide in neurons that in turn stabilizes toxic
alpha-synuclein oligomers. Interestingly, accumulation of alpha-synuclein
interferes with ER to Golgi trafficking of wild-type lysosomal enzymes which in
turn leads to decreased lysosomal activity. These findings suggest that this
molecular pathway also applies to patients with idiopathic PD or other
synucleinopathies who have a normal glucocerebrosidase gene. The bidirectional
effects of alpha-synuclein and glucocerebrosidase forms a positive feedback
loop that, after a threshold, leads to self-propagating disease. This study
identifies glucocerebrosidase as specific target for therapeutic development in
synucleinopathies and highlights the importance of rare diseases for
understanding of more common conditions.
O12
Structural
imaging for PD: MRI and transcranial sonography (TCS)
Klaus
Seppi
Department of Neurology, Medical
University Innsbruck, Austria
Clinical diagnosis of Parkinson’s
disease (PD) can be straightforward in classical cases, even though
differentiation from other clinical entities such as essential tremor, atypical
parkinsonian disorders (APDs) or symptomatic parkinsonism may be challenging
especially in the early stages of the disease, when symptoms and signs are
often vague. The correct diagnosis of PD is important for prognostic and
therapeutic reasons and essential for clinical research. Despite limitations,
the different modern magnetic resonance (MR) techniques have undoubtedly added
to the differential diagnosis of neurodegenerative parkinsonism. Conventional
MRI with visual assessment of T2- and T2-weighted imaging as well as various
advanced MRI techniques offer objective measures and may therefore be useful
tools in the diagnostic workup of PD and APDs. In clinical practice,
conventional MRI is a well-established method for the exclusion of symptomatic
parkinsonism due to brain pathologies. Over the past two decades, advances in
MR techniques have enabled to quantitatively illustrate abnormalities in the
basal ganglia and infratentorial structures in APDs by methods such as volumetric
methods, diffusion-tensor imaging, proton magnetic resonance spectroscopy and
multimodal imaging. Assessment of the echomorphology of the substantia nigra
(SN) with transcranial sonography (TCS) can also be helpful for the diagnosis
of PD. Indeed, several independent studies have detected consistently
hyperechogenicity in the SN region (SN+) by TCS in about 80-90% of patients
with PD, while only 10% of healthy adult controls and patients with APDs and a
slightly higher number of patients with ET show this echofeature. Moreover, SN+
has been shown to be related to a number of pre-motor features and risk factors
for PD such as RBD and hyposmia and determines a high risk to develop PD in
healthy people. This presentation aims to review research findings on the value
of MRI techniques and TCS for the early diagnosis of PD.
O13
Neurochemical imaging
Nicola Pavese
Imperial College London, London,
UK
PET
and SPECT remain the most useful techniques to assess in vivo the neurochemical changes associated with the
neurodegenerative process in Parkinson’s disease (PD). Both techniques have
been used to assess the integrity of the dopaminergic system in idiopathic PD
and other Parkinsonisms. [18F]-dopa PET, [11C]-dihydrotetrabenazine
(DTBZ) PET and PET and SPECT with a variety of ligands for the dopamine
transporter (DAT) are all reliable markers of dopaminergic pre-synaptic
function. While [18F]-dopa PET mainly measures the activity of the
aromatic amino acid decarboxylase, providing a marker of dopamine synthesis and
storage, DTBZ PET and DAT SPECT/PET respectively bind
to the type-2 vesicular monoamine transporter and dopamine transporter, which
are expressed on dendrites and axons of dopaminergic neurons. In general, these three
techniques show a similar finding of reduced tracer uptake in the striatum of
PD patients indicative of loss of nigrostriatal dopaminergic terminals and are
able to differentiate early PD from normal subjects with a sensitivity of
around 90%. Several PET and SPECT tracers including [11C]-raclopride and [123I]-IBZM have been used to assess post-synaptic
dopaminergic receptor availability in Parkinsonian syndromes. Compared to
healthy controls, dopamine receptor binding is generally normal or mildly affected
in PD but is significantly reduced in patients with Multiple System Atrophy and
Progressive Supranuclear Palsy, suggesting that a
degeneration of striatal dopamine receptors occurs in these conditions. [11C]-raclopride PET has also been used to assess fluctuations in synaptic
concentrations of dopamine following pharmacological or behavioural challenges.
More
recently, PET has been used to assess the involvement of non-dopaminergic brain
pathways in the pathophysiology of both motor and non-motor symptoms in PD.
Neurochemical changes associated with occurrence of dementia, fatigue, sleep
disturbances, depression and impulse control disorders in patients with PD
begin to be elucidated with potential implications for the treatment of these
complications.
O14
Functional
connectivity
David Eidelberg
The
Feinstein Institute for Medical Research, Manhasset, NY, USA
Over
the past two decades, functional imaging techniques have become commonplace in the
study of brain disease. Nevertheless, very few validated analytical methods
have been developed specifically to identify and measure systems-level
abnormalities in living patients. Network approaches are particularly relevant
for translational research in the parkinsonian movement disorders, which often
involve stereotyped abnormalities in brain organization. In recent years,
network analysis applied mainly to metabolic images acquired in the resting
state, has provided a useful means of objectively assessing brain disorders at
the network level. By quantifying network activity in individual subjects on a
scan-by-scan basis, this technique makes it possible to objectively assess
disease progression and the response to treatment on a system-wide basis. To
illustrate the utility of network imaging in Parkinson’s disease, I will review
recent applications of the approach in the assessment of preclinical disease
progression, and as an aid to differential diagnosis. I will also discuss novel
uses such as predicting cognitive responses to dopaminergic therapy, and the
evaluation of placebo effects.
O15
Role of noradrenaline
and serotonin systems for the development of non-motor symptoms
Abdelhamid Benazzouz
Institut des Maladies
Neurodegeneratives, CNRS UMR 5293, Bordeaux, France
Parkinson’s
disease (PD) is characterized by the degeneration of dopamine (DA) neurons in
the substantia nigra pars compacta,
and motor symptoms including bradykinesia, rigidity and tremor at rest. These
symptoms are exhibited when striatal dopamine level has decreased by around
70%. In addition to motor deficits, PD is also characterized by the non-motor
symptoms. However, depletion of DA alone in animal models has failed to
simultaneously elicit both the motor and non-motor deficits of PD, possibly
because the disease is a multi-system disorder that features a profound loss in
other neurotransmitter systems. Our hypothesis is that additional loss of
noradrenaline (NA) and/or serotonin (5-HT) neurons could be involved in the
clinical expression of motor as well as in non-motor deficits. Our behavioral
data show that NA as well as DA depletion significantly decreased locomotor
activity and enhanced the proportion of bursty and irregular STN neurons in the
rat. Anxiety-like states required DA depletion plus the depletion of 5-HT or
NA. Anhedonia and “depressive-like” behavior emerged only from the combined
depletion of all three monoamines, an effect paralleled by an increase in the
firing rate and the proportion of bursty and irregular STN neurons.
Furthermore, we show that the beneficial effects of L-dopa and STN high
frequency stimulation can be limited when NA and 5-HT systems are affected in
addition to DA depletion. Our data provide evidence for the exacerbation of
behavioral deficits when NA and/or 5-HT depletions are combined with DA
depletion, bringing new insight into the combined roles of the three monoamines
in PD.
O16
Impact of cholinergic
dysfunction on the development of non-motor symptoms
Nicolaas I. Bohnen1,2
1Departments of Radiology and Neurology,
University of Michigan, Ann Arbor, MI, USA
2Department of Veterans Affairs,
Neurology Service and GRECC, Ann Arbor, MI, USA
Objective:
Non-motor
symptoms are common in PD, are a significant cause of disability, and often do
not respond to dopaminergic therapy. Evidence is accumulating that cholinergic
system dysfunction is a significant contributor to non-motor morbidity in PD.
The cholinergic system is implicated in non-motor functions in PD because of
loss of cholinergic basal forebrain (FB) neurons and also secondary to
degeneration of degeneration of cholinergic neurons in the peduncolopontine
nucleus (PPN). We have used in vivo PET imaging to characterize non-motor
correlates of cholinergic denervation in PD.
Methods:
[C-11]PMP
acetylcholinesterase PET imaging and clinical non-motor assessment in PD and
control subjects.
Results:
We
showed previously that cholinergic FB denervation is associated with cognitive
decline. These studies have also shown that cholinergic FB degeneration is
associated with depressive symptoms in PD, at least in the presence of
cognitive impairment. Limbic, in particular hippocampal, cholinergic losses
correlate strongly with more severe impairments of odor identification in PD. Olfactory dysfunction in PD may be most marked in subjects
at risk of incipient dementia and may reflect the transition of PD toward a
stage with more heterogeneous multi-system neurodegenerations.
There is significant heterogeneity of
cholinergic denervation in PD without dementia with about 1/3 of subjects
having FB and about 1/6 PPN denervation. Using [C-11]PMP acetylcholinesterase
PET, we showed recently that cholinergic denervation, especially of the
thalamus, reflecting PPN cholinergic afferent degeneration, is associated with
symptoms of REM sleep behavior disorder. These findings may explain why REM
sleep behavior disorder is a risk factor for development of dementia in PD.
Collectively, these results indicate that cholinopathy has variable presence in
PD without dementia and associates with cognitive, olfactory, mood and sleep
disturbances. Identification of subjects with PD with cholinopathy provides a
non-dopaminergic window of therapeutic opportunity to manage non-motor
morbidity and reduce disability in PD.
O17
Role of
non-dopaminergic systems in the development of L-DOPA-induced dyskinesias
M. Angela Cenci
Lund
University, Lund, Sweden
L-DOPA-induced
dyskinesias (LID) are abnormal involuntary movements that complicate the
dopaminergic pharmacotherapy of Parkinson´s disease (PD). The bulk of
experimental studies indicate that LID results from the combined effects of a
severe nigrostriatal dopamine (DA) lesion and fluctuating presynaptic levels of
DA, eliciting abnormal responses in striatal neurons via supersensitive DA
receptors. This pathophysiological cascade is both modulated and sustained by
several non-dopaminergic neurotransmitters. Hence, much translational research
is now focused on developing antidyskinetic treatments that target
non-dopaminergic systems, particularly glutamate and serotonin
(5-hydroxytryptamine, 5-HT). Dysregulated glutamate transmission and increased
stimulation of perisynaptic and extrasynaptic glutamate receptors are
attributed an important role in the pathophysiology of LID. Metabotropic
glutamate receptor type 5 (mGluR5) is abundantly expressed in striatal neurons,
where it shows a predominantly perisynaptic localization. In rodent models of
PD, pharmacological antagonism of mGluR5 blunts the supersensitive striatal
activation of signaling proteins and gene expression induced by L-DOPA. These
molecular effects are paralleled by an attenuated development of dyskinesia
during chronic L-DOPA treatment. In the same animal models, mGluR5 antagonism
attenuates the severity of already established LID. These experimental results
have prompted a rapid clinical development of mGluR5 negative modulators for
the treatment of LID, and three Phase-2 clinical trials have recently reported
positive results. The serotonin system can drive the expression of dyskinesia
by providing an aberrant source of DA release following the administration of
L-DOPA. Selective agonists of the serotonin autoreceptors, 5-HT1A and 5-HT1B
blunt L-DOPA-induced DA efflux in the brain and attenuate peak-dose dyskinesia.
Compounds with agonistic activity at 5-HT1A receptors have been tested in PD
patients with mixed results. A future clinical development of this strategy
will rely on the generation of suitable 5-HT1A/1B agonist compounds that can
reduce dyskinesia without interfering with the antiparkinsonian action of
L-DOPA. In conclusion, targeting specific glutamate or serotonin receptor
subtypes appears to be a promising approach for the future treatment and
prevention of L-DOPA-induced dyskinesia in PD.
O18
Why supporting
research is crucial: from government to private funding agencies- Introduction
Todd Sherer1,
Amy Comstock-Rick2, Etienne Hirsch3, Remi Quirion4,
Tom Isaacs5
1The Michael J Fox
Foundation for Parkinson’s Research, NY, USA
2Parkinson's Action Network
(PAN), Washington DC, USA
3Aviesan, French
Institute for Neurosciences, Cognitive Sciences, Neurology and Psychiatry,
Paris, France
4McGill University,
Montreal, QC, Canada
5The Cure Parkinson’s
Trust, London, UK
Objectives
·
To
outline the scope of funding opportunities in furthering Parkinson’s research
·
To
identify the sources of funding for different stages in the therapeutic
pipeline process
·
To
illustrate why Parkinson’s has suffered from a lack of investment relative to
other conditions
·
To
suggest new sources and methods of funding in the Parkinson’s arena and how
funding from philanthropic sources can kick-start other investment
·
To
identify new opportunities and funding models for group discussion
Methods: The panel will provide
different perspectives on the issues facing them both as recipients and
providers of funding for Parkinson’s research. E. Hirsch will look at the need
for greater collaboration and cooperation between funding sources so that the
most important research is prioritised, as well as the need to have a more
coordinated approach to funding research in the entire neurological sector. R.
Quirion will discuss specific funding models in Canada and the role that ‘Brain
Canada’ has taken in respect of Alzheimer’s. T. Sherer will discuss the role of
Foundations in providing needed funding along the drug development pipeline in
PD – using some examples from the MJFF portfolio over the past few years. A.
Comstock Rick will cover the importance of ensuring US government agencies such
as the NIH, FDA and DoD are allocated sufficient funds for research by central
government, the role of government in caring for people with Parkinson’s, and
the role that the Parkinson’s advocacy community has in facilitating this. T.
Isaacs will provide a personal overview of the barriers that exist to more
effectively fund Parkinson’s research and possible methods to overcome them.
Results: The presentations will
be restricted to 12 minutes each. There will be half an hour for questions,
comments and suggestions at the end.
O19
Case presentations
Carolyn M Sue1,
Susan B Bressman2
1Department of
Neurology, Royal North Shore Hospital and University of Sydney, Sydney,
Australia
2
Department
of Neurology, Beth Israel Medical Center, NY, USA
Parkinson’s
disease can be caused by mutations in genes that follow both autosomal dominant
and autosomal recessive inheritance patterns. Also, genetic risk factors for
Parkinson’s disease have been identified. We will discuss case presentations to
demonstrate the basic principles of Mendelian genetics, the significance of a
family history in Parkinson’s disease and the genetic contribution to
Parkinson’s disease.
O20
Overview:
sexual challenges in Parkinson’s and therapeutic options
Paul Rabsztyn1,
Gila Bronner2
1Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
2Sheba Medical Center, Tel Hashomer, Israel
Objective: Motor and nonmotor
symptoms in Parkinson’s disease (PD) can cause many problems in daily
functioning. Intimacy and sexuality can be affected too and have
a significant impact on the quality of life of both the patients and partners.
Sexuality is an important factor of quality of life, but it plays a minor part
in research and patient care. The focus in research and care is primarily aimed
at motor symptoms and problems. Although slightly improving, healthcare
professionals still find it difficult to discuss sexual life with patients and
their partner. Healthcare professionals have a major role in this area. They
can proactively address sexual health issues by providing information, by
recognizing sexual needs of PD patients and partners and also by referring them
to specialists for further treatment. This meeting will discuss changes in
sexual function, in Parkinson’s disease, possible sexual and intimate problems
experienced by PD patients and partners, the therapeutic options and the role
of a multidisciplinary team approach.
Methods: Presentation of PD related sexual problems and the available therapeutic
options. The second part of the meeting has an interactive character during
which case reports will be discussed with the audience.
Results: Healthcare
professionals will increase their awareness of the impact of PD on sexual life
and quality of life of both patients and partners. After this meeting
healthcare professionals will increase their capability to discuss and cope
with sexual aspects of their patients.
O22
Quality of life and comfort in the late stages of
Parkinson's disease
Janis Miyasaki, Lisa Mann
University of Toronto,
Toronto, ON, Canada
Oregon Health and
Science University, Portland, OR, United States
Objective: At the
conclusion of this session, participants should be able to: (1) define key late
stage Parkinson’s disease (PD) symptomatology and treatment problems; (2)
identify biopsychosocial issues for patients and caregivers during these
stages; (3) discuss treatment options for both psychological and physical
comfort during late stage PD; (4) recognize how an interdisciplinary team may
contribute to late stage PD patients and caregivers’ QOL and comfort.
Methods:
Presentation, case study discussion, and panel response to questions by
audience.
Results: Participants
will achieve a better understanding of quality of life and comfort issues
encountered during late stage Parkinson’s disease.
O23
Is there a functional
defect with mitochondrial in Parkinson’s disease?
Miquel Vila1,2,3,4
1Neurodegenerative
Diseases Research Group, Vall d’Hebron Research Institute (VHIR)
2Center for Networked
Biomedical Research on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain
3Department of
Biochemistry and Molecular Biology, Autonomous University of Barcelona (UAB),
Barcelona, Spain
4Catalan Institution
for Research and Advanced Studies (ICREA), Barcelona, Spain
Mitochondria are highly dynamic organelles
with complex structural features that play several important cellular
functions, such as the production of energy by oxidative phosphorylation, the
regulation of calcium homeostasis, or the control of programmed cell death
(PCD). Given its essential role in neuronal viability, alterations in
mitochondrial biology can lead to neuron dysfunction and cell death. Defects in
mitochondrial respiration have long been implicated in the etiology and
pathogenesis of Parkinson’s disease (PD). However, the role of mitochondria in
PD extends well beyond defective respiration and also involves perturbations in
mitochondrial dynamics, leading to alterations in mitochondrial morphology,
intracellular trafficking, or quality control. Whether a primary or secondary
event, mitochondrial dysfunction holds promise as a potential therapeutic
target to halt the progression of dopaminergic neurodegeneration in PD.
O24
Clinical Trials:
Present challenges and emerging breakthroughs
Olivier Rascol
Departments
of Clinical Pharmacology and Neurosciences, CIC-9302/INSERM UMR825, Faculty of
Medicine Purpan, University UPS of Toulouse III, Toulouse, France
The
scope of clinical trials in Parkinson’s disease (PD) has largely enlarged
within the last few years. The objective of new candidates for the treatment of
PD is not any more restricted to the improvement of motor symptoms or motor
complications, but has also expended to the treatment of non motor symptoms
like depression, pain, cognitive impairment, falls... and to the reductive of
the progression over time of symptoms and disability (disease modification).
Moreover, the drugs in development for the treatment of PD are not anymore only
dopaminergic agents, but include also compounds interfering with non dopamine
neurotransmitters, including glutamate, serotonin, noradrenalin, adenosine and
others. In this presentation, Professor Rascol will review the main clinical
challenges to assess efficacy and safety on motor and non-motor symptoms and
disease progression with dopamine and non-dopamine agents.
O25
Practical
solutions to driving, early job loss and relationship issues
Peter
Fletcher
Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, UK
Objectives:
Regarding people with Parkinson’s disease:
To understand the issues affecting driving. To understand
potential employment issues.
To appreciate there may be a variety of ways to maintain family
and social relationships under the broad headline banner maintaining
independence.
To understand a sense of loss can underpin all of these issues and
while expectation may exceed reality, fear may compromise both.
To see all of these issues as major bricks in he wall that is
quality of life.
Methods: People
with Parkinson’s disease (pwp) remain individuals. While the response of each
person to its diagnosis and subsequent progression is bespoke, an expectation
of loss is common. Its nature will vary in breadth and depth but will not infrequently
include the fear of losing one’s driving license, a loss of paid work and most
pernicious and potentially devastating the loss of relationships. These issues
overlap each other and others too. This contribution will explore these major
pillars of quality of life.
Conclusions: The
breaking bad news paradigm of a little often may give not just an opportunity
to temper expectation with reality but in accentuating the positive also find practical
solutions to the issues raised. Planning ahead and asking ‘what if’ questions,
in a disease that progresses over many years, lies at the centre of maintaining
independence in driving, employment and relationships.
O26
Psychological
solutions to dealing with pity, dignity, sense of worth and communication
Diane Cook
Colorado Neurological Institute, Denver, CO, USA
Parkinson’s is characterized as much by psychological and
psychosocial challenges as by physical challenges, and psychological solutions
are increasingly utilized to assist patients in coping with their disease.
These approaches have also shown to be a greater determinant of quality of life
in Parkinson’s patients than the severity of the disease. The role of attitude
and self-efficacy will be explored and their impact on one’s ability to address
the challenges of a progressive, chronic disease, develop and commit to better
health habits, engage in better self-care, and more effectively communicate
with and utilize health professionals. Self-efficacy, which evolved from the
field of cognitive social theory, is the belief in one’s ability to manage
one’s condition, and is being increasingly recognized as a tour de force in
fields such as healthcare. Self-efficacy beliefs influence how we feel, think
and behave. High self-efficacy is characterized by a positive attitude,
proactive approach, high degree of engagement, goal-setting for desired
behavior change, confidence in one’s ability to manage stressors, problem
solving around obstacles, and tenacity and resilience when confronted by
adverse conditions. Achieving a degree of control over one’s condition can
translate into a sense of pride, self-worth, emotional well-being and realistic
optimism, which in turn can lessen the effects of apathy, anxiety and
depression. The three most effective methods for developing self-efficacy
skills will be discussed as well as suggestions for applications in clinical
and support group settings.
O27
Physical
solutions to coping with pain, motor/non-motor, cognition, mood and behavior
Soania
Mathur
Designing A Cure Inc., Toronto, ON, Canada
Objective:
Parkinson’s Disease permeates every aspect of a person’s life.
Once thought of as primarily a movement disorder, it is now apparent that this
illness affects many other systems and that these non-motor symptoms (NMS) are
significant and can be debilitating. Along with a diagnosis of Parkinson’s,
comes potential future disability and quality of life issues. Until there are
better drug treatments and better yet, a cure, management must focus on helping
patients live more fulfilling and comfortable lives; providing them with
physical solutions to cope with some of the less highlighted difficulties seen
in Parkinson’s Disease such as pain, constipation, sleep disorders, sexual
dysfunction, depression, cognitive difficulties and apathy.
Methods: A
comprehensive literature review was conducted using standard search engines as
well as the comprehensive online medical resource, MD Consult which has access
to a wealth of medical journals and publications.
Results: Along with
standard medical interventions, pharmacologic or otherwise, there are ways that
patients themselves can take an active role in the treatment of their disease.
In fact to live well with Parkinson’s patients must be active participants in
their own management. Studies show that an approach to managing pain, in
conjunction with conventional treatment, should include a regular exercise
regimen incorporating passive and active exercises and full range of movement.
Constipation can be mitigated through high fiber diets, increased fluid intake
and again, regular exercise. Sleep disorders benefit from sleep hygiene,
regular bedtimes and wake times as well as other physical measures to make the
bed itself less restrictive. Nutrition, exercise, stress management techniques
and staying involved socially and recreationally help manage mood and
behavioral challenges. These as well as many other practical solutions
addressing NMS to improve quality of life, will be presented.
O28
Memory and attention
issues in Parkinson's disease: clinical characteristics and mechanisms
David Burn
UK
Even
in the earliest stages of Parkinson’s there may be issues with memory and attention,
although these are frequently subtle, and only revealed by detailed
neuropsychological testing. With progression, memory issues may become more
noticeable although, characteristically, are typically less severe than in
Alzheimer’s disease. There is on-going uncertainty as to whether memory
impairment in Parkinson’s relates more to an over-riding executive dysfunction,
so impacting upon effective retrieval strategies, rather than retention issues.
There is likely to be variability in the underlying pathological basis for the
memory impairment (for example, the degree of amyloid pathology in the medial
temporal lobe) and, in turn, this leads to clinical heterogeneity. Attentional
impairment is a defining aspect of the dementia associated with PD. Typically
this can vary from minute to minute. This can be frustrating for the person
with PD and also their family, and has a major impact upon activities of daily
living. The person may appear to sleep excessively during the day, have
sentences that come our jumbled, or appear to stare vacantly into space (“the
lights are on but no-one in”). These observations have been show to predict
fluctuating attention quite accurately. The neural basis for impairment
attention is not fully established but synaptic dysfunction is likely, given
the variability in performance, and cholinergic systems have been implicated.
Cholinesterase inhibitors may lead to gratifying improvements in impaired
attentiveness, and this has been confirmed using a number of different experimental
paradigms. These agents are generally less effective for managing impaired
memory in the face of relatively preserved alertness.
O29
Clinical Assessment of
Cognition in PD
Connie Marras
Morton
and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in
Parkinson’s Research, Toronto Western Hospital, University of Toronto, ON,
Canada
The clinical assessment of
cognition in Parkinson’s disease aims to identify cognitive impairment relative
to normal or decline from an individual’s baseline level of cognitive function
prior to being affected by Parkinson’s disease. These states of impairment have
been classified as either Parkinson Disease - Mild Cognitive Impairment
(PD-MCI) or Parkinson Disease Dementia (PDD). The latest criteria for each will
be discussed, and the instruments or methods to make these determinations will
be reviewed. The evidence for the usefulness of cognitive scales for screening
or diagnosis of PD - MCI or PDD and for assessing longitudinal change will be
reviewed. Finally, there are a number of unmet needs in this area and the next
steps for research in this field will be proposed.
O30
Practical management of cognitive deficits in Parkinson's disease:
what can occupational therapists offer?
Margarita Makoutonina
ParkiLife
Australia Pty Ltd, Melbourne, Victoria, Australia
Objective: Non-motor symptoms (NMS) are identified as a
direct cause of reduced quality of life (QoL) in people with Parkinson’s (PwP)
(Politis et al., 2010). Many of these symptoms and, in particular, cognitive
dysfunctions are not responsive to pharmacological management.
A comprehensive care model with
multidisciplinary teams (MDT) incorporating medical, rehabilitative and
supportive services, is important in preventing the disability amongst PwP
(Bloem, 2010). The purpose of our study was to examine the role of Occupational
Therapist (OT) within MDT and effect of OT’s interventions to optimise
cognitive function amongst PwP, thus to prevent the onset of disability and
improve QoL.
Method: A cohort
of 10 patients with PD was evaluated for cognitive, motor and non-motor
domains. The impact of their cognitive impairment on daily functioning was also
assessed. The results were compared with 10 controls matched for overall age,
gender and education distribution.
The measures undertaken on
admission to the outpatient program demonstrated that at least 75% of
participants described cognitive difficulties with routine daily activities.
Those measures were used for designing the OT specific interventions. The
benefits of OT interventions in optimizing cognition, applicability to practice
and improvement of QoL amongst PwP were assessed on discharge from the program.
Results: It was concluded
that the rehabilitative philosophy and its specific application to the OT
interventions, in addition to evidence based approach, enables OT to obtain a
bigger picture on cognitive related issues and broadens up spectrum of
interventions. Also it was demonstrated that OT’s interventions empowers the
patients, through education and client centered approach, to take ownership in
addressing a variety of cognitive deficits, postpones the earlier development
of disability and improves participation in daily activities.
O31
Animal models of hyperdopaminergic behavior in Parkinson’s disease
Christelle Baunez
CNRS,
Marseille, France
Inactivation
of the subthalamic nucleus (STN) is the current strategy for the treatment of Parkinson’s
Disease. However, using various behavioural tasks assessing non-motor functions
such as attention, impulsivity, compulsivity and motivation, we have shown that
STN lesion or high frequency stimulation can induce a variety of non-motor
deficits that persists in a rat model of Parkinson’s Disease. Among these
non-motor deficits, are hyperdopaminergic-like behaviours (impulse control
disorder, dysfunctional motivation). Interestingly enough, the effects of STN
inactivation on impulsive/compulsive behaviour in the rat can be opposite
depending on the reward obtained in the task: natural reward (such as food) or
drugs of abuse (such as cocaine or heroin) (Baunez et al, 2005, Nature
Neurosci.; Rouaud et al, 2010, PNAS). The presentation will review these
different findings and their contribution to the understanding of
hyperdopaminergic behaviour observed in Parkinsonism and also the latest model
currently developed.
O32
Animal models of sleep disorders in Parkinson’s disease
Ingrid
Philippens
Biomedical
Primate Research Centre (BPRC), Rijswijk, The Netherlands
Objective: Sleep problems are a
common phenomenon in most neurological and psychiatric diseases. In Parkinson
disease (PD), for instance, sleep problems may be the most common and
burdensome non-motor symptoms in addition to the well-described classical motor
symptoms. REM sleep behavior disorder (RBD) precedes PD in one-third of
patients. Since sleep disturbances generally become apparent in the disease
before motor symptoms emerge, they may represent early diagnostic tools and a
research tool to investigate early mechanisms in PD and disease modifying
strategies. Although classic PD motor signs have been studied for
years, it would be ideally that premotor symptomatology, such as sleep, can be
distinguished in animal models. We therefore
investigated sleep changes in a non-human primate model for idiopathic PD, the
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated marmoset
monkey.
Method: Mild parkinsonism was induced in
marmosets (3M/2F) over a 2-week period of subchronic MPTP treatment (total dose
7 mg/kg s.c.). Telemetric electroencephalograms (EEGs) and electromyograms
(EMGs) for sleep analysis were recorded weekly. Motor activity and hand-eye
coordination performance were measured weekly, and clinical signs of
parkinsonism were noted each day. Data of sleep parameters, motor function, and
parkinsonian signs, before and after MPTP treatment, were compared with control
marmosets (1M/3F).
Results:
MPTP increased the number of sleep epochs with high-amplitude EMG bouts during
REM sleep relative to control monkeys (mean ± SEM percentage of REM 58.2 ± 9.3
vs. 29.6 ± 7.7; P < 0.05). Of all sleep parameters measured, RBD-like
measures discriminated best between MPTP-treated and control monkeys. On the
other hand, functional motor behavior, as measured by hand-eye coordination
performance, was not affected by MPTP treatment in the dose used (correct
number of hits 23.4 ± 3.6 vs. control 36.1 ± 5.9; P = 0.32). This REM sleep-specific change, in the absence of profound changes in
motor function, suggests that the MPTP marmoset model of PD can be used for
studies into the mechanisms of sleep disorders in PD and for validation of
early disease modifying treatment in PD.
O33
Animal models of gastrointestinal dysfunction in Parkinson’s
disease
Marie-Francoise
Chesselet
Department
of Neurology, UCLA, Los Angeles, CA, USA
Objective: Gastrointestinal
dysfunction is prevalent in Parkinson’s disease (PD) and symptoms can precede motor
dysfunction by many years. Multiple mechanisms may be involved and these are
not well understood. Treatment is imperfect and would benefit from a better
understanding of mechanisms. This presentation will review results of studies
to model gastrointestinal dysfunction related to PD in rats and mice and what
we have learned.
Methods: Various aspects of
gastrointestinal dysfunction have been analyzed in a variety of toxin-induced
and genetically-based models of PD
Results: Some groups have
reproduced aspects of gastroinstestinal dysfunction seen in patients with PD in
animal models of nigrostriatal dopamine cell loss, suggesting that the loss of
dopamine neurons may contribute to these symptoms. However, other studies have
shown that early gastrointestinal deficits can be produced in animals many
months before any loss of dopamine by overexpressing alpha-synuclein in neurons
that innervatie the digestive system, indicating that local pathology, as
observed in patients with early stages PD, may play a critical role in the
gastrointestinal dysfunction. This suggests that treatments that target
alpha-synuclein pathology (over-expression, aggregation) and/or its local
consequences on gastrointestinal functioning, may provide better relief for the
gastrointestinal symptoms of PD and that some of the genetic models of the
disease provide useful tools to test these new treatments pre-clinically.
O34
Optical neural
engineering
Antoine Adamantidis
McGill
University, Douglas Mental Health University Institute, Montréal, QC, Canada
Objective: Recent developments of microbial
light-sensitive opsins as a tool to manipulate the activity of neural circuits
in the brain have opened new perspectives in systems neuroscience. Optogenetic
technology allows to reverse engineer intact neural circuits by directly
probing the necessity and sufficiency of cellular and topological circuit
characteristics with high-speed optical and cell type-specific perturbations.
We implemented in vivo optogenetics
to probe the modulatory functions of arousal circuits on wakefulness and
goal-oriented behaviors.
Methods: We will detail the development of in vivo optical neural interface combined with
electrophysiological, imaging, and behavioral readout methods.
Results: Using this technology, we established causal link
between activation of genetically targeted neural circuits and the modulation
of arousal and goal-oriented behaviours. In particular, we showed that
activation of dopaminergic neurons in the ventral tegmental area (VTA) facilitates
conditioned place preference, as well as the development of positive
reinforcement behavior during a food-seeking operant task. We further found that phasic activation of dopaminergic neurons
is sufficient to reactivate previously extinguished food-seeking behavior in
the absence of external cues. This was also confirmed using a reversal
paradigm. Collectively, these data suggest that dopamine is sufficient to
assign incentive salience to reward-predicting
cues and participates to cognitive processes during reward-seeking and
behavioral flexibility.
O35
Regulation of Parkinsonian motor behaviors by optogenetic control
of basal ganglia circuitry
Anatol C. Kreitzer1,2
1Gladstone Institutes,
San Francisco, CA, USA
2Depts. of Physiology and
Neurology, University of California, San Francisco, CA, USA
Neural
circuits of the basal ganglia are critical for proper motor function. Two
parallel basal ganglia pathways have been described, which are proposed to
exert opposing influences on motor function. According to this classical model,
activation of the direct pathway facilitates movements/actions and activation
of the indirect pathway inhibits movements/actions. We directly activated basal
ganglia circuitry in vivo, using
optogenetic control of direct- and indirect-pathway medium spiny projection
neurons (MSNs), achieved through Cre-dependent viral expression of
channelrhodopsin-2 in the striatum of D1-Cre and D2-Cre BAC transgenic mice.
Activation of direct- or indirect-pathway basal ganglia circuits yielded
distinct motor behaviors, reminiscent of hyper- or hypo-dopaminergic states.
Moreover, in an operant self-stimulation paradigm, direct pathway activation
reinforced operant responding, while stimulation of D2-expressing neurons was
punishing, demonstrating that direct activation of these circuits is sufficient
to modify the probability of performing future actions. Together, these
findings provide important insights into the circuit basis of motor and
cognitive dysfunction in basal ganglia disease.
O36
Optical interrogation
of the dopamine and reward systems: opportunities for understanding Parkinson's
Antonello Bonci
1Intramural Research
Program, National Institute on Drug Abuse, Baltimore, MD, USA
2Department of
Neurology, University of California San Francisco, San Francisco, CA, USA
3Department of
Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD, USA
4Solomon H. Snyder
Neuroscience Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA
Objective: The dopaminergic neurons,
originating in the ventral tegmental area (VTA) and projecting to forebrain
areas, including the amygdala, prefrontal cortex, and nucleus accumbens (NAc)
are essential for the manifestation of goal-directed behavior for both natural
rewards as well as drugs of abuse, including ethanol. My laboratory has spent
the past several years to elucidate the role of plasticity at excitatory
synapses in the VTA in physiological and pathological behaviors, such as
reward-related learning, motivation and substance abuse.
Methods: Recently, my
laboratory has been using a
multidisciplinary
approach combining electrophysiology, optogenetic and behavioral procedures to
better investigate the role of the dopaminergic signaling on substance use
disorders.
Results: During my presentation
at the World Parkinson Congress, I will show the most recent optogenetic
studies from my laboratory focused on the use of optogenetics in understanding
the motivational system and highlight the implication for Parkinson’s disease.
O37
Overview: What is genetics?
Carolyn M Sue1,
Susan B Bressman,2
1Department of
Neurology, Royal North Shore Hospital and University of Sydney, Sydney,
Australia
2Department of
Neurology, Beth Israel Medical Center, NY, USA
Genetics,
or the study of genes (derived from the Greek word for “origin”) has
revolutionized the clinical approach to many common neurodegenerative diseases,
including Parkinson’s disease.
Genetic
studies provide insights into inheritance patterns of diseases that are passed
on from parents to children. Genetic causes of Parkinson’s disease were
originally discovered using techniques known as genetic linkage and DNA
sequencing; methods that allow investigators to locate which regions of the
gene are responsible for causing disease. We now know that Parkinson’s disease
can be caused by mutations in genes that follow both autosomal dominant and
autosomal recessive inheritance patterns.
In
addition to identifying monogenic forms of Parkinson’s disease, newer technologies
such as genome-wide association studies (GWAS) and next-generation sequencing
(NGS) have further identified genetic risk factors that increase an
individual’s risk of developing Parkinson’s disease and other genes that cause
Parkinson’s disease. Only a small fraction of patients with Parkinson’s disease
have monogenic causes. However, clinicians should be aware of related
phenotypes to enable genetic counseling to affected families. Furthermore,
identification of causative genes and genetic risk factors of Parkinson’s
disease has provided insights into the molecular mechanisms that lead to the
development of commoner forms of Parkinson’s disease. We now understand that
disturbances in pathways involved in protein clearance and mitochondrial
function play a critical role in the degeneration of neurons in Parkinson’s
disease. We conclude that genetic studies using new technologies greatly
enhance our ability to identify new causes of Parkinson’s disease and
contribute to our understanding of disease mechanisms that play a role in this
disorder.
O38
What we all can learn
from each other - international advocacy
Linda Morgan1, Steve DeWitte2, Tom Isaacs3
1Parkinson's Disease Foundation Research Advocate, PCORI Reviewer,
PCORI Prioritization Study Group, Asheville, NC
2Parkinson's Patient Advocate ; President / Keep the Faith
LLC;Founder / Parkinson's Young On Set Support Group of CT Inc., New Preston,
CT USA
3The
Cure Parkinson’s Trust, President and Co-founder, London UK
Objective:
Traditionally, people with Parkinson's disease (PwP)
have participated in research as the subject of
trials. New treatments and therapies exist because of these volunteers. Theirs is
a very important yet undervalued role as statistics show that 1% of individuals
with the condition enroll in a trial. 80% of research trials are delayed due to
a lack of volunteer participation. This workshop will 1) review considerations
of how to become involved in clinical research including the questions to ask
2) review misnomers that may keep PwP’s from enrolling 3) describe the need for
a greater and unified patient engagement with the design and the outcome
measures of trials to accelerate the availability of Parkinson’s therapies 4) and suggest a new model for accelerating
Parkinson’s trials.
Methods: Three
individuals with Parkinson's and experience with clinical trials will speak.
Between the three of them they have participated in more than 40 trials. S
DeWitte will discuss dilemmas with clinical trials; how to find and how to get
involved. L Morgan will lead us away from direct trial participation
and discuss our emerging roles and influences on the research process
and how we can all benefit from that research-patient partnership. Lastly, T
Isaacs whose organization has been responsible for funding several clinical
trials, will give us an international perspective and suggest a new model for
accelerating available new treatments.
O40
Overview: Innovations
in neuroscience technologies as they apply to finding target molecules to the
point of pre-clinical studies
Howard Federoff, Salim
Shah, Habtom Ressom, Linda McArthur
Georgetown
University Medical Center, USA
Objective: Parkinson’s disease is a movement disorder
driven principally by the progressive and slow death of dopaminergic neurons in
the pars compacta of the substantia nigra with the concomitant formation of
α-synuclein containing intracellular inclusion bodies. There is no unifying
mechanism for the disease, and while symptoms may be relieved with drugs that
increase dopamine levels or with devices for deep brain stimulation, there is
no effective therapy to halt the progression of the disease. Therefore, to
develop therapeutics intervention for PD, there is a need to better understand
how the risk factors, both genetic and environmental, contribute to the onset
and progression of the disease.
Problem: Current
efforts in this direction are based on “omics” data acquisition and analysis
from patient samples (protein, mRNA, microRNA, lipids, metabolites, DNA
methylation sites) and identify effector molecules of therapeutic and/or
predictive value. To understand relationship between diverse effector
molecules, one approach is to predict biological networks and identify
potential causal relationships- directly or indirectly related to either a
known target or a known effect. Building networks and identifying nodes in
networks is first step but the significant challenge lies in nodes
prioritization according to their role in disease progression.
Results: An effect-centric
network validation approach with respect to the genes such as α-synuclein,
tau, parkin, and LRRK2 and modulating their expression using combinatorial
siRNA approach and monitor their effects on neuronal cell death. Additionally,
we propose that the approach to study global gene expression, and building a
network that could causatively relate to observed phenotypic effects observed
in the disease.
O41
Use of Reiki as a
complementary therapy to help those living with Parkinson's disease (PD) and
carepartners/caregivers
Angela Robb
PD
Carepartner & Reiki Master, GiveReiki.com
Objective: To share my knowledge
as a Parkinson's disease (PD) carepartner/caregiver and Reiki Master about how
the use of Reiki as a complementary therapy can benefit those living with
Parkinson's disease and their carepartners/caregivers. I will educate the workshop
audience about:
1) What is Reiki?
2) How Reiki can benefit
those living with PD and carepartners/caregivers.
3) Share my personal
anecdotal evidence, articles, and student feedback of the benefits of Reiki.
Methods: I will use a
PowerPoint presentation to share this information. I will also provide handouts
either via paper or electronically to those who attend the presentation. I will
also be available to take questions from the audience about Reiki. I will share
my personal experiences as a fourteen year Reiki practitioner and two years as
a Reiki Master. I will describe how I've worked with those within the PD
community to train them to use Reiki to help themselves. I will also explain
that Reiki is not a mono-therapy for PD but part of a PD self-care plan. I will
encourage carepartners that Reiki is an excellent practice to cope with being a
carepartner, improve carepartner health, and enhance their own self-care plan.
I hope to dispel any Reiki myths or mysteries.
Results: To have the workshop attendee to come away
with a general understanding of how Reiki can be used to enhance and complement
their current self-care strategies. My goal is to encourage attendees to learn
more about Reiki, find a practitioner in their area and learn how to use Reiki
to help themselves.
O42
Is there a role for
gene- and cell-based therapies in the treatment of Parkinson disease?
Stephane Palfi
APHP/Paris University, Créteil,
France
Oral dopaminergic treatments have remained the primary
standard of care for Parkinson’s disease (PD) for the last 40 years. Although
highly efficacious in the early stages of disease they are associated with
debilitating long term side effects that impact on the quality of life and
restrict the longevity of such treatment. The severity of PD, lack of a cure
and the limited long term effectiveness of current therapies allow for the
consideration of novel therapeutic approaches based on cell and gene therapies.
The purpose of the presentation is to describe the current statut of different
therapeutic approaches aiming at restoring local and continuous release of
dopamine or delivering neurotrophic factors to restore and protect dopaminergic
neurons from degeneration.
O43
Sleep, fatigue, and apathy in Parkinson’s disease
Nico J Diederich
Department
of Neuroscience, Centre Hospitalier de Luxembourg, Luxembourg-City
Reduced
sleep quality is among the five most cited complaints in PD patients.
Large-scale studies have shown that almost half of all PD patients suffer from
sleep problems. Confusing terminology.
The terms apathy, fatigue, exhaustion and sleepiness are often uncritically
interchanged. Apathy or lack of drive may already be encountered at the stage
of idiopathic REM sleep behaviour disorder. Apathy is neither synonymous nor
necessarily associated with depression. By “fatigue”, the patient often
expresses exhaustion due to motor and non motor “off”-periods. Paradoxically,
sleepiness during the day with non refreshing naps is combined with longer
night-time sleep. Multiple primary or
disease-inherent causes. Neuropathology has convincingly demonstrated that
several nuclei in the brainstem regulating sleep/wakefulness are primarily
affected by disease propagation, among them nucleus pedunculopontinus, locus
coeruleus and Raphé nuclei. PD patients show a reduction of hypocretin neurons
in the hypothalamus. Finally, secondary dysfunction of the thalamocortical
arousal system has been postulated. Intertwining
of secondary causes. Exhaustion due to motor impairment and dysautonomia
further exacerbates the soporific effects of the medication. This interplay of
multiple factors renders identifying the underlying cause complex. Pragmatic treatment. Despite this causal
complexity of apathy and sleep problems, a scrutinized exploration should
nevertheless search for the predominating syndrome. Focused pragmatic therapy
mostly relies on established general treatment strategies as randomized
controlled trials (RCT) are rare and the Quality standards Subcommittee of the
American Academy of Neurology has not given a single level A recommendation.
Recently, however, several RCT have shown that long-acting dopaminergic
stimulation, while abating nocturnal akinesia, also improves subjective sleep
quantity. One RCT suggested treating insomnia in PD with eszopiclone. The use
of stimulants during daytime is not supported by RCT. The long-term effect of
disease modifying agents on sleepiness is unknown. Thus, evidence based
therapeutics remain limited.
O44
Table #1: Speech
Pathology & Parkinson's
Lorraine Ramig
University
of Colorado-Boulder, National Center for Voice and Speech-Denver, Columbia
University-NYC, LSVT Global-Tucson
Speech
and voice disorders are key elements in the diagnosis and management of
individuals with Parkinson Disease (PD). Nearly 90% of individuals with PD will
have these problems with the classic voice symptoms of reduced loudness,
monotone and hoarse voice appearing early in the course of the disease, and
imprecise articulation and rate problems occurring as the disease progresses.
Such symptoms contribute to frustration, embarrassment and social isolation and
as such have a negative impact on quality of life. The complex origin of these
disorders includes motor problems
(hypokinesia/bradykinesia reflecting reduced muscle activation and reduced
movement scaling), sensory problems (resulting
in abnormal perception of one’s own voice) and cueing problems (reflecting deficits in internal/implicit cueing).
Historically, speech disorders in PD have been unresponsive to speech or
medical treatment. However progress has been made in the treatment of speech in
PD. In this session, speech treatment for PD will be described with special
emphasis on the Lee Silverman Voice Treatment (LSVT® LOUD), an
intensive, exercise-based intervention, which is a PD-specific,
neuroplasticity-principled, standardized protocol. The recommendation is made
for early referral to efficacious
speech treatment and continued life-long practice for optimum management of
speech and voice disorders in PD. Advances in access to treatment through
technology (telemedicine and software) will be discussed.
Financial Disclosure: Research supported
in part by NIH-NIDCD R01 DC01150, R21 DC006078, R21 NS043711, Michael J. Fox
Foundation, Parkinson Alliance, Davis Phinney Foundation)
O45
Table #2: Physical
therapy & Parkinson's: Can it really help?
Terry Ellis
Boston University, Boston, MA, USA
In this roundtable session, participants will become
more informed regarding the benefits of physical therapy and exercise. In
addition, participants will gain an appreciation of the role that physical
therapy can play in the management of Parkinson’s over the course of the
disease. The evidence demonstrating the benefits of physical therapy and
exercise for persons with Parkinson disease will be summarized and the impact
on reducing disability, improving physical function and enhancing quality of
life will be reviewed. In addition, the key elements of an exercise program
will be explored. The importance of long-term adherence to exercise and
adopting an active lifestyle to optimize outcome will also be emphasized.
Practical tips for integrating increased activity levels in daily life will be
shared. This session will also include a discussion of the nature of the
treatment provided by physical therapists and the goals of physical therapy
intervention. Optimal timing and frequency of physical therapy intervention
will also be considered. This session will culminate in a discussion of how to
benefit most from physical therapy intervention.
O46
Table
#3: Blogging and Parkinson's: How people with Parkinson's can educate and raise
awareness via blogging
Bob Kuhn1,
Jean Burns2
1Positively Parkinson’s
(Blogspot), Canada
2www.PDPlan4life.com
(website) and PDBLOGGER (WordPress), USA
Objective: Provide both general
and detailed information about blogging and how it is being used within the
Parkinson’s community. Our ultimate goal is to encourage collaboration among
bloggers and to create a new group of bloggers who will become founding members
of something new: World Parkinson Congress “Blog Partners.”
1.
Blogspot:
Positively Parkinson’s Bob Kuhn
2.
WordPress:
PDBLOGGER Jean Burns
3.
Website:
www.pdplan4life.com Jean Burn
Methods: We will start by
questioning the round-table attendees. It may be that some attendees may be
experienced, and others may be totally new to blogging. After initial Q&A,
Bob and Jean will decide if they should split the attendees into two groups according
to experience, or need, or some other criteria.
We
will be prepared to cover the following topics:
Goals
Basic
“how to”
Blogspot
WordPress
Collaborating
Tips
and Tricks
Statistics
– how to increase your readership
Dangers:
legal liability
We
will provide quick reference (QR) guides on these topics. The QRs will be
displayed on laptop or IPad. We will provide links so the attendees can
download the documents.
Results: An enthusiastic cadre
of Parkinson’s bloggers, who will become the founding members of a new group:
“WPC Blog-Partners.” This will help shrink the Parkinson’s community by
encouraging greater communication through the Internet. Bloggers will have the
additional benefit of living intentionally.
O47
Table #4: What to ask
before joining a clinical trial: PwP to PwP
Israel Robledo1,
Jon Stamford2
1USA
2UK
Objective: To give background
information on the research process from the patient perspective and discuss
questions to ask before joining a clinical trial that will allow for quality
involvement in the process.
Methods: Given the fact that clinical trial participation within the
Parkinson’s Disease community, reasons to participate in clinical trials will
be presented. Beginning with patient safety during the course of a trial, time
commitment, what to expect during a trial, being able to stop participation at
any point in the trial, and asking about trial results when a trial is
completed, to finding about trial outcomes when a trial is cancelled.
Participants will be given the opportunity to ask questions about their
concerns with clinical trial participation.
Results: Participants will be able to decide if clinical trial participation is
right for them based on the information presented during the session.
O48
Table #5: Young Onset Parkinson's: Unique Challenges
Peter Davison
Person
with Young Onset Parkinson's, Bedford, NS, Canada
Objective: The purpose of understanding the unique
challenges and opportunities facing young onset Parkinson's folks is to improve
the effectiveness of outreach, offer appropriate wellness and lifestyle
strategies and increase support group attendance. Participants will be invited
to share their insights and personal experiences as they learn how to set up
sustainable and relevant young onset groups and teleconferences. This session
is recommended for young onset participants, support group leaders and
organizations who want to improve their outreach to persons with young onset Parkinson's.
O49
Table #6: Psychiatric Changes in Parkinson's disease
Laura
Marsh
Michael E.
DeBakey VA Med Center/Baylor College Medicine, Houston, TX, USA
Objective:
To describe psychiatric changes in Parkinson’s disease (PD) and
approaches to their recognition, monitoring, and treatment.
Methods: This
Roundtable will begin with an overview of the prevalence of the various
psychiatric conditions that can occur in individuals with PD. The general and
distinguishing characteristics will be discussed as well as pharmacological and
non-pharmacological treatments.
Results: Up to 80%
of individuals with PD experience psychiatric changes over the course of their
disease. These disturbances include mood and anxiety disorders, psychosis, and
behavioral changes such as apathy or impulse control disorders. Often, these
have a greater impact on quality of life than motor dysfunction and compound
the severity of PD-related motor and cognitive dysfunction. Since effective
treatments are available, early recognition and aggressive treatment of
psychiatric symptoms is critical to comprehensive management of PD.
Accordingly, individuals with PD, their families, and carers should be aware of
the potential for psychiatric changes and monitor in an ongoing fashion.
O50
Table
#7: Sex & Parkinson's disease
Gila Bronner
Sex
Therapy Service, Sexual Medicine Center
Sheba
Medical Center Tel-Hashomer, Israel
gilab@netvision.net.il
Objectives: To enable the
participants an opportunity to discuss openly sexual issues, evaluate their
etiology and learn about adequate solutions.
Methods: A healthy sex life
plays an important role in quality of life and the quality of relationships. If
one partner in a relationship experiences problems with intimacy, sensuality or
sexual activity, it is likely to impact on the sexual enjoyment of the other
partner. Consequently, resolving such difficulties can improve sexual
satisfaction. People with Parkinson’s disease (PD) and their partners have to
cope with multi-faceted challenges regarding their sensuality, intimacy and
sexuality. Sexual difficulties can be associated with motor and non-motor
symptoms of PD, all of which can impact on self-esteem, quality of life, mood
and relationships. Sensual perception and intimate communication may be
affected by the physical and emotional changes PD may bring, and a less active
and enjoyable sex life may result.
Results: This “Meet the expert”
session will present the essence of sex therapy and treatment of sexual
dysfunctions. The field of sex therapy is relatively new. Many people are
unaware of the extensive support and variety of treatments and solutions that
they can gain from a sex therapy session. Participants will be able to discuss
with the expert most frequent sexual problems in PD (e.g. decreased sexual
desire, increased sexual desire (hypersexuality), arousal problems, lack of
lubrication, erectile dysfunction, premature ejaculation, difficulties to reach
orgasm, sexual pain and sexual dissatisfaction). This session will provide an
opportunity to discuss sexual issues openly in a comfortable atmosphere. No
personal questions will be asked. On the other hand, those who wish to raise
specific questions, will get an opportunity for a professional evaluation and
adequate solutions. Such difficulties can place an additional strain on couples
who live with PD and a proper intervention can relieve the stress.
O51
The spectrum of
non-motor symptoms in PD
K. Ray Chaudhuri
Parkinson
Centre of Excellence, London, UK
Non-motor
symptoms of Parkinson’s disease (NMS) are the leading cause of poor quality of
life for both people with Parkinson’s and their caregivers. The slowness,
stiffness and tremor of Parkinson’s disease (PD) are well known, but non-motor
symptoms afflict more Parkinson’s patients. Though NMS affect every patient,
they are under-recognised and under-treated. In a Parkinson’s UK survey, members rated symptoms such as sleep
disturbance, pain, constipation, urinary problems and dizziness as more
debilitating than their motor symptoms. Hospitalisation from PD is most likely
to have been caused by NMS. This loss of independent living has devastating
social and economic consequences. Despite the profound and negative effects of
NMS, there is a dearth of research into causes and therapies. Treatment remains
poor and quality of life progressively deteriorates. The National Institute for
Health and Clinical Excellence (NICE) and Parkinson’s UK have identified the
recognition and treatment NMS across all stages of PD as a key unmet need.
Little research explores the cause and progression of common NMS because
funders have focused their attentions elsewhere. An integrated and interactive
combination of clinical and laboratory-based investigation is required that
will focus on the causes and consequences of sleep disturbance, pain and
autonomic dysfunction in PD. Using imaging and post-mortem brain tissue to
identify the areas of the brain responsible for NMS, we are developing models
of the disease that will increase our understanding of the origin of neglected
NMS of Parkinson’s and provide a test bed for devising effective treatments.
This
research promises to increase our understanding of the effects of PD on the
brain in order to uncover the underlying causes of NMS. This research will lead
to advances in the detection and treatment of NMS, thereby improving the
quality of life of millions of people with Parkinson’s, both today and in the
future. By exploring the practical clinical issues that are the biggest hurdle
to the improvement of the symptomatic treatment of PD, we will begin to solve
the NMS enigma.
O52
Dementia and
psychiatric manifestations in PD
David Burn
UK
Some
people with Parkinson’s disease (PD) may exhibit early cognitive deficits,
increasingly referred to as mild cognitive impairment (PD-MCI), which do not
evolve to PD dementia (PDD), or do so over an extended period of time. PD-MCI
is common in non-demented PD and includes a spectrum of deficits, ranging from
so-called single domain (e.g. non-amnestic) to multiple domain impairments.
Overall, non-amnestic, single-domain impairment is the most common PD-MCI
subtype encountered. Probably because of improved management of motor problems
and secular trends in life expectancy, up to 80% of people with PD may
eventually develop dementia. Features commonly associated with PDD include
fluctuating levels of attention and visual hallucinations. Anti-psychotic
medications have a very limited place at present in the management of PDD.
Although drugs like cholinesterase inhibitors can improve several symptoms,
this remains an area of major unmet therapeutic need. (Neuro)psychiatric
manifestations of PD may precede the diagnosis; so mood disorder, for example,
is well documented to predate motor symptoms. During the course of PD
psychiatric features may wax and wane, often being under-recognised by both the
person with PD and/or their physician. Despite this, psychiatric symptoms
frequently have a greater impact upon quality of life than motor features. The
spectrum includes depression, anxiety, apathy, fatigue, hallucinations and
delusions. They commonly occur together; for example, anxiety and depression
frequently co-exist. In contrast to the cognitive aspects, many psychiatric
symptoms may be effectively treated, so recognition is important, given the
potential impact upon the person and their family. In terms of evidence-base,
there have been remarkably few randomized trials of any size evaluating, for
example, antidepressants in the context of PD. Non-drug therapies such as
cognitive behavioural therapy or exercise should be considered, and also
require further evaluation.
O53
Contribution of
functional neuroimaging to the understanding of non-motor manifestations of PD
Antonio P. Strafella
University
of Toronto, Canada
In
the last few years, Non-motor symptoms like cognitive dysfunction and impulse
control disorders are increasingly been reported in Parkinson’s disease (PD)
patients. Given the social implications, these disorders represent a cause of
significant distress not only for the patients but mostly their families. To
date, the mechanisms underlying cognitive abnormalities and behavioral
addictions in PD are poorly understood. Proposed mechanisms include abnormal
functioning of nigrostriatal and mesocorticolimbic networks resulting in a
dysregulation of dopamine.
O54
The challenge of
'prodromal' Parkinson's disease
Ronald B.
Postuma
Montreal
General Hospital, McGill University, Canada, Hopital du Sacre Coeur, Universite
de Montreal, Canada
Parkinson's
disease, like almost all neurodegenerative diseases, does not start suddenly.
This implies a period during which subclinical degeneration is present, but has
not crossed the threshold to full clinical presentation. In addition,
Parkinson's disease has the unique feature of an additional prodromal period
that is mostly characterized by non-motor symptoms. This prodromal interval
provides an opportunity to detect disease several years before full clinical
symptoms, and could eventually lead to neuroprotective therapy to prevent
clinical disease.
Recognition
of this prodromal period has led to concerted efforts to define prodromal PD,
and perhaps even to change the definition of PD. Both population-based studies
and at-risk cohorts have been created to assess prodromal disease. The
advantages and disadvantages of each will be discussed. These studies have
begun to provide clear directions as to how to identify prodromal PD, including
the identification of non-motor clinical markers (olfactory loss, REM sleep
behavior disorder, color vision loss, autonomic dysfunction, etc) and
neuroimaging markers (dopaminergic functional neuroimaging, transcranial
ultrasound, etc). Current evidence for the utility of these markers will be
summarized, particularly focusing upon their specificity and positive
predictive value. Finally, the work of the Movement Disorders Society task
force on definition of PD, which includes development of a prodromal PD
definition, will be introduced.
O55
Redefining Parkinson's
disease: possible approaches to developing new diagnostic criteria
Daniela Berg on behalf
of the task for “Definition of Parkinson’s disease” of the MDS
Department
of Neurodegeneration, Hertie-Institute of Clinical Brain Research and German
Center for Neurodegenerative Diseases, Tübingen, Germany
Objective: To summarize the
various factors that will need to be taken into account in developing new
diagnostic categories/criteria.
Methods: In 2011
the Movement Disorders Society established a task force on the definition of
Parkinson’s disease. Critical issues the group has been working on are:
A) What is essential
for the diagnosis of PD?
B) How can diagnostic
criteria account for subtypes?
C) Can PD be defined
before the classic motor features develop?
Results: Several current findings in different fields of PD research seem neither
compatible with other fields of research nor with the current gold standard of
PD diagnosis. To fill knowledge gaps in an unbiased way a three tiered approach
with a clinical, pathology and genetic tier is proposed, which does not commit
to insisting on a specific clinical syndrome or a specific pathology and permits
incorporation of new information as it becomes available. More specifically
approaches will include
(i)
for
the clinical tier to:
-
create
models to group subtypes
-
better
characterize non-motor symptoms and develop algorithms for earlier diagnosis
(ii)
for
the pathology tier to:
-
create
models that include formation, site and mechanism of alpha-synuclein pathology and
account for PD cases without classical Lewy bodies and Lewy bodies in
individuals without PD
-
recognize
way and direction of spreading of pathology
(iii)
for
the genetic tier to:
-
group Mendelian
forms into mechanistically homogenous categories by elucidating molecular
mechanisms also up- and downstream
-
understand
how common and medium risk variants can contribute to the differentiation of
subgroups of PD patients
Imaging may constitute a bridging element of the pathology,
genetic and clinical tier. Here, development of a ligand that permits
imaging of brain and extra-cerebral alpha-synuclein in vivo and identification
and validation biochemical markers mirroring the pathological process will be
essential.
O56
Prototypical and less
common hallucinations
Regina Katzenschlager
Department
of Neurology, Donauspital / SMZ-Ost, Vienna, Austria
Hallucinations
are typically associated with advanced stages of Parkinson´s disease (PD) and
after 10 years´ disease duration, they have been foundin 60% of PD patients. However,
a minority of patients develop hallucinations on their first antiparkinsonian
treatment and the presence of dementia is not strictly required for the
formation of hallucinations. Once they do occur, however, the risk of
subsequent dementia is considerably increased.
The
most common form of hallucinations in PD is visual. Patients may initially have
the feeling of a person´s presence in the room, or they may perceive inanimate
objects as animals or persons, movements where there are none, or changes in
patterns or colour. These visual misperceptions may preceed frank
hallucinations, which do not have a basis in reality, but hallucinations may
occur without prior illusions. Visual hallucinations are typically well-formed,
often involve persons or animals and often consist of repetitive scenes.
Non-visual hallucinations rarely occur in isolation and are usually associated
with advanced PD. Patient with marked visual hallucinations may have auditory
or, less commonly, tactile hallucinations as well, for example, they may hear
their imaginary visitors speak and may then interact with them. Initially,
patients often retain at least partial insight into the nature of their
misperceptions but this tends to get lost over time. Mild and moderate forms of
hallucinations may go almost unnoticed by the care-givers as patients are not
always bothered by them or do not mention them due to embarrassment.
Nevertheless, hallucinations have a clear tendency to progress over time, they
are an important indicator of possible future dementia and their presence
guides the choice of antiparkinsonian drugs. They may lead to delusions, which
usually have a dramatic impact on the patients´ and care-givers´ quality of
life. For all these reasons, hallucinations should be routinely enquired about.
O57
Where is the nucleus
hallucinatorius and how it gets stimulated?
Nico J
Diederich
Department of Neuroscience, Centre Hospitalier de Luxembourg,
Luxembourg-City
Approximately
one third of PD patients suffer from hallucinations. The breadth of the
phenomenology is remarkable, ranging from illusions, minor hallucinations of
passage or presence, to vivid scenery, multisensory hallucinations and
full-blown secondary paranoid psychosis. After a phase of pseudo-benign
hallucinations, there is usually intractable progression over the years.
Unimodoal models of pathogenesis have focused on levodopa psychosis, sleep/wake
dysregulation and visual impairment, among others. While there is fruitful
clinical applicability of these models, none has succeeded in identifying a
single nucleus or network responsible for hallucinations in PD. In contrast,
theoretically conceptualized models embracing multiple domains, such as the
Perception and Attention Deficit model (PAD) and the
Activation-Input-Modulation model (AIM) by Hobson have been largely confirmed
by recent clinical and neuroimaging data. Indeed patients with hallucinations
demonstrate simultaneous impairments in several domains, especially in terms of
sustained attention and complex visual processing. Within the hypothesis of
default network dysfunction several nodes of breakdown have also been posited.
It is thus no surprise that diffusion tensor imaging, successfully applied in
schizophrenia, is a new strategy to be applied in PD hallucinations. To date,
reduced fractional anisotropy in parieto-occipital white matter tracts has been
documented along with neuropathological demonstration of multiple areas with
high burden of Lewy bodies, such as the amygdala and the cholinergic
neocortical areas of the temporal lobe. Other areas within attention loops and
primary and secondary visual pathways remain to be examined in detail, in the
quest for the Holy Grail of one “nucleus hallucinatorius”.
O58
Mitochondrial quality
control: a matter of life and death for neurons
Heidi M.
McBride
Montreal
Neurological Institute, McGill University, Montréal, QC, Canada
Objective: Mitochondrial dysfunction has been
increasingly implicated in the development of neurodegenerative diseases,
including Parkinson’s disease. There are 3 established mechanisms that regulate
mitochondrial quality control pathways, including the action of mitochondrial
proteases, retrotranslocation of substrates for degradation in the proteasome,
and the entire removal of organelles through mitochondrial autophagy, or
mitophagy. At least two distinct Parkinson’s disease genes coding Parkin and
PINK1 are required for mitophagy, suggesting that mitochondrial quality control
is interrupted in patients with PD. I will describe a fourth pathway in
mitochondrial quality control, which is the removal of selected, damaged
mitochondrial content through a vesicular transport route.
Methods: The experiments presented will include imaging and biochemical
approaches to establish the generation, content and fate of mitochondrial
derived vesicles (MDVs). Using siRNA and other molecular biology approaches we
address the functional contribution of PD and other genes in these pathways.
Results: The data
outline a novel pathway for mitochondrial quality control, and identify new
functions for PD genes in the generation of MDVs.
O59
Mechanisms of
mitophagy in Parkinson's disease
Charleen T. Chu1,
Hülya Bayır2,3 and Valerian E.
Kagan3
1Department of
Pathology, Pittsburgh, PA, USA
2Department of Critical Care Medicine, Pittsburgh, PA, USA
3Department of Environmental and Occupational Health, University of
Pittsburgh, Pittsburgh, PA, USA
Objective: Dysregulation of mitochondrial autophagy has
been implicated in sporadic and familial Parkinson’s disease. A key feature of
mitophagy regulation is the ability to selectively recognize damaged
mitochondria for autophagic degradation. These studies were designed to
elucidate the nature of “eat-me” signals expressed by damaged mitochondria in
neurons.
Methods: As decreased complex I activity may contribute to Parkinsonian
neurodegeneration, we utilized low-dose treatments with rotenone or other
parkinsonian toxins to induce mitophagy in primary cortical neurons and SH-SY5Y
cells. A combination of fluorescent imaging, immunochemistry, mass
spectrometry, site directed mutagenesis and computational methods were used to
study changes in mitochondrial surface phospholipid composition and potential
interactions with the autophagy protein microtubule-associated protein 1 light
chain 3 (LC3). In some studies, the expression of PTEN-induced kinase 1 (PINK1)
was manipulated to determine its functional relationship to mitophagy pathways
stimulated by complex I inhibitors.
Results: Our data indicate that multiple mitophagy-inducing injuries
trigger the externalization of cardiolipin, which targets damaged mitochondria
into autophagosomes by direct binding to LC3. Unlike HeLa cells, which can
tolerate complete clearance of mitochondria, we found that elevated levels of
mitophagy cause dendrite retraction in toxin and dominant genetic models of PD.
Residues of LC3 that are involved in binding cardiolipin are located adjacent
to a phosphorylation site that we previously identified. Mimicking LC3
phosphorylation reduced mitophagy and protected against dendrite retraction.
These data suggest that a proper balance of mitophagy activators and brakes are
essential for maintaining neuron health.
O60
Mitochondrial
remodeling in the control of apoptosis
Luca Scorrano1,2
1University of Padova, Padua, Italy
2Dulbecco-Telethon
Institute, Venetian Institute of Molecular Medicine, Padua, Italy
Objective: Mitochondrial ultrastructural and
morphological changes have been implied in the control of several physiological
and pathological changes, including the progression of apoptosis. However, the
precise role of mitochondrial dynamics in the response to reversible and
irreversible cellular damage is not completely understoodOur data indicate that
the shape of mitochondria dictates function of the organelle and therefore
complex tissue responses, opening the possibility for treatment of pathological
conditions where mitochondrial dysfunction plays a crucial role.
Methods: Today we will present our recent data obtained in genetic models
of ablation and up-regulation of the key mitochondrial shaping proteins Optic
atrophy 1 (Opa1) and mitofusin in D. melanogaster and in the mouse. The in vivo
experiments of tissue damage by inducing atrophy, apoptosis or
ischemia/reperfusion indicate that the master cristae biogenetic regulator Opa1
can prevent multiple forms of tissue damage by controlling mitochondrial
cytochrome c release and metabolic efficiency. On the other hand, the interplay
between mitochondria and the endoplasmic reticulum is highlighted by the
ablation of the multifunctional mitofusin of the fruitfly, that results in the
development of ER stress that
contributes to the lethality of the phenotype.
Results: Our data
indicate that the shape of mitochondria dictates function of the organelle and
therefore complex tissue responses, opening the possibility for treatment of
pathological conditions where mitochondrial dysfunction plays a crucial role.
O61
Why and
how people with Parkinson's need empowerment - Finding your own niche
Fulvio Capitanio
Unidos contra el Parkinson,
Barcelona, Catalonia, Spain
Objective: What is
patient empowerment?
Patient empowerment is simply a process to help people gain control,
which includes people taking the initiative, solving problems, and making
decisions, and can be applied to different settings in health and social care,
and self-management.
This is only a definition of patient empowerment.
The questions now are: Do PwP really need to be empowered, and
how?
Methods: Since we were child we
were constantly learning and preparing ourselves to live an adult productive
life as part of the mechanism that runs our society.
We
developed a set of skills, we acquired and enriched a tool box perfectly
designed to commit our tasks. Unfortunately nobody prepared us to face a
breakthrough event like the diagnosis of Parkinson’s disease. We need to adjust
our skills, to learn different ways to use the tools we already have, to acquire
new abilities and to renew out toolbox.
Results: The
benefit of empowered patients is particularly true for
chronic diseases, the treatment or management of which have been moved
gradually from the doctor’s office or hospital to the patient’s day-to-day
life. While this gain in independence is a blessing for affected patients and
can dramatically increase their quality of life, it also means that patients
need to take a more active role in the management of their condition, from
lifestyle changes to the use of medical devices and implementation of therapy
adjustments following discussion with their doctor or nurse.
O62
Evidence-based
self-management practices
Patrick McGowan
University
of Victoria, Victoria, BC, Canada
Over
the last 30 years there has been a growing perception that people experiencing
chronic health conditions are capable and should participate in managing their
health, and the notion of “patient as the passive recipient of care” is not
appropriate. The aging population, increasing prevalence of chronic conditions,
burgeoning costs of providing health care, and focus on quality of life have
further accentuated this perception. Chronic disease management has emerged as
a viable paradigm of care and patient activation and self-management support
are integral components in this model. With the acknowledgement that persons
with chronic conditions mainly manage on their own, patient education began
including behavioral change interventions, competency in problem-solving and
“empowerment” enhancing strategies. Self-management programming focussing on
skill and confidence development emerged and became popular across the spectrum
of health conditions. This presentation will provide an overview of the
emergence of self-management programming and the theoretical and research
studies conducted over the past decade. Self-management support strategies
provided by health professionals during clinical care represent another viable
mechanism of developing informed and activated patients and will be described.
A case will be made that self-management as a strategy to create and enhance
patient empowerment is essential with Parkinson’s disease.
O63
Introduction: Overview
of genetic testing
Oksana
Suchowersky
University
of Alberta, Edmonton, Canada
Since
1997, it has been recognized that approximately 10% of patients with Parkinson
disease (PD) have a family history of this condition. With the advent of genome
sequencing, eight genes have now been identified that are associated with PD,
the 2 most common being LRRK2 and parkin. It is now possible to perform
genetic testing for mutations in these genes, thus confirming a specific
diagnosis. It is also possible to identify asymptomatic individuals who carry
these mutations and may develop symptoms in the future (presymptomatic
testing). This type of testing has limitations. For example, a negative gene
test does not rule out a diagnosis of PD, or mean that the condition is not
hereditary. Alternatively, having the gene does not mean the person will get
PD. The physician arranging for genetic testing needs to be knowledgeable, as
many different genes may cause a similar clinical picture (phenotype), or the
same genetic mutation may cause different phenotypes. In addition to the
limitations of the genetic testing itself, it is important to recognize the
ethical, legal, and psychosocial implications. Secondly, the testing is
currently quite expensive. It is also important to realize that in over 90% of
individuals, even with a family history, a specific causative gene cannot be
identified. In this workshop, the pros and cons, as well as limitations of
genetic testing for PD will be discussed.
O64
Introduction: Overview
of sleep, sleepiness and fatigue in PD
Joseph H. Friedman
Brown
University, RI, USA
Sleep
disorders affect 90% of PD patients in some populations. Fatigue has a
consistent prevalence of about 50% in all reports from a variety of cultures.
While sleepiness and fatigue are often thought of as a single problem, they are
quite different, although often seen together. Fatigue refers to a sense of
severe lack of energy. Napping does not help, and, paradoxically, exercise
does. Fatigue is an early symptom of PD, often developing in the “pre-motor”
phase and is unrelated to motor dysfunction. This talk will stress the
difference between fatigue and sleepiness, and treatment recommendations will
be made although evidence to support treatment is scant. Excessive daytime
sleepiness (EDS) is often the result of poor quality sleep at night, but may be
due to an increased need for sleep in some PD patients who develop a
narcolepsy-type of disorder as a result of changes in the hypothalamus. PD
patients may have difficulty falling asleep, staying asleep, returning to sleep
once awake, or awakening too early. Pain, daytime naps, difficulty getting
comfortable, overactive bladder, depression, nightmares, tremor, medication
side effects and a variety of other problems may complicate sleep. Approaches
to dealing with the manifold problems will be discussed, but no medication has
been proven to improve sleep in PD.
O65
Panel discussion
Tricks of the trade: clever strategies to improve mobility
Graziano Mariella
European Parkinsons’ disease
Association, Esch-sur-Alzette, Luxembourg
Objective: To motivate
people from the audience to share their own strategies to overcome their daily
mobility obstacles.
Methods: Through
interactive discussions and using illustrations, like video clips from the
Coping strategies Tips and Tricks multilingual website www.epda.eu.com/en/resources/coping-strategies-tips-and-tricks/
and tricks examples brought by the public, people will be able to share and
understand strategies developed by themselves.
Results: Willing
participants will have their tips and tricks captured on video (those who agree
to sign a waiver provided onsite) which will be added to the EPDA Coping Strategies - Tips and Tricks website.
O66
Introduction: Overview of Strategies for Improving Mobility
Terry Ellis1,
Mariella Graziano2, Samyra Keus3, Pamela Quinn4
1Boston University, Boston, USA
2Board Member of the European Parkinson Association,
London, UK
3Radboud University Nijmegen
Medical Centre, Nijmegen, The Netherlands
4Brooklyn Parkinson
Group, Brooklyn, NY, USA
Persons with Parkinson
disease often find it challenging to navigate effectively in the home and
community environments. Many describe difficulty maneuvering through doorways,
over thresholds and in small spaces. Movement can be difficult to initiate, is
typically small in amplitude, slow and less automatic. Some may experience
freezing where the feet feel glued to the floor. With a deficiency in dopamine,
the basal ganglia no longer act as an internal cueing mechanism contributing to
the loss of automaticity and movement regulation. However, various forms of
external cueing have been used effectively to help improve mobility by
bypassing the basal ganglia circuitry. Auditory cues are typically rhythmic and
be generated by a metronome or embedded into music. Persons with Parkinson
disease are able to “entrain” or synchronize their movements to the music
resulting in a faster, more fluid movements. Visual cues in the form of lines
on the floor have been shown to improve stride length and walking speed. Laser
lines projected on the floor provide a visual cue to step over - helping
persons with Parkinson disease to initiate walking or to overcome a freezing
episode. Strategies involving consciously paying more attention to walking are
known to be effective in improving upright posture, arm swing and step length
for example. Other forms of cueing, such as verbal and tactile cues, can also
be helpful in improving daily mobility. This session will explore the use of
clever cueing strategies to facilitate mobility in the form of live
demonstrations and video case studies. In addition, this session will include a
discussion of the mechanisms thought to underlie the effectiveness of cueing
strategies in persons with Parkinson disease.
O67
Advances in the
genetics of Parkinson’s disease
Nicolas Dupré2
1Laval University,
Montréal, QC, Canada
2McGill University
Hospital Centre, Montréal, QC, Canada
In families with a non-mendelian
form of Parkinson’s disease (PD), first-degree relatives of an affected
individual are between 2.7 and 3.5 times more likely to develop PD than
individuals without a family history of PD. Their cumulative lifetime risk of
developing PD is between 3% and 7%. Individuals with onset before age 20 years
are considered to have juvenile-onset PD, those with onset before age 50 years
are classified as having early-onset PD, and those with onset after age 50
years are considered to have late-onset PD. The genetic cause of some forms of
mostly juvenile and early-onset PD has been identified. Even if most cases of
PD are thought to result from the effects of multiple genes as well as
environmental risk factors, PD can be inherited in an autosomal dominant or autosomal
recessive manner. Several disease genes have been implicated. Mutations in
three genes, SNCA (PARK1), UCHL1 (PARK5), and LRRK2 (PARK8) result in autosomal
dominant PD. Mutations in three genes, PARK2 (encoding for parkin), PARK7
(PARK7), and PINK1 (PARK6), result in autosomal recessive PD. Molecular genetic
testing is clinically available for PARK2, PINK1, PARK7, SNCA, and LRRK2. Once
results are available, genetic counseling of affected individuals and their
family members must be done on a family-by-family basis.
O68
The experimental
models of Parkinson’s disease: Are they useful?
Marie-Francoise Chesselet
Department of Neurology, UCLA,
Los Angeles, CA, USA
Objective: De nombreux modèles de
la maladie de Parkinson ont été développés par les chercheurs pour comprendre
ses mécanismes et tester de nouveaux traitements. Beaucoup de controverses ont
émergé à ce sujet. Le but de cette présentation est de présenter les modèles
utilisés aujourd’hui et de clarifier leur limites et avantages, et d’expliquer
comment ils contribuent à nos efforts pour développer de nouveaux traitements.
O69
Drug Induced
Parkinsonism
Stewart A. Factor
Emory
University, Atlanta, GA, USA
Parkinsonism
is a serious complication of many drugs. Most prominent are the dopamine
receptor blocking agents (DRBA) including antipsychotics and antiemetics. The
frequency in treated patients is ~50% in the elderly and up to 60% in
schizophrenics depending on several risk factors. Drug-induced parkinsonism
(DIP) makes up 10-20% of parkinsonism patients seen in movement disorders
clinics. Clinically, DIP can be indistinguishable from Parkinson’s Disease
(PD), with unilateral or bilateral onset and akinetic-rigid or tremor
predominant forms. Differentiating clinical features in DIP include the
subacute onset, rapid progression, and co-occurrence of tardive dyskinesia.
Older woman are at greatest risk for developing DIP. DIP is serious because of
its potential chronicity, disability, morbidity, admissions to nursing homes
and mortality. Atypical antipsychotics (AA) have largely replaced typical
neuroleptics and are frequently used to treat the elderly. Recent studies have
suggested that AA do not decrease the risk of DIP. DIP is under-recognized as
patients are either diagnosed with PD or not diagnosed at all. Large population
studies based on Medicare and Medicaid record reviews demonstrated that
patients treated with neuroleptics were 2-5 times more likely to be diagnosed
with PD and treated with anti-PD medications as those not exposed. Over 70%
maintain the inciting agents. One way to detect this difference would be to
stop the DRBA but reversal can take a year. The development of 123I-FP-CIT
SPECT imaging has changed that problem being normal in DIP but abnormal
when the drug worsened already present PD or hastened its development. To treat
DIP the first step besides recognition is the removal of DRBA or switching to a
less potent one. The role of anti-PD agents is unclear. Other non-neuroleptic
drugs are important causes of DIP including: Valproate (5%), tetrabenazine
(4-15%), amiodarone, cysclosporine, lithium, and SSRI’s.
O70
PD or progressive
supranuclear palsy
Irene Litvan
University
of California San Diego, CA, USA
The
early and accurate diagnosis of progressive supranuclear palsy (PSP) and
Parkinson’s disease (PD) is at times challenging. There are no biological
markers that could help diagnose these disorders. However, differentiating them
early is crucial as their prognosis and management differs. PSP is the most
common atypical parkinsonian disorder. It is a 4-repeat tauopathy, usually
presenting in the sixties with various phenotypes. The most common and
classical PSP phenotype should be easy to differentiate from PD as it is
characterized by features would be very unusual in early PD. PSP classically
presents with progressive postural instability and falls, non-levodopa
responsive axial parkinsonism, difficulties with vertical ocular movements,
early dysarthria, dysphagia and executive dysfunction. However, there are other
PSP phenotypes that pose major challenges. PSP patients may present with a
progressive asymmetric parkinsonism benefiting from levodopa therapy,
PSP-parkinsonism, or with freezing of gait, PSP-akinesia and freezing of gait.
Early suspicion and search for tell-tell signs help the clinician differentiate
PSP from PD.
O71
PD or Multiple system
atrophy
Cheryl Waters
Columbia
University Medical Center, NY, USA
Multiple system atrophy (MSA) and Parkinson's
disease (PD) are both degenerative diseases of the basal ganglia. MSA is a
progressive disease associated with autonomic features. Diagnosis can only be
made with certainty with pathological confirmation showing characteristic glial
cytoplasmic inclusions in a variety of regions of the brain (basal ganglia and
cerebellum, spinal cord). As MSA carries a worse prognosis than PD it is
important to try to distinguish them. MSA is divided into MSA-P (Parkinsonism)
and MSA-C (Cerebellar) reflecting the prominent initial symptom. MSA-P can
sometimes be difficult to distinguish from PD as there are many overlapping
features. PD may have features that were formerly thought to be found only in
MSA, such as significant autonomic involvement. Both diseases are treated with
levodopa, although with MSA-P there may be greater need to treat the
orthostatic hypotension with medications. Levodopa responsivity and motor
fluctuations can be seen in cases of MSA-P. Also, it is now recognized that
there are examples of MSA-P which are benign and of long duration. There are
some well described “red flags” to distinguish MSA-P from PD including
orofacial dystonia, cold hands and feet, myoclonic (jerky) tremor, camptocormia
(extreme forward flexion of spine),disproportionate antecollis (neck flexion),
severe dysphonia (impaired voice) and sighing. Autonomic testing, anal
sphincter EMG, neuroimaging including MRI, PET and SPECT can be supportive. The
imaging characteristics will be discussed in further detail. There are distinct
differences in prognoses between these disorders, with MSA-P being more rapidly
progressive and more challenging to manage. Therefore, it is important for the
clinician to distinguish and diagnose the patient with MSA-P.
O72
The placebo effect: how it complicates clinical trial results
Christopher G. Goetz
Rush
University Medical Center, Chicago, IL, USA
When
a clinical trial of a new medication or surgery is conducted for patients with Parkinson’s
disease (PD), researchers are trying to test whether the new treatment improves
a specific element of the disease or overall disability. The testing program
necessarily involves more visits to the study center, more attention by the
study staff, and more focus by the patient, family, and raters on the
possibility of change in the PD. All of these latter issues can positively
affect patients and changes induced by study participation independently of the
actual new treatment being studies are collectively known as
“placebo-associated improvements”. Because these effects can be striking
specifically in PD, almost all important studies of new treatments are
“placebo-controlled”, meaning that patients are randomly assigned to receive
the study intervention or an inert treatment (empty pills or sham-surgery) so
that neither the patient nor the raters know to which group a given patient is
assigned. In this way, both groups experience whatever placebo-associated
improvements occur, and an added benefit documented in the study treatment
group can be safely ascribed to that specific intervention. Prior studies have
indicated that placebo-associated improvements are quite marked, but varied, in
PD studies. In an evaluation of 11 clinical trials, covering mild, moderate and
advance PD subjects and both medication and surgical interventions, an overall
placebo-associated improvement occurred in 16% of patients and reached as high
as 50% in surgical interventions. In this analysis, the primary criterion for determining
“placebo-associated improvement” was a 50% improvement in objective ratings of
PD impairment using the internationally recognized scale known as the UPDRS
that measures tremor, bradykinesia, rigidity, gait and balance. Whereas from a
clinical management perspective, clinicians and patients are happy to see
improvement from any cause, placebo-associated improvements pose a very
significant challenge to clinical trials. If the placebo effect is strong, the
challenge increases to document a benefit from the study intervention. Further,
because the frequency of placebo response is varied, it is difficult to
estimate this effect for a given study beforehand. Many studies of seemingly
effective treatments for PD have failed and been abandoned, not because the
treatment group failed to improve, but because the placebo-treated group
improved too, making the difference between placebo treatment and new
intervention treatment statistically equivalent. The particular sensitivity of
PD to placebo effects is likely due in large part to the activation of dopamine
that occurs when the human brain responds to novelty, expectation, and risk.
Enrollment in clinical trials naturally activates all of these behaviors.
Scientists cannot reduce novelty or risk, because they are implicit to the
experience of a clinical trial, but potentially expectation is controllable.
The aim of a clinical study is to test a new intervention, and ideally, raters
and patients who participate are those who are ready to rate whatever they see or
experience. Their role is accurate reporting. They cannot help from hoping for
improvement, as they wish to establish new treatments for PD; however, they may
be able to discipline themselves against expectation and to concentrate on
accurate reporting whether there is improvement, decline or no change.
Paradigms to test this type of control can be implemented, and efforts have
been developed to try to reduce expectation in programs.
O73
Slowing clinical
progression in PD - Can it be proven in clinical trials?
Fabrizio
Stocchi
Institute for Research and Medical Care IRCCS
San Raffaele, Rome, Italy
No drug has yet been established to have a
neuroprotective effect in PD. Several clinical trials of putative
neuroprotective agents have shown positive results, but it could not be
determined with certainty if the benefit was due to neuroprotection because of
potentially confounding pharmacologic or regulatory effects of the study agent.
In an attempt to separate an early symptomatic from a disease modifying effect,
the delayed washout and delayed start studies have been proposed. Both are two
period studies that rely on change from baseline in UPDRS score. In the first
period of each of these studies, patients are randomized to active treatment
(early start) or placebo. In the second period of the delayed washout study,
the active intervention is stopped and patients in both treatment groups
receive placebo. If the early start group maintains a benefit in comparison to
placebo at the end of the second period, this is consistent with the treatment
having a disease-modifying effect. This design, however has ethical and
practical issues. In the second period of the
randomized start design, patients in the placebo group are placed on the active
intervention (delayed start) while those in the early start group are
maintained on their original treatment. If at the end of the trial the early
start group continues to show a benefit in comparison to the delayed start
group, even though both groups are on the same treatment, this suggests that
the treatment has slowed the rate of clinical deterioration. Such studies are
complex and difficult to carry out. Another approach is the long-term simple
study, where subjects are randomized to active treatment or placebo, and then
followed for a prolonged period of time in which the physician can manage the
patient in any way they deem to be appropriate. The outcome measure capture
factors related to the development of cumulative disability. A combination of
the delayed start and long term simple studies offers assessments of mechanism
and clinical significance, and provides a roadmap for the development of a
neuroprotective drug. Adaptive design is another approach that can be of great value.
Here, unannounced but predetermined interim analyses examine data accumulated
during the course of the trial without compromising the blind or the integrity
and validity of the study. Such an approach can permit early termination of a
study for adverse events or futility, examination of large numbers of doses
with rejection of those doses that are futile, re-estimation of sample size,
and early planning and streamlining of next phase studies. These approaches can
substantially reduce the cost and time of the development program for a
putative neuroprotective drug.
O74
Infusion therapies and other non-oral routes of drug
delivery
Angelo Antonini
Department for Parkinson's disease and Movement
Disorders
IRCCS Hospital San Camillo Venice, Department of
Neuroscience, Padua University Hospital, Italy
Chronic
pulsatile oral administration of dopaminergic drugs, particularly levodopa,
contributes to the development of motor fluctuations and dyskinesia in
Parkinson’s disease (PD). Motor complications also
represent a significant burden for patients and their caregivers and are an
important cost driver in overall PD management. Infusion and transdermal
delivery of dopaminergic drugs (levodopa and dopamine agonists) helps providing
continuous receptor stimulation that in turn would minimize motor fluctuations
and improve dyskinesias in advanced patients. The following options are
available: rotigotine patch, apomorphine subcutaneous infusion and
levodopa-carbidopa intestinal gel (LCIG). Rotigotine is a dopamine agonist that
has shown its effectiveness at all PD stages and may be particularly helpful in
patients with specific non-motor symptoms like sleep and mood disturbances as
well as in presence of permanent or transient gastrointestinal problems (thanks
to its transdermal delivery). Continuous subcutaneous infusion of apomorphine
has shown benefit in advanced patients. Apomorphine exerts its
anti-parkinsonian effect by direct stimulation of striatal postsynaptic
dopamine D1 and D2. Alternative routes of apomorphine delivery such intranasal
or inhaled are under development. Finally, LCIG treatment was recently shown to
not only reduce off time and extend on time but also to have a beneficial
effect on troublesome dyskinesia. LCIG was also shown to have effect on
non-motor symptoms.
The rationale for favoring a continuous dopaminergic delivery instead of
pulsatile regimen regards primarily the avoidance of peaks and troughs in
plasma. Such therapeutic strategy may improve quality of life and decrease patient disability likely resulting in economic benefits
because of reduced costs for medical care, physician visits and
hospitalization.
O75
Delivering therapeutic genes into the brain - a future way of drug
delivery?
Stephane Palfi
APHP/Paris University, Créteil,
France
The brain is an highly heterogeneous structure divided in
many interacting circuits involved in complexe behavioral tasks. These neuronal
networks are composed by neuronal populations expressing receptors and neurotransmiters
that can be involved in either motor, associative or limbic territories. Thus,
systemic drug administration may induced adverse reactions due to a diffusion
of its action behong the therapeutic target stressing the need to develop local
delivery methods. Gene transfer technology is one of the most advance delivery
method capable of locally delivering protein of therapeutic interest to highly
specialized subpopulation of neurons. The presentation will give an overview of
the gene transfer technology dedicated for brain diseases as well as methods to
surgically administered viral vectors.
O76
Pathological evidence
for axonopathy in Parkinson's disease
Dennis W. Dickson
Mayo
Clinic, Jacksonville, FL, USA
Objective: To review the role of axonal pathology in
PD.
Methods: Overview of the neuropathologic literature on axonal pathology in
PD, as well as personal experience from evaluating over 1000 brains with Lewy
body pathology, including over 250 with PD.
Results: While
neuronal perikaryal inclusions composed of α-synuclein (referred to as
Lewy bodies) are the histologic hallmark of Parkinson’s disease and related
α-synucleinopathies, including dementia with Lewy bodies, much evidence
suggests that the greatest disease burden in PD is in neuritic processes that
are axonal in origin or in presynaptic axonal terminals. Inclusions with
morphologic characteristics of Lewy bodies are also detected in axons
(so-called intraneuritic Lewy bodies) in certain vulnerable brain regions,
notably the dorsal motor nucleus of the vagus and the basal nucleus of Meynert.
Lewy neurites, lesions that are not visible with routine histologic methods,
were first described with ubiquitin immunohistochemistry in the hippocampus and
amygdala, but with the advent of α-synuclein immunohistochemistry, it
became clear that they were widespread and a fundamental characteristic of PD
and not only a feature of advanced disease, but also one of the earliest
neuronal alterations. Another pervasive but subtle pathology is accumulation of
abnormal conformers of α-synuclein in axonal termini at the synapse. In
addition to these α-synuclein-immunoreactive lesions, there is evidence to
suggest that nigrostriatal dopaminergic degeneration in PD may have its origin
in the distal axonal termini analogous to a dying back process. While there may
be α-synuclein pathology in dopaminergic cell bodies in the substantia
nigra, the central dying back axonopathy in the striatum does not seem to be
associated with striatal α-synuclein pathology. In contrast, in advanced
disease, the striatum in PD and related α-synucleinopathies has extensive
neuritic pathology that increases with disease duration.
O77
Evidence for synaptic
dysfunction in Parkinson’s disease
Karina Vargas1,
Taylor Davis1, Sachin Makani2, Christopher H. Westphal1,
Pablo E. Castillo2, Pietro De Camilli1, Sreeganga S.
Chandra1
1Program in Cellular
Neuroscience, Neurodegeneration and Repair, Yale University, New Haven, CT, USA
2The Dominick P. Purpura
Department of Neuroscience, The Albert Einstein College of Medicine, Bronx, NY
USA
Objective: α-Synuclein (α-Syn)
is an abundant, soluble presynaptic protein that is broadly expressed in brain.
Point mutations, duplication and triplication of the α-Syn gene have been
shown to cause Parkinson disease, yet its physiological functions remain
unknown. The objective of this study is to investigate the normal synaptic
functions of α-Syn and its role in Parkinson’s disease.
Methods: We
generated αβγ-Synuclein knockout (αβγ-Syn-/-)
mice that lack all murine synucleins. These mice are viable but have a shorter
lifespan than wildtype controls. The overall brain architecture and morphology
of neurons in young αβγ-Syn-/-
mice appears normal but the size of synapses is decreased. We carried out an
unbiased proteomic screen to identify proteins that are changed in αβγ-Syn-/-
synapses and observed increases in the levels of select membrane curvature
sensing/generating proteins. These proteomic data suggest that α-Syn
participates in the exo- or endocytic steps of the synaptic vesicle cycle—two
steps that require membrane bending. To directly determine the roles of
α-Syn in the synaptic vesicle cycle, we have used vGlut-pHluorin imaging
as well as slice electrophysiology.
Results: Our data suggest that
α-Syn regulates the kinetics of the endocytic step in the synaptic vesicle
cycle and the deficits in this function could contribute to the initiation of
Parkinson's disease.
O78
Alterations
in axonal transport in Parkinson’s disease
Scott T.
Brady1 and Gerardo Morfini1
1University of Illinois at Chicago, Chicago, IL USA
Intracellular aggregates of α-synuclein known as Lewy bodies
(LB) or Lewy filaments (LF) are a pathological hallmark of Parkinson’s disease (PD).
Further, point mutations in α-synuclein are linked to some familial
Parkinson’s (fPD) cases, but no consensus explanation has emerged to elucidate
the roles α-synucleins play in PD pathogenesis. Recombinant
α-synucleins were used to evaluate changes in axonal transport associated
with both fPD mutant α-synucleins and LF made from wild type (WT)
α-synucleins in a cell-based model of synucleinopathy. Mutant
α-synucleins (A30P and A53T) activated specific isoforms of a neuronal
protein kinase C (PKC) leading to increased dynein-based retrograde transport,
reduced kinesin-based anterograde transport and failure of neurotransmission.
The net effect of these changes in fast axonal transport is a reduction in
synaptic vesicles and other components needed for the continued function of the
presynaptic terminal, leading to failure of neurotransmission in affected
neurons and an associated loss of adequate neurotrophin supplies. Pathogenic
forms of α-synucleins or LB/LF alter regulatory pathways critical for
maintaining the normal balance between anterograde and retrograde transport in
dopaminergic neurons. Altered trafficking of organelles in axonal transport
affects trophic interactions and synaptic function, leading to synaptic loss
and eventual neuronal death.
O79
Introduction:
Overview of care models and options
Elaine Book
Pacific
Parkinson’s Research Centre, University of British Columbia, Canada
Considering
residential care for a loved one can be an emotional process as well as
challenging as one navigates the health care system. A variety of options exist
offering varying levels of care and often with complicated processes for
accessing the services. This workshop will address some of the issues in
deciding when it is time to plan for facility care, considerations to think
about when choosing a care facility and what options are available. The
panelists each representing Canada, USA, Australia, India and the Netherlands
will present an international perspective on care models and how Parkinson’s
concerns are addressed. The discussion will identify some of the challenges and
successful approaches used to meet the needs of PD patients and their families.
O80
Case
presentation: Care models in the Netherlands
Marten Munneke1,2,
Bastiaan R. Bloem1,2, Nico Weerkamp3
1ParkinsonNet,
Nijmegen, The Netherlands
2Parkinson Centre
(PARC), Radboud University Nijmegen Medical Centre, The Netherlands
3Department of
Neurology, Atrium Medical Centre, Heerlen, The Netherlands
The situation in Dutch nursing homes for patients with
Parkinson’s disease is highly variable and, unfortunately, often not optimal.
In many Dutch nursing homes, patients with Parkinson’s disease are not treated
optimally. We recently performed a research project aiming to examine the clinical
characteristics, motor impairments, and drug treatments of nursing home
residents with Parkinson’s disease. Based on this study we concluded that PD in
nursing home residents is characterized by severe motor impairment and a high
proportion of daily “off” time. Non-motor symptoms were very common, and
quality of life was poor, largely due to non-motor symptoms. In addition, 20%
of diagnoses within the parkinsonian spectrum were inaccurate. Almost 9% of
residents had inadvertently received a diagnosis of parkinsonism. Interviews
with patients, informal caregivers and healthcare workers revealed that PD care
in Dutch nursing homes is suboptimal. Three core areas for improvement were
identified, including a need for greater attention to psychosocial problems, a
need for improved PD-specific knowledge among nursing home staff, and a need
for better collaboration with hospital staff trained in movement disorders.
These findings underscore the need for improved management of PD in nursing
homes, but also the need to avoid admission altogether by enabling patients to
remain in their homes. ParkinsonNet (www.parkinsonnet.nl) has started a
healthcare innovation project aimed to reach these targets.
O81
Case presentation:
Care models in the USA
Ruth Hagestuen
Struthers
Parkinson’s Center, Golden Valley, MN, USA
National
Parkinson Foundation
Objective: This presentation will provide an overview
of the Struthers Parkinson’s Center’s integrated approach to clinical,
educational, research, support, outreach and wellness programs. The Center,
established over 30 years ago, is a free-standing facility which is part of the
Park Nicollet Health System.
Methods: The SPC integrated system of care is designed to provide access
to the right care, information, and support at the right time, over time. The
majority of programs which will be presented are team based. The full day
assessment clinic, for example, includes physician, nurse, social worker,
physical therapy, occupational therapy, speech therapy. Different combinations
of the team members are part of the FOCUS program for persons newly diagnosed,
the Caregiver Skills-building series, and the DBS educational sessions for
patients and families considering Deep Brain Stimulation. The same is true of
the regularly scheduled professional education days for nurses, rehabilitation
therapists and social workers. Two other unique programs of this Center are (1)
the CREATE (Center for Research Education Artistic and Therapeutic Endeavors)
program which includes a therapeutic day program, an arts café, and a variety
of exercise based wellness and support programs and (2) The Struthers
Parkinson’s Care Network (SPCN), working with senior residential communities to
improve PD awareness, staff education and support services.
Results: Attendees at this session will (1) be
able to list at least two unique program initiatives from Struthers Parkinson’s
Center that can be replicated in other locations, (2) Discuss the role of a
Parkinson’s Center as a regional hub of specialized care in the U.S.
O82
Overview
Anthony Lang1,
Serge Przedborski2, Etienne Hirsch3, Ted Dawson4.
1University of Toronto,
Toronto, ON, Canada
2Columbia University,
NY, USA
3INSERM, Paris, France
4Johns Hopkins University
School of Medicine, Baltimore, MD, USA
Experimental
animal models of Parkinson's disease are characterized in a variety of ways
including the "animal" used (e.g. invertebrates, rodents, nonhuman
primates) and the "disease" producing mechanism (e.g., neurotoxins,
transgenic models of Parkinson-related mutations, overexpression of alpha
synuclein using viral vectors, direct brain injections of fibrillar synuclein).
Features of these models that are generally considered in evaluating their
utility include behavioral manifestations, whether or not the model
demonstrates progression over time, nature and involvement of dopaminergic
neurons of the substantia nigra, additional non-nigral involvement, nature of
the underlying neuropathological features (including synuclein aggregation/Lewy
body formation), and the presence of various pathogenic features (e.g.,
mitochondrial dysfunction, neuroinflammation, abnormalities of proteolytic
pathways, cell-to-cell spread of pathology, etc.). These models can be used for
a variety of purposes depending on the underlying
neuropathological/neurochemical disturbances including the assessment of
possible pathogenic factors underlying the disease, evaluation of putative
neuroprotective or disease modifying therapies, and the study of novel
symptomatic therapies for both the disease and the complications of its
treatment. In this workshop the panelists will discuss the advantages and
disadvantages of available experimental models particularly emphasizing their
utility in predicting outcomes of various forms of treatment.
O83
Introduction: Insights
into Complementary Therapies
Monique Giroux1, Louis Tan2, Angela Rob3
1Movement &
Neuroperformance Center of Colorado, 499 Englewood, #250, CO, USA
2Department of
Neurology, National Neuroscience Institute, Singapore
3
PD
Carepartner & Reiki Master, GiveReiki.com
Objective: To provide an
overview of complementary and alternative therapies and their use in
Parkinson’s disease.
Background: Complementary and
Alternative therapies (CAM) are traditionally defined as therapies outside of
the realm of traditional medicine. These therapies are playing a greater role
in the self-care of people with Parkinson’s disease to improve symptoms,
influence disease, improve personal wellbeing and enhance innate natural
healing abilities. The field is broad and difficult to define as the boundaries
between what represents traditional medicine and CAM therapies are blurred.
This workshop will begin with a discussion of healing based therapies,
contribution to health and wellbeing and the philosophical differences that
often separate these modalities from traditional medical treatment. A brief
overview of CAM therapies and their role in categorical review of CAM therapies
to include: Natural Products, Manipulation and Body Therapy, Mind-Body
Medicine, Energy Medicine, and Health Systems. Panelists Angela Rob and Dr.
Louis Tan will share their insights on the role of CAM and the potential use
for people with Parkinson’s disease. An exploration of possible mechanism of
action(s), safety considerations and practical guidance for use will be offered
given the limited controlled research results to date.
O84
Overview:
How do we know dance helps people with Parkinson's?
Gammon M. Earhart1,
Diane Cote2, Maura Fisher3, David Leventhal4,
Joanabbey Sack3
1
Washington
University School of Medicine, St. Louis, MO, USA
2
The
Ottawa Hospital, Ottawa, ON, Canada
3
Mark
Morris Dance Group, Brooklyn, NY, USA
4
The
Parkinson’s Dance Project, Montréal, QC, Canada
Objective: This workshop has
three main objectives: 1) to review the scientific literature supporting the
use of dance in the management of Parkinson disease (PD), 2) to discuss various
dance approaches (e.g. merengue, improvisation, modern dance, ballet and tango)
tailored specifically for people with PD, and 3) provide examples of how dance
programs for people with PD can be implemented in community settings.
Methods: Through individual
presentations we will summarize the evidence to date regarding the benefits of
different dance approaches for people with PD. A comprehensive bibliography of
literature regarding dance for people with PD will be provided to participants.
Participant input will be encouraged during the panel discussion which will
provide multimedia demonstrations of successful ongoing dance programs for
people with PD.
Results: Over the past several years there is
growing evidence that dance is beneficial for people with PD. Specific benefits
include reduction of PD symptom severity, enhanced balance and walking, and
improved quality of life. Workshop participants will come away from the session
with a broad overview of the literature on dance for PD, knowledge of the
different forms of dance that have been employed, and specific recommendations
and guidelines for implementing community-based dance programs for people with
PD.
O88
The
problem of the accumulation of toxic proteins and the significance of the
quality control mechanisms in Parkinson’s disease
Edward A. Fon
McGill Parkinson Program,
Montreal Neurological Institute, and Department of Neurology and Neurosurgery,
McGill University, Montreal, QC, Canada
Même
si les causes de la maladie de Parkinson (MP) demeurent inconnues, l’identification
de plusieurs gènes responsables de formes héréditaires de la MP a permis des
percées importantes et prometteuses. Plusieurs de ces gènes semblent agir à
l’intérieur des neurones pour maintenir le bon fonctionnement cellulaire en
éliminant les protéines mal repliées ou désuettes. Ce travail de dégradation
est particulièrement important pour maintenir un équilibre à l’intérieur des
neurones et empêcher l’accumulation des déchets qui pourraient être toxiques.
Mon programme de recherche se penche sur parkin, un gène qui est intimement
impliqué dans la voie ubiquitin-protéasome, le principal système cellulaire de
dégradation des protéines. Le but de cette conférence est de présenter un
aperçu des découvertes récentes concernant parkin ainsi que plusieurs gènes
apparentés.
O89
Non-motor
manifestations of Parkinson’s disease
Sylvain Chouinard
Unité des troubles du mouvement
André Barbeau, Université de Montréal, QC, Canada
La maladie de Parkinson (MP) est surtout connue pour
ses manifestations motrices toutefois, les symptômes non moteurs (SNM) occupent
une place importante. Parfois ils vont précéder les manifestations motrices
sinon ils vont inévitablement apparaître avec la progression de la maladie.
Dans les stades plus avancés de la maladie ils peuvent même dominer le tableau
clinique et interférer significativement avec la qualité de vie.
Malheureusement ces symptômes non moteurs sont souvent mal appréciés tant par
le patient que par son médecin traitant. Dans cette présentation, nous nous
attarderons pluslonguement aux symptômes non moteurs de la MP et
surtout, nous aborderons les traitements non pharmacologiques et
pharmacologiques de ceux-ci.
O90
Table #2: Effective
Fundraising models for PwP founded non-profit organizations: How to survive
Fulvio Capitanio1, Tom Isaacs2
1 Unidos contra el Parkinson, Barcelona, Catalonia, Spain
2
The Cure Parkinson’s Trust, London, UK
Objective: To provide information about how to start, run and maintain a ‘not for
profit’ organisation to help improve the quality of life of people with
Parkinson’s whether this be through enhancing psychological or physical
wellbeing. To illustrate the different types of non-profit organisation and the
resources required to establish, expand and retain their effectiveness over
time. To suggest fundraising ideas, give examples of successful fundraising
campaigns and to reveal some tricks of the trade to ensure the best results. To
have an interactive discussion with those present, to answer questions and share
experiences.
Methods: Tom Isaacs has lived with Parkinson’s for 18 years and is President and
Co-founder of The Cure Parkinson’s Trust which was set up in 2005. Since that
time the organisation has invested over $5 million (Canadian) into research
projects around the world. The organisation has been responsible for some major
advances in the Parkinson’s arena and has also funded and facilitated several
clinical trials which have all shown the promise of delaying or reversing the
disease process. Fulvio Capitanio (Spain) is an economist and ITC manager. He
was diagnosed with Parkinson's in 2007. In January of 2008, with a group of PD
friends he met over the Internet, he started an online organization called
"Unidos contra el Parkinson” (together against Parkinson's disease) at
http://portal.unidoscontraelparkinson.com.Since October 2009 UCP coordinated
the group's International Meetings in Spain. In March 2010 UCP edited a comic
"Through the eyes of a child” to help parents to explain PD to their
children. In April 2010 started the project "Run 4 PD”, a worldwide yearly
event involving about 100 cities from different countries.
Results: At this round table
session, Tom will share his fundraising experiences and will pass on valuable
insights into which income generation schemes work and which don’t. There will
be some amusing anecdotes among these. Fulvio will be happy to share his
experience starting a network community organization, building and promoting
events using the “Zero Budget” model.
O92
Table #3: Non-motor
Symptoms & PD
Ronald F. Pfeiffer
University
of Tennessee Health Science Center, USA
In
recent years, recognition has grown that Parkinson’s disease (PD) encompasses
much more than difficulty with movement. A whole host of features that have
little or nothing to do with movement are important, and sometimes dominant,
features of PD. Changes in mood, loss of motivation, increased anxiety,
difficulty with thinking and memory, excessive fatigue, sleep disturbances,
problems with bowel, bladder, and sexual function, excessive sweating,
impairment of sense of smell and therefore also taste, changes in some aspects
of vision, and a variety of types of pain all are examples of these “nonmotor”
features of PD. Although some nonmotor features characteristically appear later
in the course of PD, others may occur very early, even before the classic motor
features of PD develop and sometimes before PD is even diagnosed. Recognition
of the nonmotor aspects of PD is important because they do not always respond
to traditional PD treatment measures that typically target dopamine, but may
respond to other treatment approaches. The fact that nonmotor features of PD
often cause more distress - both for persons with PD and for their family
members – makes it especially important that these features are recognized and
addressed. This session will be open to questions and discussion of any and all
of these nonmotor features of PD.
O93
Table #4: Genetic
Testing & PD: What questions you should be asking
Susan Bressman
Beth
Israel Medical Center, NY, USA
Over
the last 15 years we have learned that mutations in several different genes
cause Parkinson’s disease (PD); other genetic changes may greatly or moderately
increase the chances of developing PD and are not fully determinative. Testing
for some of these mutations is now available either through a request by a
physician or through “direct to consumer” testing. Although testing has yet to
be widely and routinely adopted, increasingly individuals are becoming interested
in knowing their “gene status” or in understanding the potential advantages and
disadvantages of testing. In this roundtable we will review questions or issues
people often need to consider when contemplating genetic testing for PD.
Examples of such questions include: How likely am I to be positive for the gene
being tested? What is the cost? Do I need a background understanding of
genetics in order to interpret results? Will knowing the results affect my
current treatment? Will results influence other life decisions? Will results
affect my insurance? My job? Can a test result have implications regarding the
genetic status of my relatives? It is hoped that by considering these questions
participants will have a better understanding of the testing process and feel
more comfortable about personal decision making in regard to genetic testing.
O94
Table #5: Parkinson's
disease and cancer
Rivka Inzelberg
The
Sagol Neuroscience Center, Department of Neurology, Sheba Medical Center, Tel
Hashomer and Tel Aviv University, Israel.
Objective: To discuss the particular relationship
between Parkinson's disease (PD) and skin and non-skin cancers.
Methods: There
is evidence based on well-designed epidemiological studies for unusual cancer
rates in PD patients as compared to the general population. These findings will
be reviewed and discussed.
Results: PD patients are at
significantly low risk for most cancers as compared to the general population.
This risk reduction cannot be attributed to the recognized low incidence of
smoking in patients with PD, since not only smoking-related cancers but also
non-smoking related ones are less common in PD. While the risk for most cancers
appears to be relatively low in patients with PD, breast cancer and melanomas
occur more frequently in the PD population as compared to controls. These
peculiar patterns of cancer rates in PD might be related to the involvement of
common genes in both diseases. Recently, increased risk for non-skin cancers
has been reported in LRRK2 related PD. Furthermore, genes involved in
familial forms of PD appear to be abnormally expressed in cancers. Cell
survival signals may differ due to mutated genes and represent two opposite
extremes such as cell proliferation in cancer and cell death in PD. Unraveling
the link between PD and cancer may open a therapeutic window for both diseases.
O95
Table #6: Staying engaged and raising children after a Parkinson's
diagnosis
Soania Mathur1,
Sharon Daborn2
1Designing A Cure Inc., Toronto, ON, Canada
2Australia
When a parent is diagnosed with any chronic
illness, it undoubtedly affects the whole family unit in many ways. Of utmost
concern are the children and their ability to cope with having a parent with a
progressive illness. Likewise, parents that are struggling with their diagnosis
often have trouble dealing with the idea that their parental role may now have
to adjust given the change in their health. It becomes challenging from a
physical point of view to manage some of the practical aspects of parenting as
well as an emotional one as the uncertainty of functioning day to day can lead
to feelings of frustration and guilt. Although initially overwhelmed by their
unexpected diagnoses, Mathur and Daborn made it their mission to ensure that
they provided their young children with the coping skills necessary to deal
with this challenge and to find new parenting strategies to help themselves and
other parents remain effective caregivers for their families. In their
experience key elements to navigate this process were to first to prioritize
their own self care, adapt and accept the sometimes inevitable changes that
need to be made to their parenting techniques and create a positive family
environment through truthful dialogue, education and optimism. Through their
own personal experiences of raising young children as well as the perspectives
that they have received from other parents with Parkinson’s Disease and allied
health professionals, Daborn and Mathur will present methods they have found
helpful in staying engaged and inspired as parents as well as ways to help
children feel empowered despite this family challenge. They will discuss how parents
can continue to create happy, productive family environments after a diagnosis
of Parkinson’s Disease.
O96
Table #7: Parkinson's
disease and women
Claire Henchcliffe1,
Sara Riggare2
1Weill Cornell Medical
College, NY, USA
2Karolinska Institute, Stockholm,
Sweden
Objective: Parkinson’s disease (PD) affects over a
million women worldwide, and women comprise over 40% of those with young onset
PD. In addition to differences in reproductive and social roles, growing data
now indicates gender-specific differences in PD itself, in treatment effects,
and disparity in access to specialty care. This Roundtable will provide a
focused discussion group addressing issues affecting women with PD.
Methods: This focused discussion group, including people with PD and
members of the medical and scientific community, will review current knowledge
of how Parkinson’s disease affects women, and examine issues specific to women
with PD. Importantly we will share experiences of women with PD, and of those
involved in their lives and their medical care. Using this knowledge, we will
enhance our understanding of the specific needs of women with PD, and of what
pathways of further action are needed.
Results: It is well known that PD manifests differently in women than men,
for example women are more commonly affected by certain non-motor symptoms such
as depression, and are more likely to develop medication-associated
dyskinesias. Moreover, a number of PD risk factors are differently associated
in women and men, and genetic burden may also differ. Despite this, he majority
of PD study participants are men. There is also very little research into
issues affecting women with PD specifically, such as child bearing, sexual
function, or effects of menopause.
Conclusion: In striving to
provide the most appropriate individual care, it is imperative that we better
understand gender differences in PD. Approaches to provide improved
neurological care and empowering women with PD will need to consider
reproductive issues, caregiver roles, and facilitating better specialty
healthcare access. Moreover, a better understanding of fundamental differences
in PD between women and men needs to be addressed by targeted clinical data
collection.
O97
Table
#8: Flying solo - living alone with Parkinson's
Cathi A. Thomas1,
Ryan Tripp2
1BUMC Parkinson's Disease and Movement
Disorders Center, Boston, MA, USA
2Retired Teacher; PLWP,
Bracebridge, ON, Canada
Living
single with Parkinson’s disease presents challenges that require careful
planning in the immediate and for the future. Many people with Parkinson’s live
alone and are quite successful. In order to accomplish this, adjustments in the
home environment and activities of daily living may be needed to increase
safety, and improve quality of life. This session will provide an opportunity
for attendees to share common concerns and challenges of living alone at home
with Parkinson’s on a daily basis. A guided discussion will be facilitated by a
person who lives at home alone and a specialized RN. The discussion will focus
on strategies to modify and equip the home, build a support system to deal with
motor and non-motor symptoms, and identify important human and financial
resources.
F – freedom L
– listen Y – yahoo I – independence N
– network G – goal setting
S – smile O
– openly L – laugh O – often
O99
Table #9: Service dogs
and Parkinson's: Everything you need to know
Carolyn Weaver and
Renee Le Verrier
Living
with a mobility service dog can redefine living with Parkinson's. The fear of
falling or getting stuck becomes less overwhelming with a canine companion
because specialized training teaches the dog to assist with symptoms such as
slow or uneven walking, instability, freezing and getting in and out of chairs.
In
this roundtable discussion, Carolyn and Renee share their stories of increased
confidence, independence, social connectedness, and dog food bills. This
interactive forum presents information on the steps before, during and after
applying for a service dog with question-and-answer opportunities throughout.
In addition, the session includes video clips and demonstrations on the
benefits as well as the corresponding responsibilities of this medicine-free,
surgery-free option to improved well-being. Carolyn Weaver of Michigan has been
living with PD for thirteen years and with her service dog, Selma, for two
[will be 2-1/2 years come the October mtg]. Renee Le Verrier of Massachusetts
has been living with PD for ten years and with her service dog, Sir Thomas, for
six months [will be one year come the Oct mtg.] Read about life with a service
dog on Renee's blog:
http://www.limyoga.com/service_dog_parkinsons/
O100
Cell and gene-based
technologies for restorative and
neuroprotective
therapies
Roger A Barker
Cambridge Centre for Brain
Repair, Department of Clinical Neuroscience, University of Cambridge, UK
The ability to more effectively rescue
the brain from the pathology of Parkinson’s Disease (PD) has long been sought.
One particular area that has been the subject of several clinical trials
involves trying to restore the dopaminergic nigrostriatal pathway back to
normal using either cell transplants or gene therapies.
In the case of cell therapies
this has largely involved implanting the dopaminergic neurons from the
developing midbrain (ventral mesencephalon - VM) of aborted foetuses. Other
cell types have been trialled but none have the pre-clinical data to support
their use in the way that VM tissue does. Even then, these VM transplants have
produced mixed results in terms of clinical benefits and side effects and in
this talk I will attempt to summarise the trials that have used these cells and
explain why the results have been so variable. This will lead on to a
description of the new FP7 funded EU study of VM transplants in patients with
PD (TRANSEURO), which also serves to provide a framework for future stem cell
based therapies for PD. In terms of gene therapies these have involved two main
strategies. One involves trying to rescue the nigrostriatal pathway using
growth factors (i.e. Neurturin), whilst the other involves trying to correct
some of the pharmacological abnormalities within the basal ganglia. This latter
approach embraces attempts to better deliver striatal dopamine as well as
increase the inhibition outflow of the subthalamic nucleus. These trials have
yet to show the benefits of some of the cell based approaches but nevertheless
still offer hope for selective groups of patients with PD. I will conclude by
discussing the challenges that trials with these agents engender which if not
properly addressed could undermine this whole therapeutic area.
O101
Exercise,
diet, and other lifestyle activities as treatments for Parkinson disease
Marten Munneke1,2
1ParkinsonNet,
Nijmegen, The Netherlands
2Parkinson Centre
(PARC), Radboud University Nijmegen Medical Centre, The Netherlands
Many patients with Parkinson’s disease become
progressively incapacitated, not only because of the well-known motor symptoms
but also because of a wide variety of non-motor symptoms. Drug treatment and
brain surgery are important cornerstones of the treatment program but evidence
is growing to support the effectiveness of various additional treatment
options. Accumulating evidence suggests that patients with PD might benefit
from physical activity and exercise in a number of ways, ranging from general
improvements in health to disease-specific effects and, potentially,
disease-modifying effects (although this is thus far only suggested by animal
data). So the time might be ripe to regard exercise as a real intervention –
much like a drug – for people with Parkinson’s Disease. Notwithstanding the positive
effects of exercise, many patients adopt a sedentary lifestyle because of their
motor (e.g. gait disturbances) and non-motor (e.g apathy) limitations.
Identifying ways to induce a sustained behavioral change, using specifically
tailored programs that address potential barriers such as depression, apathy
and postural instability, may lead to an improved quality of life in
individuals with PD. Another frequently mentioned treatment option includes the
use of special diets, to counter malnutrition, to avoid interference with
medication, and (again) to possibly modify the course of the disease.
Unfortunately, scientific evidence to support a specific diet for these
purposes is still lacking. In this presentation I will review the existing
evidence supporting the use of lifestyle activities in the treatment of
Parkinson’s Disease. In addition I will give an overview of effective
strategies to change lifestyle. This overview will clearly show that changing a
lifestyle is for everyone, with or without Parkinson’s Disease, one of the most
difficult things to do.
O102
Living Positively
After a Diagnosis of Parkinson's
Rich Clifford
I
was diagnosed with early onset Parkinson Disease in 1994 at the age of 42. I
was an Astronaut with two space shuttle missions already completed. I was aware
of the progressive and degenerative path the disease follows but, I was not
ready to quit flying into earth orbit. NASA managers responsible for crew
selection and certification were fully behind my desire to continue in the cue
for another space mission. With the exception of the NASA leadership I kept my
condition as a secret for 17 years. I was assigned to a third space shuttle
mission and I performed a space walk during the mission in March 1996. This was
very rewarding. I told myself to “Live life to the fullest extent possible”. My
message to those with Parkinson Disease is you can do anything you want to do -
maybe not as well as you use to perform. I still play golf. My game is not as
good as it was years ago but I enjoy the game. My friends enjoy playing with me
and the exercise is good therapy. The disease has progressed as expected. I no
longer fly privately and I do miss the exhilaration of precise flying. I still
live life’s adventures to the fullest. I encourage those with Parkinson Disease
to be well informed of current research and the multitude of varied therapy
options. Any program that improves the quality of your life should be explored.
Exploration is fun and beneficial. Stories from my space shuttle missions will
be interjected at appropriate places for emphasis. The theme of the
presentation is “Life is Good - Make the most of your opportunities.”
O103
Living Positively
After a Diagnosis of Parkinson's
Soania Mathur
Designing A Cure Inc., Toronto, ON, Canada
Dr. Soania Mathur was diagnosed with Young
Onset Parkinson’s Disease at the age of 27 at the start of her medical career
and just as she and her husband were starting a family. This diagnosis was met
with denial, fear and secrecy, a battle that lasted almost a decade - a time
during which thoughts of disability and a focus on all that she was losing,
consumed her. Now 15 years later Dr. Mathur has found herself on a more
positive path - one of patient education and advocacy, inspiring patients to
live well with this challenge while advocating for better treatments and that
much needed cure. Embracing her diagnosis was not an easy process but through
personal reflection and struggle, she began to recognize that although
Parkinson’s Disease was part of her future for now, her life experience would
ultimately depend on how she confronted her illness. That the power to choose
to tackle this disease with a positive outlook and hope, was truly hers. In her
words “At some point you have to abandon your fear of the future in order to
begin living your present.” She encourages others to recognize that they are so
much more than their disease and that they too can take back some measure of
control in what appears to be an uncontrollable situation. She stresses that
living positively after a diagnosis of Parkinson’s Disease includes many
factors that go beyond conventional multidisciplinary care and begin with a
fundamental paradigm shift and recognition of true personal power. Also
critical to this process and integral to coping with any chronic illness is
education, stress reduction, a strong support network, proactivity and making
crucial lifestyle changes that, combined with conventional treatments, improve
disease management and experience.
O104
What is new about the
link between Gaucher and Parkinsonism
Roy Alcalay
Columbia
University, Department of Neurology, NY, USA
The
link between Gaucher disease (GD), glucocerebrosidase (GBA) mutations and Parkinson’s disease (PD) has been established in
multiple genetic epidemiology studies. GD is the most common lysosomal storage
disease in the world and the most common genetic disease among Ashkenazi Jews.
Individuals affected by the benign form of the disease, Type-1, inherit two GBA mutations (autosomal recessive) and
produce insufficient amounts of the enzyme, glucocerebrosidase. Consequently,
lipid-substrates accumulate in the cells of the bone marrow, spleen, and liver
and can lead to hepatosplenomegaly or bone disease. Both Type-1 GD patients and
carriers of a single GBA mutation are
at an increased risk for PD. Large studies conducted at GD Centers estimate the
risk for PD in GD patients at 9-12% by age 80 compared to 1-1.5% among
non-carriers. The estimated risk for PD in heterozygote carriers varies from
6.8% at age 75 among GBA carriers
with no family history of PD to 29.7% at age 80 among those with a first degree
family history of PD. The PD characteristics of carriers are often similar to
idiopathic PD, but carriers may also present with atypical features including
more rapid motor progression. Cognitive impairment is more common among
carriers than non-carriers, and autopsy studies suggest GBA mutations are more common in autopsies of patients with PD and
Lewy Body Dementia compared to autopsies of controls or patients with
Alzheimer’s disease. Given the pathological similarities between GBA mutation carriers and non-carriers,
further understanding of the link between GBA
mutations and PD may shed light on the pathological mechanism of PD in general.
It is possible that low enzymatic activity of glucocerebrosidase is important
in mediating this association. Considering the risk of PD among GD patients and
heterozygote carriers is comparable, it is likely the mechanism underlying the
PD-GD association is more complex.
O105
Exploring mechanisms
that underlie the link between mutations in the Gaucher disease gene and
synucleinopathy risk
Michael G. Schlossmacher1,2,
Priyanka Singh1,2, S. Pablo Sardi3, Lamya S. Shihabuddin3,
Steffany Bennett4, Julianna J. Tomlinson1
1Program in Neuroscience, Ottawa Hospital
Research Institute, Ottawa, ON, Canada
2Department of Cellular & Molecular
Medicine, and 4Department of Microbiology, Biochemistry and
Immunology, University of Ottawa, Ottawa, ON, Canada
3Genzyme-Sanofi Corporation, Framingham, MA, USA
Introduction: The molecular mechanisms that underlie the risk
association between mutations in the acid beta-glucosidase-1 (GBA1) gene, Parkinson
disease and dementia with Lewy body disease remain elusive. The two disorders
are characterized by misprocessing of neuronal alpha-synuclein. GBA1-mediated
activity within lysosomes promotes the degradation of specific glycolipid
substrates, glucosylceramide and glucosylsphingosine. Reduction in GBA1’s
normal enzyme activity below 20% leads to variable organ dysfunction and
results in Gaucher disease. Several scenarios have been considered to explain
the strong risk association between the expression of one (or two) mutant GBA1
alleles and synucleinopathy risk.
Methods: To
better understand the molecular
cascade that links GBA1 mutations
to alpha-synuclein accumulation,
we pursued 3 experimental avenues: 1.) the exploration of over-expressing GBA1 mutants
in neural cell cultures and their effects on enzyme activity as well as
alpha-synuclein steady-states; 2.) the analysis of already available mouse
models of mutant Gba1 expression to monitor the effects on endogenous
alpha-synuclein; and 3.) the generation of bigenic animals to examine the
interaction between murine Gba1 knock-in mutations (D409V) and multiple copies
of human alpha-synuclein-encoding transgenes that carry a mutation (A53T). We
refer to the latter as “SYNerGY mice”.
Results: We observed that the expression of mutant GBA1 variants promoted
a dose-dependent rise in total alpha-synuclein; however, these mutants did not
lower the activity of endogenous, wild-type GBA1 enzyme, thereby excluding a
dominant-negative effect. We found that in bona fide Gaucher cells and mouse
brain, activity of GBA1 at less than 20% did not immediately elevate the
concentration of total alpha-synuclein, but rather led to global lysosomal
impairment. Finally, the expression of Gba1 D409V mutants in SYNerGY mice
elevated the concentration of total human alpha-synuclein to ~120% throughout
the neuroaxis when compared with alpha-synuclein transgenic mice that express
wild-type Gba1 alleles.
Conclusion: Our collective results suggest that GBA1 mutants increase the steady-state
of alpha-synuclein in cells and in vivo. Furthermore, likely more than one
mechanism is responsible for the association: 1) a gain-of-toxic function by
mutant GBA1 that impairs alpha-synuclein degradation; 2) a partial
loss-of-GBA1-mediated enzymatic function in neurons leading to an indirect rise
in alpha-synuclein; or 3) a combination of both. Finally, the interaction
between mutant Gba1 and human alpha-synuclein was confirmed in mouse brain.
O106
How the understanding
of Gaucher could lead to new therapies for Parkinson's
S. Pablo Sardi
Genzyme,
a Sanofi Company. Framingham, MA, USA
Introduction: Biallelic mutations in
the glucocerebrosidase gene (GBA1) cause Gaucher disease (GD),
the most prevalent lysosomal storage disease. Routine administration of glucocerebrosidase has been shown to be
effective in treating hematological, skeletal, and visceral disease
manifestations. However, the
recombinant enzyme is unable to traverse the blood-brain barrier to address the
increasingly recognized CNS manifestations. Monoallelic mutations in GBA1 have been recognized as the most
common genetic risk factor for developing synucleinopathies, including
Parkinson’s disease (PD) and dementia with Lewy bodies. In addition, PD
patients with or without GBA1 mutations
exhibit lower enzymatic levels of glucocerebrosidase in the CNS.
Objective: To probe the link
between glucocerebrosidase and alpha-synuclein and shed light into putative
therapeutic approaches for Gaucher-related PD.
Methods: We evaluated the
presence of synucleinopathy features in mouse models of Gaucher disease as well
as the existence of Gaucher characteristics in alpha-synuclein transgenic mice.
In addition, we evaluated the efficacy of glucocerebrosidase augmentation in
the CNS of these animal models.
Results: We found that a mouse
model of Gaucher disease (Gba1D409V/D409V)
exhibits characteristics of synucleinopathies, including progressive
accumulation of proteinase
K-resistant α-synuclein/ubiquitin aggregates in hippocampal neurons and a
coincident memory deficit. Glucocerebrosidase augmentation in the CNS of
symptomatic Gba1D409V/D409V
mice reduced the levels of ubiquitin/alpha-synuclein aggregates. Importantly,
hippocampal expression of glucocerebrosidase in Gba1D409V/D409V mice also reversed their cognitive
impairment when examined using the novel object recognition test.
Correspondingly, overexpression of glucocerebrosidase in the CNS of A53T
alpha-synuclein mice reduced the levels of soluble alpha-synuclein, suggesting
that increasing this glycosidase activity can restore alpha-synuclein
processing and modulate the progression of synucleinopathies.
Conclusion: The data support the
contention that mutations in GBA1 can
cause Parkinson disease-like alpha-synuclein pathology, and that increasing
glucocerebrosidase activity in the CNS represents a potential therapeutic
strategy for GBA1-related and non-GBA1-associated synucleinopathies.
O107
Use of human ES and
iPS cells for cell replacement in Parkinson´s disease
Agnete Kirkeby1,
Ulrich Pfisterer1, Jenny Nelander1, Shane Grealis1h,
Malin Parmar1
1Department of
Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell
Center, Lund University, Lund, Sweden.
Objective: Parkinson’s Disease (PD)
is a particularly interesting target for stem cell based therapy. The central
pathology is confined to a small group of neurons in the midbrain, the nigral
dopamine (DA) neurons and their projection to the striatum. Transplants of DA
neurons could be used to restore DA neurotransmission in the striatum,
substitute for the lost neurons, and bring back normal motor behavior.
Proof-of-principle that this can work has been obtained in trials where fetal
DA neuroblasts, have been transplanted to the putamen in patients with advanced
PD. Despite these encouraging results, work with human fetal tissue presents a
number of ethical and logistical problems and therefore does not represent a
realistic therapeutic option in the future. Further progress in this field is
critically dependent on the development of a bankable and renewable source of
transplantable DA neurons.
Methods: We have
developed a method to generate human neural progenitors and neurons from human
embryonic stem cells (hESCs), which recapitulates human fetal brain
development. By addition of a small molecule to activate canonical WNT
signalling, we induced rapid and efficient dose-dependent specification of
regionally defined neural progenitors ranging from telencephalic forebrain to
posterior hindbrain fates. In parallel, we also
develop cell reprogramming as an alternative source of neurons. We have found
that the neural conversion genes (Mash1, Brn2a, Myt1l) can convert human
fibroblasts into induced neurons (iNs). When combined with DA fate determinants,
functional DA neurons can be obtained with this technique.
Results: The DA neurons
obtained via our protocol closely resembled their fetal counterparts, making
them useful as a model system for studies of human fetal brain development and
also for developing transplantable therapeutic cells.
O108
Role of Sonic hedgehog in maintaining striatal homeostasis
Luis E. Gonzalez-Reyes1,8,
Miguel Verbitsky1, Javier Blesa3,4,
Vernice Jackson-Lewis2,4, Daniel Paredes6; Karsten
Tillack7, Sudarshan Phani2,4, Edgar
R. Kramer7, Serge Przedborski2,3,4, and Andreas H.
Kottmann1,3,4,5
1
Department
of Psychiatry, 2 Department of Neurology, 3Department of
Pathology and Cell Biology, 4 Center for Motor Neuron Biology and
Disease, Columbia University, NY, USA
5 Department of
Physiology, Pharmacology and Neuroscience, Sophie Davis School of Biomedical
Education, City University New York, NY, USA
6 Lieber Institute for
Brain Develoopment, Johns Hopkins Medical Campus, Baltimore, MD, USA
7 Center for Molecular
Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf,
Hamburg, Germany
8 Department of
Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
Objective:
Non-neurotransmitter mediated cellular signaling is
thought to play critical roles in the maintenance of neuronal circuits in the
healthy and diseased brain but mechanistic details remain unclear. We
investigated the relevance of neurotrophic and growth factor signaling in the
mature basal ganglia for the structural and functional integrity of
nigro-striatal neuronal circuitry.
Methods:
Utilizing gene expression tracer and conditional
gene ablation strategies targeting Sonic Hedgehog (Shh) expression in the nigro
striatal pathway we produced an unanticipated genetic model of progressive
neuronal dysfunction and -degeneration reminiscent of Parkinson’s disease.
Results:
The interruption of a non-cell autonomous mode of
Shh signaling originating from dopaminergic neurons causes progressive,
adult-onset degeneration of dopaminergic, cholinergic, and fast spiking
GABAergic neurons of the mesostriatal circuit, imbalance of cholinergic and
dopaminergic neurotransmission, and motor deficits. Variable Shh signaling
results in graded inhibition of muscarinic auto-receptor- and GDNF- expression
in the striatum. Reciprocally, graded signals that emanate from striatal
cholinergic neurons and engage the canonical GDNF receptor Ret inhibit Shh
expression in dopaminergic neurons. Our work reveals a novel mechanism for
neuronal subtype specific and reciprocal communication that is essential for
neurochemical and structural homeostasis in the nigrostriatal circuit. These
results provide integrative insights into non cell-autonomous processes likely
at play in neurodegenerative conditions such as Parkinson’s disease,
Parkinson’s disease with fronto temporal dementia and related conditions.
O109
Nurr1 as a therapeutic
target for neuroprotection and disease modification in PD
Mickael Decressac and
Anders Björklund
Wallenberg
Neuroscience Center, Lund University, Lund, Sweden
The
transcription factor Nurr1 is an orphan nuclear receptor that is known to be a
key regulator of the survival and maintenance of dopamine neurons during
embryonic development. Recently, however, it has been recognized that this gene
regulator may play an important role also in adult dopamine neurons, and as a
mediator of the degenerative changes seen in Parkinson´s disease (PD). Rare
cases of familiar PD have been associated point mutations in the Nurr1 gene,
and recent observations in brains from PD patients have shown that the
expression of Nurr1 is greatly reduced in affected dopamine neurons. These data
suggest that reduced cellular levels of Nurr1 may be associated with increased
vulnerability and impaired function in the nigro-striatal dopaminergic system.
Studies in mice and rats have provided further support for this idea, showing
that reduced Nurr1 expression, induced either by deletion of the Nurr1 gene or
by overexpression of the disease-causing protein alpha-synuclein, leads to a
PD-like state characterized by impaired dopamine neurotransmission and loss of
responsiveness to trophic factors like GDNF. These observations suggest that
reduced Nurr1 expression, induced by increased cellular levels of alpha-synuclein,
is a key element in the induction of dopamine neuron dysfunction seen in early
stages of the disease, and that loss of Nurr1 function may lead to increased
vulnerability of the affected dopamine neurons and thus contribute to the
progession of the disease. Together, the clinical and experimental data point
to Nurr 1 as key player in the pathogenesis of PD and identifies Nurr 1 an
interesting novel therapeutic target for disease intervention in PD.
O110
Maladaptive plasticity
in L-DOPA-induced dyskinesia: emerging role of serotonin transmission and other
presynaptic factors
M. Angela Cenci
Lund
University, Lund, Sweden
The
development of L-DOPA-induced dyskinesia (LID) in Parkinson´s disease (PD) is
attributed to maladaptive neuroplasticity resulting from the combined effects
of dopamine (DA) denervation and dopaminergic drug treatment. Once LID has
developed, it becomes difficult to reduce or reverse, and it can also be
elicited by strong emotions or stress. Studies of striatal gene expression in
animal models of LID have shown upregulation of genes involved in synaptic and
neuritic plasticity, extracellular matrix remodeling, endothelial and cellular
proliferation. By reviewing these studies, this lecture will first highlight the
complex plastic adaptations associated with LID, which clearly affect cells,
processes, and circuits in the brain at many different levels. Thereafter, the
lecture will zoom in on the role of serotonin transmission and other
presynaptic factors. Serotonin neurons express enzymes that mediate conversion
of L-DOPA to DA and storage of DA in synaptic vesicles, but they lack
high-affinity DA reuptake capacity and DA autoreceptors. Hence, they cannot
sense and autoregulate a possible, aberrant DA release. In the 6-OHDA-lesion
rat model of PD, L-DOPA-derived peak DA efflux in the striatum is reduced by
60-80% upon either chemical lesion of the serotonin innervation or treatment
with agonists of the serotonin autoreceptors, 5-HT1A/1B. Moreover, chronic
treatment with L-DOPA has a growth-promoting effect on serotonin axon
terminals, an effect that may further contribute to the presynaptic
dysregulation of DA release associated with LID. In addition to these
mechanisms, recent studies are highlighting the role of cortical serotonin
receptors, 5-HT1A in the presynaptic regulation of glutamate release both
locally and in the target areas of corticofugal projections. In the rat, the
increased striatal glutamate efflux accompanying the expression of LID is
attenuated by 5-HT1A selective agonists, which also improve dyskinesia. These
and other studies warrant further investigations on the role of anatomically
distinct populations of 5-HT1A and 5-HT1B receptors in the pathophysiology and
treatment of LID.
O111
Pre - and post-synaptic molecular mechanism underlying L-DOPA-induced
dyskinesia as possible new pharmacological targets
Erwan Bezard1, 2, 3, 4
1Univ. de Bordeaux, Institut des Maladies
Neurodégénératives, UMR 5293, F-33000 Bordeaux, France
2Service de Neurologie, CHU de Bordeaux,
F-33604 Pessac, France.
3Institute of Lab Animal Sciences, China Academy of
Medical Sciences, Beijing, China
4Motac Neuroscience Ltd, Manchester, UK
Objective: Levodopa induced dyskinesia (LID) has been recognized since the
introduction of levodopa for the management of Parkinson’s disease (PD) and
continues to be one of the most clinically challenging factors in long term
management of patients with PD. Most patients develop LID within ten years of
PD onset. Various risk factors including disease demographics, pharmacological
and possibly genetic causes might play a role. The pathophysiology of
established LID is however now better known and the potential armamentarium to
address and manage LID has significantly increased in the last decade.
Methods: Seminar is based upon exhaustive literature search through PubMed and
based upon original data collected by presenter’s laboratory.
Results: This seminar
describes the molecular mechanisms implicated in the emergence and
manifestation of LID. Particular emphasis is given to the role played in this
condition by abnormalities in signal transduction at the level of the medium
spiny neurons of the striatum, which are the principal target of L-DOPA. Recent
evidence pointing to pre-synaptic dysregulation is also discussed.
O112
Multiple dopamine-dependent synaptic mechanisms underlying dyskinesia in
animal models
Barbara Picconi
Laboratory
of Neurophysiology, Santa Lucia Foundation, IRCCS, Rome, Italy
It has been suggested that the
impairment in activity-dependent modifications in synaptic efficacy, such as
long-term depression (LTD) and long-term potentiation (LTP), could account for
the onset and progression of motor symptoms of Parkinson’s disease (PD).
Understanding of these maladaptive forms of plasticity has mostly come from the
electrophysiological, molecular and behavioural analyses of experimental animal
models of PD. In PD condition, a host of cellular and synaptic changes occur in
the striatum in response to the massive loss of dopamine innervation. Chronic
L-DOPA therapy restores physiological synaptic plasticity and behaviour in
parkinsonian treated animals, but most of them, similarly to patients, exhibit
reduction in the efficacy of the drug and disabling abnormal involuntary
movements (AIMs) defined in their complex as L-DOPA-induced dyskinesia. In
those animals experiencing AIMs, synaptic plasticity is altered and is
paralleled by modifications in the postsynaptic compartment. In particular,
dysfunctions in trafficking and subunit composition of NMDA receptors (NMDARs)
on striatal efferent neurons result from chronic non-physiological dopaminergic
stimulation and contribute to the pathogenesis of dyskinesias.
O113
Myopathy
causing camptocormia in idiopathic Parkinson's disease
Simone Spuler1,
Maximilian Berger1, Henriette Krug2, Stefan Kempa3
1Charité Medical
Faculty and Max Delbrück Center for Molecular Medicine, Berlin, Germany
2Charité
Universitätsmedizin Berlin, Germany
3Max Delbrück Center
for Molecular Medicine, Berlin, Germany
Objectives: Some patients with
idiopathic Parkinson's disease develop severe unfixed bent forward posture, a
symptom called camptocormia or head drop. The cause is a matter of debate.
Controversial concepts include dystonia of abdominal wall muscles versus
isolated myopathy of the deep thoracic and cervical extensor muscles.
Methods: We studied 17
patients Parkinson's disease and camptocormia or head drop clinically and
electrophysiologically and obtained muscle biopsy specimens from deep back
extensor muscles after IRB approval. Back extensor muscle obtained during back
surgery served as age-matched controls (n=6). We performed histological and
immunohistochemical analysis. Further, stable isotope labeling by amino acids
(SILAC)-based LC-MS/MS proteomics was performed on eight muscles obtained from
camptocormia-patients and four controls.
Results: Our results
demonstrate that deep extensor muscles from camptocormia patients exhibit
myopathic features. Inflammation, mitochondrial damage or neurogenic atrophy
were only occasionally associated with camptocormia or head drop. Aggregates of
desmin positive and dystrophin positive material were also identified. Proteome
analysis revealed altered expression of a high number of proteins in
camptocormia muscle.
Conclusion: The results point
towards a primary myopathic cause of camptocormia in Parkinson's disease.
O114
Camptocormia:
pathogenesis, classification, and response to therapy
Joseph Jankovic
Parkinson's
Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor
College of Medicine, Houston, TX, USA
James
Parkinson in his 1817 “Essay on the Shaking Palsy” drew attention to “a
propensity to bend the trunk forward” as one of the classic signs of
Parkinson’s disease (PD). Postural deformities involving the neck and trunk,
such as the ”head drop”, “bent spine”, “pisa sign”, and “camptocormia” (extreme
truncal flexion), have been receiving growing attention and have been subjected
to several recent reviews (Jankovic, 2010; Doherty et al, 2011). Camptocormia
is characterized by severe, often 90 degree or even greater flexion of the
trunk, that may be present in a sitting position and typically increases during
walking and resolves in supine position or when patient achieves an erect
posture while performing the “climbing on the wall” maneuver. Camptocormia may
be a feature of axial dystonia but is also often associated with PD and other
parkinsonian disorders. No factors have been identified that reliably predict
which patients with PD will develop this deformity, although it appears to be
more common in patients with more severe, postural-instability-gait-difficulty
(PIGD) form of PD. The pathogenesis of this disabling PD feature is not well understood,
but the two most frequently proposed mechanisms include dystonia-rigidity or
extensor truncal myopathy. Although these and other hypotheses have been
debated for some time, many experts agree that the deformities associated with
PD are somehow related to dysfunction of the basal ganglia resulting in axial
dystonia and rigidity, which leads to truncal flexion and other abnormal
postures (such as striatal hand and foot deformities) with secondary muscle
atrophy, inflammation, fibrosis and other non-specific changes. Additional
support for dystonia, rather than myopathy, as the primary mechanism of
camptocormia and the head drop syndrome associated with PD, is provided by the
finding of muscle contraction associated with these abnormal postures and that
the abnormal posture often improves during certain maneuvers (sensory tricks),
such as wearing a backpack (Gerton et al. 2010). Furthermore, botulinum toxin
when injected into the rectus abdominus and paraspinal muscles, and deep brain
stimulation can at least transiently improve the abnormal posture in some
patients.
Doherty
KM, van de Warrenburg BP, Peralta MC, Silveira-Moriyama L, Azulay JP, Gershanik
OS, Bloem BR. Postural deformities in Parkinson's disease. Lancet Neurol
2011;10:538-49.
Gerton
BK, Theeler B, Samii A. Backpack treatment for camptocormia. Mov Disord
2010;25:247-248.
Jankovic
J. Camptocormia, head drop and other bent spine syndromes: heterogeneous
etiology and pathogenesis of parkinsonian deformities. Mov Disord
2010;25:527-8.
O115
Dropped head syndrome
in Parkinson's disease
Kenichi Kashihara
Okayama
Kyokuto Hospital, Okayama, Japan
Objective: Dropped head syndrome
(DHS), characterized by forward neck flexion is a common occurrence in
neuromuscular disorders, but it is also known to occur in approximately 5.8% of
patients with Parkinson’s disease (PD). I update current knowledge of DHS in PD.
Method: Using PubMed, English publications were reviewed on
antecollis or dropped head associated with PD.
Results: One
of the main causes of DHS in PD is antecollis. Patients
with PD and DHS typically show little or no muscle weakness and instead display
disproportionately increased tonus of the neck extensor muscles. In fact,
bulging of the neck extensor muscles, with a hard wooden feel on palpation, is
a useful indicator of antecollis in PD. Antecollis in PD
was more often found in patients whose prominent parkinsonian signs were
rigidity and akinesia. Myopathy of the neck
extensor muscles also has been reported in PD to
induce DHS. Majority of myopathic changes in muscle biopsy specimen or EMG
study, however, could be induced secondarily to a chronic dystonic posture. In some cases, dopaminergic medications,
especially dopamine agonists, reportedly aggravate antecollis, while improving
symptoms in other patients. The mechanism by which it induces these
paradoxical effects requires further investigation. Once elucidated, these
findings will help us understand the underlying event leading to antecollis and
assist in the development of new therapeutic approaches for the treatment of
DHS in PD. Besides dopaminergic medication, several authors have reported on
the efficacy of botulinum toxin or lidocaine injection for the treatment of
DHS. Intensive physiotherapy and deep brain stimulation (DBS) might also be
beneficial, even though there is insufficient evidence to justify the use of
DBS to solely treat antecollis. Lastly, use of a soft neck brace can help
elevate the chin, and thus improve the patient’s visual field and reduce
discomfort.
O116
Overview: Deep brain
stimulation
Michael S. Okun 1,
Elena Moro 2
1University of Florida
Center for Movement Disorders and Neurorestoration, FL, USA
2
Service de Neurologie, CHU de Grenoble, Grenoble, France
Objective: To review the most
important information for patients and families regarding deep brain
stimulation (DBS) therapy for Parkinson’s disease.
Background: The field of DBS
therapy for Parkinson’s disease has been changing rapidly. Recently many
prospective randomized DBS trials have been published, and also there have been
many advances in both technology and management. In this session we will aim to
review the most important advances in the field, and we will present several
illustrative cases to emphasize best management strategies. The session will
cover patient selection, brain target selection, interdisciplinary DBS
management teams, and troubleshooting DBS problems. Additionally, the session
will briefly cover new and emerging technologies.
O117
Overview: Aging and PD
Timothy J. Collier1,
James Surmeier2, Jeffrey Kordower3
1 Michigan State
University, Grand Rapids, MI, USA
2 Northwestern
University, Chicago, IL, USA
3 Rush University
Medical Center, Chicago, IL, USA
Aging
is the best-documented primary risk factor for Parkinson’s disease (PD). This
workshop will examine the connections between aging and PD. We will highlight
evidence of selective neuronal vulnerabilities in aging and PD and the
relevance of models of normal aging to PD.
Selective Vulnerability.
One
feature of PD is that subpopulations of midbrain dopamine (DA) neurons are more
vulnerable to degeneration than those immediately adjacent to them. We
exploited this regional variation to test the hypothesis that if aging is
related to PD at a cellular level, markers with known associations to PD would
accumulate in the vulnerable DA cell population with advancing age. We
conducted this study with tissue from nonhuman primates ranging in age from
9-30 years. We found that all markers associated with PD that we examined were
increased in PD-related vulnerable DA neurons during normal aging – markers of
oxidative stress, dysfunction of degradation of abnormal proteins, and
inflammation. In other studies, evidence indicates that neurons with the greatest
vulnerability in PD have high mitochondrial oxidant stress in healthy animals.
We have data now from vulnerable DA neurons and other neurons at risk in PD
indicating they have very high mitochondrial oxidant stress levels. Genetic
mutations associated with PD (e.g., DJ-1
deletion) or intracellular alpha-synuclein inclusions increase mitochondrial
oxidant stress, providing a means of explaining the effects of genetic
alterations associated with increased risk.
Aging as a Model of
PD.
Modeling
PD is problematic. We know that aging is a primary risk factor for PD. Yet
aging is seldom incorporated in models of PD for preclinical testing of
experimental therapeutics. Whenever it is, results are clearly different than
in young subjects. The majority of clinical testing involves elderly
individuals and has yielded inconclusive results. Is aging the best test
platform for testing therapeutics for PD?
O118
Overview: Pain in PD
Blair Ford
Columbia
University, New York, NY, USA
Pain
is a common symptom in Parkinson’s disease and accounts for substantial
morbidity in up to 80% of patients. Despite contributing to disease-related
discomfort and disability, pain in PD is frequently overlooked and undertreated
in clinical practice. Converging evidence from recent neurophysiology and
neuropathology studies has led to an improved understanding of the
neuroanatomical and electrophysiological substrate of pain in PD. Although the
underlying neurophysiology remains unclear, there is increasing understanding
of the role of the basal ganglia in somatosensory processing as well as
involvement of additional brainstem structures and non-dopaminergic pathways.
Categorizing painful symptoms based on their clinical description into
musculoskeletal, dystonic, radicular/peripheral neuropathic and central pain
categories provides a useful framework for management. The precise breakdown of
painful symptoms into each category varies between studies but it would appear
that most pain in PD is related to a musculoskeletal cause or painful dystonia.
Pain in PD is often cyclical and should be evaluated in relation to motor
symptoms and dopaminergic therapy: musculoskeletal pain associated with
rigidity and immobility benefits from addition of dopaminergic agents; dystonia
related to levodopa therapy responds to medication adjustment. For intractable
pain, a multi-disciplinary approach is recommended: physical therapy, liaison
with pain management and consultations to rheumatologic, orthopedic and
neurosurgical services should be considered.
O119
Overview: Models of
care on speech for people with Parkinson's
Angela Roberts-South1-2
1Western University
Health and Rehabilitation Sciences, London, ON, Canada
2
Movement
Disorders Laboratory/NPF Centre of Excellence, London, ON, Canada
The
ability to be understood by others, intelligible communication, is one of the
primary goals of speech and language therapy. Individuals with Parkinson
disease and other parkinsonism related conditions (e.g., PSP, MSA) may face
substantial challenges in being understood by others. Effective and
intelligible communication depends on a variety of factors including the
severity of speech impairment (e.g., voice loudness, clarity of speech sounds,
intonation). Further, changes in language and cognition (e.g., finding words,
formulating thoughts, understanding others) can also affect communication in
PD. Environmental factors, sensory impairments (e.g., hearing and vision), and
also listener variables contribute to the complexity of communication in PD.
This complex interaction highlights the need to address communication from the
perspective of the individual with the communication impairment and also the
perspective of the communication partner. Today there are a myriad of
treatments available for individuals with communication impairments in PD and
related disorders. These include exercise treatments based in theories of
neuroscience, treatment approaches focused on enhancing everyday participation
in communication activities, and technologies to support communication. In this
session an overview of current models of speech treatment in PD will be
presented to enhance understanding of the complexity of communication, provide
a survey of the most recent science relative to communication challenges in PD
and related disorders, and to enhance knowledge of options available for
treating communication changes associated with PD and related disorders.
O120
Is there a
link between Parkinson’s disease and the Gaucher metabolic disorder?
Anne Noreau1,3, Jean-Baptiste Rivière1, Sabrina
Diab1, Patrick Dion1,3, Sylvain Chouinard1,
Michel Panisset1, Nicolas Dupré2, Guy A. Rouleau1,3.
1Centre d’Excellence en Neurosciences, Centre de recherche du CHUM et
Département de Médecine de l’Université de Montréal, Québec, Canada.
2Faculté de Médecine, Université Laval, Département de Sciences
Neurologiques, CHA-Enfant-Jésus, Québec, Québec, Canada.
3Institut neurologique de Montréal, Université McGill, Québec, Canada.
Contexte: La maladie de Gaucher est une
maladie génétique rare caractérisée par une déficience de l'enzyme
glucocérébrosidase lysosomale (GBA) conduisant à l’accumulation de lipide dans
les cellules. Dans les familles des gens souffrants de la maladie de Gaucher,
on note une augmentation de l’incidence de la maladie de Parkinson (PD).
D’ailleurs, une étude multicentrique a démontré une fréquence plus élevée de
mutations dans le gène GBA chez les
patients parkinsoniens par rapport aux individus sains contrôles. Le principal objectif de notre étude était d'évaluer
l'implication éventuelle des mutations du gène GBA dans une cohorte canadienne-française PD.
Méthodes: Nous avons procédé au reséquençage
du gène GBA dans une cohorte de 213
patients canadiens-français avec un diagnostic clair PD et 190 contrôles sains,
d’âges similaires. Les amorces ont permis l’amplification des 11 exons codants
du gène GBA préférentiellement à son
pseudogène.
Résultats: Des mutations hétérozygotes ont été
retrouvées chez 10,8% des patients PD comparativement à 5,8% chez les
contrôles. Cette étude nous indique de l’implication probable du gène GBA dans la maladie de Parkinson dans la
population canadienne-française.
O121
Freezing:
Underlying mechanisms and the role of cueing
Alice Nieuwboer, Elke Heremans, Sarah Vercruysse1
1Leuven University, Leuven, Belgium
Objective: To summarize the
evidence on the origins of freezing of gait (FOG) and highlight the
contribution of cueing in preventing FOG in Parkinson’s disease (PD).
Methods: Literature review and
experimental pre-post cueing studies during turning. We compared groups of age-
and disease-matched freezers and non-freezers during straight-line gait and
turning using 3D Vicon technology off medication.
Results: FOG may be related to
5 hypotheses. The first is that there is a specific spatiotemporal deficit of
stepping which brings on freezing. The second is that there is a deficit of internal
generation of gait, especially when adaptations are required. A third motor
hypothesis is that the coupling between postural control and step generation is
deficient, probably also related to an incomplete weight shift to the
supporting leg. A fourth is that FOG is brought on by executive dysfunction.
Finally, the fifth hypothesis states that FOG is due to reduced visuospatial
perception.
Cueing
has the potential to regulate the stepping deficit and aid the generation of
movement through the provision of discrete (visual or auditory) external
information as a motor trigger or target. Neuroimaging studies indicate that
fronto-parietal and dorsal neural networks are less active in FOG, networks
which are thought to be activated by cueing. Our gait lab studies and other
work show that cueing can reduce the severity of FOG and the number of episodes
but cannot convert freezers to non-freezers. Cues remain effective during
obstacle crossing and dual tasking up to an extent. Cues do not correct
postural control, yet are effective in reducing FOG. Hence, the effects of cues
confirm the first and second motor hypotheses. Impaired cognitive function
would predict that applying cues to daily life and in a variety of situations
is hampered in patients with FOG, which needs to be addressed in
rehabilitation.
O122
Why do
persons with PD fall? Does treatment help to reduce falling?
Fay B. Horak
Oregon Health and Science
University, Portland, OR, USA
This
presentation will review a system’s framework for understanding how postural
disorders in Parkinson’s disease result in falls. All six postural systems
involved in controlling postural control can be affected by Parkinson’s
disease: 1) The musculoskeletal system is impaired by flexed postural
alignment, position of the body CoM near limits of stability, and axial
rigidity; 2) The postural limits of stability are reduced and verticality
perception may be abnormal; 3) Automatic postural responses to external
perturbations are slow and weak, but not late and show inflexible strategies
with changes in conditions; 4) Anticipatory postural adjustments are reduced
and do not scale; 5) Sensory orientation is affected by poor kinesthesia with
compensatory visual dependence; and 6) Postural stability during gait is affected
by trunk stiffness, increased double support time, reduced foot clearance, lack
of arm swing, and variable timing. In addition, both posture and gait require
more attention than in subjects without Parkinson’s disease. Early in the
disease, postural control is primarily affected by bradykinesia and rigidity
that can be reduced with levodopa. However, later in the disease
nondopaminergic postural problems, such as inflexible changes in strategy and
poor kinesthesia may be added. Levodopa and Deep Brain Stimulation have been
shown to worsen some postural disorders but improve others, but not always in
the same manner. In contrast, many studies have shown that exercise or physical
therapy can improve balance and gait and reduce falls in people with Parkinson’s
disease. However, the best exercise approach and dose of exercise to improve
mobility and prevent falls is uncertain. Recently, integrative exercise
approaches that include agility training with cognitive challenges, such as Tai
Chi, Tango dancing and an Agility Boot Camp have shown to be particularly
effective in improving mobility and preventing falls.
O123
The
benefits of exercise in reducing falling in PD
Victoria
Goodwin
University of Exeter, UK
Background: Despite the extensive evidence, particularly
for exercise-based programmes, for preventing falls amongst the general
population there has been comparatively little research evaluating effective
interventions for people with Parkinson’s. Studies have identified a number of
risk factors for falling that may be amenable to exercise such as freezing,
impaired balance and gait, lower limb muscle weakness and fear of falling.
Current evidence: To date, the evidence for
the effectiveness of exercise-based interventions to reduce both the number of
people with Parkinson’s who fall and the number of falls remains uncertain.
However, the trends are encouraging and there are a number of large randomised
controlled trials and economic evaluations underway in Europe and Australia
that will provide a clearer understanding of what may be effective and
cost-effective management strategies that can be implemented into clinical
practice in the future.
This
presentation will provide:
·
A
rationale for the potential benefits of exercise to prevent falls among those
with Parkinson’s;
·
An
update of the existing evidence;
·
An
overview of ongoing research.
O124
What are
biomarkers and why do we need them?
David G. Standaert
University
of Alabama at Birmingham, Birmingham, AL, USA
Biomarkers are measurable and
quantifiable biological features which can be used to assess a disease
condition and enable the development of therapeutics. Biomarkers can be used to
identify those at risk for developing a disease, to assess the severity and
rate of change of the disorder, or to assess the response to therapy. A wide
variety of different technologies can be employed, ranging from simple
biochemical measurements to complex imaging modalities. Biomarkers may be
discovered through rationale, disease-based strategies or may be found through
open-ended empiric approaches. There are a number of biomarkers which have been
accepted in common clinical practice. Examples include tumor markers such as
the prostate specific antigen, and markers of cardiac injury such as serum
troponin levels. Biomarkers are also employed in neurological disorders and
have played a key enabling role in the development of new therapies; an example
is the use of MRI imaging to assess disease activity and severity in multiple
sclerosis. In Parkinson disease, the most pressing need is for a biomarker to
assess the rate of disease progression. This would be a critical tool in the
search for neuroprotective therapies, but at the present time no marker with
sufficient reliability has been identified. Several strategies are being
pursued but there are substantial challenges to be overcome, particularly the
validation of potential markers in human disease populations.
O125
Update on
unbiased methodologies to identify biomarkers
Howard Federoff, Massimo Fiandaca, Amrita Cheema, Yuriy Gusev and Subha
Madhavan
Georgetown University
Medical Center, USA
Objective: Detecting Parkinson’s disease
(PD) at the earliest stage possible holds the greatest promise for evaluating
interventions that may modify natural history. This talk will review unbiased
methods that are used to detect and stage PD including research methods that
may be useful in preclinical diagnosis.
Problem: PD is proposed to be
initiated outside of the midbrain and may possibly be a systemic disease.
Efforts to identify preclinical PD need to consider the Braak staging and the confluence
of epidemiological data implicating relatively soft symptoms and signs that
antedate the classical presentation of PD most typically involving motor
features. The Braak staging commends consideration of Stage 1 with involvement
of the dorsal motor nucleus of IX/X, anterior olfactory nucleus and enteric
nervous system. The clinical observations of hyposmia, constipation, and
dysautonomia may be correlated with the proposed Stage 1 pathologies.
Results: A brief description of
methods to assess GI, cardiovascular and smell are described along with the
application in the evaluation of patients at-risk and those presenting with
possible PD. A summary of these methods will be discussed. In addition, new and
robust peripheral methods relying in the informational molecules harbored by
circulating blood cells, plasma and
CSF will be discussed
using new data to explore the potential clinical utility of these methods.
Overall, we will review the methods that are used to identify and validate
biomarkers in an effort to detect preclinical PD. We will illustrate the use of
multimodal data integration to strengthen biomarker utility.
O126
Emerging biomarkers
Claire Henchcliffe
Weill
Cornell Medical College, NY, USA
Objective: To examine the most recent molecular,
genetic, and imaging biomarkers for Parkinson’s disease (PD), and to critically
evaluate their potential for diagnosis, measuring disease progression, and
defining response to treatment.
Methods: Survey of recent peer-reviewed publications including fluid-based
and neuroimaging markers.
Results: Hypothesis-driven studies have identified specific proteins, transcripts,
and metabolites that alone or in combination are associated with PD. Recent
studies have highlighted alpha-synuclein, DJ-1, markers of oxidative stress,
and markers of inflammation. While none of these are yet validated, coordinated
efforts inclduing BioFIND and the Parkinson’s Progression Markers Initiative
(PPMI) are underway to facilitate marker discovery and validation. Sophisticated
imaging techniques are also proving promising. The 123I-ioflupane ligand with single photon emission computed tomography is
approved as an aid to diagnosis. Other ligands targeting nigrostriatal pathway
integrity, for example the vesicular monoamine transporter (VMAT), may also
prove useful but at present are only available in the research community.
Moreover, whether these will accurately measure neurodegeneration remains
to be
determined. Ultrasound provides valuable information on the substantia nigra, and
is under intensive investigation, but is not yet in use in clinical practice.
MRI measures of fractional anisotropy, arterial spin labeling, and diffusion
tensor imaging are of great interest, and magnetic resonance spectroscopy
provides distinct neurochemical profiles that associate with PD. Ligands that
target other processes, such as amyloid deposition, or integrity of the
acetylcholinergic system, are predicted to provide complementary information
but are early in development in PD.
Conclusion: With rapidly evolving technology, multiple candidates are presenting as
putative PD biomarkers. Most likely a battery of complementary markers will be
required, and one marker will not suit all needs. Despite progress in
developing diagnostic markers, there remains a critical need for progression
and treatment response markers, and for markers of endophenotypes to aid in
personalizing
therapeutic strategies.
O127
Drug development challenges - Pharmaceutical industry
perspective
Bernard Ravina
Biogen
Idec, Cambridge, MA, USA
There
are numerous challenges in developing new therapeutics for Parkinson’s disease.
Dopamine replacement therapies and interventions, such as deep brain
stimulation, that are based on basal ganglia physiology have been successful. However,
efforts to develop agents that modify the disease course and slow progression
have not been fruitful. This presentation will focus on process of drug
development, from bench to bedside, and the challenges of developing disease
modifying interventions, which can be broadly grouped in three categories:
preclinical research including target validation and animal models; biomarker
development to assess target engagement and downstream effects; and clinical
trial design and clinical measurement. Each of these categories contributes to
risk and attrition in the drug development process. The emphasis of this
presentation will be on the roles of biomarkers and clinical trials.
O128
Recognizing the subtypes and assessing severity of
dyskinesia and the clinical impact
Beom S. Jeon
Department
of Neurology and Movement Disorder Center, Seoul National University Hospital,
Seoul, Korea
Objective: After the introduction of
high dose levodopa oral therapy in the 1960s, levodopa has been established and
remained as the gold-standard in the medical treatment of Parkinson’s disease
(PD). Long-term treatment with levodopa, however, is associated with the
development of motor fluctuations and drug-induced dyskinesias, which cause
significant disability to patients and represent a huge challenge to
clinicians.
Methods: This presentation will
review the various spectrum of motor fluctuations and dyskinesia and the
assessment of their severity as well as impact on the health related quality of
life of patients.
Results: Motor
fluctuations and drug-induced dyskinesias are common and important problems for
advanced PD patients. Careful history of present illness and examination are
the first step in identifying these complications and can elicit useful
patterns of symptoms and phenomenology. The duration, frequency, intensity,
time factors to “on” or “off” period, anatomical distribution, patient
perceptions, functional disability, and objective impairment are the major
dimensions of subtype classification of motor complications. In clinical
practice, motor fluctuations are commonly measured by patients’ home diaries or
obtained from unified PD rating scale (UPDRS) part IV responses. More objective
evaluation tools, such as actigraphs, portable video monitoring units, or patient-worn
compact motion sensor devices (using accelerometers and gyroscopes) can be used
in conjunction with the conventional procedures. Several clinical scales which
are proposed for the assessment of drug-induced dyskinesia in PD will be
discussed and practical applications will be suggested. Early detection and
prompt management of motor fluctuation and dyskinesia are crucial to the
ongoing care of the PD patients with advanced disease.
O129
Current management of LID - medical and surgical
Jose A. Obeso
University
of Navarra, Pamplona, Spain
Objective: Sample language for WPC abstract objective.
To review the pharmacological tools and the surgical options to treat
levodopa-induced dyskinesias in Parkinson’s disease.
Methods: Sample language for WPC abstract methods. Literature search of
clinical trials using anti-dyskinetic drugs and the effect of surgery (DBS and
ablative surgery). Personal experience in the management of patients with
severe LID.
Results: Sample
language for WPC abstract results. The most efficacious anti-dyskinetic
treatment is sugery of the globus pallidus pars interna. Deep Brain Stimulation
has the advantage of a bilateral effect when LIDs are generalized or have a
predominant axial distribution. Pallidotomy is reserved when an unilateral
effect is sufficient. There is no single drug available which have an
anti-dyskinetic effect that parallels the one of surgery. Duodendal levodopa
administration or subcutaneous apomorphine delivery can substantially
ameliorate LIDs.
Conclusions. Patients with severe LID require first,
careful adjustment of levodopa and other dopaminergic drugs. A trial with
Amantandine is worth pursing but with relatively limited value. Continuous
dopaminergic stimulation may provide significant improvement. When highly
disabling, LIDs are best controlled with surgery.
O130
Future
Management of LID: What's in the pipeline?
Susan Fox
University
of Toronto, Toronto, ON, Canada
Objective: to review potential therapies for treatment
of levodopa-induced dyskinesia (LID)
Method: Preclinical studies and RCTs published in the past 2-3 years
investigating treatment options for LID will be reviewed.
Results: Options for managing LID include agents that a) reverse
parkinsonism, without inducing dyskinesia as well as b) therapies that directly
reduce dyskinesia. Preclinical studies have been performed using a range of
strategies, including non-dopaminergic drugs and novel agents that target
second messenger systems that are implicated in the pathophysiology of LID.
Clinical studies involving a range of pharmacological targets including
glutamate antagonists; serotonin and adrenoceptor antagonists, that have
progressed to phase II/III studies, will be presented.
O131
Introduction:
Overview of the research process and advances in communication between
researchers and participants
Diane Cook1, Benzi Kluger2, Veronica Todaro3, Claire Meunier4
1Colorado Neurological Institute, Denver, CO,
USA
2University of Colorado, Denver, CO, USA
3Parkinson’s Disease Foundation, New York, NY,
USA
4The Michael J. Fox Foundation, New York, NY,
USA
This
workshop will present an overview of research in Parkinson’s disease, but will
focus on clinical trials including the following areas: identification of
research need, study design, funding, research team, recruitment, trial
participation and participant protection. There will be discussion of the
collaborative nature of the process that will highlight organizations,
resources and tools that offer information, education and support at various
stages, such as the Fox Trial Finder, a Parkinson’s clinical trial matching
tool. The emphasis will be on why it is important to engage people with
Parkinson’s and care partners in the research process and how they can play a
role at different points in that process, such as clinical trial participation,
providing input into study design, or serving on an Institutional Review Board.
Discussion will also cover how people with Parkinson’s and care partners can
prepare to take leadership roles in educating and promoting participation by
others through programs such as the Parkinson’s Disease Foundation’s
Parkinson’s Advocates in Research Program (PAIR). The important partnership
between trial participant and researcher will be explored, as well as ways to
strengthen and expand that relationship through improved communication and
collaboration. The benefits of this collaboration to both patient and
researcher will be emphasized. The panel will share personal stories that
promote deeper understanding of the significance and broad implications of
personal involvement in the research process.
O132
Overview:
depression, apathy, and anxiety in Parkinson’s disease
Laura Marsh1,
Roseanne Dobkin2
1Michael E. DeBakey VA Med
Center/Baylor College Medicine, Houston, TX, USA
2Robert Wood Johnson
Medical School, Piscataway, NJ, USA
Objective: To recognize the everyday presentations of
depression, apathy, and anxiety in Parkinson’s disease (PD), including the
behavioral changes that can occur in each type of affective disturbance, how to
distinguish psychiatric disturbances from non-clinical emotional changes, and
their treatments using non-medication and medication-based therapies.
Methods: The clinical
features and treatment of depressive, apathy, and anxiety disturbances in PD,
with an aim towards increasing early recognition and treatment of clinically
significant mood disturbances. Details of behavioral treatments of depression,
apathy, and anxiety will be described along with the role of coping with
everyday stressors. The impact of stigma on obtaining psychiatric treatment
will also be reviewed.
Results: Depressive, apathetic, and anxiety
disturbances involve emotional, cognitive, and physical features that can
overlap with features of PD. Awareness of their distinguishing features and
course helps with early identification and monitoring response to treatments,
which include medications and psychotherapies. Effective treatments are
identified for depressive disorders and there is ongoing research on treatments
for apathy and anxiety. Once mood disorders are effectively treated, there
remains a role for effective coping strategies to address the challenges of PD.
In addition, stigma about seeking psychiatric care remains a major barrier to
care to effective treatment.
O133
Dyskinesias:
Mechanism and treatment
Erwan Bezard1
1 Univ. de Bordeaux, Institut des Maladies
Neurodégénératives, UMR 5293, F-33000 Bordeaux, France
2 Service de Neurologie, CHU de
Bordeaux, F-33604 Pessac, France
3 Institute of Lab Animal Sciences, China Academy of
Medical Sciences, Beijing, China
4 Motac Neuroscience Ltd, M15 6WE Manchester, UK
Objective: Les dyskinésies dopa-induites sont une conséquence invalidante du remplacement
de la dopamine par la levodopa. Les quinze dernières années ont vu les
connaissances de leur physiopathologie progresser à grand pas, autorisant
maintenant l’espoir de développer des stratégies thérapeutiques efficaces.
Cette présentation a pour objectif de présenter l’état de l’art des
connaissances sur les causes de ces dyskinésies ainsi que sur les solutions
thérapeutiques prometteuses en cours de développement préclinique et clinique.
Methods: Le séminaire est basé sur une revue exhaustive de la littérature utilisant
le moteur de recherche PubMed.
Results:
Les avancées conceptuelles dans la genèse de
modèles expérimentaux heuristiques seront mises en avant ainsi que les cibles
thérapeutiques potentielles que sont les agonistes des récepteurs à la
sérotonine 5-HT1A et 1B, les antagonistes ou modulateurs allostériques du
récepteur mGluR5, le contrôle de la voie des MAPKs ou encore la diminution de
la disponibilité des récepteurs dopaminergiques, notamment de type D1. Nous
terminerons avec les dernières études cliniques testant ces hypothèses.
O134
Parkinson’s
disease is much more than a disease of dopamine
Etienne C. Hirsch
Centre de recherche de l’Institut
du cerveau et de la moelle épinière, INSERM UMR975, CNRS UMR 7225, UPMC,
Hôpital de la Salpêtrière, Paris, France
La maladie de Parkinson est
caractérisée par une lente et progressive des neurones dopaminergiques associée
à la présence de corps de Lewy contenant de l’α-synucleïne.
Les symptômes qui sont la conséquence de cette dégénérescence à savoir :
akinésie, rigidité et tremblement sont relativement bien corrigés par des
traitements dopaminergiques qui restaurent la neurotransmission altérée.
Toutefois, avec l’évolution de la maladie d’autres symptômes qui ne répondent
pas aux traitements dopaminergiques apparaissent. Ceux incluent la
détérioration intellectuelle, l’altération de l’odorat (anosmie), les troubles
de la parole (dysarthrie), la douleur, la constipation, les troubles de l’humeur
et l’apathie ainsi que dans des stades avancés de la maladie les troubles de
l’équilibre et les chutes. Ce dernier symptôme est particulièrement préoccupant
car associé à la détérioration intellectuelle il réduit l’espérance de vie des
malades. Il constitue aussi un problème en termes d’économie de la santé car il
multiplie par trois le cout de prise en charge. Récemment, plusieurs analyses
en IRM fonctionnelle ont montré que la marche implique une structure du tronc
cérébral appelé le noyau pedunculopontin. Postmortem une diminution du nombre
de neurones cholinergiques a été mise en évidence chez les parkinsoniens
chuteurs mais pas chez ceux qui ne chutent pas. Enfin, la lésion de ces
neurones chez l’animal provoque des troubles de la marche et de l’équilibre.
L’analyse des corrélations entre
la mort des neurones non-dopaminergiques, les dépôts d’α-synucleïne dans ces neurones et les symptômes ouvre la voie vers
l’identification de nouvelles cibles thérapeutiques pharmacologiques ou par
chirurgie fonctionnelle pour la maladie de Parkinson.
O135
Table #1:
How can occupational therapists help manage memory challenges?
1ParkiLife Australia
Pty Ltd, Melbourne, Victoria, Australia
2Elgin Street
Rehabilitation Services, Melbourne, Victoria, Australia
Objective: Non-motor symptoms (NMS)
represent the biggest challenge faced by those working with the Parkinson’s
disease (PD) community and are the primary determinants of quality of life
(Chaudhuri, 2011). Many of these symptoms are not responsive to dopaminergic
therapy (Crossiers et al., 2010) or resistant to surgery (Bloem et al., 2009).
Cognitive dysfunction in PD contributes to disability, caregiver strain, and
diminished quality of life (Calleo et al., 2012) Many health professionals lack
expertise, understanding of the symptoms and complexities of PD, or the latest
assessment and treatment techniques in their own discipline (Hagestuen et al.,
2010).
Methods: This roundtable discussion will
outline the vital role of the Occupational Therapist (OT) in managing memory
challenges using the rehabilitative philosophy. The emphasis will be on the
OT’s interventions that enable the patient and family to address a variety of
cognitive problems, improve cognitive skills (Calleo et al., 2012), thus
encouraging participation in activities of daily living.
Specific
considerations for effective interventions to overcome cognitive challenges will
be discussed. An example of a 9 week cognitive education program used for
patients and caregivers will be presented.
Results: This
roundtable crosstalk will provide a hands-on practical approach in assisting
PwP to overcome cognitive challenges. The intended outcome of this roundtable
discussion is to:
·
empower patients through information sharing and provide them with
practical tips that are proactive and preventative in nature to help manage the
memory challenges thus assisting them to stay active and involved
·
advance effectiveness of OT services in assessing and making
recommendations on how to promote participation and quality of life amongst PwP
O136
Table #2: Motor
fluctuations and dyskinesias
Joseph Jankovic
Parkinson's
Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor
College of Medicine, Houston, TX, USA
Motor fluctuations in
patients with Parkinson’s disease (PD), such as wearing-off and on–off effects,
and dyskinesias are related to a variety of factors, including duration and
dosage of levodopa, age at onset, stress, sleep, food intake, and other
pharmacokinetic and pharmacodynamic mechanisms. The majority of patients,
particularly those with young onset of PD, experience these levodopa-related
adverse effects after a few years of treatment. Assessment of these motor
complications is difficult because of the marked clinical variability between
and within patients. Daily diaries and various scales have been used in
clinical trials designed to assess the effects of various pharmacological and
surgical interventions on motor fluctuations and dyskinesias. The most common
type of dyskinesia, called “peak-dose dyskinesia”, usually consists of
stereotypical choreic or ballistic movements involving the head, trunk, and limbs,
and occasionally, the respiratory muscles (Mehanna and Jankovic, 2010).
Dystonia is also typically seen in patients with diphasic dyskinesia and
wearing-off effect and may contribute to pain often associated with PD (Ha and
Jankovic, 2012). Proper recognition of the full spectrum of clinical
phenomenology of levodopa-related motor complications is essential for their
treatment and prevention. Therapeutic approach to the treatment of these
levodopa-related complications must be individualized, although some general
guidelines for medical and surgical interventions have been proposed (Jankovic
and Poewe, 2012). Novel therapeutic strategies include novel deliveries of
levodopa and dopamine agonists (IPX066, XP21279, Duodopa intestinal gel),
adenosine A2A antagonists (tozadenant), and other experimental approaches, such
as, MAO and glutamate release inhibitors (safinamide), AMPA antagonists
(perampanel), mGluR5 antagonists (ADX48621), and others (Poewe et al, 2012).
O137
Table #3: Speech and PD
Angela Roberts-South1-2,
Lorraine Ramig3-5, Bonnie Bereskin6
1Western University
Health and Rehabilitation Sciences, London, ON, Canada
2
Movement
Disorders Laboratory/NPF Centre of Excellence, London, ON, Canada
3
University
of Colorado-Boulder, Boulder, CO, USA
4
National
Center for Voice and Speech, Denver, CO, USA
5
Columbia
University, New York City, NY, USA
6
Private
Practice Speech Language Pathologist, Toronto, ON, Canada
The
ability to be understood by others, intelligible communication, is one of the
primary goals of speech and language therapy. Individuals with Parkinson
disease and other parkinsonism related conditions (e.g., PSP, MSA) may face
substantial challenges in being understood by others. Effective and
intelligible communication depends on a variety of factors including the
severity of speech impairment (e.g., voice loudness, clarity of speech sounds,
intonation). Further, changes in language and cognition (e.g., finding words,
formulating thoughts, understanding others) can also affect communication in
PD. Other factors that contribute to the success of being understood by others
include the listener’s familiarity with the person speaking, the familiarity of
the topic being discussed, sensory impairments (e.g., hearing or vision loss),
speaking rate, and the degree of background noise or distraction. Collectively,
the interaction of these factors underscores the complexity of communication in
PD. Furthermore, this complex interaction in PD and parkinsonism related
conditions highlights the need to address communication from the perspective of
the individual with the communication impairment and also the perspective of
the communication partner. Recent advances in neuroscience have substantially
increased our knowledge of and treatment options for communication disorders in
Parkinson disease including exercise based programs and technology solutions.
These advances build on 20 years of proven efficacy in treating speech
disorders in PD using systematic exercise programs such as LSVT LOUD. New
advances in telemedicine enable increased access to communication therapies
including LSVT LOUD and conversation support strategies. In this session
attendees will gain an understanding of the complexity of communication,
understand the most recent science relative to communication challenges in PD
and related disorders, and learn about proven interventions for treating
communication changes associated with PD and related disorders. Case study
illustrations and group discussions will be used to explore these issues in
detail.
O138
Table #4: Nonmotor Symptoms & PD
K. Ray Chaudhuri
Parkinson
Centre of Excellence, London, UK
Non-motor
symptoms of Parkinson’s disease (NMS) are the leading cause of poor quality of
life for both people with Parkinson’s and their caregivers. The slowness,
stiffness and tremor of Parkinson’s disease (PD) are well known, but non-motor
symptoms afflict more Parkinson’s patients. Though NMS affect every patient,
they are under-recognised and under-treated. In a Parkinson’s UK survey, members
rated symptoms such as sleep disturbance, pain, constipation, urinary problems
and dizziness as more debilitating than their motor symptoms. Hospitalisation
from PD is most likely to have been caused by NMS. This loss of independent
living has devastating social and economic consequences. Despite the profound
and negative effects of NMS, there is a dearth of research into causes and
therapies. Treatment remains poor and quality of life progressively
deteriorates. The National Institute for Health and Clinical Excellence (NICE)
and Parkinson’s UK have identified the recognition and treatment NMS across all
stages of PD as a key unmet need. Little research explores the cause and
progression of common NMS because funders have focused their attentions elsewhere.
An integrated and interactive combination of clinical and laboratory-based
investigation is required that will focus on the causes and consequences of
sleep disturbance, pain and autonomic dysfunction in PD. Using imaging and
post-mortem brain tissue to identify the areas of the brain responsible for
NMS, we are developing models of the disease that will increase our
understanding of the origin of neglected NMS of Parkinson’s and provide a test
bed for devising effective treatments. This research promises to increase our
understanding of the effects of PD on the brain in order to uncover the
underlying causes of NMS. This research will lead to advances in the detection
and treatment of NMS, thereby improving the quality of life of millions of
people with Parkinson’s, both today and in the future. By exploring the
practical clinical issues that are the biggest hurdle to the improvement of the
symptomatic treatment of PD, we will begin to solve the NMS enigma.
O139
Table #5: Issues
specific to Adolescents of Parents with Parkinson's disease
Elaine Book
Pacific
Parkinson’s Research Centre, University of British Columbia, Canada
Parkinson’s
disease (PD) is a family affair and as a result, everyone in the family is
affected by the disease. As a parent of children/adolescents/young adults or as
a professional working with families with PD, it is important to consider how
PD specifically impacts children and family life. There is a great deal of
research in the area of parental illness and its impact on children. However,
the specific area of parental PD and its affect on children is ripe for further
understanding as well as for the development of support and resources. This
roundtable session will plan to address issues related to disclosure of
diagnosis, how, what and when to share information and strategies to manage the
impact on daily life for children. There will be opportunity to gain insight
into common emotions and reactions of younger family members and to discuss
options for support. The session will also provide a venue to explore and
generate ideas for the future development of resources critical to meeting the
needs of children/adolescents/young adults of parents with Parkinson’s disease.
O140
Table #6: What are animal
models and why are they important in PD research? What are the challenges in
using them?
Marie-Francoise
Chesselet
Department
of Neurology, UCLA, Los Angeles, CA, USA
Objective: Advances in
understanding the mechanisms of Parkinson’s disease (PD) to develop better
treatments require modeling the disorder in animals. Animal studies are also
critical to test the safety and efficacy of drugs before administering them to
humans in clinical trials. This round table will discuss the many attempts to model
PD and how they can be used to advance our quest for a cure.
Methods: Various aspects of PD
have been modeled using toxins or genetic manipulations in different animals.
Results: Animal models remain
indispensable for PD research. They are developed based on scientific
principles and submitted to rigorous oversight. Choices of animal models for
specific purposes are dictated by our advancing scientific knowledge but need
to recognize the advantages and limitations of each model. Patients play an
essential role in educating the public about the need for the responsible use
of animals in PD research.
O141
Table #7:
Parkinson's disease and cancer
Rivka Inzelberg
The
Sagol Neuroscience Center, Department of Neurology, Sheba Medical Center, Tel
Hashomer and Tel Aviv University, Israel
Objective: To discuss the particular relationship
between Parkinson's disease (PD) and skin and non-skin cancers.
Methods: There
is evidence based on well-designed epidemiological studies for unusual cancer
rates in PD patients as compared to the general population. These findings will
be reviewed and discussed.
Results: PD patients are at
significantly low risk for most cancers as compared to the general population.
This risk reduction cannot be attributed to the recognized low incidence of
smoking in patients with PD, since not only smoking-related cancers but also
non-smoking related ones are less common in PD. While the risk for most cancers
appears to be relatively low in patients with PD, breast cancer and melanomas
occur more frequently in the PD population as compared to controls. These
peculiar patterns of cancer rates in PD might be related to the involvement of
common genes in both diseases. Recently, increased risk for non-skin cancers
has been reported in LRRK2 related PD. Furthermore, genes involved in
familial forms of PD appear to be abnormally expressed in cancers. Cell
survival signals may differ due to mutated genes and represent two opposite
extremes such as cell proliferation in cancer and cell death in PD. Unraveling
the link between PD and cancer may open a therapeutic window for both diseases.
O142
Table #8:
Open Discussion on Parkinson's disease
A. Jon Stoessl1,
Stanley Fahn2
1University of British
Columbia, Vancouver, BC, Canada
2Columbia University,
New York, NY, USA
This
is an open discussion on topics of broad interest to the Parkinson community.
Discussion will be guided by the interests of the attendees, but suggested areas
might include: (i) What is needed in treatment? (ii) How can we improve models
of care? (iii) What areas are should research focus on? (iv) What is the role
of the WPC with respect to the Parkinson community and other Parkinson
organizations?
O143
Table #9: Deep Brain Stimulation
Michael S. Okun
University of Florida Center for Movement Disorders
and Neurorestoration, Gainesville, FL, USA
There have been many new developments in the field
of deep brain stimulation (DBS) for Parkinson’s disease. In this meet the
expert forum, we will cover important changes in the field from a patient
perspective, and we will do so in an open style question and answer format.
Potential topics include patient selection, interdisciplinary teams, the
operative procedure, target choice, programming, medication management, and
troubleshooting. We will also potentially cover questions on emerging research.
Poster Presentations
Basic
Science: Etiology, genetics, epidemiology, and toxicants
PO1.01
Calmodulin regulation of L-type calcium channels in SNc DA neuron
culture
Paul J. Adams1
and David T. Yue1,2
Departments
of Biomedical Engineering1 and Neuroscience2Johns Hopkins
University, Baltimore, MD, USA
Objective: Motor symptoms are the
first clinical manifestation of Parkinson’s disease (PD) and are primarily
linked to degeneration and death of dopamine (DA) neurons in the substantia
nigra pars compacta (SNc). Over the past decade, there has been an intense
effort to uncover why SNc DA neurons in particular are susceptible in PD. There
is growing evidence that a high cytosolic calcium (Ca2+) load leads
to mitochondrial stress and high levels of reactive oxygen species (ROS) in
these cells; making them particularly susceptible to genetic and environmental
factors associated with PD. The high Ca2+ load is primarily a
consequence of Ca2+ influx through voltage-gated L-type Ca2+
channels (the CaV1.3 subtype) during continuous autonomous pacing.
Yet, a complete understanding of the role of endogenous CaV1.3
channels in PD pathophysiology and their potential as a target in PD therapy is
hindered by limited understanding of their biophysical properties, modulation
by other proteins, and their precise role in action potential (AP) generation
and pacing rate.
Method: Here we have
developed long term SNc DA neuron cultures from juvenile mice to explore
endogenous CaV1.3 channels. This system permits in-depth
electrophysiological interrogation of CaV1.3 channel function, as
well as genetic manipulation to explore channel-protein interactions and
modulation.
Results: With this
approach we provide the first evidence for a powerful form of Ca-dependent
feedback inhibition of endogenous CaV1.3 channels mediated through
the Ca sensing protein calmodulin (CaM). Furthermore, by over-expressing
dominant-negative mutant CaM through viral infection, we provide compelling
evidence for the contribution of CaM regulation of endogenous CaV1.3
and small-conductance potassium (SK) channels to action-potential shape and
pacing rate. Results such as these furnish new insights into the role that
L-type Ca2+ channels play in mediating Ca2+ dynamics
within SNc neurons, and the potential therapeutic benefit entailed by
manipulating Ca2+ influx through these channels.
P01.02
Analysis
of Gene Expression in Peripheral Blood of Patients with Parkinson’s Disease
Anelya Alieva1,
Elena Filatova1, Maria Shadrina1, Aleksey Karabanov2,
Sergey Illarioshkin2, Petr Slominsky1
1Institute of Molecular
Genetics, Russian Academy of Sciences, Moscow, Russian Federation
2Scientific Centre of
Neurology, Russian Academy of Medical Sciences, Moscow, Russian Federation
Objective: To date a number of genes is known to be
involved in pathogenesis of Parkinson’s disease (PD). However, causes and
mechanisms of progression of PD are not sufficiently clarified. In order to
identify new genes involved in the pathogenesis of PD, we carried out an
expression analysis of candidate genes, which may be involved in the
pathogenesis of PD.
Methods: At the first stage of our work we performed a bioinformatics
analysis and selected 8 candidate genes on the basis of their possible roles in
the pathogenesis of PD. Studies of gene expression (ZNF746, ALDH1A1, PINK1, PARK7, PDHB, PGC1-A, ATP13A2, LRRK2) were carried
out in two groups: newly diagnosed PD patients and patients with different
neurological disorders as a control.
At the second stage, we carried
out a whole transcriptome analysis in the peripheral blood of untreated PD
patients by using HT-12-V4 Expression BeadChip (Illumina Comp.).
Results: Expression
analysis of 8 candidate PD genes revealed no statistically significant
differences of expression of these genes between patients with PD and the
control group. At the second stage seven new metabolic processes, which may be
involved in the PD pathogenesis, were revealed. Subsequently we plan to conduct
further investigations of chosen metabolic processes from the whole
transcriptome analysis for selection of possible candidate genes which may be
involved in the pathogenesis of PD. Also we will continue to carry out
expression analysis of 8 candidate genes and new selected genes in formed
groups of the patients and control groups, and we plan to increase groups of
patients and form additional comparison groups.
P01.03
Acute and
Sub-acute oral toxicity study of L-dopa and Hyoscine hydrobromide in
combination in rodents
Sabir
Husain F. Attar1, Dharmendra K khatri2, DnyneshwarM
Nagmoti3, Archana R. Juvekar4, Manasi, R. Juvekar
1Institute of Chemical Technology, Matunga, Mumbai, India
Objective:
The present investigation was carried out to evaluate the safety
of a combination of L-Dopa ( a known Antiparkinson Drug) and Hyoscine
hydrobromide ( which is employed for treatment of Parkinsonism in Homoeopathic
System of medicine) by determining its potential toxicity after acute and
sub-acute administration in rats.
Methods: The acute
and sub-acute oral toxicity of combination of L-dopa and Hyoscine hydrobrmide
was investigated according to OECD Guideline 423 and 407 respectively. In acute
toxicity study, combination of L-dopa and Hyoscine hydrobrmide was administered
at 5 times the upper limit of Therapeutic dose of each drug which is 1200 mg
per day for L-Dopa and 0.75 mg per day for Hyoscine Hydrobromide for adult
human being and which was converted to required dose for Wistar rats (3 males
and 3 females). In sub-acute toxicity study, the dosing was done in combination
at 3 levels, first at lower level of the aforesaid therapeutic dose, second at
twice the upper limit of therapeutic dose and third at 5 times the upper limit
of therapeutic dose. Animals were divided in to 6 groups of 6 Animals each (3
males and 3 females) for 28 days study.
Hematological, biochemical and histological analyses and other
parameters were recorded.
Results: The
combination of L-dopa and Hyoscine hydrobromide at 5 times the upper
therapeutic dose produced no treatment-related signs of toxicity or mortality
in any of the animals tested during 14 days of the study. In the repeated dose
28-day oral toxicity study, there was no significant difference in any of the
assigned parameters between the control and all treatment groups. No
significant change has been noticed in reversal group. It is established that the
combination therapy is safe at 5 times the upper limit of therapeutics dose of
each drug.
P01.04
Case
report with a novel homozygous PARK2 gene mutation in early onset Parkinson´s
disease
Sarah
Bernsen1, Saskia Biskup2,3, Ulrich Liebetrau1,
Volker Limmroth1
1Cologne City Hospitals, Cologne, Germany
2Department of Neurodegenerative Diseases, Hertie-Institute for
Clinical Brain Research, Tübingen, Germany
3CeGaT GmbH, Tübingen, Germany
Objective:
To report a case of a 38-year old Turkish patient first diagnosed
with Parkinson´s disease (PD) with a novel homozygous PARK2 gene mutation.
Case
report: A 38-year old patient of Turkish descent presented with
progressive slowness and stiffness of movement accompanied with fatigue and
cognitive impairment.
Neurological examinations revealed symptoms of PD with brady- and
hypokinesia and rigidity of the body predominantly on the right side with mild
action tremor and postural instability. Dystonia as a frequent symptom with
parkin-linked parkinsonism could not be found. Neuropsychological examination
showed mild cognitive deficits concerning attention, concentration and delayed
memory. The patient showed a god response to levodopa therapy.
MRI of the brain was normal, Dopamine transporter imaging
(DaTSCAN) demonstrated a reduced uptake of [123I]FP-CIT in both putamen with an
asymmetrical pattern.
Genetic examinations of the patient´s DNA revealed a novel
homozygous duplication of the exons 7, 8 and 9 and intronic regions 6 and 9
within the PARK2 gene. DNA analysis of the parents confirmed the mutation in a
heterozygous state in both parents.
Conclusion: Mutations
in the parkin (PARK2) gene are known to cause autosomal recessive inherited
Parkinson disease (PD) and are associated with early disease manifestation.
This case report illustrates a patient with early onset
Parkinson´s disease revealing a novel homozygous genetic mutation in the PARK2
gene, which to our knowledge has not been previously reported. Functional
studies in fibroblasts or differentiated stem cell lines might help to further
understand the role of the PARK2 protein in PD pathogenesis.
P01.05
Dietary administration
of paraquat for 13 weeks does not result in a loss of dopaminergic neurons in
the substantia nigra of mice
Charles Breckenridge1,
Melissa Beck2, Philip Botham3, Mark Butt4,
Andrew Cook3, James Mathews5, Daniel Minnema1,
Lewis Smith6, Nicholas Sturgess3, Merrill Tisdel1,
Kim Travis3, Jeffrey Wolf7, Dan Zadory7
1Syngenta LLC,
Greensboro, NC, USA
2WIL Research Laboratories
Ltd, Ashland, OH, USA
3Syngenta Ltd,
Bracknell, Berkshire, UK
4Tox Path Specialists
LLC, Frederick, MD, USA
5RTI International,
Research Triangle Park, NC, USA
6LLS (Cheshire)
Services, Holmes Chapel, Cheshire, UK
7EPL Inc, Sterling, VA,
USA
Objective: The i.p. administration of
high doses of paraquat to C57BL/6J male mice has been reported to cause a
reduction in the number of dopaminergic neurons in the substantia nigra pars compacta (SNpc). These studies have been
cited as providing biological plausibility for the limited epidemiological
evidence of an association between paraquat exposure and Parkinson’s disease.
The i.p. mouse model is not relevant
to humans. Dietary administration is used as a surrogate for the technically
difficult, but occupationally relevant, dermal and inhalation exposure of
operators. Therefore, we have conducted
a 13-week dietary study in C57BL/6J mice to evaluate the potential
neurotoxicity of paraquat.
Methods: Brains
were examined for evidence of dopaminergic neuronal cell loss using stereology,
changes in striatal neurochemistry and pathological changes using stains to
detect neuronal cell damage and glial cell activation. Dietary
concentrations of 10
& 50 ppm paraquat dichloride were used; achieved doses were 2.4 & 14.1
and 3.7 & 21.5 mg (paraquat ion)/kg/day for males and females,
respectively. MPTP (4 x 10 mg/kg i.p.
at 2 hr intervals) was administered to a separate group 7 days prior to the end
of the dietary study, serving as a positive control.
Results: Paraquat did not
result in a reduction in the number of tyrosine hydroxylase positive (TH+)
dopaminergic neurons in the SNpc, did not alter the concentration of striatal
dopamine or its metabolites and did not cause neuronal cell damage or glial
activation. With MPTP, the numbers of TH+ neurons in the SNpc and striatal
dopamine were reduced and pathological changes indicative of neuronal damage
and cell death were observed. These results bring into question the human
relevance of previous studies using i.p. administration
of paraquat.
P01.06
AD GWAS
top hits and risk of Parkinson’s disease in Korean population
Sun Ju
Chung1; Yusun Chung2; Myunghee Hong2; Mi Jung
Kim3; Sooyeoun You4; Young Jin Kim1; Juyeon
Kim1; Kyuyoung Song2
1Department of Neurology, Asan Medical Center, University of Ulsan
College of Medicine, Seoul, Korea
2Department of Biochemistry and Molecular Biology, University of
Ulsan College of Medicine, Seoul, Korea
3Department of Neurology, Bobath Memorial Hospital, Seongnam,
Republic of Korea
4Department of Neurology, Dongsan Medical Center, Keimyung
University, Daegu, Korea
Objective:
Alzheimer’s disease (AD) and Parkinson’s disease (PD) have
overlapping clinical and pathological features, suggesting a common pathway for
these two neurodegenerative disorders. Here we investigated the association of
both AD GWAS top hits with PD susceptibility.
Methods: We
selected nine single nucleotide polymorphisms (SNPs) in the five genes (ABCA7,
APOE, CLU, CR1, and PICALM) based on results of the recent GWAS on AD and all
selected genes were listed in the AlzGene top 10 results
(http://www.alzgene.org) and genotyped in 1,108 PD cases and 1,208 controls.
Cases and controls are all ethnic Koreans.
Results: None of the
AD GWAS top hits showed a statistically significant association with PD
susceptibility. The SNP rs677909 in the PICALM gene that previously had a
significant association with AD in Korean population showed no association with
PD. The SNP rs7412 in the APOE gene that reproducibly associated with AD
worldwide showed no association with PD susceptibility.
Conclusions: Our
results show no significant associations of AD GWAS top hits with PD
susceptibility in Korean population. Although AD and PD may have overlapping
clinical and pathological features, two disorders may have distinct genetic
risk factors for the disease susceptibility.
P01.07
Enabling research
through informatics: a researcher turned patient's point of view
Sue Dubman
Patient
and Bioinformatics Professional in Sanofi’s R&D Organization
Objective: Translating biomedical
research into safe and effective treatments remains a slow, expensive, and
failure-prone endeavor. Informatics is an essential and powerful way to enable
science, reduce costs and speed new treatments to market. Yet biopharmaceutical
companies have been extremely slow to adopt these innovations; instead they
often continue to use tools and processes that were invented 20+ years ago. The
objective of this presentation is to provide one researcher turned patient’s
view of how we might streamline and accelerate clinical and translational
research by enabling them with new, innovative informatics capabilities.
Methods: Now a patient but having
worked almost my entire life in the biopharmaceutical industry as well as in
government health care research organizations, I know we can do much better.
Suggestions on how to address and remove the social, organizational, and cultural
barriers to innovations enabled by informatics will be discussed. In addition, examples of informatics innovations from other therapeutic
areas that could be applied to Parkinson’s research will be reviewed.
Results: There are so many
opportunities to streamline and accelerate the whole clinical development process
with Informatics. In presenting some examples from other therapeutic areas, my
hoped for outcome is that some of these new, innovative approaches will be
adopted by Parkinson’s researchers. Time is a patient’s
most precious commodity. Patients can’t wait 15+ years for new treatments. This
is a call to action to ensure informatics-enablement is considered from the
start of every investment in research, to develop an informatics strategic
roadmap that supports the needs of research, to create an informatics manifesto
that includes principles to ensure success for informatics-enabled research and
to ensure that informatics investments support new paradigms as opposed to
automating yesterday’s practices.
P01.08
Transcriptome analysis
in MPTP mouse models of early stages of Parkinson’s disease
Elena Filatova1,
Anelja Alieva1, Maria Shadrina1, Elena Kozina2,
Gulnara Khakimova2, Petr Slominsky1, Michael Ugrumov2
1Institute of Molecular
Genetics, Russian Academy of Sciences, Moscow, Russia
2Koltzov Institute of
Developmental Biology Russian Academy of Sciences, Moscow, Russia
Objective: To date, etiopathogenesis of early stages of
Parkinson’s disease (PD) remains largely obscure. One of the main approaches to
the study of this problem is the investigation of the transcriptome changes in
PD. In connection with the above we analyzed transcriptome alterations in MPTP
mouse models of pre-symptomatic and early symptomatic stages of PD.
Methods: As part of this objective we extracted total RNA from substantia
nigra and striatum of mice with pre-symptomatic and early symptomatic stages of
PD. Further, we analyzed levels of transcripts using the MouseRef-8 v2.0
Expression BeadChip Kit (Illumina) and Genome Studio (Illumina). Next we
conducted a bioinformatic analysis using DAVID Bioinformatics Resources. After
selection of seven transcripts we performed additional analysis of relative
expression of these genes in substantia nigra, striatum, and frontal cortex of
mice with pre-symptomatic and early symptomatic stages of PD using reverse
transcription reaction and real-time PCR.
Results: As a
result of the experimental and bioinformatics analysis, we selected 60 genes,
which may be involved in the pathogenesis of PD. These genes take part in
neurosynaptic signal transmission, endo- and exocytosis, protein transport,
protein catabolism (including ubiquitin-mediated). Thus, we selected Drd2, Clb2, Cplx2, Exoc4, Snca, Epsn2,
and Ntrk2 genes from the 60
previously described for more detailed analysis. Our results will help to build
a complete picture of all molecular and genetic processes, involved in the
etiopathogenesis of the disease, in the future and will help to understand
mechanisms of functioning of individual neurons and the whole nervous system
better. These data also will allow us to select transcriptomic markers for
development of a panel of biomarkers for diagnosis of PD on early stages.
P01.09
LRRK2 Expression in Innate Immune Cells during Microbe-Induced
Inflammation of Nervous System Structures
Mansoureh
Hakimi1, Shawn Hayley2, Thirumahal Selvanantham3,
Elizabeth Abdel-Messih1, David S. Park1, Matthew J.
LaVoie4, Dana Philpott3, Jean Michaud5, John
Woulfe6, Michael G. Schlossmacher1
1Department
of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa,
Ottawa, ON, Canada
2Department
of Neuroscience, Carleton University, Ottawa, Ontario, Canada
3Department
of Immunology, University of Toronto, Toronto, ON, Canada
4Center
for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical
School, Boston, MA, USA
5Department
of Pathology and Laboratory Medicine Faculty of Medicine, University of Ottawa,
ON, Canada
6Department
of Pathology, University of Ottawa, Ottawa, ON, Canada
Objective: The
mechanisms by which altered LRRK2 genotypes are linked to the risk of
parkinsonism and Crohn’s disease, and possibly leprosy, remain unanswered. We
recently demonstrated robust LRRK2 expression in monocytes and macrophages, we
have now focused to characterize LRRK2 in granulocytes.
Methods: We have used FACS analysis to determine
LRRK2 expression in organs from adult mice monocytes, granulocytes and
dendritic cells. We visualized LRRK2 expression in human organs and mice using
immunohistochemistry and immunofluorescence. Also, we have determined cytokine
profile of WT mice vs. PD-linked R1441C knock-in mice in various inflammatory
paradigms using ELISA and multiplex assays.
Results: Here we report that human lymph nodes,
spleen and distal ileum contain numerous LRRK2-expressing macrophages and
granulocytes. In LRRK2-deficient mice and PD-linked R1441C knock-in animals
versus wild-type cells (Tong et al., PNAS 2010, 2011), LRRK2 did not detectably
regulate the release of select cytokines in stimulated macrophages. However,
the gene was strongly expressed in activated leukocytes during acute and
chronic infections of neural structures. Also, We found that LRRK2-positive
leukocytes were overrepresented among infiltrating,
myeloperoxidase-reactive
granulocytes and CD68-positive macrophages in diseases such as viral
encephalitis, idiopathic radiculitis, neuropathy of the skin due to M. leprae infection, terminal ileitis
and abscess formation. In post mortem midbrain sections from patients with
sporadic and genetic variants of Parkinson disease, we detected
LRRK2-reactivity mostly in intravascular leukocytes including in areas of
dopamine cell loss. This finding is consistent with the known distribution of LRRK2 mRNA in mammalian brain (Galter et
al. Ann Neurol 2006).
P01.10
COMT × DRD4 epistasis impacts cognitive flexibility
during the Trail Making Test
Sebastian Heinzel1, Raphael Niebler3, Claudia Schulte1,
Ulrike Sünkel1, Gerhard W. Eschweiler3, Andreas J.
Fallgatter3, Walter Maetzler2,4, Daniela Berg1,2,
and the TREND Study Consortium
1Department of
Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research (HIH),
University of Tuebingen, Germany
2German Center for Neurodegenerative
Diseases (DZNE), Tuebingen, Germany
3Department of
Psychiatry and Psychotherapy, University of Tuebingen, Germany
4Functional
Neurogeriatrics, Hertie Institute for Clinical Brain Research (HIH), University
of Tuebingen, Germany
Objective: Dopaminergic neuromodulation of prefrontal
inhibition/excitation has been linked to mediating between neural states
favoring stable (e.g., working memory) or flexible (e.g., set shifting)
representations and behavior. Moreover, polymorphisms in dopaminergic genes
such as catechol-O-methyltransferase (COMT)
degrading dopamine, and the inhibitory dopamine receptor D4 (DRD4), as well as their epistatic
interaction, have been shown to impact neurobehavioral stability/flexibility.
Methods: As part of the TREND study (Tübinger evaluation of Risk factors for Early detection of NeuroDegeneration) cognitive flexibility was
measured by the Trail Making Test (TMT) in elderly, neurodegeneratively healthy
subjects. We genotyped for COMT
(Val158Met, rs4680) and DRD4 (‑521C/T, rs1800955)
polymorphisms in 637
subjects and analyzed genetic main and epistatic effects on TMT performance.
Results: COMT and DRD4 genotypes showed no main effects,
but a significant gene‑gene interaction. At intermediate COMT-dependent
dopamine levels (COMT Val/Met) TMT
performance was impacted by DRD4
genotype. Here, subjects with relatively decreased D4 function (DRD4 T-allele carriers) showed
14.2 % lower cognitive flexibility (7.2 s slower, TMT B-A) compared to
subjects with relatively increased D4 function (C/C homozygotes).
In line with previous
electrophysiological and behavioral findings, increased neural/cognitive
stability at intermediate dopamine levels might be accompanied with the risk of
overly decreased flexibility, if inhibitory D4 receptor function is reduced.
An independent
replication sample (n~450) is currently analyzed, and further analyses of COMT × DRD4 epistasis on cognitive flexibility (n~1100) will also include
analyses of allele-dose effects and DRD4
48bp-VNTR data.
P01.11
PARK18 SNP is
Associated with Differential Expression of MajorHistocompatibility Complex II
genes in Healthy Controls and Parkinson's Disease Patients
George T. Kannarkat1, Nancy M. Choi2,
Darcie A. Cook1, Jaegwon Chung1, Jae-Kyung Lee1,
Stewart Factor3,4, Jeremy M. Boss2, Malu G. Tansey1,5
1Department of
Physiology, Emory University School of Medicine, Atlanta, GA, USA
2Department of
Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA,
USA
3Department of
Neurology, Emory University School of Medicine, Atlanta, GA, USA
4Movement Disorders
Center, Emory University School of Medicine, Atlanta, GA, USA
5Center for
Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA,
USA
Objective: A single nucleotide
polymorphism (SNP) in the first intron of the HLA-DRA gene termed PARK18 was shown to be associated with a
higher risk of Parkinson’s disease (PD) in a genome-wide association study.
Individuals homozygous for the rs3120882 G SNP (PARK18GG) have a 1.7 fold
higher risk (p=5x10-8) for PD than individuals homozygous for the A
allele (PARK18AA). HLA-DRA is located in the major histocompatibility complex
II (MHCII) locus that encodes proteins that present antigens on the surface of
immune cells to activate adaptive immunity. We tested whether PARK18GG versus
PARK18AA carriers (+/- PD) displayed differences in MHCII expression.
Methods: We used flow
cytometry and real-time PCR to measure MHCII expression under resting or
stimulated conditions in human B cells and monocytes.
Results: We found clear
differences in expression of HLA-DR and DQ in peripheral blood cells of
individuals related to PARK18GG and/or disease status. Monocytes from PD
patients with the risk allele also responded differently in MHCII expression
after stimulation. Preliminary results suggest the existence of regulatory
activity associated with PARK18 at the MHCII locus. These results may provide
evidence for a novel, pathogenic mechanism involving adpative immunity for PD
as well as be used as a disease biomarker. PARK18GG is associated with altered
expression of immune molecules and thus, provides clues about the role of
adaptive immunity in PD pathogenesis and progression.
P01.12
SCA 8 mimicking excellent levodopa responsive Parkinson
disease and amyotrophic lateral sclerosis
Jumin Kim1, Ji Sun Kim2, Jinyoung
Youn1, Jin Whan Cho1
1Sungkyunkwan
University School of medicine, Samsung Medical Center, Seoul, Korea
2Soonchunhyang University
School of Medicine, Hospital Soonchunhyang University College of Medicine,
Seoul, Korea
Objective: Spinocerebellar ataxia type 8 (SCA8) is an
inherited neurodegenerative disorder caused by the expansion of untranslated
CTA and CTG triplet repeats on 13q21. The phenomenology of SCA8 is relatively
varied when compared to the other types of SCAs and its spectrum is not well
established.
Methods: We describe two newly detected families with
the nonataxic phenotype of SCA8 with unusual clinical manifestations such as
levodopa responsive parkinsonism and amyotrophic lateral sclerosis. Nonataxic
phenotypes of SCA 8 and its possible pathogenic mechanisms which have been
described in theliterature is also reviewed and critically examined.
Results: Family A expressed excellent
levodoparesponsive parkinsonism as an initial manifestation and developed mild
cerebellar ataxia, and additional movement including dystonic gait and unusual
oscillatory movement of trunk during the disease course. The proband of family B
presented as a probable ALS with cerebellar atrophy on brain MRI, positive
family history in his brother with typical cerebellar ataxia and genetic
confirmation for SCA 8. The phenotype of SCA 8 was categorized into following 3
groups; 1) typical ataxia predominant syndrome including scanning
dysarthria, oculomotor dysfunction, limb and gait ataxia, 2) atypical movement
predominant syndrome 3) incidental detection of CTG repeat expansion in various
neurodegenerative disorders.
Conclusions: Our finding support that the unusual
nonataxic phenotypes could be caused by a mutation of the SCA8 locus which
might affect neurons other than the cerebellum.
P01.13
Role of MAPT variation in Parkinsonian disorders
Catherine Labbé1,
Alexandra Ortolaza1, Sruti Rayaprolu1, Ryan Uitti2,
Dennis Dickson1, Zbigniew Wszolek2, and Owen Ross1
1Department of
Neuroscience, Mayo Clinic, Jacksonville, FL, USA
2Department of
Neurology, Mayo Clinic, Jacksonville, FL, USA
Objective: Rare variants in the microtubule associated protein tau
gene (MAPT) cause tau dysfunction leading to neurodegeneration. Additionally,
a common non-recombining MAPT
haplotype (MAPT H1) has been shown to
increase the risk of both Parkinson’s disease and progressive supranuclear
palsy. Preliminary sub-haplotype analyses suggest that different genetic
variants on the MAPT H1 haplotype
associate with each of these Parkinsonian disorders. To date it remains unclear
which variant(s) at the MAPT locus is
(are) responsible for the risk and what is the underlying pathomechanism of
disease. The objective of this study is to identify causal variants for
Parkinson’s disease and progressive supranuclear palsy within the MAPT region using next generation
sequencing technologies.
Methods and Results: We captured the
entire MAPT gene and 10kb on each
side, a 154kb genomic region that was sequenced in 300 patients with
Parkinson’s disease, 300 patients with progressive supranuclear palsy and 300
controls using a pooling strategy (10 DNA samples/pool). We used the Haloplex
system and designed 4248 amplicons for a total coverage of 96.3%. We selected:
(a) common variants tagging each of the MAPT
sub-haplotypes (frequencies >5%); and (b) rare variants most likely to
be functionally relevant. Common and rare genetic variants identified will be
genotyped in an independent case-control series (747 progressive supranuclear
palsy patients vs 727 controls; Parkinson’s disease: 692 clinically diagnosed
patients vs 689 controls). We will use linear regression analyses to study all
variants with a minor allele frequency (MAF) ≥1%. A collapsed marker
approach will assess joint effects of variants with MAF<1%. We will perform
follow-up association studies in additional independent series. We will present
results using the latest sequencing and genotyping technologies to
comprehensively define the MAPT locus
associated with Parkinson’s disease and progressive supranuclear palsy and thus
identify novel targets for both neuroprotective and symptomatic therapies.
P01.14
Exome sequencing of
Norwegian families with PD reveals novel gene mutations
Michelle K. Lin1*,
Jan Aasly2*, Daniel Evans1, Carles Vilarino-Guell1,
Brinda Shah1, Chelsea Szu Tu1, Heather Han1,
Holly Sherman1, Christina Thompson1, Mathias Toft3,
Karin Wirdefeldt4, Andrea C. Belin5, Maria S. Petersen6,
Joanne Trinh1, Vanessa Silva1, Frederick Pishotta1
and Matthew Farrer1 on behalf of the GEO-PD consortium.
1Centre for Applied
Neurogenetics, University of British Columbia, Vancouver, Canada
2Department of
Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway
3Department of
Neurology, Oslo University Hospital, Oslo, Norway
4Department of Medical
Epidemiology and Biostatistics and Department of Clinical Neuroscience,
Karolinska Instiutet, Stockholm, Sweden
5Department of
Neuroscience, Karolinska Instiutet, Stockholm, Sweden
6Department
of Occupational Medicine and Public Health, The Faroese Hospital System, Torshavn,
Faroe Islands
*authors contribute equally to this work
Objective: Approximately 14% of
patients with Parkinson disease (PD) have a family history of parkinsonism. In
larger, multi-incident families, pathogenic mutations/genes have now been
identified using traditional linkage and contemporary exome sequencing methods.
We report a clinical and comparative genetic study of Norwegian families.
Methods: Four Norwegian
families (pedigree structure of 3-5 generations, 93 individuals, of whom 22
have parkinsonism) were invited; 17 affected (mean age-of-onset 62.8±4.9SD,
range=55-75 years) and 10 unaffected members participated in the study.
Late-onset, asymmetric, levodopa-responsive PD appears to segregate in an
autosomal dominant fashion. Three affected members from each pedigree, screened
negative for known genetic mutations using a proprietary diagnostic panela,
were exome-sequenced on an Illumina HiSeq platform. Genome alignment,
annotation and pair-wise bioinformatic comparisons of affected family members
were performed. Coding variants observed at <1% frequency were validated by Sanger
sequencing in all family members and matched control subjects. Mutations
segregating with PD but not observed in controls were genotyped in 3112
subjects (1613 patients) of Scandinavian origin. Subsequently, mutations were
genotyped in multi-ethnic GEO-PDb samples using Sequenom and TaqMan
technologies. Additional exonic sequencing was performed in candidate genes.
Results: One mutation in each
family was ultimately found to segregate with PD in four genes (NOVA2, PABPC1L, RPE65 and OR56B4). Each mutation was highly
conserved through evolution, and those substitutions were predicted to have
deleterious consequences on protein function. Mutations in PABPC1L and RPE65 were
observed in additional unrelated patients but not control subjects. The
functions of the encoded proteins are not well characterized but are involved
in RNA splicing in developing neurons, translation, retinal regeneration and
olfaction. In conclusion, pair-wise exome-sequencing is an efficient method to
identify novel gene mutations in familial PD that enhances traditional linkage
efforts in disease gene mapping.
a see abstract by Lin,
Evans et al.
b see www.geopd.org
P01.15
The effects of
previous cigarette smoking on olfaction in Parkinson’s patients
Elisabeth B. Lucassen1,
Nicholas W. Sterling1, Eun-Young Lee1, Honglei Chen2,
Mechelle M. Lewis1, Lan Kong1, Xuemei Huang1
1Pennsylvania
State University-Milton S. Hershey Medical Center, Hershey PA, USA
2National
Institute of Environmental Health and Sciences, Research Triangle Park, NC, USA
Objective: Smokers
have a lower risk for Parkinson’s disease (PD) than nonsmokers. Olfactory
dysfunction is a non-motor symptom in Parkinson’s patients that may precede
motor symptom onset by years. We therefore examined the hypothesis that among
PD patients, smokers may have better olfaction than nonsmokers.
Methods: Smoking
history was obtained from 76 PD subjects (23 ever smokers, 53 nonsmokers) and
67 healthy control subjects (16 ever smokers, 51 nonsmokers). Olfactory
function was assessed using the standardized 40 item University of Pennsylvania
Smell Identification Test (UPSIT). Comparisons between groups and subgroups
were performed using two-way analysis of covariance with correction for
multiple comparisons.
Results: PD
patients and controls showed different patterns of association between smoking
and olfaction. Among PD patients, ever smokers had a better olfactory function
than never smokers (UPSIT score 24.4 vs. 20.3, P=0.046). Among controls, no
difference was observed between ever smokes and never smokers (UPSIT score 32.5
vs. 33.9, P=1.000).
Discussion/Interpretation: These
data suggest that previous smoking may be protective against PD-related
olfactory dysfunction. Further studies are needed to investigate the mechanism
underlying this observation.
P01.16
Investigation of PD
brain DNA for SNCA (alpha-synuclein) mutations, and cellular study of the
recently reported H50Q
Christos Proukakis,
Chrysia-Maria Pegasiou, Maria Katsianou, Maryiam Shoaee, Angelika Hummel, Timothy
Brier, Henry Houlden, J Mark Cooper, Anthony H Schapira
Institute
of Neurology, University College London, UK
Objective: To investigate PD brain DNA for somatic SNCA
mutations, and establish and study cell lines overexpressing the H50Q mutation
we recently reported. Misfolding
of alpha-synuclein (SNCA) appears crucial to the PD pathogenesis, yet mutations
in the gene are very rare. The possibility of sporadic cases being due to
somatic mutations in early embryogenesis, which might be restricted to the
neuroectoderm and undetectable in peripheral lymphocyte DNA, has not been
formally investigated. We recently detected a novel missense change
(c.150T>G, p.H50Q) in DNA from the cerebellum and substantia nigra of one
apparently sporadic, late onset, typical PD case, and demonstrated an effect on
co-ordination of copper (Proukakis et al, Neurology 2013). To investigate the
possibility of a somatic origin of H50Q, as no relatives or other DNA sources
were available, we sought indirect evidence of mosaicism by analysis of phase
in relation to a nearby intronic polymorphism, but none was found. H50Q has now
been reported in another case (Appel-Cresswell et al, Movement Disorders 2013),
and appears to be a pathogenic rare germline variant.
Methods: We
analysed 457 PD brain DNA samples (from more than one region in 25 cases) using
High Resolution Melting (HRM) analysis, which has higher sensitivity than
sequencing for low level mosaicism. Serial dilution confirmed HRM could detect
1-5% level of H50Q/ A53T. We introduced the H50Q mutation in a plasmid encoding
HA-tagged SNCA, transfected neuroblastoma cells, selected and characterized
expressing clones, and treated them with copper added as Cu(II) to the medium.
Results: No
evidence of exonic somatic mutations was seen, but other types of mutation (eg
CNV) could not be excluded. We did not detect any evidence of oligomers or
aggregates in response to Cu(II), or differential toxicity of Cu(II) to wild
type and H50Q overexpressing cells. Further work is ongoing.
P01.17
Revisiting
Smoking and Parkinson’s: Marker, Cause or Effect?
Beate
Ritz 1, Pei-Chen Lee1, Christina Funch2,
Onyebuchi A. Arah 1
1 Fielding School of Public Health,
UCLA, LA, USA
2 Danish Cancer Society, Copenhagen,
Denmark
Objective: Almost all epidemiologic
studies conducted on this found a negative association between smoking and
Parkinson’s disease (PD). However, it is not known whether this is due to
neuroprotection by smoking or nicotine or a common cause resulting in the
avoidance or ability to quit smoking and in PD. This distinction is important
because smoking may either provide important leads for the prevention of PD or
simply be a marker of insidious PD onset or risk. Here we examine the role of
difficulty to quit smoking and of nicotine replacement in PD.
Method: We studied 1,808
patients with medical record confirmed PD diagnosed between 1996 and 2009 and
1,876 randomly selected Danish population controls matched on sex and birth
year in Denmark. Information on lifelong smoking habits was collected in
telephone interviews. We conducted logistic regression analyses adjusting for
matching factors and confounders.
Results: Among former smokers,
the risk of developing PD was 43% higher (95% CI=1.00-2.05) in participants who
said it was “easy to quit” smoking compared to “extremely difficult”. The
strongest inverse associations with PD were observed for smokers who used
nicotine substitutes in order to quit: odds ratio (OR)=0.47, 95% CI=0.27-0.81
for former smokers and OR=0.15; 95% CI=0.06-0.34 for current smokers using
nicotine substitutes compared to nonsmokers. Nicotine substitute usage was
strongly positively associated with quitting difficulty and duration of
smoking, perhaps indicating that the insidious onset of PD influences the ability
to quit smoking. Our findings are compatible with there being an unidentified
strong risk factor for PD that prevents smoking, facilitates quitting of
smoking, and prevents the need to use nicotine.
P01.18
Household
organophosphorus pesticide use and Parkinson’s disease
Shilpa
Narayan1, Zeyan Liew1, Kimberly Paul1, Pei-Chen Lee1, Janet S Sinsheimer2, Jeff M Bronstein3, Beate Ritz1,3
1Department of Epidemiology, Fielding School of Public Health, UCLA,
Los Angeles, CA, USA
2Departments of Human Genetics and Biomathematics, David Geffen School
of Medicine, and Department of Biostatistics, Fielding School of Public Health,
UCLA, Los Angeles, CA, USA
3Department of Neurology, School of Medicine, UCLA, Los Angeles, CA,
USA
Objective: Household pesticide use is widespread in the
United States. Since the 1970s, organophosphorus chemicals (OPs) have been
common active ingredients in these products. Parkinson’s disease (PD) has been
linked to pesticide exposures but little is known about the contributions of
chronic exposures to household pesticides. Here we investigate whether
long-term use of household pesticides, especially those containing OPs,
increases the odds of PD.
Methods: In
a population based case-control study, we assessed frequency of household
pesticide use for 357 cases and 807 controls relying on the California
Department of Pesticide Regulation product label database to identify
ingredients in reported household pesticide products and the Pesticide Action
Network pesticide database of chemical ingredients. Using logistic regression
we estimated the effects of household pesticide use.
Results: Frequent use of any
household pesticide increased the odds of PD by 47% [odds ratio (OR) =1.47 (95%
confidence interval (CI): 1.13, 1.92)]; frequent use of products containing OPs
increased the odds of PD more strongly by 71% [OR=1.71 (95% CI: 1.21, 2.41)]
and frequent organothiophosphate use almost doubled the odds of PD. Sensitivity
analyses showed that estimated effects were independent of other pesticide
exposures (ambient and occupational) and the largest odds ratios were estimated
for frequent OP users who were carriers of the 192QQ paraoxonase genetic
variant related to slower
detoxification of OPs. We provide
evidence that household use of OP pesticides is associated with an increased
risk of developing PD.
Previously
presented subset of findings in a poster at: The 2013 Parkinson’s Action Network
Forum on Monday, February 25th, 2013
P01.19
NOS genes and PD: Marginal
associations and gene environment interactions with pesticides
Kimberly Paul1,
Shannon L. Rhodes1, Janet S. Sinsheimer1, Myles Cockburn2,
Jeff M. Bronstein1, Beate Ritz1
1University of
California, Los Angeles, Los Angeles, CA, USA
2University of Southern
California, Los Angeles, CA, USA
Objective: Nitric oxide (NO)
produced by nitric oxide synthase (NOS) enzymes is a potent pro-oxidant that
can damage dopaminergic neurons. Thus, the NOS
genes are candidates for Parkinson’s disease (PD). Organophosphates (OPs) are
widely used agricultural and household pesticides that can induce oxidative
stress and have been previously associated with PD. We investigated the
contribution of genetic variation in the NOS
genes to PD risk alone and in combination with OP pesticide exposure.
Methods: In 357 incident PD
cases and 495 population controls from Central California, we investigated 10
single nucleotide polymorphisms (SNPs) under a dominant genetic model for
association with PD; and considered gene-environment interactions for NOS1 rs2682826 with self-reported
household OP use and computer-modeled ambient OP exposure.
Results: Replicating previous
findings, we estimate 1.6-2 fold increases in PD risk for variant allele
carriers of NOS1 rs1047735, NOS2 rs1060826 and NOS2 rs2255929. Additionally, we replicate the interaction between NOS1 rs2682826 and any household
pesticide use (Odds ratio (OR)=1.81, 95% Confidence Interval (CI)=1.02-3.24).
When we limit to subjects reporting household OP pesticide use, we estimate a
stronger interaction (OR=2.63, 95% CI=1.23-5.63). Specifically, there was no
effect of the genetic variant in subjects unexposed to household OPs, yet when
a subject was exposed to OPs the variant T allele was associated with an
increased risk of PD beyond that observed for the CC genotype (ORCC+OP
=1.09, 95% CI=0.65-1.82 vs. ORCT/TT+OP=2.37, 95% CI=1.34-4.18). We
also found risk increases for high ambient OP exposure (ORCC+OP
=2.09, 95% CI=1.18-3.71 vs. ORCT/TT+OP=3.35, 95% CI=1.79-6.30).
Results did not change when we mutually adjusted for household pesticide use,
ambient exposures and occupational exposures to pesticides. Our findings support NOS1
and NOS2 as risk factors for PD and NOS1 rs2682826 as a modifier of OP
associations with PD.
P01.20
Exploring the impact
of Parkinson disease (PD) susceptibility loci in older persons without PD
Joshua M. Shulman1,
Lei Yu2, Aron Buchman2, Denis A. Evans2, Julie
A. Schneider2, David A. Bennett2, Philip L. De Jager3
1Baylor College of Medicine,
Houston, TX, USA
2Rush University
Medical Center, Chicago, IL, USA
3Brigham and Women’s
Hospital, Boston, MA, USA
Objective: Recent studies have identified a number of
loci significantly associated with PD; however, little is known about the impact
of these alleles on disease related clinical and pathologic outcomes in elders
without a PD diagnosis. We therefore investigated if PD susceptibility loci are
associated with PD endophenotypes, including parkinsonian motor signs, Lewy
body pathology, and substantia nigra neuronal loss in older individuals.
Methods: We studied 1,698 subjects (mean age=78) from the Religious Orders
Study and Rush Memory and Aging Project with longitudinal clinical evaluations,
and a nested neuropathologic cohort including 789 brains. Genotypes were
available for 19 single nucleotide polymorphisms previously associated with PD
susceptibility from published genome-wide scans. The primary outcomes included
a clinical summary measure of parkinsonism, based on a modified motor unified
Parkinson’s disease scale, and the presence of Lewy bodies or neuronal loss
within the midbrain substantia nigra at autopsy. Linear or logistic regression
analyses were adjusted for subject age and gender.
Results: PD risk
alleles at the MAPT (p=6x10-4),
CCDC62 (p=0.004), and MED13 (p=0.006) loci were associated
with parkinsonian signs, even after excluding subjects with clinical diagnosis
of PD. In secondary analyses, MAPT
and CCDC62 were predominantly
associated with bradykinesia, whereas MED13
and another risk allele, SREBF were
associated with gait impairment. Surprisingly, none of the PD susceptibility
loci were associated with Lewy body pathology; however, LRRK2 (p=0.01), MED13 (p=0.03),
and nominally BST1 (p=0.05) were
related to nigral neuronal loss. Besides their established link to PD
susceptibility, our results support a broader role for several risk loci on the
development of mild parkinsonian motor signs and associated motor disability in
older persons.
P01.21
The complex interaction
of LRRK2 with the cytoskeleton
Victoria
A Spain1, Bernard MH Law1, Veronica HL Leinster1, Daniel C Berwick1 and Kirsten Harvey1
1Department
of Pharmacology, UCL School of Pharmacy, London, UK
Objective: The interaction
of LRRK2 with microtubules has pathogenic relevance, since mutations in PARK8 segregating with Parkinson's
disease reduce neurite outgrowth and cause an accumulation of
hyperphosphorylated tau. In turn, defective post-translational modifications of
tubulin and microtubule-associated proteins alter the dynamic instability of
microtubules. The overall effect is aberrant axonal transport, synaptic
dysfunction and axonal degeneration. The aims of this study were to identify the
determinants of the association between LRRK2 and microtubules and the
subcellular distribution of LRRK2 at the cytoskeleton.
Methods: The LRRK2-microtubule association was investigated using yeast two-hybrid, quantitative yeast two-hybrid and
co-immunoprecipitation. LRRK2 distribution at the cytoskeleton was determined using
confocal microscopy.
Results: The interaction
between LRRK2 and tubulin is specific to β-tubulin isoforms TUBB, TUBB4
and TUBB6, and is conferred by the LRRK2 Roc GTPase domain and β-tubulin
C-termini. It is dependent on guanidine nucleotide binding and is disrupted by
both the pathogenic PARK8 mutation R1441G and artificial mutations
mimicking Roc autophosphorylation. The interaction requires Lys-362 and Ala-364
and is blocked in β-tubulin isoforms expressing serine at these positions.
Endogenous LRRK2 is expressed in growth cones of dopaminergic neuronal cell
lines. Overexpression of the LRRK2 wild-type and G2019S mutation influences
growth cone parameters and posttranslational modifications of cytoskeleton-associated
proteins. These results demonstrate the specificity of the LRRK2-tubulin
interaction and suggest phosphorylation of b-tubulin isoforms at
Ser-362 and Ser-364 could hinder LRRK2-tubulin interactions. We propose that
reciprocal mutations affecting the C-terminal β-tubulin residues could
disrupt LRRK2 interaction without compromising microtubule integration. In
addition, we suggest an effect of overexpression of LRRK2 wild-type and the
familial G2019S mutant on growth cone function and microtubule stability.
P01.22
Identification of
LRRK2 G2019S modifiers of disease penetrance
Joanne Trinh1,
Alan Donald1, Dan Evans1, Carles Vilariño-Güell1,
Michelle Lin1, Faycel Hentati2, Rachel Gibson3,
Matthew Farrer1
1Department of Medical Genetics,
Centre for Applied Neurogenetics, University of British Columbia, Vancouver,
BC, Canada.
2Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis,
Tunisia
3
Research
and Development, GlaxoSmithKline Pharmaceuticals Ltd., Harlow, England
Objective: LRRK2
p.G2019S is a major risk factor for parkinsonism with a frequency >30% in
North African Arab-Berber patients. The estimated age-associated penetrance of
p.G2019S at 50 years is 30%, rising to 80% by age 70. However, some carriers develop
early-onset (<45 years) parkinsonism and some elderly carriers remain
asymptomatic. We hypothesize that genetic factors influence phenoconversion of
p.G2019S carriers from an asymptomatic to motorically-affected state.
Methods: To
identify genetic modifiers of age of onset (AAO) we performed whole-genome
sequencing (WGS) in seven LRRK2 p.G2019S carriers with early-onset of disease
(AAO 34.9 SD±7.2 years, range 22-42) and seven elder asymptomatic carriers (age
77 SD±6.9 years, range 68-90) from Tunisia. In
addition, we also performed whole-exome analysis on four patients with
early-onset (AAO 42.5 SD±1.9 years)
and five with late-onset of disease (AAO 84 SD±4.2 years).We used
locus-based logistic regression methods to prioritize genes and variants for validation.
Sanger sequencing and subsequent SNP genotyping in 580 Tunisian cases and 480
controls was used for replication. Gene-environment interactions for smoking
and caffeine intake were also explored with this data. Survival curves
were plotted for each genotyped variant.
Results: WGS
identified ~11 million variant per person, including 287 coding
changes which are differentially represented in early-onset and asymptomatic
groups. Four variants in TMTC4
(p=0.0478), LOC149134 (p=0.0197), CENPQ (0.0492) and CYFIP1 (0.0292) were observed at significantly different
frequencies between early-onset patients and asymptomatic carriers. Smoking
(p=0.08) and caffeine intake (p=0.33) appear to have no effect on AAO.
Conclusions: Despite
the ethnic, genetic and environmental homogeneity in this population, the AAO
of disease for p.G2019S carriers spans over 60 years. WGS have identified four
variants which appear to modulate AAO and may provide novel therapeutic
strategies to delay the onset of disease.
P01.23
Movement disorders in
Ethiopia
Dawit K.Worku
Addis
Ababa University, Department of Neurology, Addis Ababa, Ethiopia
Background: In this
country of 80-million plus people, there is a shortage of physicians - only 15 neurologists
serve the entire country and most are concentrated in the capital city - making
it difficult for all who need care to see a neurologist.
Methods: A review
of journals was done on papers: movement disorders in Ethiopia available until
the end of June, 2011 at main Library of Addis Ababa University, School of
Medicine, Department of Neurology.
Results: There is little
information on the frequency of movement disorders seen by physicians in the
continent of Africa. In one retrospective study in a university-based neurology
clinic in Addis Ababa, Ethiopia, over 1 year period a total of 15.1% of the
neurological patients were seen for movement disorders. Of these, most were for
Parkinsonism (47.7%), followed by ataxia (16.5%), dystonia (8.3%), essential
tremor (8.3%), chorea (7.3%), and miscellaneous (11.9%). Data on Parkinson's disease in
sub-Saharan Africa is limited but it appears that the age-adjusted prevalence
may be a little lower than other parts of the world. The likely explanation for
this is a lack of diagnosis, and therefore treatment, leading to early
fatality. Diagnostic
evaluations are limited, but treatment is available, although expensive. In
spite of the limitations, patients with movement disorders require and seek
care in Ethiopia in proportions comparable to developed nations.
Conclusions: There are no adequate
prevalence studies to conclude with figures. The magnitude of the disease
prevalence needs to be studied with further research to reach for those
desperate patients. In a county where patients with movement disorder highly
stigmatize the problem even become worse. These findings underline the need for
adequate training in movement disorders for physicians and neurologists, and
community education in Ethiopia.
Basic
Science: CELL DEATH, NEUROPROTECTION AND TROPHIC FACTORS
P02.01
Neuroprotective
properties of oleuropein against 6-hydroxydopamine-induced cytotoxicity in
neuronal PC12 cells
Imène Achour1,
Manon Legrand1, Anne-Marie Arel-Dubeau1, Everaldo Attard2
and M-G. Martinoli1
1Cellular Neurobiology,
Dept. of Medical Biology, Université du Québec à Trois-Rivières, Québec, Canada
2Institute of Earth Systems, University of Malta, Msida, Malta
Objective: Oleuropein (Ole) is a
phenolic compound found in the olive leaf from Olea europaea, it is believed to have various pharmacological
benefits, including antioxidant and anticarcinogenic properties. The aim of
this study was to investigate whether Ole may protect neuronal cells against
degeneration in a cellular model of Parkinson’s disease (PD), neuronal PC12 cells exposed to the potent neurotoxin 6-hydroxydopamine (6-OHDA).
Methods: cytotoxicity assays,
DNA fragmentation apoptosis assay as well as epifluorescent
dyes and immunofluorescence by autophagy-specific proteins have been used in
6-OHDA- treated versus normal cells.
Results: Cytotoxicity assays
showed that the administration of Ole prior to the oxidative insult prevents
cell death induced by 6-OHDA. Furthermore, the results obtained by measuring
specific apoptotic DNA fragmentation, demonstrate that Ole significantly
decreases apoptosis. Currently, a growing body of evidence shows that autophagy
plays a key role in the pathogenesis of PD. Indeed, we observed autophagic
vacuoles in the cytoplasm of neuronal cells treated with Ole and we identified
them by labeling with acridine orange, Cyto-ID and by measuring LC3 expression,
a reliable marker for monitoring autophagy-related
processes, including autophagic cell death. Altogether, the results obtained suggest
that Ole has interesting neuroprotective properties which might be related to
the increased number of autophagic vacuoles. Other studies are in progress to
better define the role of Ole in apoptosis and autophagy.
P02.02
The phytosterol Cucurbitacin E exerts neuroprotective and pro-autophagic
effets in an “in vitro” model for Parkinson’s disease.
Anne-Marie Arel-Dubeau1, Fanny Longpré1, Everaldo
Attard2, Maria-Grazia Martinoli1
1Cellular neurobiology, Department of Medical Biology, Université du
Québec à Trois-Rivières
2Institute of Earth Systems, University of Malta, Msida, Malta
Objective: Neuroprotective therapies are
currently investigated because of their potential to reduce the incidence of
neurodegenerative disorders such as Parkinson’s disease (PD). As such, natural
molecules such as polyphenols and phytosterols are studied as neuroprotective
strategies to preserve cells from a variety of toxic effects often linked to PD
neurodegeneration, oxidative stress, mitochondrial dysfunction, protein
aggregation and formation of intracellular inclusions. In this study, we have
analyzed the neuroprotective potential of Cucurbitacin E (CuE), a triterpene
phytosterol extracted from the Cucurbitaceae Ecballium elaterium, on an in
vitro model of PD.
Methods: Our experimental paradigm uses
nerve growth factor (NGF)-differentiated PC12 cells treated with
1-methyl-4-phenylpyridinium (MPP+), a well known neurotoxin provoking a PD-like
syndrome. To evaluate the neuroprotective effects of CuE, we administered this
natural molecule to neuronal PC12 cells prior and during MPP+ exposure. We
measured the cytoprotective effect of CuE by cytotoxicity and apoptosis assays.
The antioxidant potential of CuE has also been analyzed using the intracellular
ROS production andthe superoxide anion content of the dopaminergic neurons.
Then, epifluorescent dyes and immunofluorescence by autophagy-specific proteins
have been used to observe autophagosome amounts in treated versus normal cells.
Results: While CuE proved to be an
effective neuroprotective molecule, as measured by cytotoxicity and the
expression of apoptotic parameters, it failed to present antioxidant effects,
leading our researches towards new cellular pathways of CuE activities. Indeed,
we studied whether CuE may modulate autophagy, a complex organelle- and
protein-degradation and recycling pathway. We can conclude that CuE is a
pro-autophagic compound and its implication in the autophagy cascade may be
accounted for its neuroprotective properties.
P02.03
Neuroprotective
treatment with PPAR-gamma agonist modulates microglia phenotype in the MPTPp
model of Parkinson disease
Anna R. Carta1, Augusta Pisanu2
1Dept. of Biomedical
Sciences, Univ. of Cagliari, Italy
2CNR Institute of Neuroscience,
Section of Cagliari, Cagliari, Italy
Objective: A dysregulated
cytokines production by microglia is a pathological event in Parkinson’s
disease (PD) neuropathology, conferring a neurotoxic phenotype to these cells.
In the chronic MPTP/probenecid (MPTPp) model of nigrostriatal degeneration, we
sought if stimulation of PPAR-gamma modulates microglia phenotype, since
PPAR-gamma is highly expressed in CNS immune cells, and receptor agonists, such
as rosiglitazone, mediate neuroprotection in PD models (Carta et al, 2011).
Methods: Mice
received 10 MPTPp injections over 5 weeks. As previously shown, rosiglitazone
(10 mg/kg i.p.) arrested the dopaminergic degeneration when administered late
in the treatment, starting after the 7th neurotoxin injection. To
evaluate microglia phenotype, the colocalization of pro- and anti-inflammatory
cytokines with CD11b-positive microglia was measured.
Results: In vehicle-treated
mice, microglia expressed low levels of the pro-inflammatory cytokine TNF-alpha
and of the anti-inflammatory cytokine TGF-beta. Across the chronic MPTPp
treatment microglia progressively acquired a highly activated morphology. The
percentage of microglia expressing high levels of TNF-α progressively
increased, as measured after 0 (6.83%), 1, 3, 7, 10 (23.94%) neurotoxin
injections. In contrast, the percentage of microglia expressing high levels of
TGF-beta initially increased, as shown by measures after 0 (17.54%) and 3
(34.97%) MPTPp injections, to be reverted to control levels after 10 (18.56%)
injections, indicating that MPTPp treatment directed microglia activation
toward a pro-inflammatory phenotype. Rosiglitazone administration in the late
part of neurotoxin treatment did not counteract microglia activation as
indicated by morphological analysis, however it reduced TNF-alpha production,
reverting to control levels the percentage of microglia highly expressing this
cytokine (11.15%). Moreover, rosiglitazone induced an overproduction of
TGF-beta, increasing the percentage of microglia expressing high levels of this
cytokine (44.44%), suggesting that rosiglitazone induced a switching in
microglia phenotype from pro-inflammatory to anti-inflammatory. Driving
microglia activation toward a beneficial phenotype may arrest the
“microgliosis” and underlie the neuroprotective activity of PPAR-gamma
agonists.
P02.04
Measurement of plasma
cytokines suggests T helper type 2 dominated T cell dysregulation in
Parkinson’s disease.
Keri Csencsits-Smith1,
Diane L.M. Bick1, Mary F. McGuire1, and Mya C. Schiess1
1University of Texas
Health Science Center at Houston Medical School. Houston, TX USA
Objective: The specific role of
CD4+ or “helper” T cells in the course of Parkinson’s disease (PD) is unclear.
It has been hypothesized that pro-inflammatory cytokines secreted by T cells,
including IL-17 and IFNγ, are associated with progression of PD. The
presence of specific T helper (Th) cytokine signals in the blood may indicate
systemic imbalance of T cell responses that contributes to PD pathology. We
questioned whether the Th-associated cytokines secreted in the blood of PD
patients would differ significantly from those measured in age-matched
controls.
Methods: Plasma samples were
collected from PD patients and age matched controls every 6 months over the
course of 2 years. Cytokine levels (pg/ml) were determined using a Millipore
Multiplex MAP human cytokine/chemokine panel and analyzed with a BioPlex 100
(BioRad). Unknowns were extrapolated using standard curves generated from
manufacturer-supplied standards. Mean +/- SD of cytokine concentrations were
compared between PD and control and significance determined via Student’s t
test with Welch’s correction.
Results: Surprisingly,
secretion of inflammation-associated IL-17 was lower in PD patients than
control, as was secretion of IFNγ, which is the hallmark of Th1 response.
In contrast, plasma isolated from PD patients contained significantly greater
IL-4 and IL-13 (* p < 0.001), which are linked to Th2 response.
The significant increase in IL-10 expression (which directly down-regulates Th1
response) in PD patients also indicated an overall shift towards Th2 response.
Importantly, cytokine levels did not significantly change in patients over the
course of the study, suggesting that a stable, Th2-skewed, systemic T cell
response is maintained in PD.
P02.05
Lmx1a and Lmx1b regulate survival of midbrain
dopamine neurons
Hélène Doucet-Beaupré1, Martin Lévesque1
1Institut Universitaire en
Santé Mentale de Québec, Université Laval, Québec, Canada
Objective: During embryonic
development, a combination of transcription factors specifies neural fate and
promotes differentiation by inducing distinct gene expression profiles. Lmx1a
and Lmx1b are transcription factors expressed by dopaminergic progenitors and
their expression persists in mature dopaminergic neurons. However, the role of
these factors in mature dopaminergic neurons remains unknown and the objective
of this study is to define it.
Methods: Conditional mutant
mice were used for the inactivation of Lmx1a and Lmx1b specifically in
postmitotic midbrain dopamine neurons without affecting the specification or
the proliferation of dopaminergic progenitors. In order to elucidate the
mechanisms by which Lmx1a and Lmx1b influence the maintenance of dopaminergic
circuits, the gene expression profile of Lmx1a and Lmx1b mutants was analyzed.
Results: The results suggest
that Lmx1a and Lmx1b are required to maintain mature dopaminergic neurons.
Inactivation of Lmx1a and Lmx1b causes progressive degeneration of dopaminergic
neurons, preferentially affecting the SNpc. Reduced dopaminergic axons
innervating the dorsal striatum and the onset of motor problems were observed.
The study of gene expression profiles of Lmx1a and Lmx1b mutants suggests that
these factors regulate genes from complexes I, III and V of the mitochondrial
respiratory chain. These results show that the maintenance of dopaminergic
systems is underpinned by the continued action of Lmx1a and Lmx1b beyond the
stages of development process. Lmx1a and Lmx1b could prove to be master
regulators coordinating and regulating mitochondrial biogenesis and signaling
cascades to meet the specific energy needs of neurons. Considering that
mitochondrial dysfunction is involved in Parkinson's disease, these findings
could lead to the identification of therapeutic targets to prevent the
degeneration of dopaminergic neurons in patients suffering from the disease.
P02.06
Determination of the
neuroprotective effects of SIRT3 in Parkinson’s disease.
Jacqueline A. Gleave1,
Krisitn Lizal1, Sherri L. Thiele1, Joanne E. Nash1
1Department of
Biological Sciences, Centre for the Neurobiology of Stress, University of
Toronto Scarborough, Toronto, ON, Canada
Objective: SIRT3 is a
NAD-dependent deacetylase localized in the mitochondria where it deacetylates
mitochondrial proteins resulting in enhanced ATP production and decreased reactive
oxygen species (ROS) levels. This globally enhances mitochondrial health. In
Parkinson’s disease (PD) mitochondrial dysfunction is central to the pathogenic
process. Therefore, we hypothesized that SIRT3 may have a neuroprotective role
in PD. The aim of this study was to utilise in
vivo and in vitro models to test
this hypothesis, and to determine the mechanisms underlying the neuroprotective
effects of SIRT3.
Methods: Endogenous SIRT3
levels were assessed in a rat model of PD by Western blot three weeks following
infection with mutant (A53T) human α-synuclein. The neuroprotective effect
of ectopic over-expression of SIRT3 in this rat model of PD was also
determined. Rats were infused with recombinant adeno-associated viruses
expressing SIRT3-myc or α-synuclein in the substantia nigra. Three and six
weeks following infection, behavioural deficits were assessed using the
cylinder test. To investigate the mechanism underlying SIRT3-induced
neuroprotection, a catecholaminergic cell line (SH-SY5Y) stably overexpressing
SIRT3-myc was used as a cellular model of PD. They were exposed to two agents
to induce neurotoxicity, dopamine (65m) and rotenone
(30nm). Cellular toxicity and ROS production were assessed using propidium
iodide and DCF-FA respectively.
Results: We found that SIRT3
levels were elevated in the early stages of parkinsonian pathology in the
α-synuclein rat model of PD. In parkinsonian rats, overexpressing SIRT3 in
the substantia nigra reverses behavioural abnormalties. Overexpression of SIRT3
resulted in a decrease in cellular toxicity after exposure to dopamine and
rotenone (35 and 36% respectively). Overexpression of SIRT3 also decreased ROS
production by 29% after dopamine exposure and 50% after rotenone-induced
toxicity.
Conclusion: These results suggest
that SIRT3 is neuroprotective in a rat model of PD. These neuroprotective
effects are likely due to decreasing ROS production.
P02.07
Nuclear Receptors
Agonists as Neuroprotective Agents in Parkinson's disease Alleviation
Mohammad Jodeiri1,
Kamran Ghaedi1,2, Abbas Kiani-Esfahani2, Ali Ghoochani2,
AlirezaShoaraye Najati2, Khadijeh Karbalaie2, Maryam
Norbakhshnia1, Soheila Rahgozar1,Mohammad Hossein Nasr
Esfahani2
1 Biology Deparment, School of Sciences, University
of Isfahan, Isfahan, Iran
2 Department of Cellular Biotechnologies at Royan
Institute for Biotechnology, Cell Science Research Center, ACECR, Isafan, Iran
Objective: Parkinson's disease
(PD) is the second prevalence neurodegenerative disorder characterizing by tremor,
rigidity, dyskinesia and dementia. The main pathology of this disease
underlying selective degeneration of dopaminergic neurons in the substantia
nigra (SN). Orphan nuclear receptors such as PPARγ and Nurr1 have
important roles in many cardinal pathways in cells. Previous studies confirmed
PPARγ agonists' protective effects in neurological disorder such as PD.
Nurr1 as an important transcription factor which has a critical role in stem
cells differentiation into dopaminergic neurons can be focused as a potential
target to ameliorate PD symptoms.
Methods: In this study we
used PC12 as an in vitro model of PD. These cells were treated with various
concentration of MPP+, it caused the death of PC12 cells in a time- and
dose-dependent manner. GW1929 (PPARγ agonist) and 6-mercaptopurine (Nurr1
agonist) act as neuroprotective agents in in this experiment and we analyze
their influence on TH, Ferritin Light Chain, Nurr1 and Ephrin A1 expressions.
In addition we tested ROS level and Mitochondrial Membrane Potential (MMP) by
flow cytometry.
Results: We found that Nurr1
agonist beyond its neuroprotective feature can increase ferritin light chain
expression which important in iron metabolism. In addition PPARγ agonist
combination with Nurr1 agonist has impressive effect on Ephrin A1 expression
that has a critical role in dopaminergic neurogenesis. Present study suggests
that Nurr1 agonist might be a new compound to alleviate PD patients' symptoms
by controlling various pathways in neurons.
P02.08
IRX4204
as a novel disease-modifying therapeutic agent in Parkinson’s disease
Giulio Maria Pasinetti
Icahn School of
Medicine at Mount Sinai, New York, NY, USA
Objective: IRX4204 is
a second-generation retinoid X receptor (RXR) agonist currently being tested for
prostate cancer treatment with an excellent safety record. Nurr1-RXR
heterodimer selective agonists have been actively pursued as a potential
pharmacological target for Parkinson’s disease (PD) due to their
neuroprotective effects in models of PD. The objective of our study is to
evaluate the effects of IRX4204 as a potential novel therapeutic in PD
neuropathology.
Methods: Primary rat
mesencephalic cultures were used study the role of IRX4204 on Nurr1-mediated
neuroprotection. The 6-hydroxydopamine (6OHDA) induced rat model of PD was used
to examine the potential neuroprotective role IRX4204 on PD pathology. Nuclear
magnetic resonance (NMR) and photo-induced cross-linking of unmodified protein
(PICUP) were used to evaluate the role IRX4204 on prevention of
α-synuclein binding and oligomerization.
Results: We found
IRX4204 can selectively promote dimerization of the nuclear factor Nurr1-RXR at
nM concentration in vitro and can promote expression of neurotrophic factors
for the survival and maintenance of nigral dopaminergic (DA) neurons in a
dose-dependent manner in vivo. This evidence is consistent with a significant
attenuation of PD-type motor impairments following 6-OHDA lesions in response
to IRX4204. Using a combination of NMR spectroscopy and PICUP assays, we found
that IRX4204 shifts and prevents oligomerization of α-synuclein. Our data
suggest that IRX4204 may benefit PD by providing neuroprotective support for DA
neurons and by protecting DA neurons from α-synuclein neurotoxicity. We hypothesize
that IRX4204 may neuroprotect DA neurons through Nurr1 mediated neuroprotective
mechanisms intracellularly and possibly at more advanced PD-like states through
inhibition of α-synuclein oligomerization.
P02.09
Novel low heparin
affinity neurturin variants with disease modifying effect in a rat model of
Parkinson’s disease
Anna-Maija Penttinen1, Pia Runeberg-Roos1,
Elisa Piccinini1, Kert Mätlik1, Satu Kuure1,
Maxim M. Bespalov1,2, Johan Peränen1, Nisse Kalkkinen1,
Mikko Airavaara1, Richard Penn3, Mart Saarma1
1Institute of Biotechnology, University of Helsinki,
PB 56 (Viikinkaari 9), FI-00014, University of Helsinki, Finland
2Stem cells and Neurogenesis Unit, Division of
Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, Milan, Italy
3CEO at NTF Therapeutics, Inc, 332 Minnesota Street,
Ste W1750, St. Paul, MN, USA
Objective. Neurturin is a
neurotrophic factor with therapeutic potential in Parkinson’s disease. One of
the main problems with parenchymal neurturin injections has been the inadequate
distribution of the protein. Therefore, we have developed novel, biologically
active neurturin variants with improved spreading in the brain.
Methods. Mutations were
introduced to the putative heparin binding site of neurturin and the variants
were produced in mammalian cells. The biological activity of the variants was
tested with RET phosphorylation assay and the spreading capacity by injecting
5μg of variants into rat striatum. To assess the disease modifying
effects, 5μg of the proteins were injected into striatum two weeks after
6-OHDA (4x7μg). The behavioral effects were evaluated by
amphetamine-induced rotations. The histological effects were analysed by
quantification of TH-positive fibers and cell somas.
Results. Neurturin variants with
reduced heparin binding capacity showed improved spreading in tissue. Neurturin
variant N4 reduced significantly the rotational behavior. The histological
analyses showed both neurturin variants N2 and N4 to protect the dopaminergic
neurons in substantia nigra from degeneration. In addition, the N4 variant was
efficient in protecting the striatal TH-positive neurites. These results
together suggest that especially the novel neurturin variant N4 has an
increased potential to protect the dopaminergic nigrostriatal pathway from
degeneration in Parkinson’s disease.
P02.10
Resveratrol protects
dopaminergic cells against high glucose-induced oxidative stress and apoptosis:
role of glucose-regulated protein 75
Justine Renaud1,
Julie Bournival1 and Maria-Grazia Martinoli1,2
1Université du Québec à Trois-Rivières,
Trois-Rivières, Canada
2Neuroscience Research Unit, Université Laval,
Canada
Objective: Resveratrol (RESV), a
natural polyphenolic compound, has long been acknowledged to have
cardioprotective,
anticarcinogenic and anti-inflammatory actions. RESV holds antioxidant
properties reducing the formation of reactive oxygen species (ROS) which lead
to oxidative stress and apoptotic death of dopaminergic (DAergic) neurons, a
hallmark of Parkinson’s disease (PD). Recent literature has recognized
hyperglycemia as a cause of oxidative stress reported to be harmful for the
nervous system. In this context, our study aimed: a) to evaluate the
effect of RESV against high glucose-induced oxidative stress in DAergic cells
b) to study the anti-apoptotic properties of RESV on DAergic cells in a
high-glucose condition, and c) to investigate the role of glucose-regulated
protein 75 (GRP75), a marker of mitochondrial homeostasis known to be depleted
in post-mortem PD patient brains, in mediating the beneficial actions of RESV.
Methods: Differentiated PC12
cells were treated with low-glucose medium (1 g/L) or high-glucose medium (4.5
g/L) for 96 hours. For the last 24 hours, PC12 cells were administered RESV at
a concentration of 0.1 µM. Mitochondrial superoxide anion was measured to
assess oxidative stress while the apoptotic cascade was investigated using DNA
fragmentation assays, Western blotting and immunofluorescence measurements.
Results: Our results showed that RESV protects DAergic
neurons against high glucose-induced oxidative stress by diminishing levels of
superoxide anion. Then, RESV reduced high glucose-induced apoptosis in DAergic
cells by modulating DNA fragmentation and the expression of apoptotic markers
such as Bax, Bcl-2, p53, cleaved caspase-3 and cleaved PARP-1. Moreover, RESV
rescued expression levels of GRP75 which were significantly decreased by
high-glucose treatment. GRP75 is known to bind and sequestrate pro-apoptotic p53
in the cytosol, preventing its translocation to the nucleus. Altogether, our
data evoke a correlation between hyperglycemia and neurodegeneration, which
provides new insight on the high occurrence of PD in diabetic patients.
P02.11
Fasudil administration
elevates striatal dopamine and protects against alpha synuclein mediated
toxicity
Caryl Sortwell1,
Fredric Manfredsson1, Christopher Kemp1, Sara
Gombash-Lampe1, Nathan Kuhn1, Katrina Paumier1,
Jack Lipton1, Kathy Steece-Collier1, Apryl Pooley1,
Nathan Levine1, Gregory Fink1, Hannah Garver1,
Puliyur MohanKumar1, Sheba MohanKumar1, Konstantinos
Petritis2, Tony Tegeler2, Audra Kauffman3 and
Jeffrey MacKeigan3
1Michigan State
University, Grand Rapids, MI, USA
2Translational Genomics
Research Institute, Phoenix, AZ, USA
3Van Andel Research
Institute, Grand Rapids, MI, USA
Objective: No treatments exist
to slow nigrostriatal degeneration in Parkinson’s disease (PD). Repurposing of
drugs with known safety profiles in humans can accelerate clinical trials and discovery
of effective treatments. The present experiments were conducted to determine
whether fasudil, an orally available Rho-kinase (ROCK) inhibitor with a
favorable safety profile in humans, could be successfully repurposed as a
neuroprotective agent for PD.
Methods: We conducted
preclinical studies in cell culture and in vivo rat models of alpha-synuclein
mediated toxicity. Fasudil was orally administered in chow (10 or 25
mg/kg/day), rats were assayed for a number of outcome measures including levels
of striatal monoamines, levodopa-induced dyskinesias, and number of surviving
nigral DA neurons following intranigral injection of recombinant
adeno-associated virus expressing human wild-type alpha-synuclein (rAAV
α-syn).
Results: Fasudil and other ROCK inhibitors provide
neuroprotection from α-syn mediated toxicity in H4 cell cultures. Oral
administration of fasudil to rats: 1) significantly increased fasudil and
hydroxyfasudil levels in plasma and brain, specifically in the substantia nigra
(SN), in a dose-dependent manner, 2) resulted
in no overall impact on heart rate and arterial pressure, 3)
significantly increased (doubled) DA and DA metabolites in the striatum, 4) did
not exacerbate existing levodopa-induced dyskinesias, and 5) provided
significant neuroprotection from rAAV α-syn mediated toxicity.
Specifically, rAAV α-syn injected rats fed control chow exhibited a 70%
reduction in tyrosine hydroxylase immunoreactive (THir) neurons in the SN pars
compacta (SNpc) eight weeks after vector injection. In contrast, rats fed 25
mg/kg/day fasudil chow (high dose) exhibited only a 40% reduction in THir
neurons. Counterstaining with cresyl violet verified that high dose fasudil
provided true neuroprotection of SNpc dopamine neurons. To our knowledge this
is the first orally available compound to provide neuroprotection in the AAV
α-syn PD model and suggests that fasudil holds great potential for the
treatment of PD.
P02.12
Activin A is
neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease
Sandy Stayte1,
Anna Troscher1,2, Maximilian Bamberger1,3, Andrea
Abdipranoto1, Bryce Vissel1
1Garvan Institute of
Medical Research, Darlinghurst, NSW, Australia
2University of Veterinary
Medicine, Veterinaerplatz, Vienna, Austria
3FH Krems University of
Applied Science, Krems, Austria
Objective: There still remains a
pressing need to identify therapeutic targets that effectively protect against
the dopaminergic degeneration that is characteristic of Parkinson’s disease
(PD). Growth factors have been demonstrated to promote survival,
differentiation and maintenance of neuronal cells within the central nervous
system and as such, are promising disease-modifying targets. Activin A, a
member of the transforming growth factor-b
superfamily, has significant neuroprotective effects against the Parkinsonian
toxin 6-OHDA in vitro. In addition,
activin A has been shown to possess potent anti-inflammatory effects in an
acute brain injury model. The aim of this study was to investigate if activin A
was neuroprotective in an in vivo
model of PD.
Methods: 12 week old male C57BL/6
mice were implanted subcutaneously with osmotic micro-pumps, filled with
recombinant activin A (24ng/ml) or
vehicle control, and connected to an infusion cannula in the right lateral
ventricle (AP -0.26mm, ML -1.0mm). The following day mice were administered
MPTP subcutaneously (4 x 20mg/kg, 2 h interval). Tissue was harvested 7d later
and analyzed for dopaminergic neurons, total neurons, astrocytic and microglial
populations by immunolabelling for tyrosine hydroxylase (TH), NeuN, GFAP, and
Iba1, respectively, and quantified in the substantia nigra pars compacta via
stereology. Quantification of striatal dopamine transporter expression was
performed by measuring binding of [3H]-mazindol.
Results: MPTP-injected animals that received activin A had significantly higher
numbers of TH and NeuN-positive cells compared to animals receiving vehicle.
Treatment of MPTP-injected animals with activin A significantly protected
striatal dopamine terminals as measured by increased [3H]-mazindol binding.
Stereological analysis revealed a significant decrease in GFAP and
Iba1-positive cells in the substantia nigra in activin A-treated animals
following MPTP compared to controls. Our study suggests that activin A is
neuroprotective in the MPTP mouse model, indicating its potential as a novel
therapeutic target in the treatment of PD.
P02.13
Enhancement of ATF4 and parkin function as a
neuroprotective strategy for Parkinson disease
Xiaotian Sun1, Pascaline Aime1,
Lloyd A. Greene1, Oren A. Levy1
Columbia
University Medical Center, New York, NY, USA
Objective: The lack of disease-modifying
treatments is a critical unmet need in the treatment of Parkinson disease (PD).
Our group recently identified a novel neuroprotective pathway in PD models:
activation of the transcription factor ATF4 maintains parkin levels in response
to PD-mimetic stressors. In this study, we show that multiple neuroprotective
interventions require ATF4-parkin signaling for their beneficial effects, thus
further validating the therapeutic potential of enhancing ATF4-parkin function.
Methods: Differentiated PC12 cells
or primary ventral midbrain cultures were pretreated with the different
protective regimens, then exposed to the PD-mimetic stressors 6-hydroxydopamine
(6-OHDA) or 1-methyl-4-phenylpyridinium (MPP+). Silencing of ATF4 or parkin was
achieved by lentiviral infection with specific shRNA constructs. Survival was
assessed by counting viable nuclei. Analysis of protein expression was
performed by Western blotting of total cell lysates. Analysis of mRNA
expression was performed by real-time quantitative PCR.
Results: We assessed two different
approaches to activating ATF4 function. First, cells were exposed to sub-lethal
doses of thapsigargin in order to activate the ER stress response. Indeed, this
preconditioning regimen led to a greater increase in ATF4, mitigated the
reduction in parkin, and also protected PC12 cells against 6-OHDA-induced cell
death. ATF4 is necessary for this protection, as silencing ATF4 abolished the
protective effect of the preconditioning treatment. Second, we used guanabenz,
an FDA-approved drug that inhibits the GADD34-PP1 complex, leading to enhanced
translation of ATF4. Guanabenz attenuated 6-OHDA-induced cell death in both
PC12 cells and primary ventral midbrain dopaminergic neurons. Guanabenz leads
to an increase in ATF4 and parkin levels; if either one of these is silenced,
then the protective effect of guanabenz is lost. In sum, these data support
ATF4-parkin as potential neuroprotective targets. Furthermore, we identify a
specific drug for further evaluation as a disease-modifying treatment for PD.
P02.14
Neuroprotective
effects of blueberry anthocyanins in Parkinson’s disease models
Mitali A.
Tambe1, Katherine Strathearn1, Susan L. Roy1,
Gad G. Yousef2 Mary Grace2, Qing-Li Wu3, James
E. Simon3, Mary Ann Lila2 and Jean-Christophe Rochet1
1Department
of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West
Lafayette, IN, USA
2Department
of Food, Bioprocessing and Nutrition Sciences, North Carolina State University,
NC, USA
3Department
of Plant Biology & Pathology, Rutgers University, New Brunswick, NJ, USA
Objective:
Parkinson’s disease (PD) is characterized by a loss of
dopaminergic neurons in the substantia nigra. Epidemiological evidence
suggests that the consumption of dietary polyphenols reduces the risk of
neurodegeneration. We hypothesize that a blueberry (BB) extract rich in
anthocyanins may be neuroprotective in PD models. Our goal is to assess if a BB
extract can rescue dopaminergic cell death triggered by PD-related insults and
to identify the underlying mechanisms of neuroprotection.
Methods: We tested
a BB extract in a dopaminergic cell viability assay. Primary midbrain cultures
obtained from E17 rat embryos were exposed to PD-related insults including
rotenone, paraquat and virus encoding mutant alpha-synuclein (A53T αSyn)
in the presence and absence of the extract. Dopaminergic cell viability and
neurite length and number were assessed by immunocytochemical analysis. We also
determined the effect of the BB extract on expression levels of DJ-1, a
redox-sensitive chaperone protein implicated in PD, by Western blot analysis.
In addition, we tested the effect of the extract on the transcriptional
activity of Nrf2 (nuclear factor erythroid 2-related factor 2), a transcription
factor that regulates the expression of antioxidant enzymes, using an
adenoviral reporter construct encoding the EGFP gene downstream of the heme
oxygenase promoter.
Results: The BB
extract was found to alleviate dopaminergic cell death and neurite loss in primary
midbrain cultures exposed to rotenone, paraquat and A53T αSyn. Preliminary
results suggest that the extract induces an increase in the transcriptional
activity of astrocytic Nrf2 and up-regulates DJ-1. Current efforts are aimed at
determining whether Nrf2 and DJ-1 up-regulation are necessary and/or sufficient
for the neuroprotective effects of BB anthocyanins in PD models. Ultimately
these studies may yield valuable insight into neuroprotective strategies to
decrease the risk of PD or slow disease progression.
P02.15
Effect of a co-administration of neurotrophic
factors CDNF and GDNF in a 6-OHDA model of Parkinson’s disease in rats
Merja H. Voutilainen1,2, Susanne Bäck1, Päivi
Pulkkila2, Mart
Saarma2, Pekka T. Männistö1 and Raimo K. Tuominen1
1Division of
Pharmacology and Toxicology, Faculty of Pharmacy, Viikki Biocenter, University
of Helsinki, FIN-00014, Helsinki, Finland
2Institute of
Biotechnology, Viikki Biocenter, University of Helsinki, FIN-00014, Helsinki,
Finland
Parkinson’s disease (PD)
is a neurodegenerative disease associated with a progressive loss of
dopaminergic neurons of the substantia nigra (SN) and accumulation of
intracellular inclusions containing α-synuclein. Current therapies of PD
do not stop the progression of the disease and their efficacy wanes over time.
Neurotrophic factors (NTF) are naturally occurring proteins promoting survival
and differentiation of neurons and maintenance of neuronal contacts. CDNF
(cerebral dopamine neurotrophic factor) and GDNF (glial cell line-derived
neurotrophic factor) have shown neurorestorative activity in the unilateral
6-hydroxydopamine (6-OHDA) lesion model of PD in rats when administered
individually.
Objective: Study the effect
of a low dose of CDNF
alone or in combination with a low dose of GDNF in a unilateral 6-OHDA lesion
model in rats.
Methods: CDNF was given with or
without GDNF into the striatum four weeks after a unilateral intrastriatal
injection of 6-OHDA (20 µg). Amphetamine-induced (2.5 mg/kg, i.p.) rotational
behavior was measured every two weeks for 3 months. Tyrosine hydroxylase
(TH)-positive cells from SN pars compacta and striatal TH-positive fiber
density were analyzed at 12 weeks post lesion.
Results: CDNF (1-10 µg) and
GDNF (1-10 µg) alone had robust neurorestorative effect in the 6-OHDA model of
PD but one specific dose combination had an additive effect: CDNF (2.5µg) and
GDNF (1µg) co-administration led to stronger trophic effects relative to the
injection of either NTF alone at the same dose. Our results indicate, for the
first time, that a co-administration of two NTFs with different mechanism of
action, i.e. CDNF and GDNF, shows stronger trophic and functional effects than
either NTF alone. The results may have clinical implications in the future use
of NTFs in therapy of PD.
P02.16
Lewy body fractions from patients with
Parkinson’s disease initiate α-synuclein-dependent neurodegeneration in
mice and non-human primates
Ariadna
Recasens1, Benjamin Dehay2, Jordi Bové1, Iria
Carballo-Carbajal1, Sandra Dovero2, Ana Pérez3,
Pierre-Olivier Fernagut2, Javier Blesa4, Annabelle Parent1,
Celine Perier1, Isabel Fariñas3, José A. Obeso4,
Erwan Bezard2 and Miquel Vila1,5,6
1Neurodegenerative
Diseases Research Group, Vall d’Hebron Research Institute (VHIR)-Center for Networked
Biomedical Research on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain
2Université de Bordeaux, Institut
des Maladies Neurodégénératives, CNRS UMR 5293, Bordeaux, France
3Department of Cell
Biology, University of Valencia, Valencia, Spain
4Basal Ganglia and
Movement Disorders Unit, Center for Applied Medical Research (CIMA), University
of Navarra, Pamplona, Spain
5Department of
Biochemistry and Molecular Biology, Autonomous University of Barcelona (UAB),
Barcelona, Spain
6Catalan Institution
for Research and Advanced Studies (ICREA), Barcelona, Spain
Objective: Mounting evidence indicate that
neuropathological a-synuclein lesions may
self-propagate and spread progressively throughout
the brain of Parkinson’s disease (PD) patients by a cell-to-cell transmission
mechanism, thereby contributing to the extension and progression of the disease
process. While synthetic α-synuclein fibrils can lead to
α-synuclein pathology in mouse brain, the physiopathological significance of
disease-associated, Lewy body (LB)-linked human α-synuclein
is
unknown.
Methods: Here,
we stereotaxically inoculated a-synuclein-containing LB
fractions derived from nigral post-mortem PD samples into the substantia
nigra or striatum of wild-type mice and non-human primates (NHP).
Results: In mice, a single LB
nigral injection resulted in progressive nigrostriatal neurodegeneration
starting at striatal dopaminergic terminals.
At the onset of LB-induced denervation, endogenous murine α-synuclein
adopted a pathological conformation and accumulated within nigral neurons.
LB-induced pathogenic effects required both human α-synuclein present in LB fractions and host expression of
α-synuclein. In NHP, striatal or nigral LB injections caused nigrostriatal
degeneration and accumulation of pathological α-synuclein in anatomically
interconnected regions.
Our study unravels a pathogenic prion-like species-barrier crossing effect of
human-derived pathological α-synuclein.
BASIC SCIENCE: PROTEIN MISFOLDING AND HANDLING
P03.01
Administration of
L-tyrosine with levodopa prevents insertion of levodopa into proteins and could
be neuroprotective in Parkinson’s disease
Kenneth J Rodgers,
Cameron Votano and Sandra Chan
School of Medical and Molecular
Biosciences, University of Technology, Sydney, Australia
Objective: The 20 ‘protein’ amino
acids (AA) account for less than 2% of all AA in nature. Most ‘non-protein’ AA
are made by plants and can be used to defend against predation. Canavanine,
from jack bean, kills larvae by replacing arginine in the peptide chain and is
lethal to rats. L-DOPA (levodopa), from mucuna plants, also kills larvae1.
LDOPA replaces L-tyrosine in protein synthesis2. Proteins containing
incorporated LDOPA are present in brain and plasma of L-DOPA-treated
patients3,4 and induce apoptosis in human neurons in vitro5. Here we
test the ability of L-tyrosine to prevent LDOPA incorporation into proteins in
vivo.
Methods: Rats (n=22) were
administered L-dopa (6.5mg/kg) and benserazide (1.5mg/kg), IP, twice daily with
or without L-tyrosine (100 mg/kg). After sacrifice (21 days), proteins were
extracted from the motor cortex (MC), substantia nigra (SN) and striatum (CPu)
and levels of DOPA-containing proteins measured by HPLC.
Results: At sacrifice there was
a 2-fold increase in tyrosine levels in the brain regions examined but no
difference in levels of DOPA and dopamine. Levels of DOPA in hydrolyzed
proteins increased 5 fold in the CPu of DOPA-treated rats but were unchanged in
SN and MC. Co-administration with L-tyrosine reduced DOPA levels in CPu
proteins by 60% (p<0.01).
Discussion: The question as to
whether levodopa produces long-term toxicity in PD patients remains unresolved.
Mischarging of tRNAtyr with L-DOPA and incorporation into neuronal cell
proteins is a mechanism of L-DOPA toxicity that has been overlooked4. Ltyrosine
is protective in vitro4 and in the present study we demonstrate that
after a relatively short exposure to L-DOPA, proteins containing incorporated
L-DOPA are detectable in the rat brain and incorporation can be significantly
reduced with L-tyrosine.
P03.02
Modulation of alpha-synuclein protein folding by a
marine-sourced extract
James C. Giffin1, Robert C. Richards2,
Cheryl Craft2, Nusrat Jahan2, Thierry Chopin3,
M. Szemerda4, Shawna L. MacKinnon2, and K. Vanya Ewart2
1Department of Biology,
Dalhousie University, Halifax, Nova Scotia, Canada
2Aquatic and Crop
Resource Development Portfolio, National Research Council of Canada, Halifax,
Nova Scotia, Canada
3Canadian Integrated
Multi-Trophic Aquaculture Network, University of New Brunswick, Saint John, New
Brunswick, Canada
4Cooke Aquaculture
Inc., Blacks Harbour, New Brunswick, Canada
Objective: Protein misfolding has increasingly
recognized causative roles in several human neurological diseases.
Alpha-synuclein is a protein involved in the regulation of several neuronal
synaptic functions. When misfolded and aggregated into an amyloid form, it has
been implicated in neuronal dysfunction and degeneration in Parkinson’s disease
and related disorders. Marine species, notably those exposed to extreme or
fluctuating conditions, offer new understanding of cellular protein folding
challenges as well as novel opportunities to address them. Therefore, preventive
and therapeutic options are being sought from our cold oceans to limit amyloid
formation in alpha-synuclein. The goal of this project was to evaluate the
effects of several marine species-derived extracts from the Bay of Fundy,
Canada, on the fold stability of alpha-synuclein.
Methods: Marine samples were collected and aqueous
extracts were prepared from them. The effects of the extracts on protein fold
stability were measured using a standard thermofluor melting point assay. The
identified active extract was fractionated and the fractions were assessed
using the same method. The active extract and fractions thereof were then
analyzed for modulation of amyloid formation in alpha-synuclein using a
standard thioflavin T assay, which was confirmed by fibril determination using
transmission electron microscopy. Additionally, effects of the active extract
and its fractions on the secondary structure of alpha-synuclein were examined.
Results: Activities that increased and decreased the
alpha-synuclein fold stability were identified within a single extract.
Components with these contrasting activities were separated both by acetone
precipitation and by size fractionation, providing insight into the distinct
sources of these activities. The effects on amyloid formation and protein
structure were also assessed. Compounds identified in this way may lead to
novel marine-sourced products that directly address the protein misfolding that
appears to be causative in Parkinson’s disease.
P03.03
Protein misfolding
cyclic amplification (PMCA) as an alpha-synuclein anti-aggregation
drug-screening tool
Maria E Herva1, Shahin Zibaee2,
Graham Fraser2, Roger Barker1, Michel Goedert2
and Maria Grazia Spillantini1.
1
John
Van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK
2 MRC Laboratory of
Molecular Biology, Cambridge, UK
Objectives: The hallmark of
Parkinson’s disease is the presence of intraneuronal inclusions known as Lewy
bodies. Their main component is a misfolded isoform of an otherwise normal
protein called alpha-synuclein. The spread of the aggregated alpha-synuclein in
the brain is related to the progression of the disease. Inhibiting
alpha-synuclein aggregation could halt the spread and therefore slow or even
arrest the disease progress.
Formation
of alpha-synuclein filaments can be reproduced in vitro using recombinant protein, but the filament growth is very
slow and so unsuitable for high throughput anti-aggregation drug screening. To
overcome this obstacle we have investigated whether the protein misfolding
cyclic amplification (PMCA) technique, used for fast amplification of prion
protein aggregates, could be adapted for growing alpha-synuclein aggregates.
Furthermore we explored the application of the alpha synuclein PMCA for drug
screening.
Methods: During PMCA,
recombinant alpha-synuclein was subjected to cycles of sonication and
incubation and the growth of fibrils was monitored by enhanced Thioflavin T
fluorescence. Circular dichroism, electron microscopy, native and SDS-PAGE gels
and enzymatic digestions were used to demonstrate alpha-synuclein aggregate
formation. A panel of drugs was studied to evaluate the sensitivity of the
system for alpha-synuclein anti-aggregating drug screening.
Results: Our results indicate
that PMCA can be used to form stable alpha-synuclein fibrils. We have
characterized the newly generated material as authentic alpha-synuclein
filamentous aggregates using several biophysical and biochemical methods. We have
also demonstrated that anti-aggregating drugs can selectively inhibit PMCA
fibril formation of alpha-synuclein.
Conclusions: Our results show
that alpha-synuclein PMCA is a fast and reproducible system that could be used
as high throughput screening for alpha-synuclein anti-aggregating compounds.
Therefore this system is relevant for identifying therapeutic compounds for
Parkinson’s disease and other alpha-synucleinopathies.
P03.04
The association between Gaucher disease and Parkinson
disease: from Human to Drosophila
Gali Maor1, Sigal Rencus-Lazar1,
Mirella Filocamo2, Hermann Steller3, Daniel Segal4
and Mia Horowitz1
1Department of Cell
Research and Immunology, Tel Aviv University
2 Centro di Diagnostica
Genetica e Biochimica delle Malattie Metaboliche, IRCCS G. Gaslini, Genova,
Italy
3Howard Hughes Medical
Institute, Strang Laboratory of Cancer Research, The Rockefeller University,
New York, NY, USA
4Department of
Molecular Biotechnology and Microbiology, Tel Aviv University, 69978, Israel
Gaucher disease, an
autosomal recessive disease, results from mutations in the GBA1 gene, encoding the lysosomal enzyme acid β
glucocerebrosidase (GCase). Mutant GCase variants undergo ERAD, the degree of
which is a major determinant of disease severity. The presence of mutant
molecules in the ER induces ER stress and the unfolded protein response (UPR).
Previous publications noted UPR in GD derived skin fibroblasts. We have
extended these studies to show that UPR exists in GD derived skin fibroblasts,
manifested by upregulation of the expression of the transcription factor CHOP
and the chaperone BiP (Grp78), phosphorylation of eIF2α and cytoplasmic
splicing of the transcription factor Xbp1. UPR exits also in skin fibroblasts
that derived from carriers of GD mutations. We assume that ERAD of mutant GCase
and UPR are a major determinant in the development of Parkinson disease among
GD patients and carriers of GD mutations. To confirm this assumption we
developed Drosophila models for
carriers of GD mutations. There are two GBA1
homologs in Drosophila, designated CG31414 and CG31148, both encoding
proteins showing ~31% identity and ~49% similarity to the human GCase. There
are two Drosophila lines available,
each with a transposable element insertion (a minos insertion) in one of the
fly GCase orthologs, expected to result in a truncated protein. We tested UPR
in double heterozygous flies, as a model for carriers of GD mutations. Our
results showed activation of the UPR machinery in the heterozygous flies as
tested by Hsc70 (the fly BiP
ortholog) activation, Xbp1 splicing and phosphorylation of eIF2a.
We also established fly lines expressing the human N370S and the L444P
mutations. Both lines portrayed UPR and climbing difficulties, reminiscent of Parkinson
disease. Our results strongly indicate that UPR is a determinant in the
development of Parkinson disease among GD patients and carriers of GD
mutations. To summarize, the Drosophila
model is the first animal model in which expression of mutant GBA1 allele in a
heterozugous state leads to development of Parkinsonian signs.
P03.05
Smoking
and Parkinson’s disease: nicotine binds to alpha-synuclein and causes large
conformational changes which may prevent it from misfolding.
Omid
Tavassoly1, Sergiy Nokhrin1, Oleg Dimitriev1,
Jeremy S. Lee1
1Department of Biochemistry, University of Saskatchewan,
Saskatoon, Canada
Objective: α-Synuclein (AS)
is an intrinsically disordered protein of 140 amino acids which is abundant in
dopaminergic neurons. Misfolding and aggregation of AS leads to the formation
of intracellular Lewy Bodies which are the hallmark of Parkinson’s disease and
related dementias. The binding of dopamine and nicotine to AS was investigated
by nanopore analysis.
Methods: In this technique
single AS molecules are interrogated electronically as they interact with an
α-hemolysin pore. The electronic signal is very sensitive to the structure
and conformation of the protein and, thus, if a drug causes a conformational
change it can be readily detected.
Results: Wild type AS adopts an
extended conformation which can pass through the pore whereas the A30P mutant
AS (found in familial PD) is mostly folded or aggregated. Upon binding dopamine
the mutant protein unfolds and can now pass through the pore. There are
independent binding sites for dopamine in both the N- and C-terminus of the
protein which was confirmed by 1H-15N-HSQC NMR. Wild type
AS also binds nicotine but the conformation is different from that of the
dopamine-AS complex. With the A30P mutant, nicotine again prevents aggregation
but the conformation of the complex is different from that of the wild type
complex. These results demonstrate a new methodology for studying drugs binding
to AS which may prove useful for developing therapeutic solutions for PD. It is
also of interest that epidemiological studies have shown that PD is less
prevalent in smokers and our results provide a direct link between nicotine
binding and the conformation of AS.
P03.06
14-3-3
chaperone protein modulates alpha-synuclein aggregation and toxicity
Nicoletta
Plotegher1, Marco Brucale2, Isabella Tessari1,
Dhruv Kumar3, Francesca Munari1, Laura Tosatto1,
Elisa Greggio1, Marco Bisaglia1, Stefano Capaldi4,
Hugo Luis Monaco4, Bruno Samorì3, Luigi Bubacco1
1Department of Biology, University of
Padova, Italy
2Institute of Nanostructured Materials
(ISMN)
3Department of Pharmacy and
Biotechnology, University of Bologna, Italy
4Department of Biotechnology, University
of Verona, Italy
Objective:
Idiopathic
and familial Parkinson’s disease (PD) is associated with the neuronal
accumulation of fibrillar forms of alpha-synuclein (aS) into proteinaceous
aggregates called Lewy Bodies. A connection between PD and the 14-3-3 chaperone
proteins was recently proposed: some 14-3-3 isoforms have been found in Lewy
bodies and 14-3-3h isoform interacts with aS. The goal of our work was the
characterization of the effect of 14-3-3η on aS aggregation in vitro and
in cells.
Methods:
Nuclear
magnetic resonance (NMR), fluorescence spectroscopy techniques, atomic force
microscopy (AFM) and transmission electron microscopy (TEM) were used to
characterize the interaction between aS and 14-3-3h in vitro. Cellular assays
were used to study the effects of 14-3-3h overexpression on aS aggregation and
toxicity in cell systems.
Results:
aS
aggregation kinetics performed in vitro showed that aS and 14-3-3η
interact during the aggregation process. 14-3-3η does not bind monomeric
aS and is not able to disaggregate amyloid fibrils. Instead, it associates with
aS aggregation intermediates to yield aggregation products that are
morphologically different from canonical fibrils. Quantitative AFM and TEM
analyses of aS aggregation products in the presence of 14-3-3h revealed that:
(i) 14-3-3h leads to curved aggregates with smaller diameter than aS fibrils;
(ii) 14-3-3η is included within these curved objects; (iii) 14-3-3η
partially interferes with the elongation of preformed fibrillar seeds due to aS
monomers addition in solution. The chaperone was found trapped within these
growing fibrils, overwhelmed by the aggregating aS. In cell system,
overexpression of 14-3-3h is protective against aS-induced toxicity, unless
massive aggregation is triggered by exogenous aS fibrillar seeds, which likely
sequester and inactivate 14-3-3h. Based on these findings, we propose that
14-3-3h counteracts aS fibrillization process by inhibiting the early phases of
aggregation, thus providing a new avenue for PD therapeutics.
P03.07
Mutations in LRRK2 potentiate
age-related impairment of autophagic flux
Shamol Saha1,
Vivek Gowda1, Liqun Liu-Yesucevitz1, Benjamin Wolozin1
Boston University
School of Medicine, Boston, MA, USA
Objective: Aging and autophagy
play an important roles in the pathophysiology of Parkinson’s disease (PD).
However, little is known about how genes linked to PD affect autophagy in the
context of aging. The objective of this study is to characterize autophagic
flux over the life-span, and to determine how LRRK2 and α-synuclein modify
autophagy during aging.
Methods: We created an optical
reporter for autophagic flux in C. elegans dopamine neurons using the dopamine
transporter promoter to drive expression of lgg-1::mCherry (lgg-1 is the C.
elegans homolog of LC3). Driving expression the dopamine transporter promoter
allowed us to selectively visualize autophagy in dopamine neurons. This
reporter line was then crossed with nematodes lines expressing WT, G2019S,
R1441C and km-17 (deletion) LRRK2 lines, and autophagy followed over the lifespan.
Autophagic flux was also investigated in triple crosses, expressing
lgg-1::mCherry, LRRK2 and WT α-synuclein.
Results: The nematodes
exhibited a progressive age-related decrease of autophagic flux upon finishing
their reproductive period. WT LRRK2 increased autophagic flux in young
nematodes, while mutant LRRK2 (G2019S and R1441C) inhibited autophagy.
Introducing α-synuclein increased autophagy in young adult nematodes, even
when G2019S LRRK2 was co-expressed.
During aging, both
mutant LRRK2 and α-synuclein inhibited autophagy and increased
dopaminergic degeneration. Co-expressing the two proteins produce a synergistic
inhibition of autophagy, a corresponding accumulation of insoluble, oligomeric
α-synuclein and synergistic increases degeneration of DA neurons. In
addition, although WT LRRK2 improves autophagy throughout the lifespan when
expressed in absence of α-synuclein, co-expressing α-synuclein with
WT LRRK2 lead to an age dependent inhibition of autophagy, and a synergistic
increase in degeneration of DA neurons. These data suggest that LRRK2 and
α-synuclein modulate autophagy through interacting pathways that lead to
age-related synergistic effects, and provide the first evidence that WT LRRK2
can directly contribute to degeneration associated with α- synuclein.
P03.08
Effect of
membranes on alpha synuclein aggregation and neurotoxicity in Parkinson’s
disease
Daniel
Ysselstein1, Amy M. Griggs1, Mehul Joshi1,
Carol B. Post, Jean-Christophe Rochet1
1Purdue
University, West Lafayette, IN, USA
Objective:
Oligomerization of the presynaptic protein alpha-synuclein (aSyn)
is a critical factor in the onset of both genetic and sporadic Parkinson’s
disease (PD). Although aSyn associates with phospholipid membranes to
modulating neurotransmission, aberrant interactions of aSyn with membranes may
promote its conversion to neurotoxic aggregates. Therefore, elucidation of this
interaction is critical to determinate pathogenicity of aSyn in PD. The goal of
this project is to analyze aSyn-membrane interactions to increase our
understanding of aSyn induced toxicity. We hypothesize that reduced membrane
interaction between the central hydrophobic region of aSyn and cellular
membranes promotes aggregation of the protein.
Method: We
generated a series of aSyn variants with familial genetic mutations or
substitutions that are predicted to affect aSyn-membrane interactions. The
association of these variants with synthetic phospholipid vesicles or isolated
intracellular organelles has been examined by circular dichroism (CD) and
solution NMR HSQC to determine secondary structure, affinity, and
residue-specific interactions upon binding of the protein to membranes.
Aggregation was examined by gradient ultracentrifugation and western blotting.
Lastly, neurotoxicity was characterized by adenoviral-mediated expression in a
primary midbrain culture model of PD.
Results: We
identified several aSyn variants which display both increased and decreased
membrane interaction. We observed little correlation between membrane affinity,
aggregation propensity and neurotoxicity. From this we hypothesize that the
conformation of membrane-bound aSyn (rather than the protein’s membrane
affinity per se) is critical for formation of toxic aggregates at the membrane
surface. We have established a powerful NMR method to analyze residue-specific
interactions of different aSyn variants with membranes to confirm this
hypothesis. The data from these studies will reveal whether reduced binding in
the central hydrophobic region correlates with aggregation and the observed
neurotoxicity. These results will set the stage for novel therapeutic
strategies to reduce aSyn aggregation through stabilization of the membrane
bound state.
BASIC SCIENCE: Mitochondria, oxidative, stress, inflammation
and pathogenesis
P04.01
Neuroprotective
effects of ATP13A2 and DJ-1 in Parkinson’s disease models
Josephat Asiago1, Vartika
Mishra1, Amy Griggs1, Susan L. Roy2, and
Jean-Christophe Rochet1
1Purdue
University, West Lafayette, IN, USA
2National
Institute of Health Library, Bethesda, MD, USA
Objective:
Parkinson’s disease (PD) involves a loss of dopaminergic neurons
from the substantia nigra and a buildup of Lewy bodies enriched with
fibrillar forms of the presynaptic protein α-synuclein (aSyn). Two proteins
implicated in familial PD are ATP13A2, a lysosomal ATPase, and DJ-1, a protein
with antioxidant and chaperone activities. Although there is evidence of
functional overlap between these two proteins, the mechanistic details are
poorly understood. The objective of this study is to elucidate cellular
protective mechanisms of ATP13A2 and DJ-1 in neurons exposed to PD-related
stresses, including aSyn-encoding virus and methamphetamine (METH), a drug that
disrupts autophagy in dopaminergic neuronal cells. We hypothesize that a loss
of function of either protein triggers defects in autophagy coupled with an
accumulation of dysfunctional mitochondria.
Methods: Rat
midbrain cultures were transduced with aSyn adenovirus and ATP13A2- or
DJ-1-shRNA lentivirus. Cells were stained with primary antibodies that
recognize tyrosine hydroxylase (TH), a dopaminergic neuronal marker, and
microtubule-associated protein 2 (MAP2), a general neuronal marker. Ratio of
viable dopaminergic neurons to total neurons was calculated, and neurite
lengths were measured by confocal microscopy. SH-SY5Y cells stably expressing a
tandem LC3 construct (GFP-RFP-LC3) were transduced with virus encoding LacZ or
ATP13A2 and scored for green and red puncta, a measure of autophagic flux.
Results: Knocking
down ATP13A2 resulted in a buildup of aSyn, whereas ATP13A2 over-expression
reduced the accumulation of autophagosomes. In addition, human wild-type DJ-1
protected against METH toxicity and induced the phosphorylation of Akt, a
protein kinase involved in modulating autophagy. Current efforts are focused on
assessing whether over-expression of WT DJ-1 rescues lysosomal and
mitochondrial deficits in ATP13A2 knockdown cells and verse versa. The results
of these studies will provide insight into cellular mechanisms underlying the
neuroprotective functions of ATP13A2 and DJ-1 and suggest new strategies to
slow PD pathogenesis.
P04.02
DJ-1
loss-of-function affects adult neurogenesis in rodent brain
Jesus Pascual-Brazo1,
Veerle Reumers1, Luisa Alexandra Mendes-Osorio1, Zeger
Debyser2, Chris Van den Haute1, Veerle Baekelandt1
1Neurobiology and Gene Therapy,
Department of Neurosciences, KU Leuven, Flanders, Belgium
3Molecular Virology and Gene Therapy,
Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Flanders,
Belgium
Objective:
Loss-of-function mutations in DJ-1 lead
to autosomal recessive early-onset Parkinson's disease (PD). On the other hand,
impaired adult neurogenesis has been involved in the pathogenesis of PD. Here
we aimed to study the role of DJ-1 in the neurogenic process in adult mouse
brain.
Methods: We developed bicistronic lentiviral vectors (LVs) encoding a short
hairpin RNA (shRNA) sequence against DJ-1 or a control shRNA, with eGFP as
reporter. We performed stereotactic injections of LVs in the subventricular
zone (SVZ) of 2 months old C57BL6 mice. In addition, primary cultures of adult
neural progenitors from the mouse SVZ were established. Proliferation was
measured using BrdU and Ki67. Mitochondrial membrane potential and superoxide
production was measured using TMRM and Mitosox red.
Results: To study the effect of DJ-1 knock-down on adult neural stem cells in
vivo, we injected shDJ-1 or control LVs in the SVZ of adult mice. eGFP allowed
to follow the fate, morphology and number of newly generated neurons. At 2
weeks post-injection we observed a reduced proliferative activity of adult
neural progenitors in the SVZ. Furthermore, the number of newborn neurons in
the olfactory bulb (OB) was significantly diminished at 1 and 4 months
post-injection, without apparent effects on neuronal morphology. In order to
further elucidate the mechanism-of-action, we transduced primary cultures of
adult neuronal progenitors from mouse SVZ with shDJ-1 or control LVs.
Knock-down of DJ-1 resulted in impaired proliferation, size and renewal
capacity of the neurospheres. In addition we observed a reduced mitochondrial
membrane potential and enhanced mitochondrial superoxide production in the knock-down
condition compared to control.
In conclusion, our data suggest that DJ-1 is involved the generation of
new neurons in the adult OB. This impairment of adult neurogenesis may shed a
new light on the role of DJ-1 loss-of-function in PD.
P04.03
Antioxidant activity
of superoxide dismutases protect dopaminergic neurons against degeneration
Filograna R, Ferrari V, Bubacco L, Beltramini
M, Bisaglia M.
Department
of Biology, University of Padova, Padova, Italy
Objective: To date, the cause of
the preferential death of nigrostriatal dopaminergic neurons in Parkinson’s
disease (PD) remains poorly understood. Although PD is considered a
multifactorial disorder, experimental evidences suggest that oxidative stress
play a central role in the pathogenesis of the disease. In the present study,
we investigated the potential protective role of superoxide dismutases (SODs)
against oxidative stress conditions in human in human dopaminergic
neuroblastoma cells.
Methods: Stable SH-SY5Y cell lines overexpressing either cytosolic (SOD1) or
mitochondrial (SOD2) superoxide dismutases were produced and used to evaluate
the cellular response to the herbicide paraquat and to disulfiram, an aldehyde
dehydrogenase inhibitor which is responsible for DOPAL accumulation in cytosol.
After treatment, cell viability was assessed by colorimetric assays and apoptotic response was
measured using fluorescence activated cell sorting.
Results:
Our data showed that paraquat decreased the viability of wild type cells
in a dose-dependent manner. While SOD1 overexpressing cells behaved as control, the
overexpression of SOD2 protected cells against the oxidative insult induced by
paraquat. Our results suggest that paraquat toxicity is due to
production of superoxide radicals at mitochondrial level. A completely
different behavior was observed after exposure to disulfiram: cell viability
was significantly recovered only in SOD1 overexpressing cells, in
agreement with the mechanism of action of disulfiram, which interferes with the
metabolism of dopamine, at cytososolic level. In conclusion, our results emphasize
the antioxidant protective effect due to SODs, ultimately also with respect to
PD-related damages.
P04.04
The role of
intramolecular interactions in parkin activation in vivo
Jonathan Krett1,
Jean-François Trempe1, and Edward A. Fon1
1Centre for Neuronal
Survival, Montreal Neurological Institute, McGill University, Montreal, Québec,
Canada
Objective: Recent work from our group
characterizing the full-length structure of parkin, an E3 ubiquitin ligase
implicated in early-onset heritable forms of Parkinson’s
Disease, has offered
clues as to the intramolecular interactions underlying its basal autoinhibition
and activation in response to mitochondrial damage. We sought to examine
parkin’s ability to translocate to the mitochondrial surface and ubiquitinate
substrates in vivo to better understand parkin activation in the context
of a model pathway for neuroprotective mitochondrial quality control.
Methods: Targeted point
mutagenesis was utilized to produce an array of eGFP-fused parkin mutant DNA
vectors. HeLa cells were transfected with eGFP parkin constructs and subjected
to treatment with the protonophore CCCP at various time points in order to
induce mitochondrial depolarization. Subcellular localization of parkin was
examined by confocal microscopy and
immunofluorescence.
Cells were assayed for mitophagy after 24 hours as a downstream readout of
parkin enzymatic function.
Results: Analysis revealed
abnormalities in parkin recruitment to the mitochondria when interactions
within the protein were disrupted by the introduced mutations. Of interest, the
S65A mutant in the ubiquitin-like domain (Ubl) shows markedly slower kinetics
of mitochondrial recruitment, suggesting that the polarity and/or ability to
phosphorylate this residue is necessary to maintain efficiency in parkin
translocation. In addition, the
PD mutation R275W
within the RING1 domain shows a similar phenotype. A common theme arising from
our experiments is that the enzymatic activity of parkin as a ubiquitin ligase
is intimately tied to its ability to translocate to the mitochondria and carry
out its adaptive function, as evidenced by the complete recruitment defect of
the active site mutation C431S.
P04.05
Functional
compensation of the motor deficits after dopaminergic nigrostriatal system
degeneration DIGE analysis of mitochondrial membranes proteins in relation to
early Parkinson’s disease
Katarzyna Kuter1,2, Manuela
Kratochwil2, Urszula Głowacka1, Klemencja
Beghauzen-Maciejewska1, Michiru Sugawa3, Krystyna
Ossowska1, Norbert A. Dencher2
1Department of
Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences,
Smętna 12, 31-343 Kraków, Poland
2Physical Biochemistry,
Department of Chemistry, Technische Universität Darmstadt, Petersenstr 22,
64287 Darmstadt, Germany
3Clinical Neurobiology,
Charité-Universitätsmedizin, 14050 Berlin, Germany
Objectives:
First
movement disorder signs of Parkinson’s disease (PD) are observed after the
irreversible loss of almost 70% of neurons in substantia nigra (SN). This
proves existence of potent compensatory mechanisms, preventing appearance of
the symptoms at the earlier, preclinical stages of disease. Some data indicate
that survived neurons increase their activity in order to compensate for the
degeneration, so their energy demand is probably higher, therefore the
functional adaptation of mitochondria is especially interesting in this aspect.
Methods:
We have
prepared rat model of selective nigrostriatal dopaminergic system degeneration
by injection of 6-OHDA into medial forebrain bundle.
Results:
Three
days after the operation behavioral analysis revealed decreased locomotor
activity in lesioned rats comparing to sham operated controls. Interestingly, 4
weeks post lesion all motor deficits disappeared even though histological
verification showed progressing decrease in number of dopaminergic cells in SN
by 16% and 41% after 4 days and 4 weeks post lesion, respectively. The dopamine
levels decreased first in the striatum by 50% already after 3 days and remained
low, while in SN its level dropped by 37% only after 4 weeks. Using solubilised
crude mitochondrial membranes fraction from SN we performed differential gel electrophoresis (DIGE) in 2D-BN/SDS gels and identified 23 proteins with significant
changes in expression between groups. 7 proteins showed significant changes
between lesioned and lesion-compensated groups of animals. The above results
indicate involvement of mitochondria in the spontaneous process of functional compensation of dopaminergic system-driven
movement disorder.
Acknowledgements: The study was supported by the Statutory Funds of the Institute of Pharmacology, PAS, Kraków, Poland, DAAD scholarship to KK and funding from the Technishe Universität Darmstadt.
P04.06
Neuroprotective
mechanisms of the Parkinson’s disease-related protein DJ-1
Vartika
Mishra1, Susan L. Roy1, Fang Liu1 and
Jean-Christophe Rochet1
1Department
of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West
Lafayette, IN, USA
Objective:
Dysfunction of the neuroprotective protein DJ-1 has been associated with
familial and sporadic cases of PD. Recently we showed that human wild-type DJ-1
protects against different PD stresses via induction of different pro-survival
mechanisms. We hypothesize that this behavior may be due to the fact that
differences in the subcellular localization of DJ-1 result in the activation of
different neuroprotective responses. Methamphetamine (METH), a widely abused
drug, can trigger preferential toxicity to dopaminergic neurons by increasing
cytosolic dopamine levels leading to formation of dopamine quinone adducts,
ultimately generating ROS. Our goal is to characterize DJ-1-mediated protective
pathways activated against METH neurotoxicity. Methods: Rat primary
midbrain cultures transduced with adenoviruses encoding WT DJ-1 or the
localization mutants MLS- and NLS-DJ-1 (targeting mitochondria and the nucleus,
respectively) were incubated in the absence or presence of METH. The cultures
were immunostained for tyrosine hydroxylase (TH) and microtubule associated
protein 2 (MAP2), and dopaminergic neurite lengths were measured via confocal microscopy.
Levels of the autophagosome marker LC3-II and endogenous DJ-1 were determined
in METH-treated versus untreated neuronal cells via Western blotting. Flow
cytometry analysis was used to study effects of DJ-1 on Nrf-2-mediated
transcription.
Results: We found
that DJ-1 over-expression protected against neurite loss triggered by METH in
primary midbrain cultures, and DJ-1 was up-regulated in METH-treated SH-SY5Y
cells. METH induced an increase in autophagic flux in N27 cells, and this
effect was potentiated in cells over-expressing DJ-1. Preliminary data also
suggest that DJ-1 activates pro-survival pathways including Akt phosphorylation
and Nrf-2-mediated transcription in METH-treated cultures. Collectively these
data suggest that DJ-1 mitigates METH-induced neurite loss by activating a
range of neuroprotective responses. Current efforts are focused on exploring
whether DJ-1 must be expressed in glia and/or neurons to alleviate toxicity
elicited by METH and other PD-related insults.
P04.07
Membrane recruitment
and activity of LRRK2 is important for innate immune cell activation
Jason Schapansky1,
2, Jon Nardozzi1,2, Fredrik Felizia1, Matthias
Berndt1, and Matthew J. LaVoie1,2
1
Center
for Neurologic Disease, Brigham and Women’s Hospital, Boston MA, USA
2 Harvard Medical
School, Boston MA, USA
Mutations in
leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of
Parkinson’s disease, but recent evidence indicates LRRK2 also plays a
significant role in monocyte immune cell function. Previously, we demonstrated
that membrane-associated LRRK2 dimers are likely the more physiologically
relevant subcellular population of LRRK2, but the cellular conditions by which
endogenous dimers form, resulting in LRRK2 activation, remain unknown. Here, we
show that activation of macrophage or microglial cell lines results in LRRK2
phosphorylation, dimerization and membrane recruitment, which then coincides
with iNOS expression and nitrate production. This activation also results in
localization to a novel membrane compartment distinct from the location of
LRRK2 at rest. Disruption of LRRK2 kinase activity reduces iNOS expression and
abolishes phagocytic activity in a macrophage cell line. A parallel analysis of
primary human macrophages revealed numerous changes in LRRK2 biochemistry,
including a similar membrane recruitment following Toll-like receptor (TLR)
activation, as observed in cell lines. This work shows, for the first time,
that acute changes in dimerization and membrane localization of endogenous
LRRK2 can be linked to a cellular role in monocytic immune cells.
P04.08
Examining the
functional interaction of the m-AAA protease AFG3L2 with PINK1
Matthew A. Seegobin1,
M. Emdadul Haque2, Rasoul Farazifard1,
Ruth S. Slack1, David S. Park1
1University of Ottawa,
Ottawa, Ontario, Canada
2United Arab Emirates
University, Al Ain, United Arab Emirates
Objective: PTEN induced putative
kinase 1 (PINK1) is known to be endogenously processed first by mitochondrial
processing peptidase (MPP) and by presenilin-associated rhomboid-like protease
(PARL). However, following the stages of mitochondrial import and cleavage, the
basal function of PINK1 and its processed forms are currently not well understood.
This study attempts to better understand PINK1 function by characterizing its
interaction with a novel protein interactor mitochondrial m-AAA protease
AFG3L2.
Methods: In this study, we
assessed PINK1 and AFG3L2 protein levels in various tissues and the interaction
of PINK1 with AFG3L2. Using an AFG3L2 knockout mouse model, the effect of
AFG3L2 loss upon PINK1 processing and protein levels in murine neuronal and
fibroblast cell models were examined. Via immunocytochemistry, we observed
mitochondrial morphology in AFG3L2 deficient fibroblasts after PINK1
overexpression and assessed Parkin translocation in AFG3L2 deficient cortical
neuronal cultures.
Results: Interestingly, with
similar protein levels of PINK1 and AFG3L2 found in all tissues analyzed, knockout
of AFG3L2 shows decreased processed PINK1 isoforms and total PINK1 levels in
mouse embryonic fibroblasts and cortical neuronal cultures examined. Decreased
processed PINK1 was also confirmed in human cell line HeLa cells with siRNA
mediated AFG3L2 knockdown. In fibroblasts examined, the fragmented
mitochondrial phenotype observed with AFG3L2 deficiency could not be rescued by
full-length PINK1 over-expression. However increased translocation of
Parkin, known to be associated with clearance of damaged mitochondria, was
observed in stressed AFG3L2 deficient primary cortical neuronal cultures. Taken
together, these results suggest that AFG3L2 is involved in PINK1 processing and
may play a role in the regulation of PINK1 mediated mitochondrial clearance.
Work is currently underway to identify AFG3L2 mediated cleavage products of
PINK1. Results obtained from these and other experiments will also be
presented.
P04.09
Inhibition of NADPH
oxidase by Apocyanin alternatively prevents microglia induced neuroinflammation
in Lipopolysaccharide induced Parkinson’s disease model
Neha
Sharma1, Bimla Nehru1
1Panjab University,
Chandigarh, India
Objective: Recent studies have revealed an essential role
for neuroinflammation that is initiated by microglial and infiltrated
peripheral immune cells and their toxic products (cytokines, chemokines etc) in
pathogenesis of Parkinson’s disease. Lipopolysaccharide, a bacterial endotoxin
is the most extensively utilized glial activator for the induction of
inflammatory dnergic neurodegeneration.
Method: To establish the neuroprotective efficacy of
apocyanin a NADPH oxidase inhibitor in inflammation driven animal model of PD.
LPS at a dose of (5ug/5ul PBS) injected stereotaxically into the Substantia
Nigra of rat brain was utilised for the establishment of PD model. Apocyanin
was administered at a dose of 10mg/kg b.wt for a period of 21 days.
Results: LPS injection leads to microglial activation
and hence increased level of pro-inflammtory cytokines and activation of NADPH
oxidase complex leading to excessive superoxide anion production which combines
with NO to form OONO- and other ROS/RNS species which further results in
neurotransmitter dopamine loss and behavioural impairment. Apocyanin
significantly lowered the production of superoxide anions which was further
supported by decreased NADPH oxidase activity and suppressed expression of
various NADPH subunits gp91(phox), p47(phox). It significantly decreased
microglial activation and suppressed mRNA expression of various proinflammatory
cytokines (TNF-α, IL-1α,β, IFN-γ, IL-6), NO/iNOS in mid
brain region hence, prevented neurotransmitter dopamine loss and resulted
behavioural impairment. Histopathological studies also indicated the
neuroprotective efficacy of apocyanin in PD. Since apocyanin treatment
attenuated ROS production which alternatively leads to decreased cytokine
production and iNOS in response to LPS further strengthened the notion that
Phox-derived ROS are crucial for proinflammatory gene expression in glial
cells. Thus, its supplementation can prove to be beneficial for curing PD.
P04.10
Paraquat
and diquat induced-toxicity in PC12 cells is mediated through the generation of
intracellular reactive oxygen species and dysregulation of redox regulated
pathways
Manjeet
Singh1, Ven Murthy2 and Charles Ramassamy3
1Health
Canada, Ottawa, Ontario, Canada
2Laval University, Québec city, Québec, Canada
3INRS-
Institut Armand Frappier, Laval,
Québec, Canada
Objective: Recent
epidemiological and toxicological studies
have shown that environmental factors especially, pesticides such as paraquat
(PQ) and diquat (DQ) represent one of the primary classes of neurotoxic agents
associated with PD. The objective of our study was to investigate the toxic
effects of PQ/DQ mixture and elucidate the mechanisms involved in their
toxicity in rat dopaminergic PC12 cell line.
Methods: Cell survival in PC12 cells was measured by XTT, LDH and
Resazurin assays. Intracellular reactive
oxygen species (ROS) and superoxide levels
were measured by using the fluorescent dyes 2′, 7′-dichlorofluorescein-diacetate
(DCF-DA) and MitoSox
red respectively. Levels of different redox-regulated proteins were measured by
western blot analysis.
Results: Our results show that a treatment with PQ/DQ mixture (80.0 µM/60.0 µM)-induced approximately 50% cell death in PC12 cells. Besides, PQ/DQ
mixture also generated intracellular ROS and increased mitochondrial superoxide
levels. PQ/DQ treatment activated the Akt, glycogen synthase kinase 3beta
(GSK3beta), nuclear factor E2-related factor2 (Nrf2) pathway however their
activation could not prevent the down regulation of glutamylcysteine synthetase
(-GCS), thioredoxin1 (Trx1), and tyrosine
hydroxylase (TH) indicating that other redox-regulated transcription factors
may also be involved in their regulation. PQ/DQ-treatment also induced the
expression of heat shock protein70 (HSP70) and 90 (HSP90). Thus, our findings
demonstrate that PQ/DQ-induced toxicity in dopaminergic cells is mediated
through generation of oxidative stress and dysregulation of various cellular
redox pathways and their modulation with antioxidants could have a therapeutic
application in the treatment of PD.
P04.11
Mutant LRRK2
expression induces calcium dysregulation and dendritic mitophagy
Erin Steer1,
Salvatore Cherra III1, Aaron M. Gusdon1, Kirill Kiselyov2,
Charleen T. Chu1,3,4
1Department of
Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
2Department of
Biological Science, University of Pittsburgh, Pittsburgh, PA, USA
3Center for
Neuroscience, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
4McGowan Institute of Regenerative
Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Objective: Parkinson’s disease
(PD) is the second most prevalent neurodegenerative disease. The most common
known genetic cause of PD is mutation of the gene for leucine-rich repeat
kinase 2 (LRRK2). Expression of the PD-associated G2019S and R1441C LRRK2
mutants has been shown to cause neurite shortening, though the mechanism of
injury has not been delineated. Because disruptions in normal mitochondrial
function and dynamics have been linked to PD pathophysiology and LRRK2 has been
shown to partially localize to mitochondria, we investigated whether mutant
LRRK2 expression disrupts mitochondrial homeostasis.
Methods: Mouse cortical
neurons, or differentiated SH-SY5Y cells were transfected with eGFPc-1,
COX8-GFP or GFP-LC3, and wild type or mutant LRRK2-HA constructs. Cells were
incubated in Fura2-AM and imaged to analyze calcium handling. Mitochondrial
content and number of autophagosomes were quantified. In some experiments,
autophagy levels and mitochondrial content were measured following treatment
with a calcium chelator or voltage gated calcium channel inhibitors.
Mitochondrial trafficking was analyzed by measuring the mobile fraction and
anterograde/retrograde velocity of dendritic mitochondria.
Results: We found a selective
loss of dendritic mitochondrial content that could be prevented by inhibiting
autophagy. This dendritic mitophagy preceded dendrite shortening in neurons
expressing mutant LRRK2. There were no significant effects on mitochondrial
transport kinetics. Mitochondrial dysfunction, in the form of disrupted calcium
handling occurred upstream of mitophagy and dendrite retraction. In further
support of a possible primary role for mitochondrial dysfunction in
LRRK2-mediated pathogenesis, overexpression of the mitochondrial PD-linked
kinase PTEN-induced kinase 1 (PINK1) prevented LRRK2-induced pathology.
Modulation of intracellular calcium levels prevented mutant LRRK2 mediated
mitophagy and dendrite retraction. These data suggest that maintenance of
calcium homeostasis may be an effective therapeutic intervention for PD, and
studies to further delineate the neuroprotective or “mitoprotective” role of
PINK1 are underway.
BASIC SCIENCE: PATHOLOGY
P05.01
Striatal pathology in
Parkinson´s disease and dementia with Lewy bodies is associated with small
α-synuclein aggregates
Christina Behrens1,
Sabine Krause2, Thomas Dyrks2, Walter J. Schulz-Schaeffer1
1Department of Neuropathology, University
of Goettingen, Goettingen, Germany
2Global Drug Discovery, Bayer
Pharma AG, Berlin, Germany
Objective: A common feature of
neurodegenerative disorders such as Parkinson´s disease (PD) or dementia with
Lewy bodies (DLB) is the deposition of misfolded proteins present in the brain.
One of these proteins, the cytosolic protein α-synuclein, appears in the
form of aggregates in Lewy bodies, a hallmark of PD and DLB. It was recently
shown that large amounts of small α-synuclein aggregates outside of Lewy
bodies are located at presynaptic terminals in DLB cases, leading to the
hypothesis that these small aggregates cause neurodegeneration in DLB. In the
present study, we investigated in more detail the significance of small
aggregates of α-synuclein for the pathogenesis of neurodegenerative
diseases. To test the possibility that striatal α-synuclein pathology is
caused by these aggregates, we analyzed the accumulation of misfolded
α-synuclein in brain tissue from the caudate nucleus from PD and DLB patients
and compared them with other brain regions.
Methods: The appearance and
amount of α-synuclein aggregates were determined in different subcellular
fractions of brain homogenates using the previously established protein
aggregate filtration (PAF) assay. The different brain samples were further
analyzed with paraffin-embedded tissue (PET) blots.
Results: We were able to show
striatal pathology in PD as well as DLB cases due to the detection of small
α-synuclein aggregates in the caudate nucleus. Based on these results we
propose that this particular α-synuclein pathology in the basal ganglia
may contribute to the clinical features observed in these diseases.
Furthermore, we detected in all other analyzed brain samples much higher
amounts of small α-synuclein aggregates than Lewy bodies, confirming that
these small aggregates play an important role in the pathological mechanism of
PD and DLB.
P05.02
High Cortical LB
burden and Aβ
pathology in Lewy Body Dementia and Parkinson’s disease Dementia
Claudio Ruffman1,
Federico C.F. Calboli1, Ilaria Bravi2, Djordje Gveric3,
Lisa K. Curry1, Sophie Molloy3, Paola Piccini3,
Federico Roncaroli2, David T. Dexter3, Steve M.
Gentleman3, and Lefkos T. Middleton1
1Neuroepidemiology and
Ageing Research, School of Public Health, Imperial College, London, UK
2John Fulcher’s
Neuro-Oncology Laboratory, Imperial College London, UK
3Division of Brain
Sciences, Department of Medicine, Imperial College London, UK
Objectives: We studied a large
sample of patients-donors to the Parkinson’s UK Brain Bank, with Lewy Body
dementia (LBD), Parkinson’s disease Dementia (PDD) and Parkinson’s disease
without clinical evidence of dementia (PDnD) to evaluate the neuropathologic
substrates of dementia in LBD and PDD. Clinical, neuropathological and genetic
data were utilised to assess the respective roles of Lewy body pathology,
Aβ burden and tau load, as well as of the MAPT and APOE genotypes on the
development of dementia in LBD and PDD.
Methods: 122 cases (56 PDD, 17 DLB
and 49 PDND) with a neuropathological diagnosis of Parkinson’s disease and
reliable clinical information on dementia status were included in the analysis.
We carried out topographical and semi-quantitative assessment of cortical and
striatal LB, Aβ plaques and tau-positive neuropil threads. APOE genotype
and MAPT haplotype status were determined.
Results: DLB cases had a
significantly higher LB burden in parietal and temporal cortex compared to PDD;
DLB cases were also characterized by a higher cortical and striatal Aβ
plaque burden compared to PDD. Higher cortical loads of both LB and Aβ
plaques were associated with a faster progression to dementia. Cortical LB body
burden was the only independent neuropathological determinant of dementia in
multivariate analysis. Total cortical Aβ plaque burden was an independent
predictor of a shorter latency to dementia from onset of motor symptoms. APOE
E4 carrier status was strongly correlated with a higher cortical LB burden. The
presence of high cortical LB burden is the key neuropathological substrate of
dementia in DLB and PDD. Similarly, cortical Aβ plaques are associated
with a faster progression to dementia from the onset of motor symptoms, with a
gradient of severity parallel to the one we see in LB, differentiating LBD from
PDD and these forms from PD without dementia.
BASIC SCIENCE: ANIMAL AND CELLULAR
MODELS OF PARKINSONISMS
P06.01
Effects of deep brain stimulation on
impulsive choice and action in a rat model of early Parkinson’s disease
Lily R. Aleksandrova 1, 2,
Bryce M. Laver 2, Daniela S. S. Lobo 3, 4, 5, Clement
Hamani 2, 6, José N. Nobrega 1, 2, 3, 7
1
Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON,
Canada
2
Behavioural Neurobiology Laboratory and Campbell Family Mental Health Research
Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
3
Department of Psychiatry, University of Toronto, Toronto, ON, Canada
4
Neurogenetics Research Section, Neuroscience Department, Centre for Addiction
and Mental Health, Toronto, ON, Canada
5
Problem Gambling Service, Addictions Program, Centre for Addiction and Mental
Health, Toronto, ON, Canada
6
Division of Neurosurgery, Toronto Western Hospital, Toronto, ON, Canada
7
Department of Psychology, University of Toronto, Toronto, ON, Canada
Objective: Deep brain stimulation (DBS) is effective
for the motor symptoms of Parkinson’s disease (PD), but has been associated
with increased impulsivity. A critical question is whether the impulse control
problems result from the treatment per se, or from interactions with the
underlying PD neuropathology and/or concommitent dopamine replacement therapy.
Here we utilized intact and PD-like rats trained to perform a rat gambling task
(rGT), which models two distinct facets of impulsive behaviour, impulsive
choice (rGT choice distribution among four holes with different reinforcement
schedules), and impulsive action (rGT premature responding).
Methods: After
initial rGT training, rats (n=45) underwent bilateral stereotaxic surgeries:
6-OHDA/vehicle microinfusions into the
dorsolateral caudate putamen (dlCPu), as well as electrode implantation
into the subthalamic (STN) or entopeduncular
(EPN) nuclei. Animals were then retested for 14 days, with EPN- or STN-
DBS (100μA, 90μs, 130Hz) administered daily for 2 hours prior to rGT
testing to separate animal cohorts.
Results: Chronic EPN- or STN-
DBS had no effect on rGT choice behaviour, suggesting that stimulation does not
seem to disrupt the ability to identify and
avoid high-risk options, on its own or in a PD-like background.
Moreover, EPN-DBS did not affect, whereas
STN-DBS tended to decrease, rGT premature
responding in both intact and dopamine-lesioned animals (p>0.05).
Significance: While we previously demonstrated that STN-DBS at lower intensities (12.5 μA) significantly
increased rGT premature responding in intact animals, stimulation at 100μA
failed to produce the same impulse control deficit, and in fact, tended to
improve rats’ ability to withhold premature responses. Our work suggests that DBS is not intrinsically associated
with increases in impulsivity in normal or PD-like rats, and the effects of
high-frequency stimulation on impulse control might be amplitude-dependent.
Future studies systematically evaluating chronic stimulation with various
current intensities would help establish the link between DBS and impulsivity.
Funding Source: L.A. is the recipient
of a Studentship from the Ontario Problem Gambling Research Centre.
P06.02
Identification of cis-
and trans-regulatory elements and signaling pathways in parkin gene expression
— A genomic fugu parkin model
Hei Sio Ao1,2,
Sandra Noble3, Marc Ekker3, Jingwei Sheng4,
Rajiv Ratan4, Lim Kah Leong5,
Tohru Kitada1,2, Julianna Tomlinson1, Michael
Schlossmacher1,2
1Program in
Neuroscience, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
2Neuroscience Graduate
Program, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
3Department of Biology,
University of Ottawa, Ottawa, Ontario, Canada
4Burke/Cornell
Medical Research Institute, White Plains, New York, USA
5National Neuroscience
Institute, Singapore
Objective: Wild-type human Parkin protein confers
several protective effects to prevent cell damage and neuronal death.
Therefore, increasing the expression of Parkin might be helpful in preventing
or treating Parkinson disease (PD). To date, the most promising signaling
mechanism is mediated through ATF4 function [Bouman et al., 2011]. The overall
goal of this study is to identify regulatory elements and signaling pathways
involved in the up-regulation of Parkin gene expression at the PARK2 locus.
Methods: Identifying cis- and trans-regulatory elements of the human
Parkin gene has been problematic because of its large size (~1.4 Mb; the second
largest human gene). We took advantage of the previously identified orthologue
of PARK2 in fugu fish (fugu parkin), which is highly similar to human Parkin in
genomic organization, tissue expression and protein function, and considerably
smaller (~4.5 Kb) [Yu et al., 2005].
Results: We successfully cloned
genomic fugu parkin tagged with a reporter (firefly luciferase or eGFP). A
strong repressor element was detected in the -820 bp to -311 bp region of the
5’-flanking region of fugu parkin. We also determined that intron 1 was
essential for reporter gene activation. Accordingly, a 310 bp-long 5’ flanking
region encompassing the putative promoter (with the repressor removed) and
containing intron 1 effectively facilitated the transcription of fugu parkin.
Moreover, we generated several hybrid constructs in which human PARK2
5’-flanking sequences of various lengths were cloned upstream of the start
codon of fugu parkin’s genomic DNA. These permitted the identification of
previously unrecognized signature response elements and a specific
transcription factor-linked signaling pathway, which is independent upon ATF4,
that led to the expression of our reporter constructs. The relevance of this pathway
in PARK2 activation under select stress conditions was confirmed for endogenous
Parkin in neural (SH-SY5Y) and non-neural (CHO) cell cultures.
P06.03
Molecular mechanisms
of neurodegeneration in the En1+/-
mouse model of Parkinson’s disease
Genevieve Beauvais1,
Ulrika Nordström2, Carla M. Lema Tomé2, Allyson
Cole-Strauss3, Jack W. Lipton3, Martin Lundblad2, Jennifer A. Steiner1, Patrik Brundin1,2
1Laboratory for
Translational Parkinson's Disease Research, Center for Neurodegenerative
Science, Van Andel Research Institute, Grand Rapids, MI, USA
2Neuronal Survival
Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden
3Department of
Translational Science and Molecular Medicine, Michigan State University, Grand
Rapids, MI, USA
Background and
Objective:
Most rodent models of Parkinson’s disease (PD) fail to replicate the slow
degeneration of midbrain dopamine (DA) neurons. Mice with a heterozygous
deletion of the gene encoding engrailed (En)
1 were recently found to exhibit a phenotype with some features resembling PD.
These En1+/- mice display
slow degeneration of substantia nigra DA neurons starting a few weeks after
birth (with ventral tegmental area DA neurons only mildly affected), striatal
DA depletion, and motor dysfunction. In the present study, we investigated the
molecular mechanisms of neurodegeneration in the En1+/- mice.
Methods: Dopaminergic
nigrostriatal degeneration was assessed by tyrosine hydroxylase
immunohistochemistry and stereological method. HPLC analysis was used to
measure DA levels in the striatum. We also used amperometric techniques to
monitor DA release and reuptake in axonal terminals in the striatum.
Results: We found that nigral
DA neurons in En1+/- mice
exhibit synaptic terminal dysfunction and degenerate retrogradely. Thus, we
identified that some of the axons of the degenerating nigrostriatal DA neurons
in En1+/- are swollen in
the striatum as early as post-natal day 15, preceding the death of the neurons.
We also observed a mild, but significant, reduction in striatal DA levels and a
loss of nigral DA cell bodies at 8 weeks of age. Interestingly, we monitored a
dramatic (>90%) decrease in potassium-evoked DA release and DA reuptake in
synaptic terminals in the most dorsal striatum of En1+/- mice at 16 weeks of age, whereas in the ventral
striatum the same parameters were unchanged compared to control mice.
Conclusion: Taken together, our
observations suggest that in En1+/-
mice a specific subset of nigral neurons innervating the most dorsal parts of
the striatum exhibits dysfunctional terminals and axonal swelling starting
during the first two months of age and die after a few additional weeks.
P06.04
The
group II p21-activated kinases as therapautic targets in LRRK2-related
Parkinson’s disease
Laura Civiero1,
Elisa Belluzzi1, Alexandra Beilina2, Isabella Russo1,
Veerle Baekelandt3, Luigi Bubacco1, Mark R Cookson2,
Jean-Marc Taymans3, Elisa Greggio1
1Department of Biology,
University of Padova, Italy
2Laboratory of
Neurogenetics, National Institute on Aging, NIH, Bethesda, MD, USA
3Laboratory for
Neurobiology and Gene Therapy, Katholieke Universiteit Leuven, Leuven, Belgium
Several
missense mutations in LRRK2 (coding
for the protein Leucine Rich Repeat Kinase 2) are associated with
a familial form of Parkinson’s disease similar to the sporadic syndrome. Despite intense
efforts, information on the physiological and pathological function(s) of LRRK2
is incomplete. Because LRRK2 mutations lead to neuronal cell
death in a kinase-dependent manner, LRRK2 kinase activity is an attractive
pharmacological target for PD. However, current knowledge of the physiological
role of LRRK2 kinase suggests that it controls several functions, not all
linked to disease. Of note, LRRK2-kinase inhibitors induce a decrease of LRRK2
basal phosphorylation at a cluster of serines (Ser910, 935, 955 and 973), which
regulates 14-3-3 binding and LRRK2 cytoplasmic localization. Interestingly,
phosphorylation at these sites is disrupted in the context of several
Parkinson's disease associated mutations (R1441G/C, Y1699C, and I2020T) as well
as the binding with 14-3-3. To gain insights into LRRK2 function, we performed
a protoarray screen for LRRK2 specific binding partners and identified
p21-activated kinase 6 (PAK6) as a robust interactor. In the nervous system,
PAKs are abundantly expressed and have been implicated in diverse cellular
functions including neurite and synapse formation. Subsequent validation of
LRRK2:PAK6 interaction with biochemical and imaging techniques demonstrated
that: (i) LRRK2 efficiently interacts with group II PAKs at the actin
cytoskeleton; (ii) PAKs induce LRRK2 de-phosphorylation at Ser910 and Ser935 in
a kinase dependent manner; (iii) PAKs-dependent LRRK2 de-phosphorylation
induces LRRK2 cellular relocalization. We are currently evaluating how PAK6
activity impacts mutant-LRRK2 mediated neurotoxicity. Given the role of
Ser910-935 phosphorylation in LRRK2 pathological function and the observed
effect of the Group II PAKs, inhibition of this class of kinases has the
potential to specifically target pathological LRRK2 function, thus providing a
new avenue for PD therapeutics.
P06.05
A reverse engineered
Parkinson’s disease gene regulatory network identifies RGS2 as adirect
modulator of LRRK2 activity
Julien Dusonchet1,2,3,
Hu Li 2,3, Maria D. Guillily1, Liliane Glauser7,
Claudio Troletti1, Adamantios Mamais4, Nora Pyenson1,
Min Liu5, Allison Citro1, Andrew Ferree1,
Shamol Saha1, Zhenyu Yue6, Rina Bandopadhyay4,
Marcie Glicksman5, Patrick Aebischer7, Darren Moore7,
James J. Collins2,3, Benjamin Wolozin1
1Boston University
School of Medicine, Boston, MA, USA
2Howard Hughes Medical
Institute, Boston University, Boston, MA, USA
3Wyss Institute for
Biologically Inspired Engineering, Harvard University, Boston, MA, USA
4Rita Lila Weston
Institute of Neurological Studies, UCL, Institute of Neurology, London, United
Kingdom
5Harvard University,
Boston, MA, USA
6Mount Sinai School of
Medicine, New York, NY, USA
7Brain Mind Institute,
EPFL, Lausanne, Switzerland
Objective: To elucidate the gene
regulatory networks linked to LRRK2, and identify key proteins
regulating LRRK2 function.
Methods: Systems biology
algorithms were applied to reverse-engineer a genome-wide LRRK2-
centered regulatory network based on transcriptomes obtained from human
Parkinson's disease (PD) brain and blood cells. Our in silico network
identified approximately 600 genes whose expression levels are highly
coordinated with those of LRRK2. To determine the extent to which these
genes modify the function of LRRK2 in-vivo, we performed an RNAi
high-throughput screen on C. elegans expressing wild type human LRRK2 in
a pan-neuronal manner. 280 (40%) of our systems biology-predicted interactors
were found to modify LRRK2-mediated dopamine (DA) neuron survival.
Results: We focused
particularly on RGS2 (regulator of G-protein signaling 2) because it
exhibited co-regulation with a number of PD-linked genes, including LRRK2,
Parkin, PINK1 and DJ-1. We observed that RGS2 and LRRK2
interact in vitro in mammalian cells and in vivo in human
striatum. RGS2 was found to stimulate the GTP hydrolysis activity of LRRK2
whilst inhibiting its kinase activity. RGS2 expression in primary cortical
neurons rescued the neurite shortening phenotype induced by the PD-associated
mutant G2019S LRRK2 Finally, we observed that protein levels of RGS2 were
significantly decreased in striata from subjects with
LRRK2-associated and
sporadic PD. Taken together, these results point to a role of RGS2 as a direct
regulator of LRRK2 GTPase activity and associated neuronal toxicity.
P06.06
Altered Alpha Synuclein degradation and
augmentation of Parkinson disease phenotype in a transgenic mouse model
Ianai Fishbein1,
Yien-Ming Kuo1, Robert Nussbaum1,
1UCSF, Institute of Human Genetics, San Francisco,
CA, USA
Objective: The involvement of the protein
α-Synuclein (Snca) in the pathogenesis of Parkinson's disease (PD) has
been well documented. Heterozygous carriers of Gaucher disease mutations, who
are otherwise healthy, have an increased risk for PD. Since mutations in the
gene encoding for the Glucocerebrosidase (GBA) enzyme are known to reduce
degradation of some proteins in the lysosome, it has been suggested that
reduced Snca degradation might facilitate its accumulation and aggregation. In
this study
we investigated the half-life of Snca in neurons. We also asked how it might be
affected by a Gaucher mutation, and what impact that would have in vivo in
a PD mouse model.
Methods: We
used cultured primary cortical neurons generated from mice expressing wildtype
mouse Snca, wildtype human Snca
or A53T Snca, in a background of
either wildtype Gba or heterozygosity
for the p.L444P Gba mutation. We also
tested these double transgenic mice for behavioral and biochemical PD related
phenotypes.
Results: We found
that Snca is very stable, with a t1/2 = ~60 hours for both the
wildtype and A53T human protein in culture, while the mouse protein had an even
greater t1/2 of ~140 hours. Heterozygosity for the Gaucher mutation
reduced Gba activity by ~40%, reduced Snca degradation and triggered
accumulation of the protein in culture. This mutation also prompted the
augmentation of motor and gastrointestinal deficits found in the A53T mouse
model of PD, albeit only when mice reached an advanced age. This study demonstrates that heterozygosity for mutations
in Gba interferes with Snca degradation and contributes to accumulation of the
protein. We have a created a mouse model for the interaction between GBA mutations and synucleinopathies,
thereby strengthening the Gba enzyme as a potential therapeutic target for PD.
P06.07
Investigating the impact of α Synuclein
overexpression in human neurons with a novel viral system
Fella Hammachi, Nicola
J. Drummond, Ratsuda Yapom, Tilo Kunath
MRC
Centre for Regenerative Medicine, University of Edinburgh, UK
Objective: αSynuclein (αSyn) plays a critical role in the pathogenesis of Parkinson’s disease
(PD). It is implicated in both familial and sporadic forms of the disease.
Duplication and triplication of the αSyn
gene, SNCA, causes autosomal
dominant, early-onset PD, with triplication patients exhibiting a more
aggressive course of the disease. This indicates that levels of αSyn impact directly on disease pathogenesis. αSyn is a natively unfolded protein that adopts
an α-helical structure when bound to lipid
membranes. However, under pathological conditions it aggregates into reportedly toxic
small oligomers and insoluble fibrillar structures that are stabilized by
β-sheet-like interactions. In this study, we
have generated a novel αSyn viral delivery system to investigate the impact of αSyn overexpression in PD-relevant human neurons.
Methods: We exploited a
modified baculovirus system (BacMam 2.0) that can efficiently overexpress proteins in human post-mitotic cells. We used the BacMam
virus to deliver a polycistronic transgene encoding mitochondrially-targeted
emerald-GFP (emGFP) and human αSyn in the same cell.
Using different viral doses we infected the neuroblastoma cell line, SH-SY5Y,
and assessed emGFP expression by FACS and αSyn
expression by immunostaining. We will investigate aggregates formation, and αSyn
post-translational modifications. Impact on mitochondrial
function will be assessed including measurements of mitochondrial respiration,
ATP production, membrane potential, dynamic movement as well as fusion and
fission. The aforementioned investigations will also be carried out using
forebrain glutamatergic and midbrain dopaminergic neurons derived from induced
pluripotent stem cells (iPSCs) from a PD patient carrying a triplication of SNCA, and an allelic series of
transgenic human embryonic stem cell (hESC) lines overexpressing varying levels
of αSyn.
Results: The BacMam system
allows efficient (97%) transduction of differentiated SH-SY5Y human
dopaminergic neuroblastoma cells, and a dose-dependent level of overexpression
was achieved using different titers of the virus with no apparent cytotoxic
effect.
P06.08
Synergistic effects of
mGluR5 antagonism and 5-HT1A/1B agonism in a rat model of L-DOPA-induced
dyskinesia
Hanna Iderberg1, Daniella Rylander1, M Angela
Cenci1
1Basal Ganglia
Pathophysiology Unit, Lund University, Lund, Sweden
Objective: L-DOPA-induced
dyskinesia (LID) in Parkinson’s disease is driven by both pre- and postsynaptic
alterations in dopamine (DA) transmission, and it is modulated by several
non-dopaminergic transmitters. Emerging pharmacological strategies for the
treatment of LID include negative modulation mGluR5 and positive modulation of
serotonin autoreceptors 5-HT1A/1B. These strategies are assumed to act through
different mechanisms, and to be associated with different profiles of untoward
effects. We set out to determine whether the two strategies in combination may
provide synergistic therapeutic benefits.
Methods: The study was
performed in 6-OHDA-lesioned rats chronically treated with either L-DOPA or the
D1 receptor agonist, SKF38393 in order to induce abnormal involuntary movements
(AIM). Rats with stable AIM scores received challenge doses of either the
mGluR5 antagonist, MTEP (2.5 and 5 mg/kg), or the 5-HT1A/1B agonists
8-OH-DPAT/CP94253 (0.035/0.75 and 0.05/1.0 mg/kg). The two categories of drugs
were given either alone or in combination.
Results: In agreement with
previous studies, 5 mg/kg MTEP and 0.05/1.0 mg/kg 8-OH-DPAT/CP94253
significantly reduced L-DOPA-induced AIM scores (reduction of peak AIM scores
by 37% and 34 % respectively). The two treatments in combination achieved a
greater effect than each treatment alone (- 66%). Moreover, a significant
attenuation of L-DOPA-induced AIM scores was achieved when combining doses of
MTEP (2.5 mg/kg) and 8-OH-DPAT/CP94253 (0.035/0.75 mg/kg) that did not have a
significant effect if given alone. Neither combination treatment had a negative
impact on the improvement produced by L-DOPA in tests of forelimb akinesia
(cylinder test) or global motor dexterity (rotarod test). SKF38393-induced AIM
scores were reduced by 5 mg/kg MTEP (-56%) but not by 0.05/1.0 mg/kg
8-OH-DPAT/CP94253.
These
results indicate that combining negative modulators of mGluR5 with positive
modulators of 5-HT1A/1B receptors may achieve synergistic antidyskinetic
effects without interfering with the antiakinetic effects of L-DOPA.
P06.09
Positive allosteric
modulators of mGluR4 can synergize with L-DOPA-in alleviating motor
abnormalities in a rodent model of Parkinson’s disease
Hanna Iderberg,1
Sylvain Celanire,2 Sonia M Poli,2 Vincent Darmency,2
Mikhail Kalinichev2 and M Angela Cenci1
1Basal Ganglia
Pathophysiology Unit, Department of Experimental Medical Science, Lund
University, Lund, Sweden
2Addex Therapeutics,
Chemin des Aulx 12, Plan-les-Ouates, Geneva, Switzerland
Objective: Metabotropic glutamate receptor type 4
(mGluR4) is a potential therapeutic target for treating motor symptoms in
Parkinson’s disease. This receptor is expressed selectively in the output
structures of the indirect pathway where it has a presynaptic location and
negatively regulates both GABA and glutamate release. Considerable effort has
gone into the discovery of positive allosteric modulators of mGluR4, that can
enhance the effects of the receptor once its endogenous ligand (glutamate) is
bound to the receptor active site. It is only recently that selective ligands
for mGluR4, have become available and very few of these compounds are
systemically active. One of these compounds, ADX88178 has been shown to reverse
haloperidol-induced catalepsy in intact rats, and to potentiate the effect of
L-DOPA on measures of forelimb use in rats with 6-OHDA lesions, without
exacerbating L-DOPA-induced dyskinesia (Le Poul E., et al., J Pharmacol
Exp Ther 2012, 343(1):167-77).
Methods: In the present study, we investigated
whether ADX88178 co-administered with low doses of L-DOPA (that do not induce
dyskinesia) can achieve comparable therapeutic effects to a high dose of
L-DOPA. ADX88178 was given alone or in combination with sub-threshold doses of
L-DOPA in rats with unilateral 6-OHDA lesions of the medial forebrain bundle
(MFB). Animals were assessed on two different behavioural tests: drug-induced
rotation and overall motor performance on the rotarod.
Results: We found that ADX88178 (30 mg/kg, p.o.)
potentiated the effect of the low dose of L-DOPA on peak rotational activity.
In the rotarod test the combination treatment was the only treatment that
induced a significant increase in motor performance (40% above baseline). The
use of mGluR4 modulators is receiving increased attention as an approach to
treat Parkinson´s disease. These data further validate the potential of mGluR4
PAM for the treatment of motor symptoms of Parkinson’s disease.
P06.10
Evaluation of
anti-parkinson activity of methanolic extract of Hyoscyamus Niger seeds in
stereotaxically induced rotenone rat modal
Dharmendra Kumar
Khatri1,Archana R. Juvekar1
1Institute of Chemical
Technology, Matunga, Mumbai, India.
Objective: To evaluate
anti-parkinson potential of methanolic extract of Hyoscyamus Niger seeds (MHN)
in stereotaxically induced rotenone rat model of Parkinson’s disease.
Methods: In the present study
we have evaluated anti-parkinson potential of methanolic exract of H. niger seeds in stereotaxically induced
rotenone rat model of parkinson’s. Air dried authenticated H. niger seeds were
extracted using methanol and were characterized by HPLC-UV and LCMS. Extract
showed presence of L-dopa with significant inhibition in DPPH, ABTS assay and
monoamine oxidase activity. Rotenone was injected unilateral in substantia
nigra pars compacta (SNPc) to induce Parkinson. Male Wistar rats were
pretreated with MHN (125, 250, 500 mg/kg body weight p.o.) twice daily for 7
days and after the induction for 21 days. Three weeks after rotenone infusion,
rats were tested for neurobehavioral (actophotometer, rotarod and Morris water
maze test) activity, estimation of lipid peroxidation (TBARS), glutathione
content, and activity of antioxidant enzymes like glutathione peroxidase [GPx],
glutathione reductase [GR], catalase [CAT], and superoxide dismutase [SOD]. The
standard antiparkinson drug used was L-dopa.
Results: The methanolic extract
of H. niger seed shows considerable anti-parkinson activity by attenuated motor
disabilities (actophotometer, rotarod and Morris water maze test) and increased
level of antioxidants in the different group of treatment.
P06.11
Human cathepsin D does
not enhance synucleinase activity in wild-type and SNCA-transgenic mice
Tohru Kitada1,2,
Qiubo Jiang1, Joerg Neddens3, Piotr Kolodziej1,2,
Daniel Havas3, Adel Farah1, Juliana Ng1, Jason
MacLaurin2, Yves De Repentigny1, Julianna J. Tomlinson1,
Ruth Slack2, Rashmi Kothary1, Birgit Hutter-Paier3,
Michael G. Schlossmacher1,2
1Ottawa Hospital
Research Institute, Ottawa, Ontario, Canada
2University of Ottawa,
Ottawa, Ontario, Canada
3QPS Austria
Neuropharmacology, Grambach, Styria, Austria
Background: Parkinson’s disease
(PD) is characterized by Lewy inclusion formation and cell loss.
Alpha-Synuclein (SNCA) is the main constituent of Lewy bodies and its
prefibrillar aggregation is thought to promote neurotoxicity. Three
laboratories including ours recently demonstrated that over-expression of human
cathepsin D (CTSD) cDNA in dopaminergic cells promotes the degradation of
excess SNCA. This result identified in CTSD a potential target to lower SNCA.
Objectives and
Methods: To
determine whether an increase in CTSD activity promotes lysosomal
'synucleinase' activity in vivo, we generated hCTSD-transgenic (tg) mice. We
furthermore generated hCTSD/SNCA double-transgenic mice to observe whether
hCTSD over-expression reduces synucleinopathy in SNCA tg mice. There, we used
two different models, i.e., “line D” of Masliah et al. (Science, 2000) and a
PAC1-SNCA A53T line of Kuo et al. (Hum Mol Genet, 2010).
Results: We confirmed the
generation of hCTSD over-expressing animals by Southern, Northern and Western
blotting, as well as immunohistochemistry. A CTSD activity assay revealed a 27%
and 31% increase in single tg mice between the ages of 9 and 18 months.
Unexpectedly, Western blots and sensitive ELISA analyses for SNCA levels in
brain lysates did not show any difference between single tg mice and controls
at the age of 9 and 18 months. We also performed quantification of SNCA by
ELISA and Western blotting using lysosomal fractions of whole brains from
double transgenic mice at the age of 6 months. Despite the 1.9 x fold
enhancement of the enzymatically active CTSD form, we failed to detect any
significant SNCA (and total Tau) differences in lysosomal fractions from tg
versus control mice.
Conclusions: In contrast to our
hypothesis, a 30% increase in neuronal CTSD activity did not lower the total
concentration of mouse or human SNCA in vivo.
P06.12
Investigating the
process of axonal degeneration in the striatal 6-hydroxydopamine lesion model
of Parkinson’s disease
Andrew Kneynsberg1,
2, Timothy J Collier2, Fredric P Manfredsson2 and
Nicholas M Kanaan2
1Neuroscience Program,
Michigan State University, East Lansing, MI, USA
2Department of
Translational Science and Molecular Medicine, College of Human Medicine,
Michigan State University, Grand Rapids, MI, USA
Objective: The 6-hydroxydopamine
(6-OHDA) lesion is the classic model of Parkinson’s disease (PD) in
experimental animals. Functioning as a specific neurotoxin for dopamine (DA)
neurons, 6-OHDA causes intracellular oxidative stress, and leads to axonal degeneration
and neuron death. This pattern of neurodegeneration has been shown to be a
primary aspect of the etiology of PD. To better understand this process, we are
using this lesion model to investigate the progression of retrograde axonal
degeneration.
Methods: To do this, striatal
axons were visualized independent of the phenotypic marker for DA neurons
(tyrosine hydroxylase (TH)) with green fluorescent protein (GFP) delivered with
recombinant adeno-associated virus (rAAV). The cells of the substantia nigra
pars compacta (SNpc) were transfected via intracranial injection. GFP
transfected rats were given unilateral injections of 6-OHDA in the striatum to
initiate axonal degeneration, to mimic the progression seen in human PD.
Animals were sacrificed in a time course of 1,3, and 7 days to allow for
analysis of the rate and extent of the axonal degeneration throughout the
striatum.
Results: Sagittal tissue
sections will be analysed with respect to the density of axonal fibers in the
striatum as well as number of remaining neurons in the SNpc expressing and not
expressing TH. The results of this study will hopefully lead to the ability to
use this classic 6-OHDA lesion model of PD as a new model of axonal
degeneration. By using an early time course and possibly lower doses of 6-OHDA,
the factors of synaptic degeneration and retrograde axon retraction will be
studied before neuron death occurs. These findings would be very valuable to
the study of PD as it is believed that the early loss of axonal DA synapses is the
first symptomatic event of PD progression.
P06.13
Longitudinal in vivo
imaging in a novel model of Parkinson’s disease in minipig
Anne M. Landau1,2,
Steen Jakobsen2, Aage K.O. Alstrup2, Anna C. Schacht2,
Arne Møller1,2, Jens Christian Sørensen3, Doris J. Doudet1,2,4
1Center of Functionally
Integrative Neuroscience, Aarhus University, Aarhus, Denmark
2Department of Nuclear
Medicine and PET Center, Aarhus University Hospital, Aarhus, Denmark
3Department of
Neurosurgery, Aarhus University Hospital, Aarhus Denmark
4Department of
Medicine/Neurology, University of British Columbia, Vancouver, Canada
Objective: The ubiquitin
proteasome system is the main intracellular pathway for protein degradation and
its dysfunction has been implicated in the pathophysiology of Parkinson’s
disease (PD). Direct intracerebral injection of proteasome inhibitors can
provide a progressive model of parkinsonism. Here we translate this approach to
an animal model, with a large brain and the ability to express complex
behaviors, and investigate the longitudinal effects of chronic exposure to a
proteasome inhibitor on monoaminergic projections using in vivo imaging.
Methods: Four female Göttingen
minipigs were implanted in the cisterna magna with a catheter connected to a
subcutaneous titanium injection port. After recovery, we performed positron
emission tomography at baseline (after saline injections through the access
port) with C-11 labeled dihydrotetrabenazine (DTBZ, a vesicular monoamine
transporter type 2 tracer) and yohimbine (a selective alpha2 adrenoceptor
tracer). Pigs received multiple doses of 20 or 50 micrograms of the proteasome
inhibitor lactacystin dissolved in saline through the access port, and were
imaged over a one-year period. Data were analyzed using standard Logan
graphical analysis to determine the binding potential of DTBZ and the volume of
distribution of yohimbine.
Results: Mild initial symptoms
including bradykinesia, freezing, and weakness of hindlimbs, progressed over
time. Striatal DTBZ binding decreased on average by 35% after 4-6 injections of
the proteasome inhibitor, and remained decreased by 26% after one year.
Yohimbine volume of distribution was increased early, by 15-25%, in various
cortical and thalamic brain regions after the 3rd lactacystin injection,
and remained increased by 30-40%
after one year. Decreased striatal binding of DTBZ is consistent with previous
studies in human PD and animal models. Increased yohimbine volume of
distribution suggests early noradrenergic deficits consistent with recent
hypotheses that noradrenergic cell loss occurs early in PD.
P06.14
Functional LRRK2
genetic interaction screen in Drosophila
Paul C. Marcogliese1,
Sameera Abuaish1, Elizabeth Abdel-Messih1, Ghassan
Kabbach1, Sarah Seang1, Gang Li1, Ruth S.
Slack1, M. Emdadul Haque2, Katerina Venderova3,
David S. Park1
1Cellular &
Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada
2Biochemistry, United
Arab Emirates University, Al Ain, United Arab Emirates
3Physiol. and
Pharmacol, University of the Pacific, Stockton, CA, USA
Objective: Using the UAS-GAL4
over-expression system we previously published a LRRK2 PD model in D.
melanogaster. This fly showed loss of DA neurons and locomotor deficits
when human (h) LRRK2 mutants were expressed under a DA promoter. Additionally,
a damaged eye phenotype was observed upon expression of hLRRK2 in the compound
eye under the GMR promoter (Venderova et al., HMG 2009). We
elucidated putative hLRRK2 genetic interactors by conducting a functional suppressor/enhancer
screen in vivo.
Methods: We genetically
crossed commercially available genomic deficiency lines with the GMR-hLRRK2
fly. This allows us to screen for potential LRRK2 interactors, which modify the
LRRK2 eye phenotype by suppression/enhancement. These preliminary interactors
are then examined for phenotypic modification under a DA promoter.
Results: We have elucidated
specific genetic interactors implicating LRRK2 in, amongst others, immune
function, vesicular trafficking, cell cycle, mitochondrial function, and cell
signaling pathways. Our screen has elucidated LRRK2 genetic pathways that may
be key to understanding LRRK2 biology and therefore PD pathogenesis.
Financial Disclosure: Funding was provided by MJFF, CIHR,
PSC and PRC.
P06.15
Intrastriatal
injection of pre-formed a-synuclein fibrils initiates
the formation of Lewy body-like
intracellular inclusions and nigrostriatal degeneration in naïve rats
Katrina L. Paumier1,
Kelvin C. Luk2, Fredric P. Manfredsson1, Nick M. Kanaan1,
Jack W. Lipton1, Timothy J. Collier1, Christopher Kemp1,
Stephanie Celano1, John Q. Trojanowski2, Virginia M. Lee2
and Caryl E. Sortwell1
1Michigan State
University, Grand Rapids, MI, USA
2University of
Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
Objective: Previous studies have
demonstrated that injections of fibrillar forms of alpha-synuclein (α-syn) into the mouse striatum can
induce Parkinson’s-like Lewy pathology in anatomically interconnected regions
and ultimately results in significant neurodegeneration of the nigrostriatal
system. The aim of this study was to evaluate whether intrastriatal injection
of exogenous pre-formed α-syn
fibrils (PFFs) into naïve rats would result in similar Lewy body (LB)-like
intracellular inclusions and neurodegeneration. The establishment and
characterization of a rat model of α-syn
PFF-induced toxicity would provide a valuable research tool for
therapeutic development
Methods: Thirty-six male Sprague Dawley rats
received unilateral intrastriatal injections of either monomeric or PFF mouse α-syn in one or two sites (8 mg
total). Rats were sacrificed at 30, 60 or 180 days post injection to assess the
temporal progression of α-syn pathology.
Animals were subjected to monthly behavioral tests to determine temporal course
of motor disability. Upon sacrifice, brains were processed for
immunohistochemistry and levels of striatal dopamine and metabolites.
Results: At 30 and 60 days
post-injection, α-syn PFF
rats and not monomeric α-syn controls,
exhibited hyper-phosphorylated α-syn
intraneuronal accumulations (i.e., diffuse Lewy neurite (LN)- and
LB-like inclusions) in several areas interconnected with the striatum, most
prominently in the frontal and piriform cortices, the amygdala, and substantia
nigra. Furthermore, α-syn pathology
in PFF-rats colocalized with ubiquitin, indicating that they share common
properties with LBs/LNs. At the 60-day time point, a slight reduction of
tyrosine hydroxylase immunoreactive neurons in the ipsilateral substantia nigra
was observed. Ongoing quantitative assessment will determine the magnitude of
nigrostriatal degeneration; however, behavioral results do not indicate
significant deficits at this time point. Our results thus far, parallel
findings in wild-type mice in which α-syn
PFFs are sufficient to seed the pathological conversion of endogenous α-syn and induce a progressive,
neurodegenerative model of α -synucleinopathy
in rats.
Financial Disclosure: Supported by the
Morris K. Udall Center of Excellence for Parkinson’s disease Research at
Michigan State University (TJC).
P06.16
LRRK2 interacts and
phosphorylates Synapsin I: implication for synaptic vesicle trafficking
I. Russo1,
A. Marte2, E. Belluzzi1, L. Civiero1, D.
Cirnaru3, L. Bubacco1, G. Piccoli3, E. Greggio1, F. Onofri2
1 Department of
Biology, University of Padova, Padova, Italy
2 DIMES Sezione
Fisiologia Umana, University of Genova, Genova, Italy
3 Institute of
Neuroscience, CNR, Milan, Italy
Objective: We recently showed that neuronal
electrophysiological properties and synaptic vesicular trafficking are
modulated by the presence of LRRK2 at pre-synaptic bouton; moreover, we reported that LRRK2, through its WD40 domain, pulls down
from mouse brain lysate different pre-synaptic proteins including Synapsin I a phosphoprotein associated with synaptic vesicles (SVs) and
involved in the neurotransmitter release. In this regard, the aim of our study was to validate the interaction between LRRK2
and synapsin I, to investigate the physiological function of this interaction
and to understand how LRRK2 pathogenic mutations might affect and alter the
synaptic transmission.
Methods: LRRK2 and Synapsin I interaction was investigated by
co-immunoprecipitation from rat cortical synaptosomes and highly pure SVs.
Phosphorylation assay was performed with purified bovine synapsin I and
recombinant 3xFlag LRRK2 wild type, G2019S pathogenic mutant and K1906M
kinase-dead constructs.
Results: We demonstrated that LRRK2 co-localizes with synapsin I and
actin filaments on SVs fraction and highly pure SVs thus confirming that LRRK2
efficiently interacts with vesicular protein complex at pre-synaptic site.
Moreover, in
vitro kinase assay revealed that LRRK2
phosphorylates synapsin I a and b and a chemical cleavage at cysteine residues
showed that LRRK2 phosphorylation occurs on the C-terminus of synapsin Ia and
b. We are now investigating the physiological
function of LRRK2 phosphorylation on synapsin I to understand whether LRRK2
modulates synapsin I binding to SVs or actin filaments and thus controls the
dynamics between vesicle pools at pre-synaptic site.
P06.17
Effect
of vinpocetine a PDE-1 inhibitor on MPTP-induced experimental Parkinson’s
disease in rats
Sorabh Sharma 1,
Rahul Deshmukh 1, P. L. Sharma 1
1Neuropharmacology
Division, I. S. F. College of Pharmacy, Moga-142001,
Punjab, India
Objective: Up regulation in
phosphodiesterase 1 (PDE1) expression and decreased levels of cyclic
nucleotides (cAMP and cGMP) have been reported in Parkinson’s disease. The
present study was designed to investigate the effect of vinpocetine a PDE1
inhibitor on MPTP- induced experimental Parkinson’s disease in rats.
Methods: To produce stable
motor deficit, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) was
repeatedly administered intranigrally (bilaterally) at an interval of one week
(day 1, 7 and 14). Following development of stable motor deficit, which was
observed after third infusion of MPTP (day 14) in rats, the animals were
treated with vinpocetine at different doses (5, 10 and 20mg/kg) from day 15-28.
Motor deficit in MPTP treated rats was assessed by grip strength, narrow beam
walk and by spontaneous locomotor activity in rats. Oxidative burden was
assessed by measuring the levels of malondialdehyde, nitrite, protein
carbonylation and glutathione in striatal brain homogenate. Striatal dopamine
levels (DA) was also measured by HPLC analysis. Further, MPTP-induced
neurotoxicity was also checked histologically in nigral regions.
Results: Intranigral
administration of MPTP produce significant stable motor deficit, increased markers of
oxidative-nitrosative stress and decreased levels of striatal dopamine. Chronic
administration of vinpocetine (for 14 days) significantly and dose dependently
improved motor behavior, attenuated oxidative-nitrosative stress and restored
striatal dopamine levels in MPTP treated rats. The current study supports the
potential role of PDE-1 in mediating neurodegenerative changes associated with
PD and PDE1 inhibition may prove to be useful therapeutic strategy in the
treatment of neurodegenerative disorders associated with motor disabilities.
P06.18
Parkinsonian features in aging GFAP.HMOX1 transgenic mice
overexpressing human HO-1 in the astroglial compartment
Wei Song, 1
Adrienne Liberman,1 Hyman M. Schipper1,2
1Lady Davis Institute, Jewish General
Hospital, Montréal, Québéc, Canada
2Department of Neurology and Neurosurgery,
McGill University, Montréal, Québéc, Canada
Objective: To determine whether mid-to-late
life overexpression of glial heme oxygenase-1 (HO-1), a stress protein induced
in the Parkinson disease (PD) substantia nigra, recapitulates neurochemical,
neuropathological and behavioural features of the disease in an animal model.
Methods: Motoric behaviour, basal ganglia
neurotransmitter levels and neuropathological markers were ascertained in
conditional GFAP.HMOX1 transgenic mice expressing human HO-1 (HMOX1) in
the astrocytic compartment from 8.5 to 19 months of age.
Results: HMOX1
expression was documented in astrocytes, ependymocytes and tanycytes. Relative
to wild-type controls, the GFAP.HMOX1 mice exhibited impaired motor
coordination (rotarod test), striatal dopamine deficiency and augmented
substantia nigra GABA concentrations (HPLC-EC), pathological brain iron
deposition (DAB-Perls stain), increased neuronal and glial MnSOD protein
(mitochondrial OS marker; IHC), and increased ubiquitin staining in astrocytes
and tyrosine hydroxylase-positive (dopaminergic) neurons (IHC). Impaired motor
performance did not occur in transgenic mice overexpressing glial HMOX1 between
1.5 and 12 months of age, attesting to the important role of brain aging in
this model.
Conclusions: Corroborating and
extending our earlier in vitro findings to the intact brain, over-expression
of astrocytic HMOX1 in mice between 8.5 and 19 months of age promotes
several behavioural, neurochemical and neuropathological features of idiopathic
PD. Curtailment of glial HO-1 hyperactivity by
pharmacological
or other means may afford neuroprotection in PD and other aging-related
neurodegenerative disorders.
P06.19
Gene expression
changes induced by long-term subthalamic nucleus deep brain stimulation in rats
Caryl Sortwell1,
Luke Fischer1, Christopher Kemp1, Allyson Cole-Strauss1,
Zach Mattingly1, Kathy Steece-Collier1, Timothy Collier1
and Jack Lipton1
Michigan
State University, Grand Rapids, MI, USA
Objective: The use of deep brain
stimulation (DBS) as a neurosurgical intervention for Parkinson’s disease (PD)
has outpaced our understanding of its effects on basal ganglia circuitry. We
have demonstrated in a rat model of subthalamic nucleus (STN) DBS that
stimulation induces the upregulation of brain derived neurotropic factor (BDNF)
mRNA in the substantia nigra (SN) and increases BDNF protein in the primary
motor cortex (M1) however a comprehensive gene expression analysis of the
impact of STN-DBS had yet to be conducted. The present experiments were
conducted to elucidate the impact of STN-DBS on gene expression within the rat
SN and M1 cortex.
Methods: 6-hydroxydopamine
(6-OHDA) lesioned and unlesioned rats were implanted unilaterally with
electrodes in the STN. Half the rats received continuous stimulation for 2
weeks; the other half were unstimulated. SN and M1 were collected for
comprehensive gene expression analysis using the Affymetrix Rat Genome 1.0 ST
Array. Data were analyzed using ArrayStar 5.0 to identify fold differences in
gene expression followed by qPCR confirmation. Pathway analysis using Ingenuity
Pathway Analysis software was conducted.
Results: Gene expression
analysis revealed that STN-DBS induced a >1.5
fold change in 66 genes in the SN of lesioned rats (11 genes upregulated and 55
genes downregulated). Pathway analysis indicated decreased expression of genes involved
in ERK1/2 signaling and nicotinic acteylcholine receptors whereas increased
expression of some trophic factor genes was identified. In the M1 cortex of
lesioned rats a >1.5 fold change in
expression was observed in a total of 52 genes in response to STN-DBS, with the
majority of these genes downregulated (48 out of 52). Ongoing direct
comparisons to unlesioned rats will provide further insight into effects of
STN-DBS-mediated gene expression changes in rats with intact nigrostriatal
circuitry. These results will provide important insight into the long-term
consequences of STN-DBS.
P06.20
Distinct
patterns of gene expression in the striatum of dyskinetic versus non-dyskinetic
responders to levodopa priming in the 6-hydroxydopamine lesioned rat
Kathy
Steece-Collier, Allyson Cole-Strauss, Kellie A. Sisson, Timothy J. Collier,
Caryl E. Sortwell, Jack W. Lipton.
Michigan
State University, Grand Rapids, MI
Objective:
Levodopa-induced dyskinesias (LIDs) are a frequent side effect of symptomatic
therapy for Parkinson’s disease (PD). The 6-hydroxydopamine (6OHDA) rat model
of parkinsonism the most commonly used animal model of PD and LIDs. It provides
insight into the compensatory changes that occur in the basal ganglia in
response to DA neuron degeneration and chronic levodopa treatment. We
previously characterized gene expression changes in tissue collected from
striatum and substantia nigra (SN) of 6OHDA, vehicle treated, or naïve rats at
1, 2, 4, 6 and 16 weeks post-lesion. In the current study, we overlaid
post-lesion levodopa administration to examine whether LIDs result in
differential gene expression in striatum.
Methods: Male
Sprague Dawley rats were sham or 6-OHDA lesioned and treated chronically with
levodopa (12.5 mg/kg daily) or vehicle. After priming, approximately 80% of
lesioned rats developed LIDs (responders) whereas 20% did not (non-responders).
Lesions were confirmed by HPLC. Striatal tissue from ‘responders’ and
‘non-responders’ was microdissected. Comprehensive gene expression analysis
using the Affymetrix Rat Gene 1.0ST array was conducted followed by analysis
using Arraystar 5 (DNAStar) to detect significant differences in gene
expression.
Results: The
average LID severity score for ‘non-responders’ was 0.33+0.14 (mean +SEM) with
DA depletion of 97.3%+0.97; the average LID severity score for ‘responders’ was
16.14+0.49 with DA depletion of 98.4%+0.29. Using a cutoff of >1.5 and a
t-test with the Benjamini-Hochberg FDR correction, 35 genes significant at the
95% confidence interval. Of these 35 genes, 34 were upregulated. Genes
associated with LIDs included those with influence on neuronal differentiation,
axonal guidance, neuronal excitability, MAP kinase and ERK pathway activation,
and several genes associated with neuroendocrine function. Comprehensive gene
expression data from the 6OHDA model when overlaid with levodopa priming for
dyskinesias provides new interventional targets and a solid foundation for
better understanding mechanistic underpinnings of dyskinesias.
Financial
Disclosure: Supported by Michigan State University Morris K. Udall Center of
Excellence in Parkinson’s disease Research (P50-NS058830).
P06.21
SYNerGY mice: modeling
GBA1 dysfunction and human synucleinopathy risk
Julianna J. Tomlinson1,
Paul Manninger1, Dina Elleithy2, Fanyi Meng2,
Mirela Hsu2, Diane C. Lagace2, Gregory A. Grabowski3,
Robert L. Nussbaum4 and Michael G. Schlossmacher1,2
1Neuroscience Program,
Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
2Faculty of Medicine, University
of Ottawa, Ottawa, Ontario, Canada
3Divison of Human
Genetics, University of Cincinnati College of Medicine, Cincinnati, OK USA
4Division of Medical
Genetics, University of California, San Francisco, CA, USA
Objective: We have created a new
animal model of genetic susceptibility to dementia, parkinsonism and related
SNCA-driven neurodegenerative diseases: the SYNerGY mouse (Synucleinopathy
related to Gaucher disease and Lewy body dementia). These mice carry three
distinct susceptibility traits at two loci (SNCA, GBA1); both of which are
independently and equally linked to dementia and parkinsonism.
Methods: The SYNerGY mouse was
created by crossing PAC-hSNCAA53T mice [Kuo et al., 2010] with Gba1D409V
knock-in mice [Xu et al., 2003] resulting in a mouse that combines (1) human
SNCA burden (gene dosage; n=4) with (2) SNCAA53T point mutation, on
an murine Snca null background; and (3) Gba1D409V knock-in
mutations. Our characterization of these mice is guided by histological,
biochemical and behavioural analysis of the parental strains as well as human
disease pathology.
Results: We
have published that homozygous mutations in the murine Gba1D409V
gene lead to accumulation of endogenous Snca protein in the hippocampus
determined using both biochemical (ELISA) and histological methods [Cullen et
al., 2011] and memory deficits that can be ameliorated by delivery of wild-type
GBA1 into the CNS [Sardi et al., 2011]. PAC-hSNCAA53T mice develop
SNCA allele dosage- and age-dependent synaptic changes in the same region of
the hippocampus and in the cerebellum. By crossing these two strains, we
hypothesized that SYNerGY mice would develop stronger, and possibly earlier
onset of synucleinopathy-type changes. Indeed, preliminary histological
analyses of brains from young SYNerGY mice revealed evidence of SNCA rise in
both the hippocampus and cerebellum. A first SYNerGY mouse cohort has been
generated, and we are now beginning the detailed characterization of SNCA
metabolism and glycosphingolipid turnover in their CNS and are performing
relevant behavioural studies.
Conclusion: The SYNerGY mouse
represents the first bigenic mouse model to examine pathophysiological events
involved in human dementia with Lewy bodies and Parkinson disease.
P06.22
Further characterization
of a novel, environmentally induced progressive rodent model of Parkinson's
disease
Jackalina M. Van
Kampen1,2, David C. Baranowski1 Christopher A. Shaw3,
Denis G. Kay1,2
1Neurodyn Inc.,
Charlottetown, Prince Edward Island, Canada
2University of Prince
Edward Island, Charlottetown, Prince Edward Island, Canada
3University of British
Columbia, Vancouver, British Columbia, Canada
Objective: Chronic exposure to dietary phytosterol
glucosides has been found to be neurotoxic. When fed to rats, β-sitosterol β-d-glucoside
(BSSG) triggers the progressive development of
neurological deficits, with behavioural and cellular features that closely
approximate those observed in Parkinson’s patients. Clinical signs and
histopathology continue to develop for several months following cessation
of exposure to the neurotoxic insult. Here, we further characterize the
progressive nature of this model, its non-motor features, and response to
levodopa administration.
Methods: Adult male Sprague Dawley rats received daily feedings of either
plain flour pellets or BSSG-containing flour pellets (3 mg) for 16 weeks.
Animals were monitored for locomotor activity, coordination, olfaction, and
cognitive function beginning immediately following cessation of toxin exposure
and continuing throughout the duration of the study. Animals were sacrificed at
4, 6, 8, and 10 months following initial toxin exposure. Tissues were assayed
by immunohistochemistry for the loss of dopaminergic neurons, appearance of
inflammatory cytokines, and abnormal protein aggregates.
Results: Chronic
exposure to BSSG resulted in the progressive loss of dopaminergic neurons of
the substantia nigra. At approximately 4 months following initiation of BSSG
exposure, animals displayed the early emergence of an olfactory deficit, in the
absence of significant dopaminergic nigral cell loss or locomotor deficits.
Locomotor deficits developed gradually over time and were reversed by levodopa
treatment. Cognitive impairment was observed in the form of spatial working
memory deficits, as assessed by the radial arm maze. In addition to the
progressive loss of TH+ cells in the substantia nigra, the
appearance of insoluble intracellular α-synuclein aggregates was also
observed. The slowly progressive nature of this model, together with its construct, face and predictive
validity, make it ideal for the screening of potential neuroprotective
therapies for the treatment of Parkinson's disease.
P06.23
PET imaging of rats
that express the LRRK2 G2019S mutation: initial findings
Matthew D Walker1,
Mattia Volta1, Katherine Dinelle1, Rick Kornelsen1,
Stefano Cataldi1, Siobhan McCormick1, A. Jon Stoessl1,
Matthew J Farrer1, Vesna Sossi1
1The University of
British Columbia, Vancouver, British Columbia, Canada
Objective: To study transgenic
rats that express the Parkinson’s disease (PD)-related, mutated form of LRRK2.
Positron emission tomography (PET) is used, enabling comparison of
pathophysiology between species. Imaging is complemented by behavioural testing
to determine if the rodents recapitulate the pathogenesis of PD and if
neurological abnormalities are progressive.
Methods: Transgenic LRRK2
G2019S (BAC) rats (n=5) aged 1 year, together with non-transgenic littermate
controls (n=3), were imaged using [11C]methylphenidate PET. Nine
month old rats (n=4 transgenic, n=4 controls) were also imaged. The radiotracer
binds to the dopamine transporter (DAT), with relative striatal DAT density
quantified by the tracer’s binding potential (BPND). Behavioural testing was performed at 7-8 months
(n=11-18 per group). Tests included the accelerating rotarod (time on the rod),
ledge-beam (time to traverse the beam) and drag test (steps per meter when
dragged backwards at constant speed, repeated on 4 consecutive days). Statistical
analysis of group differences was performed using appropriate ANOVA and
post-hoc tests.
Results: One year old
transgenic rats had the lowest BPND,
15 % lower than age-matched controls (p<0.05). No other group differences in
BPND were found. Behavioural
testing demonstrated various deficits; transgenic rats spent 26 % less time on
the rotarod, took 80 % longer traversing the ledge beam, and took 22 % fewer
steps on day 1 of the drag test (all p<0.05). On days 2-4 of drag testing,
the reduction in the number of steps was no longer significant. If additional
cohorts display reductions in DAT at 1 year, the rodent model mirrors PD in an
essential manner.
P06.24
LRRK2 G2019S knock in
Mice display progressive alterations in Dopamine release and metabolism
Mei Yue1,
Kelly Hinkle1, Paul Davies2, Erin
Bowles1, Bahareh Behrouz1, Sarah Lincoln1,
Joel Beevers1, Austen Milnerwood3, Dario Alessi2, Dennis
Dickson1, Matthew Farrer, 3 and Heather Melrose1
1Mayo Clinic
Jacksonville, Jacksonville, FL, USA
2University of Dundee,
Dundee, Scotland, UK
3University of British
Columbia, Vancouver, Canada
Objective: Mutations in the kinase leucine rich repeat
kinase 2 (LRRK2) are the leading cause of genetic Parkinsonism. The most common
mutation, G2019S has been shown to exert its toxic effects via enhanced kinase
activity. To assess the effects of this mutation in mice we created
gene-targeted knock-in mice that express the G2019S mutation within their own
genome.
Methods: Mutant littermate heterozygous, homozygous and wild-type mice
were studied up to 20 months of age. Our analysis included extensive
characterization of the dopaminergic system, using in vivo microdialysis to measure striatal extracellular release of
dopamine and dopamine metabolites 3, 4-dihydroxyphenylacetic acid and
homovanillic acid in conscious freely-moving animals, total monoamine axonal
neurochemistry in striatal lysates and stereological dopaminergic counts. A
complete behavioral battery involved motor (rotarod, gait, locomotor in open field)
and cognitive testing (novel object, elevated plus maze, water maze, fear
condition). Biochemical analysis encompassed kinase activity assays and
quantification of protein levels of LRRK2 and phospho-LRRK2 with progressing
age. Neuropathological analysis with various Parkinson’s Disease
immunohistochemical markers was also performed in aged mice.
Results: G2019S mice are viable, fertile and have normal bodyweights and
lifespans. As predicted, the G2019S mice have elevated kinase activity, with
2-fold activity in heterozygous mice and 4-fold activity in homozygous mice. At
6 months of age, the dopaminergic system was intact in G2019S mice. However by
12 months of age, a reduction both basal and amphetamine-evoked extracellular
dopamine release was observed, along with significant changes in the
dopamine:metabolite turnover ratios, though no significant reduction was
observed in dopamine neuronal number even by 20 months of age. No behavioral
alterations were detected in G20192S mice and no major neuropathological
alterations were observed, although levels of non-phosphorylated axonal tau
were reduced in aged G2019S mice.
Our data suggest that less dopamine is
available for release at the nerve terminal in G2019S mice and the increased
biochemical turnover ratios suggest a compensatory mechanism to increase
firing. Remarkably these changes are apparent with just one copy of the mutant
allele. Analogous neurochemical findings have been observed in other PD models
and in imaging studies of early stage PD and asymptomatic LRRK2 carriers. Our
model may represent a progressive preclinical model of LRRK2-PD that will be
useful for mechanistic studies to gain further insights in early LRRK2
dysfunction.
P06.25
Neuronal characterization of mesenchymal dog stem cells into
dopaminergic neurons
Ximena Zottig1, Julie Bournival1 and Maria-Grazia
Martinoli1 ,2
1Université du Québec à Trois-Rivières, Trois-Rivières, Canada
2Neuroscience Research Unit, Université Laval, Canada
Objectives: Stem cells are undifferentiated
cells that possess the ability to differentiate into several cell types. There
are various types of stem cells, but our experiments are focused on the use of
mesenchymal stem cells, found mainly in adipose tissue. They may differentiate
into several mesenchymal tissues such as fibroblasts, bones, tendons and
ligaments. The aims of our study were 1) to establish a method of
differentiation of canine stem cells towards a neuronal phenotypes 2) to
achieve the differentiation of canine neuronal cells into dopaminergic
(DAergic) neurons and 3) to develop a neuroprotective strategy to rescue
DAergic neurons from oxidative stress damages characteristic of Parkinson’s
disease (PD) degeneration.
Methods: In order to establish the
typical morphological properties and neuronal phenotype of DMSC-ad cells,
differentiation was induced by a specific medium for 4 days. Western blotting
and immunofluorescence measurements were used to confirm the differentiation.
Results: Our characterization results
show a neural character by increased expression of neuronal markers such as the
three subunits of neurofilament, β-3-tubulin, NeuN and GFAP. In addition,
we also detect the expression of tyrosine hydroxylase (TH) and dopamine
transported (DAT). However, these DAergic markers do not appear to be modulated
following treatment with differentiation medium. Our analysis demonstrates that
the neuronal character of our canine mesenchymal stem cells is properly
established and other experiments are in progress to successfully induce the dopaminergic
nature of these stem cells.
BASIC SCIENCE: BRAIN PHYSIOLOGY AND CIRCUITRY
P07.01
Sample entropy of GPi
neurons dependence on the level of alertness in 6OHDA rats
Daniela Sabrina
Andres,1,2,3,4 Daniel Cerquetti 2, Marcelo Merello 2,
Ruedi Stoop
1 Institute of
Neuroinformatics, ETH and UZH, Zurich, Switzerland
2 Institute for
Neurological Research Raul Carrea, Fleni Institute, Movement Disorders Section,
Buenos Aires, Argentine
3 Physiology and Biophysics
Department, Medicine School, University of Buenos Aires, Argentine
4 Society in Science,
The Branco-Weiss Fellowship, administered by ETH, Zurich, Switzerland
Background: The analysis of
neuronal data obtained during functional neurosurgery from alert human patients
with Parkinson’s disease, raised the question to what extent the increase in
the entropy of single parkinsonian Basal
ganglia (BG) neurons depends on the level of consciousness and to what on
the disease itself.
Objective: To assess the
dependency of sample entropy on the level of alertness in healthy and
parkinsonian rats.
Methods: Thirty-six adult
Sprague-Dawley rats were assigned randomly to two groups: control and
6OHDA-lesioned animals. Between 21 and 28 days after the lesion procedure,
animals underwent the cylinder test and went through stereotactic surgery with
the objective of registering spontaneous activity of the medial Globus Pallidum
(GPi). Animals were placed in an ad-hoc built restraining device that did not
allow any spontaneous movements during the whole recording time. The eyes of
the animals were covered; all recordings were obtained in conditions of
environmental silence. The alertness level was characterized periodically with
a standardized non-painful stimulus.
Results: We recorded the
activity of 38 single GPi neurons
during the awakening process in relaxed, head-restrained, control and
6OHDA-lesioned rats. The sample entropy increased in the 6OHDA group with an
increasing level of alertness, but it was reduced in the control group. With
increasing levels of alertness, single neurons changed their behavior
adaptively, showing that the measured characteristics should be considered as
emergent properties of the state of the neural system rather than static, intrinsic
electrophysiological
properties of GPi neurons. We interpret the increment observed in the level of
entropy of parkinsonian neurons as the inability of dopamine-depleted Basal
Ganglia to handle increased levels of input associated with higher levels of
alertness. Our results emphasize that an extrapolation from data obtained under
anesthesia to the wake subject or animal is bound to lead to incorrect results.
P07.02
Rewire dopaminergic neurons: involvement of the transcription factors
Lmx1a and Lmx1b
Audrey Chabrat1, Emmanouil Metzakopian2, Siew-Lan
Ang2 and Martin Lévesque1
1 Institut Universitaire en Santé Mentale de Québec, Université Laval,
Québec, Canada
2 National Institute for Medical Research, London, UK
Objective: Degeneration of
midbrain dopaminergic neurons (mDA) is the principal cause of Parkinson’s
disease. Graft of dopaminergic neurons newly generated from stem cells
represents a promising therapeutic avenue. However, a major factor limiting
success in transplantation studies is the inappropriate re-innervation of the
grafted neurons. It is thus primordial to identify factors regulating axon
projection and connectivity of mDA neurons. We recently discovered that
transcription factors Lmx1a and Lmx1b were essential for mDA progenitor specification,
proliferation and differentiation. In this new study we investigate the role of
Lmx1a, Lmx1b and their downstream target PlexinC1 in postmitotic mDA neurons.
Methods: Conditional mutant mice were used
for the specific inactivation of Lmx1a and Lmx1b in postmitotic midbrain
dopamine neurons. Analysis of axon projections in mutant mice was done using
both immunohistochemistry on brain sections and using optical projection
tomography. To study the role of PlexinC1 in mDA neurons development, we
performed in vitro experiments and examine the response of dopaminergic growth
cones to PlexinC1 ligand Sema7a.
Results: Analysis of dopaminergic axon
projections of Lmx1a/b double conditional mutant mice reveals a striking axon
guidance defect and confirms the essential role of Lmx1a/b in the establishment
of dopaminergic circuit formation. We also identified PlexinC1 as a target gene
regulated by these transcription factors. Our in vitro experiments show that Sema7a
and PlexinC1 regulate mDA axon development and these effects are mediated by
Src family kinases. At the light of our data, we propose a novel model to
explain the segregation of the nigrostriatal and mesolimbic pathways. Data
generated here will shed a new light on mechanisms that regulate dopamine
neuron connectivity and will certainly help in the effort to understand the
molecular factors contributing to the efficiency of cell replacement therapies
in Parkinson’s disease.
P07.03
Quantitative assessment and ultrastructural features of the cholinergic
innervation of the globus pallidus in squirrel monkeys
Lara Eid, André Parent and Martin
Parent
Centre de recherche de l’Institut
universitaire en santé mentale de Québec, Department of psychiatry and
neuroscience, Faculty of medicine, Université Laval, Quebec City, QC, Canada
Objective: The
primate basal ganglia are heterogeneously innervated by cholinergic (ACh)
varicose fibers arising mainly from the pedunculopontine tegmental nucleus
located in the brainstem. The aim of this light and electron microscopic study
is to characterize and compare the ACh innervation of the internal (GPi) and
external (GPe) globus pallidus of squirrel monkeys (Samiri sciureus).
Methods: Serial
sections immunostained with a choline acetyltransferase (ChAT) antibody were
analyzed by means of stringent stereological procedures at light and electron
microscopic levels.
Results: Light
microscopy analysis reveals ChAT+ axons seen to emerge from PPN neurons and
course mainly in the central portion of the mesopontine tegmentum. Rostrally,
this bundle splits into ventromedial and dorsolateral fascicles that arborize
in basal ganglia and thalamic nuclei, respectively. In the pallidum, several
thick fibers are oriented dorsolaterally and give rise to thinner varicose
fibers. Unbiased counts of ChAT+ axon varicosities reveal that total density of
innervation is similar in GPi (0.24 ± 0.03 x 106 axon varicosities /
mm3) and GPe (0.49 ± 0.11 x 106), with an anteroposterior
decreasing gradient in both pallidal segments. Neuronal counts on Nissl-stained
adjacent sections indicate that GPi and GPe neurons are similarly innervated by
ChAT+ axon varicosities, with an anteroposterior decreasing gradient observed
in the GPi only. At the electron microscopic level, ChAT+ axon varicosities are
comparable in size and shape in GPi and GPe. Less than 20% of ChAT+ axon
varicosities establish a synaptic contact, indicating that synaptic as well as
diffuse cholinergic transmission occur in both pallidal segments. No axo-axonic
contacts were visualized suggesting that presynaptic ACh modulation of pallidal
afferents is largely exerted through diffuse neurotransmission. Altogether,
these morphological data underline the strategic position of brainstem cholinergic
afferents in the functional organization of the basal ganglia in both normal
and pathological conditions, such as in Parkinson’s disease.
P07.04
Distribution of the
vesicular glutamate transporter in serotonin projections arising from the dorsal
raphe nucleus: A single-axon study in rats.
Dave Gagnon, Martin Parent1
1Centre de recherche de l’Institut universitaire en santé mentale de
Québec, Department of psychiatry and neuroscience, Faculty of medicine,
Université Laval, Quebec City, QC,
Canada
Objective: Serotonin ascending projections are believed
to play a significant role in non-motor symptoms of Parkinson’s disease. Being
able to store and release dopamine following L-Dopa administration,
these projections are considered as an important presynaptic determinant of L-Dopa-induced
dyskinesia. Serotonin neurons giving rise to ascending projections are located
in the dorsal raphe nucleus (DRN) and are known to contain the vesicular
glutamate transporter 3 (VGlut3) indicating that, in addition to serotonin and
dopamine, they are able to release glutamate in their target sites. This study
aimed at providing the first detailed description of single-axon projections
arising from DRN neurons, including distribution of VGlut3 within their axons.
Methods: We used electrophysiological guidance to microiontophoretically
label neurons of the rat DRN with an anterograde tracer. Somatodentritic and
axonal arborizations were reconstructed individually and entirely from serial
sagittal sections using a computerized image analysis system. High-resolution
images acquired with a confocal microscope were used to characterize the
distribution of VGlut3 protein in BDA-injected axons.
Results: DRN neurons were easily recognizable by
their highly regular (2-3 Hz) spontaneous firing patterns. They have a medium size
cell body (15-20 µm) from which emerge 3-5 primary dendrites, mainly oriented
along the anteroposterior axis. The DRN neurons are endowed with a highly
collateralized axon and display different axon morphology depending on target
sites. Typically, the axon leaves the DRN by piercing its anterior aspect, arches rostroventrally
and crosses the midbrain tegmentum to course caudorostrally in the medial
forebrain bundle where many axon collaterals are emitted. The proportion of
axon varicosities that contain the Vglut3 varies depending on target sites. Our
data support the existence of a complex trafficking mechanism of VGlut3 protein
within the highly collateralized axon of DRN neurons. We hypothesize that this feature might play a
significant role in maladaptive plasticity involved in L-Dopa-induced
dyskinesia.
P07.05
Role of postural instability in freezing of gait in Parkinson’s disease
Julie Nantel1 and Helen Brontë-Stewart2
1 Ottawa University, Ottawa, Ontario, Canada
2 Stanford University, Palo Alto, CA, USA
Objective Postural and gait deficits in
Parkinson’s Disease (PD) have mixed responses to dopaminergic medication
(meds). Meds improves mobility but increases risks for falls (Nantel et
al.,2012). Gait speed and stride length are generally responsive to meds while
gait variability is not. This suggests a regulation by different neural
pathways (Rochester et al.,2012) and possibly some shared pathophysiologic
mechanisms as freezers have larger gait variability and higher risk for falls
(Nantel et al.,2012, Plotnik et al.,2005). The aims of this study were to: 1)
to determine the contribution of the dopaminergic pathways on gait variability,
2) measure postural stability and determine its relationships with FOG and gait
variability.
Methods We measured postural stability,
FOG, stepping in place (SIP) variability in 30 PD subjects (15 freezers/15
non-freezers) and 14 healthy controls using static posturography and the SIP
(Nantel et al., 2011), which consists of alternative stepping on force
platforms. Clinical evaluation: UPDRS-III and FOG-questionnaire (FOG-Q). Gait
and UPDRS-III were performed off/on meds and posturography off-meds only.
Results Four freezers out of 15 froze
on-meds. On/off-meds, freezers had larger asymmetry than controls and
non-freezers (P<0.01). Freezers had shorter stride duration compared to both
groups off-meds only as they improved on-meds (P<0.01) while cycle
asymmetry/rhythmicity did not. CoP displacement/velocity in both directions
were higher in freezers versus controls (P<0.01) and correlated with on-meds
asymmetry (medial-lateral: R=0.46, R=0.45; P<0.05). Asymmetry correlated
with CoP displacement (anterior-posterior: R=0.44; P<0.05). UPDRS-III was
significantly higher in freezers on/off meds (P<0.02) and improved with meds
in both groups (P<0.01). Improvement of FOG occurrence on meds but not of
gait asymmetry/arrhythmicity suggests that both dopaminergic and
non-dopaminergic networks could contribute to FOG. The greater postural
instability in freezers and the correlations between CoPs and both FOG-Q and
asymmetry suggest that postural instability could play a role in the mechanisms
of FOG.
P07.06
Regional
changes in cortical neuronal density with idiopathic Parkinson’s syndrome
Caroline
Paquette1, Thomas Funck2, Michael Sidel3,
Calvin Melmed3, Oury Monchi4, Alexander Thiel2-3
1Department
of Kinesiology & Physical Education, McGill University and Centre for
Interdisciplinary Research in Rehabilitation of Greater Montreal (CRIR),
Montreal, Canada
2Department
of Neurology & Neurosurgery, McGill University and Lady Davis Institute for
Medical Research, Montreal, Canada
3Department
of Neurosciences, SMBD Jewish General Hospital, Montreal, Canada
4Functional
Neuroimaging Unit, Institut Universitaire de Gériatrie de Montréal and
Department of Radiology, University of Montreal, Montreal, Canada
Objective:
It has been hypothesized that cortical thinning in
neurodegenerative diseases such as Idiopathic Parkinson’s syndrome (IPS) might
be associated with a change in neuronal density. The aim of this study was to
determine whether changes in neuronal density are present in IPS subjects.
Methods: Fifteen
subjects with IPS (mean age: 60 years [range 42-75]) and 9 healthy controls
(mean age: 60 years [range 49-70]) underwent PET with 18-F-FMZ on a
high-resolution brain scanner (CTI/Siemens HRRT) and volumetric T1 MR imaging
(Siemens TRIO). Binding Potential (BPND) of GABA-A receptors was calculated
with parametric voxel-by-voxel Logan plots (relative to white matter activity
in the oval center). Images were corrected for partial volume effects (PVE)
using simulated PET images derived from gray matter segmentation of the T1 MRI
(e.g., Collins, et al., 1994). Regional PVE corrected GABA-A BPND were obtained
from right and left hemisphere and from bilateral primary motor (M1) and
premotor cortex (PMC).
Results: In control subjects, BPND was increased on the left side for both
M1 (Left 7.8 [SE 0.9] vs. Right 7.4 [SE 0.9], p<0.01) and PMC (Left 8.1 [SE
1.0] vs. Right 7.6 [SE 0.9], p<0.01) but was similar in the left and right
hemispheres (Left 7.8 [SE 1.1] vs. Right 7.7 [SE 1.0], p=0.91). In IPS subjects,
there was a significant increase in neuronal density on the left hemisphere
(Left 10.7 [SE 1.4] vs. Right 10.3 [SE 1.4], p<0.01), irrespective of the
most affected side. In addition, the neuronal density in IPS subjects was
significantly increased in PMC areas as compared to M1 and hemisphere (PMC 10.2
[SE 1.2] > M1 10.9 [SE 1.2], p<0.01 and > hemisphere 10.4 [SE 1.0],
p<0.05). These findings may indicate a differential susceptibility of motor
regions to the neurodegenerative process underlying IPS.
P07.07
Striatal interneurons expressing choline
acetyltransferase or calretinin in normal and 6-OHDA-lesioned mice.
Sarah Petryszyn1, Maria Gabriela Sánchez1,
Martin Parent1 and André Parent1.
1Centre de recherche de l’Institut universitaire en santé mentale de
Québec, Department of psychiatry and neuroscience, Faculty of medicine,
Université Laval, Quebec City, QC,
Canada
Objective:
The striatum is the largest and major integrative component of the basal
ganglia. Composed of a multitude of projection neurons, it also comprises a
smaller number of interneurons that play a crucial role in its functional
organization. This study provides a detailed
description of the distribution and chemical phenotype of two subpopulations of
striatal interneurons encountered in the mice striatum, under both normal and
parkinsonian (PD) conditions.
Methods: Striatal
sections immunostained for ChAT, CR, NeuN, VAChT and VGluT3 were scanned by
means of a high-resolution confocal imaging system. The data were analyzed with
stringent stereological quantitative procedures, whereas the optical density of
striatal VGlut3 immunoreactivity in normal and 6-hydroxy-dopamine
(6-OHDA)-lesioned mice was estimated with the help of a Li-Cor scanner.
Results: In the striatum of normal mouse,
ChAT+ neurons are much more abundant and widely distributed than CR+ neurons.
The large (18-22 µm), multipolar, ChAT+ interneurons are distributed according
to a rostrocaudal decreasing gradient. All ChAT+ striatal interneurons express
VGlut3, but some of the numerous ChAT+ axon varicosities that pervade the
striatum are devoid of VGlut3 immunostaining. None of the ChAT+ striatal
interneurons express CR, in contrast to the situation in human and non-human
primates. Two types of CR+ interneurons were detected in the mouse striatum.
First, there are small (5-15 µm), round and intensely fluorescent cells that
abound particularly in the area of the subventricular zone and the subcallosal
streak. These immature-looking cells are NeuN- and display a unique, markedly
varicose and moderately arborized process that extends far within the striatal
neuropil. Second, a smaller number of ovoid (15-20 µm) and less intensely
immunoreactive CR+ neurons occurred throughout the striatum. The comparison
between normal and 6-OHDA-lesioned mice revealed no significant changes in
striatal VGlut3 immunoreactivity, whereas the number of CR+ interneurons
appears significantly decreased in the denervated striatum.
P07.08
BDNF and dopamine D3
receptor agonist potentiate each other and promote asubstantial motor recovery
in the rat model of Parkinson’s disease
Luis Razgado1, Jorge Aceves1, Daniel Martinez1,
Ismael Jimenez1, Veronica Anaya1, Arturo Sierra1
1Center of Investigation
and Advance Studies of IPN (CINVESTAV), Mexico City, Mexico
Background: Parkinson’s disease
(PD) is produced by progressive degeneration of dopaminergic neurons. The
successful use of the preferential D3R agonist (Pramipexole) in PD has been
validated in several clinical trails (Hubble, 1995; Shannon, 1997). Pramipexole
is useful as monotherapy for up to 4-6 years (CALM-PD, 2009). This reduction in
the efficacy of pramipexole after several years of treatment could be due to
the fact that expression D3R gene is progressively decreased as Parkinson´s
disease progresses (Levesque, 1995; Ryoo, 1998; Joyce, 2004), becoming
dopaminergic D3R activation monotherapy less effective (Joyce, 2002). BDNF has
been implicated in several functions of dopaminergic neurons and the control of
normal expression of D3R (Guillin, et al; 2001; Sokoloff, et al; 2002).
However, it has been shown that BDNF is low in PD (Howells, 2000).
Objective: We investigated
whether the combined treatment of BDNF and dopamine D3R agonist (7-OH-DPAT)
could potentiate each other and restore the motor behavior of the 6-OHDA rat
Parkinson model.
Methods: Local non-viral BDNF
gene transfection into the substantia nigra (Alvarez- Maya, 2001) and i.p.
application of 7-OH DPAT by osmotic pumps during 18 weeks.
Results: The combined
treatment of BDNF and 7-OH-DPAT can potentiate each other, producing
significant recovery from the motor deficit and neuronal degeneration caused by
the 6-OHDA, evidenced by improvement of fine coordination during gait, gross
coordination and equilibrium on rotarod and disappearance of rigidity. All
these motor improvements were accompanied by an increment of TH+ neurons,
increase in number of TH+ neurons reinnervating the striatumand recovery of
dendritic spines of medium spiny neurons.
P07.09
Using eye movements to
differentiate subclinical and clinical types of Parkinsonism
Stuart Red1, Brian Copeland1, Annise Wilson1, Lalitha Guthikonda1, Tim Ellmore2, Richard Castriotta1, Mya Schiess1, Anne Sereno1
1UTHSC, Houston, TX, USA
2CUNY, New York, NY, USA
Objective: Patients with idiopathic REM behavior
disorder (iRBD) have a variable prognosis and are at high risk for the
development of Multisystem Atrophy (MSA) or Parkinson’s disease (PD).
Differential diagnosis of MSA and PD in early stages has proven difficult with
standard clinical measures alone. Our primary goal was to evaluate the
usefulness of reflexive and voluntary eye movement tasks to differentiate types
of preclinical and clinical Parkinsonism.
Methods: Individuals with iRBD (n=8), MSA (n=8), PD
(n=11), as well as control subjects (n=12) performed prosaccade (PS) and
antisaccade (AS) eye movement tasks. Latency and error rates of horizontal and
vertical saccades were measured with an infrared eye tracker. The University of
Pennsylvania Smell Identification
Test (UPSIT) was used
for olfactory performance.
Results: As expected, the MSA group performed
significantly better than PD on the UPSIT. MSA and PD groups showed
significantly higher error rates than controls on AS task, while MSA also
showed significantly longer PS latencies than controls.
The iRBD group was divided into two groups based on a median split of
UPSIT score. The iRBD group with higher olfactory scores showed significantly
higher AS error rates than iRBD patients with lower olfactory scores,
consistent with an earlier onset of frontal degeneration and disinhibition in
MSA. iRBD patients with higher olfactory scores also showed shorter latencies
on the PS task, indicating preclinical degeneration may result in shorter PS
latency that will secondarily show marked slowing as the disease progresses.
Thus, performance on eye movement tasks in conjunction with standard clinical
measures may prove useful as early markers of disease onset and course.
BASIC SCIENCE: DOPAMINE, RECEPTORS AND
OTHER NEUROTRANSMITTERS
P08.01
Blockade of
cannabinoid CB1 receptors attenuates behavioral and biochemical
changes following repeated MPTP assault to nigral neurons in rats
Rahul Deshmukh1,
Mayank Prabhakar1, Ankita Mehta1, Sorabh Sharma1,
Puneet Kumar1, P. L. Sharma1
1Neuropharmacology
Division, ISF College of Pharmacy, Moga-142001, Punjab, India
Objective: Parkinson’s disease is
a movement disorder that occurs due to dopaminergic dysfunction in brain,
especially in substantia nigra pars compacta (SNpc). Recently, the
controversial role of cannabinoid receptors was reported in the pathophysiology
of PD. In the present study, we have investigated the possible role of
cannabinoid CB1 receptor modulation following repeated intranigral
administration of MPTP (1-methy-4-phenyl-1,2,3,6-tetrahydropyridine).
Methods: Repeated intranigral
(day 1, 7, 14) administration of MPTP was done to produce stable motor deficits
in rats. Noladin ether a putative endocannabinoid, AM 251, a CB1
receptor antagonist were administered alone or in combination chronically
(14-28 days) in MPTP treated rats. Behaviorally, grip strength, spontaneous
locomotor activity and narrow beam walk tests were used to access motor behaviors.
Biochemically, oxidative stress and pro-inflammatory cytokine levels
(TNF-α and IL-1β) were determined in striatal and cortical brain
homogenates.
Results: Following third (day
14) intranigral administration of MPTP, rats produced stable motor deficit and
elevation in oxidative stress markers and cytokine levels (day 28). AM 251
significantly attenuated elevated levels of cytokines, oxidative stress and
improved motor behavior in MPTP treated rats. On the contrary, noladin enhanced
MPTP- mediated neurotoxicity, which was significantly attenuated by AM 251
pre-treatment. The above results indicating that chronic activation of CB1
receptors may play a significant role in the development of MPTP-induced
motor deficit in rats and suggest CB1 receptor blockade would be
beneficial in restoring motor functions in PD.
P08.02
Mechanisms of
activation of dopamine D1 receptors by rotigotine: a route to novel
Parkinson’s disease drugs
Sang-Min Lee1,
Richard Mailman1
1Department of
Pharmacology, Penn State College
of Medicine, Hershey, PA, USA
Objective: Neupro®
(Rotigotine) is a dopamine agonist used as symptomatic therapy of Parkinson’s
disease (PD). Although most clinically approved agonists target dopamine D2–like
receptors, activation of D1 receptors by high-intrinsic activity
agonists has been shown to have efficacy in PD equal to levodopa. D2
agonists as monotherapy are far less efficacious. Among the approved dopamine
agonists that do not have to be given intravenously, the D2-selective
drug rotigotine is unique in that it has high D1 intrinsic activity.
Unlike the available selective full D1 agonists (e.g., dihydrexidine
or SKF81259), rotigotine does not contain the catechol moiety that is known to
cause rapid metabolism and poor bioavailability. Thus, understanding the
molecular mechanisms by which rotigotine activates the D1 receptor
may provide leads to novel D1 agonists.
Methods: Both wild-type and
mutant human D1 receptors were expressed in HEK-293 cells. The
mutations were made in highly conserved transmembrane 5 serines (S5.42198A,
S5.43199A, and S5.46202A), as well as transmembrane 6
aromatic amino acids (F6.51288A and F6.52289A) that have
been shown to be critical for agonist interaction and receptor activation.
Results: S5.42198A
and S5.43199A mutations greatly decreased the affinity and receptor
activation mediated by rotigotine, whereas S5.46202A mutation did
not cause any significant change. This suggests that hydrogen bond formation
occurs between the hydroxyl group of rotigotine and S5.42198 and/or
S5.43199, but not S5.46202. Similarly, the F6.51288A
mutation decreased the affinity of rotigotine to a far greater extent than
F6.52289A suggesting that hydrophobic interactions with F6.51288
are particularly important. These receptor-ligand interaction data produced a
basic model of the possible docking pose of rotigotine that provides insight
into a new scaffold for non-catechol D1 receptor agonists with the
high D1 intrinsic activity of rotigotine, but with greater D1:D2
selectivity.
P08.03
P11 gene therapy for
Parkinson’s disease motor dysfunction and L-Dopa induced dyskinesias
Roberta Marongiu1,
Mihaela A. Stavarache1, Sergei A. Musatov1, Margarita
Arango-Lievano1, Paul Greengard2, Michael G. Kaplitt1
1Department of
Molecular Neurosurgery, Weill Medical College of Cornell University, New York,
NY, USA
2Laboratory of
Molecular and Cellular Neuroscience, the Rockefeller University, New York, NY,
USA
Objective:
P11
is a scaffold protein involved in the membrane localization of receptors.
Recent studies showed that P11 knockout mice have altered dorsal striatal
dopamine responsiveness in the 6-OHDA mouse model of Parkinson’s disease (PD).
We investigated the relationship between dopamine signaling and striatal p11 in
both normal and 6-OHDA unilateral lesioned mice.
Methods: We generated an AAV
vector to block production of murine p11 and stereotactically injected the
AAV.sip11 into the dorsal striatum, which is the area that receives dopamine produced
in the substantia nigra and is lost in PD.
Results: Inhibition
of striatal p11 significantly improved spontaneous motor function in both
normal and 6-OHDA mice. In 6-OHDA mice, blocking p11 on the “lesioned” side
significantly reduced the rotations that these mice develop in response to D1
and D2 receptor specific agonists and L-Dopa. This indicates that the animals
are less-sensitive to the dopamine-like drugs following blockade of p11 in the
striatum on the side in which the normal dopamine-producing cells were
destroyed. Furthermore, we expanded these findings by studying the relationship
between L-Dopa-induced dyskinesias and p11 expression. L-Dopa is the most
commonly used drug in the treatment of PD; however chronic use of L-Dopa often
leads to a variety of complications, including dyskinesias. We have scored the
dyskinesias over 3 weeks of L-Dopa treatment and observed that inhibiting
striatal p11 expression significantly reduced the dyskinesias by 50% when
compared to control mice. Taken together our results demonstrate that loss of
P11 in the dorsal striatum reduces dopamine responsiveness through a mechanism
that modifies dopamine receptors activity. Furthermore, we show that normal
striatal p11 levels are necessary for full expression of L-Dopa-induced
dyskinesias. This also suggests that blocking striatal p11 actions may be a
potential therapeutic target to improve striatal function and treat dyskinesias
following chronic dopaminergic drug therapy.
P08.04
Dopamine inhibits protein
L-isoaspartyl methyltransferase at both protein and gene levelsin SH-SY5Y cells
Dahmane Ouazia1, Louis-Charles Jr. Levros2, Éric
Rassart2, Richard Desrosiers1
1Département de Chimie, Université du Québec À
Montréal, Montréal, Québec, Canada
2Département de Sciences Biologiques, Université du
Québec À Montréal, Montréal, Québec, Canada
Objective: Parkinson’s disease
(PD) is a chronic and progressive neurological disorder that is characterized
by the loss of dopaminergic neurons in the substantia nigra. Dopamine, via the
oxidative stress that it generates in the cytosol, could contribute to the
selective loss of neurons observed in PD. Protein L-isoaspartyl
methyltransferase (PIMT) is an enzyme, with antiapoptotic properties, that
repairs L-isoaspartyl-containing proteins. PIMT expression has been shown to
decrease with age. Together, these observations prompted us to investigate
whether dopamine can regulate PIMT expression in SH-SY5Y neuroblastoma cells.
Methods: Protein expression was
monitored by Western blotting whereas gene promoter activity was measured using
dual luciferase assay. Truncated and mutated versions of the PCMT1 gene
promoter were synthesized by PCR to identify the regions that are sensitive to
dopamine action. Cell viability was measured via the MTT assay and reactive
oxygen species (ROS) production was measured via a fluorescent probe.
Results: Cells treated with
dopamine showed a PIMT down-regulation at both protein and gene levels. The
same down-regulation of PIMT protein was caused by the electron transport chain
inhibitor, rotenone, which was accompanied, in both cases, by an increase in
cell death and ROS production. PIMT dopamine-associated down-regulation was
blocked by N-acetyl cysteine pre-treatment resulting in a decrease in cell
death and ROS levels.
PCMT1 promoter mapping
experiments allowed the identifying of a 55 bp-long dopaminesensitive region.
The inhibition of PCMT1 transcription was mediated by dopamine-induced ROS. In
addition, H2O2 inhibited in a dose-dependent manner the transcriptional
activity of PCMT1 promoter. Therefore, PIMT could be a target of choice during
neuronal cell death observed in PD. This would be mediated by the ROS generated
from cytosolic dopamine that reduces the PCMT1 gene promoter activity and the
PIMT protein stability.
PC08.05
Striatal
pre-enkephalin overexpression improves motor symptoms and neuronal insults in
the MPTP mouse model of Parkinson’s disease
Bissonnette Stéphanie1, Muratot Sophie1,
Hébert S. Sébastien1, 2, Samadi Pershia1, 2.
1Axe
Neurosciences, Centre de recherche du CHU de Québec, CHUL, Québec, QC, Canada
2Département
de psychiatrie et de neurosciences, Université Laval, Québec, QC, Canada
In
Parkinson's disease (PD), the nigrostriatal lesion is associated with an
upregulation of opioid peptide pre-enkephalin (pENK) in striatopallidal
neurons. Our previous results using the MPTP parkinsonian monkeys suggested
that increased expression of pENK is a compensatory response to alleviate PD
motor symptoms. However, the exact function of this increase is still unknown.
Objective: To
determine the functional role of striatal pENK in motor behavior, and to define
whether striatal pENK may have a protective effect against the neurotoxin
insults in the MPTP mouse model of PD.
Methods: Viral
vector gene transfer was used to overexpress striatal pENK before dopamine
depletion by MPTP (i.p.). Various methodologies were carried out to assess
motor behavior, the site of injection, the level of pENK mRNA, the integrity of
nigrostriatal dopaminergic terminals, and the number of dopaminergic neurons in
the substantia nigra compacta (SNc).
Results: Our
results show that mice overexpressing pENK displayed higher locomotor activity
compared to control groups. This effect was significantly and positively
correlated with pENK mRNA expression in the striatum. Moreover, overexpression
of striatal pENK improved the impairment of associative learning task induced
by neurotoxin MPTP. Higher density of striatal tyrosine hydroxylase (TH)
positive fibers was also detected in mice with pENK overexpression in different
regions of the striatum compared to control groups. In addition, the number of
TH positive neurons in SNc of MPTP-treated mice with striatal pENK
overexpression was higher than mice treated with MPTP alone.
Conclusion: These
results provide evidence that upregulation of striatal pENK can be involved in
the delay of the appearance of PD motor symptoms, and may also have protective
effect against the MPTP insults at nigrostriatal dopaminergic nerve terminals.
Acknowledgment: This
work was supported by Parkinson’s Society of Canada.
P08.06
Differential morphological changes of D2
versus D1-expressing striatal neurons in a transgenic mice model of
Parkinson’s disease
Maria Gabriela Sánchez, Cyril Bories, Dave Gagnon, Yves
De Koninck, Jean-Martin Beaulieu, André Parent, Martin Parent.
Centre de recherche de
l’Institut universitaire en santé mentale de Québec, Department of psychiatry
and neuroscience, Faculty of medicine, Université Laval, Quebec City, QC,
Canada
Objective: Parkinson's disease involves a progressive loss of
substantia nigra pars compacta neurons resulting in a decrease of striatal
dopaminergic innervation. Such denervation is known to differentially affect
striatal projection neurons expressing dopaminergic receptors of the D1
type and which are involved in the direct pathway, compared to those expressing
the D2 type at the origin of the indirect pathway. The specific
consequences of such denervation on fine dendritic processes being poorly
known, we attempted to characterize morphological changes of three different
types of striatal projection neurons: the D1+, the D2+
and the D1+/D2+ medium spiny neurons, after dopaminergic
denervation.
Methods: We used
double transgenic BAC mice Drd1a-tdTomato/Drd2-EGFP
allowing
the identification of the direct and indirect striatal projection neurons based
on their dopamine receptor content. Striatal dopaminergic denervation was
induced by unilateral injections of 6-hydroxydopamine in the medial forebrain
bundle. Cylinder test and immunohistochemistry staining of tyrosine hydroxylase
and dopamine transporter confirmed the extent of the lesion. Single-cell intraneuronal injections of
Lucifer yellow combined to immunohistochemistry were applied to the D1+,
D2+ and the D1+/D2+ striatal neurons. Detailed
morphometric
analyses of dendritic trees and spines as well as their glutamatergic afferents
were performed on high-resolution images acquired from a confocal imaging system.
Results: Our results indicate that dopaminergic denervation causes a decrease in
dendritic length and dendritic spines density that is more pronounced in the D2+ neurons of the indirect pathway. Preliminary data indicate that a
reorganization of the corticostriatal projections also contribute to the
neuroplastic changes observed. Our data provide direct evidence for selective
morphological alterations of the D2+ striatopallidal neurons
involved in the indirect pathway following dopaminergic denervation of the
striatum that characterizes Parkinson’s disease.
P08.07
The effect of noradrenaline depletion on motor impairment and dopamine
cell loss in a rat model of Parkinson’s disease
Eunju Jenny Shin1, James Rogers1, Anders Björklund1,
Manolo Carta2
1 Lund University, Lund, Sweden
2 Cagliari University, Monserrato, Italy
Objective: Parkinson’s disease (PD) has been
mainly known as a neurodegenerative disease with loss of dopaminergic (DA)
neurons in the substantia nigra. However, studies of post mortem PD brains have
shown that not only DA neurons but also the noradrenergic (NA) neurons in the
locus coeruleus degenerate, and that the NA neurodegeneration may be as
profound, and also precedes degeneration of the midbrain DA neurons. The early
involvement of the NA system is also in line with the caudal-to-rostral disease
progression predicted by the model proposed by Braak et al. Hence, we have
investigated the effect of NA depletion on motor deficits and DA cell loss in a
rat PD model.
Methods: To generate two lesion
paradigms, rats were injected with a dopamine toxin, 6-OHDA in striatum and/or
a NA toxin, DBH-saporin in lateral ventricles. Animals have been tested in a
battery of behavioural tests to check the degree of motor impairment. Perfused
tissues were then subjected to immunohistochemistry to assess the amount of
degeneration in striatal DA fiber and nigral DA neurons.
Results: In three motor tests (cylinder,
amphetamine-induced rotation, and corridor tests) there was no significant
difference in motor deficit between groups. However, the DA- and NA-lesioned
animals showed more severe motor deficits than the DA-lesioned animals in
stepping, staircase, and rotarod tests. Post mortem analysis revealed that NA
depletion did not affect the degree of DA loss in striatum and substantia nigra
determined by optical densitometry with tyrosine hydroxylase staining and
stereological cell estimation with vesicular monoamine transporter staining,
respectively. These results suggest that Parkinsonian-like motor symptoms could
be worsened by NA degeneration and it is not due to more profound DA cell
degeneration upon NA removal but maybe by dysregulated DA cell function.
BASIC SCIENCE: NEUROPHARMACOLOGY
P09.01
Neuroprotection
and neurorescue properties of Sitagliptin in 6-hydroxydopamine rodent model of
Parkinson’s disease
Jayasankar
Kosaraju1, Santhivardhan Chinni2, Anil Dubala3,
Rizwan Basha Kharwal3, M.N. Satish Kumar2, Duraiswamy
Basavan1
1Department of Pharmacognosy, JSS College of Pharmacy,
Udhagamandalam, Tamilnadu, India
2Department of Pharmacology, JSS College of Pharmacy,
Udhagamandalam, Tamilnadu, India
3Department of Pharmaceutical Biotechnology, JSS College of
Pharmacy, Udhagamandalam, Tamilnadu, India
Objective: Type 2 diabetes (T2D) is
one of the major risk factors associated with Parkinson’s disease (PD).
Pharmacological agents, such as glucagon-like peptide-1 (GLP-1) which
ameliorates T2D, have become valuable candidates as disease modifying agents in
the treatment of PD. In addition, endogenous GLP-1 possesses neuroprotective
properties in PD. GLP-1 can be increased by inhibiting dipeptidyl peptidase-4
(DPP-4). The present study examines the efficacy of Sitagliptin, a DPP-4
inhibitor in a 6-hydroxydopamine (6-OHDA) induced rat model of PD.
Methods: Three weeks following induction of PD by
intracerebral administration of 6-OHDA, animals were orally administered with
Sitagliptin (5, 10 and 20 mg/kg) for 30 days.
The effect of the DPP-4 inhibitor on brain GLP-1 and
dopamine levels, oxidative stress, and behavioral tests were evaluated.
Results: The results reveal an attenuation of oxidative stress, improved brain GLP-1 and
dopamine levels following treatment. This remarkable therapeutic effect of
Sitagliptin mediated through DPP-4 inhibition demonstrates a unique mechanism
for protecting dopaminergic neurons by increasing GLP-1 levels and reverses the
key deficits and pathology observed in PD.
P09.02
The influence of pramipexole and imipramine on behavioral
and biochemical parameters in animal model of pre-clinical stage of PD and
comorbid depression
Katarzyna Kuter1, Klemencja
Berghauzen-Maciejewska1, Wacław Kolasiewicz1,
Urszula Głowacka1, Jadwiga Wardas1, Krystyna
Ossowska1
1Department
of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of
Sciences, Krakow, Poland
Objective: The motor dysfunction in
Parkinson’s disease (PD) is frequently preceded by comorbid depression.
Dysfunction of monoaminergic systems could be its underlying cause. Recent
studies have suggested that the administration of mixed dopamine D2/D3 receptor
agonist - pramipexole may reduce both motor symptoms and depression in PD. The
aim of study was to compare the influence of classic antidepressant -
imipramine and pramipexole on the “depressive-like” behavior and monoaminergic
systems parameters of rats with moderate lesion of the nigrostriatal system.
Methods: Male Wistar rats were
stereotactically injected, bilaterally, with 6-OHDA (15 µg/2.5 µl) into the
ventral striatum (vSTR). Imipramine was injected i.p. (10 mg/kg) once a day and
pramipexole s.c. (1 mg/kg) twice a day, both for 14 days. On the 15th day after
the surgery the locomotor activity test and forced swimming test (FST) were
performed. The lesion extent was analyzed by HPLC and tissue content of
monoamines and their metabolites and immunohistochemically. Also
autoradiographic binding of ligands to dopaminergic and noradrenergic
transporters were analyzed.
Results: The lesion of vSTR did not
influence the locomotor activity of rats but increased immobility and swimming
and decreased climbing in FST, suggesting depressive-like changes, not induced
by motor disturbances. All the above disturbances observed in FST were
decreased by pramipexole. Imipramine increased only climbing, but had no
influence on immobility in lesioned rats. Pramipexole and imipramine had no
influence on dopamine levels in lesioned rats. Pramipexole increased levels of
DA metabolites in striatum and n.accumbens and increased the turnover of
dopamine both in control and lesioned rats.
These
results indicate that moderate, presymptomatic dopaminergic lesion may induce
“depressive-like” symptoms which are reversed by dopamine agonist but not by a
classic antidepressant.
Acknowledgements: Study
supported by "DeMeTer"
(POIG.01.01.02-12-004/09-00),
co-financed by EU from European Regional Development Fund, part of the
Operational Programme "Innovative Economy 2007-2013".
P09.03
The effect of a chronic treatment with MPEP, an mGlu5
receptor antagonist, on brain basal ganglia D1/D2 receptors,
preproenkephalin/preprodynorphin mRNA levels and ERK/Akt signaling pathways in
de novo parkinsonian monkeys
Nicolas Morin1,2, Vincent Jourdain1,2,
Marc Morissette1, Laurent Grégoire1 and Thérèse Di Paolo1,2
1Neuroscience
Research Unit, Centre de recherche du CHU de Québec,
Quebec City, QC, Canada
2Faculty of Pharmacy, Laval University,
Quebec City, QC, Canada
Objective: The objective of this study
was to investigate the long-term effect of the prototypal metabotropic
glutamate 5 (mGlu5) receptor antagonist 2-methyl-6-(phenylethynyl)pyridine
(MPEP) with L-3,4-dihydroxyphenylalanine (L-DOPA) on dopamine (DA) receptors,
preproenkephalin (PPE), preprodynorphin (PPD), ERK and Akt signaling in monkeys
lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
Methods: MPTP monkeys were treated for
one month with L-DOPA and developed dyskinesias while those treated with L-DOPA
and MPEP (10 mg/kg) developed significantly less L-DOPA-induced dyskinesias (LID). Normal control and
saline-treated MPTP monkeys were also included for biochemical analysis.
Results: [3H]SCH-23390 specific
binding to striatal D1 receptors was decreased in all MPTP monkeys compared to controls and no difference was observed between saline,
L-DOPA and L-DOPA+MPEP-treated monkeys. Striatal D1 receptor mRNA levels
remained unchanged for all experimental groups and did not correlate with D1
receptor specific binding. [3H]raclopride specific binding to
striatal D2 receptors was increased in saline and L-DOPA+MPEP-treated monkeys
as compared to control and L-DOPA-treated monkeys, no difference between the
latter groups was observed. The same pattern of changes as [3H]raclopride
specific binding was observed for striatal D2 receptor mRNA levels with a
positive correlation between these measures. Following L-DOPA treatment, PPE
and PPD mRNA levels and the relative levels of phosphorylated ERK1/2 and
phosphorylated Akt/GSK3 increased in the striatum of L-DOPA-treated monkeys
compared to control, saline and L-DOPA+MPEP groups. By contrast, in the latter
experiments, no change in the L-DOPA+MPEP group compared to control and
saline-treated monkeys in the striatum was observed and there were positive
correlations between these measures and mean dyskinesia scores of the MPTP
monkeys. A chronic treatment with MPEP reduced the development of LID and was
associated with a normalization of striatal D2 receptors, PPE/PPD mRNA levels
and ERK/Akt signaling, while D1 receptors remained unchanged.
P09.04
A novel
mGlu5 receptor antagonist, LY2300979, restores motor function and normalises abnormal beta oscillations observed in animal models of Parkinson’s disease
Tracey K. Murray1, Keith Phillips1, Keith A. Wafford1,
Vanessa Barth2, Patrick Love3, Anita Teepool3,
D.O. Kellett1, Dale M. Edgar1, Wesley Seidel1,
Magnus W. Walter1, Bruce Dressman2, James A. Monn2, David L. Mckinzie2 ,
Michael J. O’Neill1
1Eli Lilly & Co. Ltd, Lilly Research Centre, Sunninghill Road,
Windlesham, Surrey, UK
2Eli Lilly & Co., Lilly Corporate Centre, Indianapolis, IN, USA
3Covance Laboratories, Greenfield, IN, USA
Objective: Metabotropic glutamate
receptor 5 (mGlu5) are G-protein coupled receptors that are highly localized in
limbic, basal ganglia and cortical brain regions. It has been reported that
mGlu5 receptors may play a critical role in motor dysfunction in (Parkinson's
disease) PD and the expression of mGlu5 is increased in both rat and monkey PD
models that exhibit L-DOPA-induced dyskinesias (LIDs). In addition mGlu5
antagonists such MPEP and MTEP reduces the severity of these LIDs and attenuate
the biochemical and molecular changes associated with dyskinesia.
Methods: We profiled a novel
mGlu5 antagonist, 5-[2-(1H-pyrazol-4-yl)ethynyl]pyridine-3-carbonitrile or
LY2300979, in vitro and in vivo. We then went on to study the efficacy
of the compound in a range of models of Parkinson’s disease in mice and rats.
Results: In vitro data indicated that
LY2300979 had good selectivity and functional negative allosteric activity for
mGlu5 rat and human receptor sub-types. LY2300979 exhibited good CNS
penetration and displaced MPEPy (ED50 = 2.3 mg/kg in mice and 1.4
mg/kg in rat) and ABP688 (ED50 2.2 mg/kg in rat) binding in the
rodent brain following oral administration. In addition, receptor occupancy and
pharmacokinetic data indicated that the compound provided
pharmacologically-relevant levels of target engagement for 6-8hr post-dosing.
Confirmed using sleep EEG, in which an increase in NREM sleep and a reduction of REM sleep
persisted for 8-10hr.
In
symptomatic models of PD, LY2300979 increased habituated locomotor activity and
reversed reserpine-induced akinesia in mice. Synchronized oscillatory neuronal
activity in the beta frequency range has been observed in the basal ganglia of
PD patients and is thought to mediate the initiation of bradykinesia. LY2300979
(10 and 30 mg/kg) normalised the 6-OHDA induced-increases in beta oscillations
in rats. In summary, these data indicate that LY2300979 has broad
pharmacological activity across a range of preclinical models of PD.
P09.05
GCSF
improves behavioral and motor coordination, monoamine levels and associates
depression in 6-OHDA induced experimental model of Parkinson’s disease (PD)
Prakash
A1, Medhi B1
and Chopra K2
1Department
of Pharmacology, Research Block: B, Post graduate Institute of Medical
Education and Research (PGIMER), Chandigarh, India
2Pharmacology
research laboratory, University Institute of Pharmaceutical Sciences (UIPS),
Panjab University, Sector 14, Chandigarh, India
Objective: Experimental
evidenced suggested role of oxidants levels, behavioral (motor) deficit,
locomotion and loss of dopaminergic neurons in SNc in Parkinson’s disease. In
our recent work we have seen the neuroprotective and neurogenesis effect of
GCSF in an in vivo model of
Alzheimer’s disease. In the present study, we have aimed to elucidate the
neuroprotective role in Parkinson’s disease, 2nd most common
neurodegenerative disease. Published literature showed unilateral intrastriatal 6-hydroxydopamine
(6-OHDA) administration produces motor decline and depressive-like
behaviors which resembles Parkinson’s disease.
Methods: In a
parallel designed experimental model, animals were divided into seven groups.
After selectively insult with 6-OHDA (12µg in 4µl) in substantial nigra par
compacta (SNc) rats were treated with the GCSF, carbidopa/levodopa and their
combinations. Neuroprotection and improvement in neuroamines were assessed with
battery of behavioral tests, biochemical and ROS levels. All results were
selectively correlated with histopathological finding of the study.
Results: 6-OHDA
significantly induced motor loss and Parkinson’s like behavior in rats. The muscle coordination, exploratory and
rotation behaviors were improved significantly in the GCSF alone and in
combination with the L-DOPA/carbidopa (p<0.05). Muscle rigidity was
significantly corrected in the adhesive tests (p<0.05) and ROS levels were
significantly declined in GCSF treated rats (p<0.05). FST observation
suggested that depression associated with the PD was also found to be
ameliorated in FST exposed rats. GCSF improved neuroprotection and
increased monoamine levels at the SNc. The important finding of the study, GCSF
also ameliorated depression like behavior associated with Parkinson ’s disease.
Conclusion:
Hence,
the present study concluded that GCSF not only improved Parkinson’s like
behavior and monoamines level in SNc but also co-morbid depression.
BASIC SCIENCE: ELECTROPHYSIOLOGY &
FUNCTIONAL IMAGING, OPTOGENETICS
P10.01
A functional magnetic
resonance imaging approach towards understanding the circuit-level effects of
deep brain stimulation
Daniel Albaugh1-3,
John Younce1,2, Hsin-Yi Lai1,2, Yen-Yu Ian Shih1-3
1Department of
Neurology, University of North Carolina at Chapel Hill School of Medicine,
Chapel Hill, NC, USA
2Biomedical Research
Imaging Center, University of North Carolina at Chapel Hill School of Medicine,
Chapel Hill, NC, USA
3Curriculum in
Neurobiology, University of North Carolina at Chapel Hill School of Medicine,
Chapel Hill, NC, USA
Objective: To evaluate, on a
whole-brain scale, the neural circuitry modulated by deep brain stimulation
(DBS) at the subthalamic nucleus (STN) and internal globus pallidus (GPi) in a
rat model.
Methods: The present study employed
blood-oxygen-level-dependent (BOLD) and cerebral blood volume (CBV) functional
magnetic resonance imaging (fMRI) to evaluate the global modulatory effects of
deep brain stimulation at the STN or GPi. Anesthetized rats were implanted with
2-channel tungsten microwire electrodes and stimulated at a range of
frequencies (10-400Hz) during fMRI acquisition with a 9.4 Tesla system. An iron
oxide contrast agent (MION, 30 mg/kg) was administered intravenously for CBV
measurements.
Results: Robust, frequency
dependent positive BOLD activation was observed in the ipsilateral motor,
somatosensory, and cingulate cortices during stimulation at either the STN or
GPi. Interestingly, these cortical responses were maximal at high frequencies
(100-130Hz) known to be therapeutic for Parkinson’s Disease. Contralateral
negative BOLD responses were additionally observed during DBS at the GPi, and
occurred diffusely throughout cortex and subcortical areas. This negative
response peaked at 40Hz, suggesting recruitment of a functionally distinct
circuit- possibly off-target stimulation of the neighboring internal capsule.
Further analysis of DBS circuit modulation using the more sensitive CBV readout
at the STN target revealed additional areas of DBS effects, including discrete
sites of thalamic activation and striatal responses both ipsi-and contralateral
to the stimulation site. Future experiments will confirm and extend these
findings using a parkinsonian rat model. This study introduced a novel imaging
methodology for studying DBS effects in animal models. The combination of DBS
with fMRI would permit examination of DBS circuits and has potential to
ultimately address a prevailing question in DBS therapy, namely, how DBS
modulates neural activity in different brain regions to achieve symptom
alleviation.
P10.02
Brain networks
involved in dance: a model mechanism for examining plasticity during dance
therapy.
Joseph FX DeSouza1,2,
Rachel J. Bar1, Hedieh Tehrani1
1Centre for Vision
Research, Department of Psychology, York University, Toronto, ON
2Department of Biology,
Neuroscience Graduate Diploma Program, CAPnet, York University, Toronto, ON
Objective: Our research program
examines the neural mechanisms of dance, with a future goal to then examine
dance in Parkinson’s disease (Earhart 2009). Although the neural mechanisms of
dance have been examined, these mechanisms have not been probed during learning
of a novel dance routine in expert, normal and in abnormal brains. Thus, our
long term goals are to examine the plasticity that occurs during learning. To
this date we have begun examining this in experts and normal controls.
Method: Ten dancers were
scanned over 8 months as they learned a choreographed. Eleven controls included
both dancers and non-dancers. Dancers were scanned up to 4 times.
Results: Using task based
random effects GLMs while the subjects visualized their dance during fMRI
scans, we found supplementary motor cortex (SMA), auditory, premotor and
parietal cortices activated with an increasing pattern up to 7 weeks of
learning/performing. This was followed by a decrease at 8 months (n=5). We will
contrast these functional findings with structural diffusion tensor imaging
(DTI) scans at three different times during learning (1, 7 and 32 weeks), using
SMA and auditory regions of interest to probe for structural changes.
Additionally, we found that the basal ganglia (caudate) activated after the 7th
week up to 34 weeks. This suggests that while experts visualize a learned
dance, their cortical network of activation decreases once the dance is
learned, while basal ganglia activation remains activated. This procedure would
be possible for PD patients since the whole scanning sequence lasts 12 minutes.
P10.03
Quantitative evaluation of hypokinesia in Parkinson disease using
sensor gloves
Tomás Díaz
Vera1, Lázaro Gómez Fernández1, Mario Álvarez Sánchez1,
Amado Díaz de la Fe1, Eduardo Martínez Montes2
1International
Center for Neurological Restoration (CIREN), Havana, Cuba
2Cuban Neuroscience
Center, Dpto de Neuroestadística, Havana, Cuba
Objective: To
evaluate the utility of sensor gloves on quantitative evaluation of
bradykinesia on Parkinson's Disease.
Methods: The
authors carried out a study of type cases and controls, organized in two
groups: 13 patients with clinical diagnosis of idiopathic PD in “on” state and
24 controls, to which were carried out a registration of the "finger
tapping" movement using sensor gloves (5DT-14Ultra) the analysis of the
amplitude was calculated through the power spectra derived from a Fourier
Transform (FFT). Also we examine the relationship between glove data obtained,
the clinical scale employed (UPDRS) and the early and late components of the
premotor potential.
Results: The authors
observed that patients presented a smaller speed in the execution of the
movements, demonstrated to reach their maximum amplitude at smaller movement
frequency (1,5-2Hz) than controls (3,5-4Hz), as well as, a significant decrease
of the amplitude of movement toward the frequencies of movement =3Hz. The most
favorable values in the clinical scale employed were in connection with broader
movements toward the high frequencies (=3.5Hz). Our study demonstrated a
relationship between amplitude of movement and the area of the earlier and
later components of the premotor potential. A bigger area associated to a
broader movement.
Conclusion: The
authors conclude that sensor gloves are a useful device as quantitative
complement of the clinical evaluation in the patients with PD.
P10.04
Pre- and post-synaptic dopaminergic dysfunction in
multiple system atrophy: combined [18F]FP-CIT and [18F]FDG-PET study
Mi-Jung Kim,1
Jae Seung Kim,2 Sooyeoun You,3 Young Jin Kim, ,4
Sung Reul Kim,5 Sun Ju Chung4
1Department of
Neurology, Bobath Memorial Hospital, Seongnam, Republic of Korea
2Department of Nuclear
Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul,
Republic of Korea
3Department of Neurology,
Dongsan Medical Center, Keimyung University, Daegu, Republic of Korea
4Department of
Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul,
Republic of Korea
5Department of Nursing,
Chonbuk National University, Jeonju, Republic of Korea
Objective: To investigate the
integrity of presynaptic nigral and postsynaptic striatal dopaminergic systems
in MSA patients, especially in relation to the presence of parkinsonism
Methods: We studied 26
patients who were diagnosed with probable or possible MSA based on the
second consensus statement on the diagnosis of MSA and underwent both [18F]FP-CIT
PET and [18F]FDG PET. The PET images were analyzed with 12 striatial
subregional volume-of-interest templates (bilateral ventral striatum, anterior
and posterior caudate, anterior, posterior and ventral putamen). The PET
results of study subjects were compared with the results of age-matched normal
controls.
Results: Of 26 MSA patients,
eight patients had no parkinsonism. Between MSA patients with parkinsonism and
those without parkinsonism, there were no significant differences in age at
onset, age at study, sex, disease duration, and
global disability scale.
Seven (87.5%) MSA patients without parkinsonism, and all MSA patients with
parkinsonism revealed decreased striatal binding value in the [18F]FP-CIT
PET. In five (62.5%) MSA patients without parkinsonism and 14 (77.8%) MSA
patients with parkinsonism showed decreased striatal glucose metabolism in [18F]FDG
PET. The dissociation between [18F]FP-CIT PET and [18F]FDG
PET were considered in 11 MSA patients with parkinsonism and 6 MSA patients
without parkinsonism. In quantitative analyses, the binding values of [18F]FP-CIT
PET and [18F]FDG PET are correlated in the caudate region (r = 0.504,
p = 0.009), but not correlated in the
putamen region.
Conclusions: High prevalence of
subclinical dopaminergic denervation in MSA without parkinsonism could suggest
that the evaluation of dopaminergic system using PET scans might be useful in
differential diagnosis of cerebellar ataxia. The dissociation between
presynaptic and postsynaptic dopaminergic denervation in MSA patients suggest
the presence of presynatic type parkinsonism in MSA. Further research is needed
to find out levodopa responsiveness according to the dissociation of
presynaptic and postsynaptic dopaminergic denervation.
P10.05
Changes
in resting state EEG following motor performance in PD.
Clara Moisello, Daniella Blanco, Jing Lin, Andrea
Loggini, Alessandro Di Rocco, M Felice Ghilardi
1CUNY Medical
School, NY, USA
2NYU School of
Medicine, NY, USA
Objective: We have recently found that the spontaneous resting-state EEG of normal
subjects shows frequency specific changes after a forty-minute visual task. As they
are confined to the areas involved in the task, these changes or traces likely
reflect use-dependent plasticity. Here, we determined whether patients with PD,
a disease associated with abnormal plasticity, show similar frequency-specific
changes in the resting state EEG after a forty-minute motor task as normal
controls.
Methods: Twenty-three patients with PD (stage 2 and 3) and 20 age-matched
controls performed a forty-minute reaching motor task with their right dominant
hand. High-density EEG was recorded in the eyes-open resting state (3 minutes)
before (RS1) and after (RS2) the motor task. We performed spectral analysis to
identify individual alpha peak (IAP) value; we aligned each individual power
spectrum on the peak. With permutation t-tests within each group, we identified
local changes. As task-related power changes were spread across the entire
scalp, average scalp power in different frequency bands was then submitted to a
mixed-model ANOVA with Time (RS1, RS2) and Group (PD, Controls) as main factors.
Results: Confirming previous results, IAP of patients was significantly lower
(9.0±1.1 Hz) than controls (9.8±1.0 Hz, p=0.01). Moreover, after the
forty-minute motor task, IAP decreased further in PD (-0.2±0.4 Hz, p=0.04) but
not in controls (+0.1±0.6 Hz, p=0.50). After the task, comparison of power on
the whole scalp showed widespread increases in alpha and beta bands in both
groups, without significant changes for theta and gamma. Average Alpha power
increased significantly after task in patients (p=0.0001) but not in controls
(p=0.63). Instead, Beta power showed a similar significant post-task increase
in both groups (p<0.03). These results indicate that motor performance
induced power increases in both groups, but only PD shows also involvement of
lower frequencies, a possible sign of abnormal plasticity.
P10.06
Increase of Intra-motor-network
connectivity in Parkinson’s disease patients – an fMRI study with graph theory
approach –
Atsuko
Nagano-Saito,1,2 Kristina Martinu,1,2 Oury Monchi1,2
1Centre de Recherche, Institut universitaire de
Gé́riatrie de Montréal, Montréal, QC, Canada
2Department of Radiology,
Université́ de Montréal, Montréal, QC, Canada
Objective:
Over-activation in the motor cortex has been reported in animal
models of Parkinson’s disease (PD), and PD patients, during resting state and
tasks. We hypothesized that the connections within the motor network increases
in PD, and investigated this hypothesis.
Methods: Fourteen
healthy volunteers and twelve PD patients performed a series of finger movement
tasks, involving self-initiated (SI), externally triggered (ET) and control
finger movements while being scanned with functional MRI. Fifty-eight regions of interest (ROIs) were selected in areas where
task-related significant activation occurred in the HV group, and divided into
two categories, the motor related areas (MTR) and the others (VisInt). Using a
specified connection number (388 connections corresponding to 23.5% of all the
connections), between ROIs, counting from the strongest connection, we counted
the number of ROIs within the intra-MTR, intra-VisInt, and between MTR-VisInt
networks, respectively. Using simple t-test, each number was compared between
the HV and PD. Correlational rate was
calculated between the number of the intra-MTR and the UPDRS motor score.
Significance level was set at p < 0.05.
Results: The number
of intra-MTR connection was significantly greater in the PD than in the HV
group (p = 0.027). The other numbers were not significantly different between
groups. The number of the intra-MTR was negatively correlated to the UPDRS
motor scores (r = -0.80, p = 0.002). We speculate that the increase of the
intra-MTR connectivity might be related to the motor dysfunction in PD, which
is more prominent for demanding tasks, but that might be compensatory for
relatively simple movement.
P10.07
Disease
and sex-related differences in daily electromyography influence functional
performance in Parkinson’s disease
Kaitlyn P. Roland1,
Gareth R. Jones2, Jennifer M. Jakobi2
1Centre on Aging,
University of Victoria, Victoria, BC, Canada
2School of Health and
Exercise Sciences, University of British Columbia Okanagan, Kelowna, BC, Canada
Electromyography (EMG) recordings made
bilaterally may reveal important information about asymmetric muscle activation
patterns associated with reduced functional performance in Parkinson’s disease
(PD). Also, sex-differences in muscle activation patterns would contribute to
understanding underlying causes of differential functional decline between
males and females with PD.
Objective: Quantify daily muscle quiescence through EMG
gap analysis and examine handgrip-strength in PD-females (n=13) and PD-males
(n=10) (Hoehn/Yahr=2.1± 0.7) compared with age-matched controls. Hypothesis:
muscle quiescence will be less in PD compared with controls and fewer EMG gaps
will be observed in PD-females compared with PD-males. The more-affected PD
side will demonstrate fewer EMG gaps and greater weakness relative to
less-affected.
Methods: Bilateral
daily EMG was recorded (7-hours) and normalized to
maximal voluntary exertions (MVE). EMG gap was
defined as <1%
amplitude of MVE for >0.1 sec and characterized as number, duration and time
occupied by gaps. Handgrip-strength was evaluated with a
dynamometer. Three-way
repeated-measures ANOVA examined differences in gap characteristics and
strength.
Results: Percentage of time leg
muscles were quiescent was less in PD compared with controls as a result of
shorter EMG gaps (p<0.04), suggesting greater burst activity in PD. Fewer
periods of muscle quiescence in PD-females compared with PD-males (p=0.004)
suggests that female muscles have less opportunity to rest and recover, and
indicates greater muscle activity necessary to execute daily activities.
PD-females were weaker than PD-males (p=0.00) for handgrip-strength. Fewer gaps
were observed on more-affected PD side (p=0.01) and decreased grip strength in
more-affected hand (p=0.04). Handgrip weakness in PD compared to controls
(p=0.04) likely results from peripheral changes and slowed onset of voluntary
contractions. Bilateral quantification of daily muscle quiescence
provides insight into the underlying neuromuscular contribution to declines in
functional performance, reflecting central and peripheral changes that may
explain differences in muscle weakness, in males and females with PD.
P10.08
Altered striatal spiny neuron activity as a therapeutic target in
Parkinson’s disease
Arun Singh1, Klaus Mewes2, Robert Gross2,
Mahlon R. DeLong2, Stella M. Papa1, 2
1Yerkes
National Primate Research Center, Emory University Atlanta, GA, USA
2Department
of Neurology, Emory University School of Medicine, Atlanta, GA, USA
Objective: The loss of striatal dopaminergic modulation
in Parkinson’s disease (PD) presumably leads to changes in firing rate and
patterns of striatal output neurons (medium spiny neurons, MSNs). The status of
the MSN activity has not yet been described in PD, and thus, we examined the
parameters of the MSN firing in patients undergoing DBS surgery.
Methods: We analyzed striatal data obtained during electrophysiologic
mapping for DBS treatment in PD patients, along with dystonia and essential
tremor (ET) patients for comparison. Strict criteria were applied for MSN
classification.
Results: The mean firing rate of MSNs was significantly higher in PD (32±9
Hz) than dystonia (9.5±4 Hz) and ET (<3 Hz). In PD, a larger fraction of
striatal neurons also exhibited burst activity. These findings are aligned with
previous data from parkinsonian monkeys (Liang et al., 2008), challenging the
classic functional model of PD. The role of glutamatergic hyperactivity in
these striatal changes suggests that manipulating the glutamate signaling is
critical for improved responses to dopamine replacement. The less increased
frequencies in dystonia highlight the relevance of specifically high MSN
activity to PD, but also suggest that there may be grounds for the frequently
alluded Dystonia-PD continuum. The very low firing rates in ET resemble MSN
activity in normal monkeys, suggesting a parallel with normal humans. These
findings demonstrate profound alterations of the MSN discharge in patients with
PD, and point to the importance of investigating its molecular basis to develop
function-restorative therapies.
References: Liang L, DeLong MR, Papa SM. Inversion of
dopamine responses in striatal medium spiny neurons and involuntary movements.
J Neurosci. 2008 Jul 23;28(30):7537-47.
P10.09
Restoration of normal striatal dopamine responses with NMDA
receptor blockade
Arun Singh1, Lisa F. Potts1, Kenneth J.
Burke1, Jessica S. Whithear1, Bhagya Laxmi Dyavar Shetty1,
Stella M. Papa1, 2
1Yerkes
National Primate Research Center, Emory University Atlanta, GA, USA
2Department
of Neurology, Emory University School of Medicine, Atlanta, GA, USA
Objective: Dopaminergic innervation of medium spiny
neurons (MSN) of the striatum is essential for normal motor behavior. However,
in patients with idiopathic Parkinson’s disease (PD), long-term levodopa replacement
therapy is associated with debilitating motor complications such as involuntary
choreodystonic movements (levodopa-induced dyskinesias, LID). In non-human
primate models of advanced parkinsonism with chronic levodopa therapy, MSNs are
profoundly hyperactive and often exhibit reversal of levodopa-induced firing
rate changes (“inversions”) that is highly correlated with the onset of LID
(Liang et al., 2008). It was hypothesized that baseline hyperactivity mediated
by hyperglutamatergic tone may lead to these abnormal inversions, and play
ultimately a primary role in the mechanisms of LID.
Methods: The electrophysiological effects of striatal NMDAR antagonism
were studied in three awake, behaving, parkinsonian rhesus monkeys. Local
microinjections of the competitive NMDAR antagonist LY235959 were performed at
the site of extracellular recordings in the striatum in monkeys receiving
systemic levodopa administration (s.c.) during the recording session.
Behavioral effects of the antagonist were evaluated in tests of systemic
co-administration with levodopa.
Results: We found that local microinjection of the vehicle (artificial
CSF) alone had no effect on firing rates and did not alter the pathological MSN
responses to systemic levodopa. However, reduction of baseline activity via
local microinjections of LY235959 completely abolished the abnormal inversion
response of MSNs to systemic levodopa. The local effects of the NMDAR
antagonist correlated with its antidyskinetic effects with systemic injections.
These findings
have profound implications for elucidating the pathophysiological mechanisms
underlying LID, and may contribute to developing new pharmacological agents to
alleviate dyskinesias in advanced PD.
BASIC SCIENCE: PREVENTION, NEUROPROTECTION, NEUROPLASTICITY
P11.01
Dose-dependent therapeutic effects of FK506 on dopaminergic
neurodegeneration and neuroinflammation in a viral vector-based
α-synuclein rat model for Parkinson’s disease
Anke Van der Perren1, Francesca Macchi, Anne-Sophie Van
Rompuy1, Cindy Casteels2, Michael Maris3,
Sophie Sarre4, Nicolas Casadei5, Silke Nuber5,
Uwe Himmelreich2, Dirk R. J. Kuypers6, Guy Bormans2,
Koen Van Laere2, Rik Gijbers3, Chris Van den Haute1,
Zeger Debyser3, Veerle Baekelandt1
1Neurobiology
and Gene Therapy, Department of Neurosciences, KU Leuven, Flanders, Belgium
2Division
of Nuclear Medicine, University Hospitals Leuven and KU Leuven, Belgium
3Molecular
Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological
Sciences, KU Leuven, Flanders, Belgium
4Department
of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel,
Belgium
5Department
of Medical Genetics, University of Tübingen, Germany
6Department
of Nephrology and Renal Transplantation, University Hospitals Leuven, Belgium
Objective: Testing of new therapeutic strategies for
Parkinson’s disease (PD) is currently hampered by the lack of a robust and
reproducible animal model that displays the hallmark features of PD. In this
study we aimed to develop a viral vector-mediated rat model based on
α-synuclein, presenting reproducible nigrostriatal pathology and
behavioral deficits in a short time period. Next, we used this optimized PD rat
model to study the therapeutic effect of the immunophilin ligand FK506 in vivo.
Methods: An adeno-associated viral vector serotype 2/7 encoding A53T
mutant α-synuclein was stereotactically injected into the substantia nigra
of adult Wistar rats and the effect was determined by histology, biochemical
analysis, non-invasive imaging, microdialysis and behavioural analysis. FK506
was administered at different doses by daily tail vein injection
Results: Overexpression of (A53T) α-synuclein in rat substantia nigra
resulted in extensive and reproducible nigrostriatal pathology and behavioral
deficits in a 4 weeks time period. Progressive dopaminergic dysfunction was
corroborated by histopathological and biochemical analysis, motor behavior and
in vivo microdialysis. L-dopa was found to revert the behavioral phenotype.
Non-invasive PET and MR imaging allowed longitudinal monitoring of
neurodegeneration, highlighting the translational value of this model. In
addition, insoluble α-synuclein aggregates were formed in this model.
Treatment with FK506 for four weeks significantly increased the survival rate
of dopaminergic neurons in a dose-dependent way. No reduction in
α-synuclein aggregation was apparent in this time window but FK506
significantly lowered the infiltration of cytotoxic T cells and the number of
microglia/ macrophages. In conclusion, the anti-inflammatory properties of
FK506 prevent neurodegeneration in this α-synuclein-based PD model,
pointing to a causal role of neuro-inflammation in the pathogenesis of PD.
P11.02
Neuroprotective
effect of plasmalogen precursor analogs, PPI-1011 and PPI-1025, in MPTP mice
Mélanie
Bourque1,2, Marc Morissette1, Sara Al Sweidi1,
Tara Smith3, Vijitha Senanayake3, Dayan Goodenowe3
and Thérèse Di Paolo1,2
1Neuroscience Research Unit, Centre de Recherche du CHU
de Québec, CHUL, Quebec City, QC, Canada
2Faculty of Pharmacy, Laval University, Quebec City,
QC, Canada
3Phenomenome Discoveries Inc., Saskatoon, SK, Canada
Objective: This study investigated a new neuroprotective mechanism:
membrane plasmalogen augmentation. This strategy is a promising neuroprotective
mechanism because of the roles plasmalogens play in
membrane structure mediated functions such as vesicular release of
neurotransmitters and membrane protein activity, free radical scavenging, and as a storage of depot of neuroprotective
polyunsaturated fatty acids (docosahexaenoic acid (DHA)).
Methods: Male mice were treated for 10 days with daily oral
administration of either the DHA-plasmalogen
precursor PPI-1011 (10, 50 or 200 mg/kg) or the linoleic
acid-plasmalogen precursor PPI-1025 (10, 50 or 200 mg/kg). On day 5 the mice received 4 injections
of MPTP (6.5mg/kg). The mice were
sacrificed on Day 11 and striatal biogenic amine
concentrations were measured by high performance liquid chromatography with
electrochemical detection.
Results: PPI-1011 (10 and 50 mg/kg) and PPI-1025 (10 mg/kg)
completely prevented the decrease of dopamine concentration induced by MPTP,
the PPI-1025 prevention at 50 mg/kg was partial and no effect was observed at
200 mg/kg for either compound. PPI-1011 and PPI-1025 at 10 and 50 mg/kg
prevented the MPTP induced decrease of DOPAC and HVA concentrations. All doses
of PPI-1011 as well as PPI-1025 at 200 mg/kg maintained serotonin concentrations
at control values. MPTP had no effect on 5-HIAA concentrations whereas mice
treated with PPI-1011 or PPI-1025 (all doses) had increased concentrations of
5-HIAA. All groups showed an increase in 5-HIAA/serotonin ratios but this
augmentation was greater in PPI-1011 (10 and 50 mg/kg) and PPI-1025 (50 mg/kg)
treated mice than MPTP and vehicle groups. In
conclusion, the neuroprotective effect of plasmalogen precursor analogs
appears to have a bell-curve dose-dependency in that the effect was reduced at the
higher doses tested. The equal activity of linoleic (PPI-1025) and DHA
(PPI-1011) plasmalogen precursors indicates that the observed neuroprotection
is principally due to the plasmalogen backbone and not DHA.
P11.03
Transient silencing of
RXRβ retinoid receptor enhanced neuronal differentiation by retinoic acid
in SH-SY5Y cells
Matheus Augusto de
Bittencourt Pasquali 1, Fares Zeidán Chulia 1, Daniel
Pens Gelain 1, José Cláudio Fonseca Moreira 1
1 Universidade Federal
do Rio Grande do Sul - UFRGS - Centro de Estudos em Extresse Oxidativo, Brazil
Objective: Retinoic Acid (RA) is
a potent inducer of catecholaminergic differentiation in vitro. Classically, it
is known that RA effects at cellular level are dependent on gene transcription
mediated by retinoid receptors, which are subdivided in to RAR and RXR.
Recently, nongenomic mechanisms (not dependent on RAR/RXR-mediated gene
transcription) have been proposed to play an important role in biological
actions by RA by influencing post-translational processes, such as protein
phosphorylation, tubulin acetylation, actin polymerization, synaptic
transmission and redox signaling. However, there is no data on the role of
nongenomic mechanisms in RA-induced neuronal differentiation. Therefore, we
studied the effect of retinoid receptor silencing in a well-characterized model
of in vitro neuronal differentiation with RA (human SH-SY5Y
neuroblastoma-derived cells).
Methods: We used an approach
of transient protein silencing with small interfering RNA (siRNA). Cells transfected
with siRNA for the receptor isoform RXRβ were subjected to neuronal
differentiation by RA. To confirm the status of retinoid receptor inhibition,
we will perform western blot and qRT-PCR analysis. Neuronal differentiation was
evaluated by contrast-phase microscopy (neurite extension and ramification) and
by using confocal microscopy and western blot analyses to detect neuronal
biochemical markers, such as neuronal-specific enolase, beta-III tubulin and
tyrosine hydroxylase.
Results: After 5 to 10 days of
RA-induced neuronal differentiation, RXRβ-silenced cells presented
increased tyrosine hydroxylase and beta-III tubulin content. Neurite extension
and ramification was also enhanced compared to control cells, as observed by
contrast phase microscopy and confocal analysis with beta-III tubulin staining.
These results suggest that effects of RA during neuronal
differentiation
may involve nongenomic actions able to modulate post-translational events. The
comprehension of such mechanisms may be applied to improve cell
replacement-based therapies for Parkinson’s disease.
P11.04
The bioavailable
plasmalogen precursor PPI-1011 reduces levodopa-induced dyskinesias in
parkinsonian monkeys: comparison with docosahexaenoic acid (DHA)
Laurent Grégoire1, Tara Smith2, Vijitha Senanayake2,
Dayan Goodenowe2 and Thérèse
Di Paolo1,3
1Neuroscience Research Unit, Centre de Recherche du CHU
de Québec, QC, Canada.
2Phenomenome
Discoveries Inc, Saskatoon, SK, Canada
3Faculty of Pharmacy, Laval University, QC, Canada.
Objectives: A majority of
Parkinson disease (PD) patients develop abnormal involuntary movements called
dyskinesias after 5-10 years of levodopa (L-DOPA) treatment that are difficult
to manage. No drug is yet available for dyskinesias, aside from a modest
benefit with amantadine in some PD patients. Hence, alternative drugs are
needed that may alleviate dyskinesias. We reported that docosahexaenoic acid
(DHA, omega-3) has antidyskinetic activity in the
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
monkey model of PD. This experiment tested a new target for dyskinesias,
plasmalogens, because of their roles in membrane structure mediated functions
such as vesicular release of neurotransmitters and membrane protein activity,
free radical scavenging, and as a storage depot of polyunsaturated fatty acids
such as DHA.
Methods: MPTP-lesioned monkeys
received L-DOPA to induce dyskinesias. First we measured the behavioral motor
effect of a daily treatment for 10 days with DHA (100 mg/kg) and the
DHA-plasmalogen precursor PPI-1011 (50 mg/kg) as compared to their plasma DHA
and plasmalogen concentrations. Then, we investigated the dose-response (10, 25
and 50 mg/kg) behavioral effect of PPI-1011.
Results: PPI-1011 and DHA
reduced levodopa-induced dyskinesias (LID) while maintaining the
antiparkinsonian activity of L-DOPA. The PPI-1011 reduction of LID was observed
at the earliest time point behavioral measure that is 2 days after PPI-1011
administration whereas the DHA effect was later at 10 days. DHA treatment led
to increased plasma levels of DHA; these levels were higher than those obtained
with PPI-1011. Next, we confirmed the effect of 50 mg/kg PPI-1011 to reduce LID
and also at 10 and 25 mg/kg, the extent of the effect being similar with these
doses but occurring earlier in the 10 days of treatment at high doses. In conclusion, PPI-1011 has
antidykinetic activity in MPTP monkeys that could be due in part but not only
to its production of DHA.
P11.05
Nigrostriatal
expression and modulation of the Sigma-1 receptor in experimental parkinsonism
Veronica
Francardo1, Francesco Bez1, Karsten Ruscher2,
Hans Nissbrandt3, Tadeusz Wieloch2 and M.Angela Cenci1
1Basal Ganglia Pathophysiology Unit, Department of Experimental
Medical Science, BMC F11, Lund University, Lund, Sweden;
2Division of Neurosurgery, Laboratory for Experimental Brain
Research, Department of Clinical Sciences, Wallenberg Neuroscience Center, Lund
University, Lund, Sweden;
3Department of Pharmacology, Institute of Neuroscience and
Physiology, The Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
Objective: Sigma-1
receptor (Sig-1R) is a chaperone protein widely distributed in the mammalian
brain, peripheral neurons and visceral organs. Several studies suggested its
implication in aging and many human diseases, but its possible role in
Parkinson’s disease has not yet been reported. In this study we examine the
nigrostriatal expression and modulation of Sigma-1 receptor in experimental
parkinsonism.
Methods: 6-OHDA
intrastriatal lesions were performed in rats and Sigma-1 receptor nigrostriatal
immunoreactivity was observed at different time points post surgery. The
time-course of Sig-1R expression was confirmed in mice sustaining intrastriatal
6-OHDA lesions.
Results: Sig-1R
immunopositive cells were found in the striatum and in the substantia nigra of
both intact and 6-OHDA lesioned animals. However, neurotoxic lesions caused a
massive and widespread upregulation of Sigma-1 receptor in the entire striatum
on the side ipsilateral to the 6-OHDA injection at 2 and 7 days post surgery.
Its expression decreased at longer time points (14 and 28 days), being
restricted to the dopamine-denervated subregions of the striatum. Cells
immunopositive for Sig-1 receptor in the striatum showed mainly glial
morphology. Changes in Sig-1R expression also occurred in the substantia nigra,
although with a different temporal pattern and cellular morphology. These
results show that Sigma-1 receptor is expressed in the nigrostriatal system and
becomes upregulated after neurotoxic lesion, as possible part of a compensatory
response to damage. The effects of Sigma-1 receptor ligands are currently being
investigated in 6-OHDA lesioned mice and will be presented at the meeting.
P11.06
A novel
thiazolidinedione protects dopamine neurons in culture and in a preclinical
model of Parkinson’s disease
Anamitra Ghosh1,
Martha L Escobar Galvis1, Jennifer A. Steiner1, Jerry
Colca2 and Patrik Brundin1
1Laboratory of
Translational Parkinson’s Disease, Center for Neurodegenerative Science, Van
Andel Research Institute, Grand Rapids, MI, USA
2Metabolic Solutions
Development Company, Kalamazoo, MI, USA
Objective: Mitochondrial
impairment is suggested to play a central role in Parkinson’s disease (PD)
pathogenesis. It is hoped that therapies that improve mitochondrial function
might retard PD progression. The mitochondrial target of thiazolidinedione
insulin sensitizers (mTOT) is a complex of pyruvate carrier proteins that is
located in the mitochondrial membrane. Modulation of mTOT improves
mitochondrial oxidative metabolism (Colca et al. 2013) and changes
nutrient-sensing pathways such as the AMP-activated protein kinase. Furthermore,
this modulation mitigates over-activation of the mammalian target of rapamycin
(mTOR) pathways.
We
hypothesize that a specific modulator of mTOT (MSDC-0160) can protect
dopaminergic neurons in models of PD.
Methods: We assessed the neuroprotective
properties of MSDC-0160 (micromolar concentrations) in a human dopaminergic
cell line (LUHMES cells) and cultured primary mouse midbrain mesencephalic
neurons in the presence of MPP+. We quantified neurite length and
numbers of surviving tyrosine hydroxylase-positive neurons. In parallel, we
examined the effects of MSDC-0160 in vivo
in a sub-acute MPTP mouse model of PD. We pretreated mice with MSDC-0160 via
oral gavage before giving them MPTP. After 5 days of MPTP treatment we assessed
motor function and 7 days following MPTP treatment we sacrificed the mice and
stereologically counted the number of TH-immunoreactive neurons.
Results: We found
that MSDC-0160 treatment attenuated MPP+-induced loss of TH positive dopaminergic
neurons and terminals in LUHMES cells and primary midbrain cultures. Moreover,
treatment with MSDC-0160 improved locomotor activity and protected
nigrostriatal dopaminergic neurons in the subacute MPTP mouse PD model. Taken
together, we demonstrate significant neuroprotective effects of MSDC-0160 in
cell culture and an established pre-clinical animal model of PD. MSDC-0160 is a
safe compound already approved for clinical evaluation (type-2 diabetes and
Alzheimer’s disease) and based on our results MSDC-0160 might be a candidate
drug for clinical trials aimed at modifying the course of PD.
P11.07
Unilateral 6-OHDA
lesion and Dopa administration in Nur77 knockout rats reveal an important role
of this transcription factor in Parkinson’s disease and its treatment
Daniel Lévesque1, Joanie Baillargeon2, Claude
Rouillard2
1
Faculty
of Pharmacy, University of Montreal, Montreal, QC, Canada
2Neuroscience, CRCHUL
and Fac. of Medicine, Psychiatry and Neuroscience, Laval University, Quebec,
QC, Canada
Objective: Nur77 (Nr4a1) is a
transcription factor of the nuclear receptor family that is associated with
neuroadaptation pathways triggered by perturbation of dopamine (DA)
neurotransmission. We have previously shown that DA denervation and repeated
L-Dopa treatment modulate Nur77 mRNA expression patterns in the striatum.
However, the exact role of this transcription factor in Parkinson’s disease
(PD) and L-Dopa treatment is still unknown. In the present study, we
investigated the role of Nur77 in a newly developed rat knockout model
(FHH-Nr4a1m1Mcwi, nonsense mutation, Y130stop).
Methods: We performed
unilateral 6-hydroxydopamine (6-OHDA) lesions in wild type and Nur77 knockout
rats. Daily L-Dopa treatments (6.25 mg/kg, benserazide 15 mg/kg) were maintained
for 21 days. Circling behavior and Abnormal Involuntary Movement (AIM) scores
were measured five times. We also evaluated the effect of striatal Nur77
overexpression using an adeno-associated viral construct in this PD model. In
addition, we quantified the effect of the neurotoxin on DA cells using
stereology (TH immunoreactivity).
Results: Nur77 knockout rats
showed a dramatic reduction in both L-Dopa-induced circling and AIM scores. On
the other hand, Nur77 striatal overexpression tended to increase these
behavioral measures. Moreover, the effect of 6-OHDA injections on TH
immunoreactivity was reduced in Nur77 knockout, compared to wild type rats.
Thus, these results suggest that Nur77 plays an important role in
L-Dopa-induced dyskinesia as well as in DA cell loss in this PD model.
Supported by the Michael J. Fox Foundation (MJFF) for Parkinson’s disease.
P11.08
Selective knockout of
the vesicular GABA transporter (VGAT) in the motor cortex completely protects
against MPTP-induced lesioning in mice
Rebecca L. Hood1,
Cynthia Moore1, Heinrich S. Gompf2, Patrick M. Fuller2,
Charles K Meshul,1,3
1 Research Services,
Veterans Hospital, Portland, OR, USA
2 Department of
Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center,
Boston, MA, USA
3 Department of
Behavioral Neuroscience and Pathology, Oregon Health & Science University,
Portland, OR, USA
Objective: Alterations in
activity of the motor cortex (MC) in patients with Parkinson’s disease (PD) provides
a new potential therapy. Recent studies suggest that rTMS or direct
targeting/stimulation of the MC of PD patients can provide motoric improvement.
Methods: To examine
physiological effects of possible MC activation and neuroprotection in PD, we infused
unilaterally an AAV-Cre-GFP vector into the motor cortex of Vgatflox/flox mice
to prevent the translation of the vesicular GABA transporter (VGAT). Mice
(C57Bl/6J) were subjected to 4 weeks of a progressive dose of
1-methyl-2-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 5 d/wk injected i.p. at
doses of 8, 16, 24, and 32 mg/kg/d, or vehicle (Goldberg, et al, 2011). One
week after the last dose of MPTP, the dorsolateral striatum (STR) and
substantia nigra pars compacta (SNpc) were processed for light microscopic
immunohistochemistry (IHC).
Results: Analysis of the
optical density of tyrosine hydroxylase-immunoreactive (TH-ir) nerve terminals
in the STR showed a 79% reduction in the C57 mice after MPTP lesioning when
compared to the vehicle group (p<0.001) that was completely prevented by the
AAV-Cre-GFP infusion (p>0.19). This protection was bilateral within the CPu.
The average number of TH-ir cells/section within the SNpc demonstrated that the
59% loss of TH-ir cells in C57 mice compared to control animals was completely
prevented in the floxed mice. The TH-ir neuronal protection was also bilateral.
Cytochrome oxidase histochemical analysis of the central substantia nigra pars
reticulata demonstrated a surprising decrease in optical density after MPTP insult
in wild type mice (60%, p<0.01) that is partially protected by the loss of
VGAT expression in the MC (36%, p<0.001). These data suggest a novel therapy
for PD, with unilateral inhibition of the GABAergic interneurons within the MC
resulting in bilateral protection against the loss of both TH-ir terminals and
neurons following progressive MPTP administration.
P11.09
GM1 ganglioside as a
disease modifying agent for Parkinson’s disease: Clinical and neuroimaging
findings
Jay Schneider1,
Stephanie Sendek1, Hiroto Kuwabara2, Dean Wong2,
Benjamin Leiby1
1Thomas Jefferson
University, Philadelphia, PA, USA
2Johns Hopkins
University, Baltimore, MD, USA
Objective: A single center,
double-blind, delayed start study was conducted to examine possible symptomatic
and disease-modifying effects of GM1 ganglioside in Parkinson’s disease (PD).
As part of this study, some subjects were studied longitudinally with [11C]Methylphenidate
([11C]MP) positron emission tomography (PET) to evaluate effects of
GM1 treatment on striatal dopamine terminals.
Methods: Seventy-seven subjects
with PD were randomly assigned to receive GM1 for 120 weeks (early-start) or
placebo for 24 weeks followed by GM1 for 96 weeks (delayed-start). Seventeen
subjects who received standard-of-care were followed for comparative
information about disease progression. Primary outcome was change from baseline
Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores. PET studies were
performed on 32 subjects (14 early-start, 18 delayed-start, 11 standard-of-care).
Ten striatal regions-of-interest were defined on MRI: left/right anterior and
posterior caudate; left/right anterior and posterior putamen; left/right
ventral striatum. Mixed effects linear regression simultaneously modeled signal
for all 10 regions. Within the mixed effects model, changes in signal were
estimated and groups were compared using appropriate linear contrasts.
Results: At week 24, the
early-start group significantly improved in UPDRS motor scores vs. a
significant worsening in the delayed-start group. PET results showed increased
signal in 7 of 10 regions in the early-start group vs. baseline and decreased
signal in all regions in the delayed-start group. At 1 yr., ([11C]MP
binding was significantly preserved in several striatal regions in the
early-start group vs. the standard-of-care group with the greatest difference
observed in the posterior putamen, the region with the most severe loss of [11C]MP
binding in PD.
Conclusions: GM1 use for 24 weeks
was superior to placebo for improving motor symptoms and extended GM1 use
resulted in lower than expected symptom progression. PET results support the
possibility that GM1 may preserve striatal dopamine terminals and may even
stimulate a sprouting response.
P11.10
Performance of movement in hemiparkinsonian
rats influences the modifications induced by dopamine agonists in striatal
efferent dynorphinergic neurons
Nicola Simola1,
Lucia Frau1, Micaela Morelli1,2,3
1Department of
Biomedical Sciences, Section of Neuropsychopharmacology, University of
Cagliari, Via Ospedale 72, 09124, Cagliari, Italy
2Centre of Excellence
for Neurobiology of Dependence, University of Cagliari, Cagliari, Italy
3CNR, Institute of
Neuroscience, Cagliari, Italy
We
have previously shown that movement performance induced by dopamine agonist
drugs in hemiparkinsonian rats unilaterally lesioned with 6-hydroxydopamine
(6-OHDA), governs the occurrence of a sensitized motor response to a subsequent
dopaminergic challenge (priming model). In the present study, we examined the
influence of movement performance (rotational behavior) on the molecular events
induced by priming in the striatum. To this end, unilaterally 6-OHDA-lesioned
rats were primed with apomorphine (0.2 mg/kg) in immobilized or freely moving
conditions (priming induction) and 3 days later the D1 receptor agonist SKF
38393 was administered (priming expression). Evaluation of striatal mRNA for
enkephalin and dynorphin, markers of the indirect and direct striatonigral
pathways, and of GAD67 showed an increase in dynorphin in primed SKF
38393-treated rats, no matter whether immobilized or freely moving during
priming induction, whilst enkephalin and GAD67 did not show any changes. In
contrast, evaluation of mRNA for the early gene zif-268 in the striatum showed
a generalized increase after administration of SKF 38393, in both primed and
unprimed rats. However, examination of zif-268 mRNA at the single-cell level,
showed that only dynorphin(+) neurons of primed not immobilized rats displayed
a significantly higher number of zif-268-positive silver grains in response to
the SKF 38393 challenge. This selective activation of zif-268 in dynorphinergic
striatonigral efferent neurons demonstrates that movement performance in
response to dopaminergic drug administration under conditions of dopamine
denervation is critical for the emergence of neurochemical modifications in
selected striatal efferent neurons. Furthermore, these results may provide
information on the first initial molecular events taking place in the complex
processes that lead to dyskinetic movements in Parkinson's disease.
CLINICAL
SCIENCES: SYMPTOMS, SIGNS, FEATURES, & NON-MOTOR MANIFESTATIONS
P12.01
Profile of Parkinson’s
disease patients presenting at the Calabar neurology clinic
Jude C. Anikwe1,
Uduak E. Williams1
1Internal Medicine
Department, University of Calabar, Calabar, Nigeria
Introduction: Calabar is a coastal
city in the Niger delta region of Southern Nigeria, with a population of about
400, 000. The Movement disorders arm of the Neurology clinic in Calabar was
established about one year ago. We have enrolled about 21 new cases so far.
Objective: To determine the
profile of newly registered patients in our clinic.
Method: Basic demographic
data and clinical features were obtained with a structured questionnaire.
Results: Twenty-one new cases
were registered of which 7(33.3%) were females and 14 (66.3%) were males.
Average patient age was 60 years, while mean age at onset of motor symptoms was
56.6 years. 10 patients had diabetes mellitus as co-morbidity, while 9 had
coexisting hypertension.
Only
17 (81%) had a correct diagnosis from the referring Physician. The interval
between onset of motor symptoms and presentation at the clinic ranged between
one week and 3 years. 95.5% of the patients had rigidity, while only 33.3% had
postural instability. A family history of PD was found in only 2 (9.5%) of the
patients.
The
patient distribution on the Modified Hoehn and Yahr staging was as follows:
stage 1=14.3%; stage 1.5=19%; stage 2=33.3%; stage 2.5=14.3%; stage 3=14.3% and
stage 4=4.8%. The initial limb affected was right upper limb in 19 (90.5%) and
left upper limb in 2 (9.5%) of the patients.
Conclusion: Very few new cases
were registered over the on year period, of which majority presented several
months after the onset of motor symptoms.
P12.02
Applause sign in clinically overlapping diseases: a case of
TDP-43 proteinopathy
David Arkadir1,
Paul E. Greene1, Cheryl H. Water1s, Carol Brown Moskowitz1
and Madeleine E Sharp1
1Department of
Neurology, Centre for Parkinson’s disease and other Movement Disorders,
Columbia University Medical Center, NY, USA
Objective: To report a case of Corticobasal syndrome with TDP-43 proteinopathy
and positive applause sign.
Background: The ‘Applause sign’
was initially considered specific for Progressive Supranuclear Palsy but its
specificity was questioned after it was also documented in clinically diagnosed
patients with Parkinson’s disease, Corticobasal syndrome, Multisystem Atrophy
and Alzheimer disease. The debate regarding the specificity of the ‘Applause
sign’, however, is based on clinical rather than definite pathological
diagnosis.
Methods: We describe the
clinical and autopsy findings of a patient with Corticobasal syndrome with
TDP-43 proteinopathy.
Results: A 64-year-old
right-handed woman developed slowness of speech and intermittent curling of her
right toes. Within a year she had right arm clumsiness and an alien hand. Two
years after the onset of her first symptoms, examination revealed slow speech
output, dementia, hyperreflexia, significant right-sided rigidity and
bradykinesia, dystonic posturing of her right hand and circumduction of her
right leg while walking. When asked to imitate the three-clap applause, she
clapped continuously. Brain MRI revealed left fronto-parietal atrophy. She was
diagnosed with Corticobasal syndrome. Her condition slowly progressed and she
died at age 69. Her autopsy revealed asymmetric cortical and subcortical
atrophy, worse on the left. Cortical and white matter intracellular inclusions
stained positively for TDP-43, staining for tau and alpha-synuclein was negative
Conclusions: This case suggests
that in debating the utility of the applause sign to differentiate between
clinically overlapping syndromes, the pathological, rather than clinical
diagnosis should be used.
Financial Disclosure: David Arkadir is
supported by a fellowship award in movement disorders from the Parkinson’s
Disease Foundation.
P12.03
Postural instability and history of falls in
Parkinson’s disease: correlation with the pull test score
Igor Barcellos1, Marina Farah1,
Gabriela Boschetti1, Renato P. Munhoz1, Hélio A. Teive2
1Pontifical Catholic University of Paraná, Curitiba, Brazil
2Federal
University of Paraná, Curitiba, Brazil
Objective: To evaluate the correlation of postural instability
as measured using the pull test (PT) and the history of falls as rated by item
13 of the UPDRS.
Methods: Were assessed 314 patients with a clinical diagnosis
of PD. Mean age 65,4(29-94) years with mean disease duration 8,65(1-33) years.
History of falls was considered positive if the item 13 of the UPDRS was scored
>0, frequent fallers were those with a score ranging from 2 (occasional
falls, less than once daily) to 4 (more than one daily fall).
Results: Of all patients, 158 (50.4%) had a normal response to the
PT; 67 (21.4%) had a score of 1; 55 (17.6%) had a score of 2; 22 (7%) had a
score of 3; and 11 (3.5%) had a score of 4. Among those with a score of 0 in
the PT, 22 (13.9%) had a history of falls with only 3 (1.9%) having frequent
falls. For patients with a score of 1 in the PT, 34 (50%) reported falls with 9
(13.4%) having a score >1 for item 13 of the UPDRS. Forty-seven of the 55
patients (85.4%) with a score of 2 in the PT reported falls, with 29 (52.7%) of
them considered frequent. All 22 subjects with a score of 3 in the PT reported
falls, frequent for most of them (2;90.1%). Among the 11 subjects scored as 4
in the PT, 10 reported daily falls (scores 3 or 4 in item 13 of the UPDRS).
Conclusions: The PT scores showed a good
correlation with scores of the item 13 of the UPDRS meaning that this parameter
of postural instability is a good predictor of falls in PD.
P12.04
Relationship
between motor laterality and nonmotor symptoms in Parkinson’s disease patients
Lorena
Barcelos1, Flávia Doná1, Camila Aquino1,
Pollyanna Castro1, Patrícia Aguiar1, Roberta Saba1,
Sonia Silva1, Beatriz Veiga1, Silvia Lestingi1,
Leonardo Medeiros1, Henrique Ferraz1, Vanderci Borges1
1Federal
University of Sao Paulo, Sao Paulo, Brazil
Objective:
To evaluate the predominant laterality of motor symptoms and its
relationship with non-motor symptoms in patients with Parkinson’s disease (PD).
Methods: A
transversal study was undertaken, including 53 patients diagnosed with PD. The
presence of non-motor symptoms was determined by applying the Non-Motor
Symptoms Scale (NMSS), Hamilton Anxiety and Depression Scale (HADS) and
Parkinson’s disease Sleep Scale (PDSS). Right PD (RPD) and Left PD (LPD) was
defined based on the motor signs on the SCOPA-motor scale and complaints
reported by the patient. T-test, Mann-Whitney and Chi-squared tests were used
for comparison, and Spearman's rank correlation coefficient was used for
analysis of correlation.
Results: 25 RPD and 28 LPD were enrolled on this study. For the entire
sample, the most prevalent symptom present in 42 patients was nocturia. There
were statistically significant differences between the PD groups in relation to
NMSS sleep-fatigue score (RPD: 6.96±5.41 points; LPD: 12.32±11.27 points,
p=0.035), PDSS total score (RPD: 105.12±27.55 points; LPD: 86.28±36.91 points,
p=0.046) and PDSS subitems on overall quality of night’s sleep (RPD: 7.40±3.20
points; LPD: 5.50±3.58 points, p=0.031) and sleep onset (RPD: 8.04±3.46 points;
LPD: 5.42±4.40 points, p=0.017). There were no significant differences between
LPD and RPD with respect to gender, Hoehn and Yahr Staging, SCOPA-motor, age at
diagnosis and/or onset of the symptoms, duration of the disease, HADS, NMSS
total, and values of NMSS for other domains. An inverse correlation was found
between mean PDSS total score and motor and non-motor aspects of the PD:
SCOPA-motor score, HADS score, NMSS total and domains scores.
P12.05
Marked Increase in Risk for Parkinson’s Disease with Olfactory
Dysfunction in LRRK2 G2385R Carriers
Ming Cao1, Zhuqin Gu1, Piu Chan1
1Xuanwu Hospital of Capital
Medical University, Beijing, China
Objective: To investigate the characteristics of olfaction
in Chinese Parkinson’s disease (PD) patients and healthy controls with or
without LRRK2 G2385R variant, and further evaluate the role of olfactory dysfunction
in predicting risk for PD.
Methods: PD
patients were recruited from the Center of Movement Disorders of Xuanwu
Hospital of Capital Medical University, and healthy controls were enrolled from
the Beijing Longitudinal Study on Aging (BLSA) cohort. Subjects had LRRK2
genotype information and agreed to give informed consent were enrolled in this
study. “Five odors olfactory detection arrays” was applied for olfactory
function.
Results: One
hundred and twenty-two subjects were enrolled in this study, with 22 LRRK2
G2385R carriers (LRRK2-PD) and 24 non-carriers (iPD) in PD patients, and 38
LRRK2 G2385R carriers and 38 non-carriers were healthy controls. PD group had
significantly higher scores in olfaction detection (OD) and olfaction
identification (OI) as compared to the control group (OD: 1.58±1.12 vs
1.00±1.22, p=0.005; OI: 2.59±0.59 vs 2.44±0.65, p=0.017), especially in
subjects who were younger than 70 years old (£70y: OD
1.52±1.16 vs 0.52±1.10, p=0.009; OI 2.59±0.50 vs 2.04±0.69, p=0.002; >70y:
OD 1.66±1.10 vs 1.24±1.21, p=0.261; OI 2.59±0.72 vs 2.64±0.53, p=0.778). OI
scores for the individual odors of banana and mint were significantly higher in
PD group than controls (banana: 2.80±0.93 vs 2.27±1.18, p=0.002; mint:
2.91±0.78 vs 2.42±1.00, p=0.001). Subjects with severe hyposmia (the olfaction
test score >2) had increased risk for PD, compared with the ones with normal
or mild hyposmia (84.8% vs 75%, p=0.017, OR=4.19, 95% CI 1.29-13.57, adjusted
for age and gender). When the individuals with severe hyposmia were LRRK2
G2385R risk variant carriers, the risk for PD significantly increased (90.9% vs
65.8%, p=0.004, OR=39.07, 95% CI 3.24-471.46, adjusted for age and gender).
P12.06
Individual and joint prevalence of three non-motor symptoms in the
US general population
Honglei Chen1,
Xuguang Guo2, Xuemei Huang3, Shyamal Peddada1
1 National Institute of Environmental Health
Sciences, RTP, NC, USA
2 Westat Inc., Durham, NC, USA
3 Penn State University-Milton S. Hershey
Medical Center, Hershey, PA, USA
Backgrounds: Non-motor symptoms are common among patients of Parkinson’s
disease (PD), and some may precede the clinical diagnosis of PD by years. The
presence of multiple non-motor symptoms in the same individual may indicate a
high risk of developing PD. Understanding the background prevalence of these
symptoms in the general population will facilitate research of PD non-motor
symptoms.
Methods: Using data from the US National Health and Nutrition Examination
Surveys 2005-2008, we examined the individual and joint prevalence of daytime
sleepiness, infrequent bowel movement, and depression among 10,468 participants
ages 20-85 years.
Results: These
symptoms were relatively uncommon in the general population, and prevalence
differs by gender. Importantly, few participants had ≥2 symptoms: 1.3% at
ages 20-29, 1.0% at 30-39, 1.2% at 40-49, 3.6% at 50-59, 1.6% at 60-69, 1.1% at
70-79, and 1.2% at 80 or older among men; among women, the percentages were
3.1%, 5.3%, 5.7%, 4.1%, 3.0%, 2.3%, and 1.2% respectively. Further analyses
showed that depression was correlated with both infrequent bowel movement and
daytime sleepiness, but the latter two were mutually independent. These
symptoms were each associated with the use of anti-Parkinsonian medication. The
age- and gender- adjusted odds ratio (OR) and 95% confidence interval (CI) were
3.0 (1.5-6.2) for depression, 2.1 (1.1-3.8) for in frequent bowel movement, and
2.0 (1.0-4.1) for daytime sleepiness. Comparing to individuals without any
symptoms, the ORs were 1.7 (0.8-3.2) for the presence of one symptom and 4.6
(1.8-11.7) for the presence of ≥2 symptoms. In conclusion, this study
showed that nonmotor symptoms were uncommon in the general population, and they
were associated with anti-Parkinsonian drug use.
P12.07
Cognitive
influence on swallowing function in patients with Parkinson’s disease
Ji Sun Kim1,
JinyoungYou, 2, Tae-Eun Kim3, Mee Kyung Suh2,
Juhee Chin2, Jin Whan Cho2*
1Department of Neurology, Soonchunhyang University Hospital,
Soonchunhyang University School of Medicine
2Department of Neurology, Samsung Medical Center, Sungkyunkwan
University School of Medicine
3Department of Neurology, Soonchunhyang University Bucheon
Hospital, Soonchunhyang University School of Medicine
Objectives: Both
dysphagia and cognitive dysfunction are common in Parkinson’s disease (PD).
Although the possibility that cognitive decline may contribute to dysphagia in
PD patients has been raised, the association between cognition and swallowing
functions has not been studied well. We evaluated cognitive influence on
swallowing function by using detailed neuropsychological profiles and video
fluoroscopic swallowing studies as objective measurement.
Methods: We
prospectively enrolled 56 non-demented PD patients. All participants received
selective neuropsychological tests covering general mental status, visuospatial
function, attention, language and related functions, learning and memory
function and frontal executive function. Video fluoroscopic swallowing studies
were also performed, and the Modified Barium Swallow Impairment Profile, a
validated and reliable scoring system, was applied to quantify the nature of
the physiologic swallowing impairment.
Results: During
the oral phase, hold position/tongue control, bolus preparation/mastication and
bolus transport/lingual motion were significantly associated with general
mental status, learning and memory domains and frontal/executive functions with
varying degree. Aspiration is associated with attention tested by digit symbol
test. Correlation analysis between motor subsets and swallowing components
revealed that oral residue of oral phase, epiglottic movement and tongue base
retraction of pharyngeal phase are associated with different motor subsets.
Conclusions: Our
findings suggest that cognitive dysfunction, especially attention, memory and
executive function, is mainly involved in the oral phase of swallowing, in PD
patients. Furthermore, we supposed that as the severe motor symptoms progress,
swallowing dysfunction will be influenced in the pharyngeal phase as well as
oral phase.
P12.08
Concurrent arm
swing-stepping (CASS) test for dual task-related movement incoordination and
hesitation in Parkinson’s disease
Taylor Chomiak1, Alexandra Cihal1, Terry Clark1, Ranjit Ranawaya2, and Bin Hu1
1DCN and Hotchkiss Brain Institute and University of Calgary, Calgary,
AB, Canada
2Movement Disorders
Clinic-Alberta Health Services, Calgary, AB, Canada
Objective: Parkinson’s disease
(PD) patients frequently show gait and balance impairments while simultaneously
performing parallel tasks under sustained and divided attention. In this study
we have developed a simple dual task by asking patients to perform concurrent
arm swing and on-the-spot stepping (CASS). Our initial aim was to examine whether
CASS can reveal deficits in movement initiation and coordination, and whether
the detected deficits were associated with self-assessment of fall risk.
Methods: The study included a
total of thirty-three PD patients (mean age: 66.6 years, SD 9.5; mean disease
duration: 8.1 years, SD 5.9) who were first instructed to swing their arms and
then to initiate the secondary task of leg stepping. We defined a lack of
arm-leg coordination as arm swing and leg stepping occurring on the
ipsilateral, instead of the contralateral side. Gait hesitations were scored as
follows: no-hesitation (0 sec), slight hesitation (<5 sec), and large
hesitation/freezing (>5 sec). The Falls Efficacy Scale-International (FES-I)
was used to assess fall-related self-efficacy.
Results: We found 78.8% patients showed some degree of deficits in coordination across three trials, whereas gait hesitation and/or freezing occurred significantly less (36.4%; p<0.01). Furthermore, multilevel regression analysis controlled for age, gender, and disease duration revealed that CASS-related hesitation/freezing, but not coordination, was a significant predictor of FES-I score (p<0.01), with R2 increasing by 33.3% after adding the hesitation variable but not the coordination variable (2.0%; p>0.05). Our results indicate that CASS can be used as a simple clinical test to reveal dual task-related movement incoordination, gait hesitation and/or freezing, as well as their relationship with self-reported functional efficacy in PD patients.
Acknowledgments: CIHR, Parkinson Alberta Society, and Dr. Sarah Furtado and the Movement Disorders Clinic-Alberta Health Services.
P12.09
Antipsychotic efficacy and motor tolerability in a phase
III placebo-controlled study of pimavanserin in patients with Parkinson’s
disease psychosis (ACP-103-020)
Jeffrey Cumming, Stuart Isaacson, Roger Mills, Hilde
Williams, Kathy Chi-Burris, Daun Bahr, Rohit Dhall, Clive Ballard
1 Cleveland Clinic Lou
Ruvo Center for Brain Health, Las Vegas, NV, USA
2 Parkinson’s Disease
and Movement Disorder Center, Boca Raton, FL, USA
3 ACADIA
Pharmaceuticals, Inc. San Diego, CA, USA
4 Barrow Neurological
Institute, Phoenix, AZ, USA
5 Institute of
Psychiatry, Kings College, London, UK
Objective: Parkinson’s disease psychosis (PDP) is
frequent, distressing and a leading cause of institutionalization. It also
complicates PD management and has been linked to increased morbidity, incident
dementia and mortality. Current antipsychotics lack efficacy and/or have
considerable tolerability and safety concerns.
Pimavanserin, a selective non-dopaminergic 5-HT2A receptor
antagonist, has shown antipsychotic effects and good tolerability in previous
Phase III trials, but a robust placebo effect precluded statistical separation.
A PhIII outpatient study, optimized to reduce placebo response, was conducted
to assess the efficacy and safety of pimavanserin in PDP.
Methods: Following 2-weeks screening, in which brief
(non-pharmacological) psychosocial therapy adapted for PD (BPST-PD) was
offered, 199 non-demented patients with moderate to severe psychosis (and on
stable PD medication) were randomized to once-daily oral doses of 40mg
pimavanserin or placebo (1:1) for 6 weeks.
Results: Pimavanserin met the primary endpoint using
SAPS-PD (a PD-adapted version of the Scale for Assessment of Positive Symptoms,
assessed by independent raters): -5.79 PIM vs -2.73 PBO change from Baseline at
Day 43 (LSM difference=-3.06; p=0.001). These results were supported by highly
significant improvement in the secondary efficacy measure, CGI-Improvement (LSM
difference ‑0.67; p=0.001), which was assessed by site investigators
blinded to the SAPS-PD. Additionally, clinical benefits were observed in all
exploratory efficacy measures with significant improvements in nighttime sleep,
daytime wakefulness, and caregiver burden. Consistent with previous studies,
pimavanserin met the key secondary endpoint for noninferiority to placebo on
motor function (using UPDRS II+III) and was otherwise safe and well tolerated.
The most common AEs were UTI (11.7% PBO, 13.5% PIM) and falls (8.5% PBO, 10.6%
PIM). The only serious AEs that occurred in more than one patient were UTI
(1-PBO, 3-PIM) and psychotic disorder (0-PBO, 2-PIM). These data suggest that
pimavanserin is effective, safe and well-tolerated for PDP. Utility in other
neuropsychiatric disorders remains to be explored.
P12.10
Role of
inflammation in the origin of fatigue syndrome in Parkinson`s disease
V.
Datieva1, O. Levin1
Russian Medical Academy of Postgraduate
Education, Moscow, Russia
Fatigue
syndrome (FS) is an overwhelming sense of tiredness, lack of energy and
feeling of exhaustion. The prevalence of fatigue in Parkinson’s disease (PD) ranges from 35% to 60%. Research on the
nature and treatment of fatigue has been challenging. The role of inflammation
in the origin of FS is being debated.
Objective:
examine
peripheral biomarkers of inflammation in relation to FS in patients with PD.
Methods:
We
included 20 PD patients with FS. Mean age was 64,5±6,5. Mean disease duration
was 5,9±4,04. Mean Hoehn&Yahr stage was 2,6±0,5. Fatigue was defined as
score>3,3 on the Parkinson Fatigue Scale (PFS).C-reactive protein (CRP) and
tumor necrosis factor-α (TNFα) were used as biomarkers of
inflammation in peripheral blood.
Results: Mean CRP level was 1,54±1,04. Mean
TNFα was 6,72±0,83 None of the 20
patients showed pathological level of these biomarkers in blood.
Conclusion: We didn`t find link
between FS severity and level of CRP and TNFα in peripheral blood. This
fact can imply that other then inflammation factors contribute to FS severity,
or role of inflammation is subtler and other biomarkers should be detected.
P12.11
Evaluation of impaired integration of
proprioception and motor information in Parkinson’s disease using extremity
drift in the absence of visual input
R. Dhall, N. Krishnamurthi, A. Lieberman, and
K. Wilhelm
Muhammad Ali Parkinson Center, Barrow
Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ,
USA
Objective: Parkinson Disease (PD)
is associated with widespread dysfunction of central and peripheral nervous
system, with basal ganglial and cortical impairment. We evaluated if
extremity drift resulting from a
“failure” to integrate proprioceptive and motor information can be reliably
used to distinguish subjects with PD from controls.
Methods: The degree of extremity
drift was measured in 11PD patients, 8 Essential Tremor (ET) patients, and 11
healthy control individuals. All subjects were seated, asked to extend their
arms in front of them at their shoulder width, pointing their index fingers
towards two targets (one target for each finger), and close their eyes. They
were asked to continue pointing to the targets without visual input for next 15
seconds while their movements of tip of their index fingers were measured using
a DynaSight 3-D optical radar system. Three trials were performed, data were
low-pass filtered to exclude tremor-induced movements, and average displacement
of index fingers in the mediolateral and upward and downward directions were
obtained across subjects in each group.
Results: PD
patients on the average exhibited a net downward displacement of 3.0 ± 2.4 cm
from their original starting position compared to 0.1 ± 1.1 cm and 1.5 ± 1.9 cm
downward displacements exhibited by control and ET subjects, respectively. The
difference in the displacement between PD patients and controls was
statistically significant at p < 0.05. In the mediolateral direction, PD
patients showed a medial displacement of 0.2 ± 1.2 cm whereas control and ET
individuals showed a lateral displacement of 0.02 ± 0.7 cm and 0.7 ± 1.3 cm,
respectively. These results suggest that extremity drift in the absence of
visual input can be useful in investigating impairments involving
proprioception and sensory motor integration in people with PD.
P12.12
A case of vascular
hemiparkinsonism responding to levodopa
Anne-Marie Dufresne 1,
Sylvain Chouinard 1
1Unité des troubles du mouvement André Barbeau, Hôpital
Notre-Dame, CHUM, Montréal, QC, Canada
Background: Vascular parkinsonism is known to be less
responsive to levodopa when compared to its response in idiopathic Parkinson’s
disease. There have been few reports of patients with a focal vascular lesion
in the striatonigral pathway that have induced a levodopa responsive
parkinsonism.
Case: The case involved an 8-year-old male who presented with a left hemiparkinsonism that
was related to an arteriovenous malformation that ruptured in the right
substantia nigra. Symptoms of resting tremor and marked rigidity occurred a few
months after the hemorrhage. The patient was unable to move his left arm due to
the rigidity and weakness. Levodopa was introduced which resulted in a
significant reduction in the resting tremor. From the initial dose of levodopa
the patient experienced peak dose effect with decreased rigidity enabling him
to move his arm despite some weakness.
Conclusion: This case reinforces the theory that
striatonigral lesions are more susceptible to respond to levodopa treatment
than diffuse vascular lesions.
P12.13
Quantitative and clinical measurements of
bradykinesia in advanced Parkinson’s disease. Are they related?
Christian Duval1-2, Jean-François
Daneault2-3, Benoit Carignan2-4, Abbas F. Sadikot3
1
Département de Kinanthropologie, Université du Québec à Montréal, Montréal, QC,
Canada
2 Centre de
Recherche de l’Institut Universitaire de Gériatrie de Montréal, Montréal, QC,
Canada
3
Department of Neurology and Neurosurgery, Montreal Neurological Hospital and
Institute, McGill University, Montreal, QC, Canada
4
Département des Sciences Biologiques, Université du Québec à Montréal,
Montréal, QC, Canada
Background: Bradykinesia is usually
assessed using clinical rating scales. In some circumstances, a laboratory assessment
of bradykinesia using tools of higher resolution is required. One task often
used for the evaluation of bradykinesia is a rapid alternating movement (RAM)
of the hand. However, the relationship between clinical scores of bradykinesia
and the properties of a RAM task assessed quantitatively has yet to be
determined.
Objective: Identify which of the
commonly used properties of a RAM task are related to a clinical score of
bradykinesia and assess the strength of this relationship.
Methods: Nineteen patients with
idiopathic Parkinson’s disease were tested ON and OFF medication. They
performed three trials of the RAM task and were assessed clinically using the
Unified Parkinson’s Disease Rating Scale in each condition and with each hand.
Results: A statistically
significant correlation was observed between the clinical score of bradykinesia
and two of the properties of the RAM task; namely mean and maximal velocity.
Conclusion: These results indicate
that a RAM task does provide a measure of bradykinesia but it is only
moderately correlated to a clinical rating of this motor symptom. We propose
that the results from the RAM task represent a measure of “core bradykinesia”
while a clinical evaluation represents a composite score of bradykinesia, movement
amplitude and motor coordination.
P12.14
Are sensory-perceptual deficits responsive to
dopaminergic replacement therapy?
Kaylena A. Ehgoetz Martens1,2, Colin G. Ellard2,
Quincy J. Almeida1
1Sun Life Financial
Movement Disorders Research and Rehabilitation Centre, Wilfrid Laurier
University, Waterloo, ON, Canada
2Department of
Psychology, University of Waterloo, Waterloo, ON, Canada
Objective: Although dopaminergic replacement therapy is
believed to improve sensory processing in PD, while delayed perceptual speed is
thought to be caused by a predominately cholinergic deficit, it is unclear
whether sensory-perceptual deficits are a result of corrupt sensory processing, or a delay in updating perceived feedback during movement. The current
study investigated whether sensory-perceptual deficits were influenced by
dopaminergic medication while manipulating visual flow speed in virtual
reality. If sensory-perceptual deficits were a result of delayed updating of perceived feedback, slowing visual flow speed
might improve perceptual judgments. Alternatively, if corrupt sensory processing underlies sensory-perceptual deficits
dopaminergic medication might be expected to improve perceptual judgments.
Methods: 14 PD were tested in the ON (~1hr after taking
L-dopa) and OFF state (after 12hr withdrawal). Participants estimated the
distance of a remembered target by walking to the location that the target
formerly occupied. This task was completed in VR in order to manipulate the
visual flow speed in 3 conditions: 1)Baseline: visual flow speed was equal to
participants’ real-time movement speed; 2)SLOW: visual flow speed was reduced
by 50% of participants’ real-time movement speed; 3)FAST: visual flow speed was
increased by 30% of participants’ real-time movement speed.
Results: Dopaminergic medication did not
significantly influence judgment error, however PD performed significantly
worse in the FAST condition compared to Baseline and SLOW. Interestingly,
judgment errors were less variable in the SLOW condition and similar in
accuracy to that of Baseline. Additionally, a significant interaction between
medication state and condition revealed that PD-ON had higher step times during
Baseline and FAST conditions compared to PD-OFF, however did not differ during
the SLOW condition. Since judgment error did not improve with dopaminergic
treatment, and slowing visual flow reduced the variability in judgment error,
these findings suggest that delayed perceptual processing might contribute to
sensory-perceptual deficits.
P12.15
Comparison of OnabotulinumtoxinA injections targeting submandibular versus parotid
glands in the treatment of sialorrhea for patients with Parkinson’s disease
Maria Fraraccio1,
Michel Panisset1
1CHUM and CRCHUM, Montréal, QC, Canada
Objective: Most studies investigating BoNT-A injections for the treatment of
sialorrhea in Parkinson’s disease (PD) report on parotid gland injections. This
study aims to compare between
submandibular and parotid glands as targets for BoNT-A injections for
the treatment of sialorrhea in PD.
Methods: Patients with PD and sialorrhea of a score of at least 3 or 4 on the
UPDRS 6 were recruited. By means of a within-subject design, patients were
randomized to receive either parotid or submandibular gland injections and the
reverse 3 months later. Comparisons between submandibular to parotid gland
injections were made in the resting and in the stimulated state. Objective
measures and subjective scales and questionnaires were administered. The
Wilcoxon signed-rank test was performed to compare parotid vs. submandibular
within group differences. Exploratory analysis to seek significant differences
between pre- and post-injections for each gland was performed. P values were
calculated at the 0.05 significance level in 2-tailed tests. We need 13
patients to reach a power of 0.90 with an alpha level of 0.05.
Results: Five PD patients have completed the study at this point. The means and
standard deviations for the parotid and submandibular injections in both the
resting and stimulated conditions during baseline (pre-injection) visits and
the one 1-month post-injection visits are shown in Table 1. Our primary
analysis reveal no significant difference while exploratory analysis suggest
that parotid injections may have a greater effect on objective measures of
drooling, that of weight and volume while both the parotid group and the
submandibular groups show a treatment effect on subjective drooling as measured
by the EDQ.
P12.16
Dental health of patients and
carepartners in Parkinson’s disease
Joan Gardner1, Daniel
Kuyper1, Michael Madden2, Catherine Wielinski1
1Struthers
Parkinson’s Center, Minneapolis, MN, USA
2University
of Minnesota, Minneapolis, MN, USA
Objective: To compare
the dental health of PD patients with their carepartners. Previous studies
indicate that dental health in PD is worse than controls, despite similar
dental health care.
Methods: Surveys
were sent to 1,499 PD patients seen at our center in the last 2 years. A
carepartner (CP) survey was included. Questions included: Rate your dental
health, with 0 being poor and 10 being excellent (rating); When were you last
at the dentist office (last visit); Was it a routine or an urgent, unplanned
visit (routine); How often do you brush your teeth (mouth care); Do you have
dry mouth (dry mouth); Do you have too much saliva (excess saliva). T-test and
chi-square was conducted using Minitab® 16, statistical significance was set at
p<.05.
Results: To date,
620 patient (41.3%) and 393 spouse surveys have been received (age: 72.2±9.2
years; 60.1% male). Survey results indicate that average rating of dental
health was 6.9±2.0 for patients versus 7.8±1.7 for CP (p<.001). There was no
significant difference in last visit and routine between patients and CP. There
was a significant difference in frequency of mouth care with 71.3% of patient’s
brushing at least twice a day compared to 80.9% of CP (p=.002). Dry mouth was
experienced by 40.4% of patients and 15.9% of CP (p<.001). Excess saliva was
experienced by 41.7% of patients and 2.3% of CP (p<.001). Interestingly,
15.0% of patients and 0.5% of CP experienced both dry mouth and excess saliva
(p<.001). Despite similar dental visits, home dental care is significantly
less frequent for PD patients as compared to their spouses. Further, PD
patients are more likely to experience dry mouth, too much saliva, and the
combination of dry mouth and too much saliva.
P12.17
Dental health in Parkinson’s disease
Joan Gardner1, Daniel Kuyper1,
Michael Madden2, Catherine Wielinski1
1Struthers Parkinson’s
Center, Minneapolis, MN, USA
2University of
Minnesota, Minneapolis, MN, USA
Objective: To determine the impact of PD
symptomatology on dental health in PD. Previous studies indicate that dental
health in PD worsens with disease severity. PD symptomatology may play a role.
Methods: Surveys were sent to 1,499 PD patients seen
at our center in the last 2 years. Questions included: Since your diagnosis of
PD, do you have more problems with your teeth and gums (dental health); Do your
PD symptoms affect your ability to do mouth and teeth care (PD symptoms); Rate
your dental health, with 0 being poor and 10 being excellent (Rating); Do you
have dry mouth (dry mouth); Do you have too much saliva (excess saliva).
UPDRS-II (ADL) score within the last year was calculated. Pearson correlation
was conducted using Minitab® 16, statistical significance was set at p<.05.
Results: To date, 620 surveys (41.3%) have been
received (age: 72.2±9.2 years; 60.1% male). Survey results indicate that 24.8%
felt that dental health was more of a problem since the PD diagnosis; 33.8%
felt that their PD symptoms affected their ability to do mouth and teeth care.
The average rating of dental health was 6.9±2.1. Dry mouth was experienced by
40.3% and 41.3% had excess saliva. 15.6% experienced both dry mouth and excess
saliva. ADL scores were available on 89.8%, average score was 12.2±7.1 (range
0-41). As ADL scores increased, ratings of dental health worsened (Pearson CC=
-0.372, p<.001). PD symptoms affect the oral health of PD patients.
P12.18
Prevalence and impact of Parkinson’s disease symptoms: A
patient survey across the range of disease severity
Claire Henchcliffe 1 and Susy Chen2
1Weill Cornell Medical College,
New York, NY, USA
2Impax Laboratories,
Inc., Hayward, CA, USA
Objective: To obtain an understanding of the complexity
and heterogeneity of Parkinson’s disease (PD) and PD patient’s perception of
their symptoms.
Methods: In April 2012, Impax Laboratories developed a
patient survey on presence and perceived impact of symptoms of PD. Disease
severity was estimated as mild, moderate, or severe, using an algorithm that
incorporated cardinal symptoms, sidedness, independent functioning, and
participant’s impression of physician-perceived symptom severity.
Results: Participants comprised 50 with mild, 50 with
moderate, and 50 with severe PD. Of these, 13% had been diagnosed within 1 year
previously, 36% within 4 years, and 32% within 10 years. 87 participants not
working full-time said PD hindered their ability to work. Symptom prevalence, types, and perceived
burden varied with disease severity. Most common were slowness of movement (81%
overall, 56% mild, 88% moderate, and 100% severe), tremors/shaking (78%
overall) and muscle stiffness (77% overall). Overall, tremors/shaking (23%),
loss of balance (12%) and cognitive challenges (9%) were the most bothersome
symptoms. On average, symptoms were deemed to be uncontrolled 4.4
h/day (3.8h mild, 3.3h moderate, and 8h severe). Largely,
participants hoped their medicine’s desired effect could improve walking (56%
overall, 42% mild, 58% of the moderate, and 68% severe), and every group ranked
physical mobility and independent self-care as the highest and second highest
concerns, respectively. The mild group collectively ranked hobbies/interests
(20%) and independent self-care (20%) high. The moderate group ranked physical
mobility (42%) and independent self-care (36%) nearly equivalently. In the
severe group, desire for physical mobility (60%) was paramount. The top
challenge of living with PD was fear of disease progression (55% overall).
Expenditure of great effort (38%) was also listed by moderate and severe
groups.
Conclusion: Patients with PD report substantial symptom
burden that varies by stage of the disease, and unmet medical need persists.
P12.19
The prevalence and severity of non-motor symptoms in
patients with Parkinson’s disease in Korea
Jae Woo Kim1, Seong-Beom Koh2,
KMDS-NATION study group
1Dong-A University
Hospital, Busan, Korea
2Guro Hospital, Korea
University, Seoul, Korea
Background and Purpose: Non-motor symptoms
(NMS) are common in Parkinson’s disease (PD) and can be the primary cause of
disability in many PD patients. The aim of the study is to assess the
prevalence and severity of NMS in Korean PD patients according to the clinical
status and motor subtypes.
Subjects and Methods: Patients with PD and normal controls
have been evaluated in the neurology department of 37 hospitals throughout
Korea. The subjects were assessed using the battery of standard assessment
measures, HY Stage, UPDRS, MMSE, MoCA, frontal lobe assessment battery, NPI,
BDI, BAI, Parkinson Fatigue Scale and PDSS. Prevalence and severity of NMS were
determined through Non-Motor Symptoms Scale (NMSS). We analyzed 323 PD patients
and 94 normal subjects. We classified PD patients according to their clinical
status as de novo, early and advanced PD patient. We also divided the PD
patients in akinetic-rigid (AR), tremor dominant (TD) and intermediate
according to motor symptoms.
Results: The prevalence of NMS and total NMSS score
were significant higher in PD patients compared to controls. The most common
domains of NMSS in PD patients were as followings: sleep/fatigue (82.0%),
mood/cognition (79.3%), attention/memory (77.4%), urinary function (73.7%).
However, the domains more related to PD are perceptual/hallucination,
gastrointestinal and miscellaneous. AR type of PD patients had more NMSS scores
than TD type. (60.0 vs 37.6, p=0.035, respectively). Gastrointestinal function
was more prevalent and severe in AR type.
Conclusions: Non-motor symptoms are common in Korean PD
patients. However, NMSs with higher prevalence in PD do not more relate to PD.
The domains of NMSS with higher scores are different depending on motor
subtype.
P12.20
R. Manso
Calderón
Neurology Deparment
Hospital Clínico Universitario, Salamanca, Spain
Aim. Falls are common in Parkinson´s
disease (PD) and can be an important source of
disability because of fractures. Our goal is
to evaluate the frequency of falls in a population of PD patients and to
determine the features associated with its development.
Patients and Methods.
A retrospective study of falls in 107 consecutive patients with PD (48 men/59 women) followed-up in a neurologic consultation
in Salamanca, Spain. The mean age of PD patients was 77,2 ± 8,3 years (age at
onset 65.6 ± 11.5 years and mean duration of PD 10.7 ± 4.8 years) and Hoehn & Yahr Staging median: 3[1-5]. Falls
were defined as any report of falls on the UPDRS (Falling>0). We assessed
the frequency of falls overall and by age. The relationship between potentially
related variables and the probability of falling was assessed using statistical
analysis.
Results. Forty-six
patients (44%) (26 men/20 women) reported at least one fall since the onset of
PD, and 30 of these patients were recurrent fallers (68% of patients with
falls). Falls led to fractures in 9 patients (22.5% of fallers). Freezers
experienced falls more frequently than non-freezers (88.1% vs 11.9%, OR=4.429,
IC95%:1.874-10.466, p<0.001). Also disease duration, UPDRS (part III) score,
Hoehn and Yahr staging, Schwab and England activities of daily living, motor
fluctuations, Mini-Mental State Examination and
neuroleptic use were associated with subsequent fall risk. No differences were
observed between fallers and non-fallers in other drug treatments, age at onset
of PD, initial predominant motor signs (tremor or akinesia-rigidity subtypes),
dyskinesias and symptoms of orthostatic hypotension and cerebrovascular
disease.
Conclusions. Falls are frequent and are associated with impaired quality of life. This symptom change in function of the PD stage.
New
investigations are required to better evaluate this important problem.
P12.21
Severe echolalia, palilalia and palipraxia in a patient
with Progressive Supranuclear Palsy syndrome
Ruben Martinez1, Stanley Fahn1
1Center for Parkinson´s
Disease and Other Movement Disorders, Department of Neurology, Columbia
University, New York, NY, USA
Background: Speech disturbances in parkinsonian
syndromes may cause severe disability affecting a patient´s QOL. Palilalia and
echolalia are repetitive speech phenomena. We present an unusual case with
disabling, severe repetitive speech and motor difficulties.
Case presentation: 58y/o woman was well until 3yrs ago when she
developed word and phrase repetitions. These became severe, and she was unable
to stop the repetitions, thereby losing her ability to continue with her
desired speech. Initially, this responded to levodopa. A year later, she
developed ocular motor abnormalities and severe generalized slowness, losing
her independency. No relevant family
history. Her exam revealed staring expression, no blinking, procerus
sign, slow horizontal ocular movements, hypometric saccades, and visual
grasping. When she tried to talk, she repeated the first words and kept
repeating them (palilalia). Occasionally, the repetitions developed after
several words were successfully spoken, blocking her speech forward. The
repetitions would continue until we broke in with a statement. Similarly, she
repeated non-stop words that we spoke to her (echolalia). Motor examination:
moderate bradykinesia/rigidity throughout. Writing: repetitions of letters and
then blocked, unable to finish the task. Feet and both arms went into a
continuous repetitive tremor-like pattern that stopped on command (palipraxia).
She arose and walked slowly on command, but she arose rapidly spontaneously
after an unrelated command. Pull test was positive. Applause Test was
“non-stop” positive.
Discussion: Repetitive disturbances have been associated
with frontal lobe alterations. Our patient has severe repetitive symptoms in
the context of PSP-like syndrome, which is well known to be related with
frontal dysfunction. The Applause Sign, common in PSP, can be considered a mild
manifestation of a repetitive motor phenomenon.
P12.22
Gender differences in
non-motor symptoms in early, drug naïve Parkinson’s disease
Marcello Moccia1,
Marina Picillo1, Marianna Amboni2, Roberto Erro1,
Katia Longo2, Carmine Vitale2,3, Roberto Allocca1,
Anna De Rosa1, Giuseppe De Michele1, Lucio Santoro1,
Giuseppe Orefice1, Paolo Barone4, Maria Teresa Pellecchia4
1Department of Neurosciences, University “Federico II”,
Naples, Italy
2IDC “Hermitage Capodimonte”, Naples, Italy
3University “Parthenope”, Naples, Italy
4Center for Neurodegenerative Diseases, University of
Salerno, Salerno, Italy
Objective: Gender differences in brain structure and function may lead to
differences in the clinical expression of neurological diseases, including
Parkinson’s disease (PD). Few studies reported gender-related differences in
the burden of non-motor symptoms (NMS) in treated PD patients, and this matter
has not been previously explored in drug-naïve patients. In consideration of
this, we assessed gender differences in NMS frequency in a large sample of
early, drug-naïve PD patients compared with age-matched healthy controls.
Methods: Two hundred early, drug-naïve PD patients and sixty age-matched
healthy controls were included in the study. Frequency of NMS was evaluated by
means of NMS Questionnaire. The difference in gender distribution of NMS was
evaluated with the X2 exact test; multiple comparisons were
corrected with Benjamini-Hockberg method.
Results: Male PD patients complained of problems having sex and taste/smelling
difficulties significantly more frequently than female PD patients.
Furthermore, men with PD complained more frequently of dribbling,
sadness/blues, loss of interest, anxiety, acting during dreams, and
taste/smelling difficulties as compared to healthy control men, while female PD
patients reported more frequently loss of interest and anxiety as compared with
healthy control women.
This study shows specific sex-related patterns of NMS in drug-naïve PD.
In contrast with previous data, female PD patients did not present higher
prevalence of mood symptoms as compared to male PD patients. Comparison with
healthy controls showed that some NMS classically present in premotor and early
stage of disease (i.e. acting during dreams, taste/smelling difficulties) are
more frequent in male than in female patients.
P12.23
Low awareness of non-motor features of Parkinson’s
disease among doctors in a tertiary institution in Nigeria: a cross-sectional
survey
Nwazor Ernest1, Wachukwu Chinyere,1 Emem-Chioma
Pedro1, Ojo Omolara2, Okubadejo Njideka2
1University of Port
Harcourt Teaching Hospital, Port Harcourt, Rivers State, Nigeria
2Lagos University
Teaching Hospital, Lagos, Nigeria
Objectives: To assess awareness of non-motor symptoms of
Parkinson’s disease (PD) among non-neurologists.
Methods: This cross-sectional study took place at
the University of Port Harcourt Teaching Hospital, Nigeria between March and
April 2013. Eighty-six doctors mostly residents were administered
questionnaires to complete. Apart from basic demographic data, they were also
asked to provide information on their awareness of both motor and non-motor
features of Parkinson’s disease, and also knowledge of various drugs used in
the treatment of Parkinson’s disease. Completed questionnaires were collated
and relevant data extracted and analyzed.
Results: Out of 86 doctors surveyed, 3(3.5%) did not
return their questionnaires. Of the 83 respondents, 25.3% were interns, 54.2%
residents, 19.3% senior residents and 1.2% consultants. Hundred percent of the
respondents admitted to be aware of motor features of Parkinson’s disease
whereas 71.1% were ignorant of non-motor features of Parkinson’s disease.
Awareness of non-motor symptoms amongst respondents is very low.
P12.24
Highlighting the significance
of pain in screening and managing Parkinson’s disease
A.Q.
Rana1, Mohammad A. Rana2, Zakera M. Kachhvi3
1Parkinson's Clinic of Eastern
Toronto & Movement Disorders Centre: Toronto, ON, Canada
2Faculty
of Medicine, James Cook University: Townsville, Queensland, Australia
3University
of Toronto Scarborough: Toronto, ON, Canada
Introduction: Pain is a common problem faced by PD patients.
Despite its impact and disabling effects pain is still frequently overlooked.
In this study we analyze current peer reviewed literature for the prevalence
and types of pain in PD, correlation of pain to depression and quality of life,
reporting to physician, and the use of analgesics. The objective of this study
was to review current literature about the various aspects of pain in
Parkinson’s disease (PD).
Methods: By using key words of PD, prevalence of pain,
quality of life and depression in relation to pain in Parkinson’s we searched the
pubmed database. Twenty-seven articles pertaining to pain in PD were found.
After a careful further review of the articles eighteen were selected for our
meta-analysis.
Results: A total of 15693 patients were studied in these
articles. The average prevalence rate was 59%. Five types of pain were noticed:
dystonia, akathisia, musculoskeletal problems, nerve or root pain, and primary
or central pain. Patients with more severe pain had increased depression and
lower quality of life. There were no significant gender differences. Analgesics
were used less frequently by PD patients despite poor pain management. In
conclusion, pain is an important symptom of PD and therefore should be screened
and adequately managed in every follow up visit.
P12.25
Effects of pain on functional
outcome in Parkinson’s disease and healthy controls
Abdul Qayyum Rana1, Mohammad A. Rana2,
Zakera M. Kachhvi3
1Parkinson's Clinic of Eastern Toronto
& Movement Disorders Centre: Toronto, Ontario, Canada
2Faculty
of Medicine, James Cook University: Townsville, Queensland, Australia
3University
of Toronto Scarborough: Toronto, Ontario, Canada
Introduction: Pain can be substantially
detrimental to one’s daily activities due to its ability to inflict the individual
by both physical and psychological means. Despite significant prevalence, pain
has not been well-studied among Parkinson’s disease patients. It is possible
that pain contributes to debilitation in patients, in additional to the
difficulties that are normally prevalent as a result of the disease. The
current study compares the severity of deficiencies in functional outcomes of
patients and healthy controls who attribute such deficiencies to existing pain.
Methods: Self-report questionnaires on several
aspects relating to pain were administered for 127 Parkinson’s disease patients
and an equivalent number of healthy controls. The subjects were not
individually matched, but the two groups were matched overall to have
equivalent gender distribution and near-equivalent mean age, and are also
expected to have similar lifestyles (given that controls in most cases were
caregivers of PD patients). The 90 patients and 76 controls who reported having
any pain were invited to complete the Brief Pain Inventory (BPI) and the Pain
Disability Index (PDI). Scores from these were used to assess deficiencies in
various aspects of functional outcome, compared across the two groups. Further,
different data collected on various aspects of pain (severity, location, duration,
etc.) were analyzed for their potential predictive effects on the various
functional disruptions.
Results: Comparison between the groups
for measures of functional outcome indicated that Parkinson’s disease patients
experience substantial debilitation on a majority of the relevant items in the
BPI and PDI. In conclusion, the results indicate that Parkinson’s disease
patients who experience pain tend to have increased functional deficits
compared to a similar group of healthy controls. Pain is implicated as the
cause of these deficiencies by both groups.
P12.26
Factors affecting pain in Parkinson’s disease
Abdul Qayyum Rana1, Adeel
Khan2, Russell Uppal2, Patrick Galange2,
Muhammad Saad Yosuf3, Ishraq Siddiqui3, Ajantha Jesudasan4,
Afshan Nazil Rana5, Mohammad Abounaja6, Kevin Hafez7,
and Mohammad Rana8
1Director Parkinson’s Clinic of Eastern
Toronto and Movement Disorders Centre, Toronto, ON, Canada
2University
of Ottawa, Faculty of Medicine, Ottawa, ON, Canada
3University of Toronto,
Faculty of Neuroscience, Toronto, ON, Canada
4Parkinson’s
Clinic of Eastern Toronto and Movement Disorders Centre, Toronto, ON, Canada
5Department of
Medicine, The Scarborough Hospital, Toronto, ON, Canada
6Rogue Valley Hospital,
Toronto, ON, Canada
7Department of Family
Medicine, University of Calgary, AB, Canada
8Faculty of Life
Sciences, York University, Toronto, ON, Canada
Objective: To study the
associations between various factors and pain in a Parkinson's disease
(PD) patient population.
Methods: This study
investigated 121 PD patients, of which 80 reported to have pain in at least one
area of the body. Exclusion criteria included patients suffering from external
causes of pain, such as trauma and patients with cognitive impairment whose accounts
may not have been reliable. Further inquiry determined the etiology of pain, as
well as aggravating and alleviating factors. The efficacies of pharmacological
or non-pharmacological therapies were assessed through additional questioning.
Individuals were also asked whether their pain was unintentionally affected by
other measures, such as prescribed PD medications.
Results: Multiple linear regression analysis with a
Wald test value of 4.070 (p = 0.044) demonstrated a statistically significant
relationship between the administration of analgesics in patients with high
reported pain and their pain relief. However, patients who experienced moderate
pain did not exhibit any statistically significant levels of pain relief with
the use of analgesics (Wald = 2.097, p = 0.148). Similarly, non-pharmacological
therapies, PD medicine, and comorbidities showed no statistically significant
correlations with pain relief.
P12.27
Factors contributing to variations in visual
hallucinations experienced within Parkinson’s disease patient populations.
Abdul Qayyum Rana1,
Patrick Galange2, Russell Uppal2, Adeel Khan2,
Ishraq Siddiqui3
1Director Parkinson’s
Clinic of Eastern Toronto and Movement Disorders Centre, Toronto, ON, Canada
2University
of Ottawa, Faculty of Medicine, Ottawa, ON, Canada
3University of Toronto,
Faculty of Neuroscience, Toronto, ON, Canada
Objective: To examine the potential effects of
patient age, Parkinson’s disease (PD) duration, dementia duration, visual
hallucination (VH) duration, and Hoehn and Yahr (H&Y) stage progression on
the experience of hallucinations within a PD patient population.
Methods: This retrospective study investigated
42 PD patients aged 63 to 95 who reported having VH. All individuals were diagnosed
with idiopathic PD and were regularly followed every three to six months at a
community-based Parkinson’s disease and movement disorders centre between 2005
and 2011. VH were diagnosed and rated by the clinic neurologist using the VH
component of the Parkinson’s Psychosis Rating Scale (PPRS).
Results: Of the 45 patients
with VH that were initially assessed, three were removed for experiencing VH
for reasons other than PD. Among the inclusion group, multiple linear
regression analysis demonstrated a statistically significant relationship
between the duration of PD and the occurrence of threatening VH (p = 0.004).
Specifically, there was a significant relationship between the duration of PD
before VH and threatening VH (p = 0.001), as well as the duration of dementia
before VH and threatening VH (p = 0.003). There were no significant
correlations found between the duration of dementia and the duration of VH with
recorded parameters of VH experience or with patient age and H&Y stage
progression with the recorded parameters of VH experience.
P12.28
Sleep disturbances in a Senegalese patients series with
Parkinson’s disease in Fann Teaching Hospital
Lala Seck1 2, Paul Mbonda2, Yannick
Fogang2, Kamadore Touré1 2 3, Moustapha Ndiaye1 2,
Gallo Diop1 2, Mansour Ndiaye1 2
1Cheikh Anta Diop
University, Dakar, Senegal
2Neurological
Department of Fann Teaching Hospital, Dakar, Senegal
3Public Health
Department, Cheikh Anta Diop University, Dakar, Senegal
Objective - Sleep disorders are common
in Parkinson's
disease
(PD). They are the consequence of both neurodegenerative process and
neurochemical changes, but also of drug intake. Despite its high incidence,
they are not included in the routine clinical examinations. Our aim was to
assess sleep disorders among PD patients followed-up in a hospital center in
Dakar.
Patients and Methods - The study enrolled 26 consecutive
patients who fulfilled criteria for idiopathic PD in the neurological
department of Fann Teaching Hospital. They were tested with standardized
scales: unified PD rating scale
(UPDRS) and Hoehn and Yahr staging scale (HY scale).
Parkinson's
disease
sleep
scale
(PDSS) was applied for the assessment of sleep problems.
Results - There were 54% of male and 46% of female.
Correlations were found between PDSS score, HY stage and the mean duration of
disease, but not between PDSS score and UPDRS. There was no difference in PDSS
scores regarding gender and age. Analyzing each item in the PDSS scale,
the lowest score was obtained for item 8 (nocturia). We did not find any
difference in PDSS score between the patients under dopamine-agonist and those
under L-dopa. In conclusion, patients in advanced stages of the disease
and worse motility are more likely to have sleep problems. This
could lead practicians to take sleep disorders into account while following-up
PD patients.
P12.29
Non-motor clinical staging using the non-motor symptoms
scale and motor correlation in an UK cohort of Parkinson’s
Sokolov E2,3, Moon T3,
Martinez-Martin P4, Ray Chaudhuri K.1,2
1King’s College London,
National Parkinson Foundation Centre of Excellence and Regional Movement
Disorders Unit, UK
2National Institute for Health Research (NIHR) Mental
Health Biomedical Research Centre and Dementia Unit at South London and
Maudsley NHS Foundation Trust and [Institute of Psychiatry] King’s College
London, UK
3Guys & St Thomas
NHS Foundation Trust, London, UK
4National Centre of
Epidemiology Alzheimer Disease Research Unit and CIBERNED, Alzheimer Center
Reina Sofia Foundation, Carlos III Institute of Health, Madrid, Spain
Objective: We recently described a novel grading system
of people with Parkinson’s (PwP) using the non motor symptoms scale (NMSS) and
assessing NMS burden (NMSB staging), the stages ranging from no NMS (stage 0)
to severe burden of NMS (NMSS > 71, stage 4).1 In this unselected
UK cohort of 517 cases, we provide a clinical categorization of cases after
allocating each case to the NMSB staging system.
Methods: Retrospective and prospective data on 517
cases have been collected in the UK for the validation studies of NMSS as well
as an ongoing NMS natural history study. All cases were staged as per NMSB and
clinical association with motor staging (Hoehn and Yahr) and other parameters
were assessed.
Results: Only 1 of 517 patients (0.19%) reported no
NMS (NMSB stage 0). 154 (30%) were at stage 2 moderate level of NMS and had a
mean age of 68± 12yrs with a median HY stage of 2, a relatively mild motor
stage. However, 23% had severe NMSB stage while HY score was moderate at a
median of 2, while 21% had very severe NMSB stage with HY score median of 2.5,
not be considered as advanced Parkinson’s from the motor perspective. Amongst
the NMSB stages 3 and 4, several NMS dominant endophenotypes were recognised
(sleep dominant, fatigue dominant for example) from a clinical perspective.
Conclusions: This study outlines the importance of
including NMS assessments, now formalized by the NMSB staging as part of a
clinical process to implement holistic care of the multi-morbid PwP.
Reference: Chaudhuri KR,1 Rojo JM,2 Schapira
AHV3, Brooks DJ,4 Stocchi F, Odin P et al. A proposal for a comprehensive gradation of Parkinson’s disease
severity combining motor and non-motor assessments: meeting the unmet need.
PLOS One. February 2013 | Volume 8 | Issue 2 | e57221
P12.30
Movement festination of
repetitive movements on the more and less affected side in patients with
Parkinson’s disease
Elizabeth L. Stegemöller1,
Mark. D. Tillman1, Colum D, MacKinnon2, Chris J. Hass1,
and Michael S. Okun1
1University
of Florida, Gainesville, FL, USA
2University
of Minnesota, Minneapolis, MN, USA
Objective: Patients
with Parkinson’s disease (PD) demonstrate movement festination (increase in
rate, decrease in amplitude, accompanied by hesitations) during repetitive
finger movements. Movement festination is not in most cases improved with
dopaminergic medication or STN-DBS, suggesting that it may not be associated
with changes in basal ganglia function. Typically the presentation of motor
symptoms in PD is asymmetric correlating with asymmetric degeneration of
dopaminergic neurons in the basal ganglia. It remains unknown if festination of
repetitive finger movements shows asymmetry between sides. The purpose of this
study was to compare the performance of repetitive finger movements between the
clinically defined more and less affected side in persons with PD. We
hypothesized there would be significant difference in clinical measures between
sides, but no difference in movement festination between both sides.
Methods:
Thirty-eight participants with idiopathic PD completed a repetitive finger
movement task “on” medication. Clinical evaluation scores were collected to
determine the most affected side. Movement rate and peak-to-peak amplitude were
obtained. For both measures, a repeated measures ANOVA was used to compare
differences between sides and across tone rates. A paired t-test was conducted
for the clinical evaluation measure.
Results: Clinical evaluation
confirmed the more affected side (p < 0.001). Movement festination was
revealed in both hands (p < 0.001). Movement amplitude (p = 0.57) and
movement rate (p = 0.06) did not differ between sides. These results
demonstrate that festination of repetitive finger movements was evident on both
sides, even though participants demonstrated a clinically more affected side.
Conclusion:
This study supports the notion that movement festination in
patients with PD may be due to changes in other motor control processes,
possibly outside the basal ganglia. Further study of movement festination in
other repetitive movements and investigation of potential treatment is needed.
P12.31
Examination of non-motor symptoms in early-stage
Parkinson’s disease
Roxanne Sterniczuk1,2,3, Kimberley P. Good1,2,
Ron Leslie4, John Fisk1,3,5, Gosia Phillips5,
Roger McKelvey5, , Kenneth Rockwood2, Magda Wojtowicz3,
Tyler Rolheiser6, Olga Theou2, Denise Lewis1,
Mackenzie Armstrong1, Paula Chiasson7 , Muhammed Naeem
Khan8, Christopher MacKnight2, Kerri Schoffer5,,
Matthias Schmidt8, Aaron Newman1,3, Benjamin Rusak1,3,
Harold Robertson1,5,9
1Department of
Psychiatry, Dalhousie University, Halifax, NS, Canada
2Geriatric Medicine
Research, Dalhousie University, Halifax, NS, Canada
3Department of
Psychology and Neuroscience, Dalhousie University, Halifax, NS, Canada
4Department of Medical
Neuroscience, Dalhousie University, Halifax, NS, Canada
5Department of
Medicine, Dalhousie University, Halifax, NS, Canada
6Department of Biomedical
Engineering, University of Alberta, Edmonton, AB, Canada
7Division of
Neurosurgery, Dalhousie University, Halifax, NS, Canada
8Department of
Diagnostic Imaging, Dalhousie University, Halifax, NS, Canada
9Department of
Pharmacology, Dalhousie University, Halifax, NS, Canada
Objective: Parkinson’s disease (PD) is currently
diagnosed on the basis of the presentation of various motor symptoms. However,
non-motor symptoms, such as olfactory deficits or sleep disturbance, may be
present years prior to the emergence of motor impairment. Our previous work
showed that newly diagnosed PD patients exhibit alterations to olfactory
regions of the brain, leading us to speculate that non-motor symptoms, and the
associated neurological changes, may precede the onset of motor symptoms, and
that this may provide a novel tool for the earlier diagnosis of PD. Preliminary
analyses of an ongoing study examining the relationship between PD and the
presence of non-motor symptoms are presented here.
Results: Comparisons between healthy controls (n =
10; 8 males) and individuals with early-stage PD without REM behaviour disorder
(n = 8; 3 males; i.e., Hoehn and Yahr <= 2; diagnosed within an average of
4.6 months of initial testing) were conducted. PD patients were found to rate
their sense of smell to be poorer than controls, and in line with this,
exhibited significantly greater impairment on the University of Pennsylvania
Smell Inventory Test (control M = 34.6; PD M = 24.7, out of 40). Those with PD
were more likely to be on sleep medication, although no significant changes
were found to specific aspects of sleep or daytime sleepiness. Diffusion tensor
imaging MRI (i.e., 1.5T) demonstrated visible alterations in the direction of
diffusion within the substantia nigra of PD patients; however, further
examination of non-motor regions is still required. Continuation of our
analyses will focus on whether the combination of olfactory, sleep, cognitive,
and DTI testing will allow for the specific and sensitive detection of early-stage
(premotor) PD.
P12.32
The impairment of
metaphor comprehension in Parkinson’s disease: the role of polysemy
Christina Tremblay1, Joël Macoir1, Mélanie
Langlois2, Laura Monetta1
1Département de réadaptation, Université Laval, Québec,
QC, Canada
2 Hôpital de l'Enfant-Jésus, Québec, QC, Canada
Objective: Metaphor comprehension
seems particularly affected in Parkinson’s disease (PD), and this impairment
has been attributed to executive dysfunctions (e.g., working memory and
inhibition deficits). However, so far, no study was conducted to measure the
influence of different type of metaphors on metaphor comprehension in PD.
Polysemy (the property of a word to have multiple related meanings) may
influence metaphor comprehension processing. In PD, inhibition and mental
flexibility impairments may lead to difficulties to switch between the literal
and figurative meanings in order to understand polysemous metaphors (such as These spies are foxes). By comparison, understanding a non-polysemous metaphor (such as These dancers are
swans) does not require switching between concepts,
so that this type of metaphors might be preserved. The main goal of this study
was to investigate the role of polysemy in metaphor comprehension in PD,
considering its high reliance on executive functions. We expected that only
polysemous metaphor comprehension would be impaired in PD individuals.
Methods: Twenty individuals with
idiopathic PD and twenty healthy controls (HC) were evaluated with an
experimental metaphor comprehension task (including non-polysemous and
polysemous metaphors) and a neuropsychological battery of tests for executive
functions (inhibition, mental flexibility and working memory).
Results: As
expected, a slowing in polysemous metaphor comprehension was observed in PD
compared to HC, an impairment significantly correlated with the executive
deficit observed in the PD group. Interestingly, PD participants made more
comprehension errors than the HC group in both types of metaphor. Our findings
indicate that, in PD, polysemy influence the processing time of metaphors, but
do not impact their comprehension.
P12.33
A comparative study of LRRK2 G2019S parkinsonism and
idiopathic Parkinson’s disease in Tunisia
Joanne Trinh1, Alan Donald1,
Christina Thompson1, Chelsea Szu-Tu1, Carles
Vilarino-Guell1, Rim Amouri2, Samia Ben Sassi2,
Emna Hentati2 ,Emna Farhat2, Fatma Nabli2,
Mourad Zouari2, Rachel Gibson3, Matthew Farrer1
and Faycel Hentati2
1Department of Medical
Genetics, Centre for Applied Neurogenetics, University of British Columbia,
Vancouver, BC, Canada
2Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis,
Tunisia
3Research and Development, GlaxoSmithKline Pharmaceuticals Ltd., Harlow,
England, UK
Objective: One third of Tunisian Parkinson’s disease
(PD) patients may be attributed to a LRRK2 G2019S mutation. Clinical data and
blood samples were recruited from 580 patients; 360 with idiopathic PD, 220
with LRRK2 G2019S. In the present study we provide the age-associated
cumulative-incidence (penetrance). We describe and compare disease onset and
clinical symptoms among homozygous and heterozygous LRRK2 G2019S patients compared with idiopathic PD.
Method: Regression was performed for autonomic
(SCOPA-AUT), cognitive, motor, psychiatric, sensory and sleep assessments.
Survival analysis techniques were used to estimate the penetrance in sporadic
cases and familial carriers.
Results: No differences were observed between LRRK2
G2019S heterozygotes and homozygotes, hence these genotypes were combined. With
the exception of cognitive testing, the scales applied were sensitive to
dysfunction in motor and non-motor domains. Motor assessments and sensory
assessments between idiopathic PD and LRRK2 Parkinsonism were comparable.
However, LRRK2 G2019S had fewer problems with REM sleep disorder (16% vs. 29%,
p<0.001) and gastrointestinal dysfunction (0.64 vs. 0.74, p<0.04). The
age-associated cumulative incidence (penetrance) of parkinsonism for LRRK2 G2019S carriers was 30% at age 50
increasing to 80% at age 70. While the cumulative of male LRRK2 carriers is comparable to idiopathic PD, female carriers
become affected 5 years earlier, and within families the same trend was
observed.
Conclusions: Findings from LRRK2 parkinsonism may be
generalized to idiopathic PD. Future
studies might include a retrospective questionnaire of first symptoms and
signs, as well as a smaller, longitudinal effort of LRRK2 families with kinetic
analysis of normal movement.
P12.34
Postprandial and orthostatic hypotension in patients with
de novo Parkinson’s disease
Tadashi Umehara1, Hisayoshi Oka1,
Chizuko Toyoda1 and Yasuyuki Iguchi2
1Department of
Neurology, Daisan Hospital, The Jikei University School of Medicine, Tokyo,
Japan
2Department of
Neurology, The Jikei University School of Medicine, Tokyo, Japan
Objective: To examine the correlation between
postprandial hypotension (PPH) and orthostatic hypotension (OH) in patients
with de novo Parkinson’s disease (PD).
Methods: Twenty-eight patients never treated with
anti-Parkinson drugs were enrolled in this study. PPH was examined via a 75-g
oral glucose tolerance test. Systolic blood pressure (SBP) was initially
measured after 20 min of rest in the supine position, and then the subjects
drank 75 g of glucose water. Thereafter, the SBP was measured every 10 min for
the next 120 min.
Plasma norepinephrine
(NE) concentrations were initially measured after the 20 min of rest, and after
the subjects drank the glucose water, NE concentrations were measured again
every 30 min for the next 120 min.
Differences in the NE
concentrations between each blood collection time and that measured after the
20 min of rest (⊿NEPPH) were
calculated. OH was examined by head-up tilt-table test. SBP was measured after
the 20 min of rest and every 1 min after tilting. NE concentrations were
measured after the 20 min of rest and after 10 min in the tilted position, and
the difference in NE concentrations between the two positions (⊿NEOH) was calculated. PPH and OH
were defined as a decrease in systolic BP of 20 mmHg or more after completion
of glucose ingestion and in a tilted position, respectively.
Results: PPH was observed in 15 (53.5%) of 28
patients. The severities of PPH and OH correlated significantly, and they also
correlated significantly with NE concentrations measured after 20 min of rest. ⊿NEOH correlated significantly with
the severity of OH but ⊿NEPPH did
not correlate with that of PPH. The correlation between PPH and OH in de novo
PD was therefore attributed to blunted sympathetic nerve activity.
P12.35
Characterization of
freezing of gait in Parkinson’s patients utilizing wearable foot pressure
sensors
Si Yu Xian1, 3, Fariborz Rahimi1,3,
Angela C. Roberts1,2, Danielle B. Boucher1,2, Mehdi Delrobaie1,3,
Mandar Jog1,2,3
1London Health
Science Center,
UK
2University of
Western Ontario,
ON, Canada
3National Parkinson
National Foundation Center of Excellence
Objective: Freezing of gait (FoG)
is a debilitating symptom of Parkinson’s disease associated with disease
duration and severity. Patients who experience FoG report their feet being
stuck to the ground during walking despite having intention to walk. Freezing
of gait is a major risk factor for falls in PD patients, but currently
rehabilitation and treatment for patients with freezing is limited. Our aim is
to characterize freezing episodes kinematically to aid in the development of
rehabilitation processes.
Methods: Patients with FoG were
identified by a movement disorders specialist. Five tasks were used to elicit
FoG in patients, including Timed-up-and-go (TuG), TuG while performing serial
subtractions, TuG with 90 degree turns, surprise 90 degree turns, as well as
360 turns. Episodes were recorded in video and identified in kinematic data
through MatLab. Freezing episodes were defined from the point where patients
stopped moving up until patient initiates/reinitiates gait. Mean CoP values for
each foot were compared within each FoG episode.
Results: Of 20 Patients
participated, six patients with a total of 145 episodes were recorded. Back and
forth (BF) movement in Center of Pressure (CoP) decreased in amplitude during
FoG episodes across all patients. Absolute differences in mean CoP between the
feet for the beginning or whole duration of freezing episodes were
significantly different than zero (t(136)=14.14, t(136)=13.90, p<.001 respectively). Overall, foot
pressure sensor technology and CoP analysis is a viable tool for characterizing
FoG episodes. Difference in mean CoP suggests an asymmetric posture in FoG,
despite resemblance to standing. This characterization could be used to
differentiate FoG from simple standing. This asymmetry is a necessary
precondition for step generation and freeze breaking. The results could be
potentially useful in rehabilitation or suggestion of strategies breaking
freeze.
P12.36
The effects of dopaminergic drugs on speech in
individuals with Parkinson’s disease
S. Elizabeth Zauber1, Jessica E. Huber2
1Indiana University
Medical Center, Indianapolis, IN, USA
2Purdue University,
Department of Speech, Language, and Hearing Sciences, West Lafayette, IN, USA
Objective: The purpose of this study was to examine
the effects of dopaminergic medications on speech in individuals with
Parkinson’s disease.
Methods: Eleven patients with Parkinson’s disease
were enrolled in the study. Patients were, on average, 63.5 years old and had
been diagnosed for 13.3 years. United Parkinson’s Disease Rating Scale (UPDRS)
scores ranged from 24-57 (mean=43) off medication; and from 9-34 (mean=20) on
medication. Average Mini Mental Status Exam (MMSE) score was 27.8. Patients
produced a monologue on a topic of their choice and read a short passage and
single sentences. Cognitive testing was completed on medication for all
patients.
Results: Patients
produced significantly shorter utterances when on medication, as compared to
off. There were no significant differences in sound pressure level (a measure
of vocal intensity/loudness) and no change in the number, duration, or
grammatical location of silent pauses. UPDRS scores off medicine were
significantly correlated with the production of shorter utterances and more
silent pauses. Six patients were categorized as primarily having difficulty
with postural instability and gait, four patients were categorized as
intermediate, the most classic form of Parkinson’s disease, and one was
categorized as tremor dominant. Examination of speech measures in the two
larger groups demonstrated lower sound pressure level, more abnormal speech
rate (faster and slower), more breaths at locations unrelated to syntax, more
speech revisions, and more filled pauses (“um” for example) in the postural
instability and gait group as compared to the intermediate group.
Results/Conclusions: Dopaminergic medications have a
slight negative effect on speech by reducing utterance length. Disease
severity, as indexed by the UPDRS off medication score, has a much greater
effect on speech impairments. Patients who show primary difficulty with
postural stability and gait also show greater speech impairments than those
patients who have more classic Parkinson’s disease symptoms.
CLINICAL SCIENCES: PROGRESSION & PROGNOSIS
P13.01
Investigating motor symptom progression
in the more-affected versus less-affected side in Parkinson’s disease
Rachel Boehm1,
Quincy Almeida1
1Sun Life Financial Movement Disorders Research and
Rehabilitation Centre, Wilfrid Laurier University, Waterloo, Ontario, Canada
Objectives: Currently, it is
unclear whether disease progression in Parkinson’s disease (PD) differs between
the more-affected side compared to less-affected side. The objectives of the
current study were to investigate the change in motor symptoms in the
more-affected and less-affected sides after one year, and to evaluate the
asymmetry between the two sides after one year.
Methods: 70
patients with PD (M:42; F:28; Age: 67.6±8.1) were evaluated twice (one year
separating the assessments) using symptom subsets of Unified Parkinson’s
Disease Rating Scale motor score evaluation (UPDRS III). The subsets included
resting tremor, action tremor, rigidity and voluntary motor control.
Participants were evaluated while ‘on’ their Parkinsonian medication. Wilcoxon signed-rank test was used to
evaluate the differences between the initial assessment and the one-year
assessment for the two sides (alpha = .0125).
Results: Overall, significant deterioration was observed in the less-affected
side after one year in resting tremor (p=.009), voluntary movement (p<.001) and rigidity (trend, p=.013). No changes were observed in the
more-affected side after one year. Despite the worsening in the less-affected
side, the more-affected side remained more impaired than the less-affected side
at both assessments in all subsets (p<.0125). Additionally, asymmetry
between the two sides decreased significantly in the action (p=.02) and resting
tremor subsets (p=.02) after one year. There was also a significant increase in
the daily dose of dopaminergic medication after one year (p<.001).
Conclusions: Separating the UPDRS III into subsections
identified progression in the less-affected side but not in the more-affected
side. Although the increased dopaminergic medication may have masked the
progression in the more-affected side, disease progression was still evident in
the less-affected side. These results suggest that clinicians and future
research trials should consider evaluating the two sides of the body
independently – according to the side-affected – when monitoring disease
progression in patients with PD.
P13.02
Clinical Outcomes in patients with Parkinson disease
treated with an MAO-B inhibitor
Khashayar Dashtipour1,
Mahmood Ghamsary2, Jack Chen1, Erin White2,
Pejman Dalai1
1Loma Linda University,
School of Medicine, Department of Neurology, Loma Linda, CA, USA
1Loma Linda University,
School of Allied Health, Loma Linda, CA, USA
Purpose: To assess differences in clinical outcomes
between patients with Parkinson disease (PD) treated or not treated with an
MAO-B inhibitor.
Methods: Demographic, treatment, and clinical outcome
data were collected retrospectively from medical records of patients with PD
treated at a single clinic of movement disorders. Patients in the MAO-B inhibitor
group were included only if duration of rasagiline or selegiline therapy was
for at least a year. Patients were excluded if: 1) less than one year on
current or previous MAO-B inhibitor therapy; 2) not currently on any of type of
PD medication; 3) incomplete/missing information for controlled variables
(i.e., age, gender, months since diagnosis, and levodopa equivalent dose).
A Wilcoxon test to
compare age, months since diagnosis and average levodopa equivalent dose (LED)
between the two treatment groups and a chi-square test to compare gender bias,
and proportion of patients prescribed amantadine, levodopa, pramipexole,
ropinirole, and deep brain stimulation were performed.
Multivariate logistic
regression was performed to calculate the odds ratio (OR) of Non-MAO-B
treatment versus MAO-B inhibitor treatment. Controlled variables (age, gender,
months since diagnosis, and levodopa equivalent dose) were included to improve
the model.
Results: Charts of 423 patients were reviewed and 287
were included for analysis. Baseline demographics were similar amongst both
groups with the exception of greater use of levodopa and less use of ropinirole
in the Non-MAO-B group. The mean LED was similar among groups. The occurrence
of dementia, dyskinesias, falls/unstable gait, freezing gait, and
hallucinations were lower in the MAO-B inhibitor group. The reduced occurrence
of dyskinesia in the MAO-B inhibitor group was statistically significant
(OR=1.874; p=0.0426).
|
MAO-B
Inhibitors: |
Non-MAO-B
Inhibitors |
Odds
Ratio |
p-value |
Hallucinations |
28.28%
(56/198) |
29.55%
(26/88) |
0.95 |
n/a |
Falls/Unstable
Gait |
46.73%
(93/199) |
57.95%
(51/88) |
1.35 |
0.266 |
Freezing
Gait |
23.74%
(47/198) |
32.95%
(29/88) |
1.42 |
0.239 |
Dementia |
25.76%
(51/198) |
34.09%
(30/88) |
1.37 |
0.272 |
Dyskinesia |
25.00%
(49/196) |
41.38%
(36/87) |
1.87 |
0.043 |
Conclusions: This retrospective analysis suggests MAO-B
inhibitors may reduce the risk of dyskinesia (OR = 1.87) in patients who take
them for at least one year.
P13.03
Rapid
disease progression in adult-onset Mitochondrial Membrane Protein associated
neurodegeneration
Okan
Dogu1, Catharine E Krebs2, Hakan Kaleagasi1,
Zafer Demirtas1, Nevra Oksuz1, Ruth H Walker2,3
and Coro Paisán-Ruiz, 2,4,5
1Dept. of Neurology, Mersin University
Hospital, Mersin, Turkey
2Dept. of Neurology, Mount Sinai School
of Medicine, New York, NY, USA
3Dept. of Neurology, James J. Peters
Veterans Affairs Medical Center, New York, NY, USA
4Depts. of Psychiatry and Genetics and
Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA
5Friedman Brain Institute, Mount Sinai
School of Medicine, New York, NY, USA
Objective: To report genetic findings of two
families with Mitochondrial Protein-Associated Neurodegeneration.
Background: MPAN is a recently
described NBIA syndrome caused by C19orf12 mutations and shows significant
phenotypic heterogeneity.
Methods: Three patients and 4 healthy
individuals from two families were included for genetic study. SNP genotyping
was performed using the HumanOmniExpressExome bead-chip that contains 700,000
genome-wide markers plus additional 240,000 putative functional exonic
variants. The entire coding region and intron-exon boundaries of C19orf12 were
PCR amplified in all available DNA samples. All purified PCR products were then
sequenced. The resulting sequencing reactions were resolved on an ABI3130
genetic analyser and analysed using Sequencher 5.0 software.
Results: Three patients from two families with
rapidly progressive extrapyraimdal syndrome and decreased signal intensities in
g.pallidus and s.nigra were included. Homozygosity mapping through genome-wide
SNP genotyping was performed. We identified a single homozygous segment common
to all three affected individuals. This homozygous segment of 2Mb and located
on chromosome 19q12. This disease-associated locus containing 613 consecutive
SNPs in length only comprised eight different genes, including the C19orf12
gene. Direct sequencing of the entire coding region of C19orf12 identified a
disease segregating p.Thr11Met mutation.
Conclusions: In conclusion, we
present three new NBIA cases with C19orf12 mutations that presented with an
adult-onset form without optic abnormalities, and, in 2 cases, with a rapidly
progressive extrapyramidal and pyramidal disorder.
P13.04
Distribution of
Clinical subtypes in Parkinson’s disease associated with Dysphagia: Comparison
of de novo drug naive stages with advanced stages.
M. Hahne1, D. Hartmann1 , E.
Rudbach1, B. Griewing1, W. Jost 2, H.
Reichmann3
1Clinic of Neurology Bad Neustadt
2Parkinson’ Disease Center Wolfach
3Clinic of Neurology, University Dresden, Germany
Objective: Prevalence of Clinical subtypes in Parkinson’s disease associated with
swallowing impairment measured by videofluorscopy, clinical examination and
scoring in stages 1-4 (Hoehn & Yahr).
Methods: Clinical Examination, videofluorscopy and scoring by UPDRS I to V, ESS,
BDI and PDNMS Questionnaire. We divided into Akinetic Rigid type (AR),
Tremordominant type (TD) or Mixed type (M). Frequency of swallowing
disturbances determined by videofluorscopy and rating scales were expressed in
terms of number, standard deviation.
Results: 57 PD patients, 17 de novo drug naïve PD in stage 1 to 2, n= 34 in
stage 3 and n= 6 in stage 4 of Hoehn & Yahr. Videofluoroscopy detected
swallowing disturbances in n=6 (35%) of de novo PD, almost in pharyngeal phase,
thereby in 3 cases AR and 3 cases M . The corresponding frequencies in stage 3
H & Y were n= 14 (41%), AR 9 and M 5; and in stage 4 H & Y n=5 (83%),
AR 4 and M1, respectively. TD subtype in stage I, II or III was not affected.
With PDNMS and ESS higher than 10 pts, we observed a small association of AR
and M with item constipation and fatigue. In contrast, regarding clinical
swallowing disturbances measured by self rating scales, we found a lower
prevalence of 17% PDNMS question 3 in de novo, 29% in stage 3 and 67% in stage
4 H &Y. Our data demonstrate early occurance of dysphagia, detected by
videofluorscopy in Parkinson’s disease. We found a preference of the clinical
subtype AR morefrequent than M within all stages. This pattern was already
observed in the early and drug naive stages of Parkinson’s disease with de novo
diagnosis.
P13.05
Motor, cognitive and affective characteristics of new-fallers
compared to non-fallers in an incident cohort of Parkinson’s disease
Lynn Rochester1, Brook Galna1, Sue
Lord1, Dadirayi Mhiripiri1, and David Burn1
1Institute of Ageing
and Health, Newcastle University, Newcastle, UK
Objective: To compare motor, cognitive or
affective characteristics in people with Parkinson’s disease (PD) who
transition from being a non-faller to a faller and those who remain
non-fallers.
Methods: We
measured prospected falls in 70 people with PD with no history of previous
falls (self-report) for 12 months. In this study, we used the term new fallers
to identify those people who transitioned from no history of falls to their
first fall. A faller was defined as someone who experienced two or more falls
over 1 year of prospective monitoring. We compared the motor, cognitive and
affective characteristics from baseline assessment between new fallers and
non-fallers using Mann-Whitney U tests.
Results: 13 participants
transitions to become new fallers (mean (SD) age 69.0 years (9.0) years) whilst
57 remained non-fallers (67.1 yr (9.4)). Participants who became new fallers
walked more slowly than non-fallers with a slower and more variable step time,
slower sit-to-stand, increased PIGD (Postural Instability and Gait Disorder)
score and poorer executive function (One Touch Stockings) (Table 1). Balance
and depression scores did not discriminate new fallers from non-fallers.
Table 1 Baseline description of new fallers compared
to non-fallers.
Variable |
PD non
fallers (n=57) |
|
PD
new fallers (n=13) |
|
p |
|||
Mean |
SD |
|
Mean |
SD |
|
|||
PIGD score |
|
2.70 |
1.75 |
|
3.95 |
1.65 |
|
.022 |
Sit to stand (s) |
12.5 |
3.6 |
|
15.0 |
3.1 |
|
.026 |
|
OTS mean latency (ms) |
19,191
|
11,030
|
|
25,829
|
11,877
|
|
.016 |
|
Global Depression Scale |
2.11 |
2.07 |
|
2.69 |
2.18 |
|
.329 |
|
Total Fatigue (MFI) |
43.7 |
16.7 |
|
48 |
14.1 |
|
.277 |
|
Ambulation and Balance Confidence
Scale |
88.1 |
16.7 |
|
85.0 |
11.6 |
|
.083 |
|
Walking speed m.s-1 |
1.17 |
.20 |
|
1.02 |
.19 |
|
.022 |
|
Step time (ms) |
548 |
43 |
|
588 |
66 |
|
.021 |
|
Stance time variability (ms) |
21.0 |
8.8 |
|
26.3 |
10.2 |
|
.031 |
|
P13.06
Gait predicts decline in attention
over 18 months in an incident cohort of Parkinson’s disease
Lynn Rochester1,
Sue Lord1, Brook Galna1, Tien Khoo1, Gordon
Duncan1, Alison Yarnall1, Dadirayi Mhiripiri1
and David Burn1
1Institute
of Ageing and Health, Newcastle University, Newcastle, UK
Objective: To examine whether gait characteristics measured at
baseline can predict cognitive decline over 18 months in an incident cohort of
Parkinson’s disease (PD).
Methods: Fifty-eight people with idiopathic PD (mean (SD)
age 67.4 (10.6) years) participating in the ICICLE-GAIT study were assessed for
age, sex, disease severity, gait and cognition within four months of diagnosis
and 18 months after the baseline assessment. Gait speed was collected using a
7m instrumented GAITrite mat whilst walking for 2 minutes at their preferred
pace. Power of Attention (PoA) was assessed using the Cogntive Drug Research
(CDR) computerised assessment system. Loess regression was used to identify the
nature of the relationship between gait and change in attention at 18 months.
Segmented linear regression was then used to test if baseline gait speed
predicted change in cognition for those who walked faster and slower than 1m.s-1
at baseline.
Results: Thirty-one males and 21 females, with average (SD)
MDS-UPDRS III scores of 10.6 (9.8) participated in the study. There was a
non-linear relationship between gait speed and change in attention, with a
slower gait speed predicting cognitive decline for slow (<1m.s-1,
n= 18) but not fast walkers (1.0 1m.s-1, n = 40). A second model
showed that gait speed remained an independent predictor of cognitive decline
for the slow walking group even after controlling for baseline attention (Fig
1). Age, sex and disease severity did not correlate with change in attention
and were not included in the model.
Fig 1: Scatter plot
for gait speed and baseline attention correlated with change in attention
scores
P13.07
The SURE-PD trial: Safety, tolerability and
urate-elevating efficacy of inosine in Parkinson disease
Michael A. Schwarzschild for The Parkinson
Study Group SURE-PD Investigators*
Massachusetts General Hospital, Boston, MA,
USA
Background: Convergent biological,
epidemiological and clinical data have identified urate elevation as a
candidate strategy for slowing disability progression in Parkinson disease
(PD). In contrast to urate, its metabolic precursor inosine has shown favorable
oral bioavailability.
Objective: To assess the safety, tolerability,
urate-elevating efficacy and other effects of oral inosine in early PD, and
thereby determine whether and how to conduct a subsequent phase 3 disease
modification trial.
Methods: The ‘Safety of URate Elevation in PD’
(SURE-PD) study, a randomized, double-blind, placebo-controlled, dose-ranging
trial of oral inosine, enrolled subjects with early PD and serum urate <6.0
mg/dL. They were randomized to three treatment arms: placebo or inosine dosed
to elevate serum urate – either mildly (to 6.1-7.0 mg/dL) or moderately (to
7.1-8.0 mg/dL). Subjects were followed up to 24 months on study drug plus 1
washout month, with visits every 3 months to assess adverse events (AEs),
tolerability and urate concentration in serum and (once after 12 weeks) in CSF,
along with multiple secondary outcome measures.
Results: Seventy-five subjects (mean age 62; 55%
women) enrolled at 16 clinical sites, with median follow-up of 1.6 years.
Serious AEs (17) including infrequent cardiovascular events occurred at the
same or lower rates in the inosine groups relative to placebo. Although no
subject developed gout, 3 (1 in the mild urate elevation group and 2 in the
moderate group) developed kidney stones. 95% of subjects tolerated treatment at
6 months (significantly above the preset 30% futility boundary for
intolerability). Serum urate rose by 2.3 and 3.0 mg/dL in the respective
inosine groups (p<0.001 for each vs placebo), and CSF urate was greater in
inosine groups (p=0.006 and <0.001, respectively).
Conclusion: Inosine was safe,
tolerable, and effective in raising serum and CSF urate levels. The findings
support advancing to phase 3 development of inosine for PD.
Funding: The Michael J. Fox Foundation
CLINICAL SCIENCES: BEHAVIORAL DISORDERS
P14.01
Impulse Control Disorders in young-onset patients
with Parkinson ’s disease: cross-sectional study unveiling
associated factors
Martin Bareš 1,2, Tomáš Gescheidt 1,2, Veronika Majerová 3, Ladislav Dušek 4, Kristína Czekóová 1,5, Petra Kotková 6, Jan Roth 3
1CEITEC -
Central European Institute of Technology, Behavioral and Social Neuroscience
Research Group, Masaryk University, Brno, Czech Republic
21st
Department of Neurology, Medical Faculty Masaryk University and St. Anne’s
University Hospital, Brno, Czech Republic
3Department
of Neurology, 1st Faculty of Medicine Charles University and General
Teaching Hospital, Prague, Czech Republic
4Institute
of Biostatistics and Analysis, Masaryk University, Brno, Czech Republic
5Institute of
Psychology, Academy of Sciences of the Czech Republic, Brno, Czech Republic
6Psychiatric
Hospital Kosmonosy, Czech Republic
Objective: The aim of our
cross-sectional study was to describe the frequency and associated factors of
ICD in young-onset PD patients in two specialized movement disorders centers in
the Czech Republic (Prague and Brno).
Methods: We have examined 34
young-onset PD patients- PD group (age 47.0 (35.0; 63.0) years, onset of PD
35.0 (28.0; 40.0) years; average duration 10.5 (4.0; 25.0) years; UPDRS 13.5 (7.0; 27.0) and 34 age and sex- matched healthy control subjects-
control group. Used questionnaires: South Oaks Gambling Screen for pathological
gambling and modified Minnesota Impulse
Disorders
Interview for other types of pathological behaviour. For detection for any
neuropsychological symptoms as possible associated factors, questionnaires for
depression (Montgomery-Asberg Depression Rating Scale), anxiety (Hamilton
Anxiety Rating Scale), psychopathology
(The Symptom Checklist 90; SCL-90) and Personality Style and Disorder
Inventory were introduced to both groups.
Results: We have found
significantly higher prevalence of pathological gambling in PD group (3 PD patients (8.8%) / no control subject) and higher
prevalence of hypersexuality (2 patients- 5.9% / no control) when compared to
the control group. 6 PD patients (17.6%) had a history of overusing of
medication. Symptoms of any ICD were more frequent in PD group (8
patients (23.5%) / 4 controls (11.76%). We have
observed following factors associated with occurence of any ICD in PD
group: anxiety, depression, personal typology and use of antidepressants. We
have not found any association related to the PD duration, actual stage of PD
or antiparkinsonian medication intake.
Discussion: We can
confirm increased incidence of ICD (especially pathological gabling and
hypersexuality) in young-onset PD patients. Other associated factors have to be
carefully detected and followed.
Acknowledgement: Supported
by unrestricted grant from Novartis.
MB, TG and KC were supported by the project “CEITEC - Central European
Institute of Technology” (CZ.1.05/1.1.00/02.0068) from European Regional
Development Fund.
P14.02
Effect of Parkinson’s disease on
proprioceptive control of reaching movements and postural stability limits
Stéphanie Bergeron1,4, Pierre Blanchet2,3, David
Mongeon1, Mariève Blanchet1, Jonathan Tremblay1,
François Prince1, Julie Messier1,4
1Département de kinésiologie, Université de
Montréal, Montréal, QC, Canada
2Département de stomatologie, Université de
Montréal, Montréal, QC, Canada
3Service de neurologie du Centre
Hospitalier de l'Université de Montréal, Montréal, QC, Canada
4Institut universitaire de gériatrie de
Montréal, Université de Montréal, Montréal, QC, Canada
Objective: The aim of
this study was to assess how medicated (ON, n=6) and non-medicated (OFF, n=9)
patients with mild to moderate Parkinson’s disease (PD) use proprioception to
control three-dimensional (3D) reaching movements and postural stability
limits, compared to healthy volunteers of similar age.
Methods: In the
reaching task, subjects performed 3D reaching movements in two conditions in
which the target location and hand positions were defined by either vision or
proprioception. The positions of the tip of the index finger and arm segments
were recorded using a NDI motion analysis system. In the postural task,
subjects stood on an AMTI force plate with bare feet at comfortable stance
width and arms crossed on the chest. Subjects were instructed to lean as far as
possible in four directions (forward, backward, rightward and leftward) without
lifting their feet or flexing their hips and to maintain this maximal position
for 10 sec. Subjects were tested in vision and no vision-proprioceptive
conditions. Accuracy of reaching movements and center of pressure (COP)
displacements during the stabilization phase of leaning movements were
analyzed.
Results: PD
patients in the ON state displayed a higher average level of 3D reaching errors
than control subjects (n=10) only when proprioceptive signals were used to
define target and hand positions (ANOVA, group by condition interaction,
p<0.05). In contrast, PD patients showed an overall smaller average level of
stability limits than healthy subjects (n=6) in both visual and proprioceptive
conditions. This difference was larger in OFF state patients, particularly
along the mediolateral axis (ANOVA, group by axis interaction, p<0.05).
Conclusion:
These preliminary findings suggest that the proprioceptive
guidance of reaching and posture are differentially affected by PD and
dopaminergic medication. An ongoing study in our laboratory assesses whether a
proprioception-based training program improves the proprioceptive control of
reaching and stability limits.
P14.03
Postural instability and future falls in
Parkinson's disease: contribution of increased tremor
Graham Kerr1, Steven Morrison2,Karl
Newell3, Peter Silburn4
1Queensland University of
Technology, Brisbane, Australia
2Old Dominion
University, Norfolk, VA, USA
3Pennslyvania State
University, PA, USA
4University of
Queensland, Brisbane, Australia
Objective: Postural instability leading to falls is a major health and injury
problem for people with Parkinson’s disease (PD). This study sought to
objectively assess relationships between tremor, postural instability and
falls.
Methods: 63 PD (67 ± 8.1 yrs) and 39 age- and gender-matched
controls (68.1±9.3 yrs) independently living in the community. Bilateral resting and
postural tremor was recorded from the hand and index finger segments of each
arm using light-weight uniaxial accelerometers. Postural motion in the anterior-posterior (AP) and medio-lateral (ML) directions were recorded from a force plate (100Hz). PD participants were assessed
while optimally medicated. Participants completed monthly falls calendars over 12
months. Tremor and postural motion data were analysed by
calculating root mean square (RMS) and approximate entropy (ApEn).
Results: 69% of PD and 46% of
older people fell over 12 months. PD fallers had longer disease duration, greater dopamine agonist
medication use and had worse measures of activities of daily living
(UPDRS II, Schwab & England) and Freezing of Gait than PD non-fallers. PD participants had 4-7 Hz peak
in resting and postural tremor whereas older people’s tremor contained peaks
between 2-4 Hz and 8-12 Hz. Both resting and postural tremor RMS and ApEn were
greater for PD fallers than non-fallers. For the older group there were no
differences in tremor RMS or ApEn between fallers and non-fallers. PD fallers
and older fallers had greater ML postural sway than non-fallers. Compared to
non-fallers, ML postural sway was more regular for PD fallers whereas anterior-posterior
postural sway was more irregular for older fallers.
P14.04
Influence of impulse control disorders on the
quality of life among cognitively-intact Parkinson’s disease patients living in
the Tomsk region, Russia
Maria Nikitina1, Irina Zhukova1,
Olga Izhboldina1, Natalya Zhukova1, Valentina Alifirova1,
Anna Agasheva2, Alexey Povalyaev3, Marina Titova1
1Department of Neurology and Neurosurgery, Siberian State Medical
University, Tomsk, Russia
2Hospital _
2, Tomsk, Russia
3State Medical and Social Examination Service, Tomsk, Russia
Background: Non-motor features of Parkinson’s disease (PD) patients are
frequent and prevalent which impair the patients quality of life. Among impulse
control disorder (ICD) the behavioral dysfunction causes the greatest impact on
quality of life. Unknown whether how prevalent ICD are among PD patients in the
Tomsk region.
Objective: To
determine the prevalence of ICD and it’s correlation with life quality among
cognitively-intact patients with PD seen at the Movement Disorders Center of
“Siberian Medical University”.
Methods and materials: 73 Tomsk patients fulfilling the UK Parkinson’s Disease Society
Brain Bank Clinical Diagnostic Criteria for PD were included in the study.
Demographic data were obtained including: age, sex, onset of disease, disease
duration and medication intake. The Mini Mental State Examination (MMSE) was
done to exclude significant cognitive impairment. The Questionnaire for
Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIPRS) was
administered to quantify ICD. The degree of ICD was correlated with the quality
of life instrument, Short form health survey (SF-36); and the functional and
motor severity using the Unified Parkinson’s Disease Rating Scales (UPDRS).
Results: Our
cohort of patients had a mean: age of 62.4±8.6 years, and disease duration of
7.2±4.6 years. Out of the 73 patients, 33 (45.2%) probably had ICD based on the
QUIP-RS. ICD greatly impacts scores on SF-36.
Conclusions: The prevalence of ICD among this Tomsk region cohort of patients
is 45.2% which is higher than commonly reported worldwide. The presence of ICD
significantly correlated with poorer quality of life.
P14.05
The relation between obsessive-compulsive behaviors and PARKIN genotype
Sharp ME 1, Alcalay RN 1,2*,
Caccappolo E 1*, Mejia-Santana H 1,
Tang M–X 1,2, Rosado L 1, Orbe Reilly M 1,
Ruiz D 1, Louis ED 1,2,3,4, Comella C 5,
Nance M 6, Bressman S 7,8, Scott WK 9,
Tanner C MD 10, Mickel S 11, Waters C
1, Fahn S 1, Cote L 1,3, Frucht S
1, Ford B 1, Rezak M 12 ,
Novak K 13, 14 , Friedman JH15, 16,
Pfeiffer R 17, Marsh L 18-20, Hiner B 21
, Siderowf A 22, Payami H 23,
Molho E 24, Factor S25, Nutt J 26,
Serrano C 27, Arroyo M 27, Ottman R
1,3,4, 28, Pauciulo M29, Nichols W 29,
Clark LN 2,30,31,Marder K,2,3, 32
1Department of
Neurology, College of Physicians and Surgeons, Columbia University, New York,
NY, USA
2Taub Institute for
Research on Alzheimer's Disease and the Aging Brain, College of Physicians and
Surgeons, Columbia University, New York, NY, USA.
3Gertrude H. Sergievsky
Center, College of Physicians and Surgeons, Columbia University, New York, NY,
USA
4Department of
Epidemiology, Mailman School of Public Health, Columbia University, New York,
NY, USA
5Department of
Neurological Sciences, Rush University Medical Center, Chicago, IL, USA
6Struthers Parkinson's
Center, Park Nicollet Clinic, Golden Valley, MN, USA
7The Alan and Barbara
Mirken Department of Neurology, Beth Israel Medical Center, New York, New York,
USA
8Department of
Neurology, Albert Einstein College of Medicine, Bronx, New York, USA
9Dr. John T Macdonald
Foundation, Department of Human Genetics, Miami Institute for Human Genomics, Miller
School of Medicine, University of Miami, Miami, FL, USA
10Parkinson's Institute,
Sunnyvale, California, USA and the Department of Health Research and Policy,
Stanford University, Palo Alto, CA.
11Marshfield Clinic,
Department of Neurology, Marshfield, WI, USA
12Central DuPage
Hospital, Neurosciences Institute, Movement Disorders Center, Winfield, IL, USA
13Department of
Neurology, at NorthShore University Health System, Evanston, Illinois, USA
14Department of
Neurology, University of Chicago, Pritzker School of Medicine, Chicago,
Illinois, USA
15Butler Hospital, Providence,
Rhode Island, USA
16Department of
Neurology, Alpert Medical School of Brown University, Providence, Rhode Island,
USA
17Department of
Neurology, College of Medicine, University of Tennessee Health Science Center,
Memphis, Tennessee, USA
18Morris K. Udall
Parkinson's Disease Research Center of Excellence, Johns Hopkins University
School of Medicine, Baltimore, Maryland, USA
19Department of
Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine,
Baltimore, Maryland, USA
20Department of
Neurology and Neurological Sciences Johns Hopkins University School of
Medicine, Baltimore, Maryland, USA
21Medical College of
Wisconsin, Milwaukee, Wisconsin USA
22Parkinson's Disease
and Movement Disorders Center, Pennsylvania Hospital, Philadelphia,
Pennsylvania, USA
23New York State
Department of Health Wadsworth Center, Albany, NY, USA
24Parkinson's Disease
and Movement Disorders Center of Albany Medical Center, Albany, NY
25Department of
Neurology, Emory University, Atlanta, GA, USA
26Portland VA Medical
Center Parkinson Disease Research, Education and Clinical Center, Portland,
Oregon, USA and Oregon Health & Science University, Portland, Oregon, USA.
27University of Puerto
Rico, San Juan, Puerto Rico
28Division of
Epidemiology, New York State Psychiatric Institute, New York, NY, USA
29Division of Human
Genetics, Cincinnati Children’s Hospital Medical Center and the Department of
Pediatrics; University of Cincinnati College of Medicine
30Department of
Pathology and Cell Biology, College of Physicians and Surgeons, Columbia
University, New York, NY, USA
31Center for Human
Genetics, College of Physicians and Surgeons, Columbia University, New York,
NY, USA
32Department of
Psychiatry, Columbia University Medical Center, NYC, NY, USA
Background:
Mutations
in PARKIN are a known genetic risk
factor for early onset Parkinson’s disease (EOPD). We have shown that people
without PD who harbor two PARKIN
mutations (compound heterozygotes) have a higher risk of depression than those
without mutations, possibly representing a pre-motor feature of future PD.
Other psychiatric symptoms, like obsessive compulsive behaviors, are also seen
in PD but the genetic contribution to these symptoms is not well characterized.
We investigated the role of PARKIN
mutations in obsessive compulsive symptoms among those with EOPD and their
relatives.
Methods:
We
collected psychiatric information using the Schedule of Compulsions and
Obsessions Patient Inventory (SCOPI), Patient Health Questionnaire and Beck
Depression Inventory II on 104 probands with (n=49) and without (n=55) PARKIN mutations. We also evaluated 169
genotyped unaffected family members of patients with PARKIN-associated EOPD (6 with two PARKIN mutations (3 of whom belong to the same family), 83 with one
mutation and 80 without (wild-type)). We compared SCOPI performance of persons
with EOPD to their family members. We then assessed for predictors of higher
scores (outcome) among people with PD using linear regression models adjusted
for demographics, disease characteristics and PARKIN mutation status. Among family members, we tested whether PARKIN mutation status was associated
with a higher SCOPI score.
Results: There was no significant difference in SCOPI
scores between people with PD and their family members (p=0.419). Among people
with PD, higher BDI scores (p=0.035), and wild type PARKIN mutation status (0.019) were associated with higher SCOPI
total score. Gender, age, education, disease duration, presence of anxiety, and
motor severity were not. Among unaffected relatives of PARKIN-associated EOPD, compound heterozygotes (who are at high
risk of PD) scored higher than either heterozygotes or non-carriers on SCOPI
total (p=0.01) and on the combination of subscales most representative of
obsessive compulsive behaviors (obsessive checking, obsessive cleanliness and
compulsive rituals) (p=0.005).
Conclusions:
People
with EOPD are not more likely to demonstrate obsessive-compulsive behavior than
their family members. However, family members who are compound heterozygote PARKIN carriers (i.e. with a high
genetic risk for PD) score higher on scales of obsessions and compulsions. Long
term follow up is required to assess whether these are pre-motor signs of PD in
PARKIN carriers.
CLINICAL SCIENCES: COGNITION/ MOOD/ MEMORY
P15.01
Personality and Depression: Factors that influence
reported quality of life among PD Patients
Susan Spear Bassett, Zoltan Mari, Gregory Pontone
Johns Hopkins School
of Medicine, Baltimore, MD, USA
Objective: Previous work has cited both personality
factors, mainly neuroticism and conscientiousness, and depression as major
factors affecting the functioning of patients with Parkinson’s disease (PD). We
were interested in understanding the contribution of each of these to reported
quality of life (QoL), an outcome measure incorporated into many clinical
studies.
Methods: 97 PD patients, under the age of 66 and
without dementia completed the NEO Five Factor Inventory (NEO-FFI) of
personality, the Parkinson’s Disease Quality of Life Questionnaire (PDQL) and
the Beck Depression Inventory. Patients were clinically assessed for motor
function using the Unified Parkinson’s Disease Rating Scale (UPDRS) - III and
evaluated for the presence of depression with the Hamilton Depression Rating
Scale (HDRS). Stepwise regression models were constructed to examine the
contribution of neuroticism, conscientiousness, depression symptomatology and
motor function (UPDRS-III) to scores on the four subscales of the PDQL
(parkinson symptoms, systemic symptoms, emotional function, social function).
Age, education, and symptom years were also included but were non-significant
and were dropped from the models.
Results: The sample was two-thirds male, with an
average of 16 years of education and an average of 6 years since the onset of
PD symptoms. The overall PDQL score was significantly associated with scores on
the Beck Depression Inventory (F= 7.41, p<.01). The four PDQL factors
however, had differing predictors. The Parkinson’s Factor was related to the
UPDRS III and Neuroticism (F=20.19, p<.001); the Systemic Factor was related
to the Beck (F=31.312, p<.001); the Social Factor was related to the Beck
and the UPDRS III (F=43.625, p<.001); and the Emotional Factor was predicted
by Neuroticism and Conscientiousness (F=26.916, p<.001). In interpreting
patient responses on the PDQL it is important to understand whether they
reflect aspects of PD, i.e. motor impairment and depression, which are amenable
to treatment, or whether they reflect personality traits.
P15.02
Impact of Parkinson’s disease on social role function:
Multi-faceted disability
Susan Spear Bassett, Gregory Pontone, Zoltan Mari
Johns Hopkins School of
Medicine, Baltimore, MD, USA
Objective: Much of the focus on understanding and
characterizing the disability that accompanies Parkinson’s disease (PD) has
focused on the impact of motor impairments on activities of daily living that
are required for maintaining independence in the home and accomplishing self
care. However, the impact of PD on the maintenance of social roles and social
integration has received little attention. This study undertook to examine
changes in social roles in this disease and the factors related to this
disability.
Methods: 101 PD patients, under the age of 66 and
without dementia were enrolled in the study. Participants were assessed for motor function using the Unified
Parkinson’s Disease Rating Scale (UPDRS) - III Motor Scale, Groove Pegboard and
Finger Tapping task. They also were administered several cognitive tests
(Hopkins Verbal Learning, Brief Test of Attention, Verbal Fluency, Trails,
Ravens) and were evaluated for the presence of depression with the Hamilton
Depression Rating Scale (HDRS). In addition they were administered the Social
Adjustment Scale, which examines functioning for six different roles.
Regression models (SPSS) were constructed for each of the 6 roles as well as
overall social functioning.
Results: Overall social functioning was predicted by
depressive symptomatology, decreased verbal fluency and decreased fine motor
skills, R2 .52 (F=22.88, p<.001). Work, (R2.268,
F=10.96, p<.001) leisure (R2.364, F=17.17, p<.001) and
extended family roles (R2.260, F=10.34, P,.001) were related to
depression and decreased cognitive performance. The parental role was the only
role related solely to motor function, the UPDRS III (R2 .086,
F=5.71,p<.02 ). The family unit role was predicted by depression and fine
motor control (R2.249, F=9.96,p<.001). Only the marital role
failed to be predicted by any of the assessments. Psychiatric and cognitive
impairments, rather than motor dysfunction, are the major factors affecting the
ability of PD patients to maintain their social roles.
P15.03
A new paradigm in neuropsychological assessment: Motor Imagery. A pilot Study with Parkinson’s disease patients
Evangelina V.
Cores, Sandra Vanotti, Angeles Merino, Sergio Rodriguez Quiroga, Tomoko
Arakaki, Nélida Garreto.
Department of Neurology,
J. M. Ramos Mejía Hospital, Buenos Aires, Argentina
Objective: To evaluate the motor imagery through mental
chronometry paradigm in patients with Parkinson's disease (PDp). Motor
Imagery (MI) is the ability to create mental images or representations of a
motor act in the absence of the actual execution of the movement. It can be evaluated through the mental chronometry paradigm, which measures the time it takes the patient to mentally imagine performing movements and
then compare it with the time for the motor execution.
The MI has been
poorly evaluated in PDp. One
previous study reported IM conservation
in these patients.
Methods: 20 PDp who participated in the “Dance Therapy
Program using Argentine Tango” were recruited. Average age: 66.11 (SD = 5.9);
male: 60%; H&Y: II-III; average disease duration: 6.3 years;
MOCA: 26,8 (20-30). The MI was assessed through the Box and Block test where
the participant must transfer 20 blocks from side to side of a box during the
real implementation phase and during the imaginary phase. The time spent
in each stage was recorded.
Results: The average time execution phase was 37.15 seconds (SD = 11.9) and the average time in the MI phase was 32.17 (SD = 10.5). This difference was not statistically significant (p > 0.05). The time in both phases was positively associated: r = .47, p < 0.05, which could indicate that depend on common processes. Patients spend similar time for imagining and for executing the task. This may reflect an appropriate temporal consistency, showing that patients adapt their imagination to reality. It would suggest that patients may benefit from rehabilitation strategies that require the use of MI. These results are consistent with previous studies.
P15.05
Interactions between cognition, depression and L-Dopa in
Parkinson’s disease
Clotilde Degroot1,2,
Marie-Andrée Bruneau1,2, Béatriz Mejia-Constain1,
Christophe Bedetti1 and Oury Monchi1,2
1Centre de recherche, institut Universitaire de
Gériatrie de Montréal, QC, Canada
2 Faculté de medicine, Université de Montréal, QC,
Canada
Objective: It has been reported
that 50% to 70% of patients with Parkinson’s disease (PD) will experiment
depressive symptoms during their disease and it is also well established that
cognitive deficits exist even at the early stages of PD. These non-motor
symptoms are thought to be the most predictive of the quality of life in those
patients. However, there is a lack of consensus regarding the nature and
interactions between neuropsychological dysfunction and depression in PD and
the effect of L-dopa on depression is controversial.
Methods: 44 PD participants at
stages I and II Hoehn and Yahr were recruited with 20 healthy matched
volunteers. They underwent a comprehensive neuropsychological evaluation and
also filled the Beck Depression Inventory scale II (BDI). The
neuropsychological battery included tests of executive, visuo-spatial and
mnesic, and language functions. The BDI items were divided into 3 different
parts: mood, cognition and somatic
Results: Patients were divided in two groups:
with and without depressive symptoms. There were significantly more PD patients
with cognitive deficits in the depressed group compared to the non-depressed
one. Furthermore, amongst cognitively affected patients, depressed ones
exhibited significantly more impairments on mnesic and executive functions than
non-depressed ones. We have found correlations with L-Dopa and
neuropsychological functions (some mnesic and executive measures worsen as
L-Dopa dosage increase) but not with dopamine agonists. An increasing number
of studies have reported early PD patients with significant mnesic deficits and
not just executive ones. Our results show that these latter impairments may be
more common in PD patients with depression. Furthermore, our study indicates
that the dose of L-Dopa may interact with depressive symptoms and that it might
have an incidence when determining the global therapeutic approach.
P15.06
Relationships between motor, cognitive and psychological
outcomes following bilateral subthalamic nucleus deep brain stimulation
(STN-DBS) in patients with Parkinson’s disease
Jelena Djordjevic1,
Maria Fraraccio2, Michel Panisset2, Abbas Sadikot1
1 Montreal Neurological Institute, McGill University,
Montréal, QC, Canada
2 Hôpital Notre-Dame, Université de Montréal, Montréal,
QC, Canada.
Objective: Motor improvements associated with bilateral
STN-DBS in patients with PD have been documented at the group level, but the
degree of symptom relief varies greatly in individual patients. Similarly,
cognitive and psychological outcomes have been heterogeneous in these patients.
The aim of this study is to examine whether motor, cognitive and psychological
outcomes of the STN-DBS surgery are related.
Methods: We analyzed the results of 17 patients (10
men, 7 women, with a mean age 61 years) who underwent bilateral STN-DBS to
relieve the symptoms of PD. All of the patients were tested before and after
the surgery (mean follow-up interval 16.5 months). Their motor outcomes were
measured as pre-post differences off-medication from the motor examination
(part 3) of the Unified Parkinson’s Disease Rating Scale. We analyzed their
cognitive outcomes using standardized pre-post change scores from 24
neuropsychological measures, grouped into 8 cognitive domains (reasoning,
short-term memory, information processing speed, verbal episodic memory,
nonverbal episodic memory, language, visuospatial and executive functions).
Psychological outcomes were measured as pre-post differences in depression
(Beck Depression Inventory-II) and anxiety (Beck Anxiety Inventory).
Results: As expected, we found significant motor
improvements following DBS-STN. Cognitive decline was noted in the
fronto-executive and speed of information processing domains, while the
symptoms of anxiety improved. In general, motor changes were not related with
cognitive and psychological outcomes. Only marginally significant correlations
were found between motor changes with visuospatial functions and short-term
memory, and with the symptoms of anxiety. The reduction of the symptoms of
depression was associated with short-term and verbal episodic memory
improvements.
Conclusion: Patients showed the expected declines in
cognition as well as the improvements in anxiety following the STN-DBS, but
these changes were not prominently associated with motor outcomes.
Nevertheless, post-surgical relief from depression was associated with some
cognitive benefits.
P15.07
The impact of
treatment response to cognitive-behavioral therapy on different clusters of
depressive symptoms in Parkinson’s disease
Roseanne D.
Dobkin1, Michael A. Gara1, Margery H. Mark 1, 2
Matthew Menza 1,2
1 Department
of Psychiatry, Robert Wood Johnson Medical School, Piscataway, NJ, USA
2Department
of Neurology, Robert Wood Johnson Medical School, Piscataway, NJ, USA
Objective: Parkinson’s disease (PD) is frequently
complicated by depression and there is limited controlled research that can
inform the management of this disabling psychiatric comorbidity. A National
Institutes of Health-sponsored randomized controlled trial (RCT) of
Cognitive-Behavioral Therapy (CBT) plus clinical management, versus clinical
management only, for the treatment of depression in PD (dPD) was recently
conducted. The goals of the current study are to describe the impact of
treatment response to CBT on different clusters of depressive symptoms in PD
and to explore the extent to which stabilized antidepressant use throughout the
trial moderated specific symptom change.
Methods: Eighty depressed
people with PD participated in this RCT. CBT was provided for 10 weeks and
incorporated behavioral activation, cognitive restructuring, sleep hygiene,
anxiety management, and caregiver psychoeducation. Treatment response was
defined a priori as a rating of depression “much improved” or “very much
improved” on the Clinical Global Impression–Improvement Scale, or a reduction
of at least 50% from baseline in the Hamilton Rating Scale for Depression (HAM-D)
total score. HAM-D and Beck Depression Inventory subscales (BDI), which reflect
the heterogeneity of depressive symptoms in PD, were the focus of this study.
Results: CBT response was associated with
significant improvements in core mood (Cohen’s d= 3.28), sleep (Cohen’s d=
.58), anxiety (Cohen’s d= 1.17), and somatic symptoms (Cohen’s d= .77) as
assessed by the HAM-D, and negative attitudes toward self (Cohen’s d= 1.74),
performance impairment (Cohen’s d= 1.60), and somatic symptoms (Cohen’s d= .83),
as measured by the BDI. Stabilized antidepressant use moderated the impact of
CBT response on symptom change for somatic complaints only (HAM-D and BDI). In
conclusion, CBT has the potential to improve a diverse array of depressive
symptoms in PD. Combination treatment (CBT plus antidepressants) may help to
optimize the management of somatic complaints associated with dPD.
P15.08
Apnea-hypopnea index and supine apnea-hypopnea index could be indicators
for severity of cognition impairment in Parkinson’s disease: Retrospective
pilot study
Choong Kun Ha1,
Jeong Jin Park1, Eun-Kee Bae1
1Inha University Hospital, Incheon, South Korea
Objective: Sleep disturbance and cognitive impairments
are frequent in Parkinson´s disease (PD) and important non-motor symptom in PD.
Some studies shows high prevalence of obstructive sleep disorder (OSD) in PD
and correlation with severity of PD. It has been assumed that sleep apnea
syndrome(SAS) may have negative impact on sleep quality and affect memory
performances of PD patients. Although, Obstructive sleep apnea is a recognized
cause of cognitive dysfunction. Yet, the relationship between cognition
impairments and sleep-disordered sleeping in Parkinson with mild cognition
impairment (MCI) and dementia was not studied before.
To assess the relationship between cognition impairments and obstructive
sleep disorder in cognitively impaired Parkinson´s disease patients.
Methods: Twenty patients with PD with cognitive
impairments (9 patients with neuropsychologic-confirmed mild cognitive
impairment(MCI) and 11 patients with neuropsychologic-confirmed dementia) were
recruited from Inha polysomnography registry and underwent full night
polysomnography (PSG).
Results: In
baseline study, body mass index (BMI) was higher in PD with dementia(PD-D)
group.(24.6 Vs. 21.7, p=0.007) Among the parameters studied apnea-hypopnea
index(AHI), supine AHI and supine and non-supine AHI ratio were statistically
different between PD-D with PD with MCI(PD-MCI) groups.
P15.09
Mild Cognitive Impairment in Parkinson’s disease is linked with
extensive cortical thinning during longitudinal analysis
Alexandru Hanganu1, Christophe Bedetti1,2,
Clotilde Degroot1, Béatriz Mejia-Constain1, Anne-Louise
Lafontaine3, Sylvain Chouinard4, Oury Monchi1,5
1Centre de Recherche de l’Institut Universitaire de
Gériatrie de Montréal, Montreal, QC, Canada
2Centre d’Études Avancées en Médicine du Sommeils,
Hôpital du Sacré Cœur de Montréal, Montreal, QC, Canada
3Movement Disorders Unit, McGill University Health
Center, Montreal, QC, Canada
4Centre Hospitalier de l’Université de Montréal, Unité
des troubles du movement André Barbeu, Montreal, QC, Canada
5University of Montreal, Department of Radiology,
Montreal, QC, Canada
Objective: We performed a longitudinal
study in patients with Parkinson’s disease (PD) with and without mild cognitive
impairment (MCI) at the beginning of the study and tested whether cortical
thickness in the MCI group would reveal significantly more changes over time
than the non-MCI patients.
Methods: We included 33 non-demented PD patients at the early
stages of the disease who were studied twice 20 months apart. On each session (Time
1 and Time 2) they participated in an MRI investigation and a comprehensive
neuropsychological assessment. Based on the Time 1 neuropsychological
assessment, patients were divided in two groups: MCI positive and MCI negative.
The construction of cortical surface was based on MPRAGE 3T images, using
FreeSurfer 5.1 image analysis suite. Images underwent a standard pre-processing
and analyzing procedure according with FreeSurfer longitudinal stream. (Reuter
et al. 2010). Misclassification of
tissue types was corrected by minimal manual adjustment. Cortical thickness was computed as the shortest distance
between the grey/white boundary and gray/cerebrospinal fluid boundary at each
vertex on the tessellated surface (Fischl
et al. 2000). Analysis of longitudinal
data was performed using the linear mixed effects model included in FreeSurfer
(Bernal-Rusiel et al. 2013).
Results: The intergroup
analysis revealed increased cortical thinning in PD-MCI compared with PD
non-MCI in the right supplementary motor area (SMA), ventral premotor cortex,
left middle temporal gyrus, supramarginal gyrus and lingual cortex. The
intragroup results showed bigger clusters of cortical thinning in PD-MCI in
occipital lobe and premotor cortex bilaterally, as well as right SMA, middle
temporal gyrus and precuneus cortex. On the other hand, the PD non-MCI group
exhibited smaller clusters in the right occipital cortex, supramarginal gyrus
and superior temporal gyrus. Our results suggest that the early presence of MCI
in PD patients is indicative of faster neural degradation.
P15.10
Subthalamic
Nucleus deep brain stimulation and impulsivity : dissociating impulse
expression and suppression in Parkinson's disease patients
Thierry Hasbroucq1, Frédérique Fluchère1,2, Borís Burle1, Franck
Vidal1,Wery van den
Wildenberg3,4, Jean-Philippe
Azulay2, Alexandre
Eusébio2
1Laboratoire de
Neurosciences Cognitives, Fédération de Recherche
Comportement-Cerveau-Cognition, Aix-Marseille Université, CNRS, Marseille,
France.
2Pôle de Neurosciences
Cliniques, Aix-Marseille Université, APHM, Marseille, France
3Amsterdam Center for the Study of
Adaptive Control in Brain and Behavior, University of Amsterdam, Amsterdam, The
Netherlands
4Cognitive
Science Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands
Objective: although deep brain
stimulation (DBS) of the subthalamic nucleus (STN) tremendously alleviates the
motor symptoms of Parkinson's disease (PD), growing evidence suggests that DBS
also induces motor impulsivity. Impulsive actions constitute a major source of
errors in daily life. They entail (i) capture of the motor system by an action
impulse, which is an urge to act and (ii) a lack of suppression of that impulse
to prevent an overt error. Most experimental studies fail to dissociate between
the effects of STN DBS on impulse capture and on the ability to keep that fast
impulse in check. We propose a novel psychophysiological approach based on
electromyographic (EMG) analyses to decipher the effects of STN DBS on the
expression and suppression of erroneous impulses.
Methods: we used a reaction
time (RT) protocol, the Simon task that elicits prepotent response tendencies.
We analyzed performance and EMG activity of sixteen PD patients on and off STN
DBS and on and off dopaminergic medication in a full factorial design.
Results: we provide the
first direct evidence that STN DBS on the one hand increases the
occurrence of erroneous response impulses and on the other hand impairs the
proficiency to suppress impulse driven errors. Dopaminergic medication
specifically impairs impulse suppression.
Discussion: STN DBS increases impulsivity
both by enhancing the excitability of cortical motor structures and by reducing
the efficiency of the indirect pathway that links the striatum to the globus
pallidus interna to the globus pallidus externa via the STN. Dopaminergic
medication may reduce the inhibitory influence of the STN through its action on
the indirect pathway of the basal ganglia.
P15.11
Initial Results of a Clinical Trial comparing a
Neurocognitive Intervention to Supportive Therapy in Individuals with
Parkinson’s disease
Sarah K. Lageman, Therese Verkerke Cash, & Melody N.
Mickens
Virginia Commonwealth
University, Parkinson’s and Movement Disorders Center, Richmond, VA, USA
Objective:
Parkinson’s
disease (PD) is now conceptualized as a whole body neurodegenerative disease
with neurocognitive symptoms that gradually develop and progressively
compromise individuals’ activity levels, quality of life (QOL), and
independence. No neurocognitive interventions have been tailored to the needs
of individuals with PD despite the prevalence of neuropsychiatric and
neurocognitive symptoms in PD. This trial aimed to adapt empirically supported
memory and problem solving techniques for use in a PD population.
Methods: This ongoing,
randomized controlled trial (RCT) seeks to evaluate the feasibility and
preliminary effectiveness of a novel neurocognitive intervention, which
incorporates memory enhancement and problem solving strategies, compared to
nondirective supportive therapy in individuals with PD and Mild Cognitive
Impairment (N=11) and their support
persons (N=6). Individual outcomes
include neuropsychological tests of attention, processing speed, memory, and
executive functioning, and self-reported mood symptoms and QOL, given at
baseline, immediate follow-up, and 6-month follow-up visits.
Results: Preliminary findings
from the immediate follow up showed trends for improved short-term memory among
participants receiving the neurocognitive intervention. Attention, processing
speed, and mental flexibility appeared relatively stable for both groups. Mood
and QOL ratings did not appear to significantly alter in either group, but
overall depression ratings were mild in both groups and QOL ratings were
generally positive. Apathy ratings of participants in the neurocognitive
intervention condition appeared to markedly decline following completion of the
trial. Ongoing enrollment of additional participants and evaluation of outcomes
at a 6-month follow-up will reveal whether these benefits are consistent in a
larger sample and whether they are maintained over time. These initial results
suggest that targeting memory and problem solving skills may be effective in
counteracting aspects of neuropsychiatric and neurocognitive symptoms
experienced by individuals with PD.
P15.12
Does rTMS enhance
memory retention in Parkinson's disease (PD)?
A. Loggini1,
L. Marinelli1, D. Blanco2, C. Moisello2, C.
Fontanesi2, J. Lin2, M. Biaggioni3, P. Kumar3,
G. Abbruzzese1, A. Di Rocco3, M. F. Ghilardi2
1Institute of Neurology, DINOGMI, University of Genova,
Genova, Italy
2Department of Physiology and Pharmacology, City
University of New York, New York, NY, USA
3Division of Movement Disorders, Department of Neurology,
New York University, New York, NY, USA
Objective: In patients with
PD, skill retention is
poorer than in normal age-matched controls, despite a generally preserved
acquisition rate. It has been
shown that, in normal subjects, treatment with repetitive transcranial magnetic
stimulation (rTMS) at 5Hz may induce phenomena of long-term potentiation at the
cortical level. Here we verified whether a 5Hz rTMS treatment enhances retention of a visuo-motor skill in a
group of patients with PD.
Methods: Eighteen right-handed patients with PD (Hoehn
& Yahr stage: 2-3) and twelve age-matched right-handed normal controls were
tested one week apart in two separate sessions (rTMS and sham), each
encompassing two consecutive days. In both sessions, on day 1, subjects learned
to adapt their movements to a progressive 60° rotation of the visual display
(counterclockwise rotation in one session, clockwise rotation in the other)
and, immediately after the task, either real or sham 5Hz rTMS was applied over
the right posterior parietal cortex (P6, 10-20 EEG system); on day 2, retention
was tested. Acquisition and retention indices were evaluated by computing
directional errors of the movement trajectories. The effect of treatment was
assessed with repeated-measures ANOVA and post-hoc tests with correction for
multiple comparisons.
Results: On day 1, controls and patients (in both sham and rTMS sessions) adapted
their movements to the rotated display in a similar manner (p>0.05). On day
2, the mean retention index in normal subjects was significantly different from
that of the PD patients in the sham session (p<0.001), but not from that of
the TMS session (p>0.3). On average, there was a significant difference
between the retention indices in the sham and rTMS sessions (p<0.05),
although this effect was not uniform across patients. These data, first,
confirm that, in PD, retention is decreased and, then, suggest that rTMS
applied after learning might enhance retention.
P15.13
Working
memory and facial expression recognition in Parkinson’s disease individuals
Pilar
Martín1, Laura Alonso-Recio1,2, Fernando Carvajal1,
Sandra Rubio1, Ángela Loeches1
1
Universidad Autónoma de Madrid, Spain
2
Universidad a Distancia de Madrid, Spain
Objective: Parkinson´s disease (PD)
is associated with cognitive and also with emotional impairments. Nonetheless,
it remains controversial the precise nature of emotional recognition problems.
Specifically, while some results point to particular and distinctive emotional
and cognitive disabilities in PD; others indicate that emotional problems may
be secondary to (a consequence of) some cognitive-executive deficits implicated
in recognition tasks (e.g., in working memory). The present study aims to
discern whether emotional facial expression recognition abilities in PD are
related to working memory abilities.
Method: we compare the performance
of 50 PD patients and 49 healthy controls in four recognition tasks by means of
an N-Back procedure. In short, task consisted of identify similarity or
difference to the previous shown (1-Back) either of (1) an emotional facial
expressions, (2) gender of the face, (3) nonsense syllables, and (4) spatial
locations of squares inside a matrix.
Results: the PD group performed
worse than healthy individuals in the emotional facial expression and in the
spatial location tasks. Moreover, statistical contrast for single effects
showed that differences between groups were significantly larger for facial
expression than for the spatial location task. Taking together these results,
we conclude that working memory seems to be partially altered in PD, in
particular when it is required to operate with visuospatial material.
Nevertheless, higher differences in the emotional task suggest an additional
and specific difficulty in emotional facial expression recognition in PD. These
set of results indicate the difficulty to clearly differentiate emotional and
cognitive problems in PD. However, it also opens the possibility to design
cognitive rehabilitation programs including emotional facial expressions as
stimuli. It may be a way to work together and improve executive and emotional
problems with very relevant and common stimuli in everyday situations, as
facial expressions.
P15.14
Dance and cognitive functioning in Parkinson's disease
Beata Michalska1, Sharon Abrahams1,
Mo Morgan2
1The University of
Edinburgh, Edinburgh, Scotland, UK
2Dance 4 People with
Parkinsons, Edinburgh, Scotland, UK
Objective:
Parkinson’s disease (PD) is commonly accompanied by reduced health related
quality of life (HRQoL) and cognitive decline which decreases participation in
activities of daily living. Moreover, worsened motor abilities exacerbate dual
tasking performance such as walking while performing another task e.g. talking.
Unfortunately, pharmacotherapies and other treatment methods employed in PD
fail to address the cognitive impairment exhibited in this population. A
growing body of evidence associates dance with increased HRQoL in PD and
ameliorated motor function. Additionally the relation between HRQoL and
cognition in PD has also been described. However, to date it has not been
investigated whether dance can ameliorate cognition in PD.
Methods: Six PD
participants took part over a 10 week
period in 90 minute dance for PD classes
once a week; three of them were described as single case studies. A battery of
cognitive tests was applied at the baseline, after dance intervention and in a
1 month follow up.
Results: Dance intervention ameliorated various aspects of functioning of
X, Y and Z. X significantly improved on scales of HRQoL, balance and balance
confidence, subtracting accuracy and walking distance in dual task condition
between 1st vs 2nd testing sessions. Y significantly
improved in walking distance in single (1st vs 2nd) and
dual task (1st vs 2nd; 1st vs 3rd)
condition and on balance confidence (1st vs 2nd). Z
significantly improved on measures of visual attention and executive function
(1st vs 2nd); moreover, his HRQoL significantly increased
by 19.5% and balance confidence increased by 37% (1st vs 2nd;
1st vs 3rd).
P15.15
Double-blind, placebo-controlled trial of donepezil for
dementia or mild cognitive impairment in Parkinson disease
Eric Molho1, Anne Barba1, Paul Feustel1,
Donald Higgins2, Stewart Factor3
1Albany Medical Center,
Albany, NY, USA
2Veterans Affairs
Medical Center, Albany, NY, USA
3Emory University
School of Medicine, Atlanta, GA, USA
Objective: Measure
the effects of donepezil on cognitive and motor function in Parkinson disease
patients with either mild cognitive impairment (MCI) or dementia.
Methods: Subjects
were classified as MCI based on Mini Mental Status Exam (MMSE) score of at
least 26 and a Clinical Dementia Rating of 0.5. Subjects with MMSE of 25 or
less were included in the dementia portion of the study. Both groups were
randomized to placebo or donepezil 5mg daily for 12 weeks and evaluated at
baseline, 6 weeks and 12 weeks. The primary cognitive outcome was the ADAS-Cog
in the demented group and the cognitive battery utilized the TEST/RETEST study
in the MCI group. Evaluations for all subjects also included MMSE, Unified
Parkinson’s Disease Rating Scale (UPDRS), Neuropsychiatric Inventory and
clinical global impression of improvement. PD medication doses were held
constant during the study. Scores were used in a two way repeated measures
analysis of variance for statistical analysis.
Results: A total of 28 subjects were enrolled (13
demented, 15 MCI). No significant changes were observed in MMSE, UPDRS total,
UPDRS motor or UPDRS tremor subscores in either group. No significant changes
were observed in the ADAS-Cog in the demented group. Donepezil was well
tolerated.
Conclusions: Donepezil was well
tolerated but did not result in significant improvents in cognition in PD
patients with dementia or MCI.
P15.16
Exercise for the mind: Investigating the
effects of exercise on cognition in Parkinson’s disease
Danielle Murray1, Matthew Sacheli1,
and A. Jon Stoessl1
1Pacific Parkinson’s Research Centre,
University of British Columbia, Vancouver, BC, Canada
Objective: The overall objective
of this systematic review was to accumulate evidence for the effects of
exercise on cognition in patients with Parkinson’s disease (PD). The rationale
for conducting this systematic review was to provide guidance on the potential
for exercise to benefit cognitive deficits in PD.
Methods: This systematic review was completed
according to the Preferred Reporting Items for Systematic reviews and
Meta-Analyses (PRISMA) statement. Original research articles were included if
the primary intervention was exercise and the primary outcome was a behavioral
or neurobiological marker of cognitive function.
Results: Searching electronic databases yielded 272 records. One hundred and
fourteen full-text records were assessed for eligibility. Eight original
clinical research articles were included in the systematic review. All eight studies
showed that exercise improved cognitive function, although the neurobiological
mechanisms have not yet been determined. Three studies examined the effects of exercise on cognition
specifically related to tasks of executive function. Improvements in cognitive
function were shown using the Montreal Cognitive Assessment, as well on tests
of reaction time and transfer of learning. Improvements in executive function
were demonstrated on tasks such as the Wisconsin Card Sorting Test,
Trail-Making Tests, tests of verbal fluency, working memory and spatial memory.
Exercise may additionally decrease levels of serum homocysteine, a marker
linked to cerebral vascular disease and cortical-hippocampal injury.
Conclusions: Exercise can be an effective treatment to
improve cognitive function. The evidence from clinical studies suggests that a
more intensive aerobic exercise program combined with strength and balance
training may promote greater cognitive gains. However, low-intensity exercise
also showed benefits. Patients should use these findings as further rationale
to be as physically active as possible. Health care providers and policy makers
should encourage aerobic exercise with resistance training to the maximum
tolerated intensity as part of the routine management of PD.
P15.17
The effects of rivastigmine therapy in Parkinson’s
disease dementia: A clinical, neuropsychological and
electrophysiological study
S. Sibel Ozkaynak1, Burcu Ekmekci1,
Ebru N. Barcın1, Ferah Kızılay1
1Akdeniz University,
Medical Faculty, Neurology Department, Antalya, Turkey
Objective: In this study, we
evaluated positive effects of rivastigmine therapy on cognition in Parkinson’s
disease dementia (PDD) by means of behavioral inventory and neuropsychological
tests and P300. In addition, we investigated the patients clinically and
electrophysiologically using UPDRS, movement related cortical potentials (MRCP)
and reaction time (RT) to show whether there are any negative effects of
rivastigmin on motor function.
Methods: Ten non-demented
idiopathic PD patients and 9 PDD patients were included the study. PDD patients
were assessed by a neuropsychological test battery (MMSE, Rey auditory verbal
learning test, Wechsler memory scale III visuel memory subtest, trail test A-B
and Luria drawing, digit span, similarities and category fluency test) which
evaluate attention, memory and executive function and also electrophysiological
tests (P300, MRCP and RT) before rivastigmine treatment (average dose
7.8mg/day) and after the sixth month of treatment. The non-demented PD patients
also evaluated in the naturel course of the disease by means of the same tests
at the start and at the end of the six month.
Results: At the end of six
months rivastigmin therapy, PDD patients showed statistically significant
improvement in neuropsychological tests related memory and shortening of P300
latency. However we didn’t found any statistically significant changes in the
measurements of MRCP and RT tests after therapy. But, although PDD patients
showed shortened RT after therapy, RT was prolonged in non-demented PD patients
after the six months.
In conclusion, our
study have suggested that while rivastigmine therapy improve cognitive
functions in PDD, it doesn’t cause any side effects on motor function of
patients.
P15.18
RECOGNISE: Rasagiline effects on cognition in Parkinson’s
patients with mild cognitive impairment
Ishita Gambhir1, Jill Farmer1,
Fernando Pagan1
[1]Georgetown University
Hospital, Washington, DC, USA
Objective: Double blinded placebo controlled trial
evaluating effects of Rasagiline 1mg on cognition and motor function in
patients with Idiopathic Parkinson’s Disease [IIT-TN-067]
Background: Numerous patients with Idiopathic
Parkinson’s Disease (PD) are treated with Rasagiline to help improve their
motor function. However, this medication may also help with improving cognitive
function as assessed by the Montreal Cognitive Assessment (MoCA), Frontal
Assessment Battery test (FAB), and Scales for Outcomes in Parkinson’s
Disease-Cognition-test (SCOPA-COG).
Results: The interim analysis includes 16 of 40
anticipated subjects (64.7% male, mean age 69.5 years, diagnosed with PD mean
5.9 years, and mean years of education 16.5). Analysis of baseline data
revealed mean MoCA score of 26.4/30, mean FAB score of 10.9/12, and mean
SCOPA-COG score of 29.5/43. Additionally, mean baseline Berg Balance Scale
score was 50.5/56 and mean UPDRS part III was 21.1.
Conclusion: This ongoing study will provide valuable
information for Parkinson’s disease patients with cognitive decline. Thus far,
no standard-of-care medications for PD have been shown to significantly enhance
cognition, so the addition of Rasagiline to a patient’s medication regimen
could potentially be of great value in addressing this issue along with
addressing motor function.
P15.19
Vitamin D
in Parkinson’s disease
Amie L
Peterson1,2, Brenna M Lobb1, Martina Mancini2,
Charles Murchison2, Thomas Montine3,4, James B Leverenz3,4,
Cyrus Zabetian3,4, Karen L Edwards3,4, Joseph Quinn1,2
1Portland VA, Portland, OR, USA
2Oregon Health Sciences University, Portland, OR, USA
3VA Puget Sound, Seattle, WA, USA
4Univeristy of Washington, Seattle, WA, USA
Objective: To review
our research on vitamin D in persons with Parkinson’s disease (PD).
Methods:
Specifically we have looked at cross-sectional data of vitamin D and measures
of cognitive function, mood, and balance performance. These data have come from
three different studies.
Results: In regard to cognitive
function, baseline data from a study following neuropsychiatric function in
persons with PD showed significant correlations between vitamin D
concentrations and semantic verbal fluency (vegetables, p=0.01), categorical
verbal fluency (animals, p=0.05; vegetables, p<0.01), and memory (Hopkins
Verbal Learning Test, immediate recall, p=0.02; delayed recall, p=0.04) in the
non-demented subset of the cohort. In regard to mood, data from the above study
also showed a correlation between Geriatric Depression Scale (GDS) and vitamin
D levels. Baseline data from a vitamin D intervention study showed significant
negative correlations between vitamin D concentrations and total PD Quality of
Life (PDQ-39 score: -0.46, p=0.02), the depression/dejection subscale of the
Profile of Mood States (POMS: -0.43, p=0.03), and the confusion/bewilderment
subscale of the POMS: -0.41 (p=0.04). In regard to balance measures, data from
a pilot study of the relationship between vitamin D and balance in PD showed
correlations between vitamin D concentration and postural response strength
asymmetry and stance weight asymmetry. Correcting for the Unified Parkinson’s
Disease Rating Scale (UPDRS), the correlation coefficients for vitamin D and
strength symmetry were 0.41 (p=0.01), 0.34 (p=0.03), and 0.32 (p=0.05) for
small, medium, and large perturbation respectively. The correlation
coefficients for vitamin D and weight symmetry were similar at 0.32 (p=0.05),
0.42 (p=0.01), 0.30 (p=0.07). It appears that vitamin D might have effects on a
number of aspects of PD. These data are all cross-sectional, limiting the
ability to infer causation. Intervention studies following multiple measures
are needed to determine the full extent of the role vitamin D plays in PD.
P15.20
Response
inhibition and emotional facial expression recognition in Parkinson’s disease
Juan Manuel Serrano1, Laura Alonso-Recio1,
2, Fernando Carvajal1, Sandra Rubio1, Ángela
Loeches1
1
Universidad Autonoma de Madrid, Spain
2
Universidad a Distancia de Madrid, Spain
Objective: Attention and emotional
recognition have often been found altered in Parkinson´s disease (PD)
individuals. Moreover, some studies have suggested that divided attention
problems of patients determine emotional recognition through facial expression.
Another attentional process that may influence emotional facial expression
recognition in PD patients is the ability to inhibit irrelevant information.
The objective of the present study is to assess the influence of this process
on facial expression recognition abilities in PD.
Methods: We observe 51 PD patients
and 51 healthy controls in two inhibition task based on the Stroop paradigm. We
design an “emotional Stroop” task in which stimuli consisted of showing an
emotion facial expression together with a different emotional category label
superimposed on it. So, we compare the performance of both groups in the
“emotional Stroop” and in the original color-name Stroop test.
Results: Both groups showed a
higher performance in the color-name Stroop task than in the “emotional Stroop”
task. However, PD group performed worse than healthy controls in the “emotional
Stroop” task but not in the color-name Stroop task. This set of results points
to that facial expression recognition problem may not be attributable to a
widespread impairment in inhibition ability. Thus, emotional recognition and
attention difficulties, when they are found in PD individuals, may be due to
different processes and brain mechanisms. This knowledge may contribute to the
design of specific intervention programs aimed to improve social communicative
abilities in PD.
P15.21
Impact of Cognitive Dysfunction in Patients with
Parkinson’s disease during the Execution of Gait
Erica Tardelli 1, 2, Erika Okamoto 1, 2,
Maria Elisa Pimentel Piemonte1, 2
1University
of São Paulo, São Paulo, São Paulo, Brasil
2Associação
Brasil Parkinson
Objective: The aim of this study was to compare the
results obtained with the evaluation of gait in single task conditions and
multiple tasks in patients with Parkinson's disease (PD) with and without
cognitive impairment. METHODS: 20 patients with idiopathic Parkinson's disease
without cognitive impairment (PDI), mean age 65.5 years (St.Dev. = 7.8) and 20
patients with idiopathic PD and cognitive impairment (CPS), with mean age of 64.5
years (St . Dev = 6.44) in stage 1, 2 and 3 of the disease according to Hoehn
and Yahr classification. Patient evaluation consisted of walking for a distance
of 12 meters where participants are instructed only to walk as fast as possible
to a table placed at the end of 12 meters called the single-task condition
(ST). And the condition of multiple-task (MT), the participants performed the
same route, with other associated tasks as Task 1, walking holding a glass of
water. Task 2, floor and exchanging a coin from one pocket to another. Task 3,
walking and holding a tray and Task 4, floor and asked how many times
particular bell was played. Participants underwent cognitive evaluation by the
Mini-Mental State Examination (MMSE), Montrel Cognitive Assessment (MoCA) and
Clock Test and equilibrium by BERG Balance Scale.
Results: The results showed a significant
interaction between task
condition (ST and MT)
and groups (DPI and DPC), which showed that, under conditions of ST, DPC has
impaired performance compared to IPR, and in conditions of MT, patients with
CPS are even more disadvantaged than the group of DPI.
P15.22
Age of acquisition effects during verbal
fluency task performance in Parkinson’s disease
Daymond Wagner1, Paul Eslinger1,2,3,
Eun-Young Lee1, Mechelle M. Lewis1,3, Xumei Huang1,3,4,5,6
Departments of Neurology1, Neural
& Behavioral Sciences2, Radiology3, Pharmacology4,
Neurosurgery5, and Kinesiology6, Penn State Hershey
Medical Center, Hershey, PA, USA
Parkinson’s disease (PD) is characterized by
a deficiency in dopamine, a neurotransmitter that has been shown to play a
neuromodulatory role in executive function and cognitive control processes.
Verbal associative fluency is a task that requires working memory and flexible
access to the lexical-semantic knowledge system under time constraints, and
hence may be sensitive to dopamine level. Specifically, reduction in dopamine
may be associated with a more limited search of long-term knowledge.
Objective: The aim of this
study was to investigate the frequency and age of acquisition (AOA) of
exemplars produced during verbal fluency tasks in PD patients and matched
controls. AOA has been shown to potentially confound frequency effects and may
better represent the organization of this system.
Methods: We compared the
frequency and AOA of exemplars produced during verbal fluency tasks by two
groups of individuals with PD differing in side of motor symptom onset
(PD-Right and PD-Left) to a control group matched on age, education,
handedness, and Mini Mental Status Exam scores. PD individuals were tested in
an off medication state.
Results: A nonsignificant
trend was observed for the PD-Right motor onset group to produce a range of
exemplars with greater frequency during a semantic fluency trial (p = .105).
Both PDRight and PD-Left groups produced a range of exemplars with
significantly earlier AOA in comparison to controls (p = .016). Hence, PD
individuals with dopamine loss may have reduced access to the lexical-semantic
knowledge system and limited to earlier acquired words. Further studies are
underway to determine if this alteration applies to other domains of knowledge
and can be modified by dopamine dose.
CLINICAL
SCIENCES: SLEEP DISORDERS/ FATIGUE
P16.01
The use of actigraphy in clinical practice for the
assessment of sleep disorders in Parkinson’s Disease Dementia
Matthew Lowe, 1 Apurba Chatterjee 2,
Luke Solomons, 1
1Berkshire NHS
Foundation Trust, Reading, Berkshire, England
2Royal Berkshire NHS
Foundation Trust, Reading, Berkshire, England
Objective: Dementia in Parkinson’s disease (PDD) and
Lewy Body Dementia (LBD) are commonly associated with sleep disturbances,
including REM sleep behaviour disorder, which have a significant negative
impact on quality of life. Sleep monitoring using polysomnography is poorly
tolerated in patients with dementia. An alternative is the use of actigraphy.
Sleep wake patterns are estimated from periods of activity and inactivity and
provides statistics of sleep quality. Actigraphy has previously been used in Parkinson’s
disease to quantify bradykinesia and assess sleep disorders but not
specifically in those with dementia.
Methods: 5 patients attending a Consultant Psychiatry
Outpatient Clinic in Berkshire, England with PDD OR LBD experiencing sleep
difficulties were actigraphy. The patients were monitored with the Respironics
Actiwatch 2 device for 7 days. Sleepiness and quality of life scales and sleep
diaries were recorded.
Results: The data analysis highlighted the sleep
problems experienced by the patients.
Pt No. |
Total time in bed |
Sleep duration |
Number of psychotropic medications |
Sleep efficiency (%) |
Differential diagnosis |
1 |
11:06:20 |
6:38:30 |
4+3 |
60.40 |
Free running sleep pattern (non – 24 hr sleep-wake) |
2 |
11:33:23 |
7:27:58 |
2+1 |
63.02 |
Lewy Body Dementia + REM behaviour disorder |
3 |
14:19:35 |
12:30:25 |
3+0 |
87.27 |
Lewy Body Dementia + Hypersomnia/ somnolence |
4 |
14:23:37 |
12:37:08 |
2+3 |
88.60 |
Parkinson Disease dementia + Hypersomnia |
5 |
8:33:11 |
7:48:58 |
2+1 |
91.43 |
Parkinsons Disease dementia + normal sleep pattern |
Behavioural and
medical management was offered to patients after analysis to improve their
sleep patterns and quality of life. In patient 1, sleep efficiency improved by
almost 10% on follow up.
Actigraphy appears to
be a well-tolerated, low cost, non-invasive tool for assessing and monitoring
of sleep in patients with dementia. Further research to assess its utility and
predictive value is needed to elucidate whether this technique can be used in
everyday clinical practice.
P16.02
REM sleep behavior disorder in Parkinson Disease:
Association with abnormal ocular motor findings
Young Eun Kim1, Hui June Yang1, Ji
Young Yun2, Jee-Young Lee, 3, Han-Joon Kim1,
Beom S Jeon1
1Department of
Neurology and Movement disorder center, Parkinson Study Group, Seoul National
University Hospital, Seoul, Korea
2Department of
Neurology, Ewha Womans University Mokdong Hospital, Seoul, Korea
3Department of
Neurology, College of Medicine, Seoul National University Boramae Hospital,
Seoul, Korea
Objective: REM sleep behavior
disorder (RBD) is related with brainstem pathology. We examined whether
patients with RBD have abnormal ocular movements suggesting brainstem or
cerebellar dysfunction in Parkinson’s disease (PD).
Methods: Total 202 patients
were included in this study. Ocular movements were examined by
video-oculography (VOG).
Results: 116 (57.4%) of the 202 patients have
clinically probable RBD, and 32 (27.6%) of the 116 with clinically probable RBD
patients had abnormal VOG findings suggesting brainstem or cerebellar
dysfunction; whereas 86 of the 202 patients did not have clinically probable
RBD, and only 8 (9.3%) of 86 patients had abnormal VOG findings suggesting
brainstem or cerebellar dysfunction. (P
=.001). This study suggests
that the presences of RBD are associated with more severe brainstem pathology
in PD.
P16.03
High intensity exercise improves skeletal muscle
mitochondrial function corresponding with reduced fatigability in Parkinson's
disease
NA Kelly1, SC Tuggle1, DR
Moellering1, CS Bickel1, MP Ford1, MJ Stec1,
ST Windham1, DG Standaert1, and MM Bamman1
1The University of
Alabama at Birmingham, Birmingham, AL, USA
Objective: Parkinson’s disease (PD) is a debilitating,
neurodegenerative
disease that manifests as disrupted motor behavior (bradykinesia, tremor,
postural instability, rigidity) which ultimately reduces physical activity and
weight-bearing ambulation. Deconditioning as a result of PD often leads to
weakness, low muscle power, and fatigability. We hypothesized that a
high-intensity exercise training prescription which simultaneously challenges
strength, power, balance, and endurance would improve muscle function and
fatigability in PD patients.
Methods: Participants (n=12, 65±6 y, Hoehn & Yahr
2-3) exercised 3 d/wk x 16 wk. Fatigue was assessed in three domains (patient
perception, cardiorespiratory fatigue, and neuromuscular fatigue) and skeletal
muscle biopsies were analyzed for changes in muscle fiber size, type
distribution (I, IIa, IIx), and mitochondrial function.
Results: Improvements were
noted in the Fatigue Severity Scale, UPDRS motor score, voluntary strength
(57%), and power (49%) (p<0.05). Muscle fiber size (type I: 14%; type II:
36%) and mitochondrial complex I activity (48%) increased (p<0.05), and
fiber type distribution shifted toward the more oxidative, fatigue-resistant
type IIa phenotype (IIa from 39% to 55%; IIx from 12% to 2% of total myofibers).
In conclusion, PD patients are capable of, and responsive to, high-intensity
exercise training with improvements in skeletal muscle phenotype,
functionality, and fatigability.
P16.04
Treatment of obstructive sleep apnea with continuous
positive airway pressure improves non-motor symptoms in Parkinson’s disease
patients
V.P. Mery1, A.-L. Lafontaine2, A.
Robinson2, L. Pinto1, A. Benedetti4, J.R.
Kimoff1, M. Kaminska1
1Respiratory Division
& Sleep Laboratory McGill University Health Centre - Montreal, QC, Canada
2Montreal Neurological
Hospital. McGill University Health Centre – Montreal, QC, Canada
3Dept. of
Medicine and Dept. of Epidemiology, Biostatistics & Occupational Health,
McGill University Health Centre – Montreal QC, Canada
4Respiratory
& Epidemiology and Clinical Research Unit, McGill University Health Centre -
Montreal, QC, Canada
Rationale: We have previously
shown that Parkinson’s disease (PD) patients with obstructive sleep apnea (OSA)
have more non-motor symptoms (NMS) than those without OSA. We hypothesize that
OSA treatment with continuous positive airway pressure (CPAP) can improve NMS
in PD.
Methods: PD patients without
known OSA underwent overnight diagnostic polysomnography. OSA was defined as an
apnea-hypopnea index (AHI) ≥15/h. PD was assessed using the Movement
Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). NMS were
assessed using: Montreal Cognitive Assessment (MoCA); Epworth Sleepiness Scale
(ESS); Fatigue Severity Scale (FSS); Apathy Scale; Beck Depression Inventory
(BDI); and Parkinson’s Disease Sleep Scale (PDSS). Patients with OSA were
offered CPAP. All patients were reassessed at six months. Linear regression was used to assess change in NMS,
comparing the three groups, non-OSA; CPAP-treated OSA (OSA-Tx) and untreated
OSA, adjusting for any change in levodopa equivalent dose (LED).
Results: We studied 28 PD
patients (60.7% male), mean age 63.0, SD 11.3 years, and motor MDS-UPDRS 21.5,
SD 12.3. Sixteen (57.1%) patients had OSA (AHI 21.4/h, SD 18.5/h). Ten accepted
CPAP; they had a similar mean AHI to those declining CPAP.
At 6
months, adjusting for change in LED, the following variables improved in the
OSA-Tx group, significantly more than in the non-OSA group: Total UPDRS
(p=0.008); Part 1 (NMS)UPDRS (p=0.004); Apathy Scale (p=0.009); MoCA (p=0.048);
ESS (p=0.02) and PDSS (p=0.01). Motor UPDRS, FSS and BDI did not show
significant change. The change in MoCA remained significant after adjusting for
ESS (p=0.01).
For OSA-Tx
patients, the MoCA at 6 months, improved by a mean of 1.6, SD 1.9 versus
baseline (p=0.043, adjusted for change in LED).
Conclusions: Our preliminary
results suggest that, in PD patients, OSA treatment by CPAP can result in improved
NMS including cognitive dysfunction.
P16.05
Focus group and quantitative assessment of sleep and
fatigue in Patients with Parkinson’s disease
Melody N. Mickens, Therese Verkerke Cash, & Sarah K.
Lageman
Virginia Commonwealth
University, Parkinson’s and Movement Disorders Center, Richmond, VA, USA
Objective: Focus group and survey data were collected
from PD patients to assess sleep problems, beliefs about sleep, strategies used
to help initiate and maintain sleep, as well as common sleep disruptions. The
purpose of these focus groups was to inform a Cognitive Behavior Therapy for
Insomnia (CBT-I) intervention that will be modified for use in a PD-population.
Methods: Participants (N=25) completed the Parkinson’s Disease Sleep Scale (PDSS),
SCOPA-Sleep (SCOPA), Dysfunctional Beliefs and Attitudes About Sleep Scale
(DBAS-16), and researcher generated instrument that assessed current sleep
habits. In the focus groups, participants discussed strategies used to initiate
sleep and maintain energy during the day, problems that disrupt sleep, and
general interest in participating in a CBT-I intervention.
Results:
Participants
endorsed sleep apnea (16%), restless leg syndrome (16%), REM sleep behavior
disorder (12%) and insomnia (4%). More than one third reported clinically
impaired scores on the PDSS (40%), SCOPA-NS, (44%), and SCOPA-DS (40%). Over
half (56%) reported that these problems interfered with their daily
functioning, and the majority (84%) reported worry/distress about their current
sleep problems. Participants reported a high degree of dysfunctional beliefs
about sleep, with 76% endorsing sleep cognitions that may perpetuate insomnia.
Frequently endorsed strategies for initiating sleep included consistent sleep
schedule (91%), physical exercise (73.9%), sleep medications (69.9%) and
napping (69.6%). Sleep disruptions were attributed to needing to use the
restroom (80%) and worry (60%). Physical exercise, activity pacing and naps were
frequent strategies for maintaining energy during the day. Over half of the
participants indicated moderate to high levels of interest in participating in
a CBT-I intervention. Findings are consistent with sleep problems reported in
the PD literature and suggest that a CBT-I focused intervention may target
dysfunctional cognitions and improve sleep habits among PD patients.
P16.06
What influence most on the quality of sleep
in Parkinson`s disease patients?
Svetlana Tomic1, Marina Hlavati2,
Marta Petek1, Mirjana Cubra1, Tomislav Pucic1,
Mirko Porobic1, Ivanka Stenc Bradvica1, Silva Butkovic
Soldo1
1Department
of Neurology, University Hospital Centre Osijek, Osijek, Croatia
2Department
of Neurology, General Hospital Nasice, Nasice, Croatia
Introduction: Sleep disturbances
are one of the most common nonmotor sypmtoms of Parkinson Disease (PD) and it`s
prevalence vary from 60-98%.
Objective: To investigate
incidence of sleep disturbances in patients with idiopathic PD and to evaluate
what kind of sleep disturbance influence most on the quality of the sleep.
Patients
and methods:
We analysed 104 PD patients treated on the University Hospital Centre Osijek
and General Hospital Nasice. All patients were asked if have sleep disturbance
or not. To evaluate sleep disturbances we used Parkinson Disease Sleep Scale
(PDSS).
Results: sleep disturbance
reported 58,7% patients, while 41,3% had not sleep disturbance. In group of
patients reported not to have sleep disturbance total PDSS score was 104,4,
while in group that have disturbance score was 87,7. We found statisticaly
significant difference between two groups of patients on this items: nocturnal
awakening (t= -2,869; p<0,005), restlessness (t= 1,941; p<0,01),
disstresing dreams (t= -2,947; p<0,005), disstresing halucinations (t=
-1,956; p<0,05), tremor on waking (t= -2,135; p<0,05) and morning
tiredness (t= -2,494; p<0,01).
Conclusion: Among sleep
disturbances nocturnal awakening, restlessness, disstresing dreams, disstresing
halucinations, tremor on waking and morning tiredness influence most on the
quality of sleep in patients with Parkinson Disease.
P16.07
1H
magnetic resonance spectroscopy study of auditory cortex metabolism in obstructive sleep
apnea syndrome combined nerve deafness
Baoshan Wang, Dongmei Song, Geng Song, Xin Lv, Tao Liu
Department of Otolaryngology and Head and Neck Surgery, the First Hospital of
Hebei Medical University, Shijiazhuang, China
Objective: Obstructive sleep
apnea hypopnea syndrome (OSAHS) is a sleep breathing disorders in patients with
idiopathic Parkinson's disease and it correlates well with the severity of the
disease. The patients with OSAHS have a higher incidence rate of nerve
deafness, but the underlying mechanism remains to be elucidated. Recently,
studies showed abnormal cerebral metabolism in patients with OSAHS. Therefore
we have investigated the characteristic changes of metabolic products in the
auditory cortex (transverse temporal gyrus) of OSAHS patients with
nerve deafness using 1H magnetic resonance spectroscopy (1H-MRS)
to discover the prognostic indicator of nerve deafness in OSAHS.
Methods: The electric response audiometry was
performed in 47 patients with OSAHS, 21 patients with nerve deafness and 15
healthy control subjects, the patients were classified into three groups: OSAHS
with no deafness, OSAHS with deafness, and the control group. Cerebral metabolism was studied by assessing the relative
contents of Nitro-acetyl aspartate (NAA) and choline (Cho) and ratio of NAA to Cho in the auditory cortex separately in these
groups. We also analyzed the changes between the abnormal and contralateral normal
auditory cortex in the group with
unilateral nerve deafness.
Results: Significantly lower values of NAA/Cho
ratio were found in the auditory cortex of OSAHS patients with
deafness compared with 15 age-matched control subjects (P < 0.05) and OSAHS
without deafness (P < 0.05). Auditory cortical
NAA and NAA/Cho ratio in OSAHS with unilateral nerve deafness were significantly lower compared with normal control
(P < 0.05 and P < 0.01, respectively), but there is no significant
difference between the abnormal and contralateral
normal
auditory cortex. Based on these data,
NAA/Cho and NAA may be the early warning marker of nerve deafness in
OSAHS.
CLINICAL
SCIENCES: DIAGNOSIS (DIFFERENTIAL, ACCURACY)
P17.01
Clinical
correlates of vascular parkinsonism
Igor
Barcellos1, Gabriela Boschetti1, Marina Farah1,
Erickson Padovani1, Hélio A. Teive2, Renato P. Munhoz1
1Pontifical
Catholic University of Paraná, Curitiba, Brazil
2Federal
University of Paraná, Curitiba, Brazil
Objective:
To identify the demographic and clinical correlates of
VP in comparison with PD.
Background:
Vascular parkinsonism (VP) is the second most common form
of non degenerative parkinsonism. In VP, signs and symptoms include disabling
features such as early axial signs and minimally responsive to dopaminergic
therapy. Also, the diagnosis is not straightforward, frequently misinterpreted
for other forms, such as rigid akinetic PD and PSP.
Methods:
Diagnosis was based on the presence of lower body predominant parkinsonism,
pyramidal tract signs, imaging evidence of multiple vascular lesions, and at
least two vascular risk factors. PD was diagnosed using the Queen Square Brain
Bank criteria. The scores utilized were UPDRS, to define motor severity; Hoehn
& Yahr; DSM-IVR to access dementia. Psychosis was clinically diagnosed. REM
sleep behavior disorder was defined by the occurrence of behavioral symptoms during
sleep.
Results:
A total of 60 patients with VP and 1142 with PD were
included. Although males were more prevalent among those with VP, differences
were not significant (p: 0.27). On the other hand, VP patients were
significantly older, had shorter disease duration, had more symmetric signs,
worse H&Y scores, were more likely to present with PIGD and only rarely
presented with tremor (all variables with p<0.0001). Psychosis was equally
common in both groups. Dementia was significantly more common in the VP group
and RDB was more common among PD patients.
Conclusions:
VP patients present a clinical picture that is
significantly distinct from PD. The presence of risk factors, a consistent
motor profile, lower prevalence of RBD, and higher frequency of dementia
despite shorter disease duration, may help distinguishing both disorders.
P17.02
An
investigation of the relationship between clinically-assessed and self-reported
measures of side affected in patients with Parkinson’s disease
Elise Bisson1, Quincy J. Almeida1,
Joan E. Norris2
1Sun Life Financial Movement Disorders Research & Rehabilitation Centre,
Wilfrid Laurier University, Waterloo, Ontario, Canada
2Wilfrid Laurier University, Waterloo, Ontario, Canada
Objective: Both
clinically-assessed and self-reported measures have been used to determine the
side that is most affected by PD. However, it is unclear if clinicians’
assessment of side affected is representative of the patients’ own perceptions.
Therefore, the objective
was to investigate the relationship between self-reported and
clinically-assessed measures of side affected. We also sought to uncover the
strongest clinical predictor of self-reported side affected.
Methods: Participants consisted of 254 (66% male) patients
with PD from the Sun
Life Financial Movement Disorders Research & Rehabilitation Centre (MDRC).
Data was collected during participants’ initial assessments. Participants
completed a self-report questionnaire assessing demographics and side affected
(right vs. left). Part III of the Unified Parkinson’s Disease Rating Scale
(UPDRS) was employed as the clinically-assessed measure of PD. Scores were
calculated for total right and left: upper limb severity, lower limb severity,
upper limb tremor, lower limb tremor, upper limb voluntary movement, and lower
limb voluntary movement.
Results: A Pearson
chi-square between self-reported and clinically-assessed side affected was
significant (χ2(1) = 71.39, p
< .001), indicating an agreement between patient and clinician. A multiple logistic
regression was also performed, with self-reported side affected as the
dependent variable, and total limb severity, tremor score, and voluntary
movement score entered as covariates. The results indicated that only total right upper limb severity predicted self-reported side
affected (β = -.675, p = .05). Therefore, participants with
higher right upper limb severity were more likely to self-report as right side
affected.
Conclusion: Taken
together, these results suggest that clinicians’ ratings of side affected are
consistent with patients’ own perceptions of side affected; however, when
individual predictors were examined, the UPDRS could not significantly predict
patients’ self-reported side affected and thus may not be fully reflective of
patients’ own experiences with PD.
P17.03
Neuropsychological testing for the detection of mild
cognitive impairment in Parkinson’s disease
Roberta Biundo1, Luca Weis1, Silvia
Facchini1, Manuela Pilleri1, Patrizia Formento-Dojot1,
Angelo Antonini1.
1UOS Parkinson's disease and Movement Disorder.
I.R.C.C.S. San Camillo Hospital, Venice, Italy
Objective: Prevalence of mild cognitive impairment (MCI)
in Parkinson’s disease (PD) is variable (range 20-58%) likely due to
methodological differences in classification criteria and lack of consensus
about neuropsychological tests used for cognitive profiling. Our previous work
identified most suitable tests for diagnosis of MCI in PD and defined
appropriate cut-off scores. In this study we expanded previous results using a
wider neuropsychological battery in a new larger PD cohort to verify
statistical validity of those tests and their cut-off scores.
Methods: One-hundred-five PD
patients and 20 healthy subjects (HC) performed an extensive neuropsychological
evaluation. PD patients were categorized as PD-CNT (PD without cognitive
impairment, 35%), PD-MCI (47%) and PDD (PD with dementia, 17%) based on established criteria. Univariate ANOVA and
Receiver Operating Characteristic (ROC) curves were adopted.
Results: We found that MoCA,
Trail Making test, Digit Ordering test, similarities, semantic fluency task,
prose memory test immediate and delayed recall, free clock
drawing test, Boston naming test and incomplete letters test reached
significant screening and diagnostic validity in predicting PD-MCI (AUC
0.721-0.825) with cut-off scores calculated by ROC analyses lying within normal
range for normative data.
Conclusion:
These
data corroborate and expand our previous results, confirming that a wide
spectrum of cognitive tests can detect cognitive abnormalities in PD without
frank dementia (verbal memory, attention/executive, visual-perceptive and
language impairments). The use of valid cut-off score can ameliorate the
accuracy of MCI diagnosis in PD.
P17.04
Development and implementation of a next
generation sequencing platform for hereditary Parkinson disease
Matthew Bower1, Bharat Thyagarajan2,
Kenny Beckman2, Kevin Silverstein2, Getiria Onsongo2,
Matthew Schomaker1, Paul Tuite2
1University of Minnesota Medical Center Fairview, Minneapolis, MN, USA
2University of Minnesota, Minneapolis, MN, USA
Objective: The purpose
of this effort was to develop a comprehensive and flexible next generation
sequencing platform to diagnose Mendelian forms of Parkinson disease and
identify hereditary risk factors for Parkinson disease in a clinical setting.
Methods: After a
thorough literature review, an Agilent SureSelect sequence capture was designed
to enrich for genes associated with Mendelian forms of Parkinson disease (e.g. SNCA and PARK2), autosomal dominant risk factors for Parkinson disease (e.g.
GBA and LRRK2), and Mendelian forms of atypical Parkinsonism (e.g. MAPT and GRN). The efficacy of the sequence capture was evaluated in a small
technical validation experiment. Baits were subsequently redesigned to
supplement coverage in low coverage regions and Sanger sequencing primers were
designed to analyze exons that did not achieve desired coverage levels. A
larger clinical validation involving 20 samples was carried out to evaluate the
ability of this assay to identify a variety of mutations. Five patients with
early onset and/or familial Parkinsonism were analyzed using these methods.
Results: A total of 19
candidate genes, comprised of 321 distinct exons, were identified in the
literature review. Greater than 20x coverage was achieved at every base for 316/321 (98.5%) of exons.
Sanger sequencing primers were designed for the remaining 5 exons. In the
initial 5 patients analyzed, an average of 60 variants per sample were
identified. The majority of these variants were interpreted as benign based
upon minor allele frequency and/or published data. In addition to one
pathogenic SNCA mutation, novel
variants of uncertain clinical significance were identified, highlighting the
need for family studies for accurate interpretation. Targeted next generation
sequencing is an effective strategy for comprehensive analysis of known PD
genes in patients with suspected hereditary Parkinsonism.
P17.05
Kinematic and kinetic continuous measurement of hand
tremor to discriminate Parkinson’s disease: a pilot single-case study
Seyed-Mohammad Fereshtehnejad1, Ali Soroush2,
Wim Grooten3, Johan Lökk1
1Division of Clinical
geriatrics, Department of Neurobiology, Care Sciences, and Society (NVS),
Karolinska Institutet; Stockholm, Sweden
2Department of Public
Health Nutrition, Karolinska Institutet; Stockholm, Sweden
3 Division of Occupational
Medicine, Department of Neurobiology, Care Sciences, and Society (NVS),
Karolinska Institutet; Stockholm, Sweden
Objective: Tremor is one of the cardinal motor symptoms
of Parkinson’s disease (PD). Although the quantification of tremors is the
object of study for several researchers, a standard method does not exist yet.
In this pilot study, we aimed to assess if continuous measurement of kinematic
and kinetic characteristics of the tremorous hand could have discriminative
value for PD.
Methods: The kinematic (movement analysis) and kinetic
(force analysis) characteristics of tremor was measured in the dominant (DH)
and non-dominant (nDH) hand of one PD patient and also a healthy individual who
was blind to tremor characteristics of PD and was asked to simulate tremor
(SH). In kinematic assessment, postural tremor of the index finger was measured
by sensor displacement and using four cameras. Data were recorded for two
continuous minutes and values were traced in each second (overall 120 seconds
for each hand) through projection in three dimensions, X-, Y- and Z-axis.
Finally, these continuous measurements were analyzed using orthogonal partial
least square (OPLS) method and principle component analysis (PCA).
Results: Kinematic
measurements of X-axis (velocity and acceleration) was shown to be the most
fitted variables in the PCA model to discriminate DH from the SH (R2>90%
and Q2>70%). Based on the OPLS data, muscle force (Mean=0.42,
SE=0.028) and velocity in the Y-axis (Mean=0.37, SE=0.029) were the most strong
variables for discriminating DH from the nDH.
Conclusions:
These preliminary findings showed that kinematic
and kinetic analysis of hand tremor could help not only to distinguish PD
patient from control subject, but also the dominant hand from the non-dominant
one. It seems that continuous measurement data such as self-quantified symptoms
assessment by smart-phone applications could provide worthy information. This
pilot case-study should be followed by larger studies to introduce some newer
aspects of personalized healthcare approaches in PD.
P17.06
DaTscanTM for prediction of
clinical diagnosis of early Parkinsonian syndromes: Sensitivity, specificity,
positive and negative predictive values, and diagnostic accuracy in clinically
uncertain cases
Robert A. Hauser1, Igor D. Grachev2,
John Seibyl3, Kenneth Marek3, Andreas Kupsch4,
Michail Plotkin5, Nin Bajaj6
1USF Byrd Parkinson's Disease and Movement Disorders Center, Tampa, FL,
USA
2GE Healthcare, Princeton, NJ, USA
3The Institute for Neurodegenerative Disorders, New Haven, CT, USA
4Otto-von-Guericke-University, Magdeburg, Germany
5Leiter des Vivantes Instituts für Nuklearmedizin Mitte/Nord, Berlin,
Germany
6Nottingham University Hospitals NHS Trust, Nottingham, UK
Objective: To assess the diagnostic efficacy data
from clinical trial Kupsch et al, 2012 (data not previously published)
conducted using DaTscanTM ([123I]Ioflupane Injection).
Methods: Study imaging group (n=92) was used to assess the diagnostic accuracy of DaTscanTM in subjects with early, clinically uncertain
Parkinsonian syndromes (PS) after 1 year follow-up. The reference standard was
final clinical diagnosis 1 year after imaging, and it was compared to baseline
clinical diagnosis and to baseline imaging diagnosis. Visual assessment of DaTscanTM images was performed by local nuclear medicine physicians. Acquisition
of SPECT data with DaTscanTM and their reconstruction were
performed using a standardized imaging protocol.
Results: The sensitivity of clinical diagnoses
at baseline was 92% when compared to final clinical diagnosis at 1 year, but
the specificity was only 52.4%. For the comparison of baseline DaTscanTM
images to the clinical diagnosis at 1 year, the sensitivity was 93.9%;
specificity was 95.4% (p=0.0005 as compared to baseline clinical diagnosis).
The PPV, NPV and diagnostic accuracy for baseline clinical diagnosis or
baseline imaging diagnosis vs. final clinical diagnosis at 1 year were
respectively: 69.7% vs. 95.8% (p<0.0001), 84.6% vs. 93.2%, and 73.9% vs.
94.6%. Performance of DaTscanTM compares
favorably in this study to the performance of clinical diagnosis relative to
final clinical diagnosis. Study
Supported by GE Healthcare.
P17.07
Posturography in differential diagnosis of patients with
vascular Parkinsonism
Geun-Ho Lee1
1Dankook University, Cheon-An, Choong-Nam, Republic of Korea
Objective: Postural
dysfunction is one of the major features of vascular Parkinsonism. This study
aimed to quantitatively evaluate balance disturbances by means of computerized
dynamic posturography(CDP) in patients with vascular Parkinsonism in comparison
with Parkinson’s disease patients and healthy people
Methods:
Thirty-four patients (18 M, 16 F) with a mean age of 73(range 51-79) with
vascular parkinsonism were included. Eleven of them were qualified as patients
with leukoaraiosis and 23 others were identified as basal ganglia
microangiopathy. Patients with vascular parkinsonism (VP) and Parkinson’s
disease patients with nigral hypotrophy were tested regarding motor function,
balance and cognition. CDP, EquiTest (NeuroCom International, Clackamas, OR),
was performed both groups of patients and age-matched healthy individuals (HI).
Results: The 35
patients had poorer balance measured with the Sensory Organizing Test (SOT)
score in every condition (p=0.01 in SOT 1 and p<0.001 in SOT 2-6) compared
to the HI. The greatest difference was in test conditions measuring mainly
vestibular function, where loss of balance (LOB) was frequent. There was an
increase in the weighted composite SOT score (p<0.05) but no significant
change in any of the SOT conditions after Madopar treatment. The sway range was
significantly greater in VP in comparison to the control group. CDP showed that the VP patients had a poorer
balance than the HI and Parkinson’s disease patients. The greatest difference
was in SOT 5-6, indicating that the postural disturbance is of primarily
central vestibular origin. There was a slight improvement of balance after
Madopar therapy.
P17.08
Targeted next-generation sequencing for Parkinson’s
disease
Michelle K. Lin1, Daniel Evans1,
Chelsea Szu Tu1, Holly Sherman1, Frederick Pishotta1,
Heather Han1, Vanessa Silva1,2, Christina Thompson1,2,
Ian R. MacKenzie3, Viera Saly4 , Joseph Tsui2,
Martin McKeown2, Carles Vilarino-Guell1,5, Alex Rajput5,
Ali Rajput5, Silke Appel-Cresswell2, A. Jon Stoessl2
and Matthew Farrer1,2,5
1Centre for Applied
Neurogenetics, University of British Columbia, Vancouver, BC, Canada
2Pacific Parkinson’s
Research Centre, Department of Medicine (Neurology), University of British
Columbia, Vancouver, BC, Canada
3Department of
Pathology and Laboratory Medicine, Vancouver General Hospital and University of
British Columbia, Vancouver, BC, Canada
4Victoria
General Hospital, Victoria, BC, Canada
5Division of Neurology, University of Saskatchewan and Saskatoon Health Region, Saskatoon, SK, Canada
Objective: Clinical diagnosis of familial and sporadic
parkinsonism can be challenging, with several forms being ascribed to a
monogenic etiology. We have developed a cost-effective, targeted assay to
simultaneously sequence 172 genes genetically linked/associated with
parkinsonism.
Methods: Patients included familial and sporadic
parkinsonism, mean age-of-onset 61.8±11.5SD years (range=20-83) of European
descent (n=200)a. Additional features consisted of dementia (n=6),
dysautonomia (n=30), dystonia (n=5) and gaze palsy (n=36); autopsy confirmation
(n=76) included alpha-synucleinopathy, tauopathy and nigral neuronal loss.
Genes implicated in Parkinson’s disease and related neurodegenerative
conditions (n=172) were selected from prior linkage and association studies.
Target-DNA-capture and next-generation sequencing was executed for 96
barcoded-samples in parallel, on a SOLiD 5500xl™ sequencer. Read alignment to
the hg19 human reference sequence and annotation was performed using LifeScope
v2.5.1™. Frequency estimates were made using proprietary and public genome
databases (NHLBI’s Exome Sequencing Project, 1000 Genomes Project). Functional
predictions were retrieved with ANNOVAR. Data were filtered into rare
known/novel mutations (<1% population frequency), intermediate variants
(1-5%) and frequent polymorphisms (>5%). Mutations were confirmed by Sanger
sequencing. Disease association analyses were implemented using PLINK and R™.
Results: Re-sequencing was successful for >94% of
target exons (average 118 read-depth/exon). Known mutations observed included
LRRK2 p.G2019S, DNAJC13 p.N855S, SOD1 p.D90A, and PARK2 p.R275W. Of 293
mutations identified, 38 were novel. The distribution of mutations clustered
within specific loci, and differed between patients and control subjects.
Targeted next-generation sequencing accelerates discovery of known and novel
variants, and may highlight specific molecular pathways in disease
pathogenesis. The significance of findings is being assessed in consecutive
replication series. For research participants, the approach provides a fast and
affordable option for diagnostic screening, without incidental findings
unrelated to neurodegeneration. Specific results can inform neurologists and
may facilitate a differential diagnosis for their patients.
asee abstract by Silva et al.
P17.09
Oro-digital synkinesia in corticobasal degeneration
Narges Moghimi1, Bahman Jabbari 2
1 Case Western Reserve
University, Cleveland, OH, USA
2 Yale University, New
Haven, CT, USA
Objective: Dyskinesias are common in Parkinson's
disease (PD) and atypical Parkinson disorders. Facial -limb synkinesias are
rare. We report two patients with atypical Parkinson disorder in whom movements
of fingers and hands activated distinct oral movements.
Methods: Patient 1 - An 80 year -old male developed
“stiffness" of the left upper and lower limbs over the past 4 years .
Examination demonstrated normal mentation, cranial nerve and cerebellar
assessments. There was marked increased tone in the left upper and lower limbs
with dystonic left clinched fist, left upper limb apraxia , alien hand and
stimulus sensitive myoclonus. Opening and closing of the left hand each time
corresponded with mouth opening and
closure (Videotape1) . This oral digital synkinesaia did not habituate and
continued over three years of follow up.
Patient 2- A 55 year
old male complained from slowing of movements, “stiffness “of the limbs and
right hand tremor for the 12 months. Examination showed moderate rigidity and
hypokinesia bilaterally; more on the right side and a resting tremor on the
right. The right upper limb was apraxic with intermittent action myoclonus.
Opening and closing of hands opened the mouth simultaneously.
Results: Magnetic resonance imaging showed diffuse
cortical atrophy in both patients and additional mild diffuse microangiopathy
in the second patient. Both patients failed levodopa treatment with doses up to
25/100 five times daily.
1- Two patients met
the clinical criteria for diagnosis probable corticobasal degeneration
presented who demonstrated prominent oral-digital synkinesia in examination.
2- Oral -digital
synkinesia did not habituate and once occurred persisted over time.
3- Oral -facial
synkinesia in CBD may be caused by activation of supplementary motor cortex as
reported for ipsilateral hand- foot synkinesia in PD (Salardini et al Neurosci
Lett 2012, 523:135).
4- An fMRI study is scheduled for the second
patient.
P17.10
Auto-segmentation and
evaluation of daily mobility tasks: whole-body kinematic assessment in
Parkinson patients and elderly adults
Fariborz Rahimi1,
Lynn Zhu2, Margaux Blamoutier3, Catherine
Lavigne-Pelletier3, Mandar Jog1,2, Patrick Boissy4,
Christian Duval3
1London Health Sciences Centre, London,
ON Canada
2University of Western Ontario, London,
ON, Canada
3Centre de Recherche Institut
Universitaire de Gériatrie de Montréal, Montréal, QC, Canada
4Université de Sherbrooke, Sherbrooke,
QC, Canada
Introduction: Aging and Parkinson disease (PD) are major causes of restriction in daily mobility. Unconstrained ambulation and its change with age, disease, or medical intervention are difficult to assess. Natural mobility is complex and understanding it requires segmentation into simpler and consistent sub-movements. Sub-movements such as sit, stand, walk, turn can occur as primary movements or have added secondary components such as carrying an object and passing obstacles. In this study, using a full-body network of inertial motion units (IMUs) and multiple variants of a Timed Up and Go (TUG) task a robust segmentation algorithm for segmentation into primary and secondary movements has been developed.
Methods: 11 PD (65±9 years) and 19 healthy (70±9 years) participants performed 5m TUG test at their normal speed along with variants of TUG: 10m normal and fast speeds, with obstacles, L-path, carrying a physical load, and with cognitive loads. TUG-5m trials were used to adjust the parameters for segmentation in both groups. Auto- and visual segmentation performance is compared. Key parameters in performance of each mobility task, such as stability in transitional task, symmetry in straight walking (including in arm swing), and degradation indices with performance of the secondary tasks will be presented.
Results: Optimal parameters for detecting some
transitions were different between PD and healthy. Performance of previously
proposed algorithms with minimal sensors was improved with multiple IMUs.
Auto-segmentation algorithm was able to correctly detect 88-100% of sitting,
89-97% of sit-to-stand, 94-100% of turns, 68-96% of turn-to-sit, 68-94% of
stand-to-sit, and 77-97% of straight walking tasks.
Conclusion: This study showed that using a full-body
network of IMUs, mobility detection algorithms optimized for a combination of
simple tasks could reasonably detect variation of those tasks. This study could
eventually help identify the best location of sensors for optimal detection of
changes in movement performance.
P17.11
Late-onset hepatolenticular degeneration presenting as
Parkinson’s disease
Maja Relja and Vladimir Miletić
Movement Disorders
Centre, Department of Neurology, Zagreb University Medical School,
Clinical Medical Center, Zagreb, Croatia
Introduction: Wilson disease (WD) is an autosomal recessive disorder of
copper biliary excretion caused by an impaired function of a metal-transporting
P-type ATPase (ATP7B) encoded by WD gene. WD is one of the very few chronic neurological diseases for which
specific and effective treatment is available. The clinical symptoms and age at
onset of WD are highly variable but it usually develop between 3 and 40 years
of age and include signs of liver and/or neurological (movement disorders)
disease. Unfortunately, a misdiagnosis appears early in the course of the
disease and late-onset WD is a frequently overlooked condition.
Objective: To report late-onset WD in 63 year-old man with symptoms of
Parkinson’s disease (PD).
Patient and Methods: At the age of 60 male patient develop resting tremor of both hands
with postural instability. He had slightly abnormal liver function. Levodopa
treatment was introduced with mild transient improvement. After 3 years he was
refered to Movement disorders centre as idiopathic PD for therapy titration. In
addition to tremor, rigdity, bradykinesia and postural instability dysarthria
was observed. On examination Kayser-Fleicher ring was demontrated as well as
low ceruloplasmin concentration and serum copper level. Hepatic copper content
in liver biopsy tissue was increased (350 microg/g dry weight). Magnetic
resonance imaging was unspecific (cotical atrophy). D-penycilamine therapy was
introduced (total 600 mg daily).
Results and Discussion: D-penycilamine therapy caused transient axacerbation of tremor. But
after 3 moths significant clinical improvemnt was observed and levodopa dose
could be reduced. WD presents with a variety of neurological signs and
late-onset WD is a frequently overlooked condition. Since early treatment may
reverse even long-lasting symptom, WD should be considered also in older
patients with symptoms of PD.
P17.12
MIBG scintigraphy and a predictive role in
clinically uncertain Parkinsonism
Anna Sauerbier1, Nikolay Dimitrov1,
Riddhika Chakravartty2, Nicola Mulholland2, Gill Vivian2,
Kallol Ray Chaudhuri1
1National
Parkinson Foundation Centre of Excellence, Dept of Neurology, King’s College
Hospital, and Kings Health Partners, London, UK
2Dept of
Nuclear Imaging, King’s College Hospital, and Kings Health Partners, London, UK
Objective: Visualisation of the heart using MIBG scintigraphy is an useful method to ascertain Parkinsonism from idiopathic Parkinson’s disease (IPD) and is an approved technology in some countries such as Japan but not in the UK. In this single centre study, we describe an UK based experience in order to analyse the predictive significance of MIBG scintigraphy for the diagnosis of IPD versus Parkinsonism in cases with clinically uncertain Parkinsonism (CUP).
Methods: Using a retrospective
single centre analysis/audit we studied the clinical diagnoses of 41 patients
(mean age 72±11.28 years) and the related static MIBG images which were
classified to 3 types (1= no visualisation of the heart, 2= borderline, 3=
clear visualisation of the heart). We then sought of correlation between these
types and the clinical diagnoses at a variable clinically determined follow up
(FU) period.
Results: Data are shown in
Table 1. 60% of CUP cases with type 1 MIBG scans had confirmed diagnosis of IPD
at FU while type 3 MIBG scans correlated with a 45.8% cases proving to have
Parkinsonism (MSA) and another 41.7% continuing a diagnosis of CUP but not IPD.
Majority of the type 2 MIBG scans also had a final diagnosis of atypical
Parkinsonian syndrome. 29 of the patients underwent a DAT scan which confirmed
striatal dopamine denervation in 75.9% of all patients. Except 1 all patients
underwent MIBI scans.
Table 1 Prevalences of type1-3
MIBG scans and clinical diagnosis in our cohort
Type |
0 (non-visualisation of the heart) |
1 (borderline) |
2 (clear visualisation of the heart) |
Idiopathic
Parkinson syndrome |
6 (60%) |
2
(28.57%) |
3 (12.5%) |
Atypical
Parkinson syndrome |
3 (30%) |
3
(42.86%) |
11
(45.83%) |
Unknown |
1 (10%) |
2
(28.57%) |
10
(41.67%) |
In
conclusion to our knowledge this is the first study in the UK analysing the
effect of MIBG in the differential diagnosis of IPD and CUP. MIBG cardiac scans
may play an useful although surrogate role in the final diagnosis of CUP cases.
Acknowledgement: National Institute
for Health Research (NIHR) Mental Health Biomedical Research Centre and
Dementia Unit at South London and Maudsley NHS Foundation Trust and [Institute
of Psychiatry] King’s College London
CLINICAL SCIENCES: CO-MORBIDITIES
P18.01
Post-stroke Parkinsonism
Arsovska A¹, Popovski A², Arsovski Z³
¹University
Clinic of Neurology, Skopje, Macedonia
²PHO “Dr A.
Popovski”, Skopje, Macedonia
³University
Clinic of Pulmonology and Allergy, Skopje, Macedonia
Objective: Parkinsonism is one
of the movement disorders that may appear after stroke and complicate the
course of the disease.
Aim: To analyse the
incidence, anatomical correlation, temporal relationship and associated risk
factors of Parkinsonism after stroke.
Material
and methods: We made a prospective analysis of 86 patients with stroke during a
period of 1 year. We analysed the CT findings, neurological status and risk
factors.
Results: Three patients
(3,4%)developed Parkinsonism after median time of 125 days after stroke. All
were male, median age 75 years. Two had ischaemic stroke, one was with
haemorrhagic stroke. These strokes were in the right hemisphere (2 in the basal
ganglia, 1 in the thalamus). Neurological status revealed motor dysfunction and
sensory loss, respectively. No statistical difference was found in the
associated risk factors among the groups with and without Parkinsonism
(p>0.05), with hypertension being the commonest risk factor.
P18.02
Managing Parkinson’s
disease related co-morbidities at a community hospital outpatient geriatrics
clinic for Parkinson’s
Joyce Lee1, 2,
Greta Mah1
1
Geriatrics Clinic for Parkinson’s and Living Well with Parkinson’s Program,
North York General Hospital, Toronto, ON, Canada
2
University of Toronto, Toronto, ON, Canada
Introduction: Ninety
percent of patients with Parkinson’s disease (PD) are over 60 years of age. In
addition to mobility symptoms, patients experience PD related co-morbidities
which are often undiagnosed and therefore untreated. A Geriatrics Clinic
for Parkinson’s with a geriatrics PD specialist - pharmacist team was
established under a community hospital’s ambulatory service. It provides
comprehensive geriatrics assessment and management to elderly patients with PD
referred by family physicians, neurologists or discharged from hospital.
Objectives: This study aimed to
determine (1) whether comprehensive geriatrics assessment could identify
previously unrecognized PD related co-morbidities (2) types and prevalence of
co-morbidities in a community-based population of elderly patients with PD.
Method: A prospective
observational study was conducted from January 2008 to December 2009. All new
patients seen at the clinic during this period were included. Each patient was
assessed through a comprehensive geriatrics assessment, including a review of
motor, neuropsychiatric and autonomic symptoms. Standardized non-motor symptoms
questionnaire and standard validated assessment scales were used.
Results: One hundred and
forty patients with the average age of 76 were seen in the clinic during study
period. Comprehensive assessment in the clinic identified 379 cases of
previously unrecognized co-morbid conditions. These include 80 cases of
dementia, 74 of anxiety/depression, 64 of constipation, 54 of osteoporosis, 45
of orthostatic hypotension, 39 of pain and 23 of acid reflux.
Conclusion: Comprehensive
geriatrics assessment in this specialized clinic has successfully identified
many cases of PD related co-morbidities in a community-dwelling elderly
population with PD.
P18.03
R. Manso
Calderón1
1Neurology Deparment.
Hospital Clínico Universitario, Salamanca, Spain
Aim: Comorbidity is common in the elderly and contributes
to the complexity of this population subgroup. Our goal is to evaluate the prevalence and contribution of comorbidities on functional decline,
disability and cognitive performance in a population of Parkinson´s disease
(PD) patients.
Patients and Methods:
Data on 107 patients with PD (48 men/59 women)
followed-up in a neurologic consultation in Salamanca, Spain, were obtained.
The mean age of PD patients was 77.2 ± 8.3 years (mean duration of PD 10.7
± 4.8 years) and Hoehn & Yahr Staging median:
3[1-5]. Comorbidity data included six common conditions
(heart/circulation problems, diabetes, arthritis, cancer, respiratory diseases
and other neurologic diseases). Also we performed
comorbidity (Charlson Index), motor (UPDRS part III), functional (Hoehn and Yahr),
activities of daily living (Schwab and England) and cognition
(Mini-Mental State Examination (MMSE))
assessments.
Results: The two most
reported comorbidities were heart/circulation problems (50.5%) and arthritis
(37.1%), with other neurologic diseases affecting 20.6% of the sample (7.5%
stroke, 5.6% essential tremor, 5.6% head injury). Diabetes was diagnosed in 18.4%, cancer in 16.3% and respiratory
diseases in 15.3%. Arthritis was more prevalent in women and respiratory
conditions in men. The Charlson Index of comorbidity median was 2[0-12]. A higher score in the Charlson Index was associated
with an older age and akinesia-rigidity subtype as initial predominant motor
sign in PD. Specific comorbidities, particularly heart/circulatory and
diabetes, independently contributed to worse cognitive performance (p=0.04).
However, comorbidity didn´t affect functional decline or disability.
Conclusion:
Comorbidities are very common in PD, especially heart/circulation problems and
arthritis. In some PD patients, essential
tremor may precede the onset of PD by several years or decades. Nevertheless, this study only provides evidence for
a small detrimental influence of comorbidities on measures of cognition.
P18.04
Pulmonary dysfunction in Parkinson’s disease patients
attending the Lagos University Teaching Hospital, Nigeria
Oluwadamilola O. Ojo1, Obianuju B. Ozoh2,
Njideka O. Okubadejo1, Olajumoke O. Oshinaike3
1Neurology Unit,
Department of Medicine, College of Medicine University of Lagos, Nigeria
2Respiratory Unit,
Department of Medicine, College of Medicine University of Lagos, Nigeria
3Neurology Unit,
Department of Medicine, Lagos State University College of Medicine, Nigeria
Objective: To determine the prevalence and pattern of
pulmonary dysfunction experienced by PD patients attending the Movement
Disorders (MD) Clinic of the Lagos University Teaching Hospital (LUTH)
Methods: 43 PD attending the Movement Disorders
clinic, LUTH were consecutively recruited between March 2011 and September
2012. 81 apparently healthy non-smoking age and sex-matched controls were also
studied. The study population did not have any current or past history of
respiratory or cardiovascular symptoms/disease capable of compromising lung
function. Pulmonary function was assessed by spirometry and the following
parameters obtained – forced expiratory volume in one second (FEV1), forced
vital capacity (FVC), FEV1/FVC ratio and peak expiratory flow rate (PEFR).
Obstructive pulmonary dysfunction was defined as FEV1/FVC ratio less
than 70% while restrictive pulmonary dysfunction was defined as FEV1/FVC
ratio equal to or greater than 70% with FVC percentage predicted below 80%.
Results:
There
was no significant difference regarding age and gender within the study
population. Mean FEV1 was significantly lower for PD (1.54 ± 0.70L) compared to
controls (1.96 ± 0.66L); p = 0.001. Mean FVC was also significantly lower for
PD (1.81 ± 0.96L) compared to controls (2.22 ± 0.85L); p = 0.02. PEFR was
significantly lower for PD (4.2 ± 2.2L/min) than controls (5.5 ± 2.0L/min); p =
0.001. There was no significant difference between the FEV1/FVC ratio of PD and
controls (p > 0.05). Respiratory dysfunction was present in 37 0f 43 PD
(86%) and 51 of 81 controls (62.9%); χ2 = 51.4, p = 0.00. The
pattern of respiratory dysfunction was restrictive in 89.2% (33 of the 37) PD
and obstructive in 10.8% (4 of 37 PD). None of the controls had an obstructive
pattern of respiratory dysfunction.
P18.05
The impact of comorbidities and
concomitant medications on falling in Parkinson disease
Sotirios Parashos1,
Catherine Wielinski1, Martha Nance1
1Struthers
Parkinson’s Center, MN, USA
Objective: To assess
the relationship between comorbidities and concomitant medications which are
known risk factors of falling in the elderly and falling in Parkinson disease
(PD). A number of systemic and neurological disorders and drug categories have
been identified as risk factors for falling in an American Academy of Neurology
Practice Parameter. We sought to explore the strength of these risk factors in
predicting falls in PD patients.
Methods: Detailed
medication regimens and 4-week diaries recording falls and near falls were
collected in 335 PD subjects. Two sets of partial correlations were obtained
with presence of falls as the main outcome measure: in the first set, the
presence of neurological, osteoarthritis, and spinal co-morbidities were used
as possible predictors, while accounting for presence of any drug risk factors,
age, and disease duration; in the second set, concomitant treatment with
benzodiazepines, other sedatives, tricyclics, antihistamines, and opioids were
used as possible predictors, while accounting for presence of any comorbidity
risk factors, age, and disease duration. Chi-square was used to test
associations. Statistic significance was set at p<.05.
Results: 53% of
subjects experienced at least one fall, 35% were on concomitant medications
known to increase falls risk and 66% had comorbidities known to increase falls
risk. None of the comorbidity categories showed any significant association to
the main outcome. Among drug categories known to increase falls risk, only
tricyclics were associated with the main outcome (p=0.009). Comorbidities and
concomitant medications commonly associated with increased falls risk in the
general population do not seem to predict falling in PD, with the only
exception of tricyclic antidepressants.
CLINICAL SCIENCES: BIOMARKERS AND NEUROIMAGING
P19.01
Usefulness of (123 I)-FP-CIT SPECT (DaT Scan) in diagnosing
drug-induced Parkinsonism (DIP): a retrospective study
Anwar Ahmed MD
Center of Neurological
Restoration, Cleveland Clinic Foundation, Cleveland, OH, USA
Objective: Objective of our study is to differentiate DIP
from Neurodegenerative Parkinsonism (NDP) with the help of a DaT Scan.
Differentiating DIP from NDP may be a challenge to clinicians. Patients who
develop DIP may unnecessarily receive dopaminergic medication due to
difficulties in making correct diagnosis. One of the factors distinguishing DIP
from NDP involves discontinuation of the suspected medication in DIP should
relieve the symptoms of Parkinsonism. However in clinical practice the
timeframe between the drug withdrawal and resolution of the symptoms of
Parkinsonism could be longer which leads to delay in the diagnosis and
treatment of patient with IPD.
Method: We designed a retrospective study of 10
patients including 4 men and 6 women presented to our clinic with suspected
symptoms of DIP. All patients had a history of exposure to the drugs known to
cause extrapyramidal side effects (EPS). All patients underwent detailed
neurological examination and Ioflupane (123 I)-FP-CIT SPECT (DaT Scan).
Results: Among nine out of ten patients with suspected
DIP the DaT Scan showed the pattern of tracer uptake suggesting normal
dopaminergic neuronal terminal density in the striatum. However in one patient
there was grade 2 loss of dopaminergic terminal density in the striatum
suggestive of NDP. A negative DaT scan in nine out of ten cases correctly
predicted a diagnosis of DIP and seems to exclude NDP reliably. One patient
with positive DaT Scan had an underlying NDP unmasked by dopaminergic blocking
drugs may be suggestive of presynaptic dopaminergic loss. These results also
suggest postsynaptic dopamine blocking effect is linked to DIP. In conclusion
DIP can be differentiated from NDP with the use DaT Scan and unnecessary use of
dopaminergic drugs can be avoided.
DIP: Drug induced
Parkinsonism
NDP: Neurodegenerative
Parkinsonism
P19.02
Effect of dopamine
receptor binding agents on Dopamine Transporter (DaT) scan result
A. Ahmed1 , S.
Oravivattanakul1, L. Benchaya1, I. Itin1, M.
Gostkowski1, S. Cooper1, J. Rudolph1, H.H.
Fernandez1
1 Center of
Neurological Restoration, Cleveland Clinic Foundation, Cleveland, OH, USA
Background: DaT scans aid
physicians in differentiating neurodegenerative vs non-neurodegenerative
parkinsonism. Drugs that may interfere with dopamine receptor binding have been
labeled as “contraindicated” with a recommendation to stop prior to scan, as
they might decrease radioligand uptake and result in a false positive
(abnormal) scan. However, many patients taking these contraindicated
medications have psychiatric co-morbidities that make it difficult to
discontinue medications without the risk of exacerbating psychiatric symptoms.
Objective: To assess the effect
of contraindicated agents on DaT scans.
Method: All patients who
obtained DaT scan that were ordered by movement disorders specialists at
Cleveland Clinic from June 1, 2011 to October 31, 2012 were analyzed, including
demographic data, medications prior to scan and the scan results. We excluded
scans that were obtained for research purposes and repeat scans on the same
patient.
Result: Forty one scans were
excluded based on our exclusion criteria, and 175 scans were included in our
analysis. 45 out of 175 patients (26%) were on “contraindicated” medications
prior to the scan. Only one patient was documented to discontinue the drug prior
to the scan. Dopamine receptor binding drugs that patients were taking included
Citalopram, Bupropion, Buspirone, Selegiline, Rasagiline, Methylphenidate,
Amphetamine, Paroxetine, Sertraline. 25 patients (53%) who were exposed to
these medications had negative DaT scans and 20 patients (43%) who were on
these contraindicated drugs had positive DaT scans.
Conclusion: Our data suggests
that patients who were on drugs that may interfere with dopamine receptor
binding can still have a negative (normal) scans. Therefore, at least in this
subset of patients, the presence of contraindicated medications did not seem to
interfere with the scans. More studies are needed in understanding the effect
of dopamine receptors binding agents on DaT scans.
P19.03
A large
Turkish Parkinson pedigree with alpha-synuclein duplication: blood expression
biomarkers elucidate predictive diagnostics and pathway
Georg Auburger1, Suna
Lahut2, Özgür Ömür2, Suzana Gispert1, Caroline
Pirkevi2, Hülya Tireli3, Nadine Brehm1, Karl Hackmann4,
Evelin Schroeck4, Nazli Basak2
1Neurology,
Goethe University, Frankfurt am Main, Germany
2NDAL,
Bosphorus University, Istanbul, Turkey
3Neurology,
Haydarpasa Numune Hospital, Istanbul, Turkey
4Clinical
Genetics, Technical University, Dresden, Germany
Objectives: To
establish a predictive blood test for synucleinopathy.
Methods: Whole
blood in PAXgene tubes from twelve presymptomatic and 2 symptomatic carriers of
a SNCA duplication in a large Turkish PD family underwent expression profiling.
Results: Eight
biomarkers from the vesicle fusion pathway (SNARE machinery) showed the best
correlation with genotype.
Conclusions: Excess
physiological function of alpha-synuclein leads to detectable significant
downstream effects in blood, which may be useful in predictive diagnostics and
complement existing methods to diagnose prodromal PD. Furthermore, they help to
elucidate a common pathway of PD pathogenesis.
P19.04
A novel blood-brain barrier permeable PET Ligand for
Parkinson’s disease
Anna Cartier1 and Ram Bhatt1
1ICB International,
Inc., La Jolla, CA, USA
Objective: Development of blood-brain barrier (BBB)
permeable biologics that specifically target alpha-synuclein
(α-syn) has great clinical potential for early diagnosis, monitoring of disease
progression and therapeutic efficacy of drugs in patients at risk or afflicted
with Parkinson’s disease (PD). We
have developed a breakthrough technology, referred to as Picotechnology that
unequivocally delivers diagnostic and therapeutic antibody mimics (AbMs) across
the BBB to specific targets within the central nervous system (CNS). AbMs display excellent BBB penetration
and pharmacokinetics, characteristics that are highly desirable for the use of
antibodies as in vivo imaging
biomarkers. Using this innovative approach, alpha-synuclein-AbM
(α-syn-AbM) was generated to detect and visualize toxic α-syn aggregates either as inclusions, pre-Lewy bodies
(LBs) or LBs. Our long-term objective is to develop a diagnostic imaging
biomarker by utilizing α-syn-AbM as positron emission tomography (PET)
ligand. In this study, the specificity and BBB permeability of α-syn-AbM
was evaluated in α-syn transgenic (tg) mice.
Methods: To assess tissue specificity of
α-syn-AbM ex vivo, brain
tissue sections from α-syn tg mice and patients with PD were immunolabeled
with α-syn-AbM. To determine the BBB permeability of α-syn-AbM in
vivo, α-syn transgenic and non-transgenic mice were injected
intravenously (i.v.) with a single low dosage of α-syn-AbM (1.5 mg/Kg) or
a conventional monoclonal antibody against α-syn. Mouse brains were
harvested 24 hours post injection and tissue sections were analyzed for the
presence of antibodies in the brain by immunostaining.
Results: Ex vivo tissue
stainings of human PD and α-syn tg
mice demonstrated that α-syn-AbM binds
and labels LBs and LB-like structures, respectively. The BBB permeability
of α-syn-AbM was substantiated in α-syn transgenic mice that received a single low dose injection of
α-syn-AbM but not the conventional mouse antibody. α-syn-AbM
was shown to cross the BBB and specifically label diffuse
aggregated (oligomeric) forms of α-syn and LB-like structures.
P19.05
Longitudinal striatal atrophy during Parkinson's
progression
Guangwei Du1, Mechelle M. Lewis1,
Zeinab Nasralah1, Nicholas Sterling1, Christopher Dimaio1,
Lan Kong1, Martin Styner2, Xuemei Huang1,2
1Penn State Hershey
Medical Center, Hershey, PA, USA
2University of North
Carolina at Chapel Hill, Chapel Hill, NC, USA
Background: Parkinson’s disease (PD) is marked
pathologically by progressive nigrostriatal dopaminergic cell degeneration.
Striatal atrophy has been suggested by postmortem pathological data and
cross-sectional imaging studies.
Objective: To test the hypothesis that PD causes
accelerated striatal atrophy using a state-of-the-art probabilistic atlas-based
segmentation approach.
Methods: High resolution (3-T) T1- and T2-weighted
MRI images were obtained from 80 PD patients and 55 healthy controls at
baseline and 18 month follow-up. Striatal structures [putamen (PUT), caudate
(CN), and global pallidus (GP)] were segmented individually based on both T1
and T2 images using a fully automatic probabilistic atlas-based pipeline
implemented in AutoSeg 2.9 (http://www.med.unc.edu/psych/research/niral/). For PD patients,
clinical measures including the United Parkinson's Disease Rating Scale,
disease duration, and levodopa equivalent daily dose also were recorded. The
dynamic volume changes between PD and controls were assessed using mixed
effects models controlling for age and gender. Associations between striatal
volume change and clinical measures were assessed using partial Pearson
correlation coefficients.
Results: The dropout rates at 18 months were 20% for
PD patients and 15% for controls, respectively. Cross-sectional comparisons
between PD and controls indicated that PD patients displayed significant volume
loss of PUT at follow-up [p=0.0065], but not at baseline [p=0.090].
Longitudinal analyses demonstrated that PD subjects had significantly faster
volume loss in all three striatal structures [p=0.036 for PUT, p=0.005 for GP,
and p=0.049 for CN] compared to controls. Volumes of all three striatal structures
were correlated with all clinical measures at baseline, but volume change was
correlated with clinical measures only in CN.
Interpretation: There
is accelerated striatal atrophy in PD, and dynamic volume changes in striatum
might be a useful marker for Parkinson’s progression.
P19.06
A promising
preclinical biomarker for Parkinson’s disease based on ocular tremor: support
from quantitative DaTscan analysis
George T.
Gitchel1, 2, Paul A. Wetzel2, Shekar Raman3,
James Tatum4, Mark S. Baron 1, 5
1Southeast Parkinson’s Disease Research, Education, and
Clinical Center (PADRECC), Hunter-Holmes McGuire Veterans Affairs
Medical Center, Department of Veterans Affairs, Richmond, VA, USA
2Virginia Commonwealth University, Department of Biomedical
Engineering, Richmond, VA, USA
3Sleep Disorder Center, Hunter Holmes McGuire Veterans
Affairs Medical Center, Department of Veterans Affairs, Richmond, VA, USA
4Nuclear Medicine, Hunter Holmes McGuire Veterans Affairs
Medical Center, Richmond, VA, USA
5Virginia Commonwealth University, Department of Neurology,
Richmond, VA, USA
Objective: Parkinson’s disease is known to have a
lengthy prodromal period preceding the onset of clinical motor symptoms.
Studies suggest that more than half of subjects with REM sleep behavior
disorder (RBD) will develop PD and that, on average, RBD predates the onset of
PD motor symptoms by over a decade. Our previous study showed that ocular
tremor was a universal feature of PD, including in those with de novo,
untreated disease. The present study aims to determine the utility of ocular
tremor as a preclinical biomarker for PD.
Methods: To date, 17 subjects with polysomnography
confirmed RBD were assessed using an Eyelink II binocular eye tracker while
following random step displaced stimuli. None of the subjects had symptoms or
clinical features of PD or other neurological conditions.
Results: Nine of 17 subjects (53%) had ocular tremor
consistent with that seen in PD, while the other 8 subjects exhibited normal
eye movements. UPDRS Part III Examination scores did not differ between groups
with and without ocular tremor. Three subjects with ocular tremor consented to
DaTscan imaging. Quantitative analysis showed unilateral reduction of uptake in
the putamen in two subjects and bilateral reduction in the putamen in the third
subject. Conclusions: These
compelling findings in a group at risk for PD suggest that ocular tremor could
serve as a highly accurate biomarker for the detection of preclinical PD.
P19.07
Metabolomic changes associated L-DOPA induced dyskinesia
in a MPTP primate model of Parkinson’s disease and the effect of DHA or
plasmalogen precursor administration
Dayan Goodenowe1, Tara Smith1,
Vijitha Senanayake1, Thérèse Di Paolo2,3 and Laurent
Grégoire2
1Phenomenome Discoveries
Inc., 204-407 Downey Road,
Saskatoon, SK, Canada
2Neuroscience Research Unit, Centre de Recherche du CHU
de Québec, QC
3Faculty of Pharmacy,
Laval University, Quebec, QC
Objective:
Development of dyskinesias with long-term treatment of dopamine precursor
L-DOPA in Parkinson’s disease (PD) remains a serious obstacle in the treatment
of PD. We have therefore investigated the metabolomics effects of L-DOPA in
MPTP monkeys before and after inhibition of dyskinesias by either
docosahexaenoic acid (DHA) or the plasmalogen precursor-PPI-1011 using
non-targeted Fourier transform ion cyclotron mass spectrometry (FTICR-MS).
Methods:
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was administered to monkeys
(n=5) to deplete dopaminergic neurons and to make monkeys parkinsonian. The
monkeys were then given L-DOPA to induce dyskinesias. Then either DHA (100
mg/kg) or plasmalogen precursor PPI-1011 (50 mg/kg) was administered in a
cross-over design with a washout period in-between the treatments. Serum was
subjected to aqueous and organic extractions followed by analysis by FTICR-MS.
Behavioral studies were done to evaluate parkinsonian symptoms and dyskinesias.
Dyskinetic scores and treatment phases were statistically correlated to changes
in the intensity of accurate masses in serum to evaluate the metabolic changes
associated with dyskinesias.
Results: There was a significant reduction in dyskinesias in monkeys at
differing time points with PPI-1011 and DHA treatments. 176 masses were
commonly associated with the reduction of dyskinesias in monkeys with either
PPI-1011 or DHA (p<0.01). Out of these 176 masses, the restoration of 10
masses were identified as being primarily responsible for reducing dyskinesias.
L-DOPA induced dyskinesias create a specific metabolic profile that responds to
therapy with either DHA or PPI-1011.
P19.08
Safety of DaTscanTM (Ioflupane I 123
Injection), a radiopharmaceutical indicated for visualization of the striatal
dopamine transporter in the brain using SPECT imaging
Igor D. Grachev1,
Paul Sherwin1, Duncan Lane1, Rick Jarecke1,
Christel Zeisse1, Emilio Moreno1, Jeff Freid1,
Donald G. Grosset2, Nin Bajaj3, Robert A. Hauser4,
John Seibyl5, Kenneth Marek5
1GE Healthcare, Princeton, NJ, USA
2The Institute of Neurological Sciences, Glasgow, UK
3Nottingham University Hospitals NHS Trust,
Nottingham, UK
4USF Byrd Parkinson's Disease and Movement Disorders
Center, Tampa, FL, USA
5The Institute for Neurodegenerative Disorders, New
Haven, CT, USA
Objective: To assess DaTscanTM ([123I]Ioflupane Injection) is
safety data from clinical trials in GE Healthcare’s clinical development and
post-marketing experience.
Methods: In GE Healthcare’s clinical trials, DaTscanTM was administered intravenously to
1236 subjects (1171 patients and 65 healthy volunteers). Clinical trials
collected information on adverse events (AEs), and collected data on laboratory
parameters, vital signs and ECG. Administered activity of [123I]ioflupane
ranged from 3 to 5 mCi (111 to 185 MBq). The calculated whole body effective
dose was 4 to 6 mSv, comparable to 1 year of natural background radiation in
the USA (3 to 4 mSv).
Results: There were mild and infrequently
reported AEs and no SAEs or deaths that were considered related to DaTscanTM
administration. The most common AE ascribed to DaTscanTM by the
investigator was headache (1%), followed by nausea, and vertigo, dry mouth,
hunger, dizziness, and formication (<1 % each). Most of these AEs were mild.
The safety profile established in clinical trials is supported by limited AE
reports (including hypersensitivity reported as rash and pruritis shortly after
dosing) from post-marketing exposure in over 300,000 patients who have been
imaged with DaTscanTM. Comprehensive review of the safety data shows
that DaTscanTM is a safe product to use. Study Supported by GE Healthcare.
P19.09
MR Volumetry and T2 relaxometry of the Basal ganglia in
Sydenham’s chorea: A study in the Indian population
Rohit Gupta
B.K. Medical centre,
Delhi, India
Objective: The purpose of our study was to
evaluate abnormalities of the basal ganglia (BG) in patients with Sydenham
chorea (SC) using MR volumetry (MRV) and T2 relaxometry (T2R) on 3 Tesla MRI.
Although SC is relatively rare in developed countries, it is often encountered
in Indian population due to the higher incidence of rheumatic fever. The
disease has recently been implicated in the etiology of Obsessive Compulsive
Disorder (OCD).
Methods: Eight patients with SC and sixteen age
matched controls were recruited for the study. In addition to the conventional
T1W, T2W and FLAIR sequences, a high resolution 3D inversion recovery (IR)
sequence was performed for calculating the basal ganglia volumes using the
manual region of interest (ROI) method. The subjects then underwent T2 mapping
using a multiecho FRFSE sequence on a 3T MR scanner. T2 values were calculated
from the caudate nuclei and putamina. Statistical analysis of the data was
performed.
Results: Our results indicate that compared with
healthy controls, patients with SC have a significant decrease (p
value<0.01) in T2R values of the caudate nuclei suggesting increased iron
deposition in these structures. The basal ganglia –frontal lobe tracts play an
important role in performing goal-directed movements and hence have been
implicated in movement disorders. Increased BG iron deposition has been
reported in SC and other such neuropsychiatric movement disorders resulting in
shortening of the BG T2 relaxation times on T2R while BG volumes are preserved
on conventional MRI sequences. Hence, we conclude that T2R at 3T MRI is a
sensitive tool for assessing BG iron content and can serve as a quantitative
imaging biomarker in movement disorders like SC.
P19.10
Cortical and subcortical brain volumes and clinical
correlates in preclinical and clinical Parkinsonism
Lalitha Guthikonda1, Stuart Red1, Annise Wilson1,
Anne Sereno1, Saumil
Patel2, Brian
Copeland1, Richard
Castriotta1, Tim
Ellmore3, Mya Schiess1
1UTHSC, Houston,
TX, USA
2BCM,
Houston, TX, USA
3CUNY, New
York, NY, USA
Objective: To correlate regional volume differences
with olfactory function, cognitive measures, and clinical severity in
preclinical and clinical Parkinsonism. Individuals with idiopathic REM sleep
behavior disorder (iRBD), considered a subclinical synucleinopathy, are at a
high risk for the development of Multisystem Atrophy (MSA), Lewy-Body Dementia,
or Parkinson’s disease (PD).
Methods: 23 confirmed PD, 10 confirmed MSA and 13
confirmed iRBD patients participated. Volumetric measurements were derived from
high resolution T1-weighted 3T MR images; volumetric reconstruction and
segmentation performed with Freesurfer.
Clinical measures included Hoehn & Yahr staging for severity, University of
Pennsylvania Smell Identification Test (UPSIT) - 40 odor olfaction, Montreal
Cognitive Assessment (MoCA). Pearson correlations of normalized brain volumes
and clinical measures were performed using SPSS 21.0.
Results: Significant negative
correlations between UPSIT scores and bilateral caudate volumes were found in
the iRBD group, demonstrating deficits in olfactory performance were associated
with larger caudate volumes and more representative of preclinical PD
pathology. Significant correlations were found between MoCA scores and volumes
bilaterally in the caudal middle frontal gyrus, but unilaterally in the caudal
anterior cingulate, posterior cingulate, precentral gyrus, and precuneus,
indicating cortical degeneration is related to decline in cognitive functioning
in iRBD patients and less representative of PD pathology. In the MSA group we
found significant correlations between UPSIT scores and the volume of left
amygdala and frontal pole, right cuneus, pericalcarine, rostral middle frontal
gyrus and insula. These results suggest brain volumetric measurements in
conjunction with clinical measures may be used as biomarkers, specific for
clinical and subclinical Parkinsonism and disease progression.
P19.11
The national institute of neurological disorders
and stroke Parkinson’s disease biomarkers program consortium
Katrina Gwinn1, Clemens Scherzer2,
Margaret Sutherland1, Beth-Anne Sieber1, Deb Babcock1,
for the PDBP Consortium3
1National
Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
2Brigham and
Women’s Hospital, Boston, MA, USA
3The NINDS
PDBP, www.pdbp.gov
Objective: The National
Institute of Neurological Disorders and Stroke (NINDS), is establishing a
Parkinson’s Disease Biomarkers Program (PDBP) (see http://pdbp.ninds.nih.gov/). The
overall purpose of the NINDS PDBP is to rapidly identify and develop potential
biomarkers to improve the efficiency of Phase II clinical trials and advance
therapy for PD.
Methods: The NINDS PDBP
coordinates efforts in the identification and development of diagnostic,
progression or prognostic PD biomarkers and related assays by: 1) standardizing
data and biospecimen collection across new PD cohort studies; 2) enhancing
efforts of current PD biomarker studies through ancillary projects that support
additional well characterized biospecimen collection; 3) accelerating the
discovery of new biomarkers; and 4) fostering and expanding collaborative opportunities. Currently
the NINDS PDBP includes four components: 1) Biomarker hypothesis testing
and collection of clinical data and biospecimens 2) Technology-based
studies 3) Biospecimen banking and distribution through the NINDS Repository and
4) Data management and standardization through a Data Management Resource
(DMR).
Results: To date, nine
projects have been awarded under this program, with a tenth and eleventh
existing project incorporated most recently. Three of the 11 projects are
technology development, and the remainder are clinical collections combined
with the development of clinical or laboratory methods and tools. In
collaboration with the PD research community, NINDS will integrate all of its
current and future PD biomarker projects within this program. Broad sharing of
data and biological specimens with academic, industry and government
researchers is a critical feature of the PDBP. Annual milestones provide clear
indicators of a project's continued success.
P19.12
Multi-modal
imaging study of the posterior cingulate in Parkinson’s disease
Chaorui
Huang,1* Jonathan P. Dyke,2 Henning U. Voss,2
Apostolos J. Tsiouris,2 Claire Henchcliffe,1 Panida
Piboolnurak,1 Lawrence Severt,3 Lisa D. Ravdin1,
James S. Maniscalco1,5,6, Lilja Solnes,2 Melissa J.
Nirenberg,4
1Department of Neurology and Neuroscience, Weill Cornell Medical
College, New York, NY, USA
2Department of Radiology, Weill Cornell Medical College, New York, NY,
USA
3Department of Neurology, Beth Israel Medical Center, New York, NY, USA
4Department of Neurology, NYU School of Medicine, New York, NY, USA
5Department of Psychology, City University of New York - The Graduate
Center, New York, NY, USA
6Department of Psychology, City University of New York - Queens College,
Flushing, NY, USA
Objective: Our goal was to test the hypothesis
that cognitive deficits in Parkinson’s disease (PD) are associated with
structural and functional changes in the posterior cingulate. To test this
hypothesis, we used multi-modal magnetic resonance imaging
(MRI) methods including high resolution
structural MRI, diffusion tensor imaging (DTI), continuous arterial spin
labeling (CASL) perfusion weighted MRI, MRI spectroscopy (MRS), in combination
with [18F]-fluorodeoxyglucose positron emission computed tomography (FDG-PET)
to assess brain glucose metabolism.
Methods: Twenty-nine PD patients (H&Y:
1-3.5) and 23 controls matched for age, gender, and educational level underwent
MRI examination, which included structural MRI, DTI, CASL, and MRS. Thirty-four
PD (H&Y: 1-3.5) and 20 control subjects underwent FDG-PET. Antiparkinsonian
medications were withheld for 12 hours prior to imaging. Pre- and
post-processing imaging were analyzed using statistical parametric mapping
(SPM).
Results: Compared with controls, PD subjects had
significantly increased mean diffusivity (MD), reduced N-Acetylaspartate
(NAA)/H2O levels, and borderline atrophy in the posterior cingulate. PD
patients also had decreased fractional anisotropy (FA) in the white matter
below the posterior cingulate and motor cortex, consistent with disrupted
microstructure and neuronal loss in PD. Significant metabolic increases on
FDG-PET were found in the bilateral posterior cingulate extending to the white
matter in PD subjects versus controls. This might potentially represent a
compensatory mechanism for structural damage in the adjacent region in PD. The
DTI MD, DTI FA, NAA/H2O and glucose
metabolism values were all associated with
memory decline in PD, as assessed by the California verbal learning test
(CVLT). There were no significant cerebral blood flow changes in PD subjects as
compared with controls, as assessed by CASL. Together, these findings show
evidence for structural damage and functional alterations in the posterior
cingulate in PD that might potentially play a role in the pathophysiology of
PD-related cognitive impairment.
P19.13
Abnormal functional
brain networks in Parkinson’s disease: A graph theory analysis of resting-state
fMRI data
M. Inglese1, R. Teodorescu1, K. Simonyan1,
M. Petracca1, Clara Moisello2, A. Di Rocco3,
M.F. Ghilardi2,3
1Dept of Neurology,
Mount Sinai School of Medicine New York, NY, USA
2Dept of Physiology and
Pharmacology, City University of New York, NY, USA
3Dept of Neurology, New
York University, NY, USA
Objective: The degeneration of dopaminergic
neurons in Parkinson’s disease (PD) is accompanied by impairment of not only
motor, but also cognitive and emotional functions. The aim of our study was to
characterize the whole brain functional connectivity in PD patients compared to
healthy age-matched controls (HC) using graph theory analysis of resting-state
(RS) fMRI data.
Methods: RS-fMRI was acquired in
twenty subjects, 10 patients with PD (6M/4F, 62.4±7.77 yrs, UPDRS score
16.9±6.8, H&Y staging 1.8±0.4) and 10 healthy controls (6M/4F, 63.5±8.84
yrs) using a 3 T scanner. The whole brain was parcellated in 206 bilateral
cortical, subcortical and cerebellum regions based on cytoarchitectonic maximum
probability map and macrolabels. Both global [clustering coefficient (γ),
path length (λ), global efficiency (E-glob)] and local [nodal betweenness
centrality (BC), degree (D), local efficiency (E-loc)] network metrics were
computed using Brain Connectivity Toolbox. To
ensure an equal number of edges, we thresholded all correlation matrices over a
wide range of sparsity (10% ≤S≤ 65% with 5% interval)
Results: Both
controls and patients with PD showed small-world network properties with
normalized clustering (γ=1.2 HC and 1.3 PD) and path length (λ=1.39
HC and 1.13 PD). However, clustering coefficient
was significantly lower (PD=0.34, HC=0.41; p=0.001) in patients compared to
controls. In addition, we found statistically significant decreased E-loc in right supramarginal and middle occipital gyri and
in left thalamus in PD as compared to HC (p ≤ 0.004). The number
of hubs was lower in PD (12) than in HC (33) based on degree. In comparison to
HC, PD patients showed statistically higher BC in right amygdala and superior
temporal gyrus, in left thalamus and bilateral insula (p ≤0.004). In summary, our results show that network topological
properties are altered in PD not only in motor areas but also in areas involved
with cognitive and emotional functions.
P19.14
Breath gas analysis for a potential
diagnostic method of Parkinson's disease
Pan-Woo Ko1, Kyung-Hun Kang1,
Joon-Boo Yu2, Jeong-Ok Lim3, Ho-Won Lee1,4
1Department of
Neurology, Kyungpook National University Hospital, Daegu, Korea
2Department of Material
Science and Metallurgy, Kyungpook National University, Daegu, Korea
3Biomedical Research
Institute, Department of Biomedical Science, Kyungpool National University
School of Medicine, Daegu, Korea
4Department of
Neurology, Kyungpook National University School of Medicine, Daegu, Korea
Objective: Exhaled breath analysis is a fast-developing topic to improve
the diagnosis and monitoring of the respiratory and systemic diseases, including
lung cancer. Not only as a lung biomarker, but also many of exhaled breath
components characterize the functioning of the organism as a systemic
biomarker. Therefore, we studied the feasibility of a novel method that is
based on breath gas analysis to identify neurodegenerative conditions,
especially for Alzheimer’s disease and Parkinson’s disease.
Methods: Exhaled breath was collected in an inert bag from 22 patients
with Parkinson's disease and 8 healthy controls. And we also collected breath
gas from 28 patients with Alzheimer's disease for another controls. Samples
were analyzed using gas chromatography mass spectrometry (GC-MS). All patients
and healthy volunteers conducted the neuropsychologic tests such as MMSE
Mini-Mental Status Examination), NPI Neuro-Psychiatric Inventory) and UPDRS
(Unified Parkinson’s Disease Rating Scale) motor scales.
Results: Among several compounds that showed statistical difference,
phenol was detected on the exhaled breath of most participants (19 out of 28
Alzheimer’s disease patients, 13 out of 22 Parkinon’s disease patients and 6
out of 8 healthy volunteers) and it showed higher concentrations in Parkinson’s
disease patients compared to healthy volunteers with statistical significance
(p < 0.01 for Phenol ; GC-MS measurements). Furthermore it also showed a
positive correlation with the UPDRS motor scale. Analysis of exhaled breath is
a non-invasive and totally painless test, so it could be an ideal method for
the diagnosis. In this study we showed the feasibility of a novel method to
diagnose Parkinson’s disease. However, phenol is usually detected in the
environmental sources and it is not well known for human metabolites. Therefore
further studies should be conducted to demonstrate more distinctive evidences
that could explain the correlation between pathology and clinical diagnosis of
Parkinson’s disease.
Acknowledgement: This research was supported by
the Converging Research Center Program through the National Research Foundation
of Korea (NRF) funded by the Ministry of Education, Science and Technology
(2012K001351 and 2012K001352).
P19.15
High field diffusion tensor imaging of the Corpus
Callosum in Parkinsonism dementia complex
Rima Kumari
Institute of Human Behaviour and Allied
Sciences, Delhi, India
Objective: The purpose of this
study was (a) to examine the regional nature of white matter (WM) abnormalities
in Parkinson’s disease (PD) using diffusion tensor imaging (DTI) parameters and
(b) to determine whether regional changes correlated with cognitive impairment
in Parkinsonism dementia complex (PDC). Patients with Parkinson’s disease (PD)
often present with cognitive deficits. The corpus callosum (CC) plays an
important role in transmitting sensory, motor and cognitive information between
cortical regions and both hemispheres. DTI is a recently developed MR imaging
technique which enables the noninvasive assessment of white matter
microstructural integrity.
Methods: We studied five
patients each with PD, PDC and twenty healthy controls using an echoplanar DTI
sequence on a 3 Tesla MRI scanner. We measured DTI parameters of the anterior
and posterior corpus callosum, including Fractional Anisotropy (FA) and Mean
Diffusivity (MD). Statistical
analysis across groups was performed using the t tests. The results were
correlated with the Mini Mental Status Examination (MMSE) scores.
Results: We found no
significant differences in the FA values of CC between PD subjects and
controls. PDC subjects had a significantly reduced FA value in the anterior
corpus callosum compared with controls and nondemented PD patients.
P19.16
Essential tremor has alterations in regional glucose
metabolism and GABAergic system
Eung Seok Oh1,
Jong-Min Kim1, Hyun Woo Kwon2, Yu Kyeong Kim2,
Byeong Seok Moon2, Byeong Chul Lee2, Sang Eun Kim2
Departments of 1Neurology and 2Nuclear
Medicine, Seoul National University College of Medicine, Seoul National
University Bundang Hospital, Borame Municipal Hospital, and Chungnam National
University Hospital, Korea
Objectives: We investigated
whether GABAergic transmission is altered in ET using [18F]
flumazenil (FMZ) PET which has a specific binding affinity to GABAA
receptor. Alteration of regional glucose metabolism was also investigated using
[18F] FDG PET.
Background: Essential tremor (ET)
is the most common movement disorder. However, the underlying etiology is not
clear. Recently, altered GABAergic neurotransmission has emerged as a key
feature of pathophysiology in ET.
Methods: Twelve patients (M:F=4:8, age=55.8±12.1)
fulfilling the criteria for definite ET according to the proposal of the Tremor
Research and Investigation Group were enrolled. All subjects performed FDG PET
and FMZ PET. Regional glucose metabolism and GABAA receptor
availability were compared with those of age-matched 18 healthy controls
(M:F=5:13, age =56.2±6.1).
Results: In the patient group, significant glucose
hypometabolism was identified in bilateral primary motor cortex and left
posterior parietal lobe (p<0.005, uncorrected: extended threshold, k=100).
GABAA receptor availability revealed no significant difference
between patient and control groups in voxel-based analysis. However, ROI
analysis showed a trend of slightly higher cerebral and cerebellar cortical
GABAA receptor availability in ET patients.
Conclusions: FMZ PET revealed mild difference in the GABAA
system between patient and control groups. FDG PET showed that ET patients have
glucose hypometabolism in bilateral primary motor cortex and left posterior
parietal lobe. Further studies are needed to elucidate the role of alterations
in the regional glucose metabolism and GABAergic system in ET.
P19.17
Influence of Dopamine Transporter (DaT) scan on medical
management in movement disorders specialists: Cleveland Clinic experience
S. Oravivattanakul1,
L. Benchaya1, A. Ahmed1, I. Itin1, M.
Gostkowski1, S. Cooper1, J. Rudolph1, H.H.
Fernandez1
1 Center of
Neurological Restoration, Cleveland Clinic Foundation, Cleveland, OH, USA.
Objective: To describe influence
of DaT scan on movement disorders specialist decisions on medical management of
patient presenting with parkinsonism.
Method: We conducted a
retrospective review of all patients, seen by a Movement Disorders neurologist,
who received a DaT scan at the Cleveland Clinic. Demographic data including pre
scan diagnosis and anti-PD medication use after the scan were collected. We
excluded all DaT scans ordered by other clinicians, scans obtained for research
and repeat scans in same patient.
Results: Total of 216 DaT
scans were performed from June 1, 2011 to October 31, 2012. Forty-one scans
were excluded based on our criteria. 175 scans were used for analysis. 45% had
positive DaT scans, 54% were negative and 1% was indeterminate. For patients
with an abnormal DaT scan, 96% were placed on anti-PD medications. Of those not
placed on anti-PD medications, two were due to the minimal degree of symptoms,
and one was due to a concern for a false positive scan due to drug interaction.
On the other hand, 25% of patients with negative scan remained on
anti-PD medications. Reasons
for these were: clinician’s belief that the scan was false
negative (N=6), mixed ET/PD diagnosis (N=2); other diagnosis responsive to anti-PD
medications, such as NPH (N=3), drug-induced parkinsonism (N=5), gait disorder
of unclear etiology (N=2), psychogenic parkinsonism (N=2), idiopathic
camptocormia (N=1), other form of dystonia (N=1), parkinsonism related to liver
disease (N=1).
Conclusion:
DaT Scan has strong influence on physician decision on initiating or continuing
on antiparkinsonian medications especially if the scan was positive. For
negative scans, the reasons why clinicians continue anti-PD medications are
varied.
P19.18
Differences in striatal dopamine transporter levels
regarding predominant motor symptom in Parkinson´s disease
M.D. Sevillano1, P. Cacabelos1,
P. Tamayo2,4, C Montes3,4, E. Perez3, E.
Martin2
1 Department of
Neurology, University
Hospital of Salamanca, Spain
2 Department of
Nuclear Medicine, University
Hospital of Salamanca, Spain
3 Department of Medical Physics
University Hospital of Salamanca, Spain
4
Institute
of Biomedical Research of Salamanca (IBSAL), Spain
Objective: Loss of striatal dopamine nerve terminal function, a hallmark of neurodegenerative
Parkinsonism, is strongly related to decreases of dopamine transporter (DAT)
density, which can be measured by single photon emission computed tomography
(SPECT) with 123I-FP-CIT. The aim of this study was to quantify the
loss of DAT, by means of 123I-FP-CIT SPECT, in patients with
Parkinson´s disease (PD) regarding predominant motor symptom at the onset of
disease.
Methods: 123I-FP-CIT SPECT studies were performed on 36
consecutive patients with clinical diagnoses of PD. 22 males; mean age: 70.67
years (46 to 88 years); Hoehn and Yahr stage: I-II and two cases in III These
patients were classified in two groups regarding predominant motor symptom at
the onset of disease: Group 1 consisted of 19 patients with tremor-dominant and
Group 2 made up of 17 patients with non-tremor dominant. Specific to
nondisplaceable binding ratios (SBRs) were calculated using version 2 of the
BasGan software (BasGan V2), that allows automatic quantification of striatal 123I-FP-CIT
uptake. SBRs in right and left caudate nucleus and putamen were the dependent
variables in a repeated measures general linear model analysis and predominant
motor symptom was the independent variable.
Results: The visual
analyses of 123I-FP-CIT SPECT studies were pathologic in all patients.
The mean values of SBRs in left and right caudate (2.59 and 2.60) and putamen
(1.55 and 1.55) of patients of Group 1 were significantly higher than in Group
2 (1.72, 1.7, 0.85 and 0.82, respectively) (p<0.002), which means higher
density of DAT in Group1. This study confirms that those patients with PD with
tremor-dominant at the onset of disease presented lower loss of DAT with regard
to non-tremor dominant phenotype, which might explain why the former is being
considered a more benign subtype of PD.
P19.19
Discrimination between patients
with neurodegenerative syndromes with brain perfusion SPECT
Maja Trošt1, Petra
Tomše2, Marko Grmek2, Milica Gregorič
Kramberger1, Zvezdan Pirtošek1
1Department for Neurology, University Medical Center
Ljubljana
2Department for Nuclear Medicine, University Medical
Center Ljubljana
Objective: To evaluate changes in brain perfusion and the expression of Parkinson
Disease Related Metabolic Covariance Pattern (PDRP) in patients with
Parkinson's Disease Dementia (PDD), Alzheimer's Disease (AD) and Dementia with
Lewy Bodies (DLB).
Methods: 99mTc-ECD/SPECT brain perfusion images were acquired in 14 PDD (age 72 ± 4
yrs, MMSE 24 ± 2), 11 DLB (age 73 ± 4 yrs, MMSE 23 ± 2), 11 AD patients (age 71
± 8 yrs, MMSE 22 ± 4), and 7 healthy controls HC (age 62 ± 3 yrs). Statistical
parametric mapping (SPM8; two group t-test, uncorrected p<0.01, extent
threshold > 100 voxel) was used to identify brain perfusion changes in each
patient group relative to HC and between patients’ groups.
Additionally, the expressions of metabolic brain marker of Parkinson’s
disease - PDRP was calculated for each individual subject. Topographic Profile
Rating technique was applied to brain perfusion images. Expression scores for
each subject were calculated and compared among patients’ groups and HC;
discrimination between groups was found significant if p<0.001.
Results: In
PDD comparing to HC hyperperfusion was found in basal ganglia, thalamus,
cerebellum, primary motor and frontal cortex. Hypoperfusion was present in
parieto-occipital cortex.
In DLB comparing to HC
changes in perfusion were similar to PDD but with lower perfusion in frontal
cortex.
In AD comparing to HC
hyperperfusion was found in primary motor and prefrontal cortex and in
cerebellum. Hypoperfusion was present in posterior cingulate and precuneus,
medial and anterior temporal lobes.
PDRP expression scores
were significantly elevated in PDD and LBD patients but not in AD patients, all
relative to HC.
Conclusion: Changes in brain perfusion can help us
differentiate among parkinsonism and dementia sindromes. PDRP analysis can be
applied to perfusion SPECT images to differentiate between neurodegenerative
disorders, although it was first identifiend form FDG/PET images. PDRP
expression is significantly more pronounced in parkinsonian syndromes compared
to AD and HC.
P19.20
Caroline
May1, Michael Turewicz1, Eckhard Nordhoff1, Martin
Eisenacher1, Ralf Gold2, Swaantje Casjens3, Thomas Brüning3, Beate Pesch3, Christian Stephan1, Helmut E. Meyer1,
Dirk Woitalla2
1St. Josef-Hospital, Ruhr-University Bochum, 44780,
Bochum, Germany
2Department Medical Proteomics/Bioanalytics,
Medizinisches Proteom-Center, Ruhr-University Bochum, 44780 Bochum, Germany
3Institute for Prevention and Occupational Medicine of
the German Social Accident Insurance, Institute of Ruhr-University Bochum,
44789, Bochum, Germany
Objective: Parkinson’s disease or idiopathic parkinsonism
is the second most common neurodegenerative disorder in the elderly. Because no
biomarker is available, the diagnosis and also the monitoring of disease
progression are still based on clinical criteria. Especially in early stages, several conditions can
mimic PD, which leads to false diagnosis. The trigger for the neurodegeneration is
still unknown; neuroinflammatory processes seem to play a crucial role. Besides
general mechanisms activating and amplifying neuroinflammation, such as
generation of proinflammatory cytokines by local glial cells, a neuronal
labeling in the substantia nigra pars compacta with PD IgG was described. Therefore antibodies
may play a critical role in the pathological process. Assuming immunological
mechanisms involved in PD and the requirements to an optimal biomarker,
antibodies are good biomarkers candidates for an early diagnosis, with a high
sensitivity and specificity and perhaps the ability to monitor disease
progression.
Methods: We performed a case-control study using
human protein microarrays to identify human autoantibodies in sera samples for
discriminating Parkinson’s disease patients from two other reference groups
(neurodegenerative/autoimmune diseases vers. non-diseased controls). For the
discovery a new protein microarray platform was used, which allows the
simultaneously analysis of around 9.500 human proteins as possible
autoantigens.
Results: Finally analysis was conducted with a
subset of 72 triplets matched 1:1:1 by gender and age fulfilling all inclusion
and exclusion criteria. We identified an autoantibody panel that classify
patients from healthy and diseased controls. An average classification accuracy
of 73.5% has been achieved. The identified autoantibodies are partially
directed against proteins, which are already described in literature in the
context with the disease pathology. These findings suggest that a panel of
autoantibodies may function as a specific biomarker for Parkinson’s disease.
CLINICAL SCIENCES: PHARMALOGICAL THERAPY
P20.01
Changes in troublesome dyskinesia and its relationship
with dose in advanced Parkinson’s disease patients treated with
levodopa-carbidopa intestinal gel infusion
Angelo Antonini1, Victor SC Fung2,
James T Boyd3, John T Slevin4, Coleen Hall5,
Jordan Dubow5, Krai Chatamra5, Janet Benesh5
1IRCCS San Camillo and
University of Padua, Padua, Italy
2Westmead Hospital and
Sydney Medical School, Sydney, Australia
3University of Vermont
College of Medicine, Burlington, VT, USA
4University of Kentucky
College of Medicine, Lexington, KY, USA
5AbbVie Inc., North
Chicago, IL, USA
Objective: To assess the effect of levodopa-carbidopa
intestinal gel (LCIG) treatment on troublesome dyskinesia (TSD), as well as
examine the relationship between the change in ON-time with TSD and change in
dose, in advanced Parkinson’s disease (PD) patients with TSD.
Methods: In a double-blind, double-dummy study,
patients received LCIG infusion + placebo capsules, or encapsulated LC-Oral
tablets + placebo gel infusion for 12 weeks. In a 54-week, open-label study,
patients all received LCIG infusion. Change in ON-time with TSD and ON-time
without TSD were analyzed in the subgroup with baseline ON-time with TSD ≥1
hour/day based on diary assessment. The correlation between change in total
daily dose of levodopa and change in ON-time with TSD was analyzed.
Results: LCIG patients in the TSD subgroup of the
double-blind study cohort (N=10) reported a significant decrement (mean [SD])
in ON-time with TSD from baseline (3.13 [1.65]) to final, change= -1.76 [1.83],
P=0.014. This was accompanied by an
increase in ON-time without TSD from baseline (7.35[2.15]) to final, change=
4.43[3.64], P= 0.004. In the
open-label study (N=139), LCIG treatment resulted in a significant reduction
from baseline to final in ON-time with TSD (baseline= 3.37[1.81], change=
-1.83[2.92], P<0.001) and
extension of ON-time without TSD (baseline= 6.84[2.44], change= 5.31[3.88], P<0.001). An increase in LCIG dose
was not significantly correlated with an increase in ON-time with TSD in either
study (double-blind: R= -0.073, P=
0.842; open-label: R= -0.001, P=
0.992). Overall, adverse events were common, mild to moderate, and generally
related to GI procedure. In patients with TSD, LCIG produced clinically
significant improvements by reducing ON-time with TSD and increasing ON-time
without TSD. While most patients increased LCIG dose during the study, there
was no correlation with increased ON-time with TSD. These results support the
effectiveness of LCIG in reducing TSD in advanced PD.
Financial Disclosure: Support: AbbVie
P20.02
Mucuna Pruriens: a
possible strategy for Parkinson’s disease patients in developing countries
Erica
Cassani 1, Michela Barichella 1, Luigi Zecca2,
Albert Akpalu 3, Momodou Cham 4, Elisa Faceli5,
Roberto Cilia1, Giulia Privitera 1, Patrizia De Marco 1, Anna Zecchinelli 1,
Alba Bonetti 1, Laura Iorio 1, Emanuele Cereda 1,
Gianni Pezzoli 1
1Parkinson Institute – Istituti Clinici di
Perfezionamento, Milano, Italy
2Institute
of Biomedical Technologies, National Research Council, Segrate, Milan, Italy
3 Korle Bu Teaching Hospital, Accra, Ghana
4Comboni Hospital Sogakofe, Ghana
5Chirundu Mission Hospital, Chirundu, Zambia
Objective: Mucuna Pruriens is a
tropical legume found in Asia, South America and Africa. It is used for many
medicinal purposes and ayurvedic Indian medicine claims that it possesses
anti-parkinsonian properties. The seeds of Mucuna Pruriens contain high levels
of levodopa (about 5.9 and 6.7%, respectively, for white and black seeds). Our
objective was to measure the levodopa
content of various legumes and to assess whether they could be used as a
therapeutic option for Parkinson’s disease patients in developing countries.
We have opened clinics for Parkinson’s disease patients in Ghana and Zambia,
which are already attended by more than 100 patients. Pharmacological treatment
is a problem as most patients cannot afford it: levodopa costs on average 1.5$
daily.
Methods: We have collected 30 different kinds of legume seeds, all sold at low
prices in markets in Africa. All the seeds have been sent to a botanist for
classification. After dry heating or boiling (soaked in water for 15 h and then
boiled in the same water for 1,5 h) they were sent to a laboratory where their
levodopa content was measured.
Results: In the group of
30 different legumes, we found Mucuna Pruriens in Togo-Ghana, both in white and
black seeds. The levodopa content was: in dry heated seeds 3,99% and 4,93%,
respectively; in boiled seeds 2,28% and 2,8%, respectively. In the others 28
legume seeds levodopa was not found. We
plan to learn how to use Mucuna
Pruriens seeds to offer safe and effective treatment to our
patients in developing countries. We are considering the option of genetic
engineering to develope a legume containing levodopa and carbidopa in the right
concentrations and the right proportions.
P20.03
Taq1A polymorphism improves dopamine agonist
therapeutic response in Parkinson’s disease
Daniel
O. Claassen1, Nelleke C. van Wouwe1, G. Fred Wooten2,
Madaline Harrison2, Scott A. Wylie1
1Vanderbilt University,
Department of Neurology, Nashville, TN, USA
2University of
Virginia, Department of Neurology, Charlottesville, VA, USA
Objective: Frontal-striatal dysfunction caused
by Parkinson’s disease (PD) can impair certain aspects of action control. The
preferential D2 and D3 Receptor Agonists can differentially impact impulsive
action tendencies; some patients improve on therapy, whereas others worsen.
This study sought to determine if functional dopamine polymorphisms in the DRD
2 and DRD 3 genes influence the response to Dopamine Agonist (DAA) therapy for
PD with respect to inhibitory action control.
Methods: The Simon Manual Conflict task was
completed by 28 PD patients On and Off DAA therapy in a counterbalanced manner.
For the Off state, participants withheld from DAA for 24 hours. Patients were
genotyped for known functional polymorphisms in DRD2 (rs6277 and rs1800497) and
DRD3 (rs6280) receptors. Proficiency of inhibitory action control, as measured
by the ability to inhibit a prepotent action impulse induced by task irrelevant
stimulus information, was defined as the measure of change in the Simon effect
at the slow end of reaction time distributions (delta plots). We calculated
within-subject effects of DAA therapy on inhibitory control, and grouped
genotype results based on known functional polymorphism effects on DRD receptor
affinity and availability.
Results: The Taq1A polymorphism in the DRD2
gene (rs1800497) appears to augment DAA therapeutic response. Patients with the
A1 polymorphism (A1/A1 or A1/A2: 12 subjects) improved the proficiency to
suppress impulsive actions when On DAA. Conversely, patients with the A2/A2
allele (16 patients) became less proficient at suppressing the incorrect
response information On DAA therapy (Medication x Genotype, (F
(1, 26) = 5.22, p<0.05). Polymorphisms in rs6277 and rs6280 were not
associated with a differential medication response. These findings suggest that
certain DRD polymorphisms may influence medication response in PD patients. We
speculate that DAA therapy may improve the ability to suppress impulsive action
tendencies in patients due to alterations in D2 receptor expression.
P20.04
Parkinson’s disease tremor
profiles across a range of loads with serial neurotoxin injections
Mehdi Delrobaei1,
Fariborz Rahimi1, Jack Lee1, Mandar Jog1, 2
1London Health Sciences Centre, London, ON, Canada
2University of Western Ontario, London, ON, Canada
Introduction: While PD
tremor is thought to be predominantly at rest (no load = only involuntary
muscle activation), rather than during action (with load = range of voluntary
and involuntary muscle activation to maximum), tremor can still be present
across the whole range of load conditions. Botulinum toxin type A (BoNT-A) is a
possible treatment for upper limb tremor in PD. However, the effect of BoNT-A
on PD tremor over a range of loads and weakness as a side effect has not been
studied.
Objectives: To
evaluate in a series of sequential neurotoxin injections the pattern of change
in:
- rest versus action tremor
across a wide range of loads in PD and BoNT-A effect at each load condition.
- weakness profile in individual
fingers along with grip strength.
Methods: 12 PD
patients (67.5±6.3) in whom tremor was not adequately controlled were enrolled
in the study. Kinematic assessment tools were used at baseline and 4 follow up
visits (at 6, 16, 22, and 32 weeks; injections every other visit). Data were
analyzed to evaluate tremor amplitudes at all joints and loads, as well as
average of finger strength.
Results: 6 weeks
after the first injection, wrist tremor at low-load and medium-load reduced by
40% and 12%, respectively. PD patients also benefitted from significant tremor
reduction of maximal load in 3 fingers: second (30%), third (24%), and fourth
(31%) digits. However, PD patients experienced weakness in 4 fingers: index
(28%), second (41%), third (46%), and fourth (37%) digits.
Conclusions: The
profiles of the changes over serial injections reveal that PD patients
benefitted from the injections over a wide range of load conditions. Kinematic
measures allow clinicians to assess both benefits and side effects of
injection. So, the effects of selecting appropriate muscles for injection and
patients' functional improvement can be monitored.
P20.05
A review of nicotine
agonist treatment for cognitive impairment in Parkinson’s disease
Maxime Doiron1,2, Martine Simard1, 2
1
École de Psychologie, Université Laval, Quebec, QC, Canada
2
Centre de Recherche de l’Institut Universitaire en Santé Mentale,
Quebec, QC, Canada
Objective: Several population-based studies have reported a dose-dependent
diminution of Parkinson’s disease (PD) risk associated with cigarette smoking.
Nicotine may be one of the components of cigarette smoke that could exert local
neuroprotective/anti-inflammatory effects on dopaminergic (DA) neurons.
Nicotine may indeed contribute to a DA increase by stimulating cholinergic
nicotinic receptors in the nigrostriatal system. Nigrostriatal and other DA
alterations in early PD may impact on cognition, as cognitive impairment in PD
is reported to affect 19%-36% of de novo
patients. Therefore, it is possible that nicotine agonists could improve
cognitive disorders in PD. This critical review aims at investigating the
potential benefit of nicotine administration on cognition in PD patients.
Methods: A search was conducted in Pubmed and
ClinicalTrials.gov databases using the keywords «parkinson» AND
«cognition» OR «mental status» AND «nicotine» OR «smoking». Inclusion criteria
were: 1) articles published in 1993-2013 and reporting cognitive results
following nicotine agonists administration in PD patients; 2) use of at least
one validated cognitive test; 3) case reports were also included.
Results: Only 6 studies (3 R-DB-PC, 2 open label, 1 case report) met the
inclusion criteria. Four studies reported some improvement in measures of
attention and global cognition and on a semantic priming/processing task in
patients with early PD (H&Y 1-3). However, 1/4 also reported deterioration
on digit span and visual tracking tasks. Two studies reported numerous side
effects (e.g. headache, dizziness, light-headedness, nausea, intestinal cramps)
that led to attrition in 59%-75% of cases. At this point, there is no clear
data regarding the therapeutic dosage of nicotine agonists. Moreover, small
sample sizes (n=2-22), lack of randomized controlled trials and lack of
exhaustive cognitive assessments made it difficult to assess the effects of
nicotine in PD-cognition. Nonetheless, ongoing clinical trials (e.g.
NCT00873392, NCT01216904) may soon provide additional data.
P20.06
Pill dispensers and medication
management strategies: helping patients take medications at the right time, on
time, every time
Judy Hamerlinck1, Rick
VandenDolder1, Martha Nance1
1Struthers
Parkinson’s Center, Golden Valley, MN, USA
Background: Parkinson’s
disease patients and carepartners report difficulty managing complex pill
schedules. Getting the right medication at the right time is a critical part of
the management of PD symptoms.
Objectives: 1) To
share creative strategies developed by patients and caregivers to manage
medication schedules. 2) To demonstrate a variety of pill-taking storage and
dispensing systems that can help health professionals and patients be sure that
medications are taken at the right time, on time, every time.
Methods: Patients
and carepartners at Struthers Parkinson’s Center meet with nurse clinicians
prior to the clinic visit with their neurologist. While updating the medication
list, the nurse asks the family to describe the pill management system they are
using, who sets up the medications, and whether their system is working.
Patients are counseled about the importance of taking medications on time,
every time. The occupational therapist also addresses issues around medication
management during Activities of Daily Living evaluations.
We have reviewed the commercially
available pill dispenser and timer options, and have catalogued and
photographed some systems that patients and families have devised.
Results: Over 100
dispenser options are available, with designs ranging from simple one day or
week systems to multiple dosing automatic dispensers. Cost ranges from $1.27 to
$500.00. We will show some commercially available options, as well as ideas and
dispensing systems that patients have come up with independently.
Conclusions:
Many of the commercially-available pill dispensers have proven
impractical for patients with limited computer skills, decreased dexterity,
poor eyesight, cognitive impairment, or financial restrictions. “Homegrown”
dispenser systems, using basic household items, are preferred by many people.
There is an opportunity for nurses and others who care for people with PD to
learn of these simplified systems and share with other patients as appropriate.
P20.07
Effects of levodopa on gait
variability of backward walking in Parkinson's disease
Jyhgong Gabriel Hou1,2, Mon S Bryan2,3,4,
Diana Rintala3, Elizabeth J Protas4
1PADRECC, Michael E
DeBakey VA Medical Center, Houston, TX, USA
2Department of
Neurology, Baylor College of Medicine, Houston, TX, USA
3Department of Physical
Medicine and Rehabilitation, Baylor College of Medicine, Houston, TX, USA
4School of Health
Professions, University of Texas Medical Branch, Galveston, TX, USA
Objective: Levodopa treatment
has been shown to improve gait performances in patients with PD. We found
previously that levodopa decreased gait variability of forward walking in
individuals with PD (Bryant MS et al. 2011). The effects of the levodopa on
gait variability of backward walking in individuals with PD, however, have not
been reported. This study is to investigate the influence of levodopa treatment
on gait variability of backward walking in patients with Parkinson's disease
(PD).
Methods: Forty-one subjects with idiopathic PD were
recruited. The mean age was 68.44 ± 7.56 yr. The average time since diagnosis
was 9.34 ± 5.67 yr. Patients were “off” levodopa for 12 hours before the first
gait test. The gait test was performed again during “on” state when the optimal
motor response was achieved after administration of levodopa. The tests were to
measure the gait variability during states of “off” and “on” medications when
the subjects walked backward at their usual speed.
Results: Variability of step time, stride length and stride velocity decreased by
2.8% (p < 0.0005), 1.66% (p = 0.036), and 1.63% (p= 0.014), respectively,
from “off” to “on” levodopa state. Variability of double support time also
decreased by 1.27% but the difference was not statistically significant (p =
0.137). The gait speed during “on” time increased by 15.51 cm/s (p <
0.0005). In conclusion, Levodopa reduced certain measurements of backward gait
variability. This indicates that dopaminergic medications may have positive
effects on gait stability of backward walking in individuals with PD. More samples
will be needed to further prove this hypothesis.
P20.08
IPX066 dose conversion in patients with advanced Parkinson's
disease
Ann Hsu1, Martin O’Connell1, Sarita Khanna1,
Sherron Kell1, Robert Rubens1, Aaron Ellenbogen2,
Paul Nausieda3, Joerg Spiegel4, Caroline M. Tanner5
and Suneel Gupta1
1Impax
Laboratories, Inc., Hayward, CA, USA
2Quest
Research Institute, Bingham Farms, MI, USA
3Wisconsin
Institute for Neurological and Sleep Disorders, Milwaukee, WI, USA
4Department
of Neurology, Saarland University, Homburg/Saar, Germany
5The
Parkinson’s Institute, Sunnyvale, CA, USA
Objective: To evaluate IPX066 dosing regimens used in
three trials.
Background: IPX066 is an oral investigational extended-release formulation of
carbidopa-levodopa (CD-LD; 1:4 ratio) designed to provide rapid increase in LD
plasma concentrations followed by sustained concentrations allowing a dosing
interval of ~6h. IPX066 was studied in 2 active-controlled double-blind studies
with immediate-release CD-LD (IR) and CD-LD+entacapone (CLE) as active
controls, respectively, and in 1 open-label study in patients previously
treated with controlled-release CD-LD (CR) alone or with IR.
Methods: All studies enrolled advanced Parkinson Disease (PD) patients with
≥2.5h “Off” time. All dose conversion to IPX066 was not blinded. The recommended initial
IPX066 LD conversion dose was ~30% higher for CLE than for IR regimens with or
without CR.
All patients were started with IPX066 approximately every 6
hours. IPX066 dosing >5X/day was not permitted. IPX066 regimen was
individually adjusted for 6 weeks. IR rescue was not allowed.
Results: The final IPX066
LD daily dose averaged ~2X IR LD dose when converting from IR alone, and ~2.7X
when converting from CLE. The ~35% higher conversion ratio with CLE regimen is
consistent with higher LD exposure (35-40%) when IR is dosed with entacapone. The conversion ratios were ~1.8X when converting
from IR+CR, and ~1.5X from CR alone; these lower conversion ratios are
generally consistent with reduced bioavailability of CR relative to IR in PD
patients. The dosing frequency of IPX066 (median 3X/day) was similar regardless
of patients’ previous LD regimens. The higher dose of IPX066 represents an ~30%
higher LD exposures than the controls after adjusting for lower bioavailability
of IPX066.
Conclusions: Conversion ratios from various LD regimens to
IPX066 are generally consistent with the pharmacokinetic profiles of IPX066 and
LD regimens presented above. IPX066 dosing frequency is similar (median:3X/day)
regardless of previous LD regimen.
P20.09
Developing Usp14 inhibitors as disease-modifying therapeutics for
neurological proteinopathies
Andres Hurtado-Lorenzo1,
Anjanabha Saha1, Jyoti Malhotra1, Mohmmad A. Hafiz1, Akhil Bhalla1,
James Soper1, Eva Nokes1, Adriana Villella1,
Eric Roskelley1, David Hurtado1, Kenneth Longo1,
Kenneth Giuliano1, Megan Foley1, Matthew Cullen1,
Dan Garza1, Bradley Tait1, Markus Haeberlein1,
Randall King2, Daniel Finley2,
and Peter H. Reinhart1.
1Proteostasis
Therapeutics, Inc., Cambridge, MA, USA
2Department
of Cell Biology, Harvard Medical School, Boston, MA, USA
Objective: Neurological proteinopathies such as Parkinson’s (PD) disease are
associated with the accumulation of misfolded proteins in the brain. Such
protein aggregates can be cleared by a number of mechanisms including protein
ubiquitination followed by proteasome-mediated degradation. The catalytic
activity of proteasome-associated deubiquitinating enzymes, such as Usp14,
limits the proteasomal turnover by trimming the associated ubiquitin chains prior to
substrate degradation. We have developed a drug discovery
platform to evaluate whether selective inhibition of Usp14 by small molecules
can decrease the accumulation of
neuropathogenic misfolded proteins, such as -synuclein
in PD, tau in AD, or TDP-43 for ALS, by enhancing their proteosomal
degradation.
Methods: We have used HTS and medicinal chemistry optimization to identify and develop
Usp14 inhibitors that enhance the clearance of disease-relevant proteins prone
to aggregation. Protein levels are determined in various cellular and neuronal
models after genetic knockdown of Usp14 or following treatment with
small-molecule Usp14 inhibitors.
Results: We are progressing two chemical series with different mechanisms
of action that exhibit drug-like properties including in vitro potencies
(IC50) below 150 nM for Usp14 inhibition. Some of these compounds
show lowering of -synuclein
in various cellular models including human iPS neurons and lowering of tau in
primary neurons. Compounds in the lead series are well tolerated in vivo,
displaying high free brain exposures in rodents with no overt toxicity. The in
vivo pharmacokinetic and pharmacodynamic relationships of Usp14
inhibitors are being investigated. Consistent with our pharmacological
findings, genetic knockdown of Usp14 also results in the lowering of soluble
and aggregated -synuclein and tau. Our results support the development of Usp14 inhibitors as a
disease-modifying strategy for the treatment of neurological proteinopathies,
which by selectively modulating proteasomal activity, enhance the degradation
of disease-relevant, aggregation-prone proteins.
P20.10
Caffeine, has antiparkinsonian and hipouricemiant
effects, what else?
Luis Clemente Jiménez-Botello 1,2, María Rosa
Ávila-Costa 2, Sonia Mujaes-Pastor1, Ángel
Barrera-Hernández 3, Luz María Del Razo 3
1 Escuela de Medicina, Departamento
de Ciencias Básicas, ITESM CCM, Ciudad de México, México
2 Laboratorio de
Neuromorfología, UIICSE FES-IZTACALA UNAM, Tlalnepantla, México
3 Sección Externa de Toxicología CINVESTAV-IPN, Ciudad
de México, México.
Objective: Aim of this study, was to determinate
caffeine potential as antiparkinsonian drug in an animal PD model (apomorphine
induced circling behavior) and to know its impact on uric acid serum levels.
Methods: Animal PD models and circling behavior. In Wistar
rats, intracerebral unilateral 6-OHDA injections (n=6) were performed, a month
after it all animals did receive intra peritoneal caffeine injection
(7.5mg/Kg), plus Apomorphine (APO) to induce circling. Uric acid serum levels.
Wistar rats, CAFFEINE group (n=6) receive caffeine intraperitoneal injections
(7.5mg/kg) and CONTROL group (n=6) only vehicle, and were immediately placed in
metabolic cages, to recollect and quantify urinary production by 12 hours.
After it, both groups according bioethics guidelines were anesthetized and
intra cardiac blood sample was obtained and uric acid in serum was determinate.
Results: Circling behavior. Intraperitoneal caffeine
did increase contralateral circling behavior and it indicates a clear
antiparkinsonian effect at used dosage. Uric acid serum levels. At same used
dosage than in Circling behavior, CAFFEINE group did have a significant
decrease in uric acid serum levels, respect to CONTROL group, and also a
significant decrease in urinary concentration without significant differences
on urinary volume, between two groups. Our results suggest that Caffeine is a
promissory molecule in PD management, with another favorable effects to
patients such decreasing uric acid serum levels. What else? Give us a few time,
we are working to know it.
P20.11
The effects of age on adverse event reporting in Parkinson’s
disease patients treated with IPX066 extended-release carbidopa-levodopa
capsules
Sherron Kell1, Martin O’Connell1, Ann Hsu1,
Margery H. Mark2, Lawrence Elmer3 Vanessa Hinson4,
and Suneel Gupta1
1Impax
Laboratories, Inc., Hayward, CA, USA
2UMDNJ
Robert Wood Johnson Medical School, New Brunswick, NJ, USA
3University
of Toledo, Toledo, OH, USA
4Medical
University of South Carolina, Charleston, SC, USA
Objective: To evaluate the effects of age on adverse
event (AE) reporting in a population of Parkinson’s disease (PD) patients
treated with IPX066.
Background: IPX066 is an investigational extended release capsule oral
formulation of carbidopa-levodopa (CD-LD 1:4 ratio), designed to provide a
rapid increase in plasma concentrations of levodopa followed by sustained
stable concentrations allowing a dosing interval of ~6h. IPX066 was studied in three Phase 3 controlled
trials, one in early PD vs. placebo and two in advanced PD, one vs.CD-LD
immediate release (IR) and one vs. CD-LD IR + entacapone (CLE).
Methods: For each study, AEs were collected at each visit and were
summarized using preferred terms from MedDRA 12.1. Comparative summaries were
examined in patients categorized by age groups of <65, 65-74 and ≥75
years old.
Results: Of the 849 patients treated with IPX066 in controlled trials, 431
(50.1%) were of age <65, 186 (38.0%) were 65-74 and 108 (12.7%) were ≥75
years old.
The table below displays the AEs
that occurred in at least 5% in any age group.
Treated with IPX066 |
|||
Age (years) |
< 65 |
65-74 |
≥ 75 |
N |
431 |
310 |
108 |
Number
of patients reporting at least one AE |
233 (54%) |
186 (60%) |
70 (65%) |
Nausea |
42 (9.7%) |
34 (11%) |
12 (11.1%) |
Headache |
34 (7.9%) |
22 (7.1%) |
4 (3.7%) |
Dizziness |
26 (6.0%) |
29 (9.4%) |
9 (8.3%) |
Dyskinesia |
25 (5.8%) |
15 (4.8%) |
6 (5.6%) |
Insomnia |
23 (5.3%) |
11 (3.5%) |
4 (3.7%) |
Conclusions: In this population of PD patients treated with
IPX066 in the Phase 3 clinical studies, the number of patients reporting at
least one AE increased with increasing age. Of the most common AEs, headache
decreased with increasing age but no clear pattern of AE frequency emerged for
nausea, dizziness, dys kinesia or insomnia.
P20.12
Safety analyses from open-label clinical trials of
levodopa-carbidopa intestinal gel in patients with advanced Parkinson’s
disease: Events not related to device or procedure
Anthony E Lang1, Sylvain Chouinard2,
Cindy Zadikoff3, Weining Z Robieson4, Jordan Dubow4,
Krai Chatamra4, Janet Benesh4
1University of Toronto,
Toronto, ON, Canada
2University of
Montréal, Montréal, QC, Canada
3Northwestern
University Feinberg School of Medicine, Chicago, IL, USA
4AbbVie Inc., North
Chicago, IL, USA
Objective: To
evaluate non-procedural or -device adverse events (AEs) during treatment with
levodopa-carbidopa intestinal gel (LCIG) in patients with advanced Parkinson’s
disease (PD).
Methods: LCIG
provides continuous drug infusion via an intrajejunal percuntaneous gastronomy
tube. Data from 3 open-label studies of LCIG were pooled. 412 patients were
analyzed, with mean (SD) exposure of 512 (320) days and total exposure of 577.8
patient treatment years.
Results: AEs occurred in 379 (92.0%) patients and
lead to discontinuation of treatment in 45 (10.9%). The most common AEs were
procedure- or device-related (e.g. abdominal pain). 367 (89.1%) subjects
experienced an AE not associated with the procedure or device (Table 1), which
lead to discontinuation in 35 (8.5%). 64.8% of subjects experienced a
non-procedure or -device AE onset during titration (Days 1-28), 84.1% during
maintenance (≥ Day 29, up to Day 1284), and 40.0% experienced an onset
during titration that lasted into maintenance with duration ≥ 7 days. AEs
of interest include compulsive behavior (10.2%, by MIDI assessment),
polyneuropathy (7.3%), sleep attacks (4.1%, by Sleep Attack Questionnaire), and
melanoma (0). In conclusion, the profile of AEs in this long-term data set is
similar to that in a 12-week, active-controlled trial (Olanow et al, Movement
Disorders Society Meeting, 2012) and comparable to AEs observed with oral
levodopa-carbidopa.
Table 1. AEs reported in ≥ 5% of patients, excluding
procedure- and device-associated AEs
Preferred
Term |
N (%) of patients |
Preferred
Term |
N (%) of patients |
|
Insomnia |
80 (19.4) |
Orthostatic hypotension |
37 (9.0) |
|
Nausea |
77 (18.7) |
Vitamin B6 decreased |
37 (9.0) |
|
Fall |
74 (18.0) |
Diarrhoea |
36 (8.7) |
|
Constipation |
69 (16.7) |
Sleep attacks |
34 (8.3) |
|
Urinary tract infection |
55 (13.3) |
Blood homocysteine increased |
33 (8.0) |
|
Anxiety |
49 (11.9) |
Dyspepsia |
29 (7.0) |
|
Parkinson’s disease |
47 (11.4) |
Oropharyngeal pain |
26 (6.3) |
|
Weight decreased |
47 (11.4) |
Hallucination |
25 (6.1) |
|
Depression |
44 (10.7) |
Arthralgia |
24 (5.8) |
|
Dyskinesia |
42 (10.2) |
Pain in extremity |
24 (5.8) |
|
Vomiting |
38 (9.2) |
Decreased appetite |
23 (5.6) |
|
Back pain |
38 (9.2) |
Musculoskeletal pain |
22 (5.3) |
|
Headache |
38 (9.2) |
Dizziness |
21 (5.1) |
|
P20.13
Effective treatment of
Parkinson tremor using kinematics to optimize Botulinum neurotoxin type A
injection
Jack Lee1,
Fariborz Rahimi1, Mandar Jog1, 2
1London Health Sciences Centre, London,
ON, Canada
2University of Western Ontario, London,
ON, Canada
Introduction: Clinically assessing
the complexity of multi-joint tremor in Parkinson Disease (PD) patients is
difficult through traditional visual observations. Results from past studies
showed injection of Botulinum neurotoxin type A (BoNT-A) to have the potential
to alleviate tremor symptoms, however efficacy was often poor with severe hand
weakness. Our study deconstructs the tremor on the arm using kinematic sensors,
thereby providing a detailed and comprehensive assessment of PD tremor
which can improve the efficacy of BoNT-A.
Methods: Kinematic recordings
were done while patients were in rest, posture, and kinesis states in 24 PD
patients. The 8 month assessment utilized 3D accelerometers, electrogoniometers
and torsiometers to measure tremor at the wrist, elbow, and shoulder, along
with clinical tremor rating scales at each visit. Flexion-extension,
pronation-supination, radial-ulnar movements were determined at the wrist, as
well as flexion-extension at the elbow and flexion-extension with abduction and
adduction at the shoulder. The information was then used by the clinician to
determine injection sites and dosage needed.
Results: 6 weeks after the
first injection the total tremor amplitude for shoulder, elbow and wrist was
reduced in PD patients by 80% overall. PD patients had only 20-30% reduction in
grip strength 6 weeks after each injection. The rest tremor UPDRS score (item
20) had decreased over 16 weeks from 2.75 to 1.81. Likewise for action tremor
(item 21) there was a decrease from 1.67 to 0.77. The Fahn-Tolosa-Marin tremor
rating scale over 8 months showed significant improvement while quality of life
assessment in PD patients had no change.
Conclusions: PD patients showed
significant reduction in their tremor and improvement in clinical scores. Using
kinematics to determine injection parameters of BoNT-A is an effective tool to
improve the standard of care to patients, not previously possible with visual
assessment alone.
P20.14
4-aminopyridine improves gait in a patient with
Parkinson's disease.
Corneliu C. Luca1, Carlos Singer1
1University of Miami,
Miami, FL, USA
Objective: Walking impairment
represents a significant therapeutic challenge in patients with Parkinson's
disease (PD). 4-aminopyridine (4-AP) is a potassium channel blocker that has
favorable effects on several neurological diseases associated with gait
dysfunction including multiple sclerosis and episodic cerebellar ataxia. We
aimed to evaluate the effects of a 4-aminopyridine in a patient with PD and
freezing of gait resistant to dopamine therapy.
Methods: One patient with
Parkinson’s disease has been evaluated in ON state before and after administration
of 5 mg of 4-AP three times daily. Clinical evaluation of gait has been
performed using Timed Up and Go Test, Timed 25 Foot Walk, Freezing of Gait
Questionnaire, MDS-UPDRS. Objective measures of gait have been collected using
wireless sensors attached to ankles (APDM Inc, Portland).
Results: While the velocity of
gait and stride length remained overall unchanged, improvements in TUG,
freezing of gait and axial UPDRS were significant after 48 hours. The FOG score
improved 50 % (from 16 points before 4-AP to 8 points after), axial UPDRS from
10 points to 3, and TUG improved from 16.7 +/-1 to 14.0+/-0.5. The effects on
freezing of gait and axial UPDRS have maintained 4 weeks after initiation of
treatment. 4-AP was been tolerated well at 5 mg pot tid with no side effects.
Interestingly, besides freezing of gait, festination has improved and this
correlated with reduction in the coefficient of variation of stride time, a
marker of gait rhythmicity (11.6%+/- 4.6 before treatment, 6.3%+/-0.5 at 48
hours). Given the recent studies that showed the 4-AP improves gait variability
in patients with various type of cerebellar disorder we posit that 4-AP can act
as a regulator of arrhythmic neuronal networks in PD. Controlled clinical
trials are necessary to evaluate the 4-AP effects on gait in patients with PD.
P20.15
Function and
expression differences between ergot and non-ergot dopamine D2 agonists on
heart valve interstitial cells
Fumiki Oana1, Hiroshi Onozuka1, Akihiro Tsuchioka1, Takayuki Suzuki1, Yuji Hoyano1, Nobuyuki Tanaka1, Kouichi Kaidoh1, Masahiro Hiratochi1, Shinji Kikuchi1, Yasuo Takehana1 and Nobuo Shibata1
1Discovery Research, Kissei Pharmaceutical Co. LTD., Azumino, Nagano, Japan
Objective: The symptoms of
Parkinson’s disease are alleviated by dopamine D2 agonists, which are
classified as ergot dopamine D2 agonists and non-ergot dopamine D2 agonists.
Among the former, pergolide has been associated with valvular heart disease,
since it has serotonin 5-HT2B agonistic properties. We aimed to analyze the
function and expression differences between pergolide, an ergot dopamine D2
agonist, and pramipexole, a non-ergot D2 agonist, on heart valve interstitial
cells (VICs).
Methods: We procured porcine
VICs and analyzed the [3H]thymidine incorporation on them treated
with pergolide or pramipexole by using of [3H]thymidine
incorporation assay. Moreover, we performed Microarray global analysis on them
and validated the varied genes between pergolide and pramipexole by using of
Real-time PCR.
Results: We demonstrated that
the 5-HT2B receptor was abundantly expressed in porcine VICs. The 5-HT2B
receptor agonist pergolide induced an increase in [3H]thymidine
incorporation accompanied by a decrease in 5-HT2B receptor mRNA expression. [3H]thymidine
incorporation was blocked by lisuride, a 5-HT2B receptor antagonist, and by
LY-294002, a specific inhibitor of PI3K and Akt. Moreover, we showed that type
2 iodothironine deiodinase (Dio2) expression in porcine VICs treated with
pergolide was markedly increased by global analysis of mRNA compared with that
induced by pramipexole. Such changes in VICs may be correlated to the mechanism
of heart valve disease pathogenesis.
P20.16
Levodopa bioavailability and variability in plasma
concentrations: levodopa-carbidopa intestinal gel infusion versus oral tablets
Ahmed A. Othman, Sandeep Dutta
Clinical Pharmacology
and Pharmacometrics, AbbVie, North Chicago, IL, USA
Background:
Maintaining constant levodopa concentrations is critical for reducing motor
complications in Parkinson's disease (PD). Levodopa-Carbidopa Intestinal Gel
(LCIG) provides continuous levodopa-carbidopa delivery by infusion through an
intrajejunal percutaneous gastrostomy tube.
Objective:
Using a population modeling approach, compare levodopa
bioavailability and intra-subject variability in plasma concentrations
following 16-hour jejunal infusion of LCIG or frequent oral administration of
immediate release levodopa-carbidopa tablets (LC-oral) in subjects with
advanced PD.
Methods: A
nonlinear mixed-effects model of levodopa pharmacokinetics (PK) was developed
using serial data from an LCIG Phase 1 PK Study and a Phase 3 12-week
double-blind, double-dummy study of the efficacy and safety of LCIG in
comparison to LC-oral in advanced PD patients (N=68 included in model
development; 45 on LCIG and 23 on LC-oral). The final model was evaluated using
stochastic simulations against observed data from the above studies and sparse
PK data from 311 subjects with advanced PD evaluated in a 12 month long term
safety study of LCIG.
Results: The final levodopa population PK model was a two-compartment model
with a transit compartment for absorption, first order elimination,
bioavailability for LCIG relative to LC-oral, different first-order transit
absorption rate constants (LCIG =9.2 hr–1 vs LC-oral=2.4 hr–1)
and residual (intra-subject) variability for LCIG versus LC-oral. Levodopa
bioavailability was 97% (95% bootstrap confidence interval= 95% to 98%) for
LCIG relative to LC-oral. The proportional residual error was 15% for LCIG
versus 29% for LC-oral. Standard deviation of the additive residual error in
levodopa concentrations was 0.3 µg/mL for LCIG versus 0.59 µg/mL for LC-oral.
Conclusions: Levodopa
bioavailability is comparable for LCIG and LC-oral administration. LCIG
administration results in approximately half the intra-subject variability in
levodopa concentrations observed with LC-oral administration. LCIG is absorbed
faster than LC-oral, consistent with direct delivery of LCIG to the jejunum.
P20.17
Lack of association between the
intensity of dopaminergic treatment and falls in Parkinson disease
Sotirios Parashos1,
Catherine Wielinski1, Martha Nance1
1Struthers
Parkinson’s Center, MN, USA
Objective: To assess
the relationship between the potency of dopaminergic treatment and falling in
Parkinson disease (PD). Falling is considered a symptom of PD that is not
responsive to changes in dopaminergic medications.
Methods: Detailed medication
regimens and 4-week diaries recording falls and near falls were collected in
324 PD subjects. Simple and partial correlations were obtained for the
following outcomes: Presence or absence of falls; number of falls; number of
near-falls; and, number of all events (falls and near-falls). Total daily
levodopa equivalent dose (LED), Age, and Disease Duration, were considered as
possible predictors. The same analysis was then restricted within the subgroup
of PD subjects who experienced falls. Chi-square was used to test
relationships. Statistical significance was set at p<.05.
Results: 54% of
subjects experienced at least one fall. LED was significantly associated with
presence (p=0.014) and number of falls (p=0.032), and total events (p=0.033);
Age was associated with number of near falls (p=0.028); Disease Duration was
associated with presence (p=0.001) and number of falls (p<0.001), and total
number of events (p=0.018). When accounting for Disease Duration, LED was no
longer a significant predictor for any of the outcomes. When the same analysis
was performed in the subgroup of PD subjects with falls, LED was not a
significant predictor for any of the outcomes. The intensity of dopaminergic
treatment is not associated with the occurrence or frequency of falling in PD.
P20.18
Lack of association between
central anticholinesterase treatment and falls in Parkinson disease
Sotirios Parashos1,
Catherine Wielinski1, Martha Nance1
1Struthers
Parkinson’s Center, MN, USA
Objective: Cognitive dysfunction is associated with falling in PD. A recent
clinical trial indicated that a centrally acting anticholinesterase medication
may reduce falling in PD.
Methods: Detailed medication regimens and 4-week diaries recording falls
and near falls were collected in 322 PD subjects. Simple and partial
correlations were obtained for the following outcomes using chi square
statistics: Presence or absence of falls; number of falls; number of
near-falls; and, number of all events (falls and near-falls). Use of a
centrally acting anticholinesterase agent (donepezil, galantamine, or
rivastigmine), Age, Disease Duration, MMSE score, and cognitive dysfunction
defined as MMSE<26 were considered as possible predictors. The same analysis
was then restricted within the subgroup of PD subjects who experienced falls.
Results: 53.7% of subjects experienced at least one fall, 14.6% were on
an anticholinesterase and 21.1% had MMSE scores less than 26.
Anticholinesterase treatment, MMSE, and cognitive dysfunction were not
significantly associated with presence or number of falls and total events; Age
was associated with number of near falls (p=0.027); Disease Duration was
associated with presence (P=0.001) and number of falls (p<0.001), and total
number of events (p=0.020). The lack of association between anticholinesterase
treatment and falling persisted after accounting for disease duration and
severity of cognitive dysfunction. Concomitant treatment with centrally acting
anticholinesterases is not associated with the occurrence or frequency of
falling in PD.
P20.19
Antidepressants and falling in
Parkinson disease
Sotirios Parashos1,
Catherine Wielinski1, Martha Nance1
1Struthers
Parkinson’s Center, MN, USA
Objective: To assess
the relationship between the use of antidepressant medications and falling in
Parkinson disease (PD). Antidepressant use is associated with falling in the
general population and in patients with PD.
Methods: Detailed
medication regimens and 4-week diaries recording falls and near falls were
collected in 322 PD subjects. Simple and partial correlations were obtained for
the following outcomes using chi square statistics: Presence or absence of
falls; number of falls; number of near-falls; and, number of all events (falls
and near-falls). Use of any antidepressant medication, number of antidepressant
medications prescribed, antidepressant category (SSRI or tricyclic), Age,
Disease Duration, and cognitive dysfunction defined as MMSE<26 were
considered as possible predictors. The same analysis was then restricted within
the subgroup of PD subjects who experienced falls.
Results: 53.7% of
subjects experienced at least one fall, 40.4% were on an antidepressant, 29.8%
on an SSRI, and 3.1% on a tricyclic; 21.1% had MMSE scores less than 26. Antidepressant
treatment was not significantly associated with presence or number of falls and
total events, with the only exception of tricyclics, which was significantly
associated with the presence of falls (p=0.003); Age was associated with number
of near falls (p=0.027); These findings persisted when accounting for disease
duration and age, and when the analysis was restricted only to subjects
experiencing falls. Among commonly used antidepressants, treatment with
tricyclics is associated with the occurrence or frequency of falling in PD.
P20.20
Potential of novel mTOT modulator to treat dyskinesia in
a 6-OHDA rat model of Parkinson’s disease (PD)
Chakrapani BP1, JA Steiner1, ML
Escobar Galvis1, JR Colca2 and P Brundin1
1Laboratory for Translational
Parkinson’s Disease Research, Center for Neurodegenerative Science, Van Andel
Research Institute, Grand Rapids, MI, USA
2Metabolic Solutions
Development Company, Kalamazoo, MI, USA
People with PD who are treated with L-DOPA
long-term often develop involuntary movements, i.e. L-DOPA induced dyskinesia
(LID). A suggested underpinning of LID is overstimulation of mTOR (mammalian
target of rapamycin), a nutrient-regulated serine/threonine kinase. Rapamycin treatment, which results in mTOR inhibition, reduces LID in rodents. Unfortunately, rapamycin has
unacceptable side effects rendering it suboptimal for LID treatment. A novel
insulin sensitizer (MSDC-0160, approved for clinical testing in diabetes
and Alzheimer's disease patients)
modifies a mitochondrial complex mTOT (mitochondrial target of
thiazolidinedione insulin sensitizers), improving mitochondrial oxidative
metabolism and leading to reduced mTOR activation. We hypothesize that
MSDC-0160 can reduce mTOR activity in the striatum in a rat model of LID,
thereby reducing LID in the absence of side effects. We generated unilateral
6-hydroxydopamine (6-OHDA) lesions in Sprague-Dawley rats by stereotactic
injection into the right medial
forebrain bundle. Lesioned rats are given L-DOPA daily for 4 weeks to induce
L-DOPA-induced abnormal involuntary movements (AIMs) Two groups receive either
control chow or chow containing MSDC-0160 (30 mg/kg/day) to assess if MSDC-0160
can mitigate AIMs that have already developed following L-DOPA priming. We are
also pre-treating with MSDC-0160 to determine if the initial development of
AIMs, can be prevented. At molecular level we determine S6
phosphorylation (to assess activation of mTOR), P-ERK and c-fos, and quantify
tyrosine hydroxylase to determine lesion changes. In brief, there is evidence
that mTOR over-activation participates in the molecular-cascade that
causes LID; thus MSDC-0160 has potential to reduce AIMs. Due to its safe
profile in humans, MSDC-0160 could be used to prevent
LIDs in PD patients.
P20.21
Non-interventional study of caregivers’ and physicians’
attitudes to drug administration via a transdermal patch in patients with
Parkinson’s disease who require caregiver support
Jörn Peter Sieb1, Peter Themann2,
Tobias Warnecke3, Thomas Lauterbach4, Reinhard Berkels4,
Frank Grieger4, Stefan Lorenzl5
1Hanse-Klinikum
Stralsund, Stralsund, Germany
2Klinik am Tharandter
Wald, Hetzdorf, Germany
3Universitätsklinikum
Münster, Münster, Germany
4UCB Pharma, Monheim am
Rhein, Germany
5Klinikum der
Universität LMU München, Munich, Germany
Objective: To
provide real-world data on caregiver and physician assessments of
advantages/disadvantages of rotigotine transdermal patch versus oral PD
medication.
Methods: Cross-sectional,
non-interventional study in routine clinical practice in Germany (NCT01330290).
Patients had PD with documented need for care, and had received rotigotine as
add-on to oral PD treatment for ≥1 month (following physician’s
independent decision to prescribe). Caregivers and physicians assessed
rotigotine transdermal patch versus oral PD medications for each patient at a
single timepoint using questionnaires comprising questions on: swallowing
dysfunction, nausea/vomiting, monitoring therapy, once-daily application,
application independently from meals, application to sleeping patients,
caregiving efforts (caregivers only) and clinical aspects (physicians only).
Each question was assessed on a 5-point scale ranging from -2 (major
disadvantage) to 2 (major advantage compared with oral treatment). Multiple
patient assessments by one caregiver/physician were averaged to obtain a single
response. Primary outcomes were mean total scores of all questions for
caregivers and physicians who provided responses for ≥4 questions.
Results:
Questionnaire responses from 128 caregivers and 41 physicians were documented
for 147 of 148 patients. 100 (68%) patients had a caregiving family member
(spouse in 72 cases); 36 (24%) were cared for by a nurse in a nursing home.
Mean PD duration was 8.2±6.3 years; 136 (93%) patients were additionally taking
levodopa. Mean total score of caregivers’ questionnaires was 1.32±0.67 and of
physicians’ questionnaires was 1.46±0.32. Mean scores for individual questions
were in the range 1.03-1.54 for caregivers and 1.15-1.87 for physicians. When
given a choice about their rationale to prescribe for each patient, physicians
cited the pharmaceutical form (patch) in 139 (95%) cases and the active agent
(rotigotine) in 89 (61%) cases.
Conclusions: In the
opinions of caregivers and physicians, rotigotine transdermal patch had some
major advantages over oral PD medication in everyday life for patients in need
of care.
P20.22
Botulinum Toxin treatment for primary and secondary blepharospasm
Achinoam Socher1, Gilad Yahalom1, Hanna Strauss1,
Sheera Lerman1, Lilach Ephraty1, Sharon Hassin-Baer1,2,
Oren S Cohen1,2
1Sheba Medical Center, Tel-Hashomer; Ramat-Gan,
Israel
2Tel Aviv University, Tel Aviv, Israel
Objective: Blepharospasm (BS) is a focal dystonia characterized by involuntary eyelid closure due to spasmodic contractions of ocular muscles. BS can be idiopathic (primary) or secondary to other disorders such as Parkinson's disease (PD). Botulinum toxin type A (BTX-A) is considered the treatment of choice. The objective of this study is to compare the efficacy of BTX-A treatment for patients with primary versus secondary BS associated with PD (with or without DBS).
Methods: 27 consecutive
patients [15 males, age: 65.11±13.66 years, disease duration 7.7±8.2], newly or
routinely treated by BTX-A were recruited including patients with primary BS
(N=10), secondary BS associated with PD (N=6), PD+DBS (N=5), and other various
types of BS (N=6). Patients were evaluated before and 4 weeks following BTX-A
injections, using the Blepharospam Disability Scale (BDS), the Blepharospasm
Disability Index (BDI), the Jankovic Rating Scale (JRS), the Blepharospasm
Movement Scale (BMS), and the Clinical Global Impression of Improvement (CGI-I).
Additionally all were recorded on a 5-minute videotape and scored by a blinded
rater.
Results: Following the BTX-A injections, our sample as a whole showed a statistically significant improvement in Severity of Illness (1.74±1.27 vs. 2.34±1.05, p=0.013), JRS severity scale Illness (1.37±1.04 vs. 1.96±1.22, p=0.0018), BMS severity scale (4.01±1.27 vs. 5.04±1.79, p=0.039), and the severity rating scale (1.19±0.84 vs.1.61±0.80 p=0.013), with the other outcome measures showing the same improvement trend. 21 patients reported improvement on CGI-I. When these effects were compared by diagnosis group, the best beneficial effect was evident in patients with BS secondary to PD and was maximal for the group of PD patients without DBS demonstrating a significant improvement in Severity of Illness compared to the other two groups. The study conclusion is that BTX-A was an effective treatment for BS. Patients with PD associated BS showed a better response than those with primary BS.
P20.23
Pharmaceutical
quality of seven generic Levodopa/Benserazide products compared with original
Madopar® / Prolopa®
Gabriel Vital-Durand2,
Isabelle Arnet3, Urs E. Gasser1; Anton Fischer2,
Jan P. Timmermans2
1F. Hoffmann-La Roche
Ltd, Basel
2Pharmaceutical Care Research Group, University of Basel
3ClinResearch Ltd, Aesch, Switzerland
Objective: To compare the pharmaceutical quality of seven generic
levodopa/benserazide combination products marketed in Germany with the original
product (Madopar® / Prolopa® 125, Roche, Switzerland).
Introduction: Madopar® / Prolopa® is a combination of levodopa
(L-Dopa) and benserazide. Generics assume the same pharmaceutical
characteristics as the reference product.
Materials: Madopar® / Prolopa® 125 tablets and capsules
were used as reference materials. The generic products tested (all 100mg/25mg
formulations) included four tablet formulations (Betapharm, CT, MYLAN and
ratiopharm) and three capsulated
formulations (HEXAL, STADApharm and TEVA).
Methods: Shape, colour, appearance and hardness (tablets) or surface, colour,
imprint and content (capsules); mass (tablets) or fill-mass (capsules);
content, degradation products, disintegration and dissolution were tested.
Results: For all seven generic products at least one of the tested parameters
fell outside specifications. Content requirements were unmet by two tablet
formulations for L-Dopa (specs: 100mg ±5%; test results: -5.6% and -7.6%) and
for benserazide (specs: 28.5mg ±5%; -6.6% and +8.4%). Average mass (specs:
275mg ±3%) was not reached for two tablet formulations (+3.3%), and average
fill mass (specs: 150mg ±5%) was not reached for three capsule formulations
(+48.2%, +99.1%, +99.3%).
Conclusions: All seven analysed generic L-Dopa/benserazide products exhibited at
least one deviation. Deviations for the active ingredients ranged from +8.4%
(benserazide) to -7.6% (L-Dopa) in two tablet products, with potential clinical
consequences. Furthermore, two of the degradation products were 26.5% above
standard. These results should lead to caution when prescribing a generic of
Madopar® / Prolopa®, and also invite further investigations, both
pharmaceutical and clinical.
P20.24
Non-interventional study of the switch from oral
treatment to rotigotine transdermal patch in patients with Parkinson’s disease
and gastrointestinal symptoms
Dirk Woitalla1, Jan Kassubek2, Lars
Timmermann3, Thomas Lauterbach4, Reinhard Berkels4,
Frank Grieger4, Thomas Müller5
1St Josef-Hospital
Universitätsklinik, Bochum, Germany
2Universität Ulm, Ulm,
Germany
3Universität zu Köln,
Cologne, Germany
4UCB Pharma, Monheim am
Rhein, Germany
5St Joseph-Krankenhaus
Berlin-Weißensee, Berlin, Germany
Background: Gastrointestinal
(GI) symptoms are common among patients with Parkinson’s disease (PD),
significantly affecting quality of life. Transdermal systems of drug
administration bypass the GI tract and may result in fewer GI problems.
Objective: We
investigated the effect of switching from oral PD medications to transdermal
dopaminergic therapy in patients with PD and GI symptoms in daily practice.
Methods: This
observational study was conducted in a routine clinical practice setting in
Germany (ClinicalTrials.gov:
NCT01159691). Patients presenting with GI symptoms (heartburn,
bloating, nausea, vomiting, abdominal pain, diarrhoea) and receiving oral PD
drug treatment were switched to rotigotine transdermal patch based on the
independent decision of their physician. Effectiveness was assessed using a
visual analogue scale that measured intensity of GI symptoms from 0 (no
disorder) to 100 mm (extremely severe disorder) and questions on the frequency
and intensity of individual GI complaints, as well as patient satisfaction
regarding GI symptoms over approximately 6 weeks after switching.
Results: Of 65
patients with baseline and follow-up data, 58 had follow-up data available for
final analysis. Intensity of GI complaints improved on the visual analogue
scale from an average of 47.5 mm at baseline to 19.7 mm after ~6 weeks. At
baseline, heartburn was reported by 39 of 65 patients, bloating by 37/65,
nausea by 38/65, vomiting by 8/65, abdominal pain by 31/65, and diarrhoea by
10/65. Fewer patients reported individual GI symptoms after ~6 weeks: heartburn
12/58, bloating 12/58, nausea 10/58, vomiting 1/58, abdominal pain 9/58, and
diarrhoea 2/58. Fifty of 58 patients who completed the “assessment of
satisfaction referring to GI complaints” after ~6 weeks were “Satisfied” or
“Very satisfied”.
Conclusion: This
study suggests that a switch from oral PD medication to rotigotine transdermal
patch may improve existing GI symptoms among patients with PD. Additional
studies are needed to confirm this finding.
CLINICAL SCIENCES: SURGICAL THERPAY,
INCLUDING CELL AND GENE THERAPY
P21.01
Chromospheres: a new source for cell replacement therapy
in Parkinson´s disease
Alejandra
Boronat-García1, Paulina Montoya-Guerrero1, Arturo
Hernández-Cruz1, Magdalena Guerra-Crespo1, Diana Millán-Aldaco1,
Marcela Palomero-Rivero1, Monika Enhart-Bornstein2, René
Drucker-Colín1
1Universidad Nacional Autónoma de México, Instituto de
Fisiología Celular, Mexico City, Mexico
2Technische Universität
Dresden, University Hospital Carl Gustav Carus, Dresden, Germany
Objective: Mammalian chromaffin cells located in the
adrenal medulla synthetize and release dopamine (DA) as well as other
neurotransmitters. Due to their neuronal properties, chromaffin cells have been
used as a source for cell replacement therapy in Parkinson´s disease (PD).
However, despite more than 20 years of extensive effort, such cells have not
yielded the expected results, mostly because differentiated chromaffin cells
have been unable to reach the long-term survival required to treat this
neurodegenerative disorder. Recently, Enhart-Bornstein and coworkers (2009)
isolated chromaffin progenitor cells (CPC) from bovine and human adult adrenal
medulla. These progenitor cells share significant properties with neural stem
cells as its self-renewal capacity and the ability to form clonal secondary
spheres, named chromospheres. In vitro, 21% of CPC are able to
differentiate into dopaminergic (DA) neurons. This percentage increases to 46%
in the presence of retinoic and ascorbic acids. In our laboratory, we have been
studying the potential of these cells to differentiate in vivo as well
as their functional integration capacity in a rat model of PD.
Methods: In order to form chromospheres, CPC were isolated from adult
bovine adrenal medulla and cultured in low-attachment conditions in presence of
fibroblast growth factor-2. Chromospheres were transplanted into the striatum
of 6-hydroxydopamine-lesioned rats.
Results: We found
by immunofluorescence assays that these grafted precursors cells were capable
to survive and differentiate into DA neurons. Moreover, we observed a gradual
and sustained behavioral improvement of dopamine-mediated motor asymmetry
(induced by apomorphine and amphetamine) and motor coordination, as evaluated
with the beam test. Together, our results suggest that chromospheres obtained
from adult tissue can be a potential source for autologous cell replacement
therapy in PD.
P21.02
Case report: transplantation of fetal porcine ventral
mesencephalic cells (FPVMC) for Parkinson’s disease (PD): long term results and
pathology
Samuel Ellias 1, Jeffrey H. Kordover2
1Boston University
Medical Center, Boston, MA, USA
2Rush University
Medical Center, Chicago, IL, USA
Objective: To study the long-term efficacy and
pathology of unilateral transplantation of FPVMC in PD.
Background: An open-label 1 year study of unilateral
FPVMC in PD reported 3 of 12 patients with excellent response. Six patients
received chronic cyclosporine (CyA), 6 received FPVMC pretreated with an F(ab’)2
antibody fragment directed against MHC class I. No patients developed
off-medicine dyskinesia. (Neurology
2000;54:1042-1050).
Subsequently, a double-blind placebo-controlled trial with bilateral
transplantation of FPVMC using only CyA did not show clinical efficacy. In both
studies 18F-fluoro-L-DOPA PET was unchanged and no porcine
endogenous retrovirus was detected. Here, results of an F(ab’)2
patient are presented with 15 year follow up.
Methods: UPDRS and timed motor tests were performed
according to a CAPIT protocol with videotaping. Testing for Parkin and PINK1
was conducted. Immunohistological investigation was done at autopsy.
Results: Pre-surgery, gait freezing and dyskinesia
were troublesome and patient could not walk during off-periods. Surgery was
performed at age 47 (PD duration-18 years, Off UPDRS/H&Y- 90/4.0). By 3-6
months post-surgery there was no gait
freezing or wearing-off. Levodopa was reduced from 700 to 500mg/d. Twelve hours
off-medicine scores improved for bilateral arm movements and stand-walk-sit
test. UPDRS/UPDRS III at (presurgery,3 mo,3 yr,7.5 yr, 9 yr.) were respectively
(90/26, 51/31, 54/27, 54/29, 61/36). On-medicine UPDRS/UPDRS III scores were:
(35/17, 22/16, 17/4, 28/13, 31/13). At 9-15 years Ldopa dyskinesia gradually
increased, and balance and gait stability decreased. Tests for Parkin/PINK1
were negative. Pathology was consistent with PD. No viable cells were observed
with TH or a porcine specific marker. Hence, a patient with pathology proven PD
given unilateral transplantation of FPVM cells with an F(ab’)2
antibody fragment had long term efficacy without side effects. [Some clinical
results were presented previously at the 2006 International Congress of
Movement Disorders, Kyoto, Japan]
P21.03
Effects of bilateral STN-DBS on non-motor and axial symptoms in
patients with Parkinson’s disease
Maria Fraraccio1,
Christiane Lepage1, Thi Thanh Mai Pham1, Elise
Lafleur-Prud’homme1, Abbas Sadikot2, Nicolas Jodoin1,
Michel Panisset1
1CHUM and CRCHUM, Montréal, QC, Canada
2Montreal Neurological Institute and Hospital, Montréal, QC, Canada
Introduction: Studies have shown that bilateral deep
brain stimulation of the subthalamic nucleus (STN-DBS) is associated with
improvements of Parkinson’s disease (PD) motor disability and levodopa-related
complications. Controversy remains however with regard to the effects of
bilateral STN-DBS on non-motor and axial symptoms associated with PD.
Methods: Ten patients with PD were evaluated in the ON-medication
state both pre- and post-surgically using tests and scales measuring axial (gait, balance and speech) and non-motor features
(mental status, word fluency, sleep-related problems, mood, fatigue and quality
of life). Measures of caregiver/family burden and patients’ subjective
experience of change were also documented. Patient
demographics and motor characteristics are summarized in Table 1. The Wilcoxon
signed-rank test was performed to compare pre-surgical to post-surgical within
group differences.
P values are 2-sided and were calculated at the 0.05 significance level.
Results: With a mean post-surgical follow-up period of 48.9 weeks, we analysed
data for 10 patients with PD treated with bilateral STN-DBS. Results for
axial tests are shown in Table 2 and Table 3 summarizes scores for non-motor
symptoms.
Discussion: Our initial findings
reveal a mild but significant decrease in balance while an amelioration of depressive symptoms was observed following bilateral STN-DBS. Results on
all other axial and non-motor features measured in this study as well as
results for caregiver burden did not reveal significant changes following surgery. Approximately one year after
surgery, the average subjective patient response concerning changes following
surgery was “Better,
and a definite improvement that has made a real and worthwhile difference.”
P21.04
Long-term safety considerations of deep
brain stimulation in treatment of Parkinson’s disease
Anna Gamaleya1,2, Alexey Tomskiy1, Ekaterina Bril2, Andrey Dekopov1,
Anna Bondarenko1, Svetlana Buklina1, Nataliya Fedorova2,
Vladimir Shabalov1
1Burdenko Neurosurgical Institute RAMS, Moscow, Russian Federation
2Russian Medical Academy of Postgraduate Education, Moscow, Russian
Federation
Introduction: In the last two
decades, DBS became a standard intervention for treatment of advanced
Parkinson’s disease. Moreover, indications for DBS in PD continue to extend,
since DBS showed benefits compared to medical treatment for patients with early
motor complications. Although, DBS is usually considered a pretty safe
procedure, it could be related to different complications that worsen the
general effect of therapy.
Objective: To evaluate the
safety of DBS therapy in PD patients in a single functional neurosurgery
centre.
Methods:
129
PD patients underwent surgery for continuous high-frequency DBS between 2002
and 2013: 99 received DBS of subthalamic nucleus, 15 had DBS of globus pallidus
internus, and 15 had DBS of ventrointermediate nucleus of thalamus. Mean age at
surgery was 54.6±0.8 years (range 25–72). Follow-up duration ranged from 6
months to 10 years. We performed the detailed assessment of complications encountered.
Results:
In
all patients, 300 electrodes were implanted: 222 targeted in STN, 35 in GPi,
and 43 in Vim. Among hardware-related complications, electrode or connector
fractures (4 cases) and migration of pulse generator (4) were observed. There
was an evidence of unexpected IPG end-of-service (1). Surgery-related
infections occurred in 5 patients. Two cases of symptomatic cerebral hemorrhage
(0.7%) were registered. In 2 patients, intraoperative seizures occurred. To
optimize the clinical effect, correction of electrode position was required in
25 cases. The prevailing adverse effect of DBS was dysarthria (15 patients,
8.5%). In 2 cases, DBS-components were permanently explanted due to different
reasons. Four patients died from the unrelated causes in prolonged follow-up.
37 patients underwent pulse generator replacement (totally, 53 IPG).
Conclusion: DBS therapy seems to
be rather safe for treatment of PD patients. The overall rate of persisted
surgery-related disability is definitely low. At the same time, unpredictable
technical and stimulation-related complications might be a challenge.
P21.05
Intraoperative subthalamic microelectrode recording for
deep brain stimulation in Parkinson’s disease
Anna Gamaleya1,2, Alexey Tomskiy1, Andrey Dekopov1, Ekaterina Salova1, Ekaterina Bril2, Vladimir Shabalov1
1Burdenko Neurosurgical Institute RAMS,
Moscow, Russian Federation
2Russian Medical Academy of Postgraduate
Education, Moscow, Russian Federation
Introduction: For successful DBS in
Parkinson’s disease, accurate placement of electrodes into sensorimotor part of
subthalamic nucleus is essential. Microelectrode
recording (MER) of specific neuronal firing became a widespread technique for
precise targeting the basal nuclei during stereotactic surgery for movement
disorders, particularly PD. However, MER is associated with the higher
operative risks and costs.
Objective: To assess the role of
MER for STN-DBS in PD patients.
Methods: In the last 5 years, 75 PD patients were operated for continuous
high-frequency STN-DBS in Burdenko NSI: 47 without intraoperative MER (98
electrodes implanted) and 28 using MER (56 electrodes). Disease duration was 12.3±3.9 years, PD severity, 3–4, according to Hoehn&Yahr, age at
surgery – 54.0±8.8 years, without significant difference between two groups.
Analysis of intraoperative strategy and related complications was performed.
Results: In patients without
MER, central MRI-calculated trajectory was used for the final electrode
placement in 96%. Implantation depth adjustments were made for 9% of
electrodes. Stereotactic correction of electrode position in early or long-term
follow-up was needed in 6 patients. Stimulation-induced dysarthria occurred in
8 patients (10.7%). In patients with intraoperative MER, 1 to 5
microelectrodes were used per one side, mean 2.3(±0.9). Image-based tracks
corresponded the best neurophysiologically defined trajectory only in 68%. For
implantation of 21% of electrodes, medial track was chosen and in 7%, lateral
one. Additional correction in placement by depth was necessary in 77% of
implantations (range -3.0–1.5mm). No electrode
replacement was required postoperatively and only 1case (3.6%) of
stimulation-related dysarthria was noticed. In one case, symptomatic
intracranial hemorrhage from meningeal vessels occurred.
Conclusion: MER serves to improve
the accuracy, optimize the placement of electrodes, and reduce side effects in
STN-DBS. Nevertheless,
direct impact of MER on clinical outcome is unclear and needs to
be verified in long-term follow-up studies in larger population.
P21.06
Weight
modifying effect of deep brain stimulation: results of a case-control study
Maja Herco1
Roy E. Strowd2 Bradley Avery, 2 Ihtsham Haq,2
Stephen B. Tatter,3 Adrian W. Laxton.,3 Mustafa S.
Siddiqui 2
1Brody
School of Medicine, East Carolina University, Greenville, NC, USA
2Department
of Neurology, Wake Forest School of Medicine, Winston Salem, NC, USA
3Department
of Neurosurgery, Wake Forest School of Medicine, Winston Salem, NC, USA
Objective: Deep brain stimulation
(DBS) is a well-recognized treatment for Parkinson’s disease (PD). Weight gain
has been consistently reported following DBS of a variety of subcortical nuclei
in PD.
Methods: A case-control study of
PD patients undergoing DBS of the subthalamic nucleus (STN) and a control group
of age, gender, and diagnosis-matched controls who did not undergo DBS was
performed. Demographic data, baseline and follow up weights, and body mass
index were collected. Pre- and post-operative Unified Parkinson’s Disease
Rating Scale (UPDRS) scores and levodopa equivalent dose (LED) were collected
at baseline and 6 months postoperatively. Descriptive statistics were
calculated for the population. For binary variables, chi square and Fisher’s
exact test were used, and for continuous variables, t-tests were used to
determine significance of weight change at follow up and over time.
Results: Thirty-five cases were
identified and matched to 34 controls. Cases had a significantly longer
duration of diagnosis than controls (10.3 vs 5.76, respectively, p=0.0015).
Cases and controls had similar baseline weights (80.4 vs 80.4 kg, respectively,
p=0.99). Cases gained an average of 2.9 kg while controls lost an average of
1.8 kg (p=0.02) over a mean follow up of 634 vs 645 days (p=0.85). At baseline,
63% of cases and 77% of controls were overweight (BMI>25) while at follow up
69% and 56% were overweight, respectively. Confirming surgical efficacy, UPDRS
scores improved by an average of 21 points and LED by 157 points. While not
statistically significant, patients who underwent bilateral lead implantation
gained 3.4 kg compared to only 1.7 kg with unilateral implantation (p=0.62).
Conclusion: DBS has a weight
modifying effect on PD patients undergoing STN stimulation compared to age,
gender, and diagnosis-matched controls. Whether this owes to increased food
intake, lowered metabolic demands, improved motor complications, or other
etiology is unclear.
P21.07
Stereotactic neurosurgery for Parkinson’s disease in a
world perspective: results from the WSSFN-supported survey
Vincent A. Jourdain 1,
Gastòn Schechtmann 2
1Université Laval, Laval, QC, Canada
2Karolinska Institutet,
Stockholm, Sweden
Objective: Most studies in the field of neurosurgical treatment
of movement disorders have been published by a small number of leading centers
in developed countries. This study aimed to investigate the clinical practice
of stereotactic neurosurgery for PD worldwide.
Methods: Neurosurgeons were contacted via email to participate
in a worldwide survey. The results obtained are presented in order of the
countries’ economical development according to the World Bank, as well as by
the source of financial support.
Results: A total of 353 neurosurgeons from 51 countries who
operated on 13,200 patients in 2009 were surveyed. Surgical procedures
performed in high-income countries were more commonly financed by a public
health-care system. In contrast, patients frequently financed surgeries
themselves in lower-middle and upper-middle income countries and lesions were
most commonly performed. Unexpectedly, ablative surgery is still used by about
70% of neurosurgeons, regardless of their country’s economic status. This study
provides a previously unavailable picture of the surgical aspects of PD across
the globe in relation to health economics and socio-demographic factors. Global
educational and training programs are warranted to raise awareness of
economically viable surgical options for PD that could be adopted by public
health-care systems in lower income countries.
P21.08
Modulation of
glutamate receptors in dyskinetic MPTP monkeys receiving a unilateral
subthalamotomy
Vincent
A. Jourdain1,2 Nicolas Morin1,2, Laurent Grégoire1,
Marc Morissette1, and Thérèse Di Paolo1,2
1Neuroscience
Research Unit, Centre de Recherche du CHU de Québec, QC, Canada
2Faculty
of Pharmacy, Laval University, QC, Canada
Objective: Subthalamotomy
is a surgical option to alleviate disabling L-DOPA-induced dyskinesias (LID) in
parkinsonian patients. Despite the fact that this surgery is known to reduce
LID, the mechanisms remain largely unknown. The subthalamic nucleus is the sole
glutamatergic nucleus within the basal ganglia and its lesion may exert changes
in the expression of glutamate receptors.
Methods: AMPA,
NMDA (containing NR1/NR2B), mGlu2/3 and mGlu5 receptors were investigated using
receptor binding autoradiography in four MPTP monkeys displaying LID that
underwent unilateral subthalamotomy and were compared to four controls and four
L-DOPA-naive MPTP monkeys.
Results: Behaviorally,
subthalamotomy allowed a 40% reduction of the L-DOPA dose for a similar
antiparkinsonian response as before the lesion, but was associated with higher
LID. Increases induced by MPTP in
AMPA receptors in the dorsal putamen and ventrolateral caudate nucleus returned
to normal values with L-DOPA and subthalamotomy. AMPA receptors were reduced by
subthalamotomy in the ventral putamen compared to controls. Striatal and
pallidal NMDA receptors remained unchanged, except for the ventrolateral
putamen which decreased after MPTP, L-DOPA and subthalamotomy. Striatal and
pallidal mGlu2/3 receptors were found to be highly decreased in the
L-DOPA-treated MPTP-monkeys that underwent subthalamotomy compared to controls
and L-DOPA-naive MPTP-monkeys, whereas mGlu5 receptor displayed an opposite
pattern and increased in the same brain regions. In the caudate nucleus of MPTP monkeys receiving L-DOPA and a
subthalamotomy, increases in NMDA and mGlu5 receptors correlated with higher
dyskinesia and putaminal increases in NMDA receptors correlated with a better
motor response to L-DOPA. Pallidal decreases in mGlu2/3 receptors correlated
with a better improvement in motor response and lower dyskinesia. Decreases in
mGlu2/3 receptors and increases in mGlu5 receptors observed in the basal
ganglia may be the result of the subthalamic lesion and L-DOPA. These changes
could participate in the alleviation of parkinsonian symptoms and LID after
subthalamotomy.
P21.09
Usefulness of the personality
assessment inventory in the patient evaluation process for deep brain
stimulation surgery in Parkinson’s disease
Scott Kaplan1, Max Newlon1, Margaret
O’Connor1, Ludy Shih1
1Beth Israel Deaconess
Medical Center, Boston, MA, USA
Objective:
Selection of patients appropriate for deep brain stimulation (DBS) for
Parkinson's disease (PD) is focused on the likelihood of improvement of motor
symptoms, yet concern remains about the possibility of emerging behavioral
symptoms following DBS surgery. There is general consensus that thorough
pre-operative assessment of non-motor symptoms is needed but little agreement
on which methods are most practical and informative. A few studies have used
validated scales of non-motor symptoms; none has focused on the use of scales
of personality and psychopathology. This study will evaluate the use of the
Personality Assessment Inventory (PAI), a self administered and validated scale
of personality and psychopathology, in patients with PD undergoing DBS
evaluation. The PAI is a questionnaire with 22 separate, non-overlapping scales
including clinical, treatment, interpersonal and validity scales. The purpose
of this pilot study is to evaluate the usefulness of the PAI in the DBS
evaluation process, quantify personality and psychopathology in this
population, and evaluate possible effects of DBS on personality as measured by
this tool.
Methods: The PAI
was administered to PD patients undergoing DBS evaluation and 6 months post
surgery. Results were compared to PDQ39, QUIP-RS and UPDRS I-IV scores. PAI
results were discussed in interdisciplinary DBS team conference and compared to
clinical assessment by the health care providers on the team.
Results: PAI scores were completed for 7 patients undergoing DBS
evaluation. The most notable results are elevated scores for somatization
(mean: 65.6 range: 48-79) and depression (mean: 62 range: 42-98). The mean
scores for all other subscales, including positive and negative impression
management, fell in the normal range. There were abnormal values in individual
patients, and in one patient high scores on the depression subscale led to
further psychiatric and social work evaluation before surgery was performed.
P21.10
Effects of low-frequency deep brain stimulation of the
subthalamic nucleus or globus pallidus internus on gait in Parkinson’s disease
N. Krishnamurthi1, R. Dhall1, S.
Akhtar2, and K. Wilhelm1
1Muhammad Ali Parkinson Center, Barrow
Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ,
USA
2University of Arizona College of
Medicine at Phoenix, Phoenix, AZ, USA
Objective: Gait difficulties in Parkinson’s disease
(PD), especially freezing of gait (FoG) in later stages of the disease does not
respond well to pharmacological treatment and high-frequency (HF) deep brain
stimulation (DBS) of subthalamic nucleus (STN) or globus pallidus internus
(GPi). Recent studies indicate that low-frequency (LF) stimulation of these
structures may improve gait and FoG. We are quantitatively examining the
effects of changing frequency of stimulation of these structures on gait in PD.
Methods: In this ongoing study, four PD patients (two
with STN-DBS and two with GPi-DBS) have been recruited and examined so far. On
the day of evaluation, the subjects were first tested in their usual high
frequency DBS setting (HF) and Med-off condition (12-hours or more after the
last dose of PD medications). They were reevaluated twice at Med-off, DBS-80 Hz
(Intermediate frequency (IF)) and Med-off, DBS-30 Hz (low frequency (LF)) after
random selection of the sequence of these conditions, with a minimum of 30
minute wait after changing stimulation frequency. Several quantitative gait
indices and motor part of the Unified Parkinson’s Disease Rating Scale
(MDS-UPDRS) were obtained in each condition.
Results: Two of the four subjects (one with STN-DBS
and one with GPi-DBS) showed improvements in gait in the IF condition when
compared to HF condition. The gait velocity, double support duration, and
stride-time variability improved in these two subjects at IF condition compared
to LF and HF conditions. The subject with GPi-DBS who exhibited above mentioned
improvements also showed increased cadence and swing time duration. Generally,
gait worsened at LF condition when compared to IF and HF conditions. These
preliminary results indicate that IF stimulation of STN or GPi can improve gait
in PD and will be confirmed by including more subjects.
P21.11
Review of published outcomes of subthalamic
nucleus deep brain stimulation (DBS) in Parkinson disease supports hypothesis
of disease-modifying effect of DBS
Andreas Michas-Martin1, Thomas
Ragole1, Elizabeth Juarez-Colunga2, Angela Moss2,
Olga Klepitskaya1
1University of Colorado School of
Medicine, Department of Neurology, USA
2University of Colorado Denver,
Department of Biostatistics &Informatics, USA
Objective: To conduct a systematic review of
literature regarding outcomes of Subthalamic Nucleus (STN) Deep Brain
Stimulation (DBS) in Parkinson disease (PD) in order to: 1) examine the
long-term effects of STN DBS on the progression of motor disability, measured
by Unified Parkinson Disease Rating Scale motor subscore (UPDRS-III) off
treatment (Off medication, Off stimulation); and 2) compare the rate of
progression with estimated expected natural progression.
Methods: An extensive PubMed search of
literature published between 1998 and 2012 was conducted using the key terms:
DBS, STN, neurostimulation, and PD. Included in the analysis were the
publications reporting bilateral STN DBS outcomes, UPDRS-III off treatment
before and after DBS implantation, and a minimum one year follow-up. The rate
of natural decline of motor symptoms was defined, based on previously reported
placebo controlled clinical trails, as an annual increase in the UPDRS-III of 5
points.
Results: 38 articles matched the search criteria
and were included in the analysis. The number of subjects per study varied from
5 to 103, the total number was 1,341. The maximum follow up time was 11.7
years. The majority of studies demonstrated unchanged UPDRS-III scores, some
demonstrated improvement. In studies that reported worsening, the annualized
change was lower than expected from natural progression. On average, no
significant change in UPDRS-III was observed in DBS treated patients. This
finding is remarkable for an otherwise progressive neurodegenerative disorder
and supports the notion that chronic STN DBS results in persistent
electrophysiological, neurochemical, and synaptic changes in the brain, known
as neuromodulation.
P21.12
A Gene Therapy for Parkinson's disease –
modifying ProSavin® to increase specific activity
Mitrophanous K2, Aron Badin R1, Binley K2,
Stewart H2, Van Camp N1, Hosomi K3, Ralph S2, Lad Y2, Naylor S2, Palfi S1,3, Hantraye P1
1CEA-CNRS URA2210, MIRCen, Fontenay aux Roses,
France
2Oxford BioMedica (UK) Ltd,
Oxford Science Park, Oxford, UK
3Henri Mondor Hospital, Paris University, France
Objective:
Oral
dopaminergic treatments have remained the primary standard of care for
Parkinson’s disease (PD) for the last 40 years. Although these are highly
efficacious in the early stages of disease, over time they lead to debilitating
long term side effects that seriously impact on the quality of life and
restrict the longevity of such treatment. The severity of PD, the lack of a
cure and the limited long term effectiveness of current therapies strengthen
the need of novel therapeutic approaches.
Methods: We have developed a
lentiviral vector (ProSavin®) derived from the equine infectious
anaemia virus (EIAV) expressing the three key dopamine biosynthetic enzymes
(tyrosine hydroxylase, aromatic L-amino acid decarboxylase and GTP
cyclohydrolase-1). Clinical evaluation of the safety and efficacy of ProSavin®
in mid to late stage PD patients is currently ongoing in fifteen patients in
three dose cohorts. There have been no serious adverse events related to
ProSavin® or the administration procedure and no severe immunlogical
responses. In terms of efficacy, an improvement in the primary endpoint, UPDRS
Part III, has been observed.
Results: In order to support further dose optimisation we sought
to increase the specific activity of the vector in order to increase the
production of dopamine. By refining the gene expression cassette for the three
genes we were able to increase dopamine production significantly. This
construct is being evaluated in vitro in primary neuronal cells and in the MPTP
NHP animal model of PD and results will be presented.
P21.13
Lower urinary tract Interventions in Parkinson’s disease:
The Indian experience at KDAH
Sanjay Pandey1, Mohit Bhatt2
1Kokilaben Dhirubhai
Ambani Hospital& Research Institute, Mumbai, India
2Kokilaben Dhirubhai
Ambani Hospital& Research Institute, Mumbai, India
Objective: Recognition of bothersome and progressive
urinary complaints by patients in Parkinson’s disease (PD) helps a clinician to
make changes in his fast deteriorating urinary health. It affects the quality
of life with bothersome obstructive and irritative voiding symptoms in such
physically challenged individuals.Stabilisation of lower tract symptoms in the
long run is a management challenge in view of ever changing presentation with
age and state of disease.
Methods: The Neuro-urology team recognized patients
with secure neurological diagnosis of PD referred with persistent and disabling urinary symptoms and evaluated
the same with symptom score, Uroflowmetry and Urodynamics, then categorized and
managed as
A. Watchful waiting
with combination pharmacological therapy
B. Active
intervention. 62 patients
Interventions
undertaken were cystoscopy- urethral dilatation, Cystoscopy- Botulinum toxin
intravesical injection, Transurethral resection of prostate (TURP) and
Botulinum toxin intrasphincteric injection as indicated
Results: 38 patients ranging in age from 51 to 77
years underwent TURP, 10 patients( males- 9, females- 5) with refractory
detrusor hyperreflexia underwent Intravesical botulinum toxin injection, 12
underwent Intrasphincteric botulinum toxin therapy.2 female patients underwent
urethral dilatation along with anticholinergics. Repeat injections were
considered in all except when they reverted to catheter in view of the
progressive disease and refractory bladder state.
Conclusions : All patients tolerated TURP well ;Four
patients were placed on catheter after surgery in view of gross urgency and
urge incontinence and treated with prolonged anticholinergics with minimal
benefit.No patients developed urinary incontinence after transurethral
resection of prostate.Thirty one patients post- TURP status showed satisfactory
flow and continence at median follow up of 6 months.Patients on medical
management were followed closely with stable results.Three patients with
progressive PD had recurrence necessitating finally requiring suprapubic
cystostomy. Thus, carefully planned interventions in Parkinson’s disease go a
long way in maintaining urinary health.
P21.14
Botulinum Toxin is the Final answer in refractory
Neurogenic Overactive bladder and Sphincter dyssenergia in Parkinsonism:
Kokilaben hospital Experience
Sanjay Pandey1, Mohit Bhatt2
1Kokilaben Dhirubhai
Ambani Hospital& Research Institute, Mumbai, India
2Kokilaben Dhirubhai
Ambani Hospital& Research Institute, Mumbai, India
Objective: Gross
neurogenic overactive bladder symptoms associated with Parkinson’s disease and
progressive obstructive voiding resulting directly from detrusor external
sphincter dyssenergia are two most debilitating and refractory urinary symptoms
that have no satisfactory medical management till date.Use of Botulinum toxin in
carefully chosen and diagnosed cases go a long way in relieving symptoms and
treating these difficult situations.
Methods: All 22
patients with above debilitating symptoms underwent urodynamics studies. Group
1 ( 10pts)-Neurogenic overactive bladder group were treated with Intravesical
botulinum toxin 200IU injected in the bladder wall spread across the bladder
dome, lateral and posterior walls by cystoscopy route.Group 2(12 pts)- Detrusor
external sphincter dyssenergia group with obstructive voiding under
Intrasphincteric Botulinum toxin injection 150 IU under cystoscopic
guidance.All patients were observed with overnight admissions as institute
protocol.They were prepared with pre and post intervention urine cultures
towards beneficial effects thus decreasing morbitiy from any urinary
infections.All patients were chosen for a second session of therapy after 6-9
months or on return of symptoms which ever was earlier.
Results: All patients reported vastly improved
quality of life after Botulinum toxin therapy in both subgroups.The neurogenic
overactive bladder group showed significant improvement in all domains of
frequency,urgency and urge incontinence without any change in nocturia.The
dyssenergia group had improved obstructive voiding commencing third week that
was sustained between 4-6 months as proven by repeat urodynamics studies.The
two groups being completely refractory to any oral medications were vastly
benefited with the above intervention and improved quality of life in face of
progressive Parkinson’s disease.
P21.15
Social support and
motor outcomes after deep brain stimulation in patients with Parkinson disease
Jon Snider1,
Laura Zeitlin2, Susan Grube2,3, Parag G. Patil,1,2,3,
Kelvin L. Chou, 1,2,3
1Department of Neurology,
University of Michigan, Ann Arbor, MI, USA
2Surgical Therapies
Improving Movement Program, University of Michigan, Ann Arbor, MI, USA
3Department of
Neurosurgery, University of Michigan, Ann Arbor, MI, USA
Objective: Levodopa response is the
only known predictor of motor outcome after deep brain stimulation (DBS)
surgery in Parkinson disease (PD). We have anecdotally observed that PD
patients with better social support seem to have more favorable motor outcomes
after DBS. The Social Provisions Scale (SPS) examines the amount of social
support that a patient perceives. We examined whether baseline SPS scores were
associated with motor outcomes after DBS in PD.
Methods: We performed a
retrospective data analysis of 15 PD patients (10M/5F) undergoing bilateral
subthalamic nucleus DBS who had completed the SPS prior to surgery (baseline)
and approximately six months following initial programming and compared them to
their MDS-UPDRS motor scores.
Results: There was no change
in total SPS score at 6 months, but the SPS reliability alliance subscale
(which measures the reliability of someone’s social support network) worsened
after surgery (15.4 ± 1.2 at baseline vs. 14.5 ± 1.8 at 6 months, p=0.05). The
MDS-UPDRS motor score improved by 38% with stimulation (43.3 ± 10.8 at baseline
vs. 26.9 ± 9.3 at six months, p =0.001), but there was no correlation between
baseline SPS scores and change in MDS-UPDRS motor score. Overall, baseline
social support does not correlate with DBS motor outcomes; however, one measure
of social support worsened after DBS. There are often numerous visits after DBS
surgery for stimulation adjustments, which may stress a patient’s support
network. Though we hypothesized that social support would affect DBS outcomes,
it seems that DBS may instead affect social support.
CLINICAL
SCIENCES: REHABILITATION SCIENCES (PT, OT, SLP)
P22.01
Impact of freezing of gait on self-perceived balance confidence for functional
activities in people with Parkinson’s disease
Lorena R. S. Almeida1,
Rebecca A. Gruber2,3, Jan Goldstein Elman2,3, Nádja
Negreiros1, Guilherme Valença1, Elen Beatriz-Pinto4,
Jamary Oliveira-Filho4
1Movement Disorders Clinic, State of Bahia Centre
for the Elderly Health Attention – CREASI/SESAB, Salvador, Bahia, Brazil
2One
Step Ahead Mobility Physiotherapy, Toronto, ON, Canada
3University of Toronto,
Toronto, ON, Canada
4Stroke
Clinic, Federal University of Bahia, Salvador, Bahia,
Brazil
Objective: To
identify associations of freezing of gait (FOG) and fear of falling in people
with Parkinson’s disease (PD); and to compare self-perceived
balance confidence between patients with and without FOG.
Methods: One hundred and three subjects in two countries
with a diagnosis of PD were included in this study. In addition to collecting
demographics and clinical data, we assessed patients with the Unified Parkinson’s
Disease Rating Scale (activities of daily living and motor sections),
Freezing of Gait Questionnaire (FOG-Q) and Activities-Specific
Balance Confidence Scale (ABC). Subjects were classified as freezers if they
scored one or more on the FOG-Q, item three. Mann-Whitney and Pearson
Chi-Square tests were performed. Results are shown as median (Q1; Q3).
Results: The sample had a median age of 70 years and 60
subjects (58.3%) were male. Forty-one (39.8%) subjects were classified as
freezers. Freezers had longer disease duration, and increased disease severity
and functional limitations (p≤0.001). Median score on the ABC for
freezers was 60 (31.87; 82.19); for non-freezers median score was 75.94 (49.22;
93.12) (p=0.017). Median scores were significantly lower for freezers on items:
walking around the house, reaching on tiptoes, standing on chair to reach,
sweeping the floor, walking across a parking lot/in the mall/being bumped/on a
slippery surface (p≤0.037). We found borderline p value for the following
tasks: walking outside (p=0.071), walking down/up a ramp (p=0.086) and riding
an escalator without holding the rail (p=0.062).
Conclusions: Our data suggest that freezers have lower self-perceived balance
confidence on tasks that are more challenging to their postural control and
that have been described as likely to elicit FOG. These results suggest that
people with PD who freeze know when they are at risk of falling, and support
the validity of the self- report ABC scale for measuring fear of falling in
this group.
P22.02
Associations of freezing of gait with fear of falling and
falls in people with Parkinson's disease
Lorena R. S. Almeida1, Silvana L. Ferreira2,
Juliana V. Freitas2, Nádja Negreiros1, Guilherme Valença1
1Movement Disorders
Clinic, State of Bahia Centre for the Elderly Health Attention – CREASI/SESAB,
Salvador, Bahia, Brazil
2Universidade Católica
do Salvador, Salvador, Bahia, Brazil
Objective: To examine
associations of freezing of gait (FOG) and clinical characteristics, fear of falling and
falls in people with Parkinson’s disease (PD); and to identify the correlation
between FOG and fear of falling.
Methods: Eighty-four patients with PD and independent
walking ability were evaluated during the “on” phase of the medication cycle.
Exclusion criteria were cognitive impairment (assessed by
the Mini-Mental Status Examination), presence of neurological conditions
other than PD, and visual disturbance. Demographics and
clinical data were gathered and individuals were assessed with the modified
Hoehn and Yahr scale, Freezing
of Gait Questionnaire (FOG-Q) and Falls Efficacy Scale-International (FES-I).
The FES-I is useful to assess concern about falling while performing certain
activities of daily living, with possible scores ranging from 16 to 64 points,
and higher scores reflecting more fear of falling. Subjects were classified as freezers if they scored one or more on the
FOG-Q, item three. The Mann-Whitney and the Pearson Chi-Square tests were used
to identify associations and the Spearman correlation was performed.
Results: The overall sample
had a median age of 70 years. Thirty-two patients (38.1%) were classified as
freezers. Freezers had longer disease duration, increased disease severity and
higher levodopa equivalent dose (p≤0.018). Motor fluctuations were also
associated with FOG (p=0.004). The median FES-I score was 39 points for
freezers versus 27 points for non-freezers (p<0.001). Among freezers, 13
(40.6%) had a history
of two or more falls
in the preceding 12 months, while among non-freezers six (11.5%) reported
recurrent falls in the last year (p=0.002). A moderate correlation was found
between the FOG-Q and FES-I (r=0.58; p<0.001).
Conclusions:
Our data suggest that freezers have more advanced
disease and degree of fear of falling. These clinical aspects have been found
to be important risk factors for falls in people with PD.
P22.03
Comparison of the effects of
exercise programs conducted at home or hospital Parkinson’s disease patients
Aysegul Arslan1,
Bilge Kara1, Arzu Genc1, Beril Dönmez Colakoglu2
1Dokuz
Eylul University, School of Physical Therapy and Rehabilitation, Izmir, Turkey
2Dokuz
Eylul University Medical Faculty, Department of Neurology, Izmir, Turkey
Purpose: This study compares the effects
of home exercises and those of exercises performed with a physiotherapist on
the functionality, balance, walking and severity of the disease in Parkinson’s
patients.
Methods: This study included 21 patients
followed in the Movement Disorders Clinic of Neurology Department of Dokuz
Eylul University Hospital. The patients were divided into two groups: those
attending a 3-day exercise program in the hospital (n=10) and those who
regularly exercised at home (n: 11). The exercise program took 45-60 minutes, 3
days a week for a period of 10 weeks. The stages of the disease were evaluated
with the Modified Hoehn-Yahr Scale and the severity of the disease with the
Unified Parkinson's disease Rating Scale (UPDRS).
The static and dynamic balance was evaluated with Berg Balance Scale (BBS) and
Functional Reach Test (FRT), functionality with (Time up-go test (TUG), turning
in bed, from lying to sitting position, from sitting to standing position,
5-repetition sit-to-stand) and walking with the dynamic walking index.
Results: The pre-exercise scores for UPDRS
part I, II (activities of daily living) and III
(motor examination), all functionality tests (except for TUG), walking, and
balance significantly improved after the hospital exercise program (p<0.05).
In the home-exercise group; after the exercise program, part II
scores of UPDRS, some functionality and balance tests (from sitting to standing
position, FRT) improved (p<0.05). The comparison of the two groups revealed
that scores for walking, some functionality tests and BBS were better in the
hospital group.
Conclusion: Balance, walking and some functionality scores in
the hospital group were better than those in the home group were. However, the
patients’ balance, functionality and UPDRS scores improved with exercise in
both groups. Therefore, we think that medical treatments should be accompanied
with exercise programs when Parkinson's patients are treated.
Key
Words: Parkinson's
disease, Exercise, Functionality, Balance
P22.04
Can singing be a treatment option for speech and language
therapists?
Caroline Bartliff1, Liz Greaves2,
Brian Greaves2, Sheena Dearle2,
1Specialist Speech and
Language Therapist, Derby Hospitals NHS Foundation Trust, Derby, UK
2Parkinson’s UK, Derby
Branch, UK
Objective: Previous research data inspired Parkinson’s
UK Derby branch and a specialist Speech and Language Therapist (SLT) to set up
a singing group for local people. The scope of this group was to be therapeutic
and prove that singing can benefit people with Parkinson ’s disease, evaluate
how it benefits and view the impact it has on people at different stages of
Parkinson’s Disease.
Method: A working party established an initial
10-week trial (April-June 2012) followed by weekly singing sessions from
September 2012 to the present day. The style and approach of the musical
director was evaluated, as was the seating arrangements and the music choice.
The group participants were between 60-70 years of age, with British origin.
All 12 individuals who completed a pre and post evaluation form were under the
care of the specialist SLT. 50% of the evaluated group could be considered to
be in the ‘maintenance’ phase of Parkinson’s disease and the other 50% in the
‘complex’ phase.
Results: The data collected
provides strong support for the socio-emotional benefits of singing as a form
of therapy. The difficulty lies in generalising the vocal gains from this
therapy into everyday talking situations. This would be the primary aim for an
NHS Speech and Language Therapist. Unfortunately, the information obtained so
far has shown that intelligibility in conversation is not affected by attending
a singing group. Clinically, singing should facilitate improvements in breath
support and aspects of voice (including pitch range and voice quality). The
scope of future work will look at the same data subjects with a view to
measuring improvements in vocal performance. This will allow us to fully
evaluate the benefits of offering singing as a treatment option in the NHS.
P22.05
Functional improvements associated with upper extremity
motor neurorehabilitation in individuals with Parkinson’s disease
Patrick Bartoshyk1,
Natalie de Bruin1 & Jon Doan1
1Engineering and Human
Performance Laboratory, University of Lethbridge, Lethbridge, AB, Canada
Objective: Non-traditional exercise neurotherapy is proving beneficial in symptom management for
people living with Parkinson’s disease (PD). Whilst traditional therapies
promote motor function, the benefits may be limited by compounding physical,
cognitive, and attentional barriers. Preliminary research from our laboratory
has shown that some people living with PD preserve the capacity to safely and
effectively ice skate despite displaying marked deficits in a range of
functional movements. Furthermore, a brief period of ice skating has been shown
to positively influence balance and coordination. We hypothesised that adding
an upper body motor coordination task (stickhandling) to ice skating may
provide upper extremity neuromotor benefit. Accordingly, the purpose of this
study was to explore the effects of a stickhandling exercise session on motor
performance amongst people with moderate PD.
Methods: Nine people with moderate PD and seven
control subjects (CTRL) completed three trials of a reaching-to-eat (fine
motor) task and a button push (gross motor) task with their dominant arm
PRE-and POST-intervention. The intervention involved completing two dynamic
stickhandling tasks (ice hockey stick and puck) either on- or off-ice depending
on the physical abilities of the subject. Reaching-to-eat trials were captured
in sagittal plane video and manually scored for movement quality. Button push
trial data were collected automatically. Reaching-to-eat and button push scores
were compared between groups (PD, CTRL) and time periods (PRE, POST).
Results: All subjects performed the stickhandling
tasks safely and effectively. The PD group demonstrated deficits in both tasks
when compared to CTRL. Both groups demonstrated an improvement in
reaching-to-eat (Figure 1A) and button push (Figure 1B) scores immediately
following the intervention. The observed improvements in upper extremity motor
performance amongst the people living with PD following a period of exercise
imply that sport-derived exercise programs may
provide neurotherapeutic benefit to PD patients in
sustaining upper extremity functional mobility.
Figure 1. Mean score for A) reaching-to-eat task and
B) button push task. Dark bars represent pre-intervention data; light bars
represent post-intervention data.
P22.06
Non-gait related
benefits of auditory cueing in Parkinson's disease
Charles-Etienne Benoit
1,2,3*, Nicolas Farrugia 2, Michael Schwartze 2,5, Simone Dalla Bella 1,3,4 and
Sonja Kotz 2,5
1
Department of Cognitive Psychology, University of Finance and Management in
Warsaw, Ul Pawia, Warsaw,
Poland
2 Max Planck Institute
for Human Cognitive and Brain Sciences, Research Group: Subcortical contributions to
comprehension, Department of
Neuropsychology, Leipzig, Germany
3 Movement to Health
Laboratory (M2H), EuroMov, 34090, Av. Pic Saint-Loup
700, Montpellier-1 University, Montpellier, France
4 Institut
Universitaire de France (IUF), Paris, Bd. Saint-Michel
103, 75005, Paris, France
5 School of Psychological Sciences, The University of
Manchester, Manchester, UK
Objective: Parkinson’s disease (PD) is a
neurodegenerative disorder that targets mainly dopaminergic neurons of the
basal ganglia. PD is characterized by motor symptoms typically leading to
dysfunctional gait. External auditory cues have shown beneficial effects on
gait kinematics in PD patients. However, little is know about potential
benefits of auditory cueing on non-motor functions. In the current study we
investigate whether auditory cueing has a positive effect on perceptual timing.
Methods: Fifteen PD patients were
submitted to a standard auditory cueing program (3 times a week for 30 min, for
one month). Gait performance was evaluated using motion capture. In addition,
motor (via tapping tasks) and perceptual timing abilities were assessed using a
new Battery for the Assessment of Auditory Sensorimotor and Timing Abilities
(BAASTA). The patients' sensitivity to temporal regularity, a crucial element
in rhythmic auditory stimulation, was also monitored using a perceptual oddball
paradigm task using electroencephalography event-related potentials (ERP;
Schwartze et al. 2011). Participants were asked to count deviant tones
presented in a sequence of either regular or random stimuli. The patients were
evaluated before the program, immediately after, and one month after the
therapy. Their performance was compared to a baseline which was established by
data collected from healthy age-matched controls.
Results: Improved gait kinematics (i.e.,
greater walking speed and step length) were observed as a result of the therapy
and persisted one month later. Interestingly, these benefits extended to
perceptual timing. Improved duration discrimination, detection of a deviant
beat in a musical stimulus and enhanced detection of misaligned sounds to the
beat of music were observed. These effects are complemented with a reduced
response to temporal regularity visible at the level of the P300 late ERP
component linked to deviance detection.
References: Schwartze
M, Rothermich K, Schmidt-Kassow M, Kotz SA., Temporal regularity effects on pre-attentive
and attentive processing of deviance, Biol Psychol. 2011 Apr;87(1):146-51.
P22.07
Effects of Parkinson’s medication on the performance of
different exercises before and after dosing
Debora F. Bergstrom1, Chris L. Bergstrom2,
Allison R. Bergstrom3
1Frederick Community
College, Frederick, MD, USA
2Independent, Freeland,
MD, USA
3Independent, Needham,
MA, USA
Objective: As a researcher with
Parkinson's, I executed a series of controlled experiments on myself to see the
relationship between exercises, before and after dosing with Parkinson's
medication. Four physical activities were done typically 5 to 7 days per week for
up to 12 weeks. Activities were done in triplicate immediately before and one
hour after taking medications. Three activities were based on Wii Fit games,
two of which were balance activities and one aerobic. The fourth task involved
small motor skills of sorting shapes.
Methods: All
activities showed improvements following medication dosing. The least
responsive activity was small motor skills sorting. Medication increased the
performance of balance activities to a typical ratio of 60% of scores before/after.
Balance exercises requiring quick, random actions trended downward with time
compared to exercises with predictable, repetitive patterns, which improved due
to learning. Variances for all tasks were lower before medications, suggesting
the body’s superior ability to regulate internal dopamine levels versus
externally administered. Small motor shape sorting activity showed performance
changes smaller and more variable than larger motor skills.
Results: Exercise studies should account for timing and dosing of
medication to get understandable trends. Large motor skills respond more to
medication than small motor. Exercises requiring random, rapid responses behave
differently than repetitive, predictable activities. Performance variability
increases with medication dosing.
P22.08
Influence of music therapy to
improve quality of gait and balance in PD patients – a pilot study
Anna Bukowska
University of Physical Education, Krakow, Poland
Objective: The aim of this
research was the evaluation of influence of music therapy to improve gait,
balance and associated motoric functions in a group of patients with
Parkinson's Disease. Research approach assumed the use of functional therapy
combined with music therapy techniques taken from Neurologic Music Therapy
Concept (NMT). The main hypothesis was that NMT sensomotoric technics can
improve the kinematics gait parameters and balance reaction in group of
patients with PD.
Methods: To evaluate
therapeutical activities objective measurement of gait by optoelectronical
complex biomechanical analysis BTS Smart was used. Static balance and dynamic
balance reactions were assessed by stabilographic platform CQ
STAB. Patients were also assessed according to author’s “Therapeutic approach
schema during session”. Measurements were done before and after one month
research cycle. Therapeutical program was conducted in The Neurology and
Neurosurgery Clinic in Krakow. 10 patients selected to the pilot group for 4
weekes, 4 times a week, attended 45 mintutes individual, therapeutical
sesions of functional therapy based on neurologic music therapy techniques.
During therapeutical session metronomes, simple percussion instruments and
rhythmical music from MP3 was used. It was all combined with functional
movement focusing on improvement of balance reactions, gait components, muscles
strengthening and movement smoothness.
Results: The pilot study shows
that neurological music therapy can help patients with PD improve gait and
balance. Still, to confirm the results this research should be continued on a
bigger group of patients. Expected results in a wider group of patients can
contribute to better recognition and understanding of mechanisms of
therapeutical influence on the symptoms which significantly impair in the
course of Parkinson's Disease. Also it can help develop therapeutical stretegy
based on music and rhythm to improve and maintain good functional state and
help this group of patients come back to social activity.
P22.09
Dancing and drumming with individuals with Parkinson’s
disease: a community based program
K. Szirony, A. Chan, J. Ryan, L. Skocaj
Cleveland Clinic
Foundation, Cleveland, OH, USA
Cleveland State
University, Cleveland, OH, USA
Objective: Current research supports the use of dancing,
specifically the partnered tango, to improve functional deficits related to
Parkinson’s disease (PD). Recent literature has indicated that music can
positively influence quality of gait in people with PD. While the type of
dancing reported to be most beneficial is the Argentine tango, there have not
been any studies that focus on the use of modern/ interpretive dancing (MID)
and drumming. Similar to tango, MID is a flexible, improvisational form of
dancing that can incorporate multi-directional movements and rhythmic
variations.
This pilot study aim
to evaluate the benefits of a 12-week community based dancing and drumming
program in individuals with idiopathic Parkinson’s disease with Hoehn and Yahr
stages I-II.
Methods: A cross-over study design will be used to
divide ten individuals who have been discharged from physical therapy service.
The individuals and their care-partners will be divided into a control and an
experimental group to participate in weekly dancing and drumming sessions.
These sessions will be lead by licensed physical therapists. The participant
will also perform a progressive home exercise program. Data collection will be
conducted by the same blind evaluator at pre assessment, 12 week, and 24 week
post assessment periods. Various tools will be use to collect data on
functional outcome, quality of life, and individual’s satisfaction with
socialization and engagement in physical activity.
Results: This ongoing pilot study will be complete in
July 2013. Result will be use to further develop a long term community based
dancing and drumming program for individuals with PD at varies disease stages.
P22.10
A novel approach to
testing freezing of gait in patients with Parkinson’s disease: the clover test
Heather Cianci1,
Joellyn Fox1, Stacy Horn2, Marcus Besser3
1The Dan Aaron
Parkinson’s Rehabilitation Center, Good Shepherd Penn Partners, University of
Pennsylvania, Philadelphia, PA, USA
2University of
Pennsylvania, Philadelphia, PA, USA
3Thomas Jefferson
University, Philadelphia, PA, USA
Objective: (1) To assess the effectiveness of a newly designed freezing of gait
(FOG) functional assessment tool. (2) To determine if the FOG questionnaire
(FOG-Q) total scores correlated with FOG episodes captured in the clover test.
Methods: A convenience sample of 31 subjects (mean age 69.58) with idiopathic
Parkinson’s disease (PD) who experienced FOG, and 22 controls without PD were
recruited from the PD and Movement Disorders Center in Philadelphia,
Pennsylvania. Subjects completed the FOG-Q and then performed the clover test.
This test had four numbered chairs placed in an “X” pattern. Chairs 1, 2, and 3
faced in and chair 4 faced out. Chairs were spaced at 18 inches and subjects
began ambulating at five feet away from chair 1. Subjects walked to chair 1,
sat in the chair, stood, and continued on to perform the same at chairs 2, 3,
and 4. The test ended when subjects sat in chair 4. The entire test was timed
and episodes of FOG were noted.
Results: The mean time to
complete the clover test was 21.8 seconds for controls, and 38.55 seconds for
subjects. It captured FOG episodes
(ranging from 0-15), with the top three causes being: turns, initiation
of gait, and reaching for the chair before turning to sit. Total scores on the FOG-Q ranged from 7-23
(mean = 12.45). The total scores on the FOG-Q did not correlate with the clover
test times, showing that the subjects’ perception of their FOG generally did
not match their actual ability.
P22.11
Using timed tasks to
determine change after LSVT® BIG treatment in three patients with young onset
Parkinson’s disease
Heather Cianci1,
Joellyn Fox1
1The Dan Aaron
Parkinson’s Rehabilitation Center, Good Shepherd Penn Partners, University of
Pennsylvania, Philadelphia, PA, USA
Objective: To present a case study showing how timed tasks can show improvement in
the function of individuals with young onset Parkinson’s disease (YOPD) using
LSVT® BIG treatment. Many current functional assessment tools do not adequately
capture the deficits of bradykinesia and hypokinesia that those with YOPD
suffer.
Methods: A random sample of 3 patient charts detailing LSVT® BIG treatment
received at the Dan Aaron Parkinson’s Rehabilitation Center in Philadelphia, Pennsylvania
were chosen. Each patient reported functional limitations. An initial
assessment was performed on each patient, followed by LSVT® BIG treatment
4x/week for 4 weeks, in hourly sessions. Prior to discharge, each patient was
reassessed, in part using timed tasks.
Results: The time to perform tasks such as typing, shoe-tying, transfers, single
leg stance, and retrieving items from the floor all decreased, indicating
improved functional ability and decreased bradykinesia. All patients improved
their step size which decreased their likelihood of LOB, and indicated less
hypokinesia. Each patient also self-reported that they felt “much better” on
their global rate of change scale. Timing functional tasks can capture
improvements in mobility gained through LSVT® BIG treatment.
P22.12
Novel GaitReminder™ technology for use in treadmill
rehabilitation using cadence matched music
Alexandra Cihal1†,
Kailie Luan1†, Nicole Meyer1†,
Bin Hu1
† Equal Contribution
1Department of Clinical Neurosciences, University
of Calgary, Calgary, AB, Canada
Objective: Treadmill training (TT) and rhythmic
auditory stimulation (RAS) are recommended gait rehabilitation methods in
Parkinson’s disease (PD). The aim of the present study was to develop a
paradigm of RAS that can be used safely for treadmill walking under harsh
weather conditions.
Methods: We first obtained step length and cadence
data from 6 healthy subjects walking under 9 different treadmill settings of
varying speeds and inclines. Data was continuously acquired using GaitReminder™
(GR), an Apple iPod touch-based application. Average cadences of each treadmill
setting were used to determine the songs with matching beats per minute (bpm).
The final songs were complied into a playlist with auditory instructions
directing users to change treadmill settings prior to each matched song.
Questionnaires regarding aspects of music most enjoyed were administered.
Results: 24 different, healthy subjects listened to
the playlists during the same 9 treadmill conditions, while wearing the GR. BPM
accuracy was tested by comparing actual walking cadences to the BPM of the song
chosen for that treadmill condition. We found a mean difference of 1.7±0.97%
and 3.7±0.80%, for the tall and short subject groups respectively. 81% of
participants indicated on the questionnaire that the beats and tempo were the
aspect of the music most enjoyed. Music triggers physiological arousal, whereas
rhythm provides an external time keeper, influencing step timing and fluidity,
and increasing the pleasure associated with exercise. Combining musical RAS
with TT may create an enjoyable rehabilitation and gait training method for
people living with PD. Such a program may be also applicable to other disorders
affecting gait, such as stroke, spinal cord, or head injuries.
P22.13
Enhanced walking function with boxing training for
persons with Parkinson disease
Stephanie A. Combs1, M. Dyer Diehl1,
Michelle Bentz1, Kateland Hojnacki1, Lindsay Sewell1,
Stephanie Steider1
1Krannert School of Physical Therapy,
University of Indianapolis, Indianapolis, IN, USA
Objective: The purpose of this preliminary study was
to compare walking function outcomes over time between people with PD who
participate in boxing training and those who do not.
Methods: Eighty-eight participants with PD were
enrolled in a 2-year longitudinal cohort study. Participants who completed all
testing at baseline, 6, and 12 months were included in the current analysis
[n=65; mean age 67.1(8.7) years; male 71%; mean months post diagnosis
71.8(55.4), mean Hoehn and Yahr 1.75]. Participants were categorized as “boxer”
if at each testing session they reported participating in boxing training
(n=39) or as “non-boxer” if at each testing session they reported participating
in other exercise activities (n=26). Demographics and PD characteristics were
collected at baseline. Exercise behaviors and walking function were collected
at each testing session. Walking variables included the comfortable and fast
10-meter walk tests and the 6-minute walk test. Data were analyzed with a 2x3
mixed-model ANOVA (p<0.05).
Results: Groups did not significantly differ in age,
gender, month since diagnosis, Hoehn & Yahr levels, or self-reported
readiness to exercise (p>.05).
Boxers demonstrated significantly greater comfortable 10-meter walking speed
compared to non-boxers [mean speed, boxers 1.29(0.23)m/s vs. non-boxers
1.18(0.24)m/s; p=.048] and increased
gait endurance on the 6-minute walk test [mean distance, boxers
503.5(120.3)meters vs. non-boxers 433.5(108.0)meters; p=.012]. Significant differences in fast walking speed were not
found between groups. Neither group demonstrated significant changes in walking
function over the 12-month period. Boxers reported significantly more minutes
of exercise per week (p=.007) and a
higher rate of perceived exertion during exercise (p=.002) than non-boxers.
Conclusion: Those who participated in boxing training
maintained better walking function over the course of one year than those who
did not box. Future study of persons with PD is warranted to determine the
effectiveness of boxing on both overall fitness and PD symptoms.
P22.14
Do clinical tests of
balance performance correlate with physical activity level in Parkinson’s
disease?
David
Conradsson 1,2, Håkan Nero 1, Niklas Löfgren 1,
Maria Hagströmer 1,2, Caroline Paquette3, Erika Franzén 1,2
1Karolinska Institutet, Department
of Neurobiology, Care Sciences and Society, Division of Physiotherapy
2Karolinska University Hospital
Department of Physical Therapy Stockholm, Sweden and 3Department of
Kinesiology and Physical Education, McGill University and Centre for
Interdisciplinary Research in Rehabilitation, Montreal, QC, Canada
Objective: Tests of balance performance are commonly
used in clinics to assess whether individuals with Parkinson’s disease (PD) are
safe to ambulate independently, however it is uncertain if these clinical
assessments relate to physical activity (PA) in real life. Hence, the aim of
this study was to examine the association between clinical test of balance
performance and objectively assessed PA in elderly with PD.
Methods: Sixty-five participants (29 female), mean
age 73 years (range 61 - 86) with mild to moderate idiopathic PD (Hoehn &
Yahr 2-3) were included in this cross-sectional study. Balance performance was
tested for mini-BESTest (total score),
modified figure of eight test, timed up and go, one leg stance and pull test
(normal/abnormal response). As a measure of total PA, average steps per day was
assessed using accelerometers (Actigraph GT3X+, 30Hz) worn around the waist
during daytime for 3 to 7 consecutive days. Based on PA data, the participants
were categorized into an active (>5000 average steps/day, n= 26) and an
inactive group (<5000 average steps/day, n= 39). Non-parametric statistics (P <0.05) were used to compare
clinical balance performance between the two groups and test associations between
clinical tests and level of PA. P-values and correlation coefficients (rs)
are presented here.
Results: Significant differences between the active
and inactive group and correlations to PA level were found for mini-BESTest (P= 0.004, rs= 0.51) and modified
figure of eight test (P= 0.034, rs=
-0.35). No group differences were found for the other tests, however a
significant correlation was found between timed-up and go and PA level (rs=
-0.40). This study implies that clinical tests that target multidimensional and
dynamic abilities of balance control, such as mini-BESTest and modified figure
of eight, reflect more PA levels than single item or more static balance tests.
P22.15
Impact of
exercise on the motor and non-motor symptoms of Parkinson disease
Khashayar Dashtipour, Eric Johnson, Ehson Hadi, Erin
Whites, Mahmood Ghamsary, Jack Chen, Pejman Dalaie, Mana Manoukian
Loma Linda University
School of Medicine, Loma Linda, CA, USA
Objective:
To determine and compare the effects of
the two different exercise programs on the motor and non-motor symptoms of
Parkinson disease (PD).
Design/Methods: Nine patients with early-middle stage PD went through a prospective,
double-blind, randomized clinical trial to compare the effect of the training
BIG vs. one-to-one exercise program. Baseline evaluations of Unified
Parkinson’s Disease Rating Scale (UPDRS), Beck Depression Inventory (BDI), Beck
Anxiety Inventory (BAI) and Iowa Fatigue Scale (IFS) were taken before exercise
intervention. Both groups received 16 one-hour supervised exercise sessions; five
patients underwent one-to-one exercise while four underwent BIG therapy. Three
follow-up evaluations were performed at 1-3 month intervals. Wilcoxon rank-sum
testing was used to assess outcomes
based on changes in UPDRS, BDI, BAI, and IFS as compared to baseline.
Results: The combined cohort
demonstrated an average decrease from baseline across all scales at all
follow-ups, with statistical significance for UPDRS and BDI (p<.05). No
significant differences between the groups were detected, except for IFS, for
which exercise group showed a significant decrease from baseline at the final
evaluation (p=.02) while the group with BIG therapy had returned to baseline
after an initial, insignificant decrease.
Conclusions: This pilot study
showed the positive effect of exercise or BIG physical therapy on motor
and non-motor symptoms of patients with PD. Our study suggested that one-to-one
exercise could be as effective as BIG physical therapy on symptoms of PD.
P22.16
Digital
inclusion for telerehabilitation speech therapy in Parkinson’s disease
Alice Estevo Dias1,
João Carlos Papaterra Limongi2, Wu Tu Hsing3, Egberto
Reis Barbosa4
1,2,4Movement Disorders
Outpatient Clinic, Hospital of Clinics of School of Medicine, University of Sao
Paulo, Brazil
3Telemedicine of School
of Medicine, University of Sao Paulo, Brazil
Objective: The purpose of this study is to identify,
among the general population of PD patients, those who could be best candidates
for enrolling in a program of speech therapy telerehabilitation.
Methods: Fifty patients with diagnosis of PD
participated in the study. Forty-eight percent (n=24) were male, ages ranged
from 45 to 87 years old and all were in stages II to IV (Hoehn & Yahr). All
patients were treated with the Lee Silverman voice therapy and submitted to
voice intensity evaluation with VoxMetria 4.7 during the on phase both before
and after therapy. Patients were then asked to fill a questionnaire aimed to
evaluate technological competence regarding basic computer operations and
internet. Also, patients were asked to inform their impression about
conventional therapy and about the possibility of receiving similar treatment
at home using a computer connected to the internet.
Results: After speech therapy, an increase of 18
dBSPL in mean voice intensity was observed (pre and post treatment mean
intensity were 45 dB and 63 dB, respectively). All patients reported a positive
impression regarding the effectiveness of the speech therapy. Most patients
(76%, n=38) informed they would seriously consider receiving speech
telerehabilitation but only 10 out of these 38 patients reported basic
knowledge of computer and internet. From the other 12 patients who were not
willing to receive treatment at distance only two were familiar with computers.
There were no correlations between considering or not telerehabilitation and
sex, age or stage of the disease.
P22.17
Treatment effects of Attention Process Training for an
individual with Parkinson disease: A single-subject study
Neila J. Donovan, Kristen Ferguson, Brittan Barker, Paul
Hoffman
Louisiana State
University, Baton Rouge, LA, USA
Aim: Evidence finds ~70% of
individuals with PD demonstrate cognitive deficits (Cooper et al., 1991),
possibly due to dopamine depletion in the frontal-striatal circuitry
(Owen2004). However, no one has proposed clinical treatment. We investigated
whether Attention Process Training (APT; Sohlberg et al, 2001) could improve
attention in a person with PD, as it has in TBI survivors with frontal lobe
dysfunction (Sohlberg & Mateer1987).
Methods: This Phase I, multiple-baseline A1-B-A2-A3,
single-subject study measured change in percent accuracy and timed performance. The
university’s Institutional Review Board approved the
study. The participant, an independent,
college-educated, 79-year old female, with
self-reported attention problems, 7 years post-PD diagnosis, Hoehn & Yahr
stage 2.5, no apathy, depression or dementia, disabling hearing or vision loss,
received informed consent prior to the study's
start. Baseline, post-treatment and treatment withdrawal phases included 3
probes of attention components, attention and working memory testing. She
received APT (B phase)
120-minutes, once a week for 6 weeks (12 hours total). Treatment was
administered by second-year Master’s student (KF) APT trained by ND.
Results: We found large change in sustained attention
for both % accuracy (A1 to A2
d=5.196; A1 to A3
d = 13.279; A2 to A3
d=1.443) and timed performance (A1
to A2 d=2.951; A1 to
A3 d = 3.153; A2 to
A3 d=0.287), based on
single-subject effect size calculations (Busk & Serlin, 1992; Olive, 2005)
and Cohen’s (1988) effect size interpretation. Selective and Divided attention
also improved, but not as much or as consistently although though they were
untrained. Alternating attention did not improve.
Conclusion: APT led to large effects
when delivered at high intensity (120 minutes
per session) for six weeks. The treatment
effect carried over to 2 of 3 untrained attention components. We cannot generalize these findings, but have preliminary evidence
to continue this line of study.
P22.18
Introducing the Communicative Effectiveness Survey: an
objective measure of communicative participation for people with Parkinson’s
disease and dysarthria
Neila J. Donovan
Louisiana State
University, Baton Rouge, LA, USA
Objective: Up to 80% of people
with Parkinson’s disease (PD) eventually experience communication disorders.
People with communication deficits do not receive the same quality healthcare
as those without (Hoffman et al., 2005). Reduced healthcare utilization may
lead to isolation, depression, reduced independence and quality of life, and
increased caregiver and societal burden (Hoffman, et al., 2005; Parkinson's Disease Society,
2012). Patient Reported
Outcome (PRO) measurement is becoming widely accepted in healthcare (Fries, Bruce, & Cella, 2005). PRO developers use Item Response Theory
and Computer Adaptive Testing to develop precise and efficient measures that
reduce burden for testers and respondents leading to increased cost
effectiveness. This study aims to
investigate the content and construct validity of the 24-item Communicative Effectiveness Survey (CES)
for people with PD using an IRT methodology–Rasch analysis.
Methods: Prospective, validation study, between-group, approved by the
university’s Institutional Review Board, informed consent obtained. 123 participants 65 to
89 years old (63 NO PD, 60 PD) participated based on the inclusion criteria: no
active or prior neurological disorders; hearing and vision within functional
limits; passed cognitive, apathy, and depression screenings; PD group only:
stable on medications, Hoehn & Yahr ratings and Dysarthria Severity Ratings
1-4.
Results: The CES represented a unidimensional construct and adequate item local
independence to perform a partial credit model Rasch analysis. Item-level
psychometric properties were strong: participants used all four units of the
rating scale reliably; item difficulty matched person ability well; a strong,
significant relationship existed between an a priori item difficulty and the actual item hierarchy (rs =
.96, df = 25, p < .01). Three misfitting items were eliminated; no floor or ceiling effect. PD
group mean (M=71.93, SEM=13.65) was significantly lower than the NOPD group mean (M=85.794, SEM=11.12)
[t(121)= -6.187, p < .001]. Clinical and research implications
will be discussed.
P22.19
A study of the effect of a one year community-based group
exercise program for people with Parkinson’s disease in Mumbai, India: A
quasi-experimental design.
Nicole D’souza1, Anjali S1, Komal
Parikh Sanghavi1, Maria Barretto1
1Parkinson’s Disease
and Movement Disorder Society, Mumbai, India
Objective: The Parkinson’s
Disease and Movement Disorder Society conducts group therapy sessions where
patients at different stages of the disease (Hoehn and Yahr stages 1 to 4)
exercise together at a community centre under the supervision of a
physiotherapist. This study aimed to investigate the effects of participation
in such an exercise program in people with Parkinson’s disease (PD) after a
duration of 1 year.
Methods: Unified Parkinson’s
Disease Rating Scale (UPDRS) was administered to 50 people with PD at baseline.
Group therapy sessions were conducted once weekly for PD patients who
voluntarily participated in the program which consisted of exercises aimed at
improving posture, range of motion, strength, balance and gait. Those
participants who attended at least 45 of the 48 session were allocated to Group
A (cases) and those who didn’t attend more than 2 of the 48 sessions were
allocated to Group B (controls). UPDRS was administered at the end of 1 year to
all patients in Group A and B.
Results: At baseline, there
was no statistically significant difference between the mean scores of Group A
and Group B (U=163.5, NA=20, NB=19,P= 0.456) however at
the end of 1 year the mean score of Group B was significantly higher than Group
A indicating greater progression of the disease in patients in Group B (U=79.0,
NA=20, NB=19, P<0.05). There was a statistically
significant difference between the pre and post UPDRS scores for Group B (NB=19,
Z= -3.724, P<0.001) while there was no statistically significant difference
between the scores for Group A (NA=20, Z= -1.169, P=0.243)
indicating the effectiveness of the exercise program in retarding the
progression of the disease.
P22.20
Balance differences between
people with and without freezing of gait in Parkinson disease
Ryan P. Duncan1,
Abigail L. Leddy2, MSCI, James T. Cavanaugh, , Leland E. Dibble4,
Terry D. Ellis5, K. Bo Foreman4, Matthew P. Ford6,
and Gammon M. Earhart1
1Washington
University, Saint Louis, MO, USA
2Rehabilitation
Institute of Chicago, Chicago, IL, USA
3University
of New England, Portland, ME, USA
4University
of Utah, Salt Lake City, UT, USA
5Boston
University, Boston, MA, USA
6University
of Alabama at Birmingham, Birmingham, AL, USA
Objective: To
determine whether balance impairments differ between groups of people with PD
who either have or do not have a history of freezing of gait (FOG), taking into
account differences in disease severity, disease duration and age. Balance was
assessed using the Balance Evaluation Systems Test (BESTest) total and section
scores, Mini-BESTest total score, and Berg Balance Scale (BBS) total score.
Methods: Balance of
78 participants (58% male; mean age ± SD = 68.1 ± 9.3 years; H&Y frequency
(stage(n)): I(5), II(30), II.5(28), III(8), IV(7)) with PD was assessed using
the BESTest, Mini-BESTest, and the BBS. Participants completed the FOG
Questionnaire; those reporting a score greater than one on item three were
classified as freezers. The Movement Disorder Society-Unified Parkinson Disease
Rating Scale subsection III (MDS-UPDRS III) was administered to measure motor
symptom severity. Analyses of covariance were used to determine differences
between freezers and non-freezers in BESTest total and section scores,
Mini-BESTest total score, and BBS total score, using a PD severity composite
score (MDS-UPDRS III score, years since diagnosis, and age) as a covariate
(α=0.05).
Results: Thirty-two
(41.0%) participants were classified as freezers. After accounting for disease
severity and duration as well as age, freezers had significantly lower BESTest
(F(1,76)=7.33; p=0.008) and Mini-BESTest (F(1,76)=12.26; p=0.001) total scores
compared to non-freezers. There were no differences in BBS scores for freezers
compared to non-freezers (p=0.27). With respect to the individual BESTest
sections, freezers had significantly lower scores on sections IV (postural
responses) (F (1,76)=14.39; p<0.001) and VI (stability in gait)
(F(1,76)=9.16; p=0.003) than non-freezers. In conclusion, regardless of motor
symptom severity, years since diagnosis, and age, freezers had more severe
balance impairment than non-freezers as measured by the BESTest and
Mini-BESTest. Physical therapists should consider addressing postural response
and stability in gait problems in PD patients with FOG.
P22.21
Benefits of
task-specific learning-principled practice to improve freezing of gait for
individuals with Parkinson disease in a small group community setting: a case series study
1,2Becky G. Farley; 1Kristin
M. Hamilton, 1Alicia B. Messer, 2Krystal
Greene, 1Lucinda
Rankin
1Physiology, University of Arizona, Tucson, AZ, USA
2PWR! Gym, Tucson, AZ, USA
Objective: Freezing of gait (FOG) is one of the most
disabling symptoms of advanced stage PD and is associated with frequent falls
and reduced quality of life (QoL). Researchers and clinicians define FOG as: An
episodic inability to generate effective stepping….most commonly experienced
during turning and step initiation, but also when faced with spatial and time
constraints, stress, and distraction. Despite the multifactorial nature of FOG,
task-specific training has not yet been applied to counteract the multiple
motor/cognitive/emotional triggers that lower threshold for the occurrence of
FOG and that may interact and deteriorate synergistically. In addition,
learning principles of practice have not been applied to task specific
“antifreeze” exercises. Instead, more general gait and balance training with
attentional strategies and external cues are typically used to circumvent
freezing episodes.
Methods: In this case series study, we investigated
the effects of a task-specific learning principled approach that targeted each
person’s unique “triggers” directly. In addition to specificity of training,
other learning principles were integrated into the program including: feedback,
intensity through high effort and dosage (5 days; 3 hours/day), and progressive
difficulty by manipulating environment, balance requirements, distractors, and
variability of practice. Attentional strategies and external cues were
integrated to enhance learning by allowing for greater success during the
practice of complex multitasking conditions. The study was held in a community
setting with a small group “boot camp” approach to take advantage of
social/emotional interactions shown to impact learning and quality of life.
Results: 5/6 S’s showed improvement in the FOG
questionnaire and objective measures including dual tasking conditions. These improvements
were related to QoL for 4/5 S’s. One subject with mild FOG did not show
improvement on any FOG outcomes. We will report on the trends across 6
individuals and discuss the implication to future studies and real world
implementation.
P22.22
Mobility training with popular music in persons with
Parkinson disease
Matthew Ford1,2, Alison Barnard1,
Laurie Malone2, Marion Haase1
1Department of Physical
Therapy, University of Alabama at Birmingham, Birmingham, AL, USA
2Department of Research
and Education, Lakeshore Foundation, Homewood, AL, USA
Objective: To study the effects
of walking with music on the walking parameters of people with Parkinson
disease (PD).
Methods: 35 persons with PD
were recruited to participate in this study. Participants were stratified
according to walking speed (< 0.8 m/s; 0.8 – 1.1 m/s; > 1.1 m/s) and
randomized to one of three training groups. Group 1 walked at a comfortable
pace without music. Group 2 trained with popular music that matched their
comfortable walking cadence, measured at baseline. Group 3 trained with popular
music that was progressively increased. Training progression in Group 3 was
determined by regularly (3 times/session) assessing the changes in walking
speed, stride length, and cadence in response to increasing the training rate.
Training consisted of walking for 30 min/session, 3 sessions/week for 6 weeks.
Results: According to
preliminary data, subjects from group 1 (n = 5) had a mean
decrease in cadence of 0.99steps/min (SD=7.82), group 2 (n = 6) had
a mean decrease of 3.52steps/min (SD=4.7), and group 3 (n = 5) had a mean
increase of 2.47 steps/min (SD = 7.33). Average stride length for group 1
decreased by 0.01m (SD= 0.06), group 2 increased by 0.05m (SD=0.12), and group
3 increased by 0.05m (SD=0.08). Mean speed gains were 10.02m/min (SD=0.11) for
group 1, 0.01m/min (SD=0.14) for group 2, and for group 3 it was 0.08m/min
(SD=0.12). The between-group and within-group differences were not found to be
significant for walking parameters due to the small sample size. Baseline PDQ-39 scores for group 2 is significantly
different from group 3 (difference = 22.69, p=0.0236) and resulted in a
significant decrease by -5.58 points (95% CI -10.94, -0.23).
P22.23
Fusion training: the effects of combined strength and
aerobic training on persons with Parkinson disease
Marcas Bamman1, C Scott Bickel1,
Laura Lieb1, David Standaert1, Craig Tuggle1,
Matthew P Ford1
1The University of
Alabama at Birmingham, Birmingham, AL, USA
Objective: The objective of this study was to examine
the effects of an exercise program on strength, aerobic capacity, and fatigue
in persons with idiopathic Parkinson disease (PD).
Methods: 12 persons PD (Hoehn and Yahr II – III; mean
= 2.4) to date have participated in a 16 week exercise program at the UAB
Center for Exercise Medicine. Participants were screened by a movement disorder
specialist in order to confirm a diagnosis of PD. One rep max was used to
assess strength, Peak VO2 for
aerobic capacity, and Fatigue Severity Scale (FSS) for fatigue. Participants
trained 3x/wk (M,W,F) with a personal trainer. Fusion training (FuT) consisted
of a combination of exercises that challenges strength, power, balance, and
endurance. Exercise sessions consisted of: (i) five movements to improve
strength and muscle mass (leg press, knee extension, chest press, overhead
press, pull down), each performed for 3 sets of 8-12 repetitions (~30 total
repetitions); (ii) trunk exercises to improve postural stability (trunk
extension and flexion); and (iii) 3-4 bodyweight exercises (selected from a
menu) to improve power and balance (e.g., step up, squat, jump squat, lunge,
side lunge, push-up, assisted pull-up, assisted dip). Heart rate (HR) was
monitored during training with participants maintaining a minimum of 50% heart
rate reserve (HRR). Wilcoxon Signed Ranks Test were used to assess the
differences in strength, aerobic capacity, and fatigue before and after
training.
Results: Analyses revealed statistically significant
improvements in bench press, leg press, shoulder press, and leg extension
strength after 16 weeks of training, however there were not improvements in
aerobic capacity. Participants did perceive that their fatigue was less (FSS; p
< .02) after 16 weeks of training.
P22.24
Intensive rehabilitation treatment improves sleep quality
in Parkinson’s disease
Giuseppe Frazzitta1,
Roberto Maestri2, Giulio Riboldazzi.3, Gabriella Bertotti
4, Gianni Pezzoli 5, Maria Felice Ghilardi 6
1Department of Parkinson Disease Rehabilitation,
“Moriggia-Pelascini” Hospital, Gravedona ed Uniti, and Fondazione Europea
Ricerca Biomedica FERB, “S.Isidoro” Hospital, Trescore Balneario, Italy
2Department of Biomedical Engineering, Scientific Institute
of Montescano, S. Maugeri Foundation IRCCS, Montescano, Italy
3Center for Parkinson’s Disease, Macchi Foundation,
Varese and Department of Rehabilitation, “Le Terrazze” Hospital, Cunardo, Italy
4Department of Neurorehabilitation, Scientific Institute
of Montescano, S. Maugeri Foundation IRCCS, Montescano, Italy
5Parkinson Institute, Istituti Clinici di Perfezionamento,
Milano, Italy
6Department of Physiology and Pharmacology, CUNY
Medical School, New York, NY, USA
Objectives: Sleep disturbances are among the most common
non-motor symptoms of Parkinson’s disease (PD). Pharmacological treatments have not been satisfactory because of side effects and
interactions with antiPD drugs. While studies in
normally aging subjects with sleep complaints have shown that regular exercise
improves sleep quality, there is no such evidence in patients with PD. Here
we explore whether an intense physical exercise program improves sleep quality
in a large group of patients with PD and sleep complaints.
Methods: PD Sleep Scale (PDSS, a 15-question visual analogue scale evaluating sleep quality,
nocturnal psychosis, nocturia, nocturnal sensory-motor symptoms, daytime
somnolence) was
administered twice, 28 days apart, to two groups of patients with PD (Hoehn and
Yahr stage 3) of comparable age, gender,
disease duration
and pharmacological treatment. UPDRS III scores were measured at the same
times. The control group (50 patients) did not receive rehabilitation
treatment. The treated group (100 patients) underwent a 28-day intensive
rehabilitation program (three one-hour daily sessions comprising cardiovascular warm-up, relaxation, muscle-stretching,
balance and gait training with stabilometric platform and treadmill,
occupational therapy to improve daily living activities).
Results: At enrolment, control
and treated groups had similar UPDRS III scores, PDSS scores and profiles. At
re-test, 28 days later, UPDRS scores significantly improved in the treated
(p<0.0001), but not in the control group (p=0.23). Similarly, the total PDSS
scores improved in the treated group (p=0.0001), but not in the control group
(p=0.32). In particular, the treated group showed significant improvement in
the PDSS scores for sleep quality, motor symptoms
and day-time somnolence, but not for psychosis and nocturia. The control group
did not show improvement in any of the items. These results suggest that
intensive rehabilitation treatment may have a positive effect on sleep quality,
nocturnal motor symptoms and day-time somnolence in patients with PD.
P22.25
An acoustic and perceptual investigation of speech and
voice in Parkinson’s and in depression
Erica G. Teixeira, David Howard, Suzanne Moffatt, Nick
Miller
Newcastle University,
Newcastle, UK
Objective: Most people with Parkinson’s experience
changes in their speech and voice. The purpose of this study was to establish
why people with Parkinson’s sound depressed when they are not.
Methods: Participants were 30 people with Parkinson’s
and no depression, 30 with Parkinson’s and depression; 18 with depression
without Parkinson’s, 30 without Parkinson’s or depression. Speech and voice
samples were acquired employing standard clinical tasks: reading a passage,
monologue, sustained vowel, diadochokinetic repetitions (DDK). Based on these
acoustic and auditory perceptual measures were derived: speech and articulation
rate, pause number and duration, mean fundamental frequency (F0) and
variability, mean intensity and variability, duration of sustained vowel, and DDK
rate; loudness/pitch level and consistency, rate of speech and voice quality.
Sixty-six listeners transcribed low-predictability sentences to gain a measure
of intelligibility.
Results:
Three
blind speech-language pathologists judged the groups with Parkinson’s as
significantly more ‘depressed’ than the groups without Parkinson’s, with the
group with Parkinson’s and depression perceived as significantly more
‘depressed’ than the others. Based on acoustic analyses, pause duration in
reading was significantly longer in both groups with Parkinson’s compared to
those without. For the perceptual analyses, significant reduced loudness level
and loudness/pitch consistency during reading and monologue tasks was reported
for both groups with Parkinson’s compared to the groups without Parkinson’s.
Regarding intelligibility people with Parkinson’s produced significantly more
impaired speech than those without, with those with Parkinson’s and depression
being most impaired. No differences were found for both groups with Parkinson’s
according to Hoehn and Yahr stage and disease duration. These findings suggest
that people with Parkinson’s sound depressed because their speech features do
not differ significantly from people with depression, whereas on these key
elements they do differ from people without Parkinson’s or depression. Some
features of speech and voice are uniquely linked to depression.
P22.26
The efficacy of a group exercise program using large
amplitude movements and functional activity training on improving mobility and
quality of life in older adults with Parkinson’s disease
Karla Gallagher1,
Sarah Monsees1, Sara Klooster1, Ryan Rhodes1
Sandra Hundza1
1University of Victoria, BC, Canada
Objective: The effect of an exercise program using large amplitude movement and
functional mobility training in those with Parkinson’s disease (PD) has not
been evaluated when delivered in a group delivery format or in an older adult
population (i.e. average age 80 years). The purpose of this study was,
therefore, to determine if an eight week biweekly group exercise program using
large amplitude movement and functional mobility training was effective at
improving mobility and quality of life in old, older adults with PD. To determine the long term training effects of the program, a follow up
assessment was conducted at four months post intervention.
Methods: 20
participants with PD were recruited through a hospital-based Seniors Outpatient
Clinic. Participants were assessed before starting (PRE) and upon completion
(POST) of the intervention. To decrease the likelihood that the results would
be affected by day-to-day fluctuations in mobility, 3 measures were gathered at
both PRE and POST. A single follow-up assessment was conducted four months
after completion. Outcome measures included: MDS-Unified Parkinson’s Disease
Rating Scale-Part III, Timed Up and Go, Berg Balance Scale, Chair Stand Test,
Gait characteristics (GaitRite system), Parkinson’s Disease Questionnaire – 39
and Goal Attainment Scale. Data was analyzed using repeated measures ANOVA and
paired dependent t-tests.
Results: Results
indicate significant improvements (p<0.05) in all measures of physical function (effect sizes
(ES) ranging from 0.33-0.88), QOL (mobility dimension, ES=0.35) and personal
goal achievement (ES=3.0). Results
of four month follow up
assessments are pending.
Conclusion: This group exercise
program model was very effective in improving mobility and QOL for an older
adult population with PD, while being cost effective to deliver. Further the program frequency and duration made it manageable for our
population to attend as well provide adequate duration to achieve desired
training effects.
P22.27
Correlations between
performance-based balance
measurement, self-report
balance confidence and freezing of gait in people with Parkinson’s disease
Rebecca A. Gruber1,2, Lorena R. S. Almeida3, Jan Goldstein Elman1,2, Nádja Negreiros3,
Guilherme Valença3, Elen Beatriz-Pinto4, Jamary
Oliveira-Filho4
1One Step Ahead Mobility Physiotherapy, Toronto,
Ontario, Canada
2University of Toronto, Toronto, ON, Canada
3Movement Disorders Clinic,
State of Bahia Centre for the Elderly Health Attention – CREASI/SESAB, Salvador,
Bahia, Brazil
4Stroke Clinic, Federal University of Bahia, Salvador, Bahia,
Brazil
Objective: To analyze patients with Parkinson’s disease (PD) scores on a
performance-based balance measure and on a measure of self-perceived balance
confidence; and to identify their correlation with freezing of gait.
Methods: One hundred and three subjects in two countries
were included in this study. Besides demographics and clinical data, patients
were assessed with the Freezing of Gait Questionnaire (FOG-Q), Berg Balance
Scale (BBS) and Activities-Specific Balance
Confidence Scale (ABC). Subjects were classified as freezers if they scored one
or more on the FOG-Q, item three.
Results: The sample had a median age of 70 years. Forty-one
(39.8%) subjects were classified as freezers. Median score on BBS for freezers
was 51 (46;54); for nonfreezers was 53 (51;56) (p=0.014). Median score on ABC
for freezers was 60 (31.87;82.19); for nonfreezers was 75.94 (49.22;93.12)
(p=0.017). BBS and ABC total scores showed moderate correlation with FOG-Q
(r=-0.44; r=-0.45; respectively) (p<0.001). All BBS tasks, except sitting
unsupported,
standing with eyes closed/feet together, were significantly correlated with
FOG-Q (range from r=-0.22 to -0.42; p≤0.025). All ABC tasks were
significantly correlated with FOG-Q (range from r=-0.23 to -0.5; p≤0.019).
For individual items on the two scales, 7/14 on the BBS and 13/16 on the ABC
were moderately correlated with FOG-Q (r≥-0.3).
Conclusions: Although both the BBS and ABC scores correlated
with FOG-Q, critical analysis reveals important differences between these
scales. Total BBS scores were high even for freezers, and fewer individual
items correlated moderately with FOG-Q scores. Total ABC scores were lower
among freezers, and a majority of individual items correlated moderately with
FOG-Q. This suggests that the ABC may be a more valid and informative measure
in freezers and nonfreezers. This is likely related to the different constructs
measured in the two scales (balance and fear of falling) and the measurement
method (performance and self-report).
P22.28
Influence
of multimodal therapies on life quality and motor performance in Parkinson’s
disease
M. Hahne
1, D. Hartmann1, E. Rudbach1, B. Griewing1,
H. Reichmann2 W. Jost 3
1Clinic of Neurology Bad Neustadt, 2Clinic
of Neurology, University Dresden 3Parkinson’ Disease Center Wolfach,
Germany
Objective: Evaluation of a 3 to
4 week hospital multimodal complexe treatment in Parkinson’s disease (PD).
Outcome parameters: Motor performance and life quality.
Methods: 35 patients with PD
were treated during 3 weeks by daily visits of a neurologist, by physiotherapy,
ergotherapy, speech therapy and physical therapy. UPDRS, CGI and PDQ 39 were
asessed before and after 3 weeks. Outcome was expressed in terms of mean value,
standard deviation und percent changement. We divided in 2 groups: Group A with
L-dopa equivalent (LED) changement lower 50 mg and group B more than 50 mg LED.
Age, PD duration and severity were similar in both groups.
Results: UPDRS III was reduced
from 36,2 ±11,3 to 29,1 ±10,3 pts according 7,1 pts in all patients. In group A
the reduction was 7,1 pts, in group B
6,9 pts. CGI was estimated as 2,4 ±.0.6 in all. PDQ 39 was improved from
41,7 ±16,3 to 32 ±15,9 by 9,3 PDQ according 21,3% in all. Group A: From 42,9
±13,4 to 31,9 ±15,9 according 11 PDQ or 25,6%. Group B: From 41,8 ±18,6 to 33,1
±15,4 according 9,7 PDQ or 20,1 %. We observed amelioration higher than 20% wihin
the subscores mobility, emotional wellbeing, stigma and bodily discomfort. No
significant differences were found in the above mentioned groups with different
amount of LED. Our results demonstrate a clear clinical benefit according the
minimal clinical important changes (MCIC) in motor outcome and life quality for
PD treated by a multimodal hospital therapy over 3 weeks. Interestingly we
could not observe significant differences concerning UPDRS and PDQ 39 with
different LED in our 2 groups.
P22.29
The impact of high
intensity exercise on outcome in people with Parkinson’s disease: A systematic
review
David Hegarty1, David Mockler1,
Emma Stokes1, Rose Galvin2
1Trinity Centre for
Health Sciences, St James’s Hospital, Dublin 8, Republic of Ireland
2HRB Centre for Primary Care Research, Dublin 2,
Republic of Ireland
Objective: The objective of this systematic review with
meta-analysis is to examine the effectiveness of high intensity exercise therapy
when compared to conventional therapy on functional outcome in people with PD.
Methods: A systematic literature search was performed
to identify all studies that met the inclusion criteria: (a) study design;
randomised controlled trials (RCTs), (b) population; individuals with PD, (c)
intervention; high intensity exercises (as defined by the individual study),
(d) comparison; conventional exercises or sham/no intervention, (e) outcome;
measures of impairment, activity or participation. Two reviewers independently
assessed the risk of bias of each study against Cochrane criteria. Cochrane
Review Manager Software was used to conduct statistical analyses to determine
the treatment effect.
Results: A total of 3,155 records were identified and
9 RCTs were included, ranging in size from ten to 44 participants. The RCTs
delivered the intervention using a variety of modalities including resistance,
eccentric, treadmill and cycling training. Duration of interventions ranged
from 8 weeks to 4 months. The frequency and duration of sessions also varied.
Overall, the methodological quality of the studies was unclear. Preliminary
results from the meta-analysis indicate that high intensity exercises have a
significant favourable impact on gait speed [SMD -0.66, 95% CI -1.07- -0.26, I2=0%]
and no significant difference on motor impairment [Unified Parkinson’s disease
rating scale (UPDRS) – motor subsection; -7.75, 95% CI -18.21- 2.71, I2=84%] when compared to
conventional therapy.
Conclusion:
This
systematic review shows high intensity exercise significantly improves levels
of activity limitation in people with PD when compared to conventional therapy.
However, there is no significant change in motor impairment despite promising
results in some studies. More research is needed to clarify the frequency,
intensity and timing of high intensity exercise, in order to optimise the
chance of motor impairment improvements using standard outcome measures.
P22.30
Patients with Parkinson’s disease: their working capacity
and employment in Sweden
Linda Hou
Department of Rehabilitations Medicine, the Sahlgrenska Hospital,
Gothenburg University, Gothenburg, Sweden
Objective: The aim of the present study is to investigate the
working capacity and employment of patients with Parkinson’s disease in
southwest Sweden in order to obtain knowledge and to set up relevant
management of multidisciplinary rehabilitation in the future.
Methods: The data were obtained with a postal
survey questionnaire answered by 264 patients, aged from 42 to 67 years old.
The patients were identified and confirmed to have a diagnosis of idiopathic
Parkinson’s disease. A comparison of years lost in working time was performed
between patients with Parkinson’s disease and a population without diseases.
Ethical approval was obtained from the local ethical committee. All patients
received information leaflets.
Results: 53% of the patients
have reduced working time the same year when they received the diagnosis, some
of the patients had already a part time work before they get their diagnosis. A
further 19% of the patients reduced their working time one year after the
diagnosis. Only a few patients had only temporarily decreased working time
after the diagnosis. These patients were satisfied with their medication. The
most disabled symptoms were hyperkinesi, tremor and stress sensitivity. About
40% patients have psychological symptoms (depression, anxiety and sleep
disturbance). The high sickness absence causes a significant socioeconomic
burden. This study shows that most of the patients reduced their working time
immediately or one year after the diagnosis, which could be correlated with
that only a few of the patients had received help from a professional
rehabilitation team.
P22.31
AmbuloSono: A sensorimotor contingent
musical walking program for Parkinson’s disease rehabilitation
Bin Hu1,
Alexandra Cihal1, Terry Clark1, Nicole
Meyer1, Kailie Luan1, Ranjit
Ranawaya2, Taylor Chomiak1
1DCN and
Hotchkiss Brain Institute and University of Calgary, Calgary, AB, Canada
2Movement
Disorders Clinic-Alberta Health Services, Calgary, AB, Canada
Objective: Postural
instability and gait disorder are important hallmarks of PD progression. They
are often associated with non-motor symptoms, such as fear of falling, anxiety,
depression and excessive avoidance of physical and social activities. Our aim
is to develop a reward and behavioural reinforcement-based music walking
program that can help patients in gaining automatic gait control while
transforming naturalistic walking into a pleasurable habit of daily activity
and exercise.
Methods:
Ambulosono program utilizes GaitRminder iPod application to create a
contingency between walking step size and musical cues enriched with rhythm,
vocal singing and uplifting emotional salience. We recruited 46 patients,
including those living in rural areas with no rehabilitation services. After
giving formal written consent and a baseline screening test, patients were
instructed to utilize the walk kit at home for regular exercise. The weekly
target of walking time was set from 60 to 350 minutes. Their walking data was
automatically sent to a central server for daily analysis and monitoring.
Results:
Participants of Ambulosono can undertake large step walking over long distance
with the walking time and speed regularly approached or surpassed the NIH
guidelines. Significant improvements were also reported in terms of gait
awareness and the amplitude of arm swings during walking. More importantly, a
sub-group of subjects reported a marked reduction in fear of falling and
increase in confidence. Our pilot study suggests that Ambulosono is an
effective behavioural training paradigm that can improve multiple domains of
motor and non-motor function for patients living with Parkinson's disease.
Acknowledgments: CIHR,
Parkinson Alberta Society, the Movement Disorders Clinic-Alberta Health
Services, Markin Undergraduate Student Research Program, and Branch Out
Neurological Foundation.
P22.32
Using the SpeechVive to treat speech impairments in Parkinson’s
disease
Jessica E. Huber1, Elaine T. Stathopoulos2,
Joan E. Sussman2, Sandy Snyder1, Kelly Richardson2
1Purdue University,
Department of Speech, Language, and Hearing Sciences, West Lafayette, IN, USA
2University of Buffalo,
Department of Communicative Disorders and Sciences, Buffalo, NY, USA
Objective: The purpose of this study was to examine the
effectiveness of the SpeechVive device for improving speech production in
individuals with Parkinson’s disease.
Method: Forty-five patients with Parkinson’s disease
were enrolled in the study. Thirty-nine completed the study. Patients were, on
average, 67 years old and had been diagnosed for 8.7 years. Speech and motor
impairments ranged from mild to severe but were most often rated as moderate.
Patients were assessed before and after an 8-week treatment period during which
they wore the SpeechVive device for 2-8 hours per day. The SpeechVive device
was developed at Purdue University and plays multi-talker babble noise in one
of the patient’s ears while they are talking. The noise induces the Lombard
effect, a reflex to talk louder and clearer in the presence of noise. Patients
were also assessed 4 weeks after treatment had ended to assess detraining. Half
of the patients were assessed for an 8-week no-treatment period prior to
treatment.
Results: There were no significant changes in sound
pressure level (measure of vocal intensity/loudness), length of utterance, or
speech rate during the no-treatment period. Ten of the patients demonstrated a
decrease in sound pressure level after treatment, potentially due to
disease-related changes. These subjects were not included in the statistical
analysis, leaving a sample size of twenty-nine. Sound pressure level was
significantly higher after treatment and remained significantly higher after
the detraining period. Ratings of communicative effectiveness by patients and
their caregivers were significantly higher after treatment. Speech rate
declined across the treatment period and was significantly lower by the end of
the detraining period, as compared to pre-treatment.
Conclusions: The SpeechVive was demonstrated to
significantly improve vocal intensity and communicative effectiveness in a
group of patients with Parkinson’s disease.
Note: A portion of
this data (subset of the subjects and measures) was presented at the Speech
Motor Control Conference in 2012.
P22.33
Rehabilitation using blowgun in patients with Parkinson’s
disease
Noriko Kawashima1, Sayaka Matsunaga1, Takeshi Watanabe1,
Aya Kumon2, Emiko
Horiuchi2, Teruo Yokoyama2, Kazuko Hasegawa2
1Kawashima Neurology Clinic, Fujisawa, Kanagawa, Japan
2Department of Neurology, Sagamihara
National Hospital, Sagamihara, Kanagawa, Japan
Objective: To
evaluate the effects of rehabilitation using the blowgun in patients with
Parkinson's disease (PD). Pneumonia is the important complication in the
patients with advanced PD. Maintenance of lung volume and breath holding might
make effective coughs and prevent patients with PD from pneumonia.
Methods: We
conducted rehabilitation using blowgun according to the Japan Sports Fukiya
Association once a week. Patients with PD were evaluated about the Unified PD
rating scale (UPDRS), pulmonary function test, Geriatric Depression Scale (GDS)
and EuroQoL (EQ-5D) before and 3, 6 and 9 months after the intervention. We
applied the formula of Japanese lung age using height and forced expiratory
volume 1.0 (FEV1.0), and evaluated peak expiratory flow (PEF).
Statistical analyses were
performed by Wilcoxon signed-rank test.
Results: Fourteen patients (male 9) were included. The mean age and disease
duration were 74.3 years and 7.3 years. Before the intervention, the mean
modified Hoehn and Yahr was 2.6 on time / 3.2 off time and 8 patients had
wearing off. The mean total UPDRS score was 33.9 on time (male 43.3, female
23.0). The lung age was older than real age + 5.93 years (male +15.87, female
-5.17) and the mean PEF was 4.50 L/sec (male 4.65, female 4.29). The mean GDS
and EQ-5D were 12.7 and 3.8. The male lung age became younger 3 months after
the intervention than before (from +15.87 to 10.75; p=0.027). PEF in total and male increased at 6 and 9 months
significantly from 4.50 to 5.35 (p=0.008),
5.23 (p=0.041); from 4.65 to 4.84 (p=0.036), 4.35 (p=0.036). The total UPDRS on time, GDS and EQ-5D did not change. However speech and posture (sub-scores of UPDRS) improved at 6 and 9 months
significantly. The rehabilitation using blowgun is effective to improve PEF, speech and
posture in patients with PD.
P22.34
European physiotherapy guidelines for people with
Parkinson’s disease
Samyra
H.J. Keus1, Marten Munneke1, Mariella Graziano2,
Jaana Paltamaa3, Elisa Pelosin4, Josefa Domingos5,
Susanne Brühlmann6, Bhanu Ramaswamy7, Jan Prins8,
Chris Struiksma9, Alice Nieuwboer10, Bastiaan R. Bloem1
1ParkinsonNet,
Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
2Association
Luxembourgeoise des Kinésithérapeutes, Luxembourg, Luxembourg
3Finnish Association of
Physiotherapists / JAMK University, Jyväskylä,
Finland
4Associazone
Italiana Fisioterapisti / University of Genoa, Rome / Genoa, Italy
5Associacão
Portuguesa de Fisioterapeutas, S.
Domingos de Rana, Portugal
6Physioswiss,
Sursee, Switzerland
7Chartered
Society of Physiotherapy, London, United Kingdom
8Patient
representative, Utrecht, the Netherlands
9Dutch
Parkinson Association, Bunnik, the Netherlands
10Katholieke
Universiteit Leuven, Belgium
Objective: We aimed to develop the 1st European physiotherapy guideline for
Parkinson’s disease, which can be used in any country but also be tailored to
country specific possibilities and constraints (e.g. concerning healthcare
organisation). The
2004 Parkinson’s guideline of the Royal Dutch society for Physical Therapy1
(KNGF) is unique in its field, but
needed an update. Members of the Association of Physiotherapists in Parkinson’s
disease Europe (APPDE) had expressed their preferences to update and adapt the
KNGF guideline into a collaborative European guideline.
Methods: Initiated by the KNGF and ParkinsonNet2, 19 member organisations of the European
Region of the World Confederation for Physical Therapy (ER-WCPT) collaborated
to develop the guideline according to international standards (e.g. AGREE and
GRADE). First, barriers in delivering optimal
care were identified, e.g. though a survey in which over 3,000 physiotherapists
throughout Europe participated. These were transformed into key questions for
which conclusions were drafted based on systematic literature search. Other
considerations to the conclusions (e.g. on availability) were collected, to
finally create the recommendations. A panel of the European Section of the MDS
was involved to develop MDS-supported referral criteria. Patients (e.g. through
the European Parkinson ’s Disease Association, EPDA) were involved at all
stages of the development process.
Results: Through a unique collaboration of 19 national professional
physiotherapy organisations, we have developed the 1st European
physiotherapy guideline for Parkinson’s disease. It is available for free in
English and Dutch (more languages to follow) at www.ParkinsonNet.nl/guidelines.
The guideline provides decision support towards evidence-based, patient-centred
care. Currently, several countries have started its implementation. At the MDS
Congress 2012, the main recommendations of the guideline will be presented.
References: 1Keus SH et al. Mov Disord 2007;22(4):451-460; 2Munneke M et al, Lancet Neurol,
2010;1:46-54
P22.35
A comprehensive dance-based movement program improves
mobility in Parkinson’s disease
N. Krishnamurthi1,2, C. Murphey3,
and E. Driver-Dunckley4
1Muhammad Ali Parkinson Center, Barrow
Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ,
USA
2Center for Adaptive Neural Systems,
Arizona State University, Tempe, AZ, USA
3School of Film, Dance, and Theater,
Arizona State University, Tempe, AZ, USA
4Department of Neurology, Mayo Clinic,
Scottsdale, AZ, USA
Objective: Mobility in Parkinson’s disease (PD) is
restricted due to impairments in gait, balance, and rigidity. Generally in PD,
balance and gait difficulties do not respond to pharmacological and surgical
treatments resulting in decreased independence and increased risk of falls.
Recently, application of dance training and practice of large and faster
movements has been shown to be beneficial in PD. This research study examined
the effects of a new comprehensive dance-based Movement and Motion (M&M)
training program created by one of the authors (CM), on mobility in people with
PD.
Methods: Nineteen subjects (11 females and 8 males;
mean age: 66.7 ± 7.2 years; range 55 – 80 years) with mild to moderate PD were
recruited to participate in the 10-week M&M training (two 1-hour sessions
per week) of which 15 subjects completed the study successfully. Several
quantitative gait, balance control, and range of motion indices and clinical
scores were obtained pre- and post-training to investigate the effects of M&M
training. Gait indices were obtained during overground walking, balance control
parameters were calculated from dynamic weight shifts tasks, and range of
motion were obtained from different joints. Non-parametric Wilcoxon signed rank
test was used to compare the changes in the above mentioned indices due to the
training and changes were considered significant at p ≤ 0.05.
Results:
Gait
velocity, stride length, double support and stance duration, degree of arm
swing, and turning parameters improved after training. Regarding posture
measures, the time taken to initiate movement shifts and to reach targets
decreased significantly due to training. Also, range of motion at many joints
increased significantly. These results suggest that the comprehensive M&M
training can be utilized to improve mobility by improving gait, balance
control, and range of motion which can subsequently lead to improved quality of
life in people with PD.
P22.36
Effects of polestriding training on gait in
Parkinson’s disease
N. Krishnamurthi1,2, H. A. Shill3,
D. O’Donnell1, A. Lieberman1, P. Mahant4, J.
Samanta4, and J.J. Abbas2
1Muhammad Ali Parkinson Center, Barrow
Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ,
USA
2Center for Adaptive Neural Systems,
Arizona State University, Tempe, AZ, USA
3Banner Sun Health Research Institute,
Sun City, AZ, USA
4Banner Good Samaritan Medical Center,
Phoenix, AZ, USA
Objective: Gait impairment is one of the most disabling
of the symptoms of Parkinson’s disease (PD) and often it does not respond well
to pharmacological or surgical treatment. It has been shown that regular
practice of polestriding (walking with poles) can improve quality of living,
exercise capacity, and some gait measures in people with PD. This research
study has quantitatively investigated if regular 12-week polestriding exercise
training could improve gait in individuals with PD by obtaining spectrum of
gait indices.
Methods: Sixteen subjects (8 males, 8 females;
mean age: 63.9 ± 5.0 years; range 53-73 years) with mild to moderate PD
(Hoehn-Yahr score: 2.5 – 3) were selected to participate in a 12-week (three
45-minute sessions per week) polestriding exercise program. Gait patterns were
quantitatively measured during overground walking in medication-off condition
(at least 12 hours after the last usual dosage of anti-parkinsonian medication)
at four time points, each separated by 12 weeks: baseline, pre-training,
post-training, and follow-up.
Results: Comparison of pre-training and
post-training gait assessments indicated significant increases in step length,
speed, and swing power as well as significant decreases
(indicating improved gait) in
step-time variability, Hoehn-Yahr score, and the gait and balance related items
of the Unified Parkinson’s Disease Rating Scale (p < 0.02 after Bonferroni
correction of multiple comparisons). Since step-time variability and step
length are associated with an increased risk of falls in PD, these results suggest
that regular practice of polestriding may reduce the risk of falls. The
observed improvements in gait due to polestriding may improve mobility for
people with PD.
P22.37
Physical activity levels and disease severity in
individuals with Parkinson’s disease
Raquel Lana1,
Lysandra Nogueira de Araújo1, Lidiane Oliveira Lima1,
Fátima Rodrigues-de-Paula1.
1 Universidade Federal
de Minas Gerais, Minas Gerais, Brazil.
Objectives: To evaluate the association between physical
activity level and disease severity in individuals with Parkinson’s disease
(PD); to investigate the physical activity level in individuals on different
disease severity stages and in different PD subtypes.
Methods: Participants were evaluated with the UPDRS and
the Human Activity Profile (HAP). They were also classified through the Hoehn
& Yahr Scale (HY). Using UPDRS items, each patient received a final ratio
score and based on its distribution, patients were assigned to one of three
clinical subtypes: tremor-dominant (T), akinetic-rigid (AR), and mixed (MX).
Correlation coefficients were used to investigate the association between
physical activity level and disease severity (motor UPDRS and HY). An
independent samples t-test was used to analyze the difference in HAP scores
between two groups of disease severity (mild group HY= 1 to 2,5;
moderate/severe group HY= 3 to 4). One–way anova was used to investigate the
difference in the HAP between PD subtypes.
Results: 45 PD patients
(65,3±10,9 years; 30 men, 15 women) participated in the study. Their UPDRS
motor score was 12,9±7,4 and it was 65,3±20,7 in HAP. 24 individuals were
classified as AR, 12 as T and 9 as MX. There were inverse, significant
(p<0,01) correlations between the HAP and the motor UPDRS (r= -0,64) and the
HY (s= -0,54). We found a significant difference in the HAP score between mild
(72,13±16,24) and moderate/severe (48,47±23,22) PD groups (p<0,05).
Individuals with mild disease presented a higher score in the HAP, showing a
higher physical activity level. We did not find any difference in physical
activity levels between the subtypes of the disease. Although
the level of physical activity was
not different between subtypes
of PD, it was reduced with disease progression. The improvement in the level of physical activity
should be prioritized in rehabilitation
programs.
P22.38
Analysis of the psychometric properties of the Human
Activity Profile in individuals with Parkinson’s disease: Rasch Model
Raquel Lana1,
Lysandra Nogueira de Araújo1, Lidiane Oliveira Lima1,
Lívia Castro Magalhães1, Fátima Rodrigues-de-Paula1.
1 Universidade Federal
de Minas Gerais, Minas Gerais, Brazil.
Objective: The aim of this study was to evaluate the
reliability and construct validity of the Human Activity Profile (HAP) in
individuals with Parkinson’s disease (PD).
Methods: PD patients classified in stages 1 to 4 in
Hoehn & Yahr scale were evaluated with the HAP. The reliability and
construct validity of the instrument was evaluated by the Rasch Model. This
model determines if the level of difficulty of the items is appropriate for the
skill level of individuals. It also reports the reliability of measurements and
the calibration of items, which provide a degree of consistency or stability,
ranging from zero to one. The coefficients higher than 0.80 are considered good
and higher than 0,90 are excellent.
Results:
44
individuals with PD (65,3±10,9 years; 29 men, 15 women; disease duration of
11,36±7,3 years). The reliability coefficient of calibration of the items
ranged from 0.90 to 0.92 indicating stability of measurements, and it ranged
from 0.94 to 0.95 for subjects indicating that the measures can be reproduced
in subsequent applications. Participant’s ability showed a good distribution,
as well as item’s difficulty. The easiest item was “walk 1 minute” and the most
difficult item was “run 3,2 km”. Only three items of the HAP did not fit to
model expectations. These items are related to reading and writing skills. The
set of items that constitute the test seems to be divided in more than one
dimension, suggesting that the HAP is a multidimensional test for individuals
with PD. Since the multidimensionality does not preclude the use of an
instrument as a clinically valid tool, the HAP seems to be a reliable and valid
tool for assessing physical activity level in subjects with PD.
P22.39
Muscular power training improves gait and balance in
individuals with Parkinson´s disease: A Proof-of-Concept Study
Raquel Lana1,
Lidiane Oliveira Lima 1, Louise Ada2, Francisco Cardoso, 1Fátima
Rodrigues-de-Paula.1
1 Universidade Federal
de Minas Gerais, Minas Gerais, Brazil
2 Faculty of Health
Sciences, The University of Sydney, Austrália
Objective: To determine whether muscular power
training is tolerated and to gather preliminary data regarding the potential
benefit in people with Parkinson’s disease (PD).
Methods: This study was a
within-participant, repeated-measures design. Patients participated in two
baseline assessments and at the end of the intervention. Subjects with PD
received training three times a week for ten weeks. The lower limb muscle
groups trained were: hip flexors, extensors, adductors, abductors; knee flexors
and extensors; ankle dorsiflexors; and plantar flexors. The Borg Scale of
Perceived Exertion was used in order to investigate the subject’s tolerance to
the exercise. Work and muscular power were measured by isokinetic dynamometer.
A lower limb bradykinesia subscore was derived by summing the Unified
Parkinson’s Disease Rate Scale motor exam items 26, 27, 29 and 31. Walking
velocity, stride length and cadence were measured by GAITRite system, and
balance was assessed by the Berg Balance Scale (BBS). Descriptive statistics
and repeated-measures ANOVAs were employed for analysis.
Results: 13 subjects with PD (eight men; five
women), with a mean age of 63.8±12.3 years (50-87), participated in the
training program. Participants reported average perceived exertion by 12.8±1.1
(11-14), which corresponds to ‘somewhat hard’ on the Borg Scale. Participants
increased their work (p = 0.001) and muscle power (p = 0.0001) compared with
baseline. There was a significant improvement of bradykinesia (95% CI -1 to -3)
and the BBS score increased 5 points (95% CI 2 to 7) with training. Walking
speed increased significantly after the intervention (0.22 m/s, 95% CI 0.14 to
0.30), there was significant gain of stride length (0.09m, 95% CI 0.04 to 0.13)
but this did not occur with the cadence (6 steps/min 95% CI 0 to 11).
Preliminary data suggest that this intervention is tolerable and may be
beneficial for balance and gait disorders in PD.
P22.40
LSVT Big Physical
Therapy: Does it improve quality of life?
Alexandra E. Landen, Lisa Ebb, Fernando L. Pagan
Medstar- Georgetown University Hospital, Washington, DC, USA
Objective: Parkinson’s disease
is a neurodegenerative disease that causes a decline in motor function.
Overtime, a person’s disability increases leading to a decline in their overall
quality of life. Physical therapy is used to improve functional mobility. Big
and Loud therapy was developed specifically for patients with Parkinson’s
disease. Our goal is to show that patients who participate in Big physical
therapy experience an improvement in their quality of life. This will be assessed
using the PDQ-39.
Method: Patients who were to
begin Big physical therapy completed the PDQ-39 on day 1 prior to beginning
therapy. They were then asked to fill out the PDQ-39 after completing their
16th and final therapy session. Only patients who completed Big therapy within
five weeks were included in the study. The mean difference in each of the eight
subcategories of the PDQ-39 was calculated as well as the standard deviation.
Results: The average age was
68.6 years old. Improvement in PDQ-39 scores following Big therapy was noted in
mobility (6.79 points), ADL’s (6 points), emotional (1.39 points), cognitive
(1.78 points) and bodily discomforts (6.75 points). No change was noted in
stigma and social support. Worsening was noted in communication (1.19 points).
Conclusion: Our study did show
that quality of life was improved in five subcategories of the PDQ-39 which
were related to mobility. One category had some worsening, and the remaining
two subcategories had no change. Due to the small sample size, this study did
not achieve statistical significance, but the results deserve closer
examination. A study with a larger sample size and one comparing traditional
physical therapy to Big physical therapy should be done to further evaluate the
benefit of Big therapy on the quality of life in our Parkinson’s patients.
P22.41
Characterization of motor performance front of the
functionality of elderly with Parkinson’s disease
Luciano Alves Leandro1,
Hélio Afonso Ghizoni Teive1
1Movement Disorders Unit, Neurology Service,
Department of Internal Medicine, Hospital de Clínicas, Federal University of
Paraná (UFPR), Curitiba, Brazil
Objective: Know
the level of functional performance in elderly patients with Parkinson's
Disease (PD) and correlate it to the scale of Hoehn Yahr staging (HY) and time
to clinical progression
Methods: Field
study, exploratory cross-sectional descriptive correlational approach were
evaluated in 145 elderly patients with PD were divided into three groups
according to age groups: G1 (60-69), G2 (70-79) and G3 (80-89) outpatients at
the Division of Movement Disorders Department of Neurology, Hospital das
Clinicas, Federal University of Parana - UFPR, Curitiba - Brazil. To collect
data, we used two instruments: the Sociodemographic and Functional Independence
Measure (FIM). We performed statistical analysis of comparison
(Kruskal-Wallis), Pearson correlation and descriptive analysis of data.
Results: The sociodemographic characteristics revealed a
higher frequency of women aged 80 to 89 years with a low education level
(38.89%), mostly coming from remote areas of the city (90.48%). High scores
were observed in MIF indicating functional independence. The comparison between
the scores of FIM and FIM HY and mean time to clinical progression through the
G1, G2 and G3 indicate the time of onset of disease and staging of HY did not
affect the performance of these functional groups and the relationship between
the three groups also showed no statistical difference between them.
P22.42
The question of long-term compliance to the recommendations made by a specialized interdisciplinary team
C. Lepage, C.
Legault, V, Lavoie, N.L'Écuyer, E.Lafleur-Prudhomme, M.Pham, S. Émond, C.
Dubuc-Boutin, M. Béland
Centre hospitalier de l'Université de Montréal (CHUM), Montréal, QC,
Canada
Background: The
Renata Hornstein Center, part of the Movement Disorders Unit at CHUM, offers an
interdisciplinary approach for patients with advanced Parkinson’s disease and
loss of autonomy. At the end of the assessment, a treatment plan is proposed to
the patient and his family and a team member follows-up with the patient 3
months later.
Objective: To
evaluate if patients keep going with team recommendations after one year following
their evaluation.
Methods: Quantitative
and qualitative data on the adherence or not to the team recommendations were
collected through phone contact with 25 patients and/or their caregivers.
Results: Of the 25 patients (17 male, 8 female), 65% had Idiopathic Parkinson’s
disease, others had Parkinsonian syndrome; the mean age was 72.3 years. The
majority (80%) had difficulty with their balance and 72% cognitive deficits.
Recommended interventions that were followed or maintained included changes
made to medication, advice on management for dysphagia and installation of
safety equipment to assist with mobility. Recommendations that met with
resistance included changes in behaviour, suggested modifications to the home
and the use of tools to assist with ADLs. Exercise
programs and voice training exercises were abandoned after a few months.
Conclusion: For this clientele,
the success of the treatment plan is largely left up to the caregiver who is
already overwhelmed by the activities of daily life. Motivation to implement
changes in behaviour or to keep on with exercises is hard to maintain. Issues
to reflect upon: ensure long-term follow-up particularly with physiotherapy;
encourage attendance in exercise classes, ensure a link with community
resources and offer respite care for the caregiver.
P22.43
Walking difficulties
is the strongest contributing factor to fear of falling among people with mild
Parkinson’s disease
Beata Lindholm1, Oskar
Hansson1, Peter Hagell2, Maria H Nilsson3.
1Department of Clinical Sciences, Lund University, Malmö, Sweden
2The PRO-CARE Group, School of Health and Society, Kristianstad University,
Kristianstad, Sweden
3Department of Health Sciences,
Lund University, Lund, Sweden
Objective: Fear of falling is
common among people with Parkinson’s disease (PD) and may cause activity
limitations and restrictions in participation. The
aim of this study was to
investigate contributing factors to fall-related self-efficacy in a clinical
sample of people with PD.
Methods:
The study included 104 people with PD that visited a
neurological clinic during 2006-2011. Those >80 years of age, requiring
support in standing or that did not understand the instructions were excluded.
Mean (SD) age
and PD-duration were 68 (9.4) and 5 (4.2) years, respectively; the mean (SD) “on” phase UPDRS
III score was 14.5 (8.1). Fall-related self-efficacy (the dependent
variable) was investigated with the Swedish version of the Falls Efficacy Scale, i.e. FES(S). Multiple linear regression analysis included independent variables
targeting walking difficulties in daily life, freezing of gait, dyskinesia, fatigue, need of help in daily activities, age, PD-duration,
history of falls/near falls, and pain.
Results: The median FES(S) score was 117 (q1-q3, 70−129; min-max, 11−130). Three significant independent variables were identified
explaining 66% of the variance in FES(S) scores. The strongest contributing
factor to fall-related self-efficacy was walking difficulties (explaining 60%),
followed by fatigue and need for help in daily activities. These observations
suggest that walking difficulties in daily life is the strongest contributing
factor to fall-related self-efficacy in a mildly affected PD-sample. Targeting
walking difficulties may help reduce fear of falling among people with PD.
P22.44
Test-retest and inter-rater reliability of the mini-BESTest in mild to
moderate Parkinson’s disease – a clinical approach
Niklas Löfgren1, Emma Lenholm2,
David Conradsson1,2, Agneta Ståhle1,2, Erika Franzén1,
2
1Karolinska Institutet, Department
of Neurobiology, Care Sciences and Society, Division of Physiotherapy
2Karolinska
University Hospital, Department of Physical Therapy, Stockholm, Sweden
Objectives:
The inter-rater reliability of the mini-BESTest, previously found to be a
reliable tool for balance assessment in individuals with Parkinson´s disease
(PD), have generally been studied using one test leader with different
observers scoring the test. However, in daily clinical practice the same person
instructs and scores the test, and the instructor may change between test
sessions, warranting for reliable tests under similar conditions. Hence, the
aims were to, in a clinical context, investigate the test- retest and inter-rater
reliability of the mini-BESTest in elderly with mild-to-moderate PD.
Methods:
Twelve individuals, diagnosed with idiopathic PD (66 – 79 years, mean age: 73;
Hoehn & Yahr: 2-3; 1-13 years since diagnosis) were included. To achieve a clinically
relevant assessment of the inter-rater reliability, two test leaders with
different experience of the test instructed and scored the test separately in
similar facilities at a hospital. To limit the possible effects of bias, the
subjects were randomized regarding which test leader to begin with. For the
test-retest assessment, all participants returned 7 days after the firsts test
session to perform the mini-BESTest under similar conditions (regarding time of
day, time since medication etc.). Intraclass correlation coefficients (ICC),
standard error of measurement (SEM) and smallest real difference (SRD) was
used.
Results: Mini-BESTest had good
to very good agreement (inter-rater: ICC= 0.775 and test-retest: ICC=0.895). On
group level, the measurement error (SEM) was 1 point for test-retest and 2
points for inter-rater reliability, whereas on individual level, the error
(SRD) was 3 and 5 points, respectively. This indicate that the mini-BESTest is
a reliable tool for assessing balance of elderly with mild-to-moderate PD.
However, on an individual level the results emphasize the importance of each
patient being assessed by the same clinician. Future studies, including greater
number of participants, needs to investigate this further.
P22.45
Development and feasibility of a novel conceptual framework for balance
training in Parkinson’s disease
Niklas
Löfgren1, David Conradsson1,2, Agneta Ståhle1,2,
Erika Franzén 1, 2
1Karolinska Institutet, Department
of Neurobiology, Care Sciences and Society, Division of Physiotherapy
2Karolinska University Hospital,
Department of Physical Therapy, Stockholm, Sweden.
Objective: Balance training needs to be designed to challenge specific impairments
of the targeted group. Moreover, to optimize a training regime, the theoretical
approach needs to be tested in practice to enable modifications for further
improvement. In addition, it is essential that the outcome measures used are
appropriate, regarding the studied population and their specific impairments.
Our aims were therefore to 1) to develop a highly challenging, progressive and varying group balance training regime specific to Parkinson’s disease
(PD) symptoms and 2) to investigate the feasibility of a this intervention as
well as the outcome measures in elderly with mild to moderate PD.
Methods: The intervention (12 weeks, 3 x 45
minutes/week) was developed through
discussions and workshops by a group of researchers and physiotherapists.
Subsequently the feasibility of this intervention was evaluated in five
subjects with idiopathic PD, mean age 72 years (range 69 - 80) and Hoehn &
Yahr score 2 to 3. Indicators of feasibility included adherence, safety,
progression, perception and adequacy of the outcome measures.
Results: Adherence was high (78%) and adverse
events, fatigue and pain were scarce. The majority of the participants and
trainers, respectively, considered the training as adequately progressive. All
participants also considered the training regime as motivating, stating that
they would recommend it to others. However, some perceived that the training
period was too long. The outcome measurements were adequate as the participants
were able complete all assessment tools. On the other hand, a critical
examination of the measurements revealed that sensory
integration and physical activity were not adequately covered by the outcome
measures. These
findings support the overall feasibility of this new highly challenging group
balance training program in elderly with mild to moderate PD. However, a RCT is
required to evaluate the efficacy of the program.
P22.46
An acute Parkinson’s Therapy Pathway; bridging the gap
between hospital and home
Christopher Lovegrove¹, Helen Guppy1
¹Royal Devon &
Exeter NHS Foundation Trust, Exeter, Devon, UK
Objective: People with Parkinson’s can often experience
long hospital admissions, and are frequently not discharged to their own homes
to continue their rehabilitation. Reports from people living with Parkinson’s
show that the hospital environment does not replicate their own home set-up,
and home-based rehabilitation programmes have been shown to be effective
(Ashburn et al 2007, Antonini et al 2008). Furthermore, home based therapy has
been shown to have positive advantages over day hospital based rehabilitation
(Parker et al 2009). The authors aim to develop a Parkinson’s Therapy Pathway
for the acute hospital setting, integrating early home-based assessment and
therapy sessions, with seamless transition to community services.
Methods: The early home assessment aims to focus and
specify further rehabilitation in the hospital environment, using photographs
of key home areas to allow the full MDT to enable the patient in hospital. Home
based therapy sessions and a staggered discharge aim to reduce readmission rate
and ease transfer to the community services. We have found that an exercise
program that works in hospital has not always been successful at home and may
need adjusting. The staggered discharge allows the patient and MDT to
troubleshoot any problems at home, which can subsequently be solved in the
hospital environment. We aim to create a template therapy discharge summary
which is e-mailed to the community services and PD nurse on discharge, to give
a comprehensive therapeutic account of admission and expedite therapy at home.
Results: The measured outcomes will be patient
satisfaction, length of stay and readmission rates, alongside Lindop and UPDRS
scores.
P22.47
Changes in vowel (co)articulation following
intensive voice treatment (LSVT) in Parkinson’s disease
Vincent
Martel Sauvageau1,2, Johanna-Pascale Roy1,3,
Mélanie Langlois4, Joël Macoir1,2
1Centre de recherche de l’Institut Universitaire en Santé Mentale de
Québec, Canada
2Université Laval, Faculté de médecine, Québec, Canada
3Université Laval, Département de langues, linguistique et traduction,
Québec, Canada
4Centre hospitalier universitaire de Québec (HEJ), Québec, Canada
Objective: LSVT (Lee-Silverman Voice
Treatment) is an intensive speech therapy program designed to reduce the
symptoms of hypokinetic dysarthria, a speech disorder frequently associated
with Parkinson’s Disease (PD). Even though the effects of this treatment on
voice intensity and intelligibility have been well documented in past studies,
changes it might generate on vowel articulation and consonant-vowel sequences
(C-V) coarticulation has been overlooked.These acoustic variables are of
particular interest because they are known to contribute directly to speech
intelligibly and they have not been studied in a systematic way.
Methods: The present study was designed to
investigate the impact of LSVT on vowel articulation and coarticulation
in C-V sequences. We report the acoustic data of 10 PD subjects with moderate
hypokinetic dysarthria, before, immediately after, then one and two months
after receiving the LSVT program. F1 and F2 formant values of the vowels
/i/ /u/ and /a/ were measured at the initial and stable portion of the vowel in
different consonant contexts: voiced and voiceless occlusive (/b/ /d/ /g/, /p/
/t/ /k/) and voiceless fricatives /f/ /s/ “ch”).
Results: Preliminary results show a small
increase of F1/F2 vocalic space in the post-treatment conditions as well as
reduced vowel dispersion, which are the acoustic correlates of better vowel
articulation and increased stability. Other measures such as “Locus of
Equation” and “Contrasts between consonant contexts” suggest an increase in C-V
coarticulation, post-treatment. This ongoing study will help clarify the impact
of LSVT on vowel articulation and coarticulation in PD. The project will
also investigate the relationships between these measures and other acoustic
variables such as speech rate and intensity.
P22.48
The type of secondary task matters in dual task walking
during the Timed Up and Go
Tara L. McIsaac1, Franchino Porciuncula1
1Teachers College,
Columbia University, NY, USA
Objective: Walking while simultaneously performing a
cognitive or manual task typically alters gait, particularly in people with
Parkinson’s disease (PD). Difficulties in turning are also associated with the
disease and can be related to falls. However, the relationship of the attention
requirements of different types of secondary tasks and walking with turns is
unclear. Therefore, we examined the effects of the type of secondary task on
performance costs to dual-task walking and turning.
Methods: Twelve participants with PD and six healthy
controls were assessed using wearable inertial sensors during the instrumented
Timed Up and Go (TUG) under six conditions; single-task and in five dual task
conditions: 1) carrying water, 2) serial-3 subtractions, 3) combined water and
subtraction tasks, 4) dialing a cell phone, and 5) buttoning a coat. The cost
to performance from dual tasking was compared across conditions and groups for
the sit-to-stand, 7-meter walk, turn, walk back, and turn-to-sit components of
the TUG, using mixed design ANOVAs on each component (total duration, stride
length, sit-to-stand peak velocity, turn duration, and turn-to-sit peak
velocity).
Results: All participants sustained performance costs
in all gait measures to different degrees according to the type of secondary
task (p<0.005), with the greatest
costs during walking while carrying water and subtracting, and the least cost
in the serial-3 subtraction condition. Compared to controls, participants with
PD sustained greater costs to stride length in all dual task conditions (p<0.05), and greater costs in time
spent turning when also carrying the water or buttoning the coat (p<0.05). We conclude that the type of
secondary task performed exacts different costs on walking and turning
components of the TUG. For individuals with PD, everyday activities such as
buttoning a coat or carrying a cup while walking may pose particular risks to
balance, especially when turning.
P22.49
Pre-stepping postural preparation in patients with
Parkinson’s disease with and without freezing of gait
Susanna Mezzarobba1,
Alice Pellizzaro2, Sgubin Giulia1, Marcovich Roberto1,
Valentini Roberto 2
1 Physiotherapy Degree,
University of Trieste, Italy
2Orthopaedics and
Traumatology Clinic, Cattinara Hospital, University of Trieste, Italy
Objective: investigate variability in postural
adjustments prior to first step of Gait Initiation (GI) in Parkinson’s Disease
(PD) patients with freezing of gait (FOG) compared to patients without FOG
(NO-FOG) and their healthy elderly peers. People with Parkinson's disease
frequently have difficulties with generating anticipatory postural adjustments
(APAs) for forward propulsion and lateral weight
transfer when initiating gait, and frequently occurring FOG episodes in GI.
Detect differences between subjects NO-FOG and FOG in GI, outside actual FOG
episodes, can support the hypothesis of FOG as a specific disorders of load
regulation.
Methods 18 patients
were enrolled and divided into 3 different
groups: subjects with PD NO-FOG
(7), subjects with PD-FOG (6), healthy subjects (5). All PD subjects
(ON-phase) underwent clinical (H&Y,UPDRS III, FOG-Q, BBS), and
kinematic-kinetic evaluation by means of motion analysis laboratory. COP displacement, COM-COP distance (stability limit), stepping features including
length, width of the first step of
GI were compared
between groups during simple and dual task.
Results: No differences were
found in clinical data between both PD patients group. In PD FOG group COP
displacement results greater than PD NO
FOG, but similar to healthy group. In APA-phase they showed
increased posterior (p=0,008) and lateral toward stepping limb COP displacement
(p=0,014). PD FOG patients also showed
reduced forward propulsion (p=0,07)
in taking the first step. In PD FOG subjects distance COP-COM
increased backwards and lateral toward stance limb compared to PD NOFOG
subjects (p=0,008). Posterior COP displacement is also increased in dual-task (p=0,03). Only patients PD FOG
initiated gait with a significantly shorter step as compared to healthy
(p=0,03) and with a significantly reduced speed (p=0,04). In PD patients the
ability to generate a consistent stepping pattern during GI may be altered but
PD FOG patients show a higher instability (not clinically manifested) and
reduced forward propulsion.
P22.50
Neurocognitive rehabilitation with motor imagery vs
treadmill training for freezing of gait in Parkinson’s disease: A randomized
controlled study
Susanna Mezzarobba1,
Lorella Pellegrini1, Sgubin Giulia1, Airi
Gorian2, Mihaela Banica2, Pierpaolo Busan3, Pizzolato
Gilberto2, Catalan Mauro2
1Physiotherapy Degree,
University of Trieste, Italy
2Department of Medical
Sciences, Neurology Unit, University of Trieste, Italy
3Department of Life
Science, University of Trieste, Italy
Objective: compare the efficacy of a neurocognitive
rehabilitation based on explicit motor learning using Motor Imagery (MI) versus
a more implicit motor learning treatment with treadmill, to improve Freezing of
gait (FOG) in Parkinson’s Disease (PD) subjects.
Methods: 21 PD patients with FOG (median age 75±4,9,
disease duration years 9±3,6, H&Y 1,8 range 1-3), no evidence of dementia
(MMSE >24) or depression (BDI<16), were enrolled and randomly assigned to
different treatment groups. Selected patients performed 20 sessions of a
rehabilitation program based on MI for Group 1, while Group 2 underwent
treadmill training. Disease stage (H&Y and UPDRS
III), FoG (FOGQ), quality of life (PDQ-39), locomotion (Timed up and go-TUG,
six minute walk test- 6MWT), balance (Berg balance test-BBT) and disability (Modified Parkinson’s Activity scale-MPAS) were assessed at baseline, after
treatment, at follow up of 4 and 12 weeks in stable pharmacological therapy;
furthermore patients underwent a brief neuropsychological test to asses frontal
and executive functions to define motor learning ability. A neurocognitive
rehabilitation treatment program, aiming to modify wrong strategies in motor
planning and improve movement control, was administered to 11 patients, while
other 10 patients underwent treadmill training.
Results:
At baseline both groups did not differ for clinical
variables, neuropsychological scores or rehabilitation scales. After treatment in
Group 1 a significant reduction in FOGQ (p=0,01) and an improvement in
some rehabilitation scales (MPAS=0,01 BBT p=0,02) were detected and retained at
the second follow up 12 weeks after (FoGQ p=0,02 MPAS=0,002 BBT
p=0,09). While no significant changes were shown in Group 2. This improvement
maintained at the second follow-up suggests that learning effects were retained
in daily life. The rehabilitation program with MI could represent an
interesting rehabilitation strategy to treat FOG in PD patients.
P22.51
Assessment
of gait therapy effectiveness in the patients with Parkinson’s disease on the basis
of three-dimensional movement analysis
Elżbieta Mirek1,2,
Jadwiga Kubica1, Jadwiga Szymura1,
Szymon Pasiut1, Monika Rudzińska2, Wiesław
Chwała1
1University
School of Physical Education in Krakow, Poland
2Department of Neurology,
Jagiellonian University Medical College, Krakow, Poland
Objective:
The purpose of this study was to asses: gait pattern disorders based on
three-dimensional gait analysis and effect of physical therapy in a group of
people with Parkinson’s Disease (PD).
Methods:
32 subjects with PD (14 women and 18 men; age range: 50-75) were qualified for
research which run for 3 weeks and included 18 PNF therapeutic sessions. 35
control subjects were included in research (13 women and 19 men; age range:
52-77). Gait analysis using the Vicon 3D system took place in the Biokinetics
Laboratory in the University School of Physical Education in Krakow. Research
group were conducted before and after treatment, control group were tested
once.
Results:
Comparing the average peak angle changes and average standard time results
(%gait cycle) corresponding with angles of movement in cervical spine, elbow
and shoulder joint statistically significant changes were observed. The study
indicates the differences in both groups in spati-temporal parameters and
angular changes of gait.
P22.52
Dancing to enhance mobility in people with Parkinson’s
disease
Meg E Morris1, Daniele Volpe2
1La Trobe University,
Victoria, Australia
2S. Raffaele Arcangelo Fatebenefratelli Hospital, Venice, Italy
Objective: Although therapeutic dance is increasing in
popularity, the feasibility of Irish dancing for older adults with idiopathic
Parkinson’s disease (PD) remains open to question. The aim of this study was to
test the feasibility and safety of Irish set dancing compared to standard
physiotherapy for the management of movement disorders in PD.
Methods: We tested 24 individuals with idiopathic PD
from Venice, Italy. Each was randomly assigned to either Irish set dancing
classes or traditional physiotherapy classes for a period of 6 months, coupled
with a home program. The main outcome measure was mobility measured on the
Unified Parkinson’s Disease Rating Scale. We also measured gait freezing and
balance.
Results: In older adults with
PD, both the Irish set dancing and the physiotherapy exercise program were
shown to be feasible and safe. Adverse events such as falls, serious injuries,
death or rates of admission to hospital were similar in the two groups.
Improvements were made in both groups although the dance group showed great
gains in motor disability. Dancing classes are safe and feasible in people with
mild to moderate levels of disability associated with Parkinson’s disease.
P22.53
An Australian model of inter-professional rehabilitation
for Parkinson’s disease
Meg E Morris
La Trobe University,
Victoria, Australia
Objective: Parkinson’s disease is a chronic and
progressive condition that can affect movement, balance, mobility, the ability
to perform daily activities, autonomic function, cognition, and psycho-social
function. It affects individuals as well as families and care-givers. Each
person living with Parkinson’s disease is unique and services need to be
comprehensive and tailed to individual needs.
Methods: In Melbourne Australia we have led
comprehensive inter-professional rehabilitation services to assist people with
Parkinson’s disease and the significant others in their lives to live well with
this condition. Rehabilitation interventions are research led and based on current
scientific findings on responses to movement rehabilitation strategies,
strength training, cognitive training, and physical activities such as walking,
dancing and hydrotherapy. Services are provided in home, community and hospital
settings. As well as adopting science informed clinical guidelines, emphasis is
placed on teaching health professional how to work effectively and efficiently
within a team and how to ensure client centred and family focussed outcomes.
Results: In both young adults and older people with
PD, a comprehensive inter-professional team based model of rehabilitation has
been found to be effective, feasible and safe. As well as optimising mobility,
functional task performance and physical activity, it is argued to reduce
care-giver burden by empowering people to be more independent. The aim is to
optimise quality and life and well-being through targeted and effective
services provided at the right time by the right person in the right
environment.
P22.54
Home-based
gait improvement in Parkinson’s disease: using video to support self-cueing
Stephanie
Morrison1, Sandi Spaulding2, Jeffrey Holmes2,
Mary Jenkins3
1 Faculty of Health Sciences, Western
University, Canada
2 School of Occupational Therapy, Western
University, Canada
3 Clinical Neurological Sciences,
Schulich School of Medicine and Dentistry, Western University, Canada
Objective: Individuals with Parkinson’s disease (PD)
who experience gait impairment may benefit from external cueing, such as
statements like “take big steps”. This external cueing approach is often
successful in establishing short-term gait improvement; however, long-term
improvements are more difficult to achieve. This study tested the effects of a
novel home-based video intervention designed to facilitate longer-term gait
improvement in individuals with mild to moderate PD.
Methods: Five participants (mean
age = 71.4) with PD related gait impairment completed a two-week home-based
gait improvement intervention, designed to help participants learn to cue
themselves. Video of each participant walking with and without verbal cueing
(e.g. take big steps) was captured in a laboratory setting, edited, and
delivered to participants for home-based viewing every-other-day for two weeks.
The video-intervention consisted of alternating periods of active viewing of
oneself walking (3x1 minute), timed walking practice (3x3 minutes), and
embedded audio coaching. Participants step length, gait speed, and functional
mobility were assessed before and after the two-week intervention, and after a
two-month period of unprescribed practice.
Results:
Immediately
after the two-week intervention, all five participants showed improved step
length, four of the five participants showed improved gait speed, and four of
the five participants showed improved functional mobility. Four participants
returned for testing after two-months of unprescribed practice. At this time,
compared to pre-intervention measurement, all four participants showed improved
step length, three of the four showed improved gait speed, and all four showed
improved functional mobility. Feedback from participants and researchers
established feasibility for larger-scale intervention testing and
implementation.
P22.55
The impact of physical environmental barriers on
accessibility problems- very old people with self-reported Parkinson’s disease
versus controls
Maria H Nilsson1, 2, 3, Björn Slaug1,2 Susanne
Iwarsson1, 2, 3
1Department of Health
Sciences, Lund University, Lund, Sweden
2Centre for Ageing and
Supportive Environments (CASE), Lund University, Lund, Sweden
3Strategic Research
Area of Neuroscience, MULTIPARK, Lund University, Lund, Sweden
Objective: To investigate which physical environmental barriers that contribute the
most to accessibility problems among very old people with self-reported
Parkinson’s disease (PD) versus matched controls.
Methods: Data collected for
the cross-national ENABLE-AGE Survey Study were used to identify people with
self-reported PD (n=20), and to select three matched controls per individual
(n=60). The matching criteria were age (mean=82 years), sex, country, and type
of housing. By means of the Housing Enabler instrument, data on individual
profiles of functional limitations and 188 physical environmental barriers (EB)
in the housing environment were collected. In addition, accessibility problem
scores were generated that represent a function of the individual profiles of
functional limitations and the presence of physical environmental barriers.
Results: The number of EB did
not differ (p=0.727) between the two samples. The PD-sample had however
significantly (p<0.001) more accessibility problems than controls: median
(q1-q3) was 192 (112-232) versus 63 (14-128). The top three physical EB that
induced the most accessibility problems were similar for the two samples:
Wall-mounted cupboards and shelves placed extremely high; No/too few seating
places (exterior surrounding); No grab bars at shower/bath and/or toilet. In
all instances, these barriers induced significantly (p≤0.016) more
accessibility problems among very old people with self-reported PD than among
controls. This was due to that the PD-sample had more (p=0.004) functional
limitations. Importantly, the 20 environmental barriers that generated the most
accessibility problems differed between the two samples. That is, six of the EB
in the top 20 list for the PD-sample did not appear in the list for the
controls: e.g. three concerned exterior surroundings and two concerned indoor
design features requiring hand use.
Conclusions: Our findings suggest
that accessibility problems and physical environmental barriers need specific
attention among very old people with self-reported PD.
P22.56
The changes of gait pattern
after arm load in Parkinson’s disease
Jinse Park1,
Jiyeon Yoon1, Nahyun Kim2
1Department of neurology, Haeundae paik hospital,
Busan, Korea
2Department of psychiatry, Hana hospital,
Chung-do, Korea
Objective: Gait disturbances characterized by slow velocity, short-step, decreased
arm-swing and festinating gait are common features in Parkinson's disease. Due
to unsatisfactory response to dopaminergic medication, much research has
focused in physical therapy for treatment. It is known that gait pattern is
influenced by amplitude of arm-swing. The purpose of this study is to evaluate
the effect of weight load to arms on gait pattern in Parkinson’s disease.
Methods: Thirty patients with Parkinson's disease were enrolled in our
study. We estimated gait parameters using three-
dimensional motion analysis system. We checked spatiotemporal
parameters such as walking speed, stride length, stride width and cadence.
Kinematic parameters including arm-swing amplitude, trunk and pelvic
rotation are also obtained. The patients walked for 6 meters with and without
0.45kg bag of sand tied in each forearm. We compared gait parameters
between two conditions.
Results: Gait disturbance was generally improved after weight load in both arms.
Arm swing amplitude is more increased in walking with arm load. Spatiotemporal
parameters such as walking speed, stride length and cadence significantly
improved after arm load. Amplitude of arm-swing is highly correlated with
walking speed and stride length. Our
result support that increased arm-swing magnitude enhanced locomotion in
Parkinson’s disease. The effect of weight load on arm-swing is obvious, and
might result in substantial changes in gait pattern. These findings might be
useful information for gait training in Parkinson’s disease.
P22.57
A pilot study based on a
proactive exercise program (PEP) for mild to moderate stage Parkinson’s disease
Mai Pham¹-², Julie Beauchemin¹, Dominique Beaudry¹, Anis Chikh¹,
Andréanne Faubert¹, Dorothy Barthélemy², Nicolas Bourgeois¹-², Lucie Plouffe²,
Michel Panisset², Christiane Lepage²
¹ Montréal University, Montréal, QC, Canada
² CHUM-HND, Montréal, QC, Canada
Objectives: Exercises are essential in the none-pharmacological treatment of
Parkinson’s Disease (PD) however guidelines for their application (type,
frequency, intensity, and duration) remain unclear. Based on new approaches
(Training Big, Tai Chi, Task oriented, Multi tasks…) a new proactive exercises
program (PEP) was developed, however its feasibility was still unproven.
The objective of the pilot study was to evaluate the feasibility and to
determine which incapacities resulting from Parkinson’s disease could be
improved using the PEP program in this population.
Methods: 11 subjects with idiopathic PD (Hoehn & Yahr stage 1-3)
participated in PEP program twice a week for 6 weeks. The feasibility criteria, amongst others,
were the subjects’ ability to perform the exercises and the occurrence of adverse
events. Axial articular mobility, balance, motor performance and quality of
life were measured to evaluate the effectiveness of the program.
Results: The majority of subjects were able to perform the PEP exercise program
with no occurrence of serious adverse events.
Significant improvements (p < 0.05) were observed with the sit to
stand test (STS), in bed mobility with and without blanket and the time up and
go (TUG) test. However the results show a reduction in the extension range of
cervical motion.
Conclusion: The feasibility of the PEP program was shown within the PD population
that was targeted. In fact, there was significant improvement with certain
variable measures which suggests the PEP exercise program could improve the
subjects’ ability to perform activities. However further studies would be
necessary to confirm this.
P22.58
Bradykinesia and timed up and go are improved
after dynamic cycling in Parkinson’s disease
Robert S. Phillips1, Kayla A. Wilson1,
Benjamin L. Walter2, Angela L. Ridgel1
1Kent State University, Kent, OH, USA
2University Hospital, Cleveland, OH, USA
Objective: Parkinson’s disease
is a neurodegenerative disorder and is estimated
to affect 7-10 million individuals worldwide. Bradykinesia or slowness of
movement, a primary symptom, can cause significant disability. Previous studies
have shown that active-assisted cycling improves bradykinesia. However, it is
important to correlate changes in clinical measures of bradykinesia with
performance during functional mobility tasks. The aim of this study is to
document changes in bradykinesia after bouts of dynamic cycling and to
establish a relationship between the UPDRS clinical scores and the Timed Up and
Go (TUG) test.
Methods: Individuals with mild to
moderate PD were randomly assigned into either a static or dynamic cycling
group. Each subject was first evaluated using the UPDRS Motor III scale, a
quantitative measure of bradykinesia (Kinesia 3.0), and the TUG and then
completed three days of cycling with one day of rest between. A post-exercise
evaluation was completed one day after the last cycling session.
Results: Analysis of combined Kinesia 3.0 bradykinesia measures shows an
improvement in amplitude for both the static and dynamic groups of 40.0% and
50.6% respectively. Frequency of movement scores indicate a similar trend with
the static group improving by 17.9% while the dynamic group improved by 42.6%.
The overall UPDRS scores show a 1.1% and 9.8% improvement in UPDRS, for the
static and dynamic groups respectively, and TUG self-selected speed worsened by
16.1% in the static group but improved by 17.3% in the dynamic group. TUG
scores show improvements in functional movement alluding to improved motor
planning and improved speed of movement. These findings are consistent with the
findings of the UPDRS motor scale as well as findings from the Kinesia 3.0.
P22.59
Efficacy of mental practice
mnemonic coupled with physical practice in improving gait of patients with
Parkinson’s disease
Maria Elisa Pimentel Piemonte1; Erika Okamoto2
1
University of São Paulo, Sao Paulo, Brazil
2 Brazil
Parkinson Association, Sao Paulo, Brazil
Objective: Strategies
to minimize the gait disruption typical of PD patients have posed a great
challenge for Physical Therapy Science. Mental practice associated with
physical practice can be a important approach to improve the efficiency of
attention control on the gait. Thus, the aim of this study was to verify the
efficiency of mental and physical training in improving gait performance of
patients with Parkinson’s disease (PD patients).
Methods: A total of
24 PD patients participated in the present study, comprising 14 men and 10
women, having a mean age of 68.3 (SD = 10.86), 8 in stage 2; 10 in stage 2.5 and
8 in stage 3 of evolution of disease, according to the Hoehn and Yahr
Classification. Patients were randomly divided into two groups: Mental Practice
group (MP), which carried out 8 sessions (twice a week) of physical training
coupled with mental practice; and a Physical Practice group (PP), which
performed only physical training. Patients were tested whilst on levodopa
medication, which remained unchanged throughout the study. All participants
signed the free informed term of consent, previously approved by the local
Ethics Committee.
Results: There was a significant improvement of performance in gait with
regard to speed, exclusively in the MP, and independent of stage of evolution
of disease (p-value < 0.001). In contrast to results at study baseline,
there was a significant difference in the gait speed between the groups after
training (p-value < 0.01).
Conclusions: Physical
training coupled with mental practice leads to significant improvements in gait
performance compared with the same training without mental practice. Thus,
mental practice can be useful in the motor rehabilitation of such patients,
constituting a straightforward, inexpensive and swift form of training for
non-demented patients.
P22.60
A vision of improved postural stability in Parkinson's
disease: enhancing balance through visual training under dual-task conditions
Gillian Porter1, Valerie Carter1
1Northern Arizona
University, Flagstaff, AZ, United States
Objective: It is well documented People with
Parkinson's disease (PWP) experience mobility impairments and an increased risk
of falls secondary to deficits in balance, posture, and vision.1,2
These deficits can cause enhanced difficulty for PWP when performing under
dual-task conditions. Research reveals PWP utilize visual feedback to maintain
upright posture and control balance as a compensatory strategy for inaccurate
processing of proprioception and sensory feedback.3-7 Vision as a
secondary task under dual-task conditions has yet to be explored. The purpose
of this poster is to discuss the relevant literature and describe dual task
treatment concepts to enhance balance and visual abilities in PWP.
Methods: Recent literature suggests visual deficits
and difficulty performing under dual-task conditions in PWP add to the
challenges of maintaining effective balance. Pertinent visual deficits include:
decreased visual attention, saccades, smooth pursuits, peripheral vision, depth
perception, and vertical eye movements.8-10 Studies indicate an
increase in postural sway secondary to saccadic suppression, difficulty
initiating saccadic movement, a hypometric saccadic gaze response, and
decreased peripheral vision contribute to PWP difficulty in detecting and
reacting to visual stimuli.5,8,9
PWP are known to
experience increased fall risk when completing simultaneous tasks.1The
'dual-task paradigm' suggests the performance in a primary task deteriorates
while a secondary task is simultaneously being performed.11 However,
studies have also shown improved performance in a primary task as well as two
concurrent tasks under dual-task conditions1,12,13 This infers with
appropriate challenges, PWP have the potential to improve under dual-task
conditions.
Results: The authors will introduce, describe, and
outline the need for dual-task training that includes visual strategies for
saccadic movement, visual attention and processing speed, pursuits, and head
turning which assist PWP in stabilizing postural control for improved balance
performance. These treatment ideas will incorporate effective dual-task visual
methods for use in the rehabilitation and home setting.
P22.61
A unique community group rehabilitative exercise and therapy (GREAT) program for people with Parkinson’s disease
1Ingrid
Pretzer-Aboff, 2Greg Hicks 1Joseph DeRanieri 2Darcy
Reisman
1 University of
Delaware, School of Nursing, USA
2 University of
Delaware, Department of Physical Therapy, USA
Lack of activity is a major risk
factor for morbidity and mortality in the aging population. There is growing
evidence that therapeutic exercise is an effective method to significantly
increase activity, function and quality of life for people with Parkinson’s
disease (PD). However, availability of appropriate community programs is rare.
The Group Rehabilitative Exercise and Therapy (GREAT) program fills a gap that
exists in the rehabilitation spectrum between traditional therapy and community
gyms in an effort to improve function and activity levels.
Objective: Our aim was to test the feasibility
and impact of a unique tri-therapeutic program that merges physical,
occupational, with speech language therapy techniques.
Method: This study utilized a single group
repeated measures design. Testing was completed at baseline, 3, and 6 months
post start of group exercise. Fifteen volunteers with PD were enrolled into a
one hour (2x per week) group session run by physical or occupational therapy
assistants under the supervision of licensed therapists. This 12 week program
incorporated vocalizations, breathing exercises, memory and recognition, fine
and gross motor mobility exercises for extremities and trunk, balance
activities and progressive distance walking techniques.
Analysis: Repeated measures ANOVA was used to
analyze significant differences in physical performance, function and quality
of life measures.
Results: Significant improvements were seen
in walking speed (6 meter walk test), voice loudness, quality of life (PDQ-39,
communication), cognition (MOCA), and disability (UPDRS, total). Additionally,
subjects reported improved clarity of voice. Post intervention interview
indicated that socialization was exceedingly important to the groups’
adherence.
Conclusions: People with PD benefit from this
tri-therapeutic program. The PT, OT and speech components were easy to
integrate during all exercise classes and demonstrated significant clinical
benefits.
P22.62
Evaluation of the upper limb in people with Parkinson’s
disease: a systematic review
Proud EL1, Miller KJ1,2,
Bilney B1, Balachandran S1, McGinley J1,
Morris, ME3
1School of Health
Sciences, The University of Melbourne, Parkville, Victoria, Australia
2 Department of
Physical Therapy, University of British Columbia, Vancouver, British Columbia,
Canada
3 School of Allied
Health, La Trobe University, Bundoora, Victoria, Australia
Objective: Treatments for people with
Parkinson’s disease (PD) include interventions to address upper limb movement
disorders. To measure the efficacy of these interventions, measurement tools
which are reliable, valid and responsive in this population are needed. A two
part systematic review was designed to examine these measurement properties in
upper limb measurement tools used in PD. The aim of part one was to identify
evaluative measurement tools described in the literature.
Methods: A systematic search was
conducted in July 2012. Studies were included if they evaluated the effects of
a treatment intervention or disease progression on upper limb impairments,
activity limitations or participation restrictions in people with PD. Studies
which utilised laboratory based equipment or measurement techniques which could
not be replicated using the information provided in the study were excluded.
The study was limited to articles published in English.
Results: Following screening, a
total of 17 measurement tools were identified. The effects of medical, surgical
and other interventions such as exercise, or changes occurring with disease
progression were evaluated, and impairments, activity limitations and
participation restrictions were quantified. The identified measures were
largely generic upper limb measures, tools developed for conditions other than
PD, and single or grouped upper limb items taken from global PD-specific scales
such as the UPDRS. One PD-specific upper limb measurement tool, the Modified
Bradykinesia Rating Scale,[1] was identified. There remains the need
to understand the measurement properties of each of these tools, and to examine
their clinimetric properties and clinical utility for the evaluation of people
with PD.
P22.63
Parkinson’s disease and forced exercise: A preliminary
study
Abu Qutubuddin 1, 2,3 Timothy Reis1, 2 Raed
Alramadhani1 David X. Cifu 1, 2Alan Towne 1,3 William
Carne.1, 2
1 Richmond Veterans
Affairs Medical Center, Southeast Parkinson’s Disease Research, Education and
Clinical Center, 1220 Broad Rock Blvd. Richmond, VA, USA
2 Department of PM&R, Virginia Commonwealth University
1223 East Marshall Street, Richmond, VA, USA
3 Department of Neurology, Virginia Commonwealth University
P.O. Box 980599, Richmond, VA, USA
Objective: The concept of forced exercise has drawn
attention for the treatment of Parkinson’s disease with anecdotal reports of
success. To ascertain any significant effect of forced exercise on Parkinson’s
disease symptoms.
Method: We examined 23 patients (13 experimental and 10
controls) in a blinded, randomized, controlled study on a number of standard
Parkinson’s measures after participation in eight weeks of twice weekly forced
exercise using a motorized stationary bicycle. Dependent measures were
UPDRS-III, Berg Balance Scale, Fingertapping, and the PDQ-39. Scores were
obtained immediately after the eight week period of exercise and then after a
three month period had elapsed.
Results: Results did not demonstrate any
differences between the exercise and control groups on any measure at any point
in time. A within subjects effect was demonstrated for forced exercise on
overall UPDRS-III scores, but no other within group effects were noted. Results
suggest that early enthusiasm for forced exercise may need tempering.
Limitations of the study are discussed as well as numerous logistical
challenges to this type of study.
P22.64
Randomized Clinical Trial (RCT) of Voice treatment for
Parkinson disease
Lorraine Ramig1,2,3,4 , Cynthia Fox, 1,2,4,
Angela Halpern,2,4 Jennifer Spielman, 2 Katherine Freeman
5
1 University of
Colorado-Boulder, CO, USA
2 National Center for
Voice and Speech-Denver, CO, USA
3 Columbia University,
New York City, NY, USA
4 LSVT Global, Tucson,
AZ, USA
5 Extrapolate
Statistics-New York City, NY, USA
Objective: This RCT was designed to evaluate the short
and long-term impact of voice treatment in PD. 89% of individuals with PD have
a speech and voice disorder that negatively impacts quality of life. Our
research team has developed and advanced an intensive, exercise-based voice
treatment for PD, known as the Lee Silverman Voice Treatment (LSVT). Published
data document improvements in variables critical to functional speech
production: vocal loudness (sound pressure level (SPL)) and pitch variability
(fundamental frequency variability) during reading and monologue that are
maintained 24 months post-treatment. The current study was designed within the
RCT structure to advance the quality of research on voice treatment for PD.
Method: Eighty four subjects (64 with PD, 20
without) ranging in age from 45-85 years old were enrolled. Subjects with PD
were assigned at random to one of three groups: intensive voice treatment
(LSVT), intensive articulation treatment (ARTIC), or no treatment (NOTX). Both
treatments were administered by expert clinicians, four 1-hour sessions per
week for 4 weeks. The primary outcome variable was: SPL across a range of
speech tasks. Acoustic data were collected on two separate days during the week
immediately before (PRE) and after (POST) treatment, and again six months later
(6MO).
Results: Following treatment, the LSVT group
increased SPL significantly on all tasks (p<0.0001) and the ARTIC group
increased SPL significantly on all but one task (p<0.05). The increase in
SPL for the LSVT group was significantly larger than those of any other group
(p<0.05). Only the LSVT group maintained significant increases in SPL
(p<0.001) from PRE to 6MO. Subjects who received LSVT had the greatest
magnitude and duration of treatment effects. The implications of these outcome
data will be discussed in the context of treating disordered speech and voice
in Parkinson disease. (NIH-NIDCD R01-DC01150)
P22.65
Development
of an intelligent bicycle for rehabilitation in Parkinson's disease
Angela L. Ridgel1, Robert S. Phillips1,
Kayla A. Wilson1, Benjamin L Walter2, Fred M. Discenzo4
and Kenneth A. Loparo 3
1Kent State University, Kent, OH, USA
2University Hospital, Cleveland, OH, USA
3Case Western Reserve University, Cleveland, OH, USA
4Rockwell Automation, Mayfield Heights, OH, USA
Objective: The benefits of exercise for people
with Parkinson’s disease (PD) have been documented but it is unclear what
constitutes an optimal exercise intervention. Every individual with PD is
unique and it is likely that exercise responses are not “one size fits all”.
The aim of this study is to construct a novel, automatically controlled cycling
test-bed to investigate the factors and features that are responsible for
significant improvements in motor skills from accelerated cycling.
Methods: Individuals with mild
to moderate PD were randomly assigned into either a static or dynamic cycling
group. Each subject was first evaluated using the UPDRS Motor III scale and
then completed three days of cycling with one day of rest between. A
post-exercise evaluation was completed one day after the last cycling session.
Results: Following
three days of cycling, improvements in the UPDRS motor scores were observed in
both the static (1.1%) and
dynamic (9.8%) groups to lesser degrees. Improvement in the upper extremity (UE) subscale (8.1% and 12.4%) and
changes in the lower extremity (LE) subscale (4.3% worsening and 15.6%
improvement) were also observed for each group. Differences were also observed
between groups for posture (improvements of 1.2% and 9.5%), tremor (9.8%
improvement and 1.4% worsening), bradykinesia (6.0% improvement and 0.4%
worsening) and gait (improvement of 5.1% and 5.3% worsening score). UPDRS
scores for UE and LE scores suggests a systemic effect, driving UE improvements
with LE cycling. In three days of dynamic cycling, participants improved their
Parkinson’s symptoms. This automated cycle provides rigorous test-bed
for correlating cycle operation with the rider’s physical state and resulting
improvement in motor skills. Future studies will use programmable aspects of
the system enable customized cycling regimens for individuals with widely
varying capabilities to be easily implemented.
P22.66
Gait velocity and step length predict aerobic
capacity in patients with Parkinson’s disease
Matthew
A. Sacheli.1, 3, Carolina Rodrigues Alves Silveira,1,
2, and Quincy J. Almeida.1
1Sun Life Financial
Movement Disorder Research and Rehabilitation Centre, Wilfrid Laurier
University, Waterloo, ON, Canada
2University of Waterloo, Waterloo, ON,
Canada
3Pacific Parkinson’s Research Centre,
University of British Columbia, Vancouver, BC, Canada
Objective: To
investigate if specific gait parameters can predict aerobic capacity in
patients with Parkinson’s disease (PD).
Methods: PD patients
(n=95) were evaluated on the Unified Parkinson’s Disease Rating Scale motor
section (UPDRS III), maximum oxygen consumption (VO2 max), and a
GAITRite® electronic walkway to measure motor symptom severity, aerobic
capacity and spatiotemporal aspects of gait respectively. Significantly
correlated variables were entered into a linear regression model to determine
what gait parameters predict aerobic capacity in patients with PD.
Results: After accounting for age and gender,
gait velocity was a significant predictor of VO2 max (R2=0.473;
p<0.001). However due to the colinearity among gait measures, step-length
was also a predictor of VO2 max (R2=0.461; p<0.001),
accounting for the same variability as velocity. The results suggest slower
gait speed/shorter step length are predictive of lower aerobic capacity.
Conclusion: We suggest gait velocity and step
length should be measured when performing aerobic capacity tests in patients
with PD. It is important to account for the severity of gait impairments as
they influence aerobic capacity. Furthermore, rehabilitation strategies focused
on improving aerobic capacity in patients with PD may also want to consider
limitations of gait velocity and step length.
P22.67
Parkinson´s disease: The addition of a concurrent task
changes postural reactions
Carolina Souza1, 3, Mariana Voos2,
Hsin Chien1, Rachael Brant1,3, Erich Fonoff3,
Egberto Barbosa1
1Movement Disorders
Clinic, Department of Neurology, Clinics Hospital, São Paulo, Brazil
2Physical Therapy, Occupational
Therapy and Speech Therapy Department, São Paulo, Brazil
3Movement Disorders
Clinic, Department of Functional Neurosurgery, Clinics Hospital, São Paulo,
Brazil
Objective: This study aimed to determine the effects of
a
concurrent task on postural stability in subjects
with Parkinson's
disease
(PD).
Background: Postural instability is one of the most
disabling features of PD. Studies have shown that the individuals with PD have
difficulty performing dual-tasks. However, few studies have investigated the
postural reactions during the performance of a concurrent task and its
relationship with executive function.
Method: Twenty subjects with Hoehn and Yahr 2-3 were
tested under two conditions: standing quietly and standing while enumerating animals.
The following descriptive measures of the centre of pressure (CoP)
displacement were collected by posturography: the total CoP trajectory over the
support surface, the circular area covered by the CoP, and the velocity of the
CoP sway. Participants also performed the Trail Making Test (TMT).
Results: T-tests showed that the three posturographic measures differed
significantly when single- and dual-task conditions were compared (p<0,001;
p=0,033; p=0,040, respectively). The CoP trajectory and velocity correlated to
the delta of TMT on dual-task condition (r=-0,567, p=0,034; r=-0,567, p=0,034),
but not on single-task condition (r=-0,176, p=0,545; r=-0,177, p=0,545).
Conclusion: The addition of a concurrent test changed postural reactions and
postural reactions correlated to an executive function measure, suggesting the
relation between balance strategies and executive function in individuals with
PD.
P22.68
The effectiveness of occupational therapy in Parkinson’s
disease
Ingrid Sturkenboom1, Maud Graff1,
Yvonne Veenhuizen1, Jan Hendriks1, Bastiaan Bloem1,
Maria Nijhuis-van der Sanden1, Marten Munneke1
1Radboud
University Nijmegen Medical Centre, Nijmegen, the Netherlands
Objective: Evidence for the added value of occupational
therapy (OT) in the care for patients with Parkinson’s disease (PD) is
inconclusive due to a lack of rigorous studies. The aim of this trial is to
evaluate the (cost) effectiveness of OT in improving daily functioning of
patients with PD.
Methods: A multicentre, assessor blinded, two armed
randomized controlled clinical trial, with evaluation at three and six months.
Home dwelling patients with PD and with an OT indication are assigned to the
experimental group or the control group (2:1). Patients and their caregivers in
the experimental group received 10 weeks of home based OT according to recent
Dutch guidelines. The intervention is
delivered by occupational therapists who have been specifically trained to
treat patients according to these guidelines. Participants in the control group
do not receive OT during the study period. The primary outcome for the patient
is self-perceived daily functioning at three months, assessed with the Canadian
Occupational Performance Measure. Secondary patient related outcomes include:
objective performance of daily activities, self-perceived satisfaction with
performance in daily activities, participation, impact of fatigue, proactive
coping skills, health related quality of life, overall quality of life, health
related costs, and effectiveness at six months. All outcomes at the caregiver
level are secondary and include self-perceived burden of care, objective burden
of care, proactive coping skills, overall quality of life, and care-related
costs. Effectiveness is evaluated using a covariance analysis of the difference
in outcome at three months. An economic evaluation from a societal perspective
is conducted, as well as a process evaluation.
Results: Hundred and ninety one patients were included
in the trial. Seven patients have dropped out. The final follow up assessments
take place in April 2013. The outcomes will be presented at the congress.
P22.69
Perceptions of participation
among people with Parkinson’s disease
Björg Thordardottir1, 2, 3, Maria H.
Nilsson 1, 2, 3, Susanne Iwarsson
1, 2, 3, Maria
Haak 1, 2, 3
1Department
of Health Sciences, Lund University, Lund, Sweden
2Centre for
Ageing and Supportive Environments (CASE), Lund University, Lund, Sweden
3Strategic Research
Area of Neuroscience, MULTIPARK, Lund University, Lund, Sweden
Objective: To
describe and deepen the knowledge of perceptions of participation in everyday
life among people with Parkinson’s disease (PD).
Methods: The
qualitative method of conducting focus groups was used, and each group was
interviewed once. The participants were recruited at the Department of
Neurology, Skåne University Hospital in Lund, Sweden, and they should have had
their PD diagnose for > one year. Strategic sampling was used to ascertain
that the participants represented men and women, different ages and a variety
regarding living arrangements, work and family situations. Recruitment
continued until saturation was reached, and the final sample consisted of 29
participants. Their mean (SD) age was 68 years (6.2) and the mean (SD)
PD-duration was 11.1 (7.9) years. Homogeneity within each focus group was based
on self-rated disease severity (mild, moderate or severe). In total, nine focus
groups were conducted (three groups per severity grade): mild (n= 11, min-max:
3-5), moderate (n=10, min-max: 3-4), and severe (n=8, min-max: 2-3). The focus
groups were led by an experienced researcher and a PhD student.
Results: The
preliminary analyses indicate that unchanged participation is important for
people in the early stages of the disease, even if it is under new
circumstances. The participants with moderate or severe symptoms express that
they are more dependent on surrounding people’s attitudes and awareness of the
disease in order to be able to participate in desired activities. Situations
considered by all focus groups as important to participate in, involved being
with other people and/or performing activities in order to maintain a
meaningful everyday life. This study provides valuable knowledge about
perceptions of participation at different stages of PD. These findings are of
importance for health care professionals in order to support people with PD
towards maintained participation in everyday life.
P22.70
Feasibility, safety and efficacy of dance for people with
Parkinson’s disease: A systematic review
Rebecca Twyerould1, Meg E Morris2,
Jennifer L McGinley1
1The University of
Melbourne, Victoria 3010, Australia
2La Trobe University,
Victoria 3086, Australia
Objective: To conduct a systematic review of the
feasibility, safety and efficacy of dance interventions for adults with
Parkinson’s disease.
Methods: Relevant studies were identified by
electronic searches of databases including CINAHL, MEDLINE, Scopus, PEDro and
PsycINFO. Studies were included if: (1) the primary focus was to examine the
feasibility or effect of dance intervention in people with PD; (2) and the
study was a primary publication in English with an available full text. The
quality of the studies was assessed by two independent authors using the PEDro
scale and a customized quality appraisal tool. Reports of feasibility and
safety were explored and an overview of the content and conduct of the dance
interventions was provided. Data were synthesized to assess the effectiveness
of dance interventions on balance and mobility.
Results:
Ten
trials (12 articles) with a total of 332 participants were identified. Study
designs included five RCT’s and five case series studies, with reported sample
sizes ranging from 11-75. The dance styles reviewed included both partnered and
nonpartnered tango, waltz and a variety of modern dance styles. In general,
studies varied from low to moderate in quality, with considerable variation in
the level of detail provided regarding feasibility and safety. Although well
reported, attrition rates varied widely from 0% to 50%. Limited information was
available regarding adherence, monitoring or the occurrence of adverse events,
and in-class supervision. The data synthesis revealed that there was a positive
trend toward improvements in balance and functional mobility when compared to a
control group. Dance has the potential to improve physical function and quality
of life in people with PD. More detailed reporting of feasibility and safety
are encouraged to enhance the application of research into clinical practice.
P22.71
Identifying when changes to
Parkinsonian gait occur within a vibratory intervention study
Kyle N Winfree1,
Barry Milcarek2, Sunil K Agrawal3, Ingrid
Pretzer-Aboff4
1University of Pennsylvania, School of Medicine,
Philadelphia, PA, USA
2University of Delaware, College of Health Sciences,
Newark, DE, USA
3Columbia University, Mechanical Engineering, New
York, NY, USA
4University of Delaware, School of Nursing, Newark,
DE, USA
Objective: The aim of this study is to identify if a statistically significant
change in unilateral step duration, stance duration, and swing duration occurs
during Parkinsonian gait when exposed to step-synchronized vibratory feedback.
Methods: Five subjects with Parkinson's disease were recruited. While wearing
the PDShoe volunteers walked 10 meter laps for a total of 22 minutes, twice a
day for 4 days as part of a vibration intervention gait study. Each subject
performed the following walking protocol: two-minutes without vibration
(pre-therapy), three bouts of six-minutes each step-synchronized vibration
(therapy), and two-minutes again without vibration (post-therapy). Two minute
rest breaks occurred between each walking bout.
Analysis: Gait data was collected using the instrumented shoe. Only the first
session of the study was considered; five twenty-two minute sessions were
considered in all. Data was sampled at greater than 10 Hz. Turns were removed
from the data stream so that all analysis was performed on straight path
walking. Each step of the left foot was analyzed for step, stance, and swing
duration. We merged consecutive bouts from each walking session (pre-therapy,
therapy, and post-therapy), with rest periods removed. Change point analysis
was performed on each session with 1000 bootstrap resamplings. The largest
change point for step, stance, and swing duration was identified and tested for
significance using a confidence level of >90%.
Results: Change point analysis illustrated significant changes in all three
measures for each subject. These change points were only present in the therapy
bouts, indicating an effect of therapy on Parkinsonian gait. Change to step
duration was not exclusively reflective of a change to either stance or swing
duration since both of those also changed. Continued analysis will include
cluster analysis to identify common change points across additional study
sessions.
CLINICAL SCIENCES: COMPLICATIONS OF THERAPIES
P23.01
Medication administration errors
and In-Hospital Complications for Patients with Parkinson’s disease: A
Retrospective Review
1Jason
Aldred, Anderw Borgert2
1Department
of Neurology, Gundersen Health System, La Crosse, WI, USA
2Department
of Medical Research, Gundersen Health System, La Crosse, WI, USA
Objective: To
determine the occurrence of errors in medication administration or
administration of medications contraindicated for Parkinson’s disease in the
inpatient setting over 1 year. The secondary endpoints of this study are to
determine reason for errors in medication administration, reason for usage of
medications contraindicated in Parkinsonism, difference in medication
administration schedule in the hospital compared to in-clinic, reasons for
admission, reason for in-hospital complication, length of stay as function of
medication errors or contraindicated medications recorded.
Methods: Our
hospital electronic health record will be used to retrospectively identify
patients who were diagnosed with Parkinson’s disease or any form of
parkinsonism and admitted to the hospital over a year. Demographics; type of
Parkinsonism; co-existing diagnoses; daily levodopa equivalent dose;
anti-parkinson medication dose and frequency as outpatient prior to admit;
anti-parkinson medication dose and frequency from EHR MAR during admission;
actual medication administration dose and frequency from EHR MAR; reason for
admission; new diagnoses at time of discharge; deterioration during admission;
reason for deterioration; duration of hospitalization.
Results: We
anticipate examining approximately 1200 PD medication administrations for the
time period in question (100 patients x 3 days in hospital x 4 PD medication
administrations per day). Descriptive statistics such as means, proportions and
prevalence, along with their respective 95% confidence intervals will be
calculated. Comparisons between groups with high versus low rates of medication
error will utilize either chi-squared and Wilcoxon rank sum tests for
non-parametric/non-normal data or Student’s t-test for normally distributed
data. Logistic regression may be utilized to model patient outcomes.
P23.02
Nicotine and nicotinic receptor drugs reduce
L-dopa-induced dyskinesias in a nonhuman primate model of Parkinson's disease
Maryka Quik1, Danhui Zhang1, F. Ivy
Carol2, Michael Decker3, Tanuja Bordia1
1SRI, Menlo Park, CA,
USA
2RTI
International, Research Triangle Park, NC, USA
3AbbVie, Inc, North Chicago, IL, USA
Objective: Although L-dopa is one of the primary
therapies for Parkinson's disease, it can lead to disabling dyskinesias for
which there is little treatment. Nicotine has recently been shown to decrease
L-dopa-induced dyskinesias (LIDs) in several parkinsonian animal models. The
goal of the current study was to identify the optimal nicotine treatment
regimen for reducing LIDs in nonhuman primates and to test if nicotine improved
LIDs in both L-dopa-primed and L-dopa naïve monkey. In addition, we investigated
the effectiveness of the nicotinic receptor drugs varenicline and ABT-089,
which acts selectively in the brain thus minimizing side effects.
Methods: Monkeys were given MPTP until parkinsonian.
Nicotine or nicotinic receptor drugs were then given to L-dopa-naïve or L-dopa
primed monkeys, with L-dopa (10 mg/kg) gavaged twice daily. Dyskinesias were
scored every 30 min. Parkinsonism was also measured.
Results: Nicotine was given to nonhuman primates in
the drinking water before L-dopa treatment was started and also to animals with
pre-existing dyskinesias. Nicotine decreased LIDs by 60-70% after several weeks
of treatment in both the L-dopa-naïve and L-dopa primed animals. The beneficial
effect of nicotine was consistently observed for the entire course of the
study, which lasted up to 23 weeks. Nicotine did not worsen parkinsonism. We
also tested the effect of the nicotinic receptor drugs varenicline, which has
been approved for use in humans as a smoking cessation aid, and ABT-089, which
has been evaluated in phase 2 clinical trials for other indications. Both
ABT-089 and varenicline reduced dyskinesias by about 50%. The effect of these
drugs persisted for the entire length of the study (several months). These
combined data suggest that treatment with nicotine and nicotinic receptor drugs
has potential as a successful antidyskinetic therapy for L-dopa-treated
Parkinson's disease patients. These studies were supported by NIH grant NS59910
P23.03
Task-coupled
dyskinesias in patients with Parkinson disease
Roople
Unia1, Thomas Mera2, and Michelle Burack1
1University of Rochester Medical Center
2Great Lakes Neurotechnologies
Objective:
To
characterize interactions between voluntary and involuntary movements in
individuals with Parkinson disease (PD) and levodopa-induced dyskinesias (LID).
Background:
Levodopa-induced
dyskinesias are a common complication of chronic levodopa therapy in patients
with PD. The phenomenology includes both choreiform and dystonic movements, and
is thought to involve abnormal signaling in basal ganglia circuits that
regulate the activity of motor pattern generators. We hypothesized that
execution of voluntary movements would modulate the severity of dyskinetic
movements in body segments engaged in the task, whereas dyskinetic movements in
remote body segments would be unaffected by the task.
Methods:
We
enrolled 15 subjects with idiopathic PD and predictable motor fluctuations with
Off period akinesia and peak dose dyskinesias. A network of 10 triaxial
inertial sensors (Kinetisense, Great Lakes NeuroTechnologies) was used to
monitor head, trunk, and extremity movements during a set of standardized
tasks, with simultaneous video recording for blinded clinical ratings of
dyskinesia severity (modified Abnormal Involuntary Movement scale). Tasks were
performed prior to, and repeated after a usual dose of medication. For this
report, we focused on the subset of tasks that engaged only one hand for
voluntary movement: drinking from a cup and combing hair.
Results:
During
video review, we noted that in individual patients, specific voluntary
movements were temporally coupled to a dyskinetic movement in a body segment
not engaged in the task. For example, stereotyped head movements were also seen
during tasks that engaged the upper extremity. Angular velocity plots from the
inertial sensors confirmed coupling between voluntary movements and involuntary
movement of a body segment that was not engaged in the task.
Conclusions:
The
observation of task-coupled dyskinesias suggests that dyskinesias are not
random but rather, may be triggered by motor pattern generators that are
somatotopically remote from body segments involved in carrying out the specific
task.
CLINICAL
SCIENCES: CLINICAL TRIALS: DESIGN, OUTCOMES, RECRUITING, ETC.
P24.01
Improving health workers’ effectiveness in
Sub- Saharan Africa
Skyler Jayden Dembe1, Ryan Evans
Ntambi1, Derrick Kawuma2 ,Mary Nambi 2
1Global Initiative Uganda (GIU),Masaka,
Uganda
2Makerere, University,
Kampala, Uganda
Objective: The aim of the study to investigate
effectiveness of human resource management initiatives in Sub- Saharan Africa
(SSA).
Methods: Effectiveness not only explores whether an
intervention has shown to be effective, but also through which strategies an
intervention produces outcomes and which contextual factors appear to be of
critical influence. Forty-eight published studies were reviewed.
Results: The results indicated that human resource
management initiatives can improve health workers' effectiveness, but that
different contexts produce different outcomes. Critical implementation aspects
were involvement of local authorities, communities and management; adaptation
to the local situation; and active involvement of local staff to identify and
implement solutions to problems. Strategies that triggered change were
increased knowledge and skills, feeling obliged to change and health workers'
motivation. Strategies to contribute to motivation were health workers'
awareness of local problems and staff empowerment, gaining acceptance of new
information and creating a sense of belonging and respect. In addition, staff
was motivated by visible improvements in quality of care and salary
supplements. Only a limited variety of human resource management initiatives
have been evaluated in the health sector in SSA. Assumptions underlying human
resource management initiatives are usually not made explicit, hampering our
understanding of how human resource management initiatives work.
Conclusion: Application of a
realist perspective allows identifying which human resource management
initiatives might improve effectiveness, under which circumstances, and for
which groups of health workers. To be better able to contribute to an
understanding of how human resource management initiatives could improve health
workers' effectiveness, a combination of qualitative and quantitative research
methods would be needed and the use of common indicators for evaluation and a
common reporting format would be required.
P24.02
Which treatments are in the
pipeline for the management of falls in Parkinson disease?
Josefa Domingos1,
Catarina Godinho2, Joaquim J Ferreira1,
1Neurological
Clinical Research Unit, Instituto de Medicina Molecular, Laboratory of Clinical
Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon,
Lisbon, Portugal
2 Instituto
Superior de Ciências da Saúde Egas Moniz, Centro de Investigação
Interdisciplinar Egas Moniz (CiiEM). Almada, Portugal
Background: Tremendous
efforts are being made to develop effective treatments for preventing falls in
Parkinson disease (PD). To determine which therapeutic interventions are being
developed in this area, we conducted a review of clinical trials listed in the
open access registries for ongoing trials.
Methods: We
searched the World Health Organization International Clinical Trials Registry
Platform, Clinical Trials gov and the European Clinical Trials Database for
ongoing controlled trials that proposed to evaluate therapeutic interventions
for the management of falls in PD. Data was extracted on characteristics of
trial design, participants, interventions and outcomes.
Results: Thirty
trials met the inclusion criteria for this review with a total of 5669
participants planned to be recruited. There were 23 trials evaluating a
non-pharmacological intervention and 7 trials for pharmacological
interventions. There were 18 randomized trials with a parallel group design and
3 with a cross-over design. Physiotherapy treatments were a main component of
non-pharmacological interventions and included: treadmill training with virtual
reality, balance programs, home-based programs, multifactorial fall prevention
program, and exercise programs. Pharmacological treatments were in smaller number
and included studies testing the efficacy of vitamin D, Donepezil,
Rivastigmine, Methylphenidate, Droxidopa and Rasagiline. Outcomes related to
falls included: rates of falling, falls frequency, fear of falling, frequency
of near falls, number of fallers, and number of injurious falls. This was
measured by using falls diaries, calendars, postcards, and telephone reminders
or interviews. The majority of the studies included patients in Hoehn &
Yahr stage II-III.
Discussion: There are
clinical trials evaluating pharmacological and non-pharmacological
interventions for falls in individuals with PD on-going. The
non-pharmacological trials include several different interventions which
reflects the heterogeneity of physiotherapy therapeutic interventions. The heterogeneity
of the study designs and outcomes reflects the absence of accepted
recommendations for the design of trials in this increasingly relevant field.
P24.03
Barriers to traditional research design: a study of
exercise and disease progression in persons with Parkinson’s disease (PD)
Matthew P Ford1, James Cavanaugh2,
Gammon Earhart3, Terry Ellis4, Kenneth B Foreman5,
Carrie Huisingh1, Gerald McGwin1, Lee Dibble5
1The University of
Alabama at Birmingham, Birmingham, AL, USA
2University of New England,
Biddeford, ME, USA
3Washington University
in St Louis, St. Louis, MO, USA
4Boston University,
Boston, MA, USA
5University of Utah,
Salt Lake City, UT, USA
Objective: The objective of this project was to assess
the effects of participant attrition on longitudinal study of physical activity
and exercise characteristics in persons with PD.
Methods: 263 persons PD (Hoehn and Yahr II – III; mean
= 2.4) participated in a two-year longitudinal study at four different sites
(Boston University; University of Alabama at Birmingham; University of Utah;
Washington University in St. Louis). Participants were assessed at baseline and
every six months after baseline assessment for two years. Investigators
collected data on patients’ health, PD symptoms, falls, physical
activity/exercise habits, quality of life (QOL), walking and balance. Over the
course of the study participants withdrew for various reasons, the most common
being worsening disease and problems with transportation. For this analysis we
categorized those participants who did not attend their 24-month post-baseline
assessment as dropped from the study. T-tests were used to compare baseline and
follow-up (12-month) characteristics between participants who did and did not
drop out of the study. Paired t-tests were used to compare baseline to 12-month
characteristics within each group. Finally, t-tests were used to compare the
change in characteristics from baseline to follow-up by dropout status.
Results: 172 remained, while 94 dropped from the
study. Participants that remained in the study were significantly different
than those that dropped out when comparing baseline characteristics (Table 1).
Furthermore, when comparing the changes over 12 months, these groups (remaining
vs. drops) showed significant differences in # of comorbidities, # of falls, 6
minute walk distance, quality of life (PDQ-39), and physical activity (PASE).
Table 1. Baseline characteristics of participants by
dropout status
|
Dropouts
(n=94) Mean
(SD) |
Remained
in study (n=172) Mean
(SD) |
p-value1 |
# of
co-morbidities |
3.4
(1.9) |
2.8
(1.6) |
0.0091 |
# of
falls |
1.0
(1.0) |
0.7
(0.9) |
0.0020 |
UPDRS
Total |
75.6
(29.3) |
55.8
(22.3) |
<0.0001 |
10 MWT
(self-selected speed)3 |
65.2
(16.5) |
72.3
(15.4) |
0.0010 |
10 MWT
(maximum speed) 3 |
87.6
(23.4) |
100.2
(24.6) |
<0.0001 |
6 MWT2 |
369.0
(124.3) |
499.9
(122.0) |
<0.0001 |
FGA
(balance)4 |
18.1
(7.0) |
21.8
(5.6) |
<0.0001 |
BERG
(balance)2 |
47.3
(8.2) |
51.8
(5.4) |
<0.0001 |
PDQ-395 |
27.7
(15.7) |
17.6 (11.4) |
<0.0001 |
PASE
(physical activity) |
111.9
(79.2) |
146.2
(82.3) |
0.0014 |
1t-test
2n=1 missing data
3n=2 missing data
4n=3 missing data
5n=4 missing data
Note: Last observation
carried forward used.
Table 2. Change in characteristics from baseline to
12-month follow-up (12-month minus baseline) by dropout status
|
Dropouts |
Remained
in study |
p-value1 |
|
Mean
(SD) |
Mean
(SD) |
|
# of
co-morbidities |
-1.2
(1.8) |
-1.8
(1.9) |
0.015 |
# of
falls |
0.1
(0.7) |
-0.1
(0.7) |
0.0027 |
UPDRS
Total |
1.6
(11.6) |
-0.3
(15.0) |
0.26 |
10 MWT
(self-selected speed) |
-3.6
(10.3) |
-2.2
(10.4) |
0.29 |
10 MWT
(maximum speed) |
-3.9
(11.3) |
-1.8
(11.5) |
0.17 |
6 MWT |
-4.2
(60.8) |
11.7
(65.1) |
0.052 |
FGA
(balance) |
-0.9
(3.9) |
-1.2
(3.7) |
0.55 |
BERG
(balance) |
-1.3
(4.7) |
-0.2
(3.6) |
0.058 |
PDQ-39
|
1.0
(7.3) |
-1.0
(6.5) |
0.023 |
PASE
(physical activity) |
-61.1
(82.1) |
-8.6
(73.3) |
<0.0001 |
1t-test
P24.04
Initial choice
of dopaminergic therapy in the NINDS Exploratory Trials in Parkinson Disease
(NET-PD) Longitudinal Study-1 (LS-1)
John L. Goudreau1,
Adriana Pérez2, Keith D. Burau2, Chad Christine3,
James T. Boyd4, Maureen Leehey5, on behalf of the NET-PD LS-1
Investigators.
1Michigan State University, East Lansing, MI, USA
2University of Texas School of Public Health, Austin, TX, USA
3University of California, San Francisco, San Francisco, CA, USA
4University of Vermont, Burlington, VT, USA
5University of Colorado School of Medicine, Aurora, CO, USA
Objective: Selecting
the initial dopaminergic therapy in early Parkinson disease (PD) is a major
clinical decision, yet associated factors for that decision have not been
extensively studied. The NINDS Exploratory Trials in PD (NET-PD) Longitudinal
Study-1 (LS-1) is a randomized, multicenter, placebo-controlled trial designed
to determine the disease modifying efficacy of creatine in early/mild PD.
Participants were enrolled in the LS-1 study after they were on stable doses of
dopaminergic therapy for at least 3 months, but not longer than 24 months.
Importantly, the selection of
dopaminergic therapy was made by providers in the community and occurred prior
to entry into clinical trial, which increases the likelihood that the results
will be relevant to treatment decisions for the general PD population. Given
the large sample size (N=1741) and relatively broad inclusion criteria, the
baseline data from the LS-1 study provides a unique opportunity to investigate
factors that may be associated with the choice on initial dopaminergic therapy
to treat early, mild PD. The hypothesis that younger age, availability of
health insurance, and lower medical comorbidities is associated with the
initial choice of dopamine agonist therapy was tested in LS-1 study
participants.
Methods: Multivariable
analysis was used to identify factors associated with the initial selection of
dopaminergic therapy (levodopa, dopamine agonist, or the combination of
levodopa+dopamine agonist) in the NET-PD LS-1 study. Health insurance
availability, education, family history of PD, time since diagnosis, use of
non-dopaminergic adjunctive medications, medical comorbidities and socio-demographic
factors were evaluated at baseline among 1616 participants with early, mild PD
selected from the overall LS-1 study.
Results: Younger age, higher education level, greater years since PD
diagnosis and use of an adjunctive, non-dopaminergic medication were associated
with more frequent use of dopamine agonist compared to levodopa or combination
therapy.
P24.05
Home-based motion sensor monitoring for Parkinson’s
disease clinical trials
Dustin A. Heldman1, Alberto J. Espay2,
Peter A. LeWitt3, and Joseph P. Giuffrida1
1Great Lakes
NeuroTechnologies, Cleveland, OH, USA
2University of
Cincinnati, Cincinnati, OH, USA
3Henry Ford Hospital
and Wayne State University School of Medicine, West Bloomfield, MI, USA
Objective:
The objective was to determine the sensitivity and reliability of
a home-based motion sensor system compared to traditional measures for gauging
Parkinson’s disease (PD) motor symptoms. Clinical trials typically rely on subjective
rating scales, which can suffer from bias, placebo effects, limited resolution,
and poor intra- and inter-rater reliability. Additionally, symptoms that tend
to fluctuate throughout the day cannot be monitored in a single visit. To
compensate for this lack of temporal resolution, subjects in clinical trials
are often asked to complete daily diaries; however, these diaries yield
suboptimal data due to poor compliance, recall bias, and inaccurate
self-assessment.
Methods: Eighteen PD patients
treated with subthalamic deep brain stimulation (STN DBS) performed tasks
evaluating tremor and bradykinesia while wearing a wireless motion sensor unit
on the index finger. The sequence of three tasks was performed three separate
times with DBS turned off and on at 10 separate stimulation amplitudes, as DBS
provides a unique opportunity slowly modulate symptom severity. This study
paradigm provided a wide range of symptom severities with relatively few
subjects. It also simulated subtle motor symptom progressions in individual
subjects in a manner that otherwise might take years to observe. Each task was
digitally videoed for subsequent clinical rating.
Results: The reliability and
sensitivity of the motion sensor system was comparable to the clinician ratings
for rest and postural tremor, but significantly better for finger tapping
speed, amplitude, and rhythm. This suggests that, when applied in the home
environment, motion sensors can provide significantly increased resolution in
both amplitude and time compared to traditional measures, which in turn could
decrease the number of subjects, costs, and time to detect significant motor
changes in clinical trials.
P24.06
Apokyn for
morning akinesia trial (AM IMPAKT)
Stuart H. Isaacson1, Jean Hubble2,
Kristen Gullo2
1Parkinson’s Disease and Movement
Disorders Center of Boca Raton, Boca Raton, FL, USA
2US WorldMeds, LLC, Louisville, KY, USA
Objective: The primary
objective of this study is to assess the effect of APOKYN (apomorphine HCl
subcutaneous injection) in Parkinson’s disease (PD) patients with morning akinesia
resulting from delayed or unreliable onset of effect of first morning dose of
L-dopa. A secondary objective is to assess APOKYN’s effect on gastric motility
in a subset of study patients with symptoms of gastroparesis. The primary study
outcome is a comparison of patient self-reported, diary-recorded Time to On
(TTO) following first morning dosing of L-dopa at baseline for one week
compared to TTO when using APOKYN each morning for one week. The study will
additionally provide data
on the effects of APOKYN, a potent dopamine agonist that bypasses
the
GI tract, on gastroparesis, a common, yet often undertreated, non-motor symptom of PD that may exacerbate L-dopa motor fluctuations.
Methods: This Phase IV, multi-center, open-label study is
enrolling eligible PD patients at 12 US study sites
with a target enrollment of 100 subjects. Subjects
complete a Baseline Period recording daily TTO following their regularly
scheduled L-Dopa morning dose for 7 days. At the end of the Baseline Period,
subjects start trimethobenzamide antiemetic therapy and begin APOKYN titration.
Once the investigator identifies an optimal dose, subjects self-inject APOKYN
at their regularly scheduled L-Dopa morning dose time (L-Dopa first morning
dose is delayed by 40 minutes) during a 7-day APOKYN Treatment Period and
record TTO following the APOKYN injection. In the gastric motility sub-study,
subjects participate in a gastric emptying imaging study following a
standardized meal during the Baseline Period (taking their usual L-Dopa dosing)
and during the APOKYN Treatment Period (following morning APOKYN injection).
Results: An interim analysis of the primary TTO
change from baseline endpoint, key secondary endpoints and gastric emptying
time results from the sub-study participants will be available for presentation
in October.
P24.07
The group
exercise program for improving self-body image and posture for Parkinson
disease
Nami Kawano1, Kayo Nakamoto2, Yutaka Uchida3,
Takeshi Miyazaki4, Ken Koguchi2, Kazuo Abe3,4,5
1Osaka Electro-Communication University, Shijonawate,
Osaka, Japan
2Shirahama Hamayu Hospital, Nshimuro, Wakayama, Japan
3Konan Hospital, Kobe, Hyogo, Japan
4Garacia Hospital, Mino, Osaka, Japan
5Osaka Health Science University, Osaka, Osaka, Japan
Objective: We attempted to develop a novel innovative group
exercise program that improving self-body recognition and postural impairment.
We studied effectiveness of this exercise program for Parkinson’s disease (PD)
patients in several hospitals.
Methods: We recruited 33 PD patients who gave informed consent
for the purpose, method of the research and voluntarily participated in the
program; mean age was 72.1 years (range, 48 to 90 years), and the severity of disease corresponded to stages 1 (n
= 2), 2 (n = 4), 3 (n =22) and 4 (n=5) evaluated by the Hoehn and Yahr stage.
The exercise program developed for improving self-body recognition and posture.
During exercise, patients leaned and push a ball on the back of the seat by the
level of the lower thoracic. Patients were told to keep moving with paces of
themselves and move without a command or music. Patients conducted 30-minutes
exercise supervised by physical and occupational therapists every week for 2
months. The unified Parkinson’s disease rating scale (UPDRS) score, posture,
and grip strength were assessed at the first session and after 2 months.
Results were analyzed by paired t-test and nonparametric Wilcoxon test using
statistical software (PASW Statistics 18).
Results: Twenty-two patients with camptocormia and scoliosis
were improved. Three patients with aids to keep standing position improved to
keep standing position without aids. Sixteen patients improved UPDRS scores.
Seventeen patients increased grip strength. On the basis of our results, our
exercise program may be useful for improving disease severity, postural
impairment in PD patients.
P24.08
Measuring clinically
important changes in disability ratings using IV levodopa for phase IIa trials
of new-anti-dyskinetic drugs in Parkinson’s disease
Tiago A. Mestre1,
Nicolas Phiellip1, Camila Henriques de Aquino1, Jane Lui2,
Yu Yan Poon1, Julie So1, Susan H. Fox1
1 Morton & Gloria Shulman Movement Disorders
Centre, Toronto Western Hospital, University of Toronto, Toronto, Canada
2 Investigational Pharmacy Services, University Health
Network, Toronto Western Hospital, Toronto,
Canada
Objective: 1. To test the feasibility of using patient-reported outcomes in the IV
levodopa model as methods of evaluating change. 2. To determine clinically important changes in dyskinesia or
parkinsonism as per patient report.
Methods: We included patients with advanced PD (UK PD Society Brain Bank criteria), age 30-80
years, stable bothersome dyskinesia (LFADLDS≥1; peak-dose dyskinesia for
>25% of the daytime) and stable anti-parkinsonian medications (>1 month).
A randomized, double blind, placebo-controlled crossover design was adopted,
with an initial run-in phase. A video protocol was used for assessment of
patient-reported clinically important events as determined by a 5-point Likert
scale. The following clinically important events were considered: onset of
dyskinesia, maximum intensity of dyskinesia, remission of dyskinesia and onset
of improvement in parkinsonism, best ON and onset of wearing-OFF. Two
blinded raters individually rated dyskinesia and/or parkinsonism by video
assessment of the clinically important events, using the UDysRS-III and
MDS-UPDRS-III, respectively and the scores averaged. Non-parametric
paired testing (Wilcoxon signed-rank paired test) was used to compare median scores at
baseline and at each clinically important event. A P value of 0.05 was significant.
Results: We recruited 6 individuals. One of those was excluded due to issues
with venous access. All patients were able to report all parkinsonism-related
clinically important events, but were less often able to identify onset of
dyskinesia (n=4) and maximum intensity (n=2) or remission of dyskinesia (n=2).
The minimal clinically important change as reported by the patient was, for dyskinesia,
11.8 points (IQR
=12) in the UDysRS-III and, for the antiparkinsonian effect, 7.3 points (IQR
=18.3) in the MDS-UPDRS-III. There were no reportable side effects.
P24.09
Clinical
research participation among people with Parkinson¹s: examining the importance
of travel assistance when deciding to join a study
Karlin
Schroeder. David Blomquist, Veronica Todaro, Robin Elliott
Parkinson¹s Disease Foundation, New York, NY,
United States
Objective: To determine the
importance of travel assistance to people with Parkinson¹s who participate in
clinical studies.
Methods: An online survey was
administered in April 2013 to people with Parkinson¹s who have participated in
a clinical study. The survey data will be analyzed to determine how travel
assistance ranks in comparison to other factors when considering whether or not
to participate in a clinical study. Data will also be analyzed to determine if
study participants are provided with travel assistance and if so, what type of
assistance is offered (reimbursement for travel, provision of a voucher for a
hotel stay, etc.).
Results: Data will be analyzed
via descriptive and correlational analysis. Patient demographic data and study
enrollment history will also be included in the analysis.
P24.10
Pair up for Parkinson’s research: the impact of local
clinical research education forums on study inquiry and enrollment
Karlin Schroeder, David Blomquist, Veronica Todaro, Robin
Elliott
Parkinson’s Disease
Foundation, New York, NY, USA
Objective: To determine the impact of Parkinson’s
Disease Foundation Pair Up for Parkinson’s Research Educational Forums on
increasing study inquiry and participation among people with Parkinson’s disease
and care partners.
Methods: An on-site survey was administered to
people with Parkinson’s and care partners who attended one of two (Arizona and
Colorado) PAIR Up for Parkinson Research educational forums in April 2013 to
determine if knowledge about clinical research increased and the likelihood of
participating in clinical research increased among attendees. A survey will be
administered in June to people with Parkinson’s and care partners who completed
the on-site survey to determine if individuals contacted a study site and if
so, whether they were eligible to participate in the study, and if they
enrolled. This survey will be administered online, with follow-up phone calls
utilized to maximize the response rate of survey recipients.
Results: Survey data will be collected, tabulated,
analyzed and reported. A comparison will be made between individuals who have
previously participated in a clinical study and those who did not make an
inquiry or participate in a clinical study prior to attending the educational
forum.
P24.11
A cohort study of
Parkinson’s disease in British Columbia
Vanessa Silva1,2,
Christina Thompson1,2, Kim Co1,2, Michelle K. Lin1,
Chelsea Szu Tu1, Heather Han1, Holly Sherman1,
Mary Encarnacion1, Frederick Pishotta1, Daniel Evans1,
Viera Saly3, Martin McKeown2, Joseph Tsui2,
Silke Appel-Cresswell2, A. Jon Stoessl2 and Matthew
Farrer1,2
1Centre for Applied Neurogenetics,
University of British Columbia (UBC), Vancouver, BC, Canada
2Pacific Parkinson’s Research Centre,
Department of Medicine (Neurology), UBC, Vancouver, BC, Canada
3Victoria General
Hospital, Victoria, BC, Canada
Objective:
Approximately 100,000 Canadians have Parkinson’s disease (PD)α
yet our understanding of disease etiology, pathogenesis, and response to
treatment remains inadequately defined. We have initiated a study to assess the
role of genetic susceptibility variants/pathogenic mutations in PD. Herein we
describe: 1) our clinic-based cohort, recruitment efforts and impediments to
subject participation; 2) preliminary data on the frequency of pathogenic
mutations. We hypothesize genetic analysis, made possible through province-wide
participation, may improve the diagnosis/prognosis of patients and may
ultimately yield disease-modifying therapies.
Methods: In BC,
subjects have been primarily recruited through the UBC Movement Disorder
Clinic, a community neurologist clinic, support groups and various lay
publications. Participants provide detailed information on ancestry and family
history of neurologic disease. For most patients, standardized clinical
questionnaires including motor and cognitive assessments are administered and
neurologic exams performed. Blood samples are collected. Extracted DNA is
screened for: i) Pathogenic mutations in genes known to cause PD (LRRK2,
DNAJC13, SNCA, VPS35, EIF4G1, PINK1, and PARK2) and; ii) genes implicated in
neurodegenerative disease β. Clinical, genealogic and genetic
data are organized in a database designed to ensure participant
confidentiality.
Results: Patients
(n=713), affected/unaffected family members (n=159) and control participants
(n=120) provided informed consent to participate. The mean age for patients was
64±13SD years (range=21-91) with early-onset PD (≤45 years) totalling 17%
of the cohort. A total of 232 patients had sporadic PD whereas 321 reported a
family history. For PD patients, where data were provided on initial symptoms
(n=154), 71% had resting tremor, 14% bradykinesia, 8% rigidity and 7% postural
instability. Mutations were found in 1.5% (11/713) of patients. In conclusion,
although we have established a substantial cohort, increased effort is needed
to expand recruitment across BC. As analysis continues, a more standardized
method of collecting clinical assessments is essential to effectively correlate
clinical with genetic data.
α
Parkinson Society Canada
β
see abstract by Lin, Evans et al.,
P24.12
Efficacy, safety and
tolerability of rasagiline as add-on to suboptimal dopamine agonist monotherapy
in Parkinson’s disease (PD): The ANDANTE study
Dee Silver1; Stuart
Isaacson2; Azhar Choudhry3; Robert A. Hauser4
1Coastal Neurological Medical Group, La Jolla, CA,
USA
2Parkinson’s Disease and Movement Disorders Center of
Boca Raton, FL, USA
3Teva Pharmaceutical Industries, Kansas City, MO, USA
4Parkinson’s Disease and Movement Disorders Center,
University of South Florida, Tampa, FL, USA
Background and Objective: Dopamine agonists
(DAs) are often used as initial PD monotherapy. However with disease
progression DA monotherapy alone becomes sub-optimal and patients often require
additional dopaminergic therapy to maintain symptomatic efficacy. Traditional
options at this stage include levodopa (associated with risk of dyskinesia) or increasing DA dose (associated with higher
risks for ICDs and other side-effects). Rasagiline is a selective, irreversible MAO-B
inhibitor, and this distinct mode of action provides a rationale as add-on
therapy to DAs for additional symptomatic benefit. The objective of this study was to determine the
efficacy, tolerability and safety of add-on rasagiline therapy for early-PD
patients sub-optimally controlled by DA monotherapy.
Methods: ANDANTE was an 18-weeks, placebo-controlled
(randomized 1:1) study of PD patients (Hoehn&Yahr 1-3) aged ≥30 years
taking stable DA dosages with suboptimal control. The primary outcome was
change from baseline in total-UPDRS score. Secondary outcomes were changes from
baseline in UPDRS motor and ADL scores, and CGI. Exploratory outcomes were
changes from baseline in Scales for Outcomes in Parkinson’s Disease
(SCOPA)–Sleep, SCOPA–Cognition, Brief Smell Identification Test, and
Parkinson’s Disease Questionnaire. Safety was assessed by AE
frequency/severity. Out of 328 patients randomized, 321 (mean age 62.6;
duration PD 2.13 years) were included in the efficacy analysis.
Results: Treatment with add-on rasagiline
significantly improved total-UPDRS scores versus placebo (Figure). Significant
improvements in UPDRS-motor scores were also observed (p=0.007). There were no
significant differences between groups for ADL, CGI or any exploratory
measures. Rasagiline was well-tolerated, with no significant difference in
percentage of patients with AEs (64.2% vs. 61.0%) or serious AEs (4.9% vs.
3.0%) versus placebo. Only 11 patients required rescue levodopa during the
study.
Conclusions: Addition of rasagiline significantly improved
motor symptoms in patients sub-optimally controlled with DA
monotherapy, and was
well-tolerated.
Figure: Change from baseline in total-UPDRS scores
P24.13
Expectations of Parkinson’s patients from the
next decade of research
Jon
Stamford1, Parkinson's Movement1
1Parkinson’s Movement, The Aldgate
Rooms, St Botolph's, Aldgate, London, UK
Introduction: Patient expectations
of future treatment prospects are influenced by the views of their treating
physician, literature from patient organisations and information gleaned from
Internet sources. Although these sources can differ substantially in
credibility and optimism, the extent to which patients views mirror these
external influences is unknown. The present study, conducted by Parkinson's
Movement (PM) examines Parkinson's (PD) patient perceptions of future
treatments and research.
Methods: A series of 4 brief (single question,
multiple choice answer) Internet polls were posted on the PM community website
(www.parkinsonsmovement.healthunlocked.com). The questions asked (Q1) the
perceived timeframe of a cure for PD, (Q2) patient expectations over the next
decade, (Q3) top three areas where PD-related funding should best be targeted,
and (Q4) the most promising areas of research toward a cure. Between 107 and
187 responded to each poll.
Results: The PM cohort was mainly young (76%
aged 50-69), highly educated (68% with at least 1 degree), with mild
Parkinson’s (Hoehn & Yahr stage 1/2: 66%) for 4-6 years. Results were as
follows: Q1: 41% felt that a cure for PD was attainable within 10 years, 16%
within five. Only 6% felt that a cure was unattainable in any timeframe. Q2: a
cure for PD (20%), treatments with fewer long-term side-effects (21%), more
effective drugs (25%) and more available treatments (20%) were the most likely
expectations of patients for the next decade. Q3: 81% felt that funds were best
directed to finding a cure. 50% wanted new symptomatic treatments for PD. 32%
prioritised long-term social support. Q4: 58% felt that stem cells were the
most promising route to a cure while 22% supported gene therapy. 6% felt that
the cure lay in surgery.
Conclusion: PM patient views generally reflect
optimistic realism and sophisticated understanding of future treatment
prospects.
P24.14
Effects of a community-based balance program on enhancing
the balance performance in people with Parkinson's disease
Irene SK Wong-Yu1, Margaret KY Mak1
1Deapartment of
Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong SAR,
China
Objective: To examine whether an 8-week blended
indoor-outdoor program is effective to enhance balance performance after
treatment completion and at 2-month follow-up in people with Parkinson's
disease (PD).
Background: Previous studies demonstrated that multi-modal
balance training program was effective in improving balance performance in
people with PD. However they did not include all the balance domains and
outdoor fall-prone activities have been overlooked. We designed an exercise
program based on the framework of the Balance Evaluation Systems Test (BESTest)
to target six balance domains including biomechanical constraints, stability
limits and verticality, anticipatory postural adjustments, reactive postural
responses, sensori-motor integration and dynamic gait control.
Methods: It is a randomized controlled trial with 39
subjects completed the 8-week program, pre-training, post-training and 2-month
follow-up assessments. Subjects were randomly assigned to an experimental group
(EXP) receiving 4-week indoor and 4-week outdoor balance exercises, or a
control group (CON) receiving 8-week upper limb exercises. Outcome measures
included BESTest total score (%), MDS-UPDRS III and
postural-instability-gait-difficulty (PIGD) scores. Two-way repeated measures ANOVA
was used to analyze within-group and between-group differences.
Results: Immediately after training, only the EXP
group significantly increased BESTest score (by 14%, p<0.001) and decreased
PIGD score (by 34%, p<0.001). Both groups significantly reduced MDS-UPDRS
III scores (by 22-27%, p<0.001). At 2-month follow-up, only the EXP group
significantly increased BESTest score (by 14%, p<0.001) and decreased PIGD
score (by 31%, p<0.001). Both groups significantly maintained the reduced
MDS-UPDRS III scores (by 21-31%, p<0.001). Between-group comparisons
indicated that the changes of BESTest and PIGD scores were significantly larger
in EXP than CON group at both post-training and 2-month follow-up (p<0.001
and p<0.01).
Conclusions: Our blended
indoor-outdoor balance program, which based on the BESTest framework, enhanced
balance performance in people with PD at post-training and 2-month follow-up.
P24.15
Xiaoyao Pill for the treatment of depressive symptoms in
patients with Parkinson’s disease: a randomized, double-blind,
placebo-controlled trial
Jinglin Zhang1, Piu Chan1
1 Xuanwu Hospital,
Capital Medical University, Beijing, China
Objective: Depression is common in Parkinson’s disease
(PD). There are seldom studies concerning alternative therapies. The objective
of this trial was to investigate the effects of herb extracts of Xiaoyao Pill,
an antidepressant medicine approved by the People’s Republic of China
Pharmacopoeia, on clinically relevant depressive symptoms in PD.
Methods: A
total of 58 patients with PD and reaching DSM-Ⅳ Criteria were
enrolled to this 12-week, double-blind, placebo-control, randomized trial. The
primary efficacy endpoint was the mean change baseline and 12 weeks in total
score on the Hamilton Depression Scale (HAMD 17), the percentage of recovered,
and the responder rate. The secondary outcome included the 30-items-Geriatric
Depression Scale (GDS-30), the Parkinson’s Disease Questionnaire (PDQ-39), and
the Pittsburgh Sleep Quality Index (PSQI).
Results: There was a trend
favoring Xiaoyao Pill group, but no significant differences were found between
groups. The mean change of HAMD 17 score is highest in the Xiaoyao Pill group
(-7.69 vs -4.57 and -4.20, p=0.001). The percentage of recovery is 46.2% for
Xiaoyao Pill, 14.3% for Bupleurum+Ginkgo, and 20% for placebo. Response rate:
Xiaoyao Pill 46.2%, Bupleurum+Ginkgo 7.1%, and placebo 30%. There was a
significant decrease in GDS score (from baseline to the endpoint: 20.62±3.80 to
16.38±5.88, P=0.007), while no significant decrease in GDS overtime in group 2
and placebo group. The same is the dimension 3, emotion well being, of PDQ-39
(P=0.015). Though the sample size
is limited, this is the third largest placebo-controlled trial done to date in
PD patients with depression. Our study shows that Xiaoyao Pill has better
efficacy and is tolerated.
CLINICAL
SCIENCES: RATING SCALES
P25.01
3D sensors, the new paradigm for assessing Parkinson´s
Disease
Mario
Alvarez1; Jorge Bosch2; Armando Martínez2;
Frank Macías2, Pedro Valdés2
1International
Center for Neurological Restauration, Havana, Cuba
2Neurosciences,
Havana, Cuba
Objective: Create
objective, automatic and relatively inexpensive tools for the evaluation of
Parkinson´s disease using the new 3D sensors like the Microsoft Kinect.
Methods: We selected 10 healthy subjects and 10 patients with
Parkinson´s disease. Each participant
performed a set of manoeuvres designed to assess their capabilities and
functions while recorded by one of these 3D movement sensors (in our specific case,
we used the Microsoft Kinect). 20 corporal reference points were recorded for
each instant of time, with an average frequency sampling of 30 fps. For each of
them, the time course of the measurement was assumed as a time series. A set of
descriptive parameters was extracted for each independent manoeuvre, which were
then analysed and compared for individual and group comparisons.
Results: The
Kinect system is useful for the evaluation of motor control and movement
disorders. Distinguishes normal pattern of gait and posture and provides
quantitative measurements of gait, posture, hipokinesia and dyskinesia.
This research demonstrates the utility of the Kinect sensor to record
and evaluate the postures and movement sequences and opens new possibilities for
assessment, diagnostic and treatment of movement disorders.
P25.02
Discriminant capacity of four Fear of Falling rating
scales in people with Parkinson’s disease
Stina B Jonasson1,2,3, Jan Lexell1,2,3, Maria H Nilsson1,2
1Department
of Health Sciences, Lund University, Lund, Sweden
2Strategic research
area of Neuroscience, MultiPark, Lund University, Lund, Sweden
3Department of
Rehabilitation Medicine, Skåne University Hospital, Lund, Sweden
Objective: To evaluate the discriminant capacity of four
Fear of Falling (FOF) rating scales in people with Parkinson’s disease (PD).
Methods: The
FOF rating scales were: the Falls Efficacy Scale-International (FES-I; possible
scoring range 16-64, higher=worse), the Swedish version of the Falls Efficacy Scale
(FES(S); 0-130, higher=better), the Activities-specific Balance Confidence
scale (ABC; 0-100, higher=better) and the modified Survey of Activities and
Fear of Falling in the Elderly (mSAFFE; 17-51, higher=worse). A postal survey was mailed to 96 non-demented
people with PD. The survey contained the four FOF rating scales and dichotomous
questions on FOF, activity avoidance due to the risk of falling and falls and
near falls during the past six months. PD-severity was self-rated as mild,
moderate or severe (in the analysis dichotomized as mild or moderate/severe).
Non-parametric group comparisons (Mann-Whitney U-test) were used to investigate
if the FOF scales were able to separate people with and without FOF, activity
avoidance, previous falls, near falls and people with different disease
severity.
Results: Fifty-six persons (52%
men) responded within three weeks and were included in the preliminary
analyses. Mean (SD) age and PD-duration were 73 (7.8) and 7 (5.3) years,
respectively. Thirty-two participants (57%) stated that they had FOF according
to the dichotomous question. Median (q1-q3) scores for the four FOF rating
scales were: FES-I; 25 (19-36), FES(S); 109 (67-128), ABC; 72 (39-90) and
mSAFFE; 24 (19-32). All four scales
detected significant (p≤0.003) differences in relation to the dichotomous
questions that targeted PD-severity, FOF, activity avoidance and falls, as well
as significant (p≤0.029) differences in relation to near falls.
Conclusion: Preliminary analyses indicate that when using dichotomous
questions, all four scales discriminate between PD-severity, FOF, activity
avoidance, falls and near falls.
P25.03
The Exo-Imaging test:
using a markerless motion tracking system to detect and monitor motor symptoms
in patients with Parkinson's disease
Benoit Carignan1-2,
Jean-François Daneault2-3, Catherine Lavigne-Pelletier2-4,
Laurent Frossard4, Christian Duval2-4
1Département des Sciences
Biologiques, Université du Québec à Montréal, Montréal, QC, Canada
2Centre de Recherche de l’Institut
Universitaire de Gériatrie de Montréal, Montréal, QC, Canada
3Department of Neurology and Neurosurgery, Montreal
Neurological Institute, McGill University, Montreal, QC, Canada
4Département de Kinanthropologie,
Université du Québec à Montréal, Montréal, QC, Canada
Background: Assessment of motor symptoms in Parkinson’s disease (PD) is currently
done using clinical scales. However, these evaluations must coincide with rare
visits to the treating physician; hence they are not done often enough to
appreciate sudden changes in health status of patients.
Objective: Accordingly, we intend to develop an automated tool to assess motor
symptoms of patients with PD; the Exo-Imaging test. Similar to other types of
imaging, this system could be installed anywhere. The test could also be
repeated multiple times so as to provide a better clinical picture of the
evolution of symptoms.
Methods: A markerless system (Biostage, Organic Motion) is used to record movement
of patients while they will perform tasks, such as standing, walking, drinking
and performing rapid alternating movements. The level of involuntary movement
is also assessed during quiet standing. To be detected by the system, the
patient only has to go into the recording zone and take a “T” pose for 2
seconds, without wearing any marker. The Biostage system integrates videos from
14 cameras to provide position of 16 different body segments. Using this
information, we are able to compute biomechanical parameters in order to assess
motor performances. Finally, motor performances is associated with severity of
PD symptoms using statistical methods, such as neural networks.
Results: Our preliminary results show that the Biostage is able to detect dyskinesia
and tremor, as well as to capture key differences during gait between healthy
participants and patients with PD. Ultimately; we hope to develop a
fully-automated test for the detection and follow-up of motor symptomatology in
PD that will provide the same information available through currently-used
clinical scales.
P25.04
Can single-leg stance time be used to
assess bilateral progression of Parkinson’s disease?
Terry Clark1, Alexandra Cihal1, Taylor Chomiak1, Ranjit
Ranawaya2, Sarah Furtado2, and Bin Hu1
1DCN and Hotchkiss Brain Institute and
University of Calgary, Calgary, AB, Canada
2Movement Disorders
Clinic-Alberta Health Services, Calgary, AB, Canada
Objective: Reduced body balance time based on single-leg
stance test (SLST) is associated with increased postural instability and risk
of fall in Parkinson’s disease (PD). This study sought to determine whether the
wide range of SLST data obtained from both lower limbs clinically actually
consists of discernible statistical pattern, corresponding to bilateral disease
progression.
Methods: Demographic and disease history information
were collected from 38 people with PD. The mean age of our study participants
was 66.3 years (SD 10.7) and the mean disease duration was 7.6 years (SD 5.7).
Each participant performed the SLST and was timed with a stopwatch by an
independent observer.
Results: SLST scores obtained among individuals were
quite variable, ranging from 1-60 seconds. Using 10 seconds, a previously
recommended cut-off level for potential fallers, as a classifier, we classified
our data into two sub-groups: those who were able to balance for at least 10
seconds on both legs (N=22) and those who could not (N=16). When looking at the
participants who had at least one leg scored below 10 seconds, two additional
sub-groups of participants emerged: 62.5% had both legs scoring below the 10 second cut-off (p<0.05 for both
legs; Wilcoxon signed-rank test) while 37.5% had only one leg score below the 10 second cut-off (p<0.05 for only one
leg; Wilcoxon signed-rank test). We postulate that the inter-leg difference SLST, combined with 10s cut-off, has the
statistical power and sensitivity to identify three patient groups: 1) those
with both leg above 10s and relatively good balance; 2) those with only one leg
below the cut-off whose postural instability could remain unilateral, and 3)
those with both legs below the 10s cut-off, in which postural stability
appeared to have progressed bilaterally. Our results indicate that SLST may be
a useful indicator for assessing bilateral disease progression.
Acknowledgments: CIHR, Parkinson Alberta Society, and the Movement Disorders Clinic-Alberta Health Services, and MITACS.
P25.05
Postural balance evaluation in a outpatient population
with Parkinson disease
Luciano Alves Leandro1,
Hélio Afonso Ghizoni Teive1
1Movement Disorders Unit, Neurology Service,
Department of Internal Medicine, Hospital de Clínicas, Federal University of
Paraná (UFPR), Curitiba, Brazil
Objective: Evaluate the
dynamic postural balance of patients with Parkinson Disease (PD) in order to
know the potential risk of falls
Methods: Field
study, exploratory cross-sectional descriptive correlational approach were evaluated
in 145 elderly patients with PD were divided into three groups according to age
groups: G1 (60-69), G2 (70-79) and G3 (80-89) outpatients at the Division of
Movement Disorders Department of Neurology, Hospital das Clinicas, Federal
University of Parana - UFPR, Curitiba - Brazil. To collect data, we used two
instruments: the Sociodemographic and Functional Independence Measure (FIM). We
performed statistical analysis of comparison (Kruskal-Wallis), Pearson
correlation and descriptive analysis of data.
Results: The sociodemographic characteristics revealed a higher frequency of women aged 80 to 89 years with a low education level (38.89%), mostly coming from remote areas of the city (90.48%). High scores were observed in MIF indicating functional independence. The comparison between the scores of FIM and FIM HY and mean time to clinical progression through the G1, G2 and G3 indicate the time of onset of disease and staging of HY did not affect the performance of these functional groups and the relationship between the three groups also showed no statistical difference between them.
P25.06
Dual-task performance assessment
(DTPA): a novel test for assessing motor and cognitive performance during
dual-task
Sandra Maria Anti Pompeu1;
Erica Tardeli Neves2; Erika Okamoto2; Maria Elisa
Pimentel Piemonte1
1University
of São Paulo
2Brazil
Parkinson Association
Objective: The aim
of this study was to analyze results following the application of a novel
protocol devised to assess motor and cognitive performance on dual-tasks,
comparing performance of healthy elderly and Parkinson’s disease (PD) patients.
Methods: Thirty
healthy elderly, mean age 67.5 years (S.D. = 7.8), 45 patients with idiopathic
PD, mean age 66.5 years (S.D.=6.44) at stages 1,2 and 3 of disease evolution
according to the Hoehn and Yahr Classification, took part in the study. The
DTPA was split into four tasks: (1) GAIT, assessing distance traveled and
number of paces taken in 1 minute; (2) BALANCE, assessing ability to balance in
unipodal support for 1 minute; (3) POSTURE, quantifying the number of times the
participant is able to stand up and sit down within 1 minute; and (4) HAND
SKILL, assessing the number of cards turned over on a table top within 1
minute. The four tasks were assessed: (i) independently i.e. under single-task
(ST) conditions; (ii) simultaneously with a cognitive test; and (iii)
simultaneously with a motor task. The impact of DT between healthy elderly
group and PD patient group was compared using ANOVA.
Results: The results revealed significant
difference in impact of DT on the groups (ANOVA, p<0.001), confirmed by
Tukey’s test which showed greater impairment between PD patients than healthy
elderly across all four DTPA sections. CONCLUSION: The DTPA was shown to be
effective for measuring differences in impact of DT between healthy elderly and
PD patients and also proved sensitive to disease progression in patients with
PD. The DTPA was shown to be a straight-forward and rapid tool, representing
the first standardized protocol for assessing the impact of dual-tasks not only
on gait but also balance, posture and manual skill.
P25.07
Quality of life assessments using the MDS-UPDRS
Yekaterina A. Salnikova1, Liana S. Rosenthal1, Paige E. Nichols1, Zoltan
Mari1, Greg Pontone1, Ted M.
Dawson1
1 Johns Hopkins
University, Baltimore, MD, USA
Objective: Depressive symptomatology and motor
impairments have been frequently associated with quality of life in Parkinson disease
(PD). This pilot study sought to determine what factors measured by the
Movement Disorder Society revised Unified Parkinson’s Disease Rating scale
(MDS-UPDRS) correlate with quality of life in PD patients.
Methods: We recruited PD patients from the Johns
Hopkins Morris K. Udall Center and movement disorder clinic. Participants were
administered the MDS-UPDRS. Part I and II of the MDS-UPDRS evaluated non-motor
and motor experiences of daily living, respectively, and Part III measured
motor function. Part IV examined complications from therapy. Quality of life
was assessed with the Parkinson’s Disease Questionnaire 39 (PDQ39).
Results: Thirteen PD patients are currently enrolled
with an average age of 66.74 years (SD=2.69). Participants were primarily early
in the disease (Hoehn and Yahr II: 9 participants; Hoehn and Yahr III: 2
participants; Hoehn and Yahr IV: 2 participants). Higher Hoehn and Yahr stages
corresponded with increasing age (p=0.02) and higher MDS-UPDRS scores (p=0.02).
Total mean MDS-UPDRS score was 63.86 (SD=20.00) and the average PDQ39 score was
29.25 (SD=16.70). As the total MDS-UPDRS score increased, patients reported a
poorer quality of life (r=0.70). Motor experiences of daily living (part II)
and motor complications subscales (part IV) were also associated with poorer
quality of life (rMDS-UPDRS II=0.60; rMDS-UPDRS IV=0.62).
However, motor function (part III) and non-motor experiences of daily living
(Part II) had less impact on quality of life (rMDS-UPDRS III=0.50; rMDS-UPDRS
I=0.39).
Conclusion: Total MDS-UPDRS scores had the strongest
correlation with quality of life, followed by motor experiences of daily living
and therapeutic complications. Non-motor experiences of daily living and motor
examination had the least impact on quality of life. Larger investigations are
needed to confirm these findings and determine the ability of the MDS-UPDRS to
assess quality of life.
P25.08
Measures of quality care reveal large variation across
NPF Centers of Excellence
Peter Schmidt1, John Nutt2, Tanya
Simuni3, Mark Guttman4, Eugene Nelson5, Jorge
Zamudio1, Michael Okun6 and QII Investigators
1National Parkinson
Foundation, Miami, FL, USA
2Oregon Health &
Science University, Portland, OR, USA
3Northwestern
University, Chicago, IL, USA
4University of Toronto,
Toronto, ON, Canada
5Dartmouth School of
Medicine, Lebanon, NH, USA
6University of Florida,
Gainesville, FL, USA
Objective: Meaningful improvements in health outcomes have
been achieved through quality improvement. For the first time, the National
Parkinson Foundation Quality Improvement Initiative (NPF-QII) has measured the
quality of care across a sample of NPF Centers of Excellence.
Methods: NPF-QII is an observational clinical study
with comprehensive data on patients with Parkinson’s from 19 NPF Centers of
Excellence. It includes both patient-reported and clinically-measured outcomes,
together with broad measures of demographics and treatments. The data was
adjusted for age, disease duration, and sex. Quality of care was measured by
examining the means and standard deviations (SD) for the two year change in
patient outcomes (data is collected annually), examining the PDQ-39 summary
index (PDQ-39), the time to complete the timed up-and-go test (TUG), and a
cognitive measure that combined verbal fluency (animals) and delayed recall and
was scaled to parallel the MoCA cognitive exam.
Results: Six of nineteen
centers had two year follow-up data on over 80 subjects (n=921 subjects). At
baseline, the average PDQ-39, TUG, and cognition scores were 23%, 12.9 seconds,
and 24.3. The results achieved at each center showed little variability in the
two-year change in PDQ-39 (average change for all subjects: 1.3%; center
averages: 0.7%-1.4%) but more significant two-year change in both the TUG
(average, all subjects: 0.85 second increase; center averages: 0.12-2.0
seconds) and cognitive score (positive values show improvement; average, all
subjects: 0.03; center averages: -0.25 to 0.26). Further, the SD also showed
wide variation for the PDQ-39 ranging from 3.5% to 5.6% and the TUG from 1.79
to 3.59 seconds, but for the cognitive measure the SD varied less: 1.23 to
1.53. Lower SD indicates more predicable outcomes and clinics with higher SD
require higher recruitment to measure an impact of care change. Future studies
will evaluate the factors contributing to this observed variability.
CLINICAL
SCIENCES: E-HEALTH AND TECHNOLOGY
P26.01
PDaily: mobile application to monitor patients with
Parkinson Disease
Juan Arango1,
Sebastián Londoño1, Andrés Navarro1, Yoseth Ariza-Araújo1,
Beatriz Muñoz2, Jorge Orozco2
1 Icesi University, Cali, Colombia
2 Fundación Valle del Lili, Cali, Colombia
Objective: To design, develop and validate a mobile
system that would support the evaluation and monitoring of people diagnosed
with Parkinson's disease in a specialized medical institution in Cali, Colombia.
Methods: In
an interdisciplinary work we developed a mobile application designed to be used
by the patient or caregiver, and thought with a medical approach. To develop
the software was used an agile methodology with iterative and incremental
cycles based on Prototyping. We defined four cycles of development, each one
with differential internal cycles according to the progress of the project.
Results: The obtained mobile
system, PDaily, has 5 software components: (1) to keep registration of the
person, condition and treatment, (2) to identify medicines through augmented
reality, (3) to notify the next dose of the drug, (4) to analyze motor
fluctuations and dyskinesias through objective measurement using
accelerometers, a brief questionnaire about dyskinesias and impact on daily
activities using Unified Parkinson's Disease Rate Scale (UPDRS: section 2.10),
and (5) to contact a family member, doctor or emergency call system of the city
for help in an emergency. These components are supported by a core component
enabling interoperation between them and facilitate the extensibility of the
system with additional modules. The collected information is stored locally on
the Smartphone, then the patient, shares it with the specialist through a web
main system. PDaily provides a summarized report about detailed records on the onset
and ending of symptoms and their temporal relation to treatment. Accurate
information will allow adjust the treatment plan, monitor the adherence and to
detect complications early.
P26.02
Multisensor
system as a clinical aid in evaluation differentiation of tremor disorders
Igor
Barcellos1, Gabriela Boschetti1, Hélio A. Teive2,
Renato P. Munhoz1, Ederson Cichaczewski3, Joaquim M. Maia3,
Percy Nohama3
1Pontifical
Catholic University of Paraná, Curitiba, Brazil
2Federal
University of Paraná, Curitiba, Brazil
3Federal
Technological University of Paraná, Curitiba, Brazil
Objective:
Develop a multisensor system for the measurement of
tremor, providing the visualization and analysis of signals to help differentiating
tremor disorders.
Background:
The differentiation of the etiology of tremor
disorders is a challenging task for most specialists. In the case of Essential
(ET) and Parkinsonian tremor (PT), this is specially difficult. From a
physiological standpoint, these tremors have their own characteristics, however
the measurement of these parameters are not part of routine clinical practice.
Methods:
The system sensors (accelerometers) were placed in
eight body parts of interest in lower and upper limbs, positioning the
measuring axes perpendicular to the longitudinal axis of the limb. Registration
assessed the limbs at rest, as well as with postural and kinetic tests.
Analyses were focused in function of the specific features of each disease and
also the signals for their RMS amplitude and frequency.
Results:
seventeen patients with ET (6 men, mean age 62 years)
and 62 with PT (30 men, mean age 65.3 years) were analyzed. Cases of PT
presented with a mean frequency of 5.3Hz at rest, 5.8Hz with posture and 6.5Hz
kinetic (average for the 3 tests 5.8Hz). Cases of ET have an average tremor
frequency of 6Hz at rest, 6.2Hz with posture and 6.5Hz kinetic (average for the
tests 6.2Hz).
Conclusions: Our system was able to
differentiate ET and PT in regards to frequency. In addition, the system
allowed us to analyze amplitude parameters, identifying cases in which there
was a significant overlap between both forms of tremor.
P26.03
Performance evaluation of an optical analysis
technique based on passive markers in the characterization of voluntary and
involuntary muscle movements in patients with Parkinson's disease
Pedro
Chaná1, Mónica Catalán2, Ítalo Bavestrello3.
1CETRAM, Universidad de Santiago de Chile, Chile
2Universidad de Valparaíso, Chile
3INFRATEC S.A., Chile
Objective: This
study aims to evaluate a system using video motion analysis (ParksysÒ) correlated with different items of the rating scale for Parkinson's
disease.
Methods: 28 patients (14 men and 14 women) with
PD with an average age of 63.7 ± 9.5 years who fulfilled the diagnostic
criteria of the Brain Bank of London and 15 healthy subjects (8 men and 7
women) with an average age of 59.8 ± 9.3 years. EP duration was 11.6 ± 6.2
years. All cases were on treatment with levodopa. Subjects were evaluated using
an optical motion analysis. Each of the individuals performed the tests 20 and
23 of the motor section of the UPDRS in both sides of the body. It was
considered the amplitude and frequency of each of the movements. In the
statistical analysis were used descriptive measures of correlation between
variables, principal component analysis (PCA), analysis of variance and the
nonparametric alternative when the data were not normally distributed.
Results: In
the analysis using PCA it was determined that there are significant differences
between the control group and the case group, with a P value of 0.013, for the
right hand UPDRS23. In this analysis the amplitude in the axis X, Y and Z
gathered 89% of variability. There are also differences between the control
group and the group of cases in the UPDRS20 in the left hand, with a p-value of
0.008. The results indicate there are differences in the UPDRS test 20 for left
hand and UPDRS test 23 for right hand between the groups. The used technique
allow to measure and characterize quickly and accurately the muscular movements
in subjects with PD.
P26.04
Application of iPod
Touch motion sensing technology for Gait measurements
Alexandra Cihal1,
Kailie Luan1, Nicole Meyer1, Taylor Chomiak1,
Terry Clark1, Bin Hu1
1Department of Clinical Neurosciences,
University of Calgary, Calgary, AB, Canada
Objective: Brisk walking is a
commonly recommended form of exercise for patients living with Parkinson’s
disease (PD). In this study we developed and validated an Application
(GaitReminder™; GR) using 4th generation iPod Touch technology that
can monitor and record stepping data during treadmill and level ground walking.
Methods: 18 control subjects and 15 PD patients walked
on a treadmill and on level ground while wearing the GR. We compared gait
parameters (step size, walking speed, and distance) obtained through GR to known
benchmarks as indicated by treadmill speeds, or pre-measured distance markers
on the ground. Within this data, we looked for relationships between cadences
and changing inclines and speeds during treadmill walking, and at GR
sensitivity to differences between the PD and control group.
Results: We found the mean percent errors of
GR-recorded walking speed and distance on a treadmill was 2.94% and -0.36%
respectively, and that GR-derived step length has a mean error of -5.15% when
compared to the line distance. GR measurements are also sensitive to walking
instructions such as walking with larger vs. smaller steps. When the subjects
were instructed to maintain their amplitude of walking steps, GR accurately
recorded a linear increase in cadence with increased treadmill speeds, but not
the increase in incline. PD patients performing the ground line-walking test
showed a significantly higher mean error rate due to their shorter step length
than controls. Our data indicates that iPod Touch can be utilized as a
versatile device for tracking gait parameters with acceptable accuracy and
reliability in both healthy subjects and PD patients.
Acknowledgments: CIHR, Parkinson
Alberta Society, the Movement Disorders Clinic-Alberta Health Services, Markin
Undergraduate Student Research Program, and Branch Out Neurological Foundation.
P26.05
Parkinson's disease
patients' opinions on use of technology for communication and education
Nathalie Duroseau 1 Wolfgang Gilliar1,
To Shan Li1, Sim Basta1, Min-Kyung Jung1,
Brian Harper1, Tobi Abramson1, David Tegay1,
Bhuma Krishnamachari1
1NYIT College of
Osteopathic Medicine, Old Westbury, NY, USA
Objective: Parkinson’s disease
(PD) is the most common neurodegenerative movement disorder in the U.S.
Patients’ opinions of technology-based tools for education and communication as
related to PD are unclear, with little documented research addressing the
issue. The goal of this research
was to investigate patient opinions about technology-based tools. Education and
communication using technology may affect satisfaction and adherence to
treatment regimens. Prior to developing technology tools for clinical use,
establishing the relevance from the patients’ perspective, specifically
accounting for the needs of geriatric patients, is crucial.
Methods: A quality assessment survey was administered
to PD patients at the Parkinson’s Disease Treatment Center at the New York
Institute of Technology. The survey assessed patient opinions on willingness to
use electronic methods including electronic forms, video education, emailed
home-care instructions and the ability to email with healthcare providers.
Additionally, patients were asked whether they felt that using technology
(online tools, etc.) to communicate with the healthcare provider would result
in a better understanding of their care or the healthcare-provider better
understanding their needs. Associations between patient
opinions of technology, having unmet needs related to PD, and being age
65 or older were assessed.
Results: 109 PD patients completed the
survey. 27.2% (n=28) of the subjects
reported having unmet needs related to PD. The majority of the patients were
age 65 and older (78.0% (n=85). Those who
were age 65 and above were less likely to believe that using technology would
result in a better self-understanding of patient care (OR=0.30, 95% CI:0.12,
0.79, p=0.01) and less likely to want an email summary of care/home
instructions (OR=0.39, 95% CI:0.15, 0.98, p=0.05) than those under age 65. The
results of our study indicate that PD patients over age 65 appear to have a
less favorable view regarding the role of technology in communicating with
healthcare providers and self-understanding of their care.
P26.06
A smartphone-based Interactive Rhythmic Auditory
Cueing Evaluation (iRACE)for gait impairments
Robert J Ellis1,2, Shenggao Zhu1,
Gottfried Schlaug2, and Ye Wang1
1School of Computing, National
University of Singapore
2Department of Neurology, Beth Israel
Deaconess Medical Center and Harvard Medical School
Objective: Rhythmic auditory cueing (RAC)
continues to receive attention as a promising therapy for gait impairments in
Parkinson’s disease. By synchronizing their movements to an external cue,
patients can reduce their motor timing variability (MTV);
MTV has been retrospectively and
prospectively linked with fall likelihood. Currently, however, there exist no
easy-to-use diagnostic tools to evaluate whether a given patient might benefit
from a longer-term therapy program with RAC, or to optimize RAC parameters.
Methods: iRACE has been developed for Apple
(iOS-based) iPhone/iTouch. The touchscreen of the device is used to quantify
upper-motor timing during bimanual alternate index finger tapping, and the
device’s built-in tri-axial accelerometer to quantify lower-motor timing while
walking. Both self-paced and externally-cued conditions may be evaluated. Based
on each participant’s self-paced cadence, a “yoked” playlist is created to
determine the precise tempo at which MTV is minimized. Accuracy of the
accelerometer-derived step time series was validated using a Biometrics
wireless tri-axial accelerometer system (www.biometricsltd.com/datalog.htm).
Time-domain estimates of MTV were quantified a using widely-used method
(percent coefficient of variation) for both finger tapping (i.e., inter-tap
intervals) and walking (i.e., inter-step intervals, with steps identified using
peaks in anterior–posterior acceleration). Walking and tapping statistics are
presented directly to the user (i.e., therapist/neurologist) on the device’s
screen, and automatically uploaded to a central server for data management.
Results: The flexibility, portability, and
validity of iRACE offers both prognostic and analytic applications, including
(1) evaluating whether a given patient may benefit from the longer-term
therapeutic application of rhythmic auditory cueing; and (2) tracking the
improvement of motor timing performance after behavioral, pharmacological, or
neurostimulatory interventions. Further work from our group will provide a
large library (~3 million items) of music that has been carefully analyzed for
tempo, enabling further customization.
P26.07
SENSE-PARK: measuring Parkinson's disease in the home
environment in an objective, continuous and minimally obtrusive fashion
Tom Isaacs1, Helen
Matthews1, Joy Duffen1, Ahmed
Al-Jawad2, Frank Larsen3, Artur
Serrano3, Peter Weber4, Andrea
Thoms4, Stefan Sollinger5,
Joaquim J. Ferreira6, Josefa Domingos6, Ana T. Santos6, Tanja
Heger7, Walter Maetzler7, Holm
Graessner7
1Cure Parkinson's
Trust, London, UK
2HSG-IMIT, Villingen-Schwenningen, Germany
3Norwegian
Centre for Integrated Care and Telemedicine, University Hospital of North
Norway, Tromso, Norway
4Hasomed GmbH, Magdeburg, Germany
5AbilityNet, London, UK
6Instituto de Medicina Molecular, Lisbon, Portugal
7University of
Tuebingen, Tuebingen, Germany
Objective: The future treatment of Parkinson’s relies on
the accurate assessment of how it affects people with Parkinson’s (PwP’s) as individuals.
SENSE-PARK is a pioneering project which combines expertise from technology
with the experiences of those who live with Parkinson’s and the scientific
know-how of those who treat it. The objective of
SENSE-PARK (EU funded, INFSO-ICT-2011-288557) is to develop a patient-centered,
minimally obtrusive and empowering information system for use in the home
environment, which provides PwP’s with practical and motivating tools to
monitor their condition in a continuous and objective way. In more detail, the
SENSE-PARK system will inform the users about motor and non-motor functioning
in daily life activities (‘being’, data collection via a wrist-worn data
logger), leisure activities (‘belonging’, data collection via gaming console
and adapted interface) and scientific environment (‘becoming’, validation
purposes).
Methods: (i) Participatory approach; (ii) needs and requirements analysis;
(iii) adapt and develop a PwP’s-friendly interface; (iv) define relevant
parameters to monitor disease progression; (v) sensor system development and
data interpretation; (vi) hardware and software integration, IT infrastructure
and telemedicine; (vii) iterative testing; (viii) scenario-based multicentre
study.
Results: Through conducting a needs and requirements analysis that was facilitated
by Cure Parkinson’s Trust, project partners were able to define usability
criteria and to prioritize symptomatic domains and parameters for measurement
of Parkinson’s. The symptomatic domains of the SENSE-PARK system are: Gait, Sleep,
Bradykinesia, Cognitive function, Tremor and Sway. Pilot systems for the
measurement of these domains including hardware, software and interface are
being developed, used and systematically tested by PwP’s whose feedback will
direct modifications and improvements. Validation and relevance of the
SENSE-PARK system with respect to the selected domains and parameters have been
identified as the key issues for the use by PwP’s as well as for eventual
application in PD trials.
P26.08
Automatic assessment of touch-pad tapping performance in
Parkinson’s disease
Mevludin Memedi1, Taha Khan1, Dag
Nyholm2, Jerker Westin1
1 Dalarna University,
Borlänge, Sweden
2 Uppsala University,
Uppsala, Sweden
Objective: To develop and evaluate a computerized
method for automatic scoring of finger tapping performance in Parkinson’s
disease (PD), using a touch-pad device.
Methods: Sixty-five patients diagnosed with advanced
PD have utilized a test battery in a telemedicine setting over the course of a
3 year clinical study. On each test occasion, they were asked to perform fine
motor tests including alternate tapping of two buttons on a touch-pad screen as
fast and accurate as possible, for 20 seconds in duration. The tapping
performance was visualized by displaying graphs in a web interface. Information
presented included distribution of taps over the two buttons, horizontal tap
distance vs. time, vertical tap distance vs. time, and tapping reaction time
(Figure 1a). A neurologist (DN) used a scale between 0 (normal) and 4 (severe)
to rate firstly four tapping properties: Speed, Accuracy, Fatigue, Arrythmia,
and secondly a Global Tapping Severity (GTS). Different quantitative measures
(Table 1) were calculated for representing symptom severities of the said
dimensions. An ordinal logistic regression model, using stratified 10-fold
cross-validation, was used to map these measures to the corresponding GTS, and
to calculate and evaluate an automated GTS score.
Results: The Spearman’s rank correlations between
first principal components of the quantitative measures and their corresponding
ratings of dimensions were as follows: Speed (-0.91), Accuracy (0.69), Fatigue
(0.46) and Arrythmia (0.77). The agreement between computer ratings and
neurologist ratings was very good with a weighted Kappa coefficient of 0.89
(p<0.001, Figure 1b). In conclusion, the computer method could automatically
assess tapping performance of PD patients similarly to the visual assessments
of the neurologist.
P26.09
Quantitative motor assessment of gait and
lower extremity bradykinesia following the discontinuation of deep brain
stimulation
Thomas Mera1, David Riley2,
Benjamin Walter2, Alberto Espay3, Fredy Revilla3,
and Joseph Giuffrida1
1Great Lakes NeuroTechnologies Inc,
Cleveland, OH, USA
2University Hospitals Case Medical
Center, Cleveland, OH, USA
3University of Cincinnati Academic
Health Center, Cincinnati, OH, USA
Objective: One of the challenges of outpatient
programming of deep brain stimulation (DBS) parameters in Parkinson’s disease
(PD) is the delayed effect on gait. Therefore, the objective was to quantify
the change in gait function and lower extremity bradykinesia in PD patients
treated with DBS after stimulation is turned off using body-worn motion
sensors.
Methods: Forty sub-thalamic DBS-treated PD
patients with residual gait impairment were recruited. Evaluation took place in
the "practically defined OFF state", the morning after overnight
withdrawal of anti-parkinsonian medications. Compact and wireless motion
sensors were positioned on the feet, wrists, and torso. Subjects were then
guided through a subset of the Unified Parkinson’s Disease Rating Scale (UPDRS)
motor section: toe taps and leg lifts while seated and walking in a straight
line at a normal pace, turning in place, and returning to the starting
position. Motion sensor data were wirelessly transmitted to a computer for
storage and analysis while subjects were also videotaped for later clinical
scoring. The battery of tasks was performed first with stimulation turned on
and then repeated with stimulation turned off at approximately 15 and 30
minutes and 1, 2, and 3 hours later. Subjects were set to their previously
optimized stimulation parameters at the conclusion of the study. Multiple
linear regression scoring models were developed based on the kinematic features
extracted from motion sensor data and clinician UPDRS scores.
Results: On average, model scores and kinematic
features extracted from motion sensor data were highly correlated to clinician
scores (p>0.80). When plotted over time, kinematic features and model scores
demonstrated a gradual worsening that continued more than an hour after stimulation
was turned off. These scoring models and study results could be used to more
efficiently manage DBS programming by accounting for the delayed response of
gait to changes in stimulation.
P26.10
Metronome-paced
square step test (MPSST) in Parkinson’s disease
Nicole Meyer1, Taylor Chomiak1,
Alexandra Cihal1, Terry Clark1, Bin Hu1
1Department of Clinical Neurosciences,
Hotchkiss Brain Institute and University of Calgary, Calgary, AB, Canada
Objective:
Midline
or axial symptoms in PD are frequently associated with poor balance and gait,
reduced physical activity and cognitive decline. Here we developed a
metronome-paced square-step task (MPSST) that requires auditory timed,
bilateral midline, and diagonal stepping. We examined the relationship among
MPSST, level of physical activity, and cognitive function.
Methods: 11 age-matched controls and 21 PD
participants were recruited. As part of Ambulosono,
a home-based music walking therapy program, PD patients were further classified
as frequent vs. infrequent walkers. We developed a global performance score for
MPSST using visually rated errors and step time consistency. Specific MPSST
parameters were obtained using GaitReminerTM and the Montreal
Cognitive Assessment (MOCA) examined cognitive functioning.
Results: The global
performance score showed the control group performed the MPSST significantly
better than the PD group as a whole (p< 0.01). The coefficients of step-length variances acquired during MPSST were significantly
smaller in controls than that of infrequent, but not frequent, PD walkers (p<0.05). Correlation
analysis between MPSST and MOCA scores from individual patients showed those
patients who scored lower on the MOCA also tended to score lower on the MPSST
(Spearman r = 0.57; p<0.01),
despite mean MOCA scores being comparable between groups (p>0.05). Logistic
regression further revealed that MPSST was a significant predictor of MOCA
score outcome, able to identify patients as being above or below the published
optimal screening cut-off of 26/27 with an overall correct percentage of 81%
(p<0.05). Hence, the MPSST is a useful tool for evaluating motor and
non-motor impairments in PD patients.
Acknowledgments: CIHR, Parkinson Alberta Society, and the
Movement Disorders Clinic-Alberta Health Services.
P26.11
E-Motion capture system for movement disorders
Juan Arango1,
Sebastián Londoño1, Andrés Navarro1, Yoseth Ariza-Araújo1,
Beatriz Muñoz2, Jorge Orozco2
1Icesi University, Cali, Colombia
2Fundación Valle del Lili, Cali, Colombia
Objective: To develop a system based on human-computer
interface (HCI) motion capture, to quantify motor (stride length, width and
length step) and spatiotemporal (velocity and acceleration) variables, to
support the clinical evaluation of patients with Parkinson's disease.
Methods: To develop the software was used an agile
methodology with iterative and incremental cycles that used Agile methodology
base on Prototyping. We defined four cycles of development, each one with
differential internal iterative cycles according to the progress of the
project. The project required an interdisciplinary work, where was selected a
team of neuroscientists who worked with the main team at regular meetings, they
provided and validated the software requirements.
Results: The obtained motion capture system,
E-Motion, is prototype software able to calculate motor (stride length, width
and length step) and spatiotemporal (velocity and acceleration) variables.
Kinect sensor was selected as the main capture device because compared to
conventional gait laboratories, has advantages such as low cost, portability
and the lack of markers for capture. The Kinect provides the location in space
(3D) joint required to calculate the motor and spatial-temporal variables. The
E-Motion capture system would fit to the conditions to the neurology clinics in
low and middle income countries.
P26.12
Objectively measuring characteristics of gait in
Parkinson’s disease
1Ingrid
Pretzer-Aboff, 2Sunil K Agrawal, 2Kyle N Winfree
1University of
Delaware, School of Nursing, DE, USA
2 Columbia University,
Mechanical Engineering, NY, USA
3University of
Pennsylvania, Mechanical Engineering, School of Medicine, PA, USA
Parkinson’s disease
(PD) has a profound effect on the ability to walk. Unique features of PD gait
include shuffling and freezing of gait (FOG). Research supports walking can be
improved with medical and non-medical interventions such as exercise and
vibration therapy. However, these studies largely rely on self-report or direct
observation of gait to assess their effectiveness. Currently, no identified
“gold standard” assessment provides a direct measure of gait and mobility in a
real-life setting. Therefore, it is difficult to assess the real impact of
treatment. This study takes a look at a unique method of objectively assessing
PD gait patterns.
Objectives: The aim of this study
is to test the ability of a novel insole (SEnsole) that can be worn in a
person’s shoe to reliably and accurately assess the quality and characteristics
of PD gait.
Methods: Volunteers with and
without PD were recruited. Participants were asked to walk back and forth a 10
meter path wearing the SEnsole device; sessions were video recorded.
Analysis: Sensole data was
sampled at greater than 20Hz for several bouts of walking. Steps during turns
were removed so that analysis was based on straight path walking only. A
representative healthy step cycle was formed from a composite of 40 non-PD
subjects averaged step data. The average shuffle step was similarly processed,
but on a single subject experiencing shuffling gait. Spectral analysis was used
to characterize FOG data as stride analysis is not possible during FOG
episodes.
Results: Clear differences in
gait characteristics between PD and non PD subjects were identified. The
SEnsole and analysis program accurately detected normal gait from shuffled
gait, and FOG. In addition to the observed sensitivity, the simplicity of the
SEnsole supports its usefulness in the assessment of gait and the testing of
interventions.
P26.13
Retraining function with exercise based
computer games for people with Parkinson’s disease: PD-Kinection
Lynn Rochester1, Brook Galna1,
Patrick Olivier2,Dan Jackson2, Gillian Barry1,
Dadirayi Mhiripiri1, Madeline Balaam2, Roisin McNaney2
and Mary Webster2
1 Institute of Ageing
and Health, Newcastle University, Newcastle, UK
2 The Culture lab,
Newcastle University, Newcastle, UK
Objective: Develop and pilot test an exercise
based computer game to rehabilitate dynamic postural control in people with
Parkinson’s disease(PD) using the Xbox Kinect; and assess accuracy of the
Kinect to monitor clinically relevant movement in people with PD.
Methods: An exercise based
computer game aimed at training dynamic postural control was developed in
collaboration with people with PD and their carers. The game consisted of
multi-directional reaching and stepping, with increasing complexity across 12
levels of difficulty. Nine people with PD pilot tested the game. Participant
feedback to identify issues relating to acceptability, feasibility and safety
of the game was collected in a semi-structured interview. Concurrent validity
to measure functional movements (such as sit-to-stand, mulit-directional
stepping and reaching, foot tapping, hand clasping and walking on the spot) was
established by comparing movement in nine PD participants and 10 controls
concurrently measured with a 3D motion analysis system (VICON) and the Kinect.
Results: Participants generally
enjoyed the gameplay and all felt safe whilst playing the game. Participants
performed a high volume of reaching and stepping, reaching on average 328 times
(range 167-628) and stepping 167 times (74-276) during the ~30min session.
However, some participants found interacting with game objects appearing to
move towards them difficult and some had difficulty combining the stepping and
reaching tasks. The Kinect accurately measured the timing of movements
(Intra-class correlations (ICCs) >.9) and the range of motion for gross
movements (ICCs > .9) but did not monitor smaller movements such as hand
clasping as accurately (ICCs < .3).
P26.14
The Edmond J Safra visiting nurse faculty program:
innovations in the nursing care of people living with Parkinson’s disease
Gwyn M. Vernon1,2 Lisette Bunting-Perry3
1University of
Pennsylvania, Philadelphia, PA
2National Director,
Edmond J Safra Visiting Nurse
Faculty
3 Edmond J Safra Visiting Nurse Faculty Program
Objective: The Edmond J Safra Visiting Nurse Faculty
Program was launched in 2009 to address the paucity of content on Parkinson’s
disease (PD) in undergraduate schools of nursing. Through engaging nurse
faculty in intensive didactic, clinical, and PD support group experiences in
collaboration with leading interdisciplinary movement disorder teams in the US,
the program has exceeded expectations. Since its inception, scholars attending
the program have incorporated scientific care guidelines in PD for over 5,800
nursing students. In addition, faculty scholars have developed numerous
creative projects to enhance nursing education and patient care, thereby,
greatly influencing the care of people living with Parkinson’s. This poster
will highlight several unique projects undertaken by Edmond J Safra Nurse
Faculty Scholars.
Methods: Nursing faculty have achieved excellence in
teaching content on PD and concurrently have developed a scholarly interest in
the field. This poster highlights faculty projects focused on unique
contributions in the areas of: nursing models of care, curricula design,
nursing outreach, patient care, and nursing research.
Results:
To
date, 78 nursing faculty have completed the Edmond J Safra Visiting Nurse
Faculty Program, representing over 35 schools of nursing in the United States
and Canada. While enhancing nursing students’ understanding of PD care remains
the key objective of the program, nursing faculty attending this 37 CEU
accredited course are independently pursuing scholarly work through unique
projects presented in this poster.
CARE
DELIVERY & QUALITY OF LIFE: CAREGIVING, RELATIONSHIPS, RESPITE CARE,
FAMILIES
P27.01
The
relationship between patient symptoms and caregiver burden in advanced stage
Parkinson’s disease
Nina
Browner1, Jessica Katz1,
Lindsay Prizer2, Amber Baxley3
1 National Parkinson
Foundation Center of Excellence, University of North Carolina, Chapel Hill, NC
2Department of Health
Promotion and Behavior, University of Georgia, Athens, GA
3Perelman School of
Medicine, University of Pennsylvania, Philadelphia, PA
Objective: This study aimed to describe the characteristics of the caregivers for patients with
advanced stages of Parkinson’s disease (PD) and to analyze the association
between PD symptoms and caregiver burden.
Methods: Thirty caregivers for
advance PD patients were recruited. Caregivers
completed self-reported questionnaires
on the clinical aspects of partner’s PD, Hospital
Anxiety and Depression Scale (HADS), and Zarit Caregiver Burden Inventory
(ZCBI).
Within the questionnaire, caregivers ranked patients’ symptoms by the impact on
the caregiver’s life from 8 clusters: motor, balance, medication related,
cognitive, speech, neuropsychiatric, autonomic, and sensory deficits.
Results: PD patients (76.6 %
male) had a mean age of 72.8 years (± 10.9) with median disease duration 10
years. Caregivers (16.6 % male) had a mean age of 67.2 years (±
8.9), and 86.6 % were patients’ spouses. All but 1 patient were at home.
Average hours per week caregiving were 31.7 (range 4 – 168). Nine caregivers
had outside help and an additional 4 had home health services. On the basis of HADS scores, 46.6% of patients and caregivers
experienced anxiety equally, and 50 % of patients and 60 % of caregivers
experienced depression.
Only 20% of caregivers were on medications for mood. On ZCBI,
14 (46.6%) experienced mild–to–moderate, and 7 (23.3 %) reported
moderate–to–severe burden. There was a positive correlation between ZCBI and caregiver HADS depression scores (r = 0.60, p <0.05). By impact on their life, caregivers
subjectively ranked balance deficit as #1, followed by cognitive, motor and
speech deficits. Multiple linear
regression analysis showed balance (R2 = 0.53, p <0.001)
and cognitive (R2 = 0.6, p <0.001) changes having the biggest
impact on ZCBI. In-home support with
balance and cognitive therapy for advance PD patients, psychological support,
and treatment of affect for caregivers could positively
impact advance PD care.
P27.02
The
relationship between caregiver burden and negative social exchanges in
Parkinson’s disease
Roseanne D.
Dobkin1, Michael A. Gara1, Margery H. Mark 1,2
Matthew Menza 1,2
1Department
of Psychiatry, Robert Wood Johnson Medical School, Piscataway, NJ, USA
2Department
of Neurology, Robert Wood Johnson Medical School, Piscataway, NJ, USA
Objective: Caregiver burden has a negative impact on both people
with Parkinson’s disease (PWP) and their family members. Given the heightened
rate of caregiver stress associated with the non-motor complications of Parkinson’s
disease (PD), depressed PWP and their social supports are particularly
vulnerable to its detrimental effects. The purpose of this study is twofold: 1)
to identify predictors of emotional burden in a high-risk sample of PD
caregivers, and 2) to describe the relationship between emotional burden and
the caregivers’ provision of negative social feedback (i.e., criticism,
rejection, reinforcement of negative thoughts) to depressed PWP.
Methods: Baseline data from 80 PWP and their caregivers
enrolled in a National Institutes of Health-sponsored treatment trial of
cognitive-behavioral therapy (CBT) for depression in PD (dPD) were examined.
Caregiver and patient variables that predicted caregiver provision of negative
feedback to PWP (as reported by both PWP and caregivers) were explored.
Results: The caregivers’ past receipt of psychotherapy and the
depressed PWPs’ quality of life and coping style were significant predictors of
caregiver emotional burden. Caregiver emotional burden was significantly related
to the caregivers’ provision of negative feedback (i.e., ”Your future is hopeless”) to depressed PWP on two separate measures
(caregiver measure: r= .349, P=.002 & PWP measure: r=.337, P=.002). Emotional burden and history of psychotherapy (caregiver variables),
as well as working memory, impairment in activities of daily living, coping
style, motor disability, anxiety, and negative thoughts (patient variables)
were all significant predictors of the caregivers’ provision of negative social
feedback to PWP (as assessed by both PWP and caregivers). In conclusion,
caregiver burden significantly increases the risk that caregivers will offer
negative social feedback to depressed PWP, which may make dPD more difficult to
treat. Thus, caregiver burden remains a
critical target for intervention in dPD treatment protocols.
P27.03
Carer benefit from a domiciliary multidisciplinary
specialist rehabilitation service for people with Parkinson's and their carers:
the SPIRiTT project
Gage H1, Grainger L1, Ting S1,
Williams P2, Chorley C1, Carey G1, Borg N1,
Bryan K3, Castleton B4, Trend P5, Kaye J6,
and Wade D7
1 School
of Economics, University of Surrey, Guildford, Surrey, UK
2 Department of
Mathematics, University of Surrey, Guildford, Surrey, UK
3 Division of Health and
Social Care, University of Guildford, Surrey, UK
4 The Runnymede
Hospital, Surrey, UK
5 Department of
Neurology, Royal Surrey County Hospital, Egerton Road, Guildford, Surrey, UK
6 Parkinson’s Nurse
Specialist retired
7 Oxford Centre for
Enablement, Windmill Road, Oxford, Oxfordshire, UK
Objective: To evaluate carer benefit
from a domiciliary multidisciplinary specialist (MDT) rehabilitation service
for people with Parkinson's and carers compared to usual care.
Background: Although co-resident carers provide most care for people with
Parkinson’s, thereby reducing the need for more costly arrangements, the burden
can result in strain and adverse health effects. An MDT approach to rehabilitation is
recommended to provide coordinated care and support to patients and carers, but
has not been widely researched.
Methods:
Pragmatic
three parallel group randomised controlled trial – the Specialist Parkinson’s
Integrated Rehabilitation Team Trial (SPIRiTT), Surrey, England involving people with Parkinson’s (all stages), and
live-in carers. Groups A and B
received domiciliary MDT rehabilitation for six weeks, Group B received
ongoing support for a further four months from a trained Parkinson’s care
assistant (PCA), control group (C) received usual care. A per protocol analysis
was undertaken; effects of the MDT intervention were calculated within and
between groups using change scores at 6, 24 and 36 weeks. Primary outcome:
Modified Caregiver Strain Index; secondary outcomes: generic health-related
quality of life (General Health Questionnaire, EQ-5D, SF-36), psychological
wellbeing (Hospital Anxiety and Depression Scale (HADS).
Results: 155 carers (A - 52, B - 50, and C – 53) were analysed. At baseline, carer
strain, SF-36 Mental component and HADS Depression were positively associated
with hours spent caring. The MDT intervention (Groups A and B) had a beneficial
effect on psychological wellbeing of carers. In Group B, caregiver strain
improved marginally over weeks 6-24, and psychological wellbeing improved
slightly over 36 weeks. Carers in Groups A and C reported increased strain and
decreased psychological wellbeing over the study period.
Conclusion: A domiciliary specialist multidisciplinary
rehabilitation service delivered short-term benefits to co-resident carers,
which continued when additional PCA support was provided.
ISRCTN: 44577970
Financial Disclosure: This project was funded by the National Institute for Health Research
Health Services and Delivery Research (NIHR HS&DR) programme (project
number 08/1909/251). Visit the HS&DR website for more
information.
The views and opinions expressed therein are
those of the authors and do not necessarily reflect those of the NIHR HSDR
programme or the Department of Health.
P27.04
Determinants
of psychosocial impact of being a carer of people living with Parkinson’s
disease: a systematic review
Kate Greenwell1, Anna van Wersch2,
Richard Walker1
1Northumbria Healthcare NHS Foundation Trust, North Shields, UK
2Teesside University, Middlesbrough, UK
Objective: There is evidence to
suggest that the support provided by carers leads to improved health outcomes
and quality of life (QoL) and prevention of early nursing home placement for people
with Parkinson’s disease (PwP). Being a carer, however, can have a variety of
physical, psychological, social and financial consequences that may challenge
their ability to continue caring for a PwP. This systematic review aimed to
identify the factors which influence psychosocial outcomes of caring for a PwP.
Methods: A search of the
MEDLINE, PsychINFO, EMBASE, AMED, BNI and CINAHL databases (between
1996-January 2012) and hand searches of key journals and reference lists
yielded 48 relevant articles. The psychosocial outcomes studied were varied,
including carer burden, psychological well-being, QoL and social functioning.
Results: This review found
that PwP disease factors, carer involvement (e.g. amount and duration of
care-giving), social support and other related psychosocial factors were
consistently associated with psychosocial outcomes. PwP and carer demographics
were less consistent factors. PwP QoL and carer physical health, coping styles
and personality showed consistent associations, however, further research in
these areas is needed to draw confident conclusions. This review builds on
previous PwP carer theory and highlights the need for more
theoretically-grounded and longitudinal research to guide the development of
psychosocial interventions for PwP carers.
P27.05
Hanging by a shoestring: respecting spouses’ desire to
remain at home in advanced Parkinson’s disease
Barbara Habermann
Indiana University,
Indianapolis, IN, USA
Objective: The majority of care for people with
Parkinson’s disease (PD) is provided at home by family members. PD is
characterized by a slow progressive decline with care needs often exceeding a
decade. The experience of having advanced PD and what the family preferences
are at the advanced stages has not been studied.
Methods: Data were collected on two occasions over a
one month period utilizing semi-structured interviews, with both individual and
couple interviews. The sample was 14 couples with a mean age of 73.3 years for
the person with PD and 72.1 years for the spouse. The person with PD had been diagnosed on
average for 12 years and the couples had been married for 49 years on average.
All persons with PD were dependent on assistive devices. Data was coded by
three members of the research team.
Results: All participants discussed the strong desire
to remain in their homes for as long as possible. Some participants had made
housing modifications in order to support this goal. For the persons with PD,
placement was not an option to be considered. However for spouses,
acknowledgement there may come a time when they could no longer continue to
provide care was discussed. During the study three persons were placed in a
nursing home and in each case this was unplanned. Wanting to care for a spouse
in the home is common but the care needs may be overwhelming. Interventions to
support the couple in their planning and decision making are needed.
P27.06
Reduction of care partner burden through care partner
training
Connie Hoppe,1 Karen McDonough1
1Department of Neurology,
Gundersen Health System, La Crosse, WI, USA
Objective: Patients living with Parkinson’s have a
higher risk for isolation and require coordinated care services. As PD
progress, patients rely on care partners for assistance with daily living and socialization
for quality of life. Many care partners are not prepared and struggle resulting
in burnout. Our goal is to cycle through six sites in 19 counties, a 50 mile
radius, over 2 years, reaching 10% of the “at risk” patients and care partners.
Twenty patients and care partner pairs per site will be given disease-specific
education. We expect to see higher quality of life scores in care partners who
participate in the training program.
Methods: Members of a multi-specialty health team,
specially trained in Parkinson’s care have designed “stations” for small
groups. In these stations, specific tasks are presented. Stations cover safe
mobility, adaptive equipment, falls, medication compliance, monitoring
declines, assessing medication response, weight loss, lightheadedness, bowel
and bladder issues, handling hospitalizations, and maximization of resources.
Care partners rotate through stations over two hours. Training is offered one
day a month rotating through the 19 counties. Reinforcement is available on DVD
or on line.
Results: Care partners completing training are
compared to those receiving routine education and support through a Parkinson’s
clinic. Both groups are surveyed at three weeks, three months, and six months,
looking at retained knowledge, activities implemented and SF – 36 scores. Our
primary outcome measure will be care partner burden in our intervention group
by use of SF – 36 scores. We expect higher quality of life scores in care
partners who participated in the program.
P27.07
“Do I look like I care?” Parkinson’s disease and its
potential effects upon relationships
Jackie Hunt Christensen
National Parkinson
Foundation, Minneapolis, MN, USA
Objectives: To gather information from people living with
Parkinson’s disease about communication-related symptoms—e.g., facial masking,
flat affect, lower speech volume and altered body language—and whether any
personal relationships have been affected by those specific symptoms. To
educate family, friends, health professionals, staff who interact on a regular
basis with people living with Parkinson’s disease, and the general public about
masking, speech effects and altered body language symptoms in order to foster
greater tolerance, respect and understanding of the disease and those affected
by it.
Methods: Two voluntary self-selecting surveys were
created. They were not built with statistical analysis in mind. Rather, they
were intended to provide “snapshots” and anecdotes from the lives of those who
completed them. In addition to demographic information, questions regarding the
specific symptoms listed above, relationship changes attributed to those
symptoms, and anecdotes were collected in the surveys (available upon request).
Data were collected by the two surveys posted on Survey Monkey, each for three
months. Availability of surveys publicized was through email and social media.
Data and anecdotes from two surveys were compiled and prepared for future
publication. .
Results: Data from surveys showed that certain
symptoms of Parkinson’s disease have deleterious effects on interpersonal
communication. These effects were found to impact relationships of all
kinds—those with life partners, potential life partners, family, friends,
healthcare providers, even complete strangers. Better education about
Parkinson’s disease and increased awareness that one cannot rely on typical
body language or means of expression to interpret mood or intent are needed in
order to maintain (or create) important life relationships and to reduce the
isolation so common in people living with Parkinson’s disease.
P27.08
Different impact of Parkinson’s disease symptoms on
patients and caregivers
Kenichi Kashihara 1, Kanako Hirono2,
Tetsuya Maeda 3, Atsushi Takeda 4
1 Department of
Neurology, Okayama Kyokuto Hospital, Okayama, Okayama, Japan
2Division of
Rehabilitation, Okayama Kyokuto Hospital, Okayama, Okayama, Japan
3 Department of
Neurology, Research Institute for Brain and Blood Vessels-Akita, Akita, Akita,
Japan
4 Department of
Neurology, Tohoku University Medical School, Sendai, Miyagi, Japan
Objective: Symptoms of Parkinson's disease (PD)
influence QOL of patients and their caregivers. We examined the difference of
distress of each PD symptom for patients and their caregivers.
Methods: Pairs of PD patients and ones caregivers who
were able to answer the question were enrolled to the study. We asked each pair
to pick up presenting PD symptoms of patients, and then asked if the symptoms
disturbed their daily life or not.
Results: 184 patient-caregiver pairs were assessed in
the present study. Among motor symptoms, freezing gait (28.3%), postural
instability (27.4%), bradykinesia (21.6%), frequent falls (21.4%), and tremor
(19.7%) were the main symptoms for PD patients to feel distress. Among
non-motor symptoms, constipation (25.1%), low back pain (17.7%) and frequent
nocturnal micturition (16.9%) were complained frequently to feel distress by
patients. The distressing symptoms for caregivers were frequent falls (27.3%),
postural instability (25.1%), bradykinesia (22.3%), and freezing (21.3%) as
motor symptoms, and cognitive impairment (20.5%) and apathy (18.1%) as
non-motor symptoms. The 3 most distressing symptoms for patients were gait
freezing, constipation and postural instability, and they were frequent falls,
postural instability and cognitive impairment for caregivers. The symptoms of
which patients felt distress more prominently than their care givers were gait
freezing, constipation, pain (low back pain, head ache, and the other pain),
frequent nocturnal micturition, insomnia, drooling, orthostatic hypotension,
and taste impairment. Whereas, the ones of which caregivers felt distress more
than patients were frequent falls, cognitive impairment, apathy, psychosis,
aggression, irritability, vocalization during sleep, and sweating. Symptoms
including nocturnal vocalization, irritability, aggression, impotence, and
sweating were the symptoms of which PD patients do not care as well as
caregivers.
P27.10
Parkinson’s Spousal Caregivers and Health Care/Work
Issues
Jan Rabinowitz
PD
Caregiver/Independent Research Consultant
January Consulting,
Atlanta, GA
Objective: Determine
what health care and work related issues cause problems for spousal caregivers,
and to bring awareness within the Parkinson’s community of non-medical effects
of the disease on the family.
Methods: The link
to the online survey was posted to several PD and Caregiver-related Facebook
pages, and emailed to a variety of support group participants. It was also
posted on the NPF Caregiver and the Well Spouse Association Online Forums.
Results: These results are preliminary, based on
the first 92 respondents. Caregivers as well as their partners are
approximately 3 times more likely to be no longer working now than at the time
of diagnosis. Both groups appear to have health insurance or Medicare coverage,
with the exception of a few caregivers. Two-thirds of caregivers have
experienced anxiety since their partner’s diagnosis, and just over half
indicated that depression has also been experienced. A significant number
report pain in the back, neck, knee, leg, arms, hands and/or shoulders. About
half have received mental health counseling in the past, and about 30%
currently receive counseling. Caregivers report that the PWP is least likely to
be able to independently work outside the home, handle yard work, and/or do
household chores/repairs. Activities that caregivers have typically taken over
include making important decisions, driving, paying the bills, doing household
chores/repairs, and helping the PWP with entertainment. Respondents were split
evenly in terms of their financial situation relative to time of diagnosis,
however one in five each rated their level of concern regarding future
financial obligations as quite or extremely concerned. One third of the
caregivers say they are getting by, but barely, right now, and 5% are having to
use savings or borrow to stay afloat.
P27.11
Providing instruction of Reiki first degree as a
complementary therapy to help improve the lives of Parkinson's disease (PD)
carepartners/caregivers
Angela Robb1, Karl Robb2
1PD Carepartner &
Reiki Master, GiveReiki.com, USA
2Person with
Parkinson's disease & Reiki Master, GiveReiki.com, USA
Objective: To
instruct and educate the Parkinson's disease community about how the teaching
of Reiki (RAY-KEY) first degree as a complementary therapy to Parkinson's
disease carepartners/caregivers can be beneficial to their self-care. To give
carepartners/caregivers another tool to reduce stress, increase relaxation, and
provide mental & physical calmness. Reiki is a non-invasive therapy that
uses light touch to increase and enhance one's personal energy. Reiki first
degree instruction focuses on self-care, a self-treatment protocol, and seated
chair protocol to give Reiki to another person.
Methods: The
workshop is a twelve hour workshop in Reiki first degree. The current workshop
held in six two-hour sessions, allowing the carepartner to absorb the material.
The workshop includes instruction in Mindfulness Meditation, Energy anatomy,
Qigong, and Reiki self treatment & seated chair protocols. The workshop
highlights the importance of the caregiver/carepartner to take care of
themselves on a daily basis. Examples of how Reiki can be incorporated into
daily life are presented.
Results: Carepartners/Caregivers will be
able to treat themselves
with Reiki and have a general understanding of Reiki which can be
used to enhance and complement their current self-care strategies. Workshop participants
will be able to use Reiki to increase one's relaxation, reduce stress, and
enhance the body's own healing properties. Carepartners/Caregivers will also be
able to provide Reiki to help their love one who is living with Parkinson's
disease.
P27.12
Quality of life and caregiver burden among
Hispanic subjects with Parkinson's disease living in the US and Mexico
Mayela Rodríguez-Violante1, Claudia
Martínez2,
Margaret Anne Coles2, Amin Cervantes-Arriaga1, Azyadeh
Camacho-Ordoñez1, Paulina González-Latapi1
1Instituto Nacional de Neurologìa y Neurocirugía,
Mexico City, Mexico
2Muhammad Ali Parkinson
Center, Phoenix, AZ, USA
Objective: Ethnic and sociocultural factors may play a
role in quality of life (QoL) and caregiver burden perception. The objective is
to compare the QoL and caregiver burden between Latin-American subjects with
Parkinson’s disease living in the United States (US) and Mexico.
Methods: Immigrants or first-degree relatives of
Latin-American immigrants to the US participating in the Muhammad Ali Parkinson
Center’s Promotores Program and diagnosed by a Movement Disorder Neurologist in
Phoenix or Mexicans at the National Institute of Neurology and Neurosurgery in
Mexico City and who fulfilled UKPDBB criteria for Parkinson’s disease were
included. QoL was assessed using the PDQ-39 while caregiver burden was
evaluated with the Zarit Caregiver Burden Interview (ZCBI).
Results: A total of 27
subjects from Phoenix (63% Mexican) and 30 subjects from Mexico City were
included. No differences were found in regards to gender (p=0.58), years of
schooling (p=0.59), age (p=0.86) and disease duration (p=0.98). PDQ-39 total
score was slightly higher (worse QoL) in subjects living in the United States
but without statistical significance (38.6 ± 20.7 vs 31.6 ± 19.3, p=0.20). From
the eight dominions of the PDQ-39, the only difference found was on social
support where US subjects reported higher scores (41.3 ± 31.7 vs 15 ± 25.5,
p=0.001). Caregivers from both groups did not differ in the number of days per
week spent with the subject nor in the total years of caregiving. Little or no
caregiver burden was reported by 93% of caregivers in the US in comparison to
the 80% from Mexico (chi square p=0.17). Our data shows a statistically significant
difference in the social support dominion, being worse in subjects from the US.
Caregivers in the US reported less burden than their counterparts in Mexico.
Whether these findings are due to sociocultural factors merits further study in
a larger sample.
P27.13
Documenting the lived experience of unconditional love in
Parkinson care giving
Ramon Ruiz Sampaio1 and Sheree L. Loftus 2
1Ramon Ruiz Sampaio,
Mexico City
2Beth Israel Medical
Center, NY, NY, USA
Modern technology fosters
longevity. Degenerative diseases are more common with age. There are 65 million
family caregivers in the United States. At some point it is likely we will
provide family care or receive it. Most of us are untrained and unprepared to
assume this responsibility. Awareness of this vital issue is crucial to support
and integrate family caregivers in the health care system. Parkinson disease is
an increasingly common degenerative condition. This disorder of the central
nervous system presents with movement - related symptoms of shaking, rigidity,
slowness, and difficulty with walking and speech. As the disease progresses,
difficulty with sleep, cognitive, emotional, and behavioral problems may arise.
Parkinson disease has a relentless progression. The care needs of the person
diagnosed becomes increasingly demanding over a lifetime. The role of the
caregiver is essential. This photo documentation focuses on family managing to
overcome the challenges in the care giving journey of Parkinson disease. The psychological,
physical, and everyday aspects of care giving are starkly depicted. The long -
lived experience of Parkinson disease - related progressive symptoms takes a
toll. The once free human being is now immobilized by the disease, with soft
speech rigid limbs, unable to turn the body axis freely, swallowing difficulty,
and inability to initiate the simplest gait. The Parkinson mind well - aware of
the altered body, but unable to translate this awareness into action. The
family caregiver is ever present with encouragement, kindness, a helping hand,
concise direction and unconditional love. Every day is important, and living in
the present moment arrives with clarity as movements of freedom are limited by
Parkinson disease. Symptoms progress and family life is undermined by
increasing limited movement. The family caregiver struggles with multiple
roles, yet is a cherished resource and at once creative, resilient, flexible
and frustrated.
P27.14
What measures of disability predict caregiver burden in
Parkinson’s disease
M. Kwasny1, O. Oguh2, D. Klein1,
T. Simuni1, on behalf of the NPF QII Investigators
1Northwestern
University, Chicago, IL, USA
2University of Florida
Jacksonville, Jacksonville, FL, USA
Background: Caregiver burden is significant and increases
with progression of disability in Parkinson’s disease (PD).
Objective: To determine what measures of PD disability and patient quality of
life are associated with caregiver strain among carers of patients with PD.
Methods: Data was collected from
PD patients and their caregivers enrolled in the NPF-QII registry. 1470
patients who indicated non-professional caregivers, with complete
Multidimensional caregiver strain inventory (MCSI), and at least two clinic
visits were included in the analysis. Multivariate logistic and linear
regression models were fit to examine the relationship between caregiver burden
(MCSI≥30) and PD quality of life (PDQ-39), as well as several aspects of
PD disability including stage of disease, disease duration, concomitant
medication use, cognition, utilization of mental health care and social
services at baseline, and predicting change in MCSI at a subsequent visit.
Results: Similar to a larger
analysis of cross sectional data from the NPF-QII registry, PDQ-39 was the strongest
predictor of caregiver burden at baseline (c=0.80, p<0.001). After adjusting
for PDQ-39 (OR=1.07, p<0.001), decreased verbal fluency (OR=0.93, p=0.003),
history of mental health referrals (OR=1.99, p=0.006), were also predictive of
caregiver burden. At the next clinic visit, there was a small, but
statistically significant increase in MCSI (mean 1.31, SD 11.2, p<0.001).
The change in caregiver burden was most related to changes in PDQ-39
(p<0.001), and to decreases in verbal fluency (p=0.028) after adjusting for
baseline age (p=0.005), Hoehn and Yahr stage>3 (p=0.015), and disease
duration (p=0.398).
Conclusions: These results
demonstrate the caregivers are afflicted with strain and burden in many
psychosocial and somatic domains of PD care. PDQ-39 total score is the
strongest predictor of caregiver burden.
P27.15
Turning Strain into Strength: Investigating caregiver
growth in the loved ones of persons with Parkinson’s disease (PD)
Deborah Worboys1, Associate Professor Anne
Tolan1, Dr Andrea Langmont-Mills2
1Australian Catholic
University, Brisbane, Queensland, Australia
2University of Southern
Queensland, Toowoomba, Queensland, Australia
Objective: There is a plethora of
research into Caregiver burden. However, Caregiver
growth is an important, yet less-explored phenomenon. It is important to focus
on the positive side of PD caregiving and its benefits; not only because
experiencing growth is valuable in its own right, but also because personal
growth (such as deriving pleasure and gratification, developing skills, and
finding meaning) may buffer against the common detrimental consequences of
caregiving (such as depression, burden, and health problems). This PhD project
adopted a strength-based perspective. This project aimed firstly to investigate
whether caregiver growth is experienced, secondly to examine psychological
aspects associated with caring for a loved one with PD, and thirdly to make
recommendations for possible psychological interventions aimed at assisting in
empowering loved ones to positively adjust and grow throughout their caregiving
journey.
Methods: A Qualitative
research project, consisting of two studies. Study 1 involves in-depth
interviews (N=30) and Study 2 involves a group discussion (N=3) with the loved
ones of people with PD, about their overall caregiving experience.
Results: Interpretative Phenomenological Analysis of data has
shown emerging themes and patterns associated with personal growth in a PD
caregiving sample. Overall findings show that the majority of loved ones report
some positive transformation and growth as a result of their caregiving
experience. Many loved ones reported becoming more patient, independent,
assertive, compassionate, and empathetic, with a greater sense of life purpose
and meaning as a result of caring for their loved one with PD. These findings
support Dementia caregiving research findings.
P27.16
Quantitative
assessment of home and community mobility of persons with Parkinson disease and
their spousal caregivers
Lynn Zhu1, 9, Catherine Lavigne-Pelletier2,3,
9, Margaux Blamoutier2,3, 9, Simon Brière4, 9, Matt
Dibsdale5, Patrick Boissy4, 6, 9, Mandar Jog7,8, 9,
Christian Duval2,3, 9, Mark Speechley1,9
1Department of
Epidemiology and Biostatistics, Western University, London, ON, Canada
2Kinanthropology
Department, L'Université
du Québec à Montréal, Montréal, QC, Canada
3Centre de recherche de l’institut universitaire de
gériatrie de Montréal, Montréal,
QC, Canada
4Research Centre on Aging, Sherbrooke Geriatric
University Institute, Sherbrooke, QC, Canada
5School of Kinesiology, Western University, London, ON,
Canada
6Faculty of Medicine and Health Sciences, L'Université de Sherbrooke, Sherbrooke, QC, Canada
7National Parkinson Foundation Center of Excellence
Movement Disorders Laboratory, London Health Sciences Center, London, ON
8Clinical Neurological Sciences, Western University,
London, ON
9Ecological Mobility in Aging and Parkinson’s (EMAP)
Research Team, Canada
Objective: Spousal caregivers of people with Parkinson
disease (PwP) can experience increased level of caregiver stress. However,
whether Parkinson disease affects the day-to-day activities and mobility of
each partner in the spousal dyad has not been evaluated. This study compares the daily physical
activity (PA) duration and community mobility of PwPs and their spousal
caregivers.
Methods: Thirteen pairs of community dwelling PwPs
(nine males, four females; Hoehn and Yahr stages I and II; 67.6 ±7.9 years)
and their spousal caregivers (four males, nine females; 65.3 ±7.7 years)
participated in this study for 14 days. Analysis of covariance (ANCOVA) was
conducted to compare between spousal dyads and across the spousal caregiver and
PwP groups for: 1. same-day average daily PA duration, measured using energy expenditure armbands (PA: > three METs for > two minutes) and 2. same-day average daily area of
travel outside the home (km2), measured by a wireless inertial measurement
unit with GPS. Age and self-perceived social support received by the PwP were
added as covariates.
Results: A statistically significant difference (p = 0.04) was observed between the PA
duration of PwPs (mean = 1 hour and 6 minutes) and spouses (mean = 2 hours).
Average daily area travelled by spousal caregivers spanned 906.9 ±1558.2 km2
versus 821.6 ± 1386.1 km2 travelled by PwPs; this
difference was not statistically different, after adjusting for age and social
support (p = 0.43).
Conclusion: Results suggested spousal
caregivers maintained an active lifestyle during early PD, and spouses and PwPs
may be travelling together outside the home. It is unclear whether the
difference in PA durations is due to PD related caregiving duties, spousal pairs
maintaining pre-PD PA routines, or both. The interpretation of results is
complicated by the high variability in distance
travelled; hence it is important to consider each spousal pairing
individually.
CARE
DELIVERY & QUALITY OF LIFE: FITNESS, WELLNESS, NUTRITION
P28.01
How does a self directed exercise
class increase quality of life for people with Parkinson’s disease from a local
community perspective?
Jillian Carson
Person with Parkinson’s disease,
Victoria, BC, Canada
Objective: The
objective is to provide the opportunity for PWP to exercise together three
times a week at local community recreation centres which are accessible to PWP.
There are many barriers to exercising, including; accessing trained exercise
therapists, cost, motivational issues, isolation and transportation. PWP are
capable of teaching each other exercises and providing feedback and support as
long as they have been educated themselves on the benefits of specific fitness-
focused exercises for PWP and the latest research to back it up.
Methods: The
local recreation centre is approached and educated about Parkinson’s disease
and the importance of exercising in a self- directed group. This limits costs
for facility fees. Each PWP is initially assessed by a trained PWR!Moves
physical therapist to obtain information about underlying pathology preventing
participation, baseline function and to identify individual exercise needs to increase
present function. Small groups are taught their deficits to target. There must
be set times for PWP to go to the community recreation centre so it becomes
routine. All group members are responsible for helping each other with the
exercises and encouraging each other to push and achieve higher function. As
PWP are all different each are working independently but using similar
equipment. Reassessment by a trained therapist is advised every three months.
The trained therapist support is available as needed but need not attend all
sessions.
Results: PWP can
get better and feel better by attending an exercise group with their peers. The
above barriers are broken down. The group feels comfortable exercising with
other PWP and helping each other. New friendships are made; information is
shared resulting in better quality of life and EMPOWERMENT!
P28.02
Postural sway among elderly women with and without Parkinson
disease: a cross-sectional study
Juliana Costa1, Samuel Vidal1, Bruna Avelar1,
Ricardo Moreno1, Marisete Safons1, Ricardo Oliveira1.
1University
of Brasília, Brazil
Objective: To
compare the postural sway in a static position with and without the aid of the
visual system among Parkinson’s disease (PD) physical exercise practitioners
and healthy elderly women classified as physical exercise non-practitioners
(HE).
Methods: A total
of 26 elderly women paired by age and body mass index (BMI) were divided into
two groups, PD (n=13) 69,31±5,45 years with a BMI:27,28±5,24kg/m2 and HE (n=13)
69,15±5,50 years with a BMI:27,15±4,99kg/m2. The Hoehn & Yahr scale was
used to classify the disease level (1-4). The center of pressure sway was
measured using a force platform of two balance tasks with eyes open (EO) and
closed (EC). The subjects were instructed to stand as still as possible with
their feet 2 cm apart and arms at their sides. Data was collected with a
sampling frequency of 100 Hz and filtered with a cut-off frequency of 10 Hz.
Each test was performed twice for 30 s and the average was calculated.
Descriptive (median, average and standard deviation) and inferential statistics
(Mann-Whitney U test) were used with a significance level of 5%.
Results: There
was a difference between groups in EC protocol for the Sway Range AP variable
(p = 0,001) with HE showing lower anteroposterior displacement range than the
PD. However, for the other variables in the two protocols no differences were
found (p>0,05) (Table 1). The results suggest that elderly PD physical
exercise practitioners present values of postural sway comparable to similar
subjects older in terms of age and body mass but non-practitioners.
Table1. Main
descriptive postural sway variables (Median) characterizing postural control in
PD and health elderly women.
|
Closed Base |
Group |
|
p-level |
PD |
HE |
|||
Sway Range AP (cm) |
EO |
2,42 |
1,96 |
0,204 |
|
EC |
3,01 |
1,19 |
0,001 |
Sway Range ML (cm) |
EO |
2,84 |
2,20 |
0,335 |
|
EC |
3,03 |
2,58 |
0,091 |
Area 95 (cm2) |
EO |
4,76 |
3,28 |
0,139 |
|
EC |
6,50 |
3,92 |
0,153 |
Path Length (cm) |
EO |
40,25 |
41,69 |
0,801 |
|
EC |
55,12 |
54,65 |
0,807 |
Average velocity (cm/s) |
EO |
1,34 |
1,39 |
0,801 |
|
EC |
1,91 |
1,82 |
0,570 |
EO:Eyes open; EC:Eyes closed; Area
95: Area 95% of ellipse; AP: Anteroposterior; ML: Mediolateral
|
P28.03
Pilates
for Parkinson's disease: an interdisciplinary perspective
John
Dean1 Charlene Urbancic1 Donna McLean2
1Life Care Centers of America, Longmont,
CO, USA
2Pilates Bodies®, Longmont, CO, USA
Pilates is an exercise-based approach to
strengthening and flexibility based upon the work of Joseph Pilates. The
emphasis on core strengthening, axial rotation and breath work makes this
approach well-suited to the treatment of Parkinson's disease. In addition, there is an inherent
awareness of movement and an emphasis on controlling and maximizing function of
each component of the body during performance of exercises. By incorporating
resistive breath training and voice exercise into the activities, it is
possible to unlock the interdisciplinary potential for these activities in
rehab and exercise settings. Pilates exercises improve symptoms of postural
dysfunction by reducing kyphosis associated with Parkinson's disease in
addition to enhancing core stability and axial range of motion, resulting in
numerous benefits from an interdisciplinary perspective. Enhancing upright
posture and rotational flexibility can result in improved balance and walking
abilities. It can also also facilitate enhanced breath support which can result
in louder phonation ability. Speech production will be more properly directed
upwards towards communication partners and non-conversational pragmatics such
as eye contact may also be enhanced. Upright positioning can improve transit of
food materials from the stomach to the mouth. Enhanced breath support also
facilitates stronger cough reflex (improving airway protection). If drooling is
present, enhancing upright posture can mitigate this dysfunction. There is only
a minute amount of published material discussing improving symptoms of
Parkinson's disease with a Pilates approach and no publications in
peer-reviewed journals.
There have been a handful of peer-reviewed
articles regarding the benefits of Pilates interventions on gait and balance in
the general population. Further study into the efficacy of this treatment
approach for Parkinson's-related deficits in all rehab disciplines is merited.
P28.04
In the Clinic, in education and in the Community: A
capacity building strategy for comprehensive supportive services and wellness
programs through community partnership
Alessandro Di Rocco; Amy C. Lemen; Virgen Luce.; Roger
Rossi
1
NYULMC
Parkinson and Movement Disorders Center, New York, NY, USA
2
NYU Silver School of Social Work, New York, NY, USA
Background: In 2007, the NYU Langone Medical Center’s
Parkinson and Movement Disorders Center (NYULMC-PMDC) embarked upon an
experimental pilot program with the Jewish Community Center in Manhattan (JCC)
to develop Parkinson’s-specific wellness programs for those impacted by
Parkinson’s. Six years later, this pilot program has evolved into the
award-winning Edmond J. Safra Parkinson’s Wellness Program (EJSPWP) and become
a national model for innovative community-based Parkinson’s care.
Aims: The EJSPWP is a welcoming hub for the regional
Parkinson’s community and remains in high demand. With a focus on dignity,
hope, respect and possibility, the program offers fitness classes, support
groups and educational and socialization events for patients, caregivers and
loved ones. A range of PD-specific fitness classes with varying curriculum
impacts include: Alexander Technique; Chair Exercise; Rhythm and Functional
Movement; Water Exercise; Tai Chi/Qi Gong; Nia: Movement and Music; Chair
Exercise; PD Bootcamp; and Yoga. Psycho-educational Support Groups for Patients
and for Caregivers are facilitated by licensed social workers and monthly
education, socialization and creative expression events are provided.
Methods: The EJSPWP has become the dynamic
cornerstone of the NYULMC-PMDC’s unique and innovative Supportive Services
Program (SSP). The SSP has further developed to build much needed capacity through
partnership in education, in the clinic and in the community to meet the needs
of patients, caregivers and families. The SSP’s mission is this: 1) To keep our
patients, caregivers and families active, educated, empowered and connected in
an effort to achieve the highest possible quality of life throughout the
disease spectrum and continuum of care; 2) To build a replicable model of
supportive and wellness care and; 3) To provide support for our medical,
scientific, and healthcare professionals team. Integrated, on-site clinical
social work services, including psychotherapy, supportive counseling,
education, resource referral and limited case management for advanced patients
are provided to families within the clinic. Support Group and professional education
delivery is provided in collaborative partnership with the Hebrew Home at
Riverdale’s Geriatric Care Management Program to build the network of PD
trained supportive service providers. And the SSP has developed a nationally
unique Social Work Educational Initiative to train the next generation of PD
supportive care leaders in collaborative partnership with the NYU Silver School
of Social Work.
Results: The SSP is popular
with patients and with providers, as it provides a range of proactive and empowering
supportive care options that complement medical care. The supportive and
wellness program partnership model has expanded our capacity to provide
services, increased access to care and extended the boundaries of clinical
dialogue into the community. The trust relationships that are built with
patients, families and providers in the community and in the clinic are
allowing us greater ability to communicate and coordinate effectively as we
partner in transitions related to disease progression and medical to community
transfer.
Discussion: This poster will demonstrate in graphics and
narrative the growth, development and vision of this innovative, replicable and
poplar supportive services and wellness program model.
P28.05
Aerobic exercise
training improves health and the acquisition of new motor skills in early
Parkinson’s disease.
Catherine Duchesne1,
2, Freja Gheysen2, 4, Marie-Ève Robillard2,
Arnaud Boré2, Florian Bobeuf2, Ovidiu Lungu1, 2,
Anne-Louise Lafontaine3, Louis Bherer2, 5, Julien Doyon1,
2
1Université de Montréal, Montréal, QC, Canada
2Centre de Recherche de l’Institut Universitaire de
Gériatrie de Montréal, Montréal, QC, Canada
3McGill University, Montréal, QC, Canada
4Ghent University, Ghent, Belgium
5PERFORM Centre, Concordia University, Montréal, QC,
Canada
Objective: Aerobic exercise training (AET) has been shown to have many health
benefits in individuals with Parkinson’s disease (PD), including improvement in
previously automatized motor skills (i.e., locomotion). Yet, it is unknown
whether AET can also facilitate the acquisition of new motor skills in PD. To this end, we assessed the effects of
3-month AET on learning of a new
motor sequence, as well as on different health-related indicators (i.e.,
functional capacity, cognitive functioning, cardiorespiratory fitness, and
quality of life).
Methods: Twenty-five individuals (14 healthy, 11 early PD) participated in a
supervised stationary recumbent bike training program (3 times/week; 12 weeks).
Exercise prescription started at 20 minutes high intensity training based on
participant’s maximal volume of oxygen uptake (VO₂peak or estimate). This duration was increased by 5
minutes every week until it reached a total of 40 minutes. Participants’
ability to learn a new motor sequence was assessed using a bimanual version of
a sequence learning task before and after AET. Functional capacity, cognitive
functioning and cardiorespiratory fitness were also assessed in both groups,
while severity of PD symptoms and quality of life were evaluated in the PD
group only.
Results:
Cardiorespiratory fitness improved significantly in all participants indicating
that the AET program was effective. Moreover, the ability to learn a new motor
sequence increased significantly in both groups as a result of training.
Cognitive functioning improved in elderly individuals, but only marginal gains
were observed in their PD counterparts. UPDRS scores were reduced in 6 out of
11 individuals with PD, whereas a significant reduction of social stigma
(quality of life indicator) was recorded after training in PD patients. Our
results suggest that AET can be a valuable non-pharmacological intervention to
promote fitness and wellness in early PD, and that it helps them to acquire new
motor skilled behaviours.
P28.06
Community Wellness for people with Parkinson’s
Annette Edwards
Banner Neuro Wellness,
Gilbert, AZ, USA
Background: Studies continue to show evidence that
specialized exercise and stimulating activity in conjunction with medical
treatment slows the disease progression and increases quality of life. Up until
now, individuals with Parkinson’s disease have few if any resources to receive
specialized disease specific support.
Banner Neuro Wellness
was developed to bridge the gap between gains made during formal medical
treatment and therapies into sustainable results that enhance wellness through
activities and socialization in a supportive community setting. This approach
promotes quality of life and maintains function.
Aim/Objective: The objective of Banner Neuro Wellness is to
provide an environment that empowers people with Parkinson’s to stay engaged
and active members of society. The Parkinson’s specific exercise programs and
activities aim to promote quality of life and maintain function. Through this
highly specialized program, individuals have a place to meet their physical,
social, and emotional needs. Banner
Nuero Wellness helps individuals to stay active members of the community.
Method: Banner Neuro Wellness provides PWR! exercise,
fitness training, yoga, Tai Chi, speaking groups, art, support groups and
special interest classes to its members weekly. Members are encouraged to
attend 2 to 3 PWR! exercise classes per week and at least one special interest
class. The community based center allows
the individual with Parkinson’s an avenue to engage in multiple exercise and
wellness activities weekly.
Results:
Banner
Neuro Wellness meets the need of the Parkinson’s community by facilitating physical
activity and stimulating activities in a positive wellness environment.
Membership has grown to over 100 members in a year and offers over 30 classes
per week. Members report their ability
to maintain function with fewer falls and a higher quality of life.
P28.07
Nutritional status correlates with non-motor and motor
symptoms of Parkinson’s disease: A cross-sectional analysis in 143 patients
Seyed-Mohammad Fereshtehnejad1, Ladan Ghazi1,
Ahmad Delbari1, 2, Gholam Ali Shahidi3, Johan Lökk1
1Division of Clinical
geriatrics, Department of Neurobiology, Care Sciences, and Society (NVS),
Karolinska Institutet; Stockholm, Sweden
2Aging Research Center,
Sabzevar University of Medical Sciences, Sabzevar, Iran
3Neurology Department, Tehran
University of Medical Sciences, Tehran, Iran
Objective: Nutritional status has attracted less
research attention than it should be in Parkinson’s disease (PD). Numerous
features of PD including motor and non-motor (NMS) symptoms could make the patients
susceptible to malnutrition, and nutritional impairment may itself exert a
significant influence on PD complications to make a vicious cycle. The aim of
this study was to evaluate the relationship between nutritional status and
severity of the NMSs and motor symptoms in PD patients.
Methods: This cross-sectional study was performed in a
referral movement disorder clinic in Tehran, Iran during 2011-2012. A total
number of 143 PD (96 males and 47 females) patients with the mean age of 61.4
(SD=10.5) yr were recruited in this study. Mini-Nutritional Assessment (MNA), Hospital
Anxiety & Depression Scale (HADS), Fatigue Severity Scale (FSS), PDQ-39 and
Hoehn & Yahr and Schwab & England score of disability were filled up in
PD patients.
Results: Univariate Pearson
correlation showed that depression score was the strongest symptom to associate
with MNA score (r=-.596, P<.001). More severe anxiety (P=.023), depression
(P<.001) and fatigue (P=.006) were observed in cases at risk of
malnutrition. Multiple regression showed that communication (Beta=-.271,
P=.001) and bodily discomfort (Beta=-.208, P=.003) domains of PDQ-39,
depression (Beta=-.251, P=.003) and Schwab & England score (Beta=.233,
P=.001) were independently associated with MNA score.
Conclusions: Negative
association was found between NMS’s especially depression suggesting that
nutritional status needs to be more highlighted in PD care. Even more
interestingly, NMS’s were more correlated with nutrition than motor symptoms,
which must be taken into account in further causality evaluations.
P28.08
Tai Chi, Zumba, drumming and golf: An integrative approach to
promote PD wellness
Lissa Kapust1, Stacey Lee1, Dan Tarsy1
1Beth Israel Deaconess Medical Center, Boston,
MA, USA
Objective: There are increasing
reports in both the professional and lay press supporting the role of exercise
on the health and wellbeing of patients with Parkinson’s disease. Many patients
actively seek treatments “beyond the pill box”, searching for therapeutic activities
focused on positive health initiatives. Over the past 3 years, at our National
Parkinson’s Foundation Center of Excellence, we have fully integrated 4
different exercise programs into a Wellness Program. We describe these
specialized programs: Tai Chi, Zumba, Drumming and Golf. Videos support the
rationale for the Tai Chi and Zumba programs and capture the enthusiasm of the
participants. Program challenges and future directions are presented.
Methods: Introduce and
integrate 4 wellness programs into a hospital-based clinical program for PD
patients. Posters and flyers to market the programs emphasize the health and
social benefits of participation in these programs. Classes are carefully
designed for patients with relatively recent diagnoses who have mild symptoms.
Yearly patient surveys guide the programs which we offer. Members of our
interdisciplinary team routinely generate patient referrals to our programs.
Education and training concerning Parkinson’s disease is provided to
instructors so they can modify classes to meet the needs of participants.
Ongoing feedback from participants is elicited from the instructors so that
classes can be “tweaked” as needed. Partners of patients are invited to
participate to enhance social aspects of the program.
Results: To date, over 200
participants have enrolled in exercise classes. Our success depends on the
training and skills of our instructors, the appropriate selection of
participants and the full support from the team. Patients uniformly report
improved wellbeing while participating in these programs. We are currently
planning formal research projects to quantify the benefits to our patients.
P28.09
A continuous care model: education to rehabilitation to
wellness.
Erin Keefer1, Matthew Ford2,
Elizabeth Woolley1, Amber Brown1, Danna Weatherford1
1Southeast Alabama
Medical Center, Dothan, AL, USA
2The University of
Alabama at Birmingham, Birmingham, AL, USA
Objectives: The goals of the Southeast Alabama Medical Center
health and wellness program include: 1) to provide a comprehensive education,
rehabilitation and wellness for people with Parkinson’s through experienced
staff, 2) to provide the framework for a replicable program that ensures known
outcomes and 3) to provide a sense of community and services previously
unavailable for PWP and their families.
Methods: SAMC provides access to high quality
educational, rehabilitation and wellness opportunities in one facility in a
rural community. All program staff were identified to have an interest in
treating PWP and have participated in additional professional training to more
effectively work with PWP. The program began in January 2013. A program
participant initiates the program with a 2 hour initial evaluation compromised
of education and needs assessment. The participant transitions to any
combination of physical, occupational and speech therapy. Once rehabilitation
is completed, the participant has the opportunity to join a structured wellness
program. Systematic data is collected at the initial 2 hour visit, completion
of rehabilitation and every 6 months in the wellness program. The program
creates a sense of community by providing regular digital newsletters, assists
the local Parkinson’s support group and organizes social events. SAMC receives
guidance and assistance from SAMC Foundation, University of Alabama at
Birmingham – Department of Neurology, APDA – Birmingham, Parkinson’s
Association of Alabama and Lakeshore Foundation.
Results: To date 33 people with
Parkinson’s have entered the program. 19 PWP have completed rehabilitation
demonstrating improvements in functional mobility, ADLs, balance, physical
activity levels and quality of life measures. 14 PWP have initiated the post –
rehab wellness program and participate in aquatic, walking, balance and
cardio/strengthening classes. All wellness classes are instructed and
supervised by an exercise specialist(s) with specialized training to work with
PWP.
P28.10
Evaluation of a rhythmic exercise program for patients
with Parkinson`s disease
Audun Myskja
Objective: To evaluate a structured training program
using a series of rhythmic exercises for a group of patients with Parkinson`s
disease (PD).
Background: There is increasing interest in the
potential benfit of systematic exercis in the management of PD. However, there
is still insufficient knowledge about what type of exercise may be most
beneficial, for which symptoms, and how exercise programs may be best appplied
to aid PD patients.
Methods: PD patients (n=20) were recruited in a
Norwegian region, with patients on waiting list as controls. The group followed
a structured program with rhythmic exercises once a week, led by
physiotherapist. The mean age was 62.4 (SD 7.3) years and the mean disease
duration was 8 (SD 5.2) years. Participants were evaluated by UPDRS, Hoehn
& Yahr, Senior Fitness, Up and go before project start, at 6, 12 and 18
months. Quality of life issues were evaluated by interactive qualitative
intern\views, Montgomery-Aasberg depression rating scale and Herth Hope Index
before project start, at 6, 12 and 18 months.
Results: Functional tests showed stability in the
exercise group compared to control group (findings will be discussed inthe
presentation). Quality of life measures showed low vaues for depression
compared to control group and emphasized the value of group training and the
importance of collaboration with participants responses. Interview data suggest
a higher rate of follow-up on home training would further improve results.
Conclusions: Our data suggest benefit of a rhythmic
exercise program developed in collaboration with participants, effects becoming
more marked over time. Further research to specify benefits of structured
exercise is recommended.
P28.11
Evaluation of a rhythmic exercise program for patients
with Parkinson`s disease
Audun Myskja
Objective: To evaluate a structured training program
using a series of rhythmic exercises for a group of patients with Parkinson`s
disease (PD).
Background: There is increasing interest in the
potential benefit of systematic exercis in the management of PD. However, there
is still insufficient knowledge about what type of exercise may be most
beneficial, for which symptoms, and how exercise programs may be best appplied
to aid PD patients.
Methods: PD patients (n=20) were recruited in a
Norwegian region, with patients on waiting list as controls. The group followed
a structured program with rhythmic exercises once a week, led by
physiotherapist. The mean age was 62.4 (SD 7.3) years and the mean disease
duration was 8 (SD 5.2) years. Participants were evaluated by UPDRS, Hoehn
& Yahr, Senior Fitness, Up and go before project start, at 6, 12 and 18
months. Quality of life issues were evaluated by interactive qualitative
intern\views, Montgomery-Aasberg depression rating scale and Herth Hope Index
before project start, at 6, 12 and 18 months.
Results: Functional tests showed stability in the
exercise group compared to control group (findings will be discussed inthe
presentation). Quality of life measures shiowed low vaues for depression
compared to control group and emphasized the value of group training and the
importance of collaboration with participants responses. Interview data suggest
a higher rate of follow-up on home training would further improve results.
Conclusions: Our data suggest benefit of a rhythmic
exercise program developed in collaboration with participants, effects becoming
more marked over time. Further research to specify benefits of structured
exercise is recommended.
P28.12
Improving nutritional status in Parkinson’s disease and
the effects on Parkinson’s disease symptoms
Jamie Sheard1, 2, Susan Ash1,2,
Peter Silburn3,Graham Kerr1,2
1Institute of Health
and Biomedical Innovation, Queensland University of Technology, Brisbane,
Queensland, Australia
2School of Exercise and
Nutrition Sciences, Queensland University of Technology, Brisbane, Queensland,
Australia
3Centre for Clinical
Research, University of Queensland, Brisbane, Queensland, Australia
Objective: People with Parkinson’s disease (PD) are at
an increased risk of protein-energy malnutrition (PEM). Increasing energy and
protein intake is a useful strategy in PEM. However, protein intake in PD may
interfere with dopaminergic medication absorption and increase “off” times. The
aim was to assess the effect of a high protein-high energy (HEHP) nutrition
intervention for PEM on nutritional status and Parkinson’s disease symptoms.
Methods: Nineteen people with Parkinson’s disease at
risk of malnutrition or malnourished participated in a randomised controlled
nutrition intervention. The participants were treated as one group for data
analysis. Participants recorded dietary intake using photographic 3-day food
diaries at 3 time points. Nutrient analysis was completed using Foodworks
(2009, v6). PD symptoms, freezing of gait and “off” times were assessed using
the UPDRS assessment, Freezing of Gait Questionnaire (FOG-Q) and a 3-day on/off
diary, respectively. Objective movement assessments included the Timed Up and
Go (TUG) and finger tap count in 30 seconds. The Beck Depression Inventory
(BDI) recorded depressive symptoms.
Results:
Energy
intake ranged from 54.9-237.4kJ/kg and protein intake from 0.4-2.9g/kg at
baseline and increased by up to 83.1kJ/kg and 2.9g/kg, respectively. Median
weight gain was 2.2% of starting body weight. Increased protein intake was
associated with decreased freezing of gait (rs=-.325, p=.014) and
fewer depressive symptoms (rs=-.304, p=.022). Linear mixed models
analysis resulted in no effects of protein on UPDRS score or “off” times. TUG
times and finger taps did not significantly change. The use of a HEHP nutrition
intervention resulted in improved intake and nutritional status in this group
of malnourished/at-risk people with Parkinson’s disease. There was no reported
effect on Parkinson’s disease movement symptoms, and there may potentially be a
beneficial effect on gait and depression.
P28.13
Exercise has sustained benefit for Quality of Life in
Parkinson’s disease
M. Kwasny1, O. Oguh2, D. Klein1,
T. Simuni1, on behalf of the NPF QII Investigators
1
Northwestern University, Chicago, IL, USA
2 University of Florida
Jacksonville, Jacksonville, FL, USA
Objective: To explore the effects
of physical activity on disease related quality of life (QoL) in Parkinson’s
disease (PD).
Background: There is emerging but still limited data on
the impact of exercise on PD progression.
Methods: Data was obtained from the National Parkinson
Foundation (NPF) Quality Improvement Initiative database. Dataset includes
demographics, disease severity, exercise program, health care utilization, and
PD quality of life (PDQ-39).
Results: 2605 PD participants who had data on exercise
use and at least two annual visits were included in the analysis. The median
exercise at the first visit was 2 hours per week [0, 40], (0, 4) [min, max] (25th,
75th). Subjects were divided into three groups: no exercise (NE)
(n=881, 34%), casual exercise (CE) (0.2-2hours/week, n=528, 20%), and regular
exercise (RE) (≥2.5 hours/week, n=1196, 46%). Factors associated with
regular exercise included better total PDQ-39 (OR per 5 unit increase 0.93,
p<0.001), lower BMI (OR=0.95, p=0.002), less comorbid disorders (OR=1.69,
p=0.033). At the subsequent visit, 639 (25%) of patients increased activity
levels, (214 NE became CE; 218 NE became RE; and 207 CE became RE), whereas 479
(18%) decreased exercise levels (129 CE became NE; 216 RE became CE; 134 RE
became NE), (p for symmetry <0.001) After adjusting for age, sex, duration,
Hoehn & Yahr >3, and baseline PDQ-39 total, regular exercise at both
visits correlated with the lower PDQ-39 (mean difference from non-exercisers
-3.4, p=0.03) at follow-up.
Conclusion: Regular but not casual exercise is associated
with improved and sustained PD QOL. This data provides a strong rationale to
encourage regular physical activity and explore factors that enforce sustained
exercise in PD patients.
P28.14
Benefits
of a community based whole body voice strengthening program for persons with
Parkinson’s
Mary
Spremulli
1Voice Aerobics, LLC, Punta Gorda, FL,
USA
2Parkinson Place, Sarasota, FL, USA
Objective: To evaluate benefit
from a weekly class which couples vocal function exercises with movement. A
mixed design study was developed to determine which components of the
intervention were perceived to yield benefit (i.e. socialization and weekly
contact with the instructor and class members or specific content of the
program or both). Improvement in voice use and overall communication, and
independent home practice were outcome measures. Qualitative and quantitative
data were collected.
Methods: Voice Aerobics™, a
whole body voice strengthening program, led by a speech-language pathologist
was offered weekly at a community based Parkinson center. Participants included
persons without prior speech/voice therapy, and those who had completed speech
therapy, with LSVT® most commonly reported. A recorded version of the class was
also available for independent home use. Pre and post class surveys were
administered, and included a voice self-rating scale.
Results: Final results will be
reported at the WPC, as surveys are still being completed. Surveys reviewed
thus far indicate: age range between 65-86 years, average time since diagnosis
of Parkinson’s is 5 years, and an equal number of women and men responding to
the survey. 60 % reported no prior speech therapy, and 40% reported speech
therapy within the last 1-2 years, most often reported was LSVT®. Most
participants, including those who had speech therapy, self-rated speech clarity
pre-class participation 1 (poor) - 2. Those with the lowest pre-class scores
continued to self-rate low on post class surveys, but with an improvement shift
of at least 1 point. Approximately 25% of class participants report using a
recorded version of the class independently at home for guided practice.
P28.15
Multi-year observational study of community-based
exercise for individuals with Parkinson disease
1Rebecca
States, 1Anayo Ikeme, 2Yasser Salem, 1David
Spierer
1Long Island University
Brooklyn, Brooklyn, NY, USA
2 University of North Texas Health Science Center, Fort Worth, TX, USA
Objective: Community-based group physical activity has
immediate functional benefits for people with Parkinson’s disease (PD).
Evidence on long-term effectiveness is limited however, especially for programs
that allow participants to attend selectively and don’t individually track and
progress exercise protocols. The purpose of this study was to document changes
in physical function for people with PD who participated in such a
community-based group exercise program over several years.
Methods: Thirty-one people with mild to moderate PD
(Hoehn and Yahr stages I to III) participated for up to 4 years. Participants
attended an ongoing series of 1-hour exercise classes (2 times/week x 10
weeks/session x 3 sessions/year) which included resistance training for 12
muscle groups, floor exercises for aerobics, core strengthening, stretching,
and balance. Physical function via gait speed, Six
Minute Walk (6MW), Timed Up and Go (TUG), Berg Balance Scale (BBS), grip
strength, chair stand, and Single Leg Balance (SLBal) was evaluated
before and after the initial 10-week series and annually.
Results: High rates of participation were seen
throughout, ranging from 90% at year 1 to 62% at year 4. Significant
improvements were seen for 6MW and chair stand (p < .05) after the initial
10-week session, and for BBS and grip strength after one year. The only
significant declines throughout the four years were for SLBal after year 2. All change scores remained within the minimum
detectable change threshold.
Conclusion: Results suggest that long-term participation
in community-based exercise is feasible, can keep the interest of individuals
with PD over long periods, and assists in maintaining initial levels for most
aspects of physical function. These findings suggest that a community-based
group exercise program can be beneficial for people with PD, and may provide a
valuable adjunct to traditional rehabilitation programs at relatively low cost.
P28.16
Effects of resistance training on
bradykinesia, functional performance and disease severity in individuals with
Parkinson's disease
Ariel Vieira1, Samuel Vidal1,
Grassyara Tolentino1, Lorena Resende1, Ricardo Jacó de
Oliveira1
1University of Brasília, Brasília,
Brazil
Objective: Explore changes in the bradykinesia,
disease severity and functional performance following the completion of a
9-week program of resistance training in individuals with mild-moderate level
of involvement of Parkinson disease (PD).
Methods: Were evaluated 27 individuals with PD
(Hoehn e Yahr scale between 1-3) before and after 9 weeks: 3 weeks of
familiarization with light loads exercises and 6 weeks of training with
progression of loads. The intervention consisted on 5 exercises for upper and
lower limbs with 2 sets of 10 to 12 repetitions. To explore the objectives were
evaluated clinical assessment of bradykinesia by gait speed, using the Ten
Meters Walk Test (TMW) and by dynamic balance, using the Timed Up and Go Test
(TUG). Section III of the UPDRS was applied covering bradykinesia and disease
severity. The functional performance was assessed by TMW, TUG and functional
strength tests – 30 seconds Chair-Stand Test (T30). To compare the pre and post
intervention was performed Paired-Samples T-Test for variables paread TUG, TWM
and UPDRS III; for the T30 used the Wilcoxon Test. The level of significance
was p ≤ 0.05.
Results: The results indicate a decrease in
TUG scores (p = 0.001) and TMW (p = 0.001). The same behavior was observed in
the results of the motor examination - UPDRS III (p = 0.019). The T30 obtained
an increase of score (p = 0.001). These results suggest that resistance
training show be considered positive in clinical bradykinesia, verified into
increased functionality and reduced disease severity scores.
P28.17
Development of a community-based Nordic walking program
for persons with Parkinson’s disease
Maria Walde-Douglas
Struthers Parkinson’s
Center, Minneapolis, MN, USA
Objective: To
outline a framework of a community-based Nordic Walking program for persons
with Parkinson’s disease (PD). Research has shown the benefits of Nordic
walking in individuals with PD. Organized Nordic walking groups with trained
leaders are an effective way to implement community programs to improve
mobility, gait and conditioning in the Parkinson’s population.
Methods: An individual with PD sought out a Nordic
walking instructor to lead community walks for persons with PD. This led to
collaboration with a physical therapist specializing in PD to develop a program
to train others to lead community Nordic walking groups for people with PD.A
comprehensive 4 hour training curriculum was developed with the following
components: basic Nordic walking
technique and use of poles, group safety and education on the effect of PD on
balance and gait. Practice sessions were carried out with instructor feedback.
Results: Eleven persons completed the training
curriculum. Following completion of the training, PD Nordic walking groups were
formed at area parks and indoors at a shopping mall during the winter
months. Average attendance was 10-12
people stages I-III PD. Participants reported enjoyment of the activity,
reduced fear of falling, improved posture and ability to walk with less pain
and fatigue using the poles. Four individuals involved in the original group
leader training went on to complete an official Nordic Walking instructor
training. A community-based PD Nordic walking program offers a practical
approach to an evidence-based form of exercise. Education on Nordic walking and
PD offer a “train the trainer” approach to the development of qualified
individuals to lead community groups. This offers the opportunity to expand
programming to other communities and locations resulting in improved physical
abilities and quality of life for persons in the PD
CARE
DELIVERY & QUALITY OF LIFE: ALTERNATIVE & COMPLEMENTARY THERAPIES/
CREATIVITY
P29.01
Generating
Rhythm: Music Therapy in Parkinson’s Care
Amy
Clements-Cortes
Wilfrid Laurier University, University of
Windsor, Baycrest, Canada
Objective: To provide
participants with an overview of music therapy treatment in the care of
Parkinson’s disease.
Method: This presentation
will describe music therapy interventions and techniques in the care and
treatment of Parkinson’s disease, highlighting Neurologic Music Therapy,
songwriting and improvisation. Case studies of music therapy clinical work will
illuminate the efficacy of music therapy in holistic, alternative and
complimentary therapy interventions. Strategies for Parkinson’s patients using
music at home will also be presented.
Results: The use of music
therapy as an alternative therapy is proven in several areas of need and
concern in the care of Parkinson’s including: rhythm and gait, rhythm and
speech, entrainment, and rhythm and dyskinesia. Specific aspects of
neurological music therapy will show the results of music therapy in the areas
of sensorimotor, speech and language and cognitive training. Music therapy has
also been established to assist with additional symptoms related to Parkinson’s
such as anxiety, depression, isolation, self-esteem and sleep assistance.
P29.02
Long-term effectiveness of
Alexander Technique (AT) in managing motor symptoms of Young Onset Parkinson’s
disease (PD)
Candace Cox
Big Sky Alexander Technique
Studio, Castleton, ON, Canada
Objective: To look at
the long-term effectiveness of regular AT lessons in combination with
medication therapy.
Methods: The
patient in this case study was diagnosed with PD in 2003, at which point she
already suffered from chronic stooped & painful posture; knee pain
presented in 2005. Standard rehabilitation therapies yielded no improvement.
Cumulative damage in the left knee due to severe tremor prompted knee
replacement surgery in November 2008. Alexander Technique is an educational,
empirical treatment developed to change functional patterns. Our focus was
restoring normalcy to external functions. Lessons involved discussion and
hands-on guidance to facilitate a mental and physical ability to access stability,
and to improve static and dynamic balance. From May 2009 through June 2011, the
student received weekly or twice-weekly 45-minute AT lessons. From July, 2011
through March, 2013 she received intensive groupings of 4 – 6 lessons every 8 –
12 weeks.
Results: A greater
range and control of motion resulted, which facilitated a re-learning of daily
activities. The orthopaedic surgeon who performed the knee-replacement surgery
observed that the subject was his only patient (including non-PD patients) to
recover full movement without a limp within a year. 7.5 years after diagnosis
and 2 years after knee surgery, the subject was rated 56/56 on the Berg Balance
Scale. Since AT treatment, TUG (Timed-up-and-go) score and UPDRS Subscale III
(Motor Examination) rating continue to decrease. Only 2 minor adjustments in
medication were made since 2007. Subject reports: improved posture far beyond
pre-PD state; immediate recovery from semi-freeze; ability to walk normally
even in the midst of severe tremor; improved singing voice; ongoing ability to
travel and live with reasonable normalcy; hope.
P29.03
Yoga for Parkinson’s disease: a competency-based course
for yoga teachers
Tamara Rork DeAngelis1, Renee LeVerrier2,
Cathi A.Thomas3, Beth Gold-Bernstein4,
Lorraine Jacobsohn4
1Center for
Neurorehabilitation, Boston University, Boston, MA, USA
2LIM Yoga for
Parkinson’s and other Movement Disorders,
3Newburyport, MA, USA
4Department of
Neurology, Boston University Medical Campus, Boston, MA, USA
5TriYoga of Boston, Waltham,
MA, USA
Objective: To describe a competency-based yoga training
course where a collaborative model is used. Healthcare professionals with
expertise in PD and yoga teacher trainers provide educational training to yoga
teachers about the symptoms and needs of people with PD, as well as specific
yoga postures and practices that best address the symptoms of PD. The 5-day
program provides attendees the opportunity to gain proficiency in the practices
and gain the confidence and expertise needed to start providing yoga classes to
meet the needs of students with PD.
Methods: This 5 day course evolved from one and two
day workshops that were previously piloted. The shorter courses lacked the
depth of information for this curriculum and did not include assessment of the
participants or certification. In this course, Clinical Nurse Specialists
practicing in neurology and psychiatry presented an overview of the unique
motor and non-motor features of PD and the role of yoga in depression and
anxiety. A physical therapist presented an overview of how these features
relate to gait and balance limitations in people with PD and safety concerns
related to mobility and fall risk. In addition, target areas for stretching and
strengthening exercises unique to this population were highlighted. Yoga
faculty presented research and practices on yoga techniques including
breathing, meditation, chanting, and mantra. Participants had the opportunity
to present different types of classes with input and feedback from course
instructors and were assessed at the conclusion of the course. Post program
evaluations were completed by participants.
Results: Seventeen participants demonstrated
proficiency and received certification in this competency-based course.
Additional yoga teachers have been trained in three one-day workshops, and one two-day workshop. A total of sixty yoga teachers from the USA
have been trained to lead yoga classes for students with PD.
P29.04
Comparative biomechanics from ice skating and regular
terrain locomotion amongst people living with Parkinson disease
Jon Doan1, Natalie de Bruin2,
Patrick Bartoshyk1, Mike Amatto1, Kevin McLarty1,
Lesley Brown2
1Engineering and Human
Performance Lab, University of Lethbridge, Lethbridge, AB Canada
2Balance Research Lab,
University of Lethbridge, Lethbridge, AB Canada
Objective: Recent research suggests that
non-traditional exercises may be highly effective in the management of
Parkinson disease (PD) symptoms, encouraging PD patients with stimulating
activities at greater rates and regularity. The purpose of this project was to
compare kinematics and muscle activities in ice skating and standard gait
amongst people living with PD, with the long-term goal of developing the
paradoxically persistent skill of ice skating into an exercise neurotherapy for
PD.
Methods: Seven mild to moderate PD patients and
seven matched control subjects completed fourteen trials of walking and ten
trials of ice skating, each 12 m in length at self-selected rate. Trials were
captured in sagittal plane video, and muscle activation in lower extremity
agonists and antagonists was collected through electromyography. The central 4
m of walking and skating trials were hand-digitized, providing Cartesian
coordinate data for critical anatomical landmarks in each video frame. Three
kinematic parameters were compared between groups (PD, CTRL) and conditions
(PRE-WALK, SKATE, POST-WALK): a) arm swing – maximum resultant distance between
hip and hand; b) step length – maximum resultant distance between left and
right heels; and c) trunk inclination – average angle between trunk and
vertical. Mean muscle activation ratios (SKATE:POST-WALK) from the tibialis
anterior, gastrocnemius, vastus lateralis, and biceps femoris muscles of the
right leg were also compared between groups.
Results: For the 5 PD participants with full EMG
data, SKATE:WALK activation ratios exceeded 1.5 for all muscles, and those
ratios were significantly increased compared to CTRL subjects for TA and
VL. PD had increased arm swing, greater
step length, and smaller trunk inclination during skating trials compared to
pre-walking trials. Post-walking was also improved compared to pre-walking,
suggesting short-term benefit from skating exercise. Control participants also
changed performance in the skating trials. No PD patients fell in the course of
the skating trials.
P29.05
Developing a collaboration in music therapy and
physiotherapy for older adults with Parkinson's disease: A pilot project
Hélène Gaudreau1,
Annie Bélanger1
1Grace Dart Extended Care Centre, Montreal, QC, Canada
Objective: This research pilot
project presents a collaborative approach between music therapy and
physiotherapy with a group of older adults with Parkinson's disease and (or)
dementia. The main goal of this project was to examine the benefits of such
collaboration for the residents in order to prepare for an intervention
research. Studies have shown the positive effects of physiotherapy on patients
with Parkinson's disease (Keus, 2007; Morris, 2000). Music therapy also has
been proven an effective approach to help people with this diagnosis (Tomaino,
2002, 2011). No extensive research on a collaborative approach of these two
fields has been found.
Methods: This collaborative inquiry
was initiated by the physiotherapy program. The music therapist was invited to
join in an already existing exercise group conducted by the physical
rehabilitation therapist at Grace Dart Extended Care Centre in Montreal. This
group consists of sixteen (male and female) subjects, all residents of the
centre. Sessions are being held once a week. The pilot project was conducted
during 20 sessions and allowed the music therapist and physiotherapist to
gather observations on patients' improvements. These will be measured in phase
2: the intervention research.
Results: The
initial phase, the pilot project, showed several positive effects on the
participants. Observations were made in three important areas: participation,
communication and motor abilities. Residents started to arrive earlier at their
session, passive participants started to be more engaged and various
expressions of happiness and pride were demonstrated on many occasions.
Furthermore, manipulation of small instruments and singing seemed to diminish
tremor. According to these observations and the literature, the anticipated
results of an intervention research program would benefit the residents of this
group in the areas of motor abilities (control, coordination) and communication
abilities (breathing, pronunciation). Therefore, the next phase will be to
continue developing the program through the creation of evaluation tools and
the development of a therapeutic intervention plan. The data collected during
the pilot project and the evaluation tools will be presented.
P29.06
Neurologic music therapy interventions: a whole picture
approach for people with Parkinson’s disease
Sandra Holten
Struthers Parkinson’s
Center, Golden Valley, MN, USA
Objective: A songwriting process with 8 members of a
therapeutic adult day program diagnosed with Parkinson’s disease and related
movement disorders is chronicled.
Background: Neurologic Music
Therapy (NMT) is the therapeutic application of music to cognitive, sensory and
motor dysfunction due to neurologic disease. NMT treatment techniques are
research-based and directed towards functional therapeutic goals. Standardized
Therapeutic Music Interventions are adaptable to the patient’s needs. NMT
techniques for sensorimotor dysfunction have been well researched and provide
the underpinnings of the application of NMT techniques to Parkinson’s disease.
Methods: This poster focuses on
the use of NMT techniques beyond the sensorimotor domain with which they are
more commonly associated. At Struthers Parkinson’s Center, music therapy is an
integral part of the therapeutic adult day program, Club CREATE. Over the
course of 7 weeks, a group of 8 clients in Club CREATE participated in
Neurologic Music Therapy Interventions that included music improvisation, vocal
intonation therapy, rhythmic speech cuing, musical attention control training
and songwriting. Although the song, “Our Fight” was a final product from the
process, the process itself addressed numerous domains of functioning and
provided a creative outlet for self expression and improved connection with
each other. Clients described ways this had an impact on their coming to terms
with Parkinson’s.
Results: Although the song, “Our Fight” was a
final product from the process, the process itself addressed numerous domains
of functioning and provided a creative outlet for self expression and improved
connection with each other. They described ways that this had an impact on
coming to terms with Parkinson’s. Staff and carepartners noted these outcomes
as well. These results will be depicted in narrative description of series
process, pictures and comment samples from clients.
P29.07
An arts & movement program designed to link exercise,
creativity and social interaction
Renee Le Verrier 1,
Jane Arsham 2,
Michael S. Kleinman 3, Cathi A.Thomas 3,
Marie Saint-Hilaire 3
1 LIM Yoga, Newburyport, MA, USA
2 Moving Easy Tai Chi, Arlington, MA, USA
3 Boston University
Medical Campus, Boston, MA, USA
Objective: Exercise reduces severity of symptoms and
increases a sense of wellbeing in people with PD. In addition individuals with
PD can experience an increase in creativity, most likely related to the use of
dopaminergic medications. Research shows that loneliness in the general
population of older patients hastens a decline in motor function. Patients with
PD often identify a reduction in socializing. Evidence demonstrates that
increased social interaction has a high impact on a person’s quality of life.
People living with Parkinson’s disease should be provided opportunities to
experience creative and exercise-based therapies in a socially supportive
environment.
Methods: The Art’s and Movement Program is a two night
retreat with two full days of workshops. An alternative one day program can
also be implemented. Facilitators with expertise in a number of specialties
lead interactive workshops that encourage and focus on ability. The rotating
schedule ensures that participants experience each subject area in a
small-group setting. Workshop topics include activities that have been shown to
be beneficial for persons with PD including: creative writing, music,
storytelling, visual arts, dance, tai chi, and yoga.
Results: 110 participants have attended one of three
Arts and Movement Programs. Participants expressed overwhelming satisfaction in
a post program survey. An outline of the details
of the Arts & Movement Program has been developed to allow other
communities to set up similar interventions that tailor sessions
specifically designed for people living with PD.
P29.08
Providing instruction of Reiki first degree as a
complementary therapy to help improve the lives of those living with
Parkinson's disease
Karl Robb1 Angela Robb2
1Person with
Parkinson's disease & Reiki Master, GiveReiki.com, US
2PD Carepartner & Reiki
Master, GiveReiki.com, USA
Objective: To instruct and educate
the Parkinson's disease community about how the teaching of Reiki (RAY-KEY)
first degree as a complementary therapy to people with Parkinson's disease can
be beneficial to their self-care. To give those living with PD another tool to
reduce stress, increase relaxation, and provide mental & physical calmness.
Reiki is a non-invasive therapy that uses light touch to increase and enhance
one's personal energy. Reiki first degree instruction focuses on self-care, a
self-treatment protocol, and seated chair protocol to give Reiki to another
person.
Methods: The workshop is a twelve
hour workshop in Reiki first degree. The current workshop held in six two-hour
sessions, allowing the person with Parkinson's time to absorb the material. The
workshop includes instruction in Mindfulness Meditation, Energy anatomy,
Qigong, and Reiki self treatment & seated chair protocols. The workshop
highlights the importance of the person with PD to take care of themselves on a
daily basis. Examples of how Reiki can be incorporated into daily life are
presented.
Results: People with PD will be able to treat themselves with Reiki and have a general
understanding of Reiki which can be used to enhance and complement their
current self-care strategies. Workshop participants will be able to use Reiki
to increase one's relaxation, reduce stress, and enhance the body's own healing
properties. Previous students who attended the workshop reported: "I
always feel relaxed and hopeful after attending the class" and "I
felt like I was walking away with a treasure, suited to my particular
needs".
P29.09
Incorporating community based artists into an
established Parkinson’s disease care program at a National Parkinson Foundation
Center of Excellence
Rose Wichmann1, Sandra Holten1
1Struthers Parkinson’s Center, Golden Valley, MN
Objective: To
maximize quality of life for people with Parkinson’s through creative arts
programs in collaboration with community artists. Research has shown that
creative activities such as music, dance, painting, and theater can improve
feelings of well being for young and old alike. People with Parkinson’s (PD)
have compromised physical/cognitive skills, interfering with participation in
creative arts programs. Since 1995, Struthers Parkinson’s Center (SPC) CREATE
program has collaborated with community artists to design programs for people
living with PD.
Methods:
Weekly programs include nature based therapies (with University of MN Landscape
Arboretum), music (utilizing a neurologic music therapy fellow), dance programs
(with nationally recognized Kairos Dance Theatre), visual arts (with Artsy
Smartsy, offering programs to seniors/people with disabilities), dramatics
(with CLIMB Theatre), and SPC “Arts Café” (featuring interaction with community
artists on a monthly basis.) Funding has been obtained through the Metropolitan
Regional Arts Council, MN State Arts Board, and Park Nicollet Foundation.
Results:
Weekly arts programs at SPC average 15 participants in each group. The average
monthly Arts Café attendance has grown from 9 to 25. Participants report
benefits including increased energy, feelings of joy, opportunities for self
exploration, improved creativity, and pride in accomplishments, deeper social
connections, physical exercise, relaxation, and reduced stress. Community
artists report greater awareness of PD, heightened sensitivity to the needs of
those with physical/cognitive challenges, and improved comfort levels in communicating
/interacting with PD clients. Involvement in creative arts provides
opportunities for improving mobility, mood, and communication for individuals
with PD. Engaging community artists in collaborative relationships with PD
programs offers unique opportunities to access artists’ talents and abilities,
encourages those with physical and cognitive deficits to explore new avenues of
self expression, and contributes to quality of life.
P29.10
Combination treatment
of Osteopath and Chinese deep tissue massage improve Parkinson disease
Zhao Hong Yang
Clinique Yang`s
Ostéopath, Montréal, QC, Canada
Objective: Improve parkinson disease patient`s bodily functions.
Methods: Record the symptoms of each control PD patient`s major
claims of abnormal bodily functions by words and video. Design some behaviors
to present the abnormal bodily functions of each patient for each major claim.
Observe and analysis control PD patient`s skeletion structure problem, give
relative deep tissue massage and osteopath treatment to the control patient.
Compare the skeletion structure before and after the treatment; Compare the
designed behaviors the control patient can finish by video and words before and
after each treatment.
Results: Combination
treatment of Osteopath and Chinese deep tissue massage can comprehensively
improve Parkinson disease. Some control patients can obtain a great progress.
P29.11
School "Health" in the lives of
patients with Parkinson's disease
Irina Zhukova1, Maria Nikitina1,
Olga Izhboldina1, Natalya Zhukova1, Valentina Alifirova1,
Anna Agasheva2, Alexey Povalyaev3, Marina Titova1
1Department of neurology and neurosurgery, Siberian State Medical
University, Tomsk, Russia
2Hospital No
2, Tomsk, Russia
3State Medical and Social Examination Service, Tomsk, Russia
Objective: Show
the importance of continuing medical rehabilitation in outpatients with
Parkinson's disease (PD) from the perspective of impact on life quality and
severity of affective disorders.
Methods and materials: 68 patients with PD (28 males, 40 females) were included. The
average age was 64.3±8.2. The average stage for the Hoehn & Yahr scale was
2.6±0.8. All patients were divided into two groups (homogeneous by sex, age,
stage of PD): I- 33, engaged in the school of rehabilitation “Health”
regularly, II- 34, who didn’t. The patients' life quality was estimated with
the help of “The Short Form (36) Health Survey” (The SF-36). Affective
disorders were estimated by: Hospital Anxiety and Depression Scale, Apathy
Scale. Examination conducted twice: at the first visit and after 6 months.
Results: Analysis
of life quality, affective disorder (anxiety, depression, apathy) hasn’t shown
significant difference between groups at the first visit (p>0.05). At the
second visit the SF-36 showed that 1st group's life quality was
higher by item: General Health, Vitality, Social Functioning, Role Emotional,
Mental Health (p<0.05). In group I proportion of subjects without depression
increased by 18.1%, with subclinical– by 24.2%; in group II– did not change
(p<0.05). According to the Apathy Scale on the second visit the proportion
of people without disturbance increased by 15.1% in group I, in the II–
clinically significant apathy appeared in 8.8%. The estimation of anxiety
hasn’t shown significant difference between visits in both groups.
Conclusion: The medical rehabilitation PD patients could reduce the severity
of apathy and depression and improves quality of life.
CARE DELIVERY & QUALITY OF LIFE: LAY
& PROFESSIONAL HEALTH LITERACY
P30.01
Improving support for those affected by
Progressive Supranuclear Palsy: Phase 2
Theresa Moore1, Mark Guttman1
1Centre for Movement Disorders, Markham, ON, Canada
Background: Although PSP is the most common type of atypical parkinsonism,
there is almost no data available from the perspectives of people with PSP or
their caregivers. In Phase 1, focus groups and surveys were used to assess the
needs of people with PSP, as well as their families and professional
caregivers. Four categories of challenges were identified: symptoms, services,
lack of research, and lack of knowledge. Dissemination of information about PSP
diagnosis, symptoms, and care was identified as the priority need. This
information needed to reach physicians, community workers, long-term care
staff, patients, and families
Objective: To improve support for patients with PSP and their families by
addressing their expressed need for knowledge dissemination.
Method:
Three activities were completed: (a) development of a brochure summarizing
possible symptoms and care options and testing of the brochure with patients,
families, General Practitioners (GPs) and geriatric Nurse Practitioners (NPs);
(b) revision of the CurePSP ‘Physician Packet’ and testing of the packet with
GPs and geriatric NPs; and (c) testing of a revised PSP care presentation
through a webinar offered to staff in long term care and community settings.
Results:
The feedback on each of these new resources was positive. Meaningful feedback
for improvement was also received from the respondents. Where possible and
appropriate, their suggestions were incorporated and are reflected in the final
versions of the brochure, primary care practitioner packet, and webinar. These
three new resources are being disseminated through clinic visits, mail,
internet, publications, and this presentation. It is expected that improved knowledge
will translate into more skillful, timely, and supportive care for individuals
affected by PSP.
P30.02
Awareness of Parkinson’s disease Questionnaire (APDQ) in
an Urban Asian setting
AH Tan1, CC Lim1, YW Cheong1,
KW Loh1, NWW Ho1, PW Tan1, ST Kong1,
QH Lim1, JP Schee1, HS Gan1, KH Tan1,
SK Soo1, C Vanderschaaf2, UA Mahamad3, C
Marras4, CT Tan1, SY Lim1
1University of Malaya,
Kuala Lumpur, Malaysia
2Malaysian Parkinson’s
Disease Association, Kuala Lumpur, Malaysia
3Universiti Sains Islam
Malaysia, Kuala Lumpur, Malaysia
4University of Toronto,
Toronto, Canada
Objective: Public
awareness of Parkinson’s disease (PD) is important for early symptom recognition.
However, the literature on this is very limited. We
aimed to address this in our study.
Methods: An
Awareness of Parkinson’s Disease Questionnaire (APDQ) was designed by
neurologists with expertise in PD, and vetted by experts in PD epidemiology and
questionnaire design, and by patients, caregivers and lay members of the
public. Respondents are instructed to tick a box for “problems experienced by
people with PD” (14 symptoms that occur commonly in PD are presented); and to
provide a True or False answer for ten statements regarding PD. English,
Chinese and Malay language versions of the APDQ were administered on 1,261
members of the Malaysian public attending a health fair in Kuala Lumpur.
Demographic data of the respondents were collected.
Results: 74.5% of respondents were tertiary-educated. 19.0% knew someone with PD.
Tremor was the most widely recognized symptom (78.9%); however, 83.6% of
respondents believed that all
patients with PD will have tremor. Memory problem was the most widely
recognized non-motor symptom (51.8%); however, 30.2% considered PD and
Alzheimer’s disease to be the same disorder. Motor symptoms such as slowness of
movement (73.0%), imbalance (52.6%) and rigidity (47.1%) were better recognized
than non-motor symptoms such as depression (33.9%), weight loss (24.3%),
urinary urgency (21.0%), insomnia (19.3%), pain (18.0%), excessive daytime
sleepiness (15.5%), visual hallucinations (15.1%), reduced sense of smell
(11.6%), and constipation (9.2%). Common misconceptions were that there is a cure
for PD (50.2%) and that PD is usually familial (41.6%). 78.4% felt that
patients with PD often feel socially isolated.
Conclusion: There are significant gaps in public knowledge about PD. This could
present a barrier to early diagnosis and timely treatment of symptoms. This
highlights the need for further education and research in this area.
P30.03
Knowledge among senior
medical students on diagnosis and management of Parkinsonś disease: views
from Kenya and Uganda
Paul.O.Yonga
Moi Teaching and Referral
Hospital, Department of Internal Medicine, Eldoret, Kenya
Objective: To assess the
knowledge among senior medical students on diagnosis and management of
Parkinsonś disease.
Methods: This was a
cross-sectional study where 350 senior medical students were sampled from two
medical schools each in Kenya and Uganda and recruited. Data on their
demographic characteristics and knowledge on recognizing the clinical features,
diagnosis, and treatment of Parkinsonś disease were captured using
researcher-administered questionnaires. Data entry and analysis were performed
usng Epi-data 7 and SPSS 20.
Results: 85% of the students
were able to state the clinical features of Parkinsonś disease. 5% of the
students reported using neuroimaging as part of the diagnostic criteria in
ruling out parkinsonian-like disorders. 3% of the students noted the importance
of neuropathology during autopsy as a diagnostic marker, and 70% of the
students were aware of levodopa being used in the management of Parkinson’s
disease.
Conclusion: Despite significant
knowledge on recognizing Parkinsonś disease, there are still gaps as far
as diagnosis and management is concerned and more attention should be paid in
general to the teaching of movement disorders in medical school.
CARE
DELIVERY & QUALITY OF LIFE: DIABILITY AND QUALITY OF LIFE OUTCOME MEASURES
P31.01
The
impact of clinical symptoms on quality of life in patients with advanced stage
Parkinson's disease
Nina Browner1, Lindsay Prizer2, Amber Baxley3,
Jessica Katz1
1 National Parkinson
Foundation Center of Excellence, University of North Carolina, Chapel Hill, NC,
USA
2Department of Health
Promotion and Behavior, University of Georgia, Athens, GA, USA
3Perelman School of Medicine,
University of Pennsylvania, Philadelphia, PA, USA
Objective: Clinical status and
health-related quality of life (HQOL) of advanced stage Parkinson’s disease
(PD) patients have not been well documented. This study aimed to identify the
most bothersome clinical symptoms of advanced stage PD and their impact on
HQOL.
Methods: Advanced stage PD was
defined as Hoehn & Yahr stages 4 and 5, loss of independence in 2 or more
activities of daily living, and cognitive impairment. Thirty PD patients were
recruited from the UNC Movement Disorders Clinic. Questionnaires on clinical
aspects of PD, PDQ39, and Hospital Anxiety and Depression Scale (
Results: PD patients (76.6 % male) had a mean age of 72.8
years (± 10.9) with median disease duration 10 years. Twelve patients (40 %)
were post deep brain stimulation surgery. All except 1 patient were living at
home with a family member as a regular caregiver (96.6%), and 7 patients used
home health services (23.3%). By impact on HQoL, patients ranked
balance/falls/freezing of gait #1, followed by motor, speech, cognitive, and
lastly autonomic deficits domains. Multiple
linear stepwise regression analysis, with PDQ39 as the dependent variable and 8
symptom clusters of the PD symptoms checklist as the independent variables,
showed balance (R2 = 0.67, p <0.001) and cognitive (R2
= 0.45, p <0.0005) changes have the biggest impact on HQOL. Our
findings highlight the impact of balance and cognitive problems on overall QoL
in advance PD. Thus, policies to improve in-home support with balance and
cognitive therapy will be crucial in maintaining patients at home with
substantial improvement of the QoL.
P31.02
Quantifying the effect of deep brain electrical stimulation
on postural behavior of patients with Parkinson’s disease, in the initial weeks
post-surgery
Inês da Cruz1, Véronique Ferret-Sena2,
Catarina Godinho2,3.
1 Instituto Superior de Ciências da Saúde Egas Moniz,
Monte da Caparica, Portugal
2 Centro de Investigação Interdisciplinar Egas Moniz (CiiEM), Cooperativa de
Ensino Superior Egas Moniz, Monte de Caparica, Portugal
3 Interdisciplinary Centre for the Study of Human Performance
(CIPER), Faculdade de Motricidade Humana, Universidade Técnica de
Lisboa, Lisboa, Portugal
Objective: Quantify the effect of deep brain electrical
stimulation (DBS) on postural behavior in Parkinson’s disease patient, in the
initial weeks post-surgery.
Methods: Women with PD (stage 2, H&Y) with DBS surgery,
performed posturographic tests with the aim of quantitatively evaluate the
postural motor changes up to 9 weeks post-surgery. The posturography evaluation
was carried out in a pre-surgery phase (one month before surgery) and 3 times
after surgery (1st, 3rd and 9th weeks). This
study analyzed the results of four posturographic tests: mCTSIB-modified
Clinical Test of Sensory Interaction on Balance; LOS-Limits of Stability; WA-
Walk Across and TW-Tandem Walk.
Results: When comparing the values obtained in
pre-surgical with the values obtained in successive post-surgical evaluations,
we verified that in LOS test the reaction time remained similar, the velocity
of center of gravity increased, and the maximum distance did not change. In
mCTSIB test, the sway velocity increased when the patient stood with eyes open
on firm surface and decreased with closed eyes. Same results were obtained on
unstable surface. In WA test, the step width decreased and the step length and
stride velocity increased. In TW test, the step width and the end sway velocity
decreased but the displacement velocity increased. Some parameters related to postural behavior did not change after
surgery until 9 weeks, but gait parameters tended to return to normal control
values in a post-surgical early phase.
P31.03
Motor dysfunction, quality of life, physical activity and
life-space in advanced Parkinson's disease: what is the impact of STN DBS
Jean-François
Daneault1-2, Christian Duval2-3, Sébastien Barbat-Artigas4,
Mylène Aubertin-Leheudre2-3, Nicolas Jodoin5, Michel
Panisset5, Abbas F. Sadikot1
1Department of Neurology and Neurosurgery, Montreal Neurological Hospital
and Institute, McGill University, Montreal, QC, Canada
2Centre de Recherche de
l’Institut Universitaire de Gériatrie de Montréal, Montréal, QC, Canada
3Département de
Kinanthropologie, Université du Québec à Montréal, Montréal, QC, Canada
4Département des Sciences
Biologiques, Université du Québec à Montréal, Montréal, QC, Canada
5Unité des troubles
du mouvement André-Barbeau, Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada
Background: Understanding
how Parkinson’s disease (PD) motor dysfunctions affect mobility, physical
activity and quality of life (QoL) is essential. Furthermore, identifying the
impact of interventions such as STN DBS on these issues will help better adapt
our treatments.
Objectives: 1.
Identify differences in life-space, physical activity and QoL between advanced
PD patients and healthy controls. 2. Assess the impact of STN DBS on these
variables.
Methods: Thirty
patients with idiopathic PD and 30 age- and gender-matched healthy controls
filled out questionnaires on mobility (Life-Space Assessment), physical
activity (Phone-FITT), and QoL (SF-36). Results were compared to establish
normative values in advanced PD. Then, 20 of the PD patients underwent surgery
for STN DBS and filled-out the same questionnaires 6 months after surgery.
Pre-operative and post-operative results were compared with results from the
same age- and gender-matched healthy controls to assess the effect of
treatment.
Results: A statistically
significant reduction in life-space, physical activity and QoL was observed
between healthy controls and advanced PD patients. While STN DBS significantly
improves motor dysfunction, not all aspects of mobility, physical activity and
QoL are equally improved.
Conclusion: As mobility and physical activity are
inter-related and both are related to QoL, interventions should be aimed at
improving these factors so as to lessen the burden of disease on patients and
the health-care system. Furthermore, while STN DBS drastically improves motor
symptoms in PD, there is not a systematic normalization in mobility, physical
activity or QoL. As such, interventions should be developed to address these
issues.
P31.04
The ParkinsonAtlas:
transparency in medical practice variations in PD care in the Netherlands
Mariëtta Eimers1, Pieter van den Haak1,
Martijn van Eijk1, Bastiaan R. Bloem2, Marten Munneke1
1Radboud University Nijmegen Medical Centre; Nijmegen Centre for Evidence Based Practice; Department of
Neurology, Nijmegen, The Netherlands
2Radboud
University Nijmegen Medical Centre; Donders Center for Brain, Cognition
and Behaviour; Department of Neurology, Nijmegen, The Netherlands
Objective:
ParkinsonNet, a national multidisciplinary network of specialized health
professionals, aims to improve the quality of care for patients with
Parkinson’s disease (PD). The concept has nationwide coverage in The Netherlands with 66 regional allied
health networks in the catchment areas of Dutch hospitals. Within each network
a selected number of expert therapists are trained according to evidence-based guidelines. To date,
2500 neurologists, PD nurse
specialists, physical-, occupational therapists, speech-language
pathologists and dieticians are involved.
Recently, we introduced the ParkinsonAtlas, an online tool which provides
insight in the quality of care within all ParkinsonNet regions [1].
Methods: The following outcome-,
process- and structure indicators are visualized in the ParkinsonAtlas to
assess the quality of PD care in each region: Outcome indicators: patients’ quality of life (PDQ-39),
patient-experiences (PCQ-PD), (hip-) fractures, costs per patient, hospitalization
rate, home care and admission to rehabilitation- or nursing homes. Process indicators: utilization of
allied healthcare, anti-Parkinson medication, professionals’ adherence to
medical guidelines and healthcare team-effectiveness. Structure indicators: the estimated number of PD patients, density
of specialized health professionals and healthcare services. The data is
collected from health insurance companies, patient- and professional surveys
and the ParkinsonNet membership database. All indicators are calculated on a
national- and regional level. Each indicator is separately visualized in online
maps.
Results: Large medical practice
variations were found for all three types of indicators. For instance, the utilization
of physical therapy per region ranged from 45% to 75%. Additionally, the
percentage of PD patients consulting a ParkinsonNet physiotherapist could be
improved in several regions. The ParkinsonAtlas is now used to provide feedback
to health professionals to enhance internal quality improvement, by insurance companies to contract
high-quality PD care, and by patients to choose excellent health professionals
specialized in PD.
P31.05
Comparison of the psychological symptoms and
disease-specific quality of life (QoL) between early- versus late-onset
Parkinson’s disease patients
Seyed-Mohammad Fereshtehnejad1,2, Mahdyeh
Shafiei Sabet3, Farzaneh Farhadi3, Hasti Hadizadeh3,
Dena Khaefpanah2, Nader Naderi3, Arash Rahmani3,
Ahmad Delbari1,4, Gholam Ali Shahidi5, Johan Lökk1
1Division of Clinical
geriatrics, Department of Neurobiology, Care Sciences, and Society (NVS),
Karolinska Institutet; Stockholm, Sweden
2Firoozgar Clinical
Research Development Center (FCRDC), Tehran University of Medical Sciences, Tehran,
Iran
3Student Scientific
Research Committee (SSRC), Tehran University of Medical Sciences, Tehran, Iran
4Aging Research Center,
Sabzevar University of Medical Sciences, Sabzevar, Iran
5Neurology Department,
Tehran University of Medical Sciences, Tehran, Iran
Objective: The impact of Parkinson's disease (PD) on
psychological status and quality of life (QoL) may vary depending on age of
disease onset. The aim of this study was to compare the psychological symptoms and disease-specific QoL between
early- versus late-onset Parkinson’s disease (PD) patients.
Methods: This cross-sectional study was performed in a
referral movement disorder clinic in Tehran, Iran during 2011-2012. A total number
of 140 PD (95 males and 45 females) patients with the mean current age of 61.3
(SD=10.4) yr were recruited in this study. Conventionally, PD patients with the onset age of ≤50 yr are defined as “early-onset” (EO) group (n=45); while, the ones with >50 yr at the time of
diagnosis are categorized as the “late-onset”
(LO) PD patients
(n=95). Different questionnaires and scales were
used for
between-group comparisons including PDQ39 (PD-specific QoL), HADS
(hospital anxiety & depression scale), FSS (fatigue severity scale), MNA
(mini-nutritional assessment), Schwab & England (activity of daily living) and Hoehn & Yahr scales
(progression and level of disability).
Results: Univariate
comparisons showed that depression score was significantly higher in EO group
(6.3±4.5 vs. 4.5±4.2, P=0.023). Among different domains of QoL, emotion score was also
significantly higher in EO group (57.1±21.2 vs. 48.9±21.2, P=0.033). Results of multivariate linear regression model showed that anxiety (P=0.0002),
depression (P<0.0001), fatigue (P=0.033) and level of
morbidity (Schwab scale) (P=0.048) are the
independent factors significantly related to PD
patients' quality of life.
Conclusions: Our findings
showed more severe depression and more impaired emotional domain of QoL in
early-onset PD patients. Moreover, decreased QoL in PD was related to
depression, anxiety, fatigue and lower level of activity in daily living. It is
important to consider these psychological disturbances for improvement of QoL
in PD especially among the early-onset patients.
P31.06
The effect of disease severity on postural control
behavior in Parkinson disease
Catarina Godinho1,2, Véronique Ferret-Sena1,
José Brito1, Margarida Dias3, Ana Calado3,
Cristina Semedo3, Josefa Domingos4, Filipe Melo2
1Center for Interdisciplinary Research Egas Moniz (CiiEM), Cooperativa de
Ensino Superior Egas Moniz, Monte de Caparica, Portugal
2Interdisciplinary
Centre for the Study of Human Performance (CIPER), Faculdade de Motricidade Humana, Universidade Técnica de Lisboa, Lisboa,
Portugal
3Serviço de Neurologia do Hospital Santo António dos Capuchos (CHLC-EPE),
Lisboa, Portugal
4Neurological Clinical Research Unit, Instituto de Medicina Molecular,
Faculty of Medicine, University of Lisbon, Portugal
Objective: Most of the research
concerning postural behavior in Parkinson Disease (PD) integrates patients from
different stages in the same sample. This methodology of analysis gives us
limited information about the progression of the disease. The present research
aims to characterize the variations associated to different PD patient’s
postural sway. This allows us to identify important indexes of balance
impairment regarding each particular level of the disease progression. In this
study, we have analyzed quantitative data of the time series parameters of the
center of gravity (CoG), during different posturographic tests.
Methods: The sample was composed of 103 patients (45 female and 58 male, 70.5±8.4
years) diagnosed with PD stages 1 to 4 according to Hoehn and Yahr rating scale
(H&Y) (Stage 1 – 15; Stage 2 - 33; Stage 3 - 47; Stage 4 - 8). Clinical
information concerned patient’s diagnosis, stage of the disease and UPDRS-II
scale. The posturographic tests included the modified Clinical Test of
Sensory Interaction on Balance (mCTSIB) and the Limits of
Stability test (LOS). Statistical
analyses integrated
different tests (One-way MANOVA, one-way ANOVA
and Factor Analysis) in order to
compare the postural behavior presented by patients with PD in the different
stages.
Results: In mCTSIB test,
the alignment of the center of gravity (CoG), was significantly altered by
disease progression (p = 0.037). A forward projection of the CoG within each
stage was also observed, related to the stimulus manipulation. In LOS test, a small decrease with disease progression was suggested for the distance of
the CoG sway in the forward direction (p = 0.057). Balance changes
during PD progression are possible to be better identified. The future
development of physiotherapy programs to reduce postural instability and
prevent future falls should consider these changes.
P31.07
Neuropsychiatric symptoms impact quality of life and
caregiver burden in Mexican population with Parkinson´s disease
Paulina
Gonzalez-Latapi1, Azyadeh Camacho-Ordoñez1, Mayela
Rodriguez-Violante1,2, Amin Cervantes- Arriaga1. Pablo Martínez-Martín3
1 Neurodegenerative
Diseases Laboratory, National Institute of Neurology and Neurosurgery, Mexico
City, Mexico
2 Movement Disorders Clinic
National Institute of Neurology and Neurosurgery, Mexico City, Mexico
3 Area of Applied
Epidemiology, National Centre of Epidemiology and CIBERNED, Carlos III
Institute of Health, Madrid, Spain
Objective: The aim of this study is to determine impact
of neuropsychiatric symptoms in PD patients’ quality of life and caregiver
burden.
Methods: We applied the Scale for Evaluation of
Neuropsychiatric Disorders in PD (SEND-PD) and PD Quality of Life, eight-item
scale (PDQ-8) to PD patients and the Zarit Caregiver Burden Interview (ZCBI) to
their caregivers. Disease stage was classified according to Hoehn and Yahr
scale. SEND-PD was considered abnormal with a score greater than or equal to 1.
Results: A total of 174 PD patients and their main
caregiver were included. Of PD patients, 55% were male. Mean age was 62.23 more
or less 13.06 years. Mean school years were
8.26 more or less 5 years. Association between PDQ-8, ZCBI and abnormal SEND-PD
scores are shown in Table 1 and Table 2. After performing a linear regression
model, disease severity (p= 0.002, B=2.37), educational level (p=0.035,
B=-0.96) and SEND-PD total score (p<0.001, B=7.33) were predictive factors
for PDQ-8 score. Multinomial regression showed that mild disease (p=0.006, B =
1.73) and SEND-PD total score (p=0.001, B=2.48) were significant factors for
caregiver burden. Caregiver burden seems to be influenced by an increase in PD
motor and neuropsychiatric symptoms such as depression, hallucinations or
confusion and decreased quality of life in PD patients(1, 2). It has not been
established whether non-motor or motor symptoms have a greater impact on
caregiver burden. We report an association between SEND-PD and PDQ-8 scores,
with a greater impact in mild (HY
lesser than or equal to 2) and moderate (HY = 3) disease stages. Educational
level and disease severity are independent factors influencing PDQ-8. In our
study motor and neuropsychiatric symptoms have an equal impact on caregiver
burden.
P31.08
Factors, disabling patients on the early stages of
Parkinson's disease
E.N. Gubanova, N.V. Fedorova.
Russian
Medical Academy for Post-Graduate Education, Moscow, Russia
Parkinson's disease (PD)
is one of the most frequent neurodegenerative diseases. Social
adaptation of PD patients is significantly reduced, work
capacity is limited, quality of life and daily activities of patients are impaired even
on the early stages of the disease.
Objectives: to determine the range of factors, disabling
patients on the early stages of PD.
Material and methods: 80
patients with PD on the early
stages were included (male:
female = 30: 50). 20% of our patients had 1-1,5 stage of
modified H&Y scale, 35% - 2nd and 45% - 2,5. The mean age was 58 ± 8,0
years; the mean duration of the disease - 3,0±2,5. The mean age
of the onset was 54,5± 8,5years. The mixed form
of PD predominated over others (75%).
Disabled were 42,5% of patients with early stages PD. Dates of
treatment: 47,5% early, 10% - late, 42,5% - delayed treatment onset. We used
Hoehn and Yahr scale modified by Lindvallto to assess PD severity (Hoehn M.,
Yahr M., 1967, O. Lindvall, 1989); to assess the severity of the main symptoms
of Parkinson's disease - UPDRS scale (II and III)
(Fahn S., Elton R.L., 1987); assess affective disorders - Hamilton Rating
Scale – (M.
Hamilton, 1959, 1999); cognitive disorders - Monreal cognitive assessment scale
(MОСА,
Nasreddine M.D., 2004); non-motor symptoms - scale of non-motor
symptoms PD NMS (Chaudhuri K. R. et al., 2004); to
assess the quality of life - a
questionnaire Boer ( Boer A.G. et al., 1996) and the PDQ-39 (Peto V.
еt al., 1995), scale EuroQoL (Rabin R. et al., 2001).
Results: Quality of life (PDQ-39) were 40,5 ± 26,5; on (Boer) - 141,5 ± 31,95. Non-motor disturbances were observed in 87,5%. Cognitive impairment in 37,5% cases had cortical-subcortical type. Affective disorders were diagnosed in 57,5% cases. There was a positive correlation between disabilities and start of treatment (p = 0,000001). Positive correlation (р<0,05) of disability with the gender, stage, form, duration of disease and type of progression.
Conclusions: Cognitive,
affective disorders and other non-motor symptoms significantly deteriorate social adaptation of patients
with PD
even on the early stages
of the PD, leading to disability.
P31.09
Quality of life in Parkinson’s disease patients with motor fluctuations and dyskinesias in five European countries
Marlene Hechtnera,b,c, Thomas P. Vogtd,
York Zöllnere, Julia B. Sauerf, Maria Blettnera,
Harald Bindera,g, Susanne Singera,h, Rafael Mikolajczyki
(a)
Institute of Medical Biostatistics, Epidemiology and
Informatics (IMBEI), University Medical Centre, Johannes Gutenberg University Mainz, Germany
(b)
German Cancer Consortium (DKTK), Heidelberg, Germany
(c)
German Cancer Research Center (DKFZ), Heidelberg, Germany
(d)
Department of Neurology, University Medical Centre,
Johannes Gutenberg University Mainz, Germany
(e)
Department of Health Sciences, Faculty of Life Sciences,
Hamburg University of Applied Sciences (HAW), Germany
(f)
Department of Psychology, University of Georgia, Athens,
Georgia, USA
(g)
Institute of Medical Biometry and Medical Informatics,
University Medical Centre, University of Freiburg, Germany
(h)
Department of Psychosomatic Medicine and Psychotherapy,
University of Leipzig, Germany
(i)
Department of Epidemiology, Helmholtz Centre for
Infection Research, Braunschweig, Germany
Background: Parkinson’s disease (PD) patients treated
with levodopa frequently develop long-term motor complications. However, little
is known about the relationship between specific subtypes of motor
complications and quality of life (QoL). In addition, potential differences in
the QoL of PD patients from different countries have not yet been investigated.
Objective: To assess
QoL and its association with on-off fluctuations, peak-dose dyskinesias,
biphasic dyskinesias, and dystonias in patients with PD in five European
countries.
Methods: Data from 817 PD patients and their
physicians from the Adelphi Parkinson’s Disease Specific Programme were
collected cross-sectionally. Generic and disease-specific QoL was measured with
the EuroQoL 5-Dimension (EQ-5D) and the Parkinson’s
Disease Questionnaire-39 (PDQ-39). Multivariable analyses were performed to test the
adjusted association of motor complications and country with QoL.
Results: Approximately 30% of the patients suffered
from any type or combination of motor complications. On-off fluctuations
significantly worsened generic QoL (p<0.001) and PD-specific QoL (p=0.01).
Dyskinesia subtypes did not affect generic QoL but had detrimental effects on
the PD-specific QoL dimensions activities of daily living, cognitions, stigma,
and bodily discomfort. Significant differences in QoL were found between the
countries with patients from Spain, Italy, and France having poorer QoL scores
than patients from Germany and the UK.
Conclusion: Motor complications, primarily on-off
fluctuations, may adversely affect QoL in patients with PD. This substantiates
the importance of targeting their prevention and delay in the treatment of PD.
Country differences in QoL of PD patients should be further explored.
P31.10
Club CREATE- A program to improve quality of life for
late-stage Parkinson’s disease
Joan Hlas
Struthers Parkinson’s
Center, Golden Valley, MN, USA
Purpose: For many diagnosed
with Parkinson’s disease (PD), late stages of the disease lead to a poor
quality of life with declining movement, interests, connections and isolation.
Club CREATE is a therapeutic day program to address these concerns. Club
CREATE’s goal is to improve quality of life for people with PD by providing
programs, support, and assistance in adapting to the challenges of PD. The
program focuses on six areas: move your body, train your brain, build a
community of support, make yourself heard, express yourself creatively, and
expand your horizons.
Methods: The program
draws upon an interdisciplinary team consisting of nursing, music therapy,
occupational therapy, social work, chaplaincy, community artists, horticultural
therapy and support staff. The team provides intervention and care at various
times, matched to the client's current needs and abilities. Both structured
groups of 8-12 members and larger group activities are offered to carry out
goals. To better understand the impact of the program on members’ quality of
life, members were surveyed using gthe PDQ-8 to assess their overall health
status. Questions were asked from a staff person and data was collected at
intervals over three years.
Results: Members have been in the program an average
of two years, ranging from two months to seven years. The overall scores of the
members whose PDQ-8 scores were measured consistently over the three year
period either improved or maintained. The greatest increase in scores came in
the social support category, increasing on average 1 point per member.
Conclusions: As the numbers of those living longer with
PD increases, it is important to develop and expand programs that can improve
quality of life, especially for those in the late stages of the disease.
P31.11
Quality of life in patients with newly diagnosed untreated Parkinson’s disease
Hye Kyung
Kim, Jae-Hyeok Lee1
1Department of Neurology, Pusan National
University Yangsan Hospital, Yangsan, Korea
Objective: In order to plan an optimal treatment
in patients with newly diagnosed Parkinson’s disease (PD), it is important to
gain knowledge about the patient’s disability and quality of life (QoL) in
relation to the clinical factors, such as the motor and non-motor symptoms.
Methods: Fifty
patients with newly diagnosed PD were included. The QoL was measured by the
Parkinson’s disease quality of life questionnaire (PDQL). The clinical aspects
of the disease were assessed using the UPDRS II, III, UPDRS sub-scores (tremor,
bradykinesia, rigidity, PIGD, ADL-axial), MMSE, Beck Depression Inventory
(BDI), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS),
the nonmotor symptoms questionnaire (NMSQ).
Results: The mean age of onset of parkinsonian symptom was 58.9 (SD=12.2)
years and the average duration of disease was 14.2 (SD=16.0) months. The PDQL
total scores correlated most strongly with UPDRS III (-0.749), NMSQ total score
(-0.676), BDI score (-0.663), and UPDRS II (-0.598, all p < 0.0001). Among
UPDRS sub-score, PIGD (-0.638) and ADL axial (0.736, both p < 0.0001) scores
were the most significant predictors of poor QoL. In multivariable
regression models, UPDRS and BDI (model 1) or UPDRS and NMSQ (model 2) were
almost equivalent predictors.
Conclusions: This study demonstrates that patients
who were depressed, had more nonmotor symptoms, axial motor impairment, and had
high levels of disability are most likely to experience poor QoL. The
improvement of both motor and nonmotor symptoms should therefore become an
important target in the management of newly diagnosed PD.
P31.12
Does home-visiting improve quality of life of those
living with Parkinson’s disease living in rural areas? – a program evaluation
Tanis Robinson1, Beth Metcalf2
1Medicine Hat College,
Medicine Hat, AB, Canada
2Parkinson’s Alberta
Society, Medicine Hat, AB, Canada
A unique home-visiting
program was established in partnership with Medicine Hat College Nursing
Program and the Parkinson’s Alberta Society Medicine Hat office in 2010. Third
year nursing students were matched with person’s living with Parkinson’s
disease and caregivers (if applicable) to provide home visits over an 8-week
duration to learn what it is like to live with a chronic illness such as
Parkinson’s disease in the community, to assess their needs, strengths, and to
provide community-based nursing interventions that provide positive health
outcomes. Anecdotal evidence from participants suggested the program was successful
and improved participants quality of life; a formal evaluation of the program
was desired.
Objectives: One objective was to explore if quality of
life improved for the person living with Parkinson’s disease and their
caregiver. Second to see if over-all-health improved for the person living with
Parkinson’s disease and the caregiver. Finally, ideas on how to maintain and
improve the program were desired.
Methods: Thematic analysis was used to evaluate 11
audio-taped interviews (transcribed) of past home-visit participants. Informed
consent was provided. Data was coded for demographic data, and five themes
emerged. Information was validated with the participants.
Results: Results showed that quality of life and
over-all-health for both the caregiver and the person living with Parkinson’s
disease improved by participating in the program.
Participants were
happier, loneliness diminished; participants had increased socialization,
self-confidence, self-esteem, coping skills, patience, and overall enjoyment;
participants felt safe in expressing their feelings and felt listened to;
communication improved between couples; and, participants were empowered by
educating students nursing and by ‘giving back’ to the community. Results
indicated that student-led home-visits were an effective way to increase
understanding of what it is like to live with Parkinson’s disease in the
community for future nurses and quality of life was improved for participants.
P31.13
Quality of life and the relative importance of motor and
non-motor symptoms in Parkinson’s: the patient perspective
Jon
Stamford1, Parkinson's Movement1
1Parkinson’s Movement, The Aldgate
Rooms, St Botolph's, Aldgate, London, UK
Introduction: Most investigations
of quality of life (QoL) in Parkinson’s (PD) have focussed on the comparison or
validation of measurement scales. Others have assessed the contribution of
general affect (depression and anxiety) to QoL. Few have addressed the
contribution of motor and non-motor symptoms (NMS). Fewer still have taken a
patient-centred stance, answering questions posed by fellow patients. The
present study, conducted by Parkinson's Movement (PM) looks at personal QoL in
PD.
Methods: A series of 5 polls (single question,
multiple choice answer) were posted on the PM community website
(www.parkinsonsmovement.healthunlocked.com).
The questions asked (Q1 & Q2) the first motor and non-motor symptoms
experienced, (Q3) current motor symptom burden, (Q4) motor influence on QoL and
(Q5) relative role of motor and non-motor symptoms on personal QoL in patients.
Between 165 and 286 responded to each poll.
Results: The PM cohort was mainly young (76%
aged 50-69), highly educated (68% with at least 1 degree), with mild
Parkinson’s (current Hoehn & Yahr stage 1/2: 66%) for 4-6 years. Results
were as follows: Q1: Tremor was usually the first symptom motor experienced
(57%), with rigidity in 21%. Q2: Anosmia (25%), sleep problems (24%) and
changes in affect (19%) were the first NMS experienced. Q3: Most common motor
symptoms currently experienced were micrographia (77%) balance problems (76%)
and tremor (73%). Q4: 28% felt that their QoL was directly related to their
motor symptoms while 30% and 33% felt their QoL was better or worse than predicted
by motor symptoms. Q5: Key movement problems (bradykinesia, rigidity, tremor)
were the most common predictor of QoL in 71%. Other factors noted were sleep
disruption (49%), balance (43%), cognition (36%) and pain (35%).
Conclusions: Motor problems, although pivotal to
diagnosis, are only one factor in a complex raft of symptoms affecting
individual patient QoL.
P31.14
Patient-centered
care for PD patients in the Parkinson centers of excellence: a multicenter
study
Martijn
van der Eijk1, Marjan J. Faber2, Peter N. Schmidt3,
Marten Munneke1, Michael S. Okun3,4,
Bastiaan R. Bloem5
1Radboud University
Nijmegen Medical Centre; Nijmegen
Centre for Evidence Based Practice; Department of Neurology, Nijmegen, The Netherlands
2Radboud University
Nijmegen Medical Centre, Scientific Institute for Quality of Healthcare (IQ
healthcare), Nijmegen, The Netherlands
3National Parkinson Foundation, Miami,
Florida
4University of Florida, Center for
Movement Disorders and Neurorestoration, Gainesville, Florida
5Radboud University Nijmegen Medical
Centre; Donders Center for Brain, Cognition and Behaviour; Department of
Neurology, Nijmegen, The Netherlands
Objective:
Patient
experience questionnaires are increasingly recognized as an essential part of
quality of care assessment. We developed and validated the Dutch Patient‐Centeredness Questionnaire for PD (PCQ-PD). Here we describe the
validation of the English PCQ-PD and its initial application to a
representative patient sample from American and Canadian Parkinson centers of
excellence.
Methods: First, the PCQ-PD was
translated from Dutch into English, based on a forward-backward translation
process. Second, the applicability was evaluated by an expert consultation
round with 17 center directors. Third, the questionnaire was pre-tested within
cognitive interviews with professionals (n=7), patients (n=6) and caregivers
(n=6). Fourth, psychometric validation was performed in a multicenter study
within 20 centers. Data-analysis focused on psychometric properties of the
questionnaire and the level of patient-centeredness by calculating scores for overall patient-centeredness
[0-3], subscale experiences [0-3] and quality
improvement scores [0-9].
Results: 972 PD patients
completed the questionnaire (mean 49 per center, range 37-58). After the
validation procedure, the PCQ-PD addressed 44 items in six subscales of
patient-centeredness. The internal consistency, expressed in Cronbach’s α
per subscale, ranged from 0.677 to 0.889. The mean overall patient-centeredness
score was 2.09 (SD 0.44). The ‘providing information’ subscale received the
lowest experiences ratings (Δ1.62, SD 0.62). ‘Were you informed about what your health professionals discussed with
each other regarding your treatment?’ obtained the highest quality
improvement score (4.61). Centers differed significantly on the overall
patient-centeredness score and information-, collaboration-, accessibility-,
and patient-involvement subscales (p<.001). Centers had comparable scores on
the empathy- and emotional support subscales. The PCQ-PD is a valid instrument
to measure patient-centeredness in PD care in America and Canada. Psychometric
properties of the instrument were good. Application of the PCQ-PD revealed the
level of patient-centeredness in the centers of excellence. The main outcome
was a compelling call for the provision of information.
P31.15
Quality of life and neuropsychology assessment in
Nigerians with Parkinson’s disease
Uduak Williams1, Ekanem Philip-Ephraim1,
Sidney Oparah1
1Internal
Medicine department, University of Calabar, Calabar, Nigeria
Introduction: Parkinson’s disease (PD) is a chronic
neurodegerative disease characterised by motor features. However growing
evidence suggests that this is usually preceded by non-motor features. PD is
associated with negative quality of life and mood impairment.
Objective: To assess the self-determined quality of life
measures and mood disorder among patients living with PD.
Method: Twenty-one consecutive consenting patients
were assessed using the Parkinson's Disease Quality of Life Questionnaire
(PDQ-39), Schwab and England Activity of daily living scale, Modified Hoehn and
Yahr Staging (MHYS), and the Hospital Anxiety and Depression scale (HADS).
Result: Twenty-one PD patients made up of 7 females
(33.3%) and 14 males (66.3%) with mean age of 60 years and mean age of onset at
56.6 years were screened. 66.6% of the patients were of MHYS stage 2 or below,
while the rest were of stages 3-4. On the Schwab and England Activity of daily
living scale 66.1% of the patient performed at levels between 70-100%, while
only 4.8% of the patient performed at ≤ 40%. The average PDQ-39 score was
31.5%. Score of 30-50% were recorded mobility, activities of daily living,
stigma and bodily discomfort. The proportion of patients that were depressed
and anxious was 9.5% and 14.3% respectively.
Conclusion: There is a significant impairment in mood and
quality of life measures among Nigerians living with PD.
CARE DELIVERY & QUALITY OF LIFE: SHARED
DECISION-MAKING: PWP- CAREGIVER- DOCTOR
P32.01
Effects of group-delivered improvisational dance on
balance in adults with middle stage Parkinson’s disease: a two-phase pilot with
fMRI case study
Glenna Batson,1,2 Christina Soriano,1,3 Paul Laurienti,1,4 Jonathan
Burdette 1,4 Sara
Migliarese,1,2 Nickolai
Hristov5
1Wake Forest University
Translational Science Center, Winston-Salem, NC, USA
2 Winston-Salem State
University, Winston-Salem, N.C., U.S.A.
3 Department of Theatre
and Dance, Wake Forest University, Winston-Salem, NC, USA
4 Laboratory for Complex
Brain Networks, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA
5 Center for Design
Innovation, Winston-Salem, NC, USA
Objective: The purpose of this two-phase pilot was:
(1) To examine the effects of group-delivered dance improvisation on balance
and mobility and, (2) for one participant, to examine changes on Functional
Magnetic Resonance Imaging (fMRI) in a subsequent neuroplasticity study.
Methods: Seven community-dwelling adults (mean age
69), with middle stage Parkinson disease, completed a 7-week (21-hour) class in
improvisational dance. The protocol emphasized individual and group movement
creation without teacher mimicking or music entrainment. At termination, one
participant with significant functional gains consented to fMRI in a
neuroplastic protocol conducted two months later. After two weeks of being
sedentary, the participant underwent a brain imaging protocol: resting and
reaction (button-pressing) task. The parent group gathered again for one week
of improvisational dance (five consecutive days, same protocol). Post-fMRI
scans followed immediately.
Results: Posttest balance outcomes for the
group-delivered dance protocol were significant for the Fullerton Advanced
Balance Scale p=.017), with an
average improvement of 5 points. TUG scores were not significant, though group
performance variability decreased with a trend toward decreased timing. For
phase 2, fMRI recordings showed increased connectivity in long-range
anterior-posterior neural network communities after the intensive trial.
Previously isolated neural networks in the basal ganglia showed significant
connections with the premotor cortex.
For this sample group, dance improvisation
resulted in significant functional gains. For one participant, functional
improvements appeared to correlate with positive neuroplastic changes in brain
connectivity both in global efficiency and strength of network connectivity
between the basal ganglia and cortical motor centers. Larger studies are
warranted to substantiate correlations between functional gains and neural
efficiency through improvisational dance in adults with middle stage Parkinson
disease.
P32.02
Shared
decision making in current treatment choice in advanced Parkinson's disease
Frouke A.P. Nijhuis1,2,
Bart Post1, Bastiaan R. Bloem1, Marjan J. Faber3
1Department
of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Centre, The
Netherlands
2Department of
Neurology, Canisius Wilhelmina Ziekenhuis Nijmegen, The Netherlands
3IQ Healthcare, Radboud
University Nijmegen Medical Centre, The Netherlands
Introduction: In advanced Parkinson ’s disease (PD), three
therapies are available: deep brain stimulation, duodenal levodopa infusion,
and subcutaneous apomorphine infusion. These therapies differ in procedures,
daily care and outcomes. Evidence for first choice of treatment is lacking as
no trial has compared these therapies directly. Therefore, therapy-selection
should be personalized and shared decision making (SDM) could stimulate active
patient involvement. In this study we evaluated the current decision making
process in advanced PD and the role of SDM.
Methods: Questionnaires on current decision making
and SDM in advanced PD were developed based on qualitative data and literature
research. Questionnaires were sent to all eligible registered Dutch
neurologists (n= 869) and PD nurse specialists (n=86) in the Netherlands. A
convenience sample of patients who had undergone one of the treatments in the
past three years (n=179) were recruited through online requests and via
neurologists.
Results:
Neurologists (42% response rate): 88% considered SDM useful and 54% said
they regularly/ always applied SDM for this decision. An important barrier to
SDM was a lack of knowledge about all treatments. 66% expressed a need for a
decision aid.
PD nurse
specialists (73%
response rate): 29% were actively
involved in decision-making and 36% gave information only.
Patients
(68%
response rate): 40% were informed
about all three options. The majority of patients (63%) would have preferred
SDM for this treatment choice; 41% had actually experienced SDM and a small
proportion was referred (11%). An important facilitator for
SDM was trust between the professional and
patient.
Discussion: Most professionals and patients have a
positive attitude towards SDM, however in practice it is not used optimally. It
is important to provide equivalent information on all options to facilitate
professionals and to increase patients’ involvement. A decision aid can be such
a facilitator for SDM in advanced PD.
P32.03
Equal
options; shared decision? Development of a decision aid for treatment choice in
advanced Parkinson's disease
Frouke A.P. Nijhuis1,2,
Bart Post1,Glyn Elwyn3, Bastiaan R. Bloem1,
Marjan J. Faber4
1Department
of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Centre, The
Netherlands
2Department of
Neurology, Canisius Wilhelmina Ziekenhuis Nijmegen, The Netherlands
3Dartmouth Center for
Health Care Delivery Science, Hanover, USA
4 IQ Healthcare, Radboud
University Nijmegen Medical Centre, The Netherlands
Introduction: The three available therapies in advanced Parkinson’s
disease (PD), deep brain stimulation, duodenal levodopa infusion, and
subcutaneous apomorphine infusion, differ in procedures, daily care and
outcomes. Evidence for first choice of treatment is lacking as no trial has
compared these therapies directly. Therefore, therapy-selection should be
personalized through shared decision making (SDM). In a previous study most
professionals were positive about shared decision making (SDM) in therapy
selection. However, professionals expressed a need for a decision aid (DA) to
support this process. A decision aid helps people to make deliberative choices
and facilitates the cognitive processes, thereby stimulating patient
involvement in the decision making process. Here we describe the development of
our DA.
Methods: The process map of Elwyn et al1)
was used to develop the DA. Qualitative and quantitative data from
professionals and patients provided information about the format, content and
constraints. SDM models plus general and PD specific cognitive decision
processes gave input for the theoretical basis of the DA. These together with
the evidence synthesis of the treatments and brainstorm sessions with
stakeholders resulted in a first prototype. The prototype was tested in several
rounds by treated patients, treatment naïve patients, caregivers, neurologists,
PD specialists with expertise on these treatments, PD nurse specialists, and a
patient communication expert.
Results: Both patients and professionals expressed a
need for equivalent treatment information. PD specific cognitive processes
taken into account were impulsivity, reduced cognitive flexibility and limited
capacity to organise new information. Our qualitative data showed patients
often focused on one treatment, not searching for equivalent information on
alternatives. Using the theoretical framework, strategies were build into the
DA to reduce these possible biases in decision making and to stimulate SDM.
References: Elwyn et al. How to develop web-based
decision aids for patients: a process map. PEC. 2011
P32.04
Providing information equals
Shared Decision Making: the professionals’ view on treatment choice in Early
Parkinson’s disease
Wieteke van Dijk1,
Marjan J. Faber2, Bastiaan R. Bloem1, Bart Post1
1Department
of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud
University Nijmegen Medical Centre, Nijmegen, the Netherlands
2Scientific
Institute for Quality of Healthcare (IQ healthcare), Radboud University
Nijmegen Medical Centre, Nijmegen, the Netherlands
Objective: The Dutch
guideline on Parkinson’s disease (PD) regards levodopa and dopamine agonists as
equipotent pharmaceutical therapies in early PD. It recommends that the choice
for treatment is based on the individual patients’ characteristics,
preferences, and the neurologists’ experience. Patients increasingly
express a desire for unbiased, comparative information regarding treatment
options, and active involvement in decision making. Considering the
preference-sensitivity of the choice, this decision is well equipped for shared
decision making (SDM). The aim of this research is to clarify if and how
professionals apply SDM for this particular decision in current practice.
Methods: Semi-structured
interviews were conducted with 15 neurologists and 7 PD nurse specialists.
Saturation was pursued in both groups. Transcripts of the interviews were
independently coded by two researchers following the rules of grounded theory.
Results: Neurologists
regarded the moment to start with pharmaceutical treatment more suitable for
SDM than the choice of treatment. They often offered their patients the freedom
to wait with treatment until they considered the disease to interfere with
their daily activities. Nonetheless, the neurologists considered not all
patients suitable for a postponed patient-directed decision, due to disease
severity and the fact that levodopa response can be used to support the
diagnosis. With regard to treatment choice, the majority strongly favoured
levodopa, and did not regard dopamine agonist as equipotent. Although all
neurologists emphasized that they informed their patients about both treatment
options, they admitted that this information is likely to be biased according
to their preferences. Nurse specialists seldom discussed the possibility of choice
with patients, but offered complement information. For true SDM, substantial
efforts will be needed to overcome the perception that sharing (biased)
information equals SDM.
CARE DELIVERY & QUALITY OF LIFE:
PALLIATIVE CARE/ END OF LIFE CARE/ LONG-TERM CARE
P33.01
Improving end of life care in
Parkinson’s disease
1Royal Berkshire NHS
Foundation Trust, Reading, Berkshire, England, UK
Objectives: Management of end of life care in patients
with Parkinson’s disease (PD) is complex. Medications commonly used for symptom
relief at the end of life (metoclopramide and haloperidol) often worsen
Parkinsonian symptoms. Furthermore, patients with PD may be inappropriately
deprived of anti-Parkinsonian drugs at the end of life. We aimed to identify
current end of life prescribing practices in PD patients admitted to a District
General Hospital in England.
Methodology: All patients with PD who died at the Royal
Berkshire NHS Foundation Trust, Reading, England between 1st January
2010 and 31st December 2012 were identified using the Hospital death
Registry. Three physicians analysed medical notes and drug charts for end of
life care and involvement of specialist PD and palliative care services.
Clinical data was recorded in a proforma.
Results: 98 patients were identified from the Hospital
death Registry. 2 patients did not have PD and notes were unavailable for 8
further patients. Clinical notes from 88 patients were reviewed. Drug charts
were available for 80 patients. 55
male and 33 female patients were identified.
Haloperidol was prescribed in 24% (19/80) whilst metoclopramide was given
in 9% (7/80) of patients. 35 patients (44%) were started on a formal end of
life care pathway (Liverpool Care Pathway). Of those 60% (21/35) patients had
their Parkinson’s medications discontinued. Our results demonstrate that
patients with PD frequently receive inadequate end of life care. We have
designed a clear end of life pathway for use in patients with PD. We emphasise
the importance of continuing some of the PD medications, considering
alternative routes of administration, avoiding antidopaminergics, and seeking
specialist PD and palliative care advice. Education of medical and nursing
staff regarding appropriate medication has since been undertaken.
P33.02
End of life experience in
Parkinson’s disease and related movement disorders from the caregiver
perspective
Ruth Hagestuen1,
Martha Nance1, Catherine Wielinski1
1Struthers
Parkinson’s Center, Golden Valley, MN, USA
Objectives: To better understand the experience of patients / families at end-of-life
with parkinsonism.
Background: Although
there is recognition that needs of patients with parkinsonism and their
families are complex, actual end-of-life experiences are poorly documented.
Methods: Primary caregivers (CG) of Struthers Parkinson’s Center patients
who had died within the last 24 months were contacted for this study. The first
contact was one-page survey; those who were willing participated in a
semi-structured phone or in-person interview. Data were stored MS Excel and MS
Access.
Results: Sixty-nine CGs were identified. Forty-eight (70%) responded to
survey, and 42 were interviewed. Thirty-eight (79%) were spouses, 81% female,
average number of years caregiving was 7.3 (range 0-24). Thirty (63%) utilized
hospice average of three months, (range 3 hours – 11 months). Interview
findings included: profound and complex neurological handicap of those dying in
hospice, pneumonia as terminal event was relatively uncommon (12%) and “slow
shutting down” due to disease itself rather common (56%). Changes in care
setting and medical care teams in the months before death were common. While
23% of the 42 patients died at home, 41% of non-hospice users died in hospital.
Caregivers reported that their lives had been consumed by the caregiver role,
that they continue to experience deep grief months after patient’s death, and
identified nurses, aides, social workers as most significant to care and
support during terminal stage.
Conclusions: Strategies to prepare patients and caregivers for, assist with,
and coordinate transitions in care team, medical goals, and care setting could
impact the care process and reduce the burden to caregivers in final stages and
during the dying process.
P33.03
Struthers Parkinson’s Care
Network
Ruth Hagestuen1, Rose
Wichmann1, Joan Gardner1
1Struthers
Parkinson’s Center, Golden Valley, Minnesota, USA
Objective: Build
sustainable partnerships with community-based residential & home care
agencies dedicated to delivery of high quality care for persons with PD and
related movement disorders.
Methods: Agencies
applied for one year pilot program designed to build capacity to provide high
quality PD care and agreed to: designate two “site champions” as key leaders
and provide training for at least 80% of all staff in core module TULIPS PD
education program and 60% of direct care providers in two additional modules;
support continuing education days at SPC for 4 nurses, 1 social worker & 2
rehabilitation professionals; demonstrate evidence of facility initiative to
insure “pills on time” and track / minimize falls; sponsor and facilitate a
support group; collect data and distribute satisfaction surveys for PD
families. Struthers Parkinson’s Center (SPC) provides education for site
champions and professionals; facilitates ongoing communication; conducts site
visits; collects and reports outcomes.
Results: Six
programs were selected. Two “site champions” from each facility attended two
day orientation and conducted TULIPS training in their facility. A total of
1,200 staff completed TULIPS core and 774 direct care staff have completed
additional modules. Site champions attend quarterly network calls and submit
bi-monthly reports. All sites report policy of “pills on time” and tracking /
minimization of falls. All exceed required numbers for professional education.
Each agency hosts a support group. Seventy-five client satisfaction surveys
have been received to date at SPC.
Conclusion:
“Buy-in” from administration and lead staff is essential. As the
process unfolds and staff becomes knowledgeable, leaders describe increasing
staff enthusiasm and comfort in providing PD care. All agencies express
interest in continuing and SPC will expand the program to additional sites.
CARE DELIVERY & QUALITY OF
LIFE: HEALTH ACCESSIBILITY/ UNDERSERVED POPULATIONS
P34.01
An outreach model to educate Hispanics living with PD in
Phoenix, Arizona
Margaret Anne Coles1,
Claudia Martinez1
1 Muhammad Ali Parkinson Center, Phoenix, AZ, USA
Objective: To develop a culturally appropriate model to
educate Hispanics with PD and their caregivers who don’t attend community
programs due to barriers including transportation, mobility, cultural beliefs,
and economic constraints.
Methods: A group of 7 volunteers were trained in
partnership with a community college, Community Health Worker networking
organization and the Muhammad Ali Parkinson Center. All volunteers had a close
family member with PD or had worked as caregivers of a client with PD. All of
them attended many of the Hispanic Outreach community programs offered by the
MAPC, including support groups and recreational classes. Volunteers had
bi-monthly meetings with the MAPC Hispanic outreach coordinator and completed a
total of 30 hours of practice required by the college class.
The volunteers
identified 12 topics they considered important for Hispanic families to better
understand the disease. A flipchart was designed that tells the story of a
Hispanic family dealing with PD. Each page explains one of the 12 topics. The
language used is easy to understand and includes every day expressions to keep
it conversational. The flipchart was used to educate Hispanics with PD in their
homes. The volunteers conducted once weekly home visits for twenty-nine
families for a total of 12 visits per family.
Results: Paired samples t-tests were used to compare
PDQ-39 subscale and summary scores before and after program involvement. Social
Support and Communication are statistically significant.
PDQ
-39 n=21 |
T=1
mean |
T=12
weeks mean |
Change |
P
value |
Mobility |
54 |
53 |
-1 |
.78 |
ADL |
46 |
42 |
-4 |
.46 |
Emotional
|
42 |
43 |
+1 |
.98 |
Stigma |
34 |
38 |
+4 |
.67 |
Social
Support |
48 |
21 |
-27 |
.00 |
Cognition
|
32 |
36 |
+4 |
.43 |
Communication |
31 |
9 |
-22 |
.00 |
Discomfort |
43 |
44 |
+1 |
.86 |
Summary
Score |
38 |
35 |
-3 |
.50 |
P34.02
Increasing return on investment and access in
the health sector in developing countries
Roger Maxi Ddungu1, Edward Katongole1,
Sarah Zzalwango2
1Glassland
International Development Agency, Kampala, Uganda
2Makerere University,
Kampala, Uganda
Objective: This paper focuses on
the different mechanisms of how to maximize return on investment and access to
health care services developing countries. One of the most inhibiting factors
to health care service access and utilization is cost sharing and/ or health
insurance.
Methods: A random sampling
technique was employed to 300 households and individual interviews conducted.
Results: Health insurance
mechanisms render access to health services affordable for low income groups.
Conditional cash payments showed promise for improving uptake of initiatives,
but could also create a perverse incentive.
Conclusion:
There
is a need for improved quality of research in the area of conditional cash
transfers for health services. An evaluation of health financing initiatives is
required to ensure an evidence base that correlates to conditional cash
transfers.
P34.03
Developing
a network of interdisciplinary Parkinson's rehabilitation teams in
nontraditional settings: providing high-quality treatment to populations in
underserved settings
John Dean
Life Care Centers of America, Longmont, CO,
USA
Objective:
Interdisciplinary
approaches to treating Parkinson's disease can be extremely effective to
treating the wide range of deficits associated with this disorder. Many of the
top programs are associated with large movement disorders clinics. However,
access to this level of expertise can be difficult for individuals in
underserved regions due to barriers such as
distance as well as a lack of qualified professionals with sufficient training
and experience in treating this disorder.
Methods:
By
developing a network of Parkinson's rehab teams based in subacute
rehabilitation facilities with skilled nursing, we are attempting to improve
access to the local community as well as for inpatient and long-term care
populations that are demographically likely to be represented in higher numbers
due to their age.
Members of an interdisciplinary Parkinson's
team typically include physical, occupational and speech therapy as well as
dietitian, social worker, neuropsychologist in addition to the movement
disorders specialist (a neurologist with specialized training in the treatment
of Parkinson's disease). In contrast, the core of our program relies on rehab
disciplines (physical, occupational and speech therapy) with specialized
training in the treatment of Parkinson's disease based on the Allied Team
Training Program (ATTP) through the National Parkinson Foundation. We refer our
clients to Parkinson's specialists in other disciplines as needed. In 2012, our
program concept was integrated into 12 other Life Care facilities throughout
Colorado and Wyoming, modeled after the ParkNet program in the Netherlands.
Results: Pending a successful
trial of this concept in this region, we hope to develop an easily replicable
program for providing access to high-quality treatment to underserved regions
around the United States.
P34.04
Relationship
between patient age and resource utilization among newly diagnosed Parkinson’s
disease patients
ElizaBeth Grubb1,
Michael Treglia2, Maureen J Lage2
1Teva, Kansas City MO,
USA
2HealthMetrics Outcomes
Research, Bonita Springs, FL, USA
Objective:
Examine differences in resource utilization in newly
diagnosed with Parkinson’s disease (PD) patients.
Methods: Study utilized Truven Health MarketScan® Commercial Claims and
Encounters and
Medicare Databases, from
1/1/2006 through 12/31/2011. Patients received at least 2 diagnoses of PD, with
first date identified as index date. Patients were required to have continuous
insurance coverage 1 year prior through 3 years post index date and be at least
age 35. Unadjusted comparisons of characteristics and resource utilization
based upon patient age (<65 v ≥65) were conducted using chi-square
statistics for categorical variables and t-tests for continuous variables.
Results: 16,022 individuals met
inclusion criteria: 4,739 < 65 and 11,283 ≥65. Older patients were
more likely to be female (63.20% v 56.80%; P<0.0001), less likely to reside
in the South (27.86% v 35.01%; P<0.0001) and less likely to be diagnosed by
a neurologist (51.83% v 67.35%; P<0.0001). Older patients were more likely
to reside in Northeast (19.49% v 13.42%; P<0.0001) and be diagnosed by a
general or family practitioner (39.16% v 24.37%). In one year prior to initial
diagnosis, older patients were significantly more likely to have an office
visit (77.34% v 69.11%; P<0.0001), an emergency room (ER) visit (30.97% v
12.83%; P<0.0001), a neurologist visit (19.70% v 18.17%; P=0.0246) or a
hospitalization (22.31% v 7.22%; P<0.0001). After PD diagnosis older
individuals were significantly less likely to have an office visit (96.26% v
99.43%; P<0.0001) or a neurologist visit (72.22% v83.60%; P<0.0001).
Older age is generally associated with poorer health and increased healthcare
resource utilization, the lower utilization of office and neurologist visits
suggests potential gaps in treatment for these individuals.
P34.05
Our experience developing a service for in-patients with
Parkinson’s
Sarah Jackson1, Elly Lesser, 1
1The Royal Devon &
Exeter (RD&E) NHS Foundation Trust, Exeter, Devon, UK
Objective: In our region there are 10,500 people
living with Parkinson’s disease (PD). 1 in 3 patients with PD are admitted
annually. 75% of admissions are emergency admissions.
There are on average
10 PD in-patients at the RD&E per day. The average length of stay is 24
days (1.94 days higher than expected). In-patient care is often sub-optimal and
only 40% of PD patients receive an accurate medication regime within 24 hours
of admission.
Methods: In January 2013 we
opened a PD ward focusing on multidisciplinary, patient-centred care. We have
also designed a PD care pathway. It identifies patients at the earliest stage
of their admission ensuring they receive specialist care whether on the PD
ward, or elsewhere in the hospital. These arrangements will improve care for PD
patients, in particular medication management.
A PD Nurse Specialist
will see emergency PD admissions on arrival. These patients can then be
diverted to the appropriate setting. This will make the patient journey less
fragmented and will improve their in-patient experience. This may also prevent
unnecessary admissions, ward transfers and ensure patients ‘get to the right ward
at the right time.’
Outcomes: Our aims from
developing this service:
·
Reduced length of stay – target 20%
·
% accurate PD medication prescribed and taken
within 24 hours from 40 to 80%
·
Reduction in prescribing errors from 27% to <5%
·
Reduction in unplanned readmissions
·
Patient satisfaction measured by a patient
questionnaire
·
% of patients self-medicating increase from 30 to
70%
P34.06
Developing an innovative model of care for a Nurse
Managed Health Center - Parkinson’s disease telemedicine clinic
1Ingrid
Pretzer-Aboff 1Allen Prettyman
1University of
Delaware, School of Nursing, Newark, DE, USA
There is ample
evidence that medical, surgical and exercise interventions have potential to
significantly improve the symptoms and quality of life of people living with
Parkinson’s disease (PD). It has been demonstrated that regular visits to a
neurologist was associated with better control of symptoms, lower risk of
injury and long term facility placement, and greater survival. However, in many
areas of the USA access to PD focused care is lacking. On the Delmarva
peninsula PD patients can travel up to 10 hours for treatment by a movement
disorder specialist in one of the surrounding states. We will use a
telemedicine approach to import the expertise of a movement disorder specialist
to care for the medical needs of our PD patients.
Purpose: Describe the development of a unique PD
Telemedicine Clinic designed to specifically meet the complex needs of PD
patients.
Methods: Stakeholders included people living with PD,
caregivers, a movement disorder specialist with expertise in telemedicine, the
state Division of Services for Aging and Adults with Physical Disabilities,
BCBS, local neurologists, and Advanced Practice Nurses with PD expertise. Each
was included in discussions regarding the development, composition, and
evaluation of the clinic. Evaluation will occur at the end of three months of
operation for feasibility, cost, impact and satisfaction by users.
Results: Educational needs were identified for
patients, caregivers and staff of the Nurse Managed Health Center. Access to PD
knowledgeable providers such as movement disorder specialists, advanced
practice nurses, psychologists, speech, physical and occupational therapists
was requested. Access to relevant exercise programs, and clinical trials were
also requested. State and private insurance stakeholders requested evaluation
of impact on quality of care and cost-effectiveness of this new model of care.
Conclusion: This information will inform the structure
and function of our new PD telemedicine clinic.
P34.07
Does a specialist unit improve outcomes for hospitalised
patients with Parkinson’s disease? A prospective study
Rob Skelly, Lisa Brown, Apostolos Fakis, Lindsey Kimber,
Charlotte Downes, Fiona Lindop, Clare Johnson, Caroline Bartliff, Nin Bajaj
Royal Derby Hospital, Derby, UK
Objective: Suboptimal management of Parkinson’s
Disease (PD) medication in hospital may lead to avoidable complications and
increased length of stay. We introduced an in-patient PD unit for those
admitted urgently with general medical problems. We explored the effect of the
unit on medication management, length of stay and patient experience.
Methods: We conducted a single-center
prospective feasibility study. The unit’s core features were defined following
consultation with patients and professionals: specially trained staff, ready
availability of PD drugs, guidelines, and care led by a geriatrician with
specialty PD training. We compared patient outcomes before and after
introduction of the unit. Mandatory staff training comprised four one-hour
sessions: PD symptoms; medications; therapy; communication and swallowing. Most
medication was prescribed using an electronic Prescribing and Administration
system (iSOFT). A patient experience survey was administered.
Results:
|
General
Ward Care |
PD Unit
care |
p-value |
Baseline
characteristics |
|
|
|
Number |
20 |
24 |
|
Age – median
(Interquartile range) |
81
(75-84) |
81
(73-84) |
0.611 |
Gender: male – no.
(%) |
16 (80%) |
16 (67%) |
0.498 |
Stage (% Hoehn-Yahr 4 and
5) |
6 (30%) |
14 (58%) |
0.160 |
Outcomes |
|
|
|
PD medication doses
given (% of all prescribed doses) |
1,827
(82%) |
1,307
(86%) |
0.022 |
PD medication given
on time [within 30 minutes of scheduled time] (%) |
949
(44%) |
904
(60%) |
<0.001 |
Patients with any PD
medication prescription error(s) (%) |
12 (67%) |
11 (46%) |
0.221 |
Length of stay –
days: median (IQR) |
13 (9 -
27) |
9 (5-16) |
0.043 |
Patient experience –
overall experience of care (higher scores better): median (IQR) (n=31) |
3 (2-3) |
3 (3-4) |
0.016 |
Discussion: If replicated and generalisable to other
hospitals, reductions in length of stay would lead to significant cost savings.
The apparent improved outcomes with Parkinson’s unit care merit further
investigation. We hope to test the hypothesis that specialized units are
cost-effective and improve patient care using a cluster-randomized controlled
trial design.
CARE DELIVERY & QUALITY OF LIFE: DAILY
LIFE ACTIVITIES INCLUDING WORKING & DRIVING
P35.01
Freezing of gait symptoms in Parkinson’s impairs vision
for perception but not action: evidence from gait with obstacles
Pieruccini-Faria, F1,2;
Ehgoetz Martens K.A.1,4; Silveira C.R.A. 1,3; Jones J.A.
1,2; Almeida Q.J.1
1Sun Life Movement
Disorders Research & Rehabilitation Centre - Wilfrid Laurier University
2Wilfrid Laurier
University/Psychology
3University of
Waterloo/Kinesiology
4University of
Waterloo/Psychology
Objective: The aim of current study was to evaluate
whether the foot elevation (to step over an obstacle) in PD patients with FOG
symptoms would be influenced during height judgements of an obstacle’s height
during static condition.
Methods: Fourteen PD patients with FOG (PD-FOG),
thirteen PD patients without FOG (PD-nonFOG) and thirteen healthy control
participants (HC) judged the height of an obstacle using a measuring tape, from
the starting position (perceptual estimate) prior to walking toward, and
stepping over the obstacle. Participants had to inform the experimenter to stop
opening the tape when they perceived that the length of the tape matched the
obstacle height. Active iRED markers were placed on the 5th
metatarsal of each foot to measure the max toe elevation of each foot when
stepping over the obstacle.
Results: A group effect (F(2, 38)=5.8047; p=.006) showed that
PD-FOG had significant greater variable error and lower accuracy (typically
underestimating the obstacle height) (p=0.047) when estimating the obstacle
height compared to HC participants. There were no differences between groups
for foot elevation performance when actual walking trials were completed.
Pearson’s correlations revealed that only HC had a significant positive
correlation between perceptual estimate of the obstacle height with: i) foot
elevation (r=0.554; p=0.03) and, ii) actual obstacle height (r=0.674; p=0.008).
Conclusion: In sum, our results demonstrated that FOG
symptoms in PD affect the perceptual judgement of the obstacle height; however
it does not affect the control involved in physically stepping over an
obstacle. A selective perceptual impairment is suggested by these results, and
needs to be carefully considered for its influence on tripping and falling in
this specific population.
P35.02
The experience of motor and non-motor
symptoms during daily life with Parkinson’s disease
Shih-yu Lur, Linda Tickle-Degnen
Tufts University, Medford, MA, USA
Objective: People with Parkinson’s disease (PD)
have a variety of symptoms, yet there is very little research on how they
spontaneously describe motor and non-motor symptoms in their daily life. The
purpose of this study was to examine how people with PD experience their
symptoms relative to their participation in daily life activities.
Methods: Open-ended interviews of 38
participants with PD (Hoehn & Yahr Stages I– III) discussing their daily
life experiences in the past few weeks were transcribed verbatim and content
analyzed. A coding system was developed to detect participants’ spontaneous
talk about symptoms and daily life activities. Motor symptoms were coded as a
general movement problem, hypokinesis, hyperkinesis, or an axial or functional
motor control impairment. Non-motor symptoms were coded as a general non-motor
problem, a problem in cognition, affect, sensory experience, fatigue, sleep, or
autonomic function. Nonspecific symptoms were coded when participants referred
to the disease affecting their activity without providing distinctions between
motor and non-motor symptoms. Activities were coded as rest or sleep, basic
activity of daily living, instrumental, low-demand leisure, high-demand
leisure, social or other. The coding system demonstrated adequate inter-rater
reliability.
Results: Participants described 145 daily life
activities, 68 (47%) of which were experienced with PD symptoms (average = 1.7
activity-related symptoms per participant). Motor symptoms were mentioned more
frequently (31 times, 46%) than non-motor (22 times, 32%) and nonspecific (15
times, 22%) symptoms. Motor symptoms, especially axial or functional motor
control impairments, were mentioned most frequently during basic activities of
daily living, high-demand leisure, and social activities. Non-motor symptoms,
especially sleep problems, were mentioned most frequently during instrumental,
low-demand leisure and social activities. Nonspecific symptoms were spread in roughly
equivalent rates across activity categories. People with PD spontaneously
mention motor and non-motor symptoms as linked to specific types of daily life
activities.
P35.03
Working with Parkinson’s disease: extent and
nature of problems and adaptations
Ingrid Sturkenboom1, Maaike Storm
van‘s Gravesande2, Ronald Meijer1,2
1Radboud
University Nijmegen Medical Centre, Nijmegen, The Netherlands
2Rehabilitation Medical Center Groot Klimmendaal, Arnhem, The Netherlands
Objective: Inability to maintain
employment has considerable consequences for the person with Parkinson’s
disease, employers and society. The aim of the study was to investigate in
which way and to what extent Parkinson’s disease impacts on work and what kind
of support and adaptations patients receive.
Methods: A descriptive
quantitative research was conducted (2011/2012). Data were received from the
National Social Security Institute of Employee Insurances and a one-time survey
was executed. For the survey, persons who have (had) experienced being employed
while having the diagnosis Parkinson’s disease were invited to participate via
various media. The questionnaire was developed on the basis of the literature,
expert opinions and patient perspectives and with use of the International Classification
of Functioning, Disability and Health.
Results: In 2011, 1467
Parkinson’s disease patients in the Netherlands received disability benefits
due to (partial) incapacity to work, of whom 88% was considered completely
unable to work. The questionnaire was completed by 293 patients; 63% were still
employed. Fatigue was the most reported complaint impacting on work (61%);
diminished fine hand use (58%) and undertaking multiple tasks (51%) were most
reported activity limitations. Adaptations to work were realized in 66% of the
respondents. Accommodation of task content and working hours were most frequent
adaptations. Only 38% received information, advice or support about working
with Parkinson’s disease. One year after diagnosis 9.4% stopped paid employment;
this increased to 50% after 8 years (Kaplan Meier survival analysis). Factors
significantly associated with giving up work were age of diagnosis (hazard
ratio1.16; 95% CI: 1.096-1.219; p=0.000) and moment of first adaptations at
work (hazard ratio 0.76 (95% CI: 0.680-0.839; p=0.000) (Cox proportional hazard
analysis). So, the older the age at diagnosis and the earlier adaptations at
work are necessary, the sooner a Parkinson’s disease patient gave up work.
P35.04
Utilization of occupational therapy in management of
impairments in Parkinson’s disease
1Richard
VandenDolder, 1Catherine Wielinski, Lori McManus, OTR/L
1Struthers Parkinson’s
Center, Golden Valley, MN, USA
Objective: 1) Describe current occupational therapy
interventions to assist individuals in minimizing disability using exercise,
compensatory strategies, and adaptive equipment. 2) List examples of
strategies, exercises, and adaptive equipment frequently found to be effective
in PD.
Methods: In sample of 207 patients, referred for
outpatient occupational therapy treatment, the reported problems resulting in
OT referral were difficulties with performance of functional ADL’s (89.9%), bed
mobility (68.1%), and instruction in PD-specific exercises to promote
functional ability (76.8%), medication management (22.7%), cognition (7.7%),
driving (6.8%), falls prevention (5.3%), and writing (3.9%). Patients were
trained in home exercises to promote trunk rotation, shoulder flexion, fine
motor coordination with emphasis on stretching and large amplitude motions.
These movements were incorporated with instruction in alternate methods of
performing tasks to compensate for decreased motor control, bradykinesia,
rigidity, perceptual deficits, balance impairment, tremor, and decreased coordination.
Instructions were determined by the patient’s specific strengths and
difficulties. When appropriate, adaptive equipment was recommended.
Results: Patients reported feeling benefits of upper
body exercises relative to performing functional tasks more easily. They
reported less difficulty and demonstrated increased independence in performance
of common ADL tasks, by effectively using alternate methods and adaptive
equipment appropriate to their needs.
Conclusions: Individuals with PD report and demonstrate
benefit from instruction that addresses their specific priorities and
difficulties to increase and preserve their ability to function in daily life.
This involves the current understanding of exercise and instruction in methods
immediately addressing the functional difficulties the person experiences.
CARE
DELIVERY & QUALITY OF LIFE: SELF-MANAGEMENT, EMPOWERMENT, COPING STRATEGIES
P36.01
Reclaiming positive perspective: secrets to success
living life to the fullest with Parkinson’s disease (PD)
John Baumann
University of
Louisville, KY, USA
Objective: The objective of this presentation is to
enlighten Parkinson’s patients about the substantial control they have over the
quality of their own life.
Methods: By being forewarned about the less desirable
common emotional stages of PD, patients have the opportunity to move through
the difficult stages more quickly. Some form of shock is experienced when
diagnosed, followed by disbelief. Denial occurs because PD is frequently
misdiagnosed, and no definitive confirmatory test exists. We have a right to be
angry and depressed. Having PD is not our fault. PD will likely eventually
affect our ability to talk, walk, think, swallow, have sex, drive, and even go
to the bathroom. These emotional stages should be communicated to all,
especially newly diagnosed patients.
Results: By explaining the emotional stages involved with PD, patients can accept,
and even embrace, PD sooner. When I was diagnosed, shock, disbelief and
denial paralyzed me and anger and depression were poison to my soul. My new
“job” became to sustain the highest quality of life for the remainder of my
life. My Plan was to envision myself with the highest quality of life; to
remember to live in the moment; to create a “bucket list” and experience each
item; to keep a positive attitude; to have faith in myself; to eat healthy,
organic food; to exercise daily, gradually getting out of my comfort zone; to
perform activities that keep me mentally sharp; to discover my life’s purpose
as an inspirational speaker and author; to be more loving, kind and
compassionate; and to accept, and even embrace, PD by finding meaning (silver
linings) in the disease. The ultimate result of enacting this plan is that I am
healthier now, over ten years into my PD, than I ever was before I started
exhibiting symptoms of PD.
P36.02
Learning
experience from a family intervention research project: benefits for couples
living with Parkinson’s disease
Line Beaudet1,
Francine Ducharme2, Nathalie L’Écuyer1, France Roy1,
Sylvain Chouinard1, Michel Panisset1, Nicolas Jodoin1,
Monica Béland1, Lyne Jean1
1Centre hospitalier de l’Université de Montréal
2Université de Montréal
Background: Around the world, Parkinson disease (PD)
affects millions of people and their families. The majority live at home and
are cared for by an elderly spouse. The complex changes and trajectory of the
illness often leave these couples ill prepared to face the challenges ahead.
Many clinicians and researchers emphasize the need for studies that examine
specific family interventions oriented towards this clientele.
Objective: Describe a family intervention and the approach underpinning its development and
evaluation.
Frameworks: Transition Theory (Meleis et al., 2000), the
Calgary Family Assessment and Intervention Models (Wright & Leahey, 2009)
and the Intervention Mapping Scheme (Bartholomew et al., 2006) were selected as
frameworks for this study.
Methods: A qualitative design and a participative
process were utilized. Ten elderly couples, four health care professionals and two consultants collaborated in the
intervention development. Three new couples took part and evaluated the
intervention (contents, structure, process, usefulness). Couples were
recruited from a Movement Disorders Clinic (Montréal, Canada). Data from
semi-structured interviews with these couples was subjected to constant
comparative analysis.
Results: The intervention consisted of seven
bi-monthly sessions of ninety minutes. The themes of the sessions were based on
the couples’ needs and preferences. The intervention was oriented towards the
couples’ concerns and specific objectives; health promotion, problem solving,
access to resources, communication and role adjustment. The study results showed
the feasibility, the acceptability and the utility of the intervention. The
main benefits observed by the couples were; the ability to find solutions
adaptable to various situations which are favorable to both partners, the
skills to get help and services, an increased feeling of mastery, mutual
support, pleasure and hope.
Conclusion: Our study provides a
guide for the development and the evaluation of family interventions tailored
to the context and the needs of elderly couples living with PD.
P36.03
The Advantages of Parkinson’s and other (un)likely
stories
Paul MacDonald, Philip Beckett
Background: Two individuals who each had that unusual
combination of characteristics: Parkinsons; a penchant for sharing ideas; a
skill in communicating and a wry sense of humour, met and fed from each other’s
ideas. A cartoonist who uses his skill to illustrate many aspects of life and a
poet who can only occasionally supress his instinct for a humorous punch line
came together and produced a series of words and pictures that look at
Parkinson’s in a light hearted way, focusing on things we all might recognise,
but often we need to have it pointed out to make us smile – and we all need to
smile!
Aims/objectives:
·
primarily
to bring a smile to the faces of people by making them realise that Parkinson’s
can be laughed at
·
to
produce material for an exhibition and a book, including work from artist and
poet together, inspired by each other, as well as work from each that stands
alone.
·
to keep Parkinson’s in perspective by
commenting through their various mediums on life in general
·
to
attract attention, increase awareness and to have fun doing it.
Method : We each had a stock of work already completed
and the idea of combining those in a book and an exhibition was suggested. But
linking the two, poetry and cartoons, sparked inspiration. Not only could the
artist illustrate the poetry, but the artwork could inspire the poet – this was
a rich source of raw material for both men. The focus on searching out and
depicting advantages that Parkinson’s might give an individual generated many
ideas, from ridiculously funny to sublime. At the congress, we propose handing
out postcards containing Parkinson-related cartoons and a short poem, limerick
or similar and ask individuals to write on the card a comment about the
thoughts, emotions or feelings the images or words induced in them. To collect,
analyse and report upon the responses. Also at the congress, we will write
topical poems and draw relevant cartoons as the event progresses, picking up
aspects of the congress from people’s experiences and reporting these as a live
blog, maintaining a positive and “good fun” stance.
Outcomes: The poster will present information on
progress towards our aims, information about the book and exhibitions and any
proceeds to be donated to Parkinson’s charities, but our wish is to spark
positive attitudes through laughter and looking at life from new perspectives,
thus to broaden people’s awareness. Measuring this will be possible if
sufficient numbers of postcards are returned.
P36.04
Developing
Northumbria Parkinson’s information service: exploring health professionals’
perceptions of information provision
Kate Greenwell1, Richard Walker1,
Annette Hand1, Sally Corbett1
1Northumbria Healthcare NHS Foundation Trust, North Shields, UK
Objective: Improving
information provision is fundamental to supporting people with Parkinson’s
disease (PD) to manage their condition. It has been a primary driver in recent
UK government policies. Few research studies have focused on information
provision in PD. Participatory research was used to improve information
provision for people with PD and their carers. Specifically, this phase aimed
to: (1) Explore how information is provided within Northumbria Parkinson’s
Service; (2) Explore health professionals’ perceptions of the facilitators and
barriers to information provision; (3) Develop recommendations for practice.
Methods: Fourteen semi-structured interviews were
carried out on a purposive sample of health professionals, including four PD
nurse specialists, three doctors, six allied health professionals and one
community specialist nurse. Interviews were analysed using thematic analysis
(Braun & Clarke, 2006).
Results: Four main themes emerged:
(1) ‘information provision systems’ described the systems that were needed to
provide information to people living with PD, including participants’
perceptions of what and how information should be delivered and how information
provision should be recorded; (2) ‘providing the right information at the right
time by the right person’, included participants’ perceptions of how to avoid
information overload, how to assess people’s individual information needs and
who should provide information; (3) ‘perceived barriers to information
provision’; and (4) ‘impact of information provision’, including participants’
perceptions of whether information provision always has its intended impact.
These findings were corroborated with findings from patients and carers
consultations to make service-level and organisational recommendations on
improving information provision. An action plan was created for Northumbria
Parkinson’s Service including the development of health professional-led and
patient-led information provision models; information events for newly
diagnosed patients and their carers; new information resources; and personal
health records.
P36.05
An introduction to the Voices of Hope Choir for people
with Parkinson’s disease
Jennifer Grundulis, Christine O’Mahony
Move4Parkinson’s,
Dublin, Ireland
Objective: To
provide information on the current Move4Parkinson’s Voices of Hope choir (VoH),
created specifically for PwP, their family and friends.
Methods: The VoH was created in September 2012 after
SLP Jennifer Grundulis gave a talk on choral singing for PwP at the
Move4Parkinson’s Empowerment Day in Dublin, in June 2012.
No
formal evaluation of the choir has been undergone at present, though choir
members do submit an anonymous ‘check-in’ form which they fill out upon
beginning and then ending of rehearsal, which asks members to identify how they
are feeling at those moments. Personal statements and surveys have been
collected from members.
Results: Anecdotal evidence from choir members has been overwhelmingly positive.
Weekly check-in forms have demonstrated an immediate positive impact on choir
members:
Pre-Rehearsal Statement
Jittery
and nervous
Self-conscious/
under-confident
Nervous
with the shakes- but looking forward to the practice
Post-Rehearsal Statement
Much
happier and at ease
Heart
feels wide open! Amazing
So
enjoyed the evening. I feel uplifted
Member
statements collected in December 2012 indicate a positive impact. One wrote,
“(The Voices of) Hope choir has shown me that there are no limits. Thursday is
my oasis. Move4Parkinson’s has got me living again and provided lots of
practical support with love and kindness… This is world changing for all of us
and more.”
Survey
of choir members in April 2012 indicated 100% of participants felt their voice
had improved since joining choir. Of those with PD, 85% noted an improvement in
how good they feel, 71% an improvement in low loud they sing, and 57% an
improvement in how loud they talk, how deep a breath they can take and how well
they can follow a rhythm.
P36.06
Evaluation of a maintenance exercise program for people
with Parkinson’s disease over a three year period
Christine Huston1, Juliette Looker1
1Nottingham University
Hospital NHS Trust, Nottingham, UK
Objective: To evaluate the uptake and effect of a weekly
physiotherapy led exercise class for people with Parkinson’s disease in
maintaining physical function.
Methods: Weekly exercise groups consisting of stretching, core stability
training, strength and balance exercise was set up in a local church hall with
places for forty individuals at any one time. Participants self referred and
were permitted to attend as frequently or infrequently as they chose. On first
attendance Berg Balance Scores, Timed Up and Go test, Lindop Scores,
Parkinson’s disease questionnaire 39 and PD Non motor symptom questionnaires
were completed. These tests were repeated at 4 monthly intervals and a record
of attendance kept. Test scores were collated for individual participants over
the period of time they attended the group and results shared with the
individual. Individual data sets were then collated and analysis of data
undertaken in 4 months blocks ( e.g. cohorts of individuals attending for 4
months, 8 months 12 months etc)
Results: Preliminary results Total number of participates over three years 89. 16
individuals attended over three year period. During the first 4 months
of attending there was a 3.18% (p > 0.05improvement in Berg Balance score,
trend towards improvement was noted in TUG. This improvement was maintained in
81% who continued to attend 75% of the classes over a period of 28 months.
Beyond this individuals required targeted physiotherapy to restore TUG, and
Berg Balance score to normal ranges. (Analysis of additional scoring and
correlations not yet completed)
P36.07
An evaluation of an occupational therapy memory group for
those with mild cognitive impairment in Parkinson’s
Clare Johnson
Derby Hospitals NHS
Foundation Trust
Objective: This is an evaluation of the content and
outcomes of a group ran by Occupational Therapists for people with mild
cognitive impairment in Parkinson’s. The group aims to educate patients and
carers about memory impairment and to teach strategies to use daily to maintain
independence and confidence. With is a score between 21/30 and 27/30 on a
Montreal Cognitive Assessment (MOCA) patients were invited to attend.
Methods: The group is 90 minutes per week for seven
weeks, consisting of six patients. The weekly format included an education
topic, practical exercise and learning strategies. Topics for education
included; what is memory, how it relates to Parkinson’s, external factors and
other cognitive difficulty in Parkinson’s (dysexecutive function). Focus was
made on attention and concentration impairment. Written information was given
to take to read and share with carers. Strategies provided varied from white
boards / diaries to prompt, to association. At the beginning and the end a
memory questionnaire was completed. An evaluation of content and format was
completed at the end. A MOCA was completed following.
Results: The memory
questionnaire rated how often they have difficulties with everyday activities.
There was a reduction overall in frequency of memory problems. In the
evaluation questionnaire, education was the most useful part of the group, the
exercises were difficult to manage within the group setting. An evaluation of
the number of strategies used found there was an increase used by all patients
following the course. It was evident though that the most beneficial part of
this group was that they felt they were not alone and were able to share memory
difficulties with others without shame.
P36.08
Application of the Integrated
Chronic Care Management model using LSVT BIG and LSVT LOUD protocol framework
for care of people with PD in the home
Bernadette Kosir1,
Kerry Wilson1
1Residential
Home Health, Madison Heights, MI, USA
Objective: Health
coaching models have become prevalent and successful in facilitating effective
patient care transitions across care settings and in reducing rehospitalization
of high risk patients with chronic or progressive conditions, including people
with Parkinson's disease. The implementation of such models with PD using LSVT
BIG and LSVT LOUD treatment protocols will be presented.
Methods: Successful
coaching models, such as the Integrated Chronic Care Management (ICCM) model,
train and equip health coaches with a knowledge base of best practices for
self-management support which ultimately focus on a patient's unique goals.
Residential Home Health clinicians certified in LSVT BIG and LSVT LOUD are
trained in parallel self-management support techniques that engage and empower
patients for improved quality of life using evidence-based protocol techniques.
These sensory calibration techniques have been applied by physical,
occupational, and speech therapists at all stages of Parkinson's disease with
over 500 patients, with improvement noted in OASIS comprehensive data set
scores of critical functional skills required to maintain safety in the home
and engagement in the community.
Results: Our
experience with implementation of ICCM techniques and tools including Motivational
Interviewing, team conferencing, assessment of Confidence to Change, and
assessment of Importance of Behavior Change, to home-bound patients using LSVT
BIG and LOUD treatment framework will be discussed. Data related to improved
OASIS functional data set scores as well as a significant reduction in
rehospitalization rates for this at-risk population will be presented through
case study examples.
P36.09
Twenty-five years of discovery: A longitudinal study of
Parkinson support groups
Sheree L. Loftus, PhD 1, 2
1Beth Israel Medical
Center, NY, NY, USA,
2Hunter-Bellevue
School of Nursing, NY, USA
Objective: Alzheimer’s and
Parkinson’s have emerged as increasingly common neurodegenerative diseases
associated with the aging population. Support groups are a missing link in the
continuum of care for those with chronic illness and their caregivers.
Documentation and presentation of twenty-five years of discovery of
the cumulative lived experience of Manhattan Parkinson Groups, with focused
attention to the content and purpose of groups.
Methods: Support groups play an integral role in the
chronic care community. Data on the activities, concerns, and experiences of
support group members during meetings were recorded through transcribed meeting
minutes and longitudinal documentation. Manhattan Parkinson Group ideas and
themes were identified through the data written as text. The three Manhattan
Parkinson Groups where data was recorded were at Columbia University Medical
Center from 1985-1988, New York University Medical Center from 1990-1994 and
Beth Israel Medical Center 1994-2013. Complete anonymity was maintained as
names of participants were never recorded for this study. Consent for
transcription of meeting minutes was given by all.
Results:
Group
themes include maintaining dignity, independence, social and family roles, and
being informed. Groups provide a confidential oasis in the drought of chronic
illness care in the United States. They provide an opportunity for patients to
share issues with others living with and experiencing the same disease.
Non-motor symptoms of Parkinson disease such as hypotension, insomnia,
incontinence, depression, constipation, skin care, difficulty with sex,
exercise, speech, swallowing, mobility, balance, falls and pain, were
consistently identified as Nursing care concerns needing attention. Family
caregivers and those with long term Parkinson disease identified the medical
community “forgot” them once medical or surgical treatment options were
expended. Support groups are for patients and families alike to discuss
concerns about care, health, life, relationships and subjects too
time-consuming or controversial to discuss with their primary health care
provider.
P36.10
The effect of a music cue on gait and impact on quality
of life in Parkinson's: two case studies
Fiona Lindop
Derby Hospitals NHS
Foundation Trust, Derby, UK
Objective: To
investigate the effect of music on gait and impact on Quality of life (QoL)
Methods: Patient
A, diagnosed with Parkinson's in 2001, now experiences marked freezing of gait
(FOG), no longer responding to cognitive, visual, verbal or metronome cueing.
Patient B, diagnosed 2009, experienced FOG, axial rigidity on turning
(especially when dual tasking), reduced stride length and ground clearance.
Reduced confidence in going out was a direct result of FOG and anxiety a
prominent non-motor symptom. For both patients, gait was measured using three tasks on the Lindop Parkinson's Assessment
Scale: timed up and go (TUG) and 1800 turn to right and left. These
were immediately repeated while listening to music through headphones.
Results: Improvements in TUG and turn scores
when using the music can be seen in Tables 1 and 2. Patient A found "easy listening"
music most helpful while Patient B experimented with different genres, finding
marching music most beneficial. Using the MP3 player she demonstrated the
ability to walk backwards safely and dance a "jig", neither of which
were possible without the music. She reported that "playing the right
music is like turning on a power switch, and when the music stops it's like
turning off the power again". Using a music cue has positively impacted
both patients' mobility, reducing FOG and improving QoL, particularly for
Patient B, with improvement in all questions on the PDQ-39 stigma domain and
some areas of mobility. She reports decreased anxiety and feels she can
"walk more naturally and feel less awkward". A larger study is
planned to compare the effectiveness of a metronome with listening to music.
Table
1: Patient A |
|||
|
Timed Up
and Go (with 3-wheeled frame) |
1800
turn to Right |
1800
turn to Left |
No Music
Cue |
1 minute 33seconds |
34 steps |
36 steps |
With
Music Cue |
34.8 seconds |
14 steps |
22 steps |
Table
2: Patient B |
|||
|
Timed Up
and Go (no walking aid) |
1800
turn to Right |
1800
turn to Left |
No Music
Cue |
14.7 seconds |
5 steps |
5 steps |
With
Music Cue |
9.2 seconds |
3 steps |
3steps |
P36.11
The effectiveness of self-management support
strategies used by health care professionals
Patrick McGowan
University
of Victoria, Victoria, BC, Canada
Objective: Parkinson’s care
constitutes an ongoing process of team treatment and support provided by clinicians
and lay personnel based on the changing condition. In addition to providing
optimal medical care, health care professionals (HCP) recognize that outcomes
are largely mediated through patients’ own behaviour and lifestyle which occurs
after they leave the clinical setting. The goal of self-management support
(SMS) is to empower and prepare patients to make decisions and to engage in
healthy behaviors and acknowledges the patients’ central role in their care.
Methods: To address client
behaviour, clinicians are becoming skilled to incorporate SMS strategies
including behavioural counselling interventions into routine practice. Two
methods were employed to investigate the relative effectiveness of various SMS
strategies: a) the development of “evidence-based” best practice guidelines on
SMS by the Registered Nurses Association of Ontario; and b) an investigative
report examining SMS in primary health care by the Health Council of Canada.
Results:
Varying
levels of evidence ranging from “Expert Opinion” to “Systematic Reviews of
Randomized controlled trials” have been allocated to 10 strategies that can be
utilized by HCP’s in clinical practice.
P36.12
Home-based training with Nintendo Wii Fit and balance board
in Parkinson’s disease: Is it a tool for self-management motor activities in
long term care?
Susanna Mezzarobba1, Giulia Sgubin1,
Mihaela Banica2, Laura Iozzi3, Daniele Volpe4,
Livio Capus3
1 Physiotherapy Degree,
University of Trieste, Italy
2 Department of Medical
Sciences, Neurology Unit, University of Trieste, Italy
3 Parkinson Disease
Association Pegaso, Trieste, Italy
4 S. Raffaele Arcangelo
Hospital, Fatebenefratelli AFaR, Venezia, Italy
Objective: evaluate the efficacy on postural control of a home based training using Wii Fit with Balance Board in subjects with Parkinson ’s disease (PD), comparing the effects with a control PD group performing the same exercises without Wii Fit. Furthermore we checked patient compliance to motor activity to ensure regular self-management for implementing long term benefit of rehabilitation program.
Methods We enrolled 20 subjects with PD, recruited on a voluntary
basis throughout PD meeting group. Patients performed a
daily home based training program in “on” condition for 3 months. They independently managed after a
proper supervision and guidance of the first training session plus four
scheduled physiotherapist’s supervision meetings. Two groups were determined.
Group 1 based on exercises with Wii Fit and Group 2 with the same exercise
protocol without Wii Fit. Disease stage (H&Y and UPDRS
III), quality of life (PDQ-39), balance (Berg balance scale-BBS and force
platform analysis) and disability (Schwab and England ) were assessed at
baseline and after 3 months treatment. Patients underwent a brief
neuropsychological test to asses frontal and executive functions and compliance
to treatment. Caregiver burden was also assessed.
Results At baseline both group did not differ in
clinical variables. Group 1 significantly improve (p<0,05) in UPDRS, PDQ39,
BBS and in force platform data after treatment, compared with Group 2, with a
mean of 70h of self-managed motor activities in Group 1 and 45h
in Group 2. Furthermore neuropsychological data highlight a positive
effect on depressive state (BDI) and coping strategies. Home based balance
training using Wii Fit could improve postural control in people with
Parkinson’s disease with a better compliance for independent motor activities. In our hypothesis visual feedback and
motivating environment, continuous reinforcement and results obtained in games
are pleasant components of training that can maximize
compliance with motor activity.
P36.13
Applying the self-determination theory to gait
retraining in people living with Parkinson’s disease: potential directions for
intervention
Ashley Hope1, Stephanie Morrison1
1Faculty of Health Sciences, Western
University, Canada
The Self-Determination Theory provides a
framework that might be useful in understanding and shaping rehabilitation
interventions. The Self-Determination Theory describes different types of
motivation, as well as ways that self-determined forms of motivation can be
developed or enhanced. According to this framework, the satisfaction of three
basic psychological needs of autonomy, competence, and relatedness facilitates
the development of self-determined motivation. These types of motivation are
particularly relevant in the context of rehabilitation, because they can be related
to the initiation and maintenance of behaviour (Deci & Ryan, 1985, 2002),
such as rehabilitation activities. According to Sirur, Richardson, Wishart, and
Hanna (2009), rehabilitation interventions should be theoretically informed
such that the intervention supports practice adherence. Incorporating the
Self-Determination Theory into intervention design can enhance the possibility
of achieving adherence and, as a result, meaningful participant outcomes.
Recently a home-based gait-retraining intervention for individuals with
Parkinson’s disease was piloted in London, Ontario, which resulted in 100%
home-practice adherence. Although not initially developed as a motivational
intervention, it appears that the three basic psychological needs were
implicitly supported due to the intervention design. This pilot intervention
will be discussed in relation to the Self-Determination Theory, highlighting
the potential use of this framework in rehabilitation programs for people
living with Parkinson’s disease.
P36.14
Health information seeking in young-onset Parkinson’s
disease: sources and foci
Michael J Ravenek1, Sandi J Spaulding1,
Mary Jenkins2, Debbie Laliberte-Rudman1
1Faculty of Health
Sciences, Western University, London, ON, Canada
2Movement Disorders
Program, Clinical Neurological Sciences, Western University, London, ON, Canada
Health information
seeking refers to the purposeful behavior of trying to acquire information on a
particular health-related topic. For those with young-onset Parkinson’s disease
(YOPD), the diagnosis often leads to a number of difficult questions that
require engagement in health information seeking.
Objective: Subjects living with YOPD, for periods
ranging from one to 15 years, were asked to report on their health information
seeking behavior.
Methods: Using grounded theory methodology,
individuals with YOPD participated in at least one of three means of data
collection: multiple interviews, focus groups and/or an online discussion
board. Part of the discussion within each of these methods focused specifically
on the sources of information used to acquire health information, the value of
the information sought, difficulties encountered, and how they perceive that
their information seeking has changed over time.
Results: Based on initial data from 24 individuals
with YOPD (14 male / 10 female), a number of important categories have emerged.
In terms of the types of sources used to acquire information, participants drew
distinctions between personal sources of knowledge (physicians, other
individuals with PD, discussion boards, etc.), extant sources of knowledge
(books, articles on the Internet, etc.) and knowledge gained from one’s own
experience living with YOPD. The value placed on each of these sources varied
greatly and was influenced by a multitude of factors, such as one’s
relationship with their physician, the age of a person with PD, and one’s
expectations for finding answers to health questions. It also appears that over
time information seeking shifts from ‘general’ information about YOPD being
sought immediately after diagnosis, towards more ‘specific’ information being
sought later in the disease; depending on the unique issues confronting an
individual. Understanding health information seeking will help to optimize health
education for persons with YOPD.
P36.15
Self-monitoring in Parkinson’s disease – exploring
traveling over multiple time-zones
Sara Riggare
Karolinska Institutet,
Stockholm, Sweden
Introduction: Function and
wellbeing of people with Parkinson’s are highly dependent on dosage and
consistent timings of medication. Travelling across multiple timezones poses
particular challenges for people with Parkinson’s with respect to medication
timings.
Objective:
Exploring the effects of a changed medication schedule and of
jetlag induced by traveling over multiple timezones on the physical functions
of the author.
Methods: Data were
collected during the first 48 hours of a 10 day trip Stockholm – Chicago,
departing Stockholm at 10.15 am 27/10/2012 and arriving Chicago 12.20 pm the
same day (local times). Normally the time difference is 7 hours but during the
night of 27/28 Oct, the US shifted to daylight savings time, resulting in a
time difference of 6 hours for the remainder of the trip. The author took her
medications less often during the day of travelling to be able to start the
next day synchronised with local time.
Times for medication intakes and other relevant observations were
noted. For evaluating physical function, a 30 second smart phone finger tapping
test was used (iOS app Fast Fingers). Tapping tests are used in clinical
evaluation of medication efficiency in Parkinson’s (Westin, 2010). In all 29 measurements
were recorded with tapping at maximum speed with right and left hand
respectively.
Results and conclusion: Scores
spanned from 69 (right hand)/53 (left hand) to 135 (right)/119 (left) taps per
30 seconds. The 5 highest values for both hands were recorded during the first
24 hours and the 5 lowest during the second 24 hours.
Data
indicate that self-monitoring can be helpful when deciding the best method for
changing medication timings when travelling across multiple time-zones. More
data will be collected when the author travels to WPC in Montreal.
References: Westin, J. (2010). Decision Support for Treatment of Patients with
Advanced Parkinson’s Disease. Uppsala University
P36.16
Expressive writing improves psychosocial functioning of
patients with Parkinson’s disease and their caregivers
Therese Verkerke Cash, Melody N. Mickens, & Sarah K.
Lageman
Virginia Commonwealth
University, Parkinson’s and Movement Disorders Center, Richmond, VA, USA
Objective:
Expressive
writing is a novel psychosocial intervention that may effectively target both non-motor
symptoms (NMS) and caregiver stress in order to enhance quality of life (QOL)
for patients and caregivers coping with Parkinson’s disease (PD).
Methods: A randomized,
controlled trial was conducted at an interdisciplinary movement disorders specialty
clinic to determine the psychological, cognitive, and QOL effects of journaling
for twenty minutes on three occasions about an emotionally stressful topic
(expressive writing) (N=17) compared
to a neutral topic (control writing) (N=12)
among patients with a confirmed PD diagnosis (N=19) and their caregivers (N=10).
Results: Initial results were
analyzed using multivariate analyses of variance to determine the effects of
the different writing exercises on patient NMS and health-related QOL and
caregiver burden from baseline to immediate post-intervention, 4 month follow
up, and 10 month follow up. Trends in the results indicated that patient NMS
and QOL remained relatively stable over time in the overall sample; however,
patients in the expressive writing condition showed reductions in NMS and
improvements in QOL, while patients in the control group showed the opposite
pattern. Caregiver burden was generally alleviated over time, but larger
improvements were observed for caregivers in the expressive writing condition
than for caregivers in the control group. Expressive writing appears to improve
non-motor functioning, QOL, and caregiver stress over time, but neutral writing
does not. Use of expressive writing and other psychosocial interventions may attenuate
the typical symptom progression and increasing caregiver burden of PD and other
movement disorders.
CARE
DELIVERY & QUALITY OF LIFE: PHARMACIST, SOCIAL WORKER & NONPROFIT TEAM
MEMBERS
P37.01
Multidisciplinary
care in professional networks for Parkinson’s disease
Martijn van der Eijk1, Marten Munneke1,
Frouke A.P. Nijhuis1, Jan Koetsenruiter2, Hubertus J. M. Vrijhoef,3,4,
Bastiaan R. Bloem5, Michel Wensing2, Marjan J. Faber2
1Radboud University
Nijmegen Medical Centre; Nijmegen Centre
for Evidence Based Practice; Department of Neurology, Nijmegen, The Netherlands
2Radboud University
Nijmegen Medical Centre, Scientific Institute for Quality of Healthcare (IQ
healthcare), Nijmegen, The Netherlands
3Tilburg School of Social and Behavioral Sciences, Tranzo, Scientific center
for care and welfare, The Netherlands
4Saw Swee Hock School of Public Health, National university of Singapore,
Singapore
5Radboud University
Nijmegen Medical Centre; Donders Center for Brain, Cognition
and Behaviour; Department of Neurology, Nijmegen, The Netherlands
Objective: The ParkinsonNet concept, a national multidisciplinary network of
specialized health professionals, aims to improve the quality of healthcare for
patients with Parkinson’s disease (PD) in the Netherlands. A major challenge is
to optimize multidisciplinary collaboration between health professionals. This
study examined whether the introduction of ParkinsonNet enhances
multidisciplinary collaboration between professionals involved in PD
management.
Methods: A regional ParkinsonNet network
involving 101 health professionals from 10 different disciplines was newly
established. Using a parallel, mixed-methods design, participants received two
surveys (one aimed at documenting network connections; and the other aimed at
evaluating team-effectiveness); these were delivered at baseline (T0) and after
one year (T1). Additionally, thirteen health professionals were interviewed at
T0 and T1. Data analysis focused on collaboration within sub-networks around
three community hospitals.
Results: After one year, the number of professionals that knew
each other and worked together increased significantly compared to baseline (p
<0.001). However, large differences between sub-networks were found,
positive changes being associated with a prominent role of a neurologist and PD
nurse specialist committed to allied health interventions. Team-effectiveness
showed a small but non-significant improvement. Interviewees reported improved
communication lines between health professionals one year after the
establishment of the network. However, participants acknowledged that
interdisciplinary communication and information exchange could be further
improved. For example, professionals were not aware of the other providers
engaged in the healthcare team of individual patients. The introduction of a
regional professional network of professionals specialized in PD made a
connection between healthcare professionals, without having a major impact on
multidisciplinary collaboration. One year after the introduction of the
network, communication and information exchange across traditional echelons and institutions
could still be improved. Neurologists and PD nurse specialists committed to allied
health interventions play a vital role in the delivery of optimal
multidisciplinary care.
LIVING
WITH PARKINSON’S: PUBLIC EDUCATION OR AWARENESS PROGRAMS
P38.01
The chain that bonds not binds – a project in awareness
Philip Beckett
Background: The Parkinson chain is a project intended to
visually represent the links between people around the world whose lives are
affected by Parkinson’s. Every link in the chain – similar to a paper chain –
is signed by an individual. The symbolism of the chain linking people from
around the globe is powerful and its visual impact is an important factor in
generating interest from picture editors and the media as well as individuals.
Aims/ objectives:
·
To
attract attention and provide opportunities for discussion and increased
awareness about Parkinson’s.
·
To
illustrate the significant number of people affected and the geographical
spread of the condition
·
To
collect inspirational, amusing or heartfelt comments of those adding a link.
Method: a chain made from robust material was
constructed. Each link was written on by an individual affected by Parkinson’s,
showing name, home location and comments. As the chain grows in length it
attracts more attention. At events, attendees are encouraged to add to the
chain. The multi-coloured chain contains some 530 links at present and is 66
metres (215 feet) long and growing! It represents people from 23 different
countries. A document is maintained recording the details of each link in the
chain.
The chain is used to
attract attention and to afford the opportunity to gain publicity, so that
awareness about Parkinson’s is enhanced.
A website has been
developed and social media use is planned to broaden the appeal and
accessibility of information about the chain, publish pictures and statistics
and provide links to reliable websites where individuals or media can obtain
information, support and contacts. There is a proposal to provide a blank link
to each individual at the Montreal WPC in their joining packs and an
encouragement to add to the chain. The longer it gets the more impact it will
have!
Outcomes: The chain has been used at events in several
countries, including England, USA, Portugal, Belgium, Scotland and Sweden.
People from many other nations have attended those events and contributed to
the chain. It has attracted attention and appeared on TV and in newspapers and
has helped, in a visual way to increase awareness about Parkinson’s. It will
continue to do so.
P38.02
Implementing get it on time: a Canadian perspective
Jon Collins
Parkinson Society
Canada Central & Northern Ontario, Toronto, ON, Canada
Objective: The recently published Canadian Guidelines
on Parkinson’s disease acknowledges the primacy of medication timing as a
priority for Canadian’s living with Parkinson’s. (per guideline C27[1])
Implementing the Get it on Time program meets the established best practice
standard to ensure improved care for people living with Parkinson’s.
Method: Based on design and text created by Parkinson’s UK, Parkinson
Society Canada launched the Get it on time campaign in English and French to
educate staff and improve the quality of life of people with Parkinson’s. The
Central & Northern Ontario Region is engaged in a large scale dissemination
of this international, collaborative message through a variety of channels,
which we will share in our poster presentation.
Results: Our program has received overwhelming
positive reviews from staff including an average 4.65/5 rating from over 2000
respondents who indicated that the program materials and presentation conveyed
the importance of medication timing and would help them ensure better care of
people living with Parkinson’s. The same evaluations indicated that 96.55% of
respondents indicating that they had made changes in their management as a
result of the program and 100% acknowledging that this led to a higher quality
of life for people living with Parkinson’s. In addition to educational
materials and in-services, we have developed tools to empower people living
with Parkinson’s in their transition from home to the long term care and/or
hospital environment. Resources include an ‘official’ letter written from the
perspective of someone who has Parkinson’s and a hospital preparation kit; both
designed to ensure more positive interactions with health care professionals by
creating prepared, personal advocates out of people living with Parkinson’s and
their loved ones. These materials have been found to be successful by all who
have used them.
P38.03
Making the most of expert practice: The
association of physiotherapists in Parkinson’s disease Europe case study
project
Josefa Domingos,1 Mariella Graziano2,
Diana Jones3, Bhanu Ramaswamy4
1Neurological Clinical
Research Unit, Instituto de Medicina Molecular, Laboratory of
Clinical Pharmacology and Therapeutics, Faculty
of Medicine, University of Lisbon, Lisbon, Portugal
2 Neuro- physiotherapy practice Esch-sur-Alzette
Luxembourg
3Diana Jones, Faculty
of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK
4Independent
Physiotherapy Consultant, Sheffield, UK
Introduction: Physiotherapists
specializing in exercise and health promotion for people with neurological
conditions are ideally placed to enhance quality of life in individuals with Parkinson’s;
Association of Physiotherapists in Parkinson’s Disease Europe (APPDE) is a network of such physiotherapists.
APPDE supports educational initiatives amongst its members – clinicians,
researchers, people with Parkinson’s and carers - and recently
developed a restricted area on its website (www.appde.eu) for members to share
case examples based on clinical evidence (http://www.appde.eu/members/logon.asp).
Objectives: 1. To build a
communication platform for therapists with specific Parkinson’s knowledge.
2. To develop
clinical reporting skills transferrable to the workplace.
3. To accumulate evidence
of similarities and differences in practice for a future APPDE case series
peer-reviewed publication.
Methods: An educational tool - a template, based on the European Physiotherapy Parkinson Disease
Guideline - was created to guide the writing of case studies by members.Topics such as maintenance,
prevention and treatment of motor problems across the lifespan of the condition
were included to enable (differences in) practice to be discussed amongst APPDE
members. Cases will be peer reviewed by the Case study review group (poster
authors); one case will be presented quarterly.
Expected Results: APPDE anticipates two
key outcomes of the project for organization and members:
1.
Improvement in patient care by:
o Providing guidance on recording and reporting
evidenced-based clinical reasoning for individual cases in practice; and
o Sharing evidence-based physiotherapy treatment
options for Parkinson’s.
2. Improvement of scientific and educational activities through:
o
Stimulating debate about potential future clinical
studies; and
o
Generating evidence-based material for clinical
education.
Discussion:
This
project will assist the APPDE in advocating for the application of research to
clinical practice in each clinical encounter and in the full range of settings
and contexts in which physiotherapy is delivered across Europe.
P38.04
Project – What if you had it all
in one setting? An Innovative Parkinson Intensive Multi-Program Rehabilitation
Approach (PIMPRA)
Josefa Domingos, Rita Cardoso,
Joaquim J. Ferreira
Campus Neurológico Sénior,
Laboratory of Clinical Pharmacology and Therapeutics, and Instituto de Medicina
Molecular, Faculty of Medicine, University of Lisbon, Portugal
Background: Parkinson’s
disease (PD) still presents many challenges in its management for both patients
and health care professionals. In this changing era, programs for the treatment
of specific disease, such as Parkinson disease, must be adapted for three
reasons: the global burden of these neurologic diseases is increasing, non
pharmacological intervention programs have a supporting role in developing
health systems, and the health benefits of these programs may go beyond the
prevention of complications. Recent research suggests that intensive
rehabilitation programs can provide both short and long-term benefits to
individuals with PD and their carers. Given the variety of rehabilitation
programs that exist, the true use, safety and combination of these programs is
still unknown in the scientific and clinical community. Which treatment
programs better optimizes motor function? Should we focus on one program or the
combination of such programs when they have complementary objectives?
Objectives: To expand and
enhance care of patients and families through combining and articulating
non-pharmacological treatment options in PD.
Methods: (1)
Application and combination of current disease-specific programs, such as
Parkinson Wellness Recovery Programs®, LSVT LOUD™ and LSVT BIG™ therapy
programs, Ronnie Garden Method®, Dance for PD® and Lisbon Intenisve Fall
Treatment (LIFT) program, applied according to patient functional impairments,
preference, capacities, disease stage and context.
(2) Developing a multi-strategy
research-based intervention model capable to produce efficiently and safely
results with best possible long term benefits.
Discussion: This
innovated multi-strategy model of rehabilitation care for patients with PD may
prove to be a valuable addition to standard rehabilitation programs. We believe
our model will be unique in its integrated approach to PD care. To our
knowledge, there is still no care offered in such a manner or that has shown
the ability to join several existing rehabilitation programs in one setting.
P38.05
Parkinson’s
disease sensitivity training for first responders; the 411 for the 911
Gretchen
Garie-Church, Michael J. Church
Movers & Shakers Inc.USA, Naples, FL, USA
Background: People with
Parkinson’s face a wide variety of health & life issues that will at some
point require the assistance of a first responder; i.e. Paramedics,
firefighters, police, ER staff. This project evolved from speaking with many
people with Parkinson’s who had disastrous results with first responders.
Aim/Objective: To educate all “first
responders” about the special care people with Parkinson’s require. This
special care includes such topics as:
·
Timing of medications
·
Contra-indicated medications
·
Dementia
·
Psychological issues
·
Speech issues
Methods: This program has been
presented several times to a variety of professionals including:
·
Nursing Students
·
County Emergency Responders
·
Leaders within the Parkinson’s Community
Presentation involves:
·
Comprehensive PowerPoint presentation
·
Discussion involving people with Parkinson’s
·
DBS demonstration and DBS discussion that
helped those in attendance understand the complexities of issues
·
Video of a person with PD in a very OFF state
·
Several real life scenarios were included to
help them understand who they may assist
Results:
Attendees:
·
Gained greater understanding of Parkinson’s
·
Understood effective and ineffective
treatments
·
How DBS affects EKG readings
·
How DBS surgery complicates some medical
treatments
A random survey
was sent to participants, the results indicated:
·
A comprehensive understanding of PD and
issues faced by PWP
·
The county is currently working on a
medication change on ambulances that will alleviate a contra-indication for
widely used nausea medications
·
Interaction with people with PD very helpful
·
Greater sensitivity
·
A desire for more information
Discussion/Conclusions: This is
shown to be a powerful tool to further awareness and education of Parkinson’s
disease. We believe that by working with advocates from around the world, the
presentation could be changed to fit the needs of people with Parkinson’s in
other countries.
P38.06
Through Our Eyes Speakers Panel: Health Care Professional
and Educator/Advocates with Parkinson’s are indispensable to, and uniquely
equipped to complement training of health-care professional and educate fellow
PwP’s about Parkinson’s disease
Leonore Gordon1, David Spierer2
1New York University; New York, USA
2Long Island University, Brooklyn, NY, USA
Objective: People with Parkinson’s disease
(PWPs) have unique motor and non-motor symptoms. Specifically, they face
lesser-known cognitive challenges having to do with diminished executive
functions. By educating PWPs, their friends, and families about specifics of
our diminishing “executive functions,” we plan to correct misconceptions and
teach compensatory strategies.
Methods:
1) Educational
Handouts of “Lesser-Known Symptoms” for graduate student “helpers” in Long
Island University Exercise Class.
2) PWP Speakers Panel
serve as guest speakers in graduate programs
·
Long
Island University: PT and Exercise Physiology
·
NYU/
Langone Medical Center: PHd Research
3) PWP’s participate
in Q&A’s hosted by Mark Morris’s “Dance for PD” 3-day trainings for new PD
dance teachers. Training packets include articles written by PWP dance students
4) Presentations of “Empowerment Strategies To Deal with Our
Diminishing Executive Function”s, offered to PD Folks & Caregiver Support
Groups in following venues:
·
JCC/NYU
Langone Sunday Education Series
·
Beth
Israel Medical Center for Dr. Sheree Loftus’ PD Support Group)
Results:
·
Grad
students and their professors rate Speakers Bureau guests as “favorite class.”
·
PhD
research students report a new passion to find a cure for PD.
·
Many
LIU Grad student “EXERCISE CLASS helpers” have gone on to specialize in PD.
·
At
“Empowerment Strategies to Deal with Our Diminishing Executive Function,”
presentations, both PWPs and family members have responded with relief, and
expressed new compassion for symptoms previously seen as stubborn-ness,
laziness, or perplexing incompetence in multi-tasking exhibited by a once
highly-functioning spouse.
P38.07
Pass the baton for Parkinson’s awareness and fundraising
program
Shelby Hayter
Parkinson’s Research
Consortium, Ottawa, ON, Canada
Objective: In 2005, I was diagnosed with Young Onset
Parkinson’s Disease. Using my strengths of being an educator, marathon runner
and public speaker, I created a program for the school system which has been
successfully presented to various schools in the Ottawa Carleton Public School
Board over the past 8 years. The name of the program is; “Pass the Baton for
Parkinson’s.” This program accomplishes two goals; awareness for Parkinson’s
Disease and fundraising for continued research at the University of Ottawa’s
Parkinson Research Consortium.
Methods: The awareness is attained through a
presentation at an elementary school in which a “TEAM” of speakers (a person
with Parkinson’s, a medical professional and a researcher) explain how they
work together towards a common goal of finding a cure for Parkinson ’s disease.
The presentation is upbeat and interactive and each speaker describes their
role on the “TEAM” towards finding a cure before passing a relay-runners baton
to the next team member. The fundraising component is introduced the following
day to the same student audience, who is invited to join the “TEAM”. Donations
are collected as every class in the school is led by a facilitator through a
series of exercises; specifically chosen to reinforce the mobilities affected
by Parkinson ’s disease; strength, flexibility, speed and balance. The
awareness assembly concepts are reinforced while the students run and exercise
and have fun!
Results: The attractiveness
of this program to the School Board is that students learn about a debilitating
disease, take ownership of sharing what they have learned with family members,
and contribute to Parkinson’s research through donations. They are now a part
of the “TEAM”. To date, the program has touched approximately 30,000 students
and raised over $75,000.
P38.08
Training police about
Parkinson’s
Judy Hazlett1,
Roger Buxton1
1Unionville, Ontario, Canada
Objective: Increase the awareness and knowledge about Parkinson’s in police
services to lessen the likelihood that uniformed officers and civilian
employees will mistake the symptoms of someone with Parkinson’s for anti-social
behaviour, some other medical condition, or even criminal activity. Expose
police personnel to the types of predicaments that people with Parkinson’s can
experience, especially when out in public. Provide the police with advice on
how to respond and assist if needed.
Methods: Created a presentation entitled STOP AND ASSIST supported by graphics,
video clips, and live demonstrations illustrating pertinent examples of
Parkinson’s symptoms and circumstances. Broadened the scope to include other
types of disabilities. This was followed by advice on how to assist a person in
public, a discussion of legal and human rights issues, and sources of further
information. Beginning in 2000, this presentation has been given frequently
ever since by a person with Parkinson’s and a companion to classes of officers
and civilians in several police services in Ontario, and most often in Toronto.
Also created a short video of the highlights and printed materials which were
distributed for reference and use by others who were unable to attend the
classes.
Results: Educated thousands of police personnel over the past twelve years.
Feedback reveals that the presentation was well received and was considered
appropriate and valuable. People with Parkinson’s have also reported that they
are pleased with the project because they feel more secure in their communities
knowing that the police are familiar with their situation.
P38.09
Drive Right
Judy Hazlett1,
Roger Buxton1
1Unionville, ON, Canada
Objective: Educate people with Parkinson’s about the consequences of their
condition on their ability to drive from first onset to cessation of driving.
The goal is the ensure the safety of all those on the roads while allowing
people with Parkinson’s to continue to drive for as long as they can do so
safely. Furthermore, when the time comes, they can cease driving with dignity,
having alternative methods of transportation available to retain their
independence.
Method: Created a presentation entitled Drive Right supported by graphics and
video clips containing descriptions and demonstrations of: the physical and
mental requirements of driving; the effects of Parkinson’s and of medications
and their side effects on these requirements; the similarity of Parkinson’s
symptoms to an impaired driver’s condition and how to avoid being incorrectly
charged with a criminal offence; methods of evaluating one’s driving skills;
understanding the costs of driving and of accidents; and choosing alternative
methods of transportation. The presentation has been given by a person with
Parkinson’s, usually in conjunction with a police officer, at conferences for
people with Parkinson’s and to support groups in Ontario. In a modified form,
the presentation has also been given to Drug Recognition Expert police officers
to educate them on the distinction between Parkinson’s and the effects of
prohibited drugs.
Results: Exposed hundreds of people with Parkinson’s and police officers to this
strategy of balancing transportation needs with highway safety. Originally
undertaken in 2000, the lecture has been revised in recent years to account for
changes in understanding, laws, and technologies.
P38.10
My Parkinson’s Story:
Parkinson’s disease research, Education and Clinical Center’s online
educational videos
Susan Heath1,
Jeff Kraakevik, 2
1San Francisco VA
Medical Center, San Francisco, CA, USA
2Portland VA Medical
Center, Portland, Oregon, USA
Objectives: To share online videos
filmed with Parkinson’s disease experts who discuss clinical insight(s) and
management strategies about commonly encountered problems for persons with
limited access to specialty care services. To increase awareness within the
Parkinson’s disease community and non-Movement Disorders specialists about 16
common Parkinson’s disease clinical issues.
Methods: We filmed 16 persons
with Parkinson’s Disease seen in the Veterans Affairs (VA) Medical Centers with
their local Movement Disorders Specialists and team members (nurse, allied
health or rehab team member) discussing how to best manage their clinical
issues. Tips for the management of these issues were highlighted using short
eight-ten minute vignettes. Topics were chosen from a recent unpublished Parkinson’s disease Research Education and
Clinical Center (PADRECC) needs assessment survey of VA primary
care providers. Grant funding was obtained for the series through VA Employee
Educational System. Videos were shot on location at PADRECC sites using PADRECC
staff. Videos are posted online on the VA PADRECC website and on YouTube.
Results: The following
video
titles were posted on February 2013 (# of YouTube views as of 4/15/2013): Early
Parkinson’s disease (1,132 views); Depression (589); Impact of Falls (617);
Memory and Thinking Problems (720); Sleep Problems (808); Deep Brain
Stimulation (715). DVD only subject titles include: Genetics and Environmental
Exposures. Eight additional videos are soon to be published: Medications,
Impulse Control Disorders, Hospitalization Issues, Caregiving, Exercise,
Advanced Parkinson’s Disease, Speech/Swallowing and Driving in Parkinson’s
disease. These videos are an effective and novel way of delivering information
in an online setting.
P38.11
Community rehabilitation for
people with Parkinson's - a social worker's perspective
Deborah Herbert
Parkinson's Disease and Movement
Disorder Society, Mumbai, India
Background: In a
country as socio-culturally varied as India, the Parkinson's Disease and
Movement Disorder Society (PDMDS) had to draw on the very factors which seemed
like obstacles to reach out to people with Parkinson's. The low levels of
education, cultural and religious practices, joint family considerations, lack
of quality medical care made available to the masses and a skewed ratio of
neurologists available for the existing population – 80 neurologists for the 18
million people living in Mumbai, forced the PDMDS to find a solution within the
very problem.
Objective: The
objective of the project was to involve all the stakeholders in the treatment
and community rehabilitation for people with Parkinson's in the city of Mumbai.
Methods: The
process began by getting together a team of medical and allied health workers
to pool in their resources; the result being awareness material about
Parkinson's Disease was translated into local languages, so that people of
different linguistic and cultural backgrounds could be educated. By networking
with non-governmental organisations working with the different communities, we
were able to understand the social and economic difficulties of the people
(isolation of the person within the family or ostracising of the family within
the community, financial burden on the family if the male member has
Parkinson's) and be the link for them to access government services. Therefore,
the PDMDS decided to make its services more accessible to people with
Parkinson's by initiating support centres within the community. From conducting
its first support group in a community hall in 2005 the Society now reaches out
to over 800 patients across 10 centres.
Results: The PDMDS
created a network of support centres by providing free treatment and
rehabilitation to people with Parkinson's in their local community.
P38.12
Tango everyone? A perpetual community program
providing tango lessons to individuals with Parkinson’s disease: A mentorship
program
Jodi
James1, Valerie Carter1, Bailey McMorris1,
1Department of Physical Therapy,
Northern Arizona University
Objective: Participation in ongoing
community programs is critical for the functional success of persons with
Parkinson's disease (PWP). Engaging in regular tango dance classes has been
shown to improve symptoms specific to PD 1,2,3. However, such programs, such as
tango, are difficult to maintain due to the transient nature of teaching
commitments, volunteer availability, and space requirements. The physical
therapy (PT) students at Northern Arizona University (NAU) have solved this
dilemma.
Methods: For the past three
years, NAU PT students have been teaching weekly tango lessons to PWP. The
novelty of this program is it’s legacy, passed down from year to year. Not many
PT students have prior tango or dance teaching experience. To accommodate for
this, our tango program incorporates a lengthy mentoring protocol to assure
that all involved have mastered the skills required to teach. The fall term
begins with 2nd year PT students at the reins. Assistant volunteers are
recruited from the 1st year class. This opportunity gives them exposure to the
program at an introductory, no commitment-required level. As the spring term
begins, 1st year volunteers are again recruited. Those students ready to commit
to learning the dance and teaching the following year are folded into the
weekly schedule. Now the assistants are encouraged to take a more participatory
role, creating warm-up exercises or providing feedback to the dance
participants. At mid-term, the roles reverse. The 2nd year PT students step
back and assume the role of assistants and the 1st year students assume
leadership, under the guidance and insight from the more senior class.
Results: Tango for
Parkinson's attracts approximately 5-6 regular participants with new dancers
joining every semester. The continued success of this program relies on the
strength of its instruction, its creative outlet, enthusiastic volunteerism and
the sense of community it builds.
P38.13
Parkinson education program for community caregivers:
maximizing outreach to health Care Professionals
Tracey Jones
Parkinson Society
Southwestern Ontario, London, ON, Canada
Objective: The Parkinson Education Program (PEP) for
Community Caregivers was developed by Parkinson Society Southwestern Ontario as
a profound need for information and support was identified by both health care
professionals and families caring for people with advanced Parkinson’s.
Launched in 2007, PEP for Community Caregivers has been sustainable through the
engagement of volunteer health care professionals in a train the trainer model.
Community caregivers have embraced this unique form of education and
training. The tremendous success of this
educational program has directly impacted other areas of our mission including
increases in our support services.
PEP for Community
Caregivers supports:
• helping people with
advanced Parkinson’s to remain in their homes longer;
• reducing the number
and duration of hospital stays;
• people with advanced
Parkinson’s to enjoy increased dignity and a better quality of life whether at home,
in the hospital or in long-term care; and
• Community Caregivers
to feel better equipped with knowledge that will help ease the burden of both
the person with advanced Parkinson’s and themselves.
Methods: The unique train the trainer aspect of PEP for Community Caregivers maximizes
the number of local Parkinson’s experts through recruitment of qualified health
care professional volunteers to increase our outreach and ensure that the best
possible information about Parkinson’s is provided. The program consists of two
parts: a resource manual for Community Caregivers and ten interactive
In-service training presentations. An online discussion forum for heath care
professionals has additionally been created to compliment this program.
Results: The poster presentation will provide
statistics on the number of health care professional volunteer trainers engaged
for this program as well as the number of community caregivers trained across
the region. Additional qualitative measurements including changes in best
practices, and testimonials that show clear improvements in quality of care
will be shared as well.
P38.14
Speaking with a unified voice: National Parkinson
Foundation Minnesota’s Medical Team Advisory Board
Martha A. Nance1, Jason Aldred2,
Linda Anderson3, Gwen Cressman3, Joan Gardner1,
Mary Griffith4, Laura Guse5, Tanya Harlow5,
Bryan Klassen6, Scott Lewis7, Laura Li4, Jon
McIver8, Tsega Orcutt9, Maren Sharland3, Ann
St Jacque7, Steven Stein10, Kari Tonsager10,
Paul Tuite9, David Tullar8, Okeanis Vaou11,
Julie Steen12
1Struthers Parkinson’s
Center, Golden Valley, MN, USA
2Gundersen Lutheran,
Lacrosse, WI, USA
3Essentia Health,
Duluth, MN, USA
4Capistrant Parkinson’s
Center, St. Paul, MN, USA
5Sanford Health, Fargo,
ND, USA
6Mayo Clinic,
Rochester, MN, USA
7Minneapolis VA Medical
Center, Minneapolis, MN, USA
8Health Partners, St.
Paul, MN, USA
9University of
Minnesota, Minneapolis, MN, USA
10Minneapolis Clinic of
Neurology, Edina, MN, USa
11Noran Clinic,
Minneapolis, MN, USA
12National Parkinson Foundation
Minnesota, USA
Objective: In 2012, National
Parkinson Foundation Minnesota created a Medical Team Advisory Board, with the
goals of 1) bringing together physicians with Parkinson’s expertise from
multiple neurology practice groups around Minnesota, 2) bringing together
allied health professionals (nurses, social workers, rehab therapists) who are
part of the Parkinson’s teams in those practice groups, in order to 3) address
issues of common interest.
Methods: The team meets
quarterly, with telephone/internet conferencing available for those who are
unable to attend in person, with communication by email between meetings.
The group has
identified several issues of common interest and concern: 1) the lack of
levodopa products on the first tier of a major insurer’s formulary; 2)
hospitalization in PD patients; 3) the diagnosis and management of very early
PD; and 4) the possibility of creating templates for annual PD visits that meet
American Academy of Neurology guidelines. A number of other areas have also
been discussed.
Results: An action plan for the
first two issues was created and is underway. 1. All members of the group
jointly signed a letter to health plan leaders regarding the formulary issue.
Further work has identified other health plans that lack a levodopa product on
the first tier. 2. Members of the group were familiarized with the National
Parkinson Foundation’s Aware in Care kits about hospitalization in PD, and
agreed to give presentations in their local hospitals or clinics on this topic.
This novel approach to identifying and addressing issues common to PD
subspecialty practices within a region has the potential to improve care
throughout the region, as well as strengthening interactions among programs at
both the physician and the allied health levels.
P38.15
The European Parkinson’s disease standards of care
consensus statement
Knut-Johan Onarheim1, Susanna Lindvall1,
Lizzie Graham1
1European Parkinson's Disease Association (EPDA), London, UK
Objective: To provide guidelines for policy makers on how people
with Parkinson’s (PwPs) should be managed to ensure their effective
participation within society and areas that need to be focussed on to realise
this.
Methods: The European Parkinson’s Disease Standards of
Care Consensus Statement combines evidence of the European emotional and
economic cost (€13.9 billion annually) of 1.2 million European PwPs,
reinforcing that prevalence is forecast to double by 2030. It was developed,
reviewed and endorsed by a number of European key Parkinson’s opinion
leaders as well as representatives of the multidisciplinary team, PwPs, carers
and 45 patient organisations. All worked with the EPDA over a period of
twelve months to try to define and standardise the care, treatment and
management of the disease that will improve the quality of life of PwPs. This
consultation resulted in an 8-point plan that European policymakers need to do:
1. Support initiatives that ensure equal access to good quality, specialised
Parkinson’s care across Europe; 2. Reduce inequalities in the treatment and
management of Parkinson’s; 3. Improve funding for Parkinson’s research and
define research priorities; 4. Invest in optimum treatment and maintenance strategies;
5. Increase public and professional awareness of Parkinson’s; 6. Minimise
stigma and discrimination; 7. Strengthen the level of neurological care within
European healthcare systems; 8. Provide adequate funding that supports the
continued work of national Parkinson’s organisations.
Results: It is the
first document of its kind to support and encourage the drive for equality and
optimisation of Parkinson’s management at both a European and national level.
Following its launch (November 2011) in the European Parliament, Brussels it
has been translated into a number of European languages; has been read,
supported and endorsed by a number of European policymakers, with over 50
Member of European Parliament (MEPs) joining the EPDA’s MEP Parkinson’s support
group.
P38.16
Move for change part I
– A pan-European survey evaluating impact of EPDA charter for PwP on disease
management and QoL
Knut-Johan Onarheim1, Susanna Lindvall1,
Lizzie Graham1
1European Parkinson's Disease Association (EPDA), London, UK
Objective: To evaluate what difference the Charter for people with Parkinson’s
(launched in 1997) has made to present-day healthcare services throughout
Europe.
Methods: the EPDA is conducting the Move for Change campaign which is a three-year,
three part pan-European on-line survey (translated in 24 European languages,
across 36 countries) that asks people with Parkinson’s (PwPs) whether their
lives have improved since the launch of the 1997 EPDA Charter for PwPs that
outlines their rights in terms of standards of care. It states that all people
with Parkinson’s have the right to: be referred to a doctor with a special
interest in Parkinson’s; receive an accurate diagnosis; have access to support
services; receive continuous care; and take part in managing their illness. The
first survey (23 questions) focused on the Charter’s two initial points (see
above) and of the 2149 forms completed, 2068 (96.2%) were analyzed.
Results: The
majority of PwP who completed the survey were diagnosed within 2 years from the
onset of their first symptoms (82.7%; range 1 year to >5 years). 45.3%
stated that the diagnosis delivery was ‘poor’ or ‘very poor’ with 43.8%
reporting that during the 2 years following diagnosis they had never seen a
Parkinson’s disease specialist with their treatment being overseen by
generically active neurologists (92.5%) or family doctors (81.0%), with
considerable overlap between the two. The findings highlight the challenges
that PwP continue to face during the diagnosis period, despite the introduction
of the Charter and provides the evidence that can help healthcare professionals
and policy makers to improve PwPs management and their families across Europe.
P38.17
Move for change part
II – A pan-European survey evaluating impact of EPDA charter for PwP on disease
management and QoL
Knut-Johan Onarheim1, Susanna Lindvall1,
Lizzie Graham1
1European Parkinson's Disease Association (EPDA), London, UK
Objective: To
evaluate what difference the Charter for people with Parkinson’s (launched in
1997) has made to present-day healthcare services throughout Europe.
Methods: The
EPDA is conducting the Move for Change campaign which is a three-year, three
part pan-European on-line survey (translated in 24 European languages, across
36 countries) that asks people with Parkinson’s (PwPs) whether their lives have
improved since the launch of the 1997 EPDA Charter for PwPs that outlines their
rights in terms of standards of care. It states that all people with
Parkinson’s have the right to: be referred to a doctor with a special interest
in Parkinson’s; receive an accurate diagnosis; have access to support services;
receive continuous care; and take part in managing their illness. The second
survey (9 questions) focused on the third right of the Charter (all PwPs have
the right to have access to support services’). The definition for
accessibility of support services was services
/medication/multidisciplinary health care professions etc., being available and
on hand to manage PwP when required.
Results: Neurologists and General Practitioners (GPs) received highest
accessibility results (90.0 and 87.0% respectively) with moderate results for
physiotherapists (68.0%) and patient organisations (72.0%), Parkinson’s disease
nurse specialists (26.0%), occupational therapists (23.0%) and counsellors
(27.0%). The support provided by neurologists (59.0%) and Parkinson’s disease
Specialists (55.7%) was considered to be ‘very helpful’ whilst (31.8%) of GPs
were considered the same. Across Europe, the funding of services was variable. This data
demonstrates the challenges faced by PwPs in accessing the adequate management
and support they require throughout the course of their Parkinson’s journey and
provides the evidence that can help healthcare professionals and policy makers
to improve PwPs and their families level of access to support across Europe.
P38.18
Two centers are better than one: joining
forces to build capacity and provide robust services for the Parkinson’s
community
Lynn Klanchar, RN, MS1, Andrea
Perseghin, MEd2
1 Parkinson’s Disease
Research Education and Clinical Center, McGuire Veteran’s Affairs Medical
Center, Richmond, VA, USA
2 Parkinson’s and
Movement Disorders Center, Virginia
Commonwealth University Richmond, VA, USA
Background: In 2001, the
Department of Veterans Affairs allocated funding to establish six centers of
excellence for American military Veterans affected by Parkinson’s Disease (PD).
McGuire Veteran’s
Affairs Medical Center (VAMC) in
Richmond, Virginia was designated as a Parkinson’s Disease Research, Education,
and Clinical Center (PADRECC). From 2002 through 2009, PADRECC was the only
comprehensive PD center in Richmond, with services limited to Veterans. In 2005, members of the Richmond community
launched a fundraising and advocacy campaign to establish a comprehensive
center for non-veterans. In 2010, the Virginia Commonwealth University (VCU)
Parkinson’s and Movement Disorder Center was established to combine research,
clinical care, and education in a coordinated approach to combat PD.
Objective: To
demonstrate how the two centers partner to plan programs, and leverage resources
to expand community outreach, enriching the quality and number of education and
awareness events in Richmond and across Virginia.
Methods: Tracking data
was collated and analyzed for lay community and professional education
events produced by the centers from inception through 2013.
Results: Services for
those impacted by PD in Virginia have increased exponentially with the creation
of the PADRECC in 2001, and nearly doubled with the
formation of the VCU center in 2010. Partnering allowed the centers to
produce an additional 26 programs for the community, reaching over 2,800
attendees. Through collaboration, the centers are able to capitalize on shared
resources, additional subject matter experts, collective creativity, and
identify gaps in services to best address the needs of the community.
P38.19
The
social movement: building the More Than Motion™ Facebook community for people
living with Parkinson’s disease
Zarya
Alexandra Rubin1, Andrea Levin1
1UCB, Inc, Smyrna, GA, USA
Objective: The non-motor
symptoms (NMS) of Parkinson’s disease (PD) can be challenging for healthcare
providers, people living with PD (PLWP), and caregivers to recognize1.
Our aim was to: provide an educational social media community built around the
concept that PD is more than a movement disorder; allow PLWP and caregivers to
connect with each other and receive helpful information; inspire the community
to share their own stories, learn from others, and get involved in PD advocacy.
Methods: We developed a
program, called Parkinson’s More than Motion™, to educate PLWP and caregivers
about the broad impact of Parkinson’s disease. Parkinson’s More than Motion™ is
a multi-media resource designed to inform this audience via: Facebook, a
reality video series, a Parkinson’s Well-being Map™, a magazine, and advocacy
events. We launched the program for U.S. PLWP in April 2012.
Results: After one year in
the public domain (April 2012-April 2013), Parkinson’s More than Motion™ has
reached a significant number of U.S. PLWP:
• 42,937
“likes” on Facebook (as of April 5, 2013)
• 1,000+
people “talking about” our content by commenting on it, liking it, or sharing
it
• 7,000+
Facebook users reached per week
• 1,000+
magazine subscriptions
• Exhibited
at neurology and PD events
• Shared
information from PD advocacy groups
Conclusion: Increased awareness
of NMS is needed among healthcare providers, PLWP, and their caregivers. PLWP
and caregivers are impacted by NMS and respond well to multi-dimensional education
programs. The increasing popularity of social media among older adults makes
sites like Facebook an ideal setting for creating an educational support
community.
P38.20
Parkinson's Movement: Operationalisation and
evaluation of the web-based presence (2011-2013)
Jon Stamford1, Sara Riggare1,2,
Tom Isaacs1
1Parkinson’s Movement, The Aldgate
Rooms, St Botolph's, Aldgate, London, UK
2Karolinska Institute, Stockholm, Sweden
Introduction: Parkinson's Movement
(PM), outlined in principle at the 2010 WPC in Glasgow [1], was predicated on
the view that, of all involved with Parkinson's, the insights of people with
Parkinson's were particularly pertinent. The intention was to create a hub
combining "the best aspects of the fora, integrated into a vehicle for
information gathering, dissemination and lobbying". Here we review
progress with the web presence of PM since WPC 2010.
Methods: The web presence of PM comprises the
central website (parkinsonsmovement.com: PMC), a forum/polling website
(parkinsonsmovement.healthunlocked.com: PMHU) and associated social media.
Google analytics data harvested on 7 April 2013were supplemented where
necessary by internal data from PM, Survey Monkey and social media.
Results: Since 8 August 2011, PM has conducted
72 polls, interviewed 14 neurologists on film, broadcast 5 webinars, appointed
24 ambassadors, attended 6 scientific conferences, submitted 10 abstracts on
polls to meetings, and conducted 2 pilot research studies. In 20 months, PMC
has had 21,491 unique visitors and 79,983 page views from 4389 towns/cities in
141 countries. Peak daily visits (424) occurred on 14 April 2012. data extend
from 30 November 2011 with data loss (24-29 May 2012) for site maintenance.
During the logged period, PMHU had 86,049 visitors and 734,182 page views from
7585 towns in 168 countries. Peak daily visits (644) occurred on 13 January
2013. PM's Youtube channel had 8593 views, 2638 from the US since inception (17
November 2011). PM has 684 Facebook 'likes'.
Conclusion: following an initial surge, PM
statistics suggest consolidation of interest in the organisation. PM has
exceeded all anticipated metrics and, following ambassador consultation,
anticipates greater focus on key patient driven deliverables in 2013 and 2014.
P38.21
www.discoverMI.org – Helping patients with
Parkinson’s disease get a clear view of modern molecular imaging technology
Frederick Woodlief
Member,
SNMMI’s Patient Advocacy Advisory Board, USA
Background: The Society of
Nuclear Medicine and Molecular Imaging (SNMMI), with
over 50
years history and representing 19,000 professionals worldwide, supports a
mission
“to improve
human health by advancing molecular imaging and therapy”. SNMMI created a
Patient Advocacy Advisory Board (PAAB) whose members “help insure patients’
concerns, ideas, experiences and recommendations are reflected in the Society’s
endeavors”. With PAAB input, SNMMI developed the
discoverMI.org
website as a public resource for patients seeking information on diseases using
molecular imaging. Parkinson’s Disease is a progressive, neurodegenerative
disease involving movement disorders as well as extensive life style issues. It
affects approximately 1 million people in the United States and an estimated 5
million worldwide. With advances in technology in the past several decades and
the development of radiotracers to assist in brain imaging, more physicians and
researchers are referring their People with Parkinson’s (PWP) for advanced
molecular imaging. CT and MRI imaging allows a view of the structure of the
brain. Newer PET and SPECT scans allow for the visualization of brain function
and a measure of its chemical processes, which can lead to detecting the early
onset of neurological disorders. Neuroimaging also provides for the study of
brain circuitry or neurotransmission.
Objective: “Healing begins with
seeing precisely” The objective is to provide a comprehensive and user-friendly
website where the public can interact to get reliable information about
molecular imaging and therapy in the areas of brain disorders, heart disease,
cancer, and radiation safety. This can be especially helpful to the Parkinson’s
patient.
Discussion: This award winning
website was launched in 2011 with its 2nd edition to be released in
June, 2013.
LIVING WITH PARKINSON’S: GOVERNMENT ADVOCACY/
CAMPAIGNS/ PUBLIC POLICY
P39.01
Experiencing Parkinson´s Disease and dealing with the
health system in Colombia: the point of view of an informed patient
Víctor Hugo Alarcón Gómez1, Janeth Mosquera Becerra2,Yoseth
Ariza Araújo3
1Physician and Informed patient, Cali, Colombia
2Universidad del Valle, Cali, Colombia
3Univesidad ICESI, Cali, Colombia
Objectives: To describe a personal experience as an
informed patient dealing with the Colombia Health Care System.
Methods: It is a case report from an informed patient
living with PD. Using literature review and my own experience. To analyze
clinical registry, I selected two categories: administrative processes to get
health care (i.e. medications, surgery, and therapies) and relationship with my
colleagues (i.e. neurologists, neurosurgeons, and general practitioners
Results: I have identified barriers and facilitators
related to context, processes and actors to get health care services. In
Colombia both medications and the bilateral subthalamic nucleus stimulation are
not part of the obligatory plan of health services, so patients must face an
exhausting legal (i.e. tutela) and different administrative process (i.e.
surgical boards) in order to get them. My experience show that: a. Even though
I wanted discuss with doctors about causation, all of them showed any interest
in causation inquiry in PD; b. Doctors just know about their specialty and in
the Colombian Health System there are not teams to treat patients integrally
which is essential among people with PD; c. Doctors focus on treatments of
motor symptoms which is a consequence of available treatments and medical
training in Colombia; and d. I was able to deal with surgical boards (ex. using
technical jargon) and legal processes because I know very well my health
condition, the latest scientific evidence related to PD, and the Colombian
Health System. Doctors have limited options to attend PD, for example levodopa
remains as the gold standard treatment, access to neurostimulation is
difficult, and treatments focus on motor symptoms. Moreover, strategies to cost
containment, using legal and administrative mechanisms, do not allow offering
integrated services to PD patients. Finally, medical training is still
fragmentary which is reproduced within health care process, affecting the
quality of life of Parkisonian patients.
P39.02
The effect of Medicare Part D on Parkinson’s disease
patients: a four year retrospective study
ElizaBeth Grubb1, Michel F. Denarié,2
1Teva, Kansas City, MO,
USA
2IMS Health, Plymouth Meeting, PA, USA
Objective: Compare behavior of
Parkinson’s Disease (PD) Medicare patients reaching coverage gap (CG) and out of
pocket (OOP) expenditures over 4 years, from 2008 through 2011. Assess changes
in medication usage and spending patterns during and after implementation of
Affordable Care Act which provided a 50% reduction in patient burden for
Medicare Part D CG beginning in 2011.
Methods: 4 year retrospective
study using the IMS Longitudinal prescription database, LRx and Plantrak
managed care data. Patients were evaluated on medication usage and spending
patterns before, during and after the CG by payer type.
Results: Percentage
of patients reaching coverage gap diminished from 51% in 2008 to 39% in 2011.
Proportion of CG patients who reached catastrophic coverage (CC) slightly
increased from 26% to 29%. The percentage of patients who remained in the gap
was relatively stable (74% in 2008 and 71% in 2011). The average time spent in
the gap remained at 4.8 months. The percentage of patients who stayed on
therapy remained high and increased from 77% in 2008 to 81% in 2011.
Out-of-pocket (OOP) cost of drugs was reduced by half in 2011, we only observed
an increase of 1% in the proportion of patients who remained on therapy. The
percentage of patient who reduced therapy went from 2% to 1% over the same
period. The proportion of patients who stopped therapy declined from 12% in
2008 to 10% in 2011. Whereas the percentage of PD Medicare Part D patients
reaching the CG diminished between 2008 and 2011, mean OOP costs for PD
medications declined but compliance to PD medication remained unchanged.
P39.03
The growth, accomplishments
and challenges of the international Parkinson advocacy movement: social
history, literature review and call to action
Katherine Huseman1, Girija Muralidhar1,
Peggy Willocks1, Perry Cohen1, Linda Herman1,
Linda Ashford2, Pamela Kell1, May Griebel1
1
Parkinsons
Creative Collective (PCC), USA
2 Parkinsons Creative
Collective, (PCC) UK
Objective: to demonstrate the
positive effect Parkinson advocacy has had in the global PD community and to
illustrate some of the projects including those using internet tools for
self-care, participating in research and encouraging reforms in areas of
concern to those with PD.
Methods: survey Parkinson
disease history; identify significant issues; record actions of people with
Parkinson disease (PwP) and include historical materials such as interviews and
literature reviews. At key turning points in the history of Parkinson advocacy,
we will show what was involved and how people participated on many levels.
Examples will illustrate issues such as: using new technology, educating the
whole PD community and encouraging new thinking to cure PD. From the collected,
factual material plus contemporaneous and later commentary, we will summarize
PD advocacy and develop a timeline of significant events.
Results: This work will educate
and increase public awareness of many significant issues and accomplishments in
PD advocacy. It will encourage individuals to become active participatory
patients and join others working to improve PD care and contribute to finding a
cure for PD.
P39.04
Policy Advocacy on Parkinson's Diseases in Nepal
Shrestha, Hom L.
Non-Smokers' Rights
Association of Nepal
Objective: To create environment and
system for policy, legal and media advocacy on Parkinson's Diseases (PD) in
Nepal; and to design conceptual framework, national policy and legal framework
for the diagnosis, treatment and rehabilitation for the PD patients through
policy reform, formation of Parkinson's Diseases Society of Nepal, tripartite
partnership and collaboration among government, NGOs and donors or
international charitable institutions, etc.
Methods: A few
available patient data from neurology departments of some hospitals and National Neurology Hospital;
scientific articles published in the Lancet, Neurology, Journal of the Royal
Society of Medicine, Neuroepidemiology, Indian J. Psychiatry, etc., national health policy and second long term health
plan and stories of young lady PD patient and 88 years old women patient,
have rigorously been reviewed.
Results: The concept and idea of PD is new in Nepal. There is no such practice to neither question about symptoms of Parkinson's diseases among neurology patients nor diagnose even doing MRI test. MRI test is so expensive to look for signs of a stroke and brain tumor in Nepal but not examine PD due to lack of guidelines, protocol and training for the diagnosis of PD by neurology professionals. Also, there is no such policy and facilities even for geriatric health care in hospitals of Nepal, the health care policy should be reformed to address geriatric health care including dementia, Alzheimer's and Parkinson's disease treatment and rehabilitation facilities in particular. The PD lady patient 20 years and 88-years old women both are survived by regular physical exercise without physiotherapy to maintain and improve mobility, flexibility, strengthen and gait speed and quality of life from support of family. The further policy-relevant research and advocacy should be undertaken to create public and media education and awareness among health care professionals, media and family as global health issue.
LIVING
WITH PARKINSON’S: LIVING WELL WITH PD
P40.01
A smart phone-based application for
medication compliance and user motivation in Parkinson's disease
Caspar
Addyman1, Bruce Hellman2, Jon Stamford3
1Birkbeck College, University of London
2uMotif Ltd, London, UK
3The Cure Parkinson's Trust, UK
Introduction: There is much
current interest in patient empowerment and personal engagement.
Methods: A 6 week, randomised, double blind
trial compared two versions of an app - a minimal version (MIN), with the
uMotif 10-petal tracker and a FULL version including medicine reminders and
cognitive games. Pre and post trial surveys included two widely used Parkinson’s
questionnaires (PDQ-39 & Non Motor Symptoms survey), the Oxford Happiness
Inventory, the Quality of Life Scale a medicines management questionnaire and
several freeform responses about the app and the trial.
Results: 26 patients joined the trial. Participants
provided very positive feedback on the ease of use of the software and value of
symptom tracking. , Unfortunately, the small numbers of users that completed
the study (10 MIN, 6 FULL) obviated statistically significant differences but
FULL users saw Parkinson’s symptoms slightly improve and happiness increase.
If anything the opposite was true for MIN. Trial participants used the app for
55 days (mean), and entered data on at least 70% of days. Comparing the first
and last 5 days, there were statistically significant increases in ratings of Energy,
Water & Exercise (all Ps<0.05) and marginal improvement in
the Meds rating (0.15). There were no significant changes in any of the
Parkinson symptoms (Bradykinesia, Suppleness, Dyskinesia
& Tremor). There was marginal improvement in Sleep rating
(p<0.07) which was strongest in the FULL condition. Similarly, Mood
improved for users in the FULL but not for MIN condition (P<0.08).
Conclusion: The tracker was used
regularly by participants and gave some significant positive results that were
not picked up by more traditional questionnaires, demonstrating the value of
the uMotif tracker for research and as a monitoring tool. The positive feedback
from the participants and the overall positive trends from this limited sample
suggest that a follow up study is warranted.
P40.02
Managing
Parkinson’s disease symptoms while hospitalized for non-PD related conditions.
John Ball
Team Parkinson, Whittier, CA, USA
Objective:
Management of Parkinson’s symptoms to minimize impact of treatment of unrelated
conditions on PD, to shorten hospital stays, and to improve treatment outcomes.
Methods: The
treatment--as well as the stress—of many conditions that require
hospitalization, such as infectious disease, respiratory ailments, or trauma,
can interfere with the efficacy of treatments for PD and cause a temporary
worsening of PD symptoms. Self-identified Parkinson’s patients who require
admission to the infectious disease or respiratory ward, or the trauma center of
a hospital will typically have a neurologist assigned to their care, and will
not be under the care of their usual Movement Disorders Specialist. Thus it is
essential for patients and care-partners to advocate for self-management of
their PD symptoms since it is unlikely that hospital staff assigned will have
the level of PD management expertise required to manage individual patient
needs. A pre-hospitalization admission agreement to allow PD patients and
care-partners to manage PD medications, both dosage and timing, is a dramatic
step towards gaining positive control. I will present tools to prepare a PD
patient for a hospital stay from both patient and physician (neurologist/MDS)
points of view.
Results: With the
proper education, preparation and tools, the PD patient and care-partner can
negotiate for self-management of both timing and dosage of PD medications prior
to entry into the hospital, thus reducing the potential for misunderstanding,
mistreatment and medication conflicts. This will additionally minimize stress
and enhance the quality of life during the recovery process while enduring
hospitalization.
P40.03
Effect of organized physical activity on the
quality of life of people living with Parkinsons
B. Garrison Ballenger, Jr.
Parkinsons Disease Foundation, New York, NY,
USA
Objective: This is a patient driven study. The
objective of this project is to demonstrate whether or not participation in
organized physical activity improves the quality of life of People with
Parkinsons.
Methods: At least 25 Participants in organized
physical activities such as Group Exercise Classes at the YMCA, Chair Yoga at
the YMCA and Dance for PD by the NC Dance Theater will be asked to complete one
of the quality of life measurement tools such as PDQL, PDQ-39 and PDQUALIF. The
results will be compared to the application of the same measurement tools as
reported in existing published research over age of onset, years since
diagnosis and the age and sex of participants. The results will be tabulated
analyzed and reported.
Results: Results will be reported.
Discussion: Anecdotal evidence obtained through
informal discussions with participants, caregivers and leaders of physical
activities of all types support the conclusion that engaging in group
activities improves quality of life for people with Parkinsons.
Topic: Living well with
Parkinsons
P40.04
Shou … shou … bang: moving more quickly through the
stages of the emotional rollercoaster in order to embrace your Parkinson’s disease
on solid ground
John Baumann
Faculty, University of
Louisville, KY, USA
Objective: To enlighten and empower Parkinson’s
patients as to the significant influence that each of us has over the quality
of our own life.
Methods: I identified the emotional issues or phases
that typically result from a Parkinson’s diagnosis (shock, disbelief, denial,
anger, difficulty disclosing to others, social awkwardness, isolation and
depression) and determined what can be done to eliminate, or, at least move
through, these difficult and undesirable emotional phases more quickly. I
identified what could be done to accept and embrace life with Parkinson’s,
including what I could do to reverse, if not, slow the progression.
Results: I concluded that there
are action steps that can be followed to be more successful. I then applied
these steps to my life with Parkinson’s. I conducted an assessment of what I
could still do. I envisioned myself with the highest quality of life possible
doing what I was still able to do. On a daily basis, I reminded myself to live
in the moment; to continually update my “bucket list” and experience each item;
to keep a positive attitude; to have faith in myself; to eat healthy, organic
food; to exercise daily, gradually moving every day further out of my comfort
zone; to perform activities that keep me mentally sharp; to discover and
rediscover my life’s purpose (currently as an inspirational speaker and author:
Decide Success – You Ain’t Dead Yet);
to be more loving, kind and compassionate; and to accept, and even embrace,
Parkinson’s by finding meaning (silver linings) in the disease. The ultimate
result of enacting this plan is that I am healthier now, over ten years into my
Parkinson’s, than I ever was before I started exhibiting symptoms of
Parkinson’s. My conclusion is that anyone with Parkinson’s can take steps to
improve the quality of their life.
P40.05
Parkinson’s
disease + music therapy = higher quality of life
Concepcion
Bentz
Asociacion Catalana para el Parkinson, Barcelona, Spain
Objective: To show the importance and effectiveness of music
therapy in the treatment of Parkinson’s disease.
Methods: Music therapy is very effective in the treatment of a
wide variety of disorders. By itself, music triggers a stimulating process
which benefits various areas of the brain. The author’s own musical oeuvre
(intended especially for Parkinson’s disease patients) on which her specific
treatment is based, was composed in such a way that its rhythmic and melodic
patterns facilitate and promote the motion and mobility of these patients.
In patients treated with the RAS and PSE methods, 50%
of those in stages 1 and 2 have experienced a great improvement in their
unilateral and bilateral symptoms.
Regarding speech loss, hypophonesis and slow speech
disorders, the best results have been obtained by means of MIT, VIT and RSC
therapies. Three of the author’s musical compositions have been very effective
when applying CPMT and ISO principle techniques, obtaining an improvement in
100% of patients. With the RAS technique and two of the author’s compositions,
very positive results have been obtained when treating walking disorders. By
means of the TIMP technique, tremor at rest can be eliminated and movement and
coordination can be controlled. With two of the author’s compositions, along
with the use of the musical travel technique, micrographia improves
substantially.
In order to treat facies amimica, the face and body movement
therapy has been used, with the aid of one the author’s compositions.
Results: From the author’s practical experience and
observations, the above conclusions can be drawn regarding the motor,
psychological and cognitive benefits of this music therapy treatment, as well
as regarding the patients’ evolution, progress and improvement in their quality
of life.
P40.06
Accessibility to
Parkinson’s specific exercise
Madonna Brady
Background: Research shows the right kind of exercise can slow the progression of
symptoms of Parkinson’s disease. There is a lack of accessible exercise based
initiatives for people with Young Onset Parkinson’s Disease in Brisbane. The
level of awareness of Young Onset Parkinson’s disease (YOPD) in general medical
practitioners is delaying prompt diagnosis and early intervention
possibilities.
Aims and objectives: Become an advocate for people with YOPD, lobbying the Government,
health professionals and fitness centres to facilitate affordable accessible
Parkinson specific weekly exercise classes. Free gym use to maintain fitness
and agility, thus promoting social interaction and boosting quality of life for
all people with Parkinson’s (PwP) is the ultimate goal.
Methods: Early commencement of Parkinson’s specific exercise enables PwP to take
charge on a personal practical level.
·
Lobbying Government
and organisations for funding enabling PwP to free use of gym facilities.
·
Working with
Parkinson’s Queensland Inc. to recognise the needs of people with YOPD.
·
Encouraging mandatory
referrals to allied health professionals on diagnosis of Parkinson’s for
assessment, leading to individual exercise programs. At this stage, exercise
can be managed independently; meeting for weekly classes would be beneficial
and encourage social interaction.
·
Embracing PwP and
their families with a combination of informative, social and recreational
initiatives.
·
Review progress with
Physiotherapist regularly to assess and adjust.
Results and benefits:
·
Improved balance,
agility and capability, thus preventing falls.
·
Increased fitness
levels and confidence.
·
Maintain PwP’s
working potential, increased social interaction helps preserve self-esteem.
The poster will cover the following:
·
Author’s personal
experience of benefits.
·
Author’s photos at
the beginning of regular Parkinson’s specific exercise and after.
·
A description of
exercises.
Anecdotal evidence from people with Parkinson’s
P40.07
My
Blessing - Living With Parkinson’s
Mark
F. Burek
Objective: To instill hope in the lives of people with Parkinson’s
through personal experience.
Methods: I have lived with Parkinson’s for over six years and I am an
active advocate in the fight against Parkinson’s. I refuse to live my life for
however long God sees fit without being a part of the effort in finding a cure.
Like many, when I was first diagnosed I felt as though I was diagnosed with a
disease which in fact is true. However, what was once initially thought of as a
disease has turned into a blessing. The reason I use the word blessing is
because through my diagnosis I found my purpose in life. To be part of a group
of people called advocates. In short extraordinary people doing extraordinary
things in their search for a cure. So many people go through life wondering
what if or what could have been. Never experiencing the awakening of the inner
self, Pondering days gone by, never to be retrieved. Doors remain closed and
behind those doors are opportunities unchallenged. When we accept life’s
challenge no matter how difficult they may appear, we choose to travel a road
seldom traveled but filled with blessings. Blessings full of friends we would
have never found on any other road. The choice is up to us. Travel the road or
remain at life’s intersection.
P40.08
Don’t run and hide from stage 4 and 5! Optimizing
function and quality of life for persons with late stage Parkinson’s disease
Valerie Carter1
Karen Mueller1
Northern Arizona
University Flagstaff, USA
Objective: Persons with
Parkinson (PWP) disease who are in the later stages are often treated as if
they are not capable of making improvements. For example, when PWP who are in
later stages of the disease stop walking due to illness or injury, it is common
for them to not be referred to rehabilitation allowing the negative squeal of
immobility ensue. PWP who are in the later stages are capable of improved
mobility even after months and years of postural instability and immobility.
This retrospective case study series will introduce the possibility of
functional gains such as improvements in gait and postural instability in
persons with late stage Parkinson disease.
Methods: This case study
series will discuss the emerging literature that will indicate that PWP who are
in the later stages can make cognitive and mobility gains as well as describe
valid and reliable outcome measures for PWP who are in the later stages.
Discussion will also contain treatment concepts that are designed around the
patient’s cognitive and mobility deficits and lasting outcomes to interventions
for PWP who would not have normally been referred to rehabilitation.
Results: The data of 4 PWP who were in late stages of
PD will be shared. Three of these PWP had gains in their functional mobility post
intervention and one which had an appropriate referral to hospice and continued
physical therapy interventions to improve function and maximize comfort in the
terminal phases of PD. All 4 of these case studies demonstrated benefits such
as improved mobility and enhanced QOL from physical therapy interventions
P40.09
Persistence: Reform to rehabilitation in people with
Parkinson’s Condition
Sergio
Contreras Varas, Parkinson’s Communty of La Serena
This paper is written from the perspective of a
user with Parkinson Condition and shows the results from a joint work venture
of users, their careers and family, which eventually founded a Parkinson’s
Community of La Serena, Chile.
The main purpose of this research is to try answer
the following question: What else can we do to improve our quality of life
beyond the normal treatment? What we are looking to date, with interesting
results, has been walking our lives, watched Parkinson User binding.
Methodology: what we have done is to define what we call a Route
Parkinson, from the point of view of the physical rehabilitation, divived in
three phases:
1. Pre / Post Diagnosis
2. Reinvention process towards Persistence (Reform)
3. Reformed Rehabilitation
For phase 1, Our main effort is to try to collect
information / cases on similar experiences in childhood time, environmental
characteristics, personal traumas, in other words, a history that would
indicate some overlap between users, and try to create a correlation between
this issue in order to explain previous life, development of the disease. It
can be an important antecedent empirical complement to contribute to early
diagnosis.
Phase 2, Which we have called Reformation which
from our point of view contains innovative element which objective is to
facilitate user behaviors with the creation of systematic methods to the user
and also the caregiver (s), to educate through an appropriate teaching
methodology to achieve high levels of persistence, which favors the User be in
continuous therapy, both physical exercise as primarily oriented toward serving
others (be server rather than being served). All this is explained as part of a
process of reinvention person, reconstructive action that leads to users, to recognize,
accept (RAA in Spanish) our condition. For Phase 3, we have special
contributions beyond what is required for good link this reform phase.
P40.10
Persistence: A New Approach for Patients with Parkinson’s
disease
Sergio Contreras
Varas
Amigos del Parkinson, La Serena, Chile
Objective: This paper tries to demonstrate a new
approach for Parkinson condition which links traditional pharmaceuticals
treatment along with social support from people exposed to this disease, where
the main focus is what factor(s) really improve(s) their quality of life.
Methods: We tried this new approach in a Parkinson’s
disease group in La Serena, Chile. In order to determine their goals we
conducted a focus group with patients, doctors, family and people involved in
this condition. In addition, we conducted a reach to find similar patterns in
other groups in Chile. Also we tried to find links between treatment and
religion focused on Jesuit’s catholic spirituality and the impact on
rehabilitation.
Results: The research showed us that the Parkinson
decease treatment can be approached from we called Parkinson rehabilitation
Plan. We defined three stages:
1. Pre / Post
Diagnosis: collect information on similar experiences in childhood time,
environmental characteristics, personal traumas, in other words, a history that
would indicate some overlap between one user and another, and so they attempt a
correlation between, somehow permitting explain previous life, development of
the disease. It can be an important antecedent empirical complement to
contribute to early diagnosis
2. Reinvention process
towards Persistence (Reform): which contains innovative elements what we have
called it Reformation, in order to facilitate user behaviors with routinize
methods and also the caregiver (s). All this strategy is explained as part of a
process of reinvention person, reconstructive action that leads to users, to
recognize, accept (RAA) our condition.
3. Reformed
Rehabilitation: This stage shows the results of this combined strategy toward
Parkinson’s treatment.
We have not clinically
tested due that is not our intention but gives a new hope of relief to the
parkisons patients.
P40.11
Six month interim report on the effectiveness
of a self-efficacy learning program for newly diagnosed Parkinson’s disease
(PD) patients and their care partners
Diane Cook1, Cynthia McRae2,
Rajeev Kumar1
1Colorado Neurological Institute,
Englewood, CO, USA
2University of Denver, Denver, CO, USA
Background: Study is based on the positive results
of two existing education-focused support groups for newly diagnosed
Parkinson’s (PD) patients. This program adds an additional component focused on
increasing self-efficacy skills.
Objective: Purpose of the overall study is to
evaluate whether this 12-month program results in specific physical,
psychological and Quality of Life (QOL) improvements for the person with
Parkinson’s (PWP) and less perceived burden for the care partner, as measured
against standard care PWP and care partners. The purpose of this interim 6
month assessment was program evaluation of the self-efficacy component.
Methods: Led by two trained lay facilitators
with PD, 14 participants and their care partners attend monthly 2-hour meetings
designed specifically to inculcate self-efficacy behaviors. Patients with PD,
care partners and wait-list controls are evaluated at baseline and 12 months
using the MDS-UPDRS Parts I, II and III, and self-report psychosocial measures.
Results: Participants with PD reported a high
level of self-efficacy (mean = 40.83 [±5.69] of 48 possible points) on the 8
item self-efficacy scale (alpha = .93) developed for this study. A high degree
of certainty regarding making positive lifestyle changes was indicated by
scores on 3 individual items (all 5.42 [±.67] on a 6-point scale). The 12 item
care partner questionnaire developed for this study (alpha = .83) showed the
program is meeting their needs (44.14 [±4.98] of 48 total points) and is
helping them understand what their partner is experiencing (3.86 [±.38] on a
4-point scale).
Conclusion: Findings of this assessment suggest
that introducing the self-efficacy concept, and modeling and supporting
self-efficacy enhancing skills is helping Parkinson’s patients and care
partners. The final assessment is expected to verify that these skills play an
important role in improving disease management and QOL.
P40.12
Assessment of individuals with Parkinson’s disease
participating in Rock Steady Boxing
Ann Foster1, S. Elizabeth Zauber1, 2,
Kristy Follmar1, Christine Timberlake1, Marcia Wilson1
1 Rock Steady Boxing,
Inc., Indianapolis, IN, USA
2 Indiana University
Medical Center, Indianapolis, IN, USA
Objective: Rock Steady Boxing, located in
Indianapolis, Indiana, is the first non-contact boxing program dedicated to
people with Parkinson’s disease. Founded in 2006, the organization is steadily
growing and currently offers 16 classes/week to over 125 participants. Over
time the need to define classes appropriate for individuals in different stages
of PD was recognized. Assessment with standardized methods was initiated early
in 2011 and used as part of the evaluation by the trainer and for placement of
new individuals in classes. The class levels are roughly based upon the Hoehn
& Yahr stages. Reassessments are performed at approximately 6, 12, 18 and
24 months and the reassessment information is shared with the boxers, their
caregivers and the trainers who use the information to enhance the class plans.
Methods: Physical assessments
are completed in the following order: Fullerton Balance Assessment (FAB, 10
test measures), Timed Up and Go (TUG, 1 measurement), Sit & Reach (1
measurement), Davies Test (performed in push-up position), Jump Rope Test
(number jumps/minute) and Purdue Pegboard Test (average of 3 tests on each
hand).
Results: Assessments for class placement and
reassessments after approximately 6, 12 and 18 months are continually in
process. Some individuals go through the Rock Steady assessment process, but
never join a class. Between early 2011 and early 2013, initial assessments were
performed on 116 individuals, 30 reassessments after 6 months, 9 at 12 months
and 1 at 18 months; assessments of newcomers and reassessments of boxers are
ongoing. Preliminary results indicate
that the majority (>75 %) of boxers demonstrate improvement in one or more
functions including balance, coordination and strength after 6 months of class
participation. Other non-quantifiable improvements are noted by Rock Steady
Boxing trainers and PD caregivers; many boxers are more positive, outgoing and
enjoy socializing with fellow boxers.
P40.13
Combining Hatha yoga approaches with Bones for Life®
processes for teaching people with mild to moderate Parkinson’s disease
Ann P. Foster, 1, 2, Christopher T. Bourke, 1,
2
1 Inward Focused
Movement, LLC, Indianapolis, IN, USA
2 Rock Steady Boxing,
Inc., Indianapolis, IN, USA
Objective: Many individuals, diagnosed and undiagnosed
with Parkinson’s disease, participate in senior exercise classes. We developed
a class structure suitable for people living with PD; their caregivers are
invited and welcome to participate in these classes. Symptoms and effects of PD can be managed and progression of the
disease delayed through regular practice of focused movements based upon Hatha
yoga combined with Bones for Life processes, breath awareness, relaxation,
mental and vocal stimulation.
Methods: Providing a calming, balanced 75 – 90 minute
session which exercises all major functions (physical, mental and emotional). Classes
are designed to insure that some form of success is experienced by each and
every participant. Processes used during each class are adapted to the
functional level of the class participants.
Process Sequence |
Focus on benefits |
Minutes |
Centering/breath
awareness – Ujjayi breath |
Emotional
calming, centering |
10 |
Torso
movement – spine movement in 3 planes with Ujjayi |
Flexibility,
coordination |
15 |
Sitting
or lying – hand, arm, leg, foot and knee exercises |
Control,
coordination, flexibility |
15 |
Moving
to standing – standing, supported exercises |
Control,
coordination, balance |
15 |
Walking
using combination of BFL processes, vocalizing (music used to stimulate
movement, vocalize, fun) |
Balance,
coordination, mental stimulation, voice projection |
20 -
30 |
Standing
to sitting or lying; meditation with visualization |
Emotional
calming, self healing |
10 -
15 |
Results: Combining Hatha yoga approaches with Bones for
Life processes provide well-rounded classes for individuals living with PD and
their caregivers. These classes are complimentary to other more active PD
classes, offered at Rock Steady Boxing, since emotional calmness, flexibility,
coordination, balance, movement control, mental and vocal stimulation are
encouraged without the challenges of more intense and vigorous exercise. This
class design is suitable for active boxers and other people living with PD who
prefer to “leave off the gloves” and participate in a gentler class.
P40.14
The Parkinson’s Well-Being Map™ – a visual tool to
support patient communication with their care team
Lizzie Graham1, María Gálvez2,
Helen Matthews3, Elisabeth Dohin4, Ursula Davis4
1European Parkinson’s Disease
Association
2Federación Española de Párkinson
3The Cure Parkinson’s
Trust (UK)
4UCB Pharma, Brussels,
Belgium
Objective: Motor symptoms have so far been the
predominant focus of treatment for people with Parkinson’s (PwP). However, it
is now increasingly recognized that non-motor symptoms (NMS), which can present
at any stage of the disease, may be as disabling as motor symptoms. Common NMS
include sleep disturbances, mood disorders, gastrointestinal problems and pain.
NMS can significantly reduce the quality of life of PwP and importantly, PwP do
not frequently report these to healthcare professionals (HCPs). To encourage
PwP to discuss their condition, the
Parkinson’s Well-Being Map™ (WBM) was developed as a visual tool allowing them
to monitor their symptoms over time and to facilitate communication about these
with HCPs.
Methods: The WBM was developed in consultation with
PwP and their caregivers and in collaboration with the European Parkinson’s
Disease Association, The Cure Parkinson’s Trust (UK) and the Federación Española de Párkinson. It
consists of a radar chart with eight radial axes, each representing a
functional domain: sleep disturbances, attention/memory, digestion and the gut,
movement, bladder and sexual function, pain, mood and other NMS. PwP rate how
frequently they experience symptoms on a scale of 0–4 (Never, Occasionally,
Sometimes, Often, Always) across the axes.
Results: The WBM was refined and developed in both
print and online formats following user feedback. Since launch, it has been
translated into 10 languages and downloaded over 7000 times. The WBM provides
an ‘at a glance’ visual representation of disease status encompassing a variety
of symptoms. Indeed, physicians who have used the WBM cite the visual nature of
the map as a unique feature aiding the identification of problematic symptoms.
Ultimately, the WBM could facilitate communication between PwP and physicians,
resulting in focused, in-depth assessment and effective management of symptoms
over time.
P40.15
Cultivating community care
Sue Jackel
South Sunshine Coast
Parkinson’s Support Group, Sechelt, BC, Canada
Introduction: In small communities, a diagnosis of
Parkinson’s reveals the strengths and limits of local healthcare supports and
skills available to residents, especially aging ones. What can
Parkinson’s-affected individuals and families do to build needed medical
expertise so that longtime residents can feel confident about continuing to
live amid familiar surroundings?
Background: One answer, emerging from published
scholarship1 , is to recruit or train nurse specialists in the
management of Parkinson’s. PD Nurse Specialists have won recognition for their
multifaceted role as translator, medication teacher, self-care coach and
research manager. Their training and practice have taught them to be
respectful, resourceful and well grounded in people’s everyday circumstances.
They can contribute immensely to better quality of life, and better care, for
Parkinson’s-affected families, especially those with limited access to
neurologists and other medical specialists.
Method: This abstract proposes a real-life project in community
care resource development, on the Sunshine Coast of British Columbia (pop.
30,000). Drawing on the experience and networking of affected residents, the
project will seek strategic partnerships with healthcare providers, community
organizations, regional health authority managers and Parkinson Society British
Columbia. The goal is to have one or more PD Nurse Specialists join our community’s
established chronic disease care team within three years.
Outcomes: The project will be a form of action
research, minuted and summarized for the benefit of other small communities
facing similar constraints and challenges. Thus it will be a combination of
public education and awareness raising, and a demonstration of the feasibility
of community capacity building in the face of provincial healthcare funding
restraint.
P40.16
Parkinson's disease: It's just
all in your head
Andrew Johnson
www.youngandshaky.com, Auckland,
New Zealand
Objective: A
diagnosis of Parkinson's Disease can be devastating, especially for those
people diagnosed well before the average age. Managing the condition and its
effects on someone's day to day life is challenging for patients, their
families and the medical professionals entrusted with their care. This poster
discusses the hypothesis that quality of life in People with Parkinson's can be
improved by increasing self awareness of their condition and its effects and by
subsequent actions based on that awareness.
Methods: Diagnosed
four ½ years ago at age 35, the author has subsequently undergone successful
Deep Brain Stimulation surgery, and the paper explores this argument as he
attempts to navigate towards better outcomes during the course of his disease.
Living with the uncertainty that comes with a progressively degenerating
neurological disorder can be almost as difficult as the insidious changes to
your mind and body caused by Parkinson's. It is argued here that developing an
awareness and understanding of the unique characteristics of your condition can
help you, your doctors and loved ones understand and track the progression of
your illness and the difficulties you face. Furthermore, this knowledge can assist
in maintaining a sense of control over the illness. It is then how you use this
state of mind that can help you maintain your functionality as long as
possible.
Results: There is
no doubt that Parkinson's is a game changer. But that is no reason to let your
disease dictate the rules of the game. How a patient perceives their illness
can be a strong indicator of their quality of life. Simply put, if you consider
that Parkinson's is literally and figuratively just all in your head, a patient
may in fact be able to enhance and preserve a good quality of life over an
extended period of time.
P40.17
The perception of people with Parkinson’s by others
Ann
Keilthy
Parkinson’s Association of Ireland, Dublin, Ireland
Abstract: The objective was to guage the ability
of those who might not be familiar with the signs and symptoms of Parkinson’s
disease to understand what it is they are seeing, and therefrom to assess
people’s preconceptions about others [in this situation the people are pwps ut
the wide arena is the assessment of presumptions made and whether educating on
one prejudice will cause the subjects to assess their presumptions in the
future. and their resulting behavior. A small sample of health professional
students at universities in Ireland received a questionnaire to fill out, after
hearing a talk given by the lead author, on their perceptions of people with
Parkinson’s, and what they thought was going on in terms of understanding the
symptoms and side effects. Were they drunk? Would they be safe to approach? A
majority said they would have no problem, would recognize Parkinson’s and would
be willing to assist. A second group, the same age and also at university in a
health related area, saw the speaker arriving while in a Parkinsonian state,
and in this situation a significant percentage of people said that they would
not know what to do and some would retreat from the situation.
P40.18
Tai Chi: Eight steps to keep you stepping
Bonnie Lyons-Cohen
Toronto, ON, Canada
Objective: This poster will inform and educate viewers
that Tai Chi is of great benefit to People with Parkinson’s. The gentle,
repetitive movements benefit the body physically and the mind emotionally. Tai
Chi increases muscle mass and strength, improves balance, improves flexibility
and ease of movement and prevents worse injuries from falling. Individuals as
well as groups can practice Tai Chi, indoors or outdoors, making it an
excellent social experience. This information will be presented in a graphically
pleasing way to inform and persuade people to take up this form of exercise.
Method: Creation of a poster
showing the 8 basic steps (plus the start and end positions) of the Tai Chi
form, with each form drawn as a silhouette and the name of that position and
the benefits to the body for each one. This will be original artwork, as photos
of my Shifu and classmates practicing the form will be used to create the art.
Studies will be cited that comment on the effects of Tai Chi on Parkinson’s
symptoms as well as interviews/comments/quotes from people with Parkinson’s who
have incorporated Tai Chi into their exercise routines and from those who teach
this art.
Results: The poster will
educate people about both the medical advantages and the better quality of life
that Tai Chi provides. If a picture is worth a thousand words, then this poster
will be worth ten thousand words. It will inform and convince more People with
Parkinson’s, their caregivers and others in their lives to take up Tai Chi and
more doctors and health workers to recommend it to their patients.
P40.19
The Parkinson's Tracker - A database management tool for
People with Parkinson’s
Edmund Langlois1, Helen Mak1,2
1Parkinson Alberta, AB,
Canada
2University Hospital Foundation,
Edmonton, AB, Canada
Objective: Parkinson’s is such a
unique and complex disease that, often people living with it (PWPs) experience
very different responses to medications, diets, or even the environment. Thus
the goal of this project is to develop a user-friendly tool designed for PWPs
to a) help them better understand and document their bodies’ shift from “On” to
“Off” and vice versa, and b) serve as a
communication
tool amongst PWPs and their care partners; so that the overall disease management
process can be streamlined and quality of life may be enhanced.
Methods: The Parkinson’s
Tracker is a personal electronic diary designed for PWPs and their care
partners to document their Parkinson’s journey. This health data management
software offers an unbiased and consistent approach in documenting a user’s
disease progression and well-being by utilizing a database runtime engine to
compile and analyze data collected through a 60-item questionnaire organized
into 6 correlated categories.
Comprehensive
graphical reports are then obtainable in soft or hard copy, detailing the
user’s current well-being scores and probable disease progression trend line.
Additional features of the program include an e-journal for comments or
observations and a medications e-organizer.
Users are encouraged and reminded to share these reports with their healthcare
providers.
Results: With
a minimal use of medical terminology and a straightforward interface, this
peer-developed application is suitable for PWPs in documenting and trending
their PD progression at their own convenience. During a focus group session
held in fall 2012, the software was well received by its participants,
confirming the need/desire of such tool. Currently the software is available in
disk format but a downloadable free app version will
be available shortly.
P40.20
Off-Park:
impact of wearing-off symptoms on quality of life; matched survey of both
people with Parkinson’s (PwP) and their care partners
Helen
Matthews1, Jon Stamford2 on behalf of the Off-Park survey
steering group
1The Cure Parkinson’s Trust (CPT), UK
2Parkinson’s Movement (PM), UK
Background: The symptoms of
wearing-off in Parkinson’s affect PwP in different ways with varying impacts on
quality of life (QoL). Preliminary evidence suggests Partners/Carers/Family
Members (‘care partner, CP’) notice symptoms of wearing-off before PwP. This is
the first survey believed to capture data from both PwP and matched pairs of
PwP and their CPs.
Aim(s) /
Objectives:
To identify the impact of wearing-off symptoms (motor and non- motor) on PwP
and their CPs and identify patient defined ‘QoL’ language which could support
more effective QoL discussions between PwP, their CPs and their healthcare
professionals (HCP) to improve PD management and daily life for PwP.
Method: This is an ongoing
anonymous survey comprising open-ended and multiple- choice questions,
available online or via soft/hardcopy. Respondents are recruited through CPT
and PM contact databases. Respondents comprise individual PwP and matched pairs
PwP and their CPs. PwP respondents have a specialist confirmed diagnosis of
idiopathic PD with a disease duration of >2 years. The goal is to gather 200
completed surveys. Survey domains include daily QoL situations and impact of
wearing-off symptoms (motor and non-motor).
Discussion: The results will
provide insights into the PwP definition of wearing off, its recognition by CPs
and PwPs and its impact on QoL issues. This may produce fresh opportunities to
improve PD management and daily life for PwP.
Conclusion: The survey may raise
awareness of QoL issues and the impact of wearing- off motor and non-motor
symptoms for PwP and, for the first time, their CPs.
P40.21
Effects of Dance for PD® on
activities of daily living among persons with Parkinson’s disease
Cynthia McRae1, David
Leventhal2, Olie Westheimer3, Ivan Bodis-Wollner4
1Counseling
Psychology, University of Denver, Denver, CO, USA
2Dance for
PD®, Mark Morris Dance Group, Brooklyn, NY, USA
3Brooklyn Parkinson
Group, Brooklyn, NY, USA
4Department
of Neurology, SUNY Downstate, Brooklyn, NY, USA
Introduction: Dance for
PD® (DFPD) was developed by the Brooklyn Parkinson Group (BPG) and Mark Morris Dance
Group (MMDG) in 2001. Previous research has indicated that individuals have
benefitted in a variety of ways, including significant improvement in the UPDRS
assessment of gait, from a brief intervention of DFPD classes. The present
study assessed the effects of DFPD on activities of daily living (ADL) among
individuals who had attended classes for an extended period of time.
Methods: Participants
in three well-established DFPD classes were invited to complete a survey
related to effects of the program. Usable responses were received from 53
individuals. The majority of participants were female (76%). Average age was 67
(SD = 12.8). Average length of attendance at DFPD classes was 12 months
and more than half the participants (53%) reported attending classes an average
of once a week. In addition to items related to effects of DFPD, measures of
ADLs, self-efficacy, and QoL were included. Descriptive analyses and
correlations were calculated.
Results: Results
indicated that 67% of participants rated QoL as “Excellent” or “Very Good,” 58%
reported they were able to perform several ADLs with more ease because of the
class, and 66% indicated they had more confidence in performing daily
activities. More than 88% reported that class helped improve mood and sense of
well-being and more than 82% reported improved motor functioning and less
isolation. Strong correlations (ranging from .58 to .77) were found between
effects of DFPD, self-efficacy, and ADLs.
Conclusions: Participants
in the DFPD program reported improvements in ability to perform ADLs and in
physical, social, emotional functioning as a result of the class. It appears
that participants benefited from DFPD and gained a sense of competence in
activities outside the studio resulting from increased confidence and
activities in the class.
P40.22
“My
Life” and the positive power of singing with the Tremble Clefs
Patti
Meese
Tremble Clefs, Scottsdale, Arizona, USA
Objective: The healing power of
music through the Tremble Clefs choral group provides positive therapy for
people with Parkinson’s and their Caregivers. After Parkinson’s diagnosis in
May 2008, Patti Meese realized she was losing her singing voice; couldn’t
project or hold a note the way she had in past performances and became
embarrassed when others couldn’t hear or understand her. She would often stay
at home and not socialize.
Methods: Meese attended a
conference in which the keynote speaker, Sun Joo Lee, Director of the
Scottsdale Arizona Tremble Clefs, discussed the importance of singing and the
clinical benefits the program provides. She explained that a common symptom is
decreased vocal volume with a monotone quality. Lee, who acquired a Master’s
degree in Music Therapy and Voice Performance from Arizona State University in
Tempe, Arizona went on to explain that participation in the choir strengthens a
patient’s voice, increases the volume and quality of their voices while
engaging in a safe, fun environment.
Results: Patti Meese joined
the Tremble Clefs and with continued vocal and movement exercises has now
regained her singing voice. Her confidence has returned, she has more energy
and now describes Music therapy and singing as her ‘natural’ drug in hopes that
everyone will take their ‘daily dose’ of Music. Many PD patients enjoy the powerful
results the same way that Meese has done and are generally healthier and
happier. Meese has enjoyed the positive benefits of musical therapy with her
Tremble Clef friends so much so that she recently competed in the Ms Senior
Arizona Pageant where she won a 1st Place Trophy for Talent by singing an
uplifting rendition of ‘Get On Your Feet” made famous by Gloria Estefan. Patti
Meese often enjoys telling audiences that she now has her life and JOY back
because of the Tremble Clefs program under the excellent direction of Sun Joo
Lee. Other positive comments by Tremble Clef members: “Since being diagnosed
with Parkinson’s some 12 years ago, I have learned how difficult this journey
is. Now that I’m singing with the Tremble Clefs, my spirits have lifted.” “My
wife has speech problems. She looks forward to Tremble Clefs every week and
being with everybody. We also enjoy the special performances we give.” “I enjoy
having my voice again and am thrilled to watch the faces of audiences as we
perform for them.” “Rehearsal days are the BEST of the week because we look
forward to singing with the Tremble Clefs. We love it! It’s great to have music
in our lives again.” “We have Tremble Clef withdrawals if we miss a rehearsal!”
P40.23
CHEER>UP: drama therapy support groups for Parkinson’s
Anissa Mitchell1, Anne Curtis1,
1Florida Hospital
Neuroscience Institute, Orlando, FL, USA
Objective: To address mental, emotional, social and
physical issues arising from Parkinson’s disease through the use of drama therapy
and humor. To empower Parkinson’s patients and caregivers by demonstrating ways
to improve wellness, re-frame thought patterns, build resilience skills and
live mindfully in the present.
Methods: Cheer>Up (Creativity, Humor, Education,
Encouragement, Resilience, (>) Greater Understanding of Parkinson’s) is an
emerging drama therapy intervention to improve quality of life for Parkinson’s
patients and caregivers. Using an innovative therapeutic model,” trauma drama”,
that harnesses metaphor, drama and humor to address Parkinson’s issues related
to mind, body and spirit. Drama techniques may enhance verbal and non-verbal
expression, movement, social skills, socialization, mood, motivation,
resilience and cognitive function.
cheer>up sessions
target specific “living well with Parkinson’s” objectives using drama therapy
activities including breathing exercises, vocal practice, movement, pantomime,
art, dance, singing and improvisational comedy. Metaphor links elements of each
session together and offers participants a novel approach to expressing
difficult emotions. The pilot program meets monthly for six months and includes
surveys regarding life satisfaction or caregiver strain.
Results: Evaluation of the pilot program will emerge
through surveys. The authors hypothesize that participation in cheer>up will
cause a positive shift mentally, physically and emotionally for Parkinson’s
patients and caregivers.
P40.24
The five elements: the implementation of a self-management tool for
people with Parkinson’s (‘PWP’s’)
Margaret
Mullarney
Move4Parkinson’s, Ireland
Objective: Provide a framework for PWP’s to better understanding of the management
of the complexity of Parkinson’s disease in order to achieve an improved
quality of life. Based on our founder’s personal experience of living with
Parkinson’s we have developed the Five Elements framework (‘The Framework’).
Method: The Framework was
developed and an educational leaflet produced. A self-management workshop based
on the Framework is in development phase.
The Five Elements:
1.
Medication
Awareness & Medical Support
This is the
key to the self-management process.
Important
questions to ask yourself are ‘Do I know what I’m taking? How to take it? When
to take it? What it is supposed to do?’
Be aware of
potential side effects of any medication.
2.
Nutrition
What you
eat and when you eat may affect the impact of your medication.
Stay
hydrated.
3.
Exercise
Studies
have shown that while exercising may not increase the levels of dopamine, it
can make your brain use the dopamine you have more efficiently.
4.
Emotional
Well-Being
Be aware of
changes in mood/behaviour.
Mindfulness
therapies can be an effective tool.
5.
Optional
Treatments
Any
interventions that can support your well-being in addition to taking your medication.
Results: 18 recipients of the brochure were surveyed. 100% confirmed the framework
was clear & easily understood. 100% reported content provided information
that would support PWP's to better manage their condition. 94% would have
benefited from this information at diagnosis. 80% confirmed they will make
changes to their lifestyle based on the framework. Comments included ‘The
whole message is Positive, Punchy and Proactive’
‘I wish I’d had something of this quality.
The fact that the information has been provided by PWP for PWP is even better’.
P40.25
Why Dance?
Pamela Quinn 1,2
1 Brooklyn Parkinson
Group, Brooklyn, NY, USA
2 NYU Parkinson Wellness
Program, NY, NY, USA
Objective: To explain why dance has been found to be an
especially useful form of therapy for PD.
Method: See chart below. It shows how dance embodies
many elements that help manage PD symptoms.
PD
PROBLEM |
DANCE
AID |
Initiation,
continuation and coordination of movement |
Dance uses
aural (music) and visual (copying someone else) cuing as substitutes for
normal automatic movement. Music provides rhythmic, even structure to
equalize movement on both sides of the body. |
Contraction
of muscles, overall stiffness |
Dance
uses touch to relax contraction and to guide movement; dance involves
stretching to improve flexibility. |
Poor
posture and balance |
Intrinsic
to dance is the study and practice of alignment, posture and balance. |
Poor
self-image; self consciousness |
Dance teachers
demonstrate how to present one’s self graciously. |
Poor
physical memory |
Learning
new movement and repeating it until it is familiar is an essential part of
the dance form. Repetition of movement helps it become habitual. |
Isolation |
Dance
is social |
Loss
of different qualities of movement |
Dancers,
stretch, float, jiggle, punch, etc. |
Your
body won’t respond to your direction |
Dancers
continually direct themselves physically; they move consciously all the time. |
Depression |
Dance is
uplifting and spiritual without being dogmatic. |
Difficulty
in accessing movement quality |
Dance
uses imagery to communicate how to move; images provide students with
references they can use at other times. |
There isn’t one
exercise form that covers all needs for everyone. But dance is particularly
suited to address initiation of movement, rhythmic coordination, social contact
and joy in living. Can you name another physical activity that is responsive to
so many aspects of PD?
P40.26
Grounding advice: words of wisdom for physicians and
those newly diagnosed with young-onset Parkinson’s disease
Michael J Ravenek1, Sandi J Spaulding1,
Mary Jenkins2, Debbie Laliberte-Rudman1
1Faculty of Health
Sciences, Western University, London, ON, Canada
2Movement Disorders
Program, Clinical Neurological Sciences, Western University, London, ON, Canada
Individuals newly
diagnosed with young onset Parkinson’s disease (YOPD) and their treating
physicians struggle with many unknowns and unanswered questions. Those who have
been living with YOPD for some time have important insights that can be shared,
based on their personal experiences managing with the disease.
Objective: Subjects with YOPD were asked to share some
of these insights; specific to information and resources they perceived to be
invaluable after their diagnoses and the care provided by their physicians.
Methods: Using grounded theory methodology,
individuals with YOPD participated in at least one of three means of data
collection: multiple interviews, focus groups and/or an online discussion
board. Part of the discussion within each of these methods focused specifically
on soliciting from participants the advice they would give to someone newly
diagnosed with YOPD, as well as the advice they would give to a physician
responsible for caring for someone with YOPD.
Results: Based on initial data from 24 individuals
with YOPD (14 male / 10 female), a number of important categories have emerged.
In terms of the advice given to newly diagnosed individuals with YOPD, there
was a focus on the need for information that enables one to be proactive in
various facets of life that directly impact health (e.g., exercise and
employment), as well as the importance of taking time to manage the emotional
side of receiving the diagnosis. Advice directed towards physicians from
participants addressed the distinction between information that participants
thought should and should not be shared with patients at the time of diagnosis.
Other advice related to the importance of following-up with patients after
delivering the diagnosis, and elements of the patient-physician relationship.
It is anticipated that the knowledge generated will inform the development of
future education materials for physicians and those newly diagnosed with YOPD.
P40.27
Living, learning and laughing with
Parkinson’s disease
Beverly Ribaudo
ParkinsonsHumor.com, Yuma, AZ, USA
Objective: Teach people about Parkinson’s disease;
how it affects people’s lives and how to use laughter as medicine for all of
us, by Blogging and using Social Media.
Methods: In July of 2011, I started writing my
funny stories about my life as a Parkinson’s patient in blog form and later on,
in book form. The title of my blog and book are Parkinson’s Humor.
Results: My results were amazing. Within a
month, I had 1000 visitors from six continents reading my Parkinson’s Humor
stories. Now, a year and a half later, my blog counter is at 80,000 and I have
had readers from 132 different countries. I write about everything and anything
Parkinson’s, and always seem to make it funny. I even detailed my recent DBS
surgery (with pictures taken in the operating room). I have a knack of turning
confusing medical jargon into user friendly stories. My stories have been
shared by various Parkinson’s groups around the globe and on the Michael J Fox
website. I am donating all the profits from the sale of my book to various
Parkinson’s Foundations.
P40.29
Argentine Tango as a rehabilitation therapy
for Parkinson’s disease patients
Sergio A Rodríguez-Quiroga1,2,
Tomoko Arakaki1,2, Sandra Vanotti1,2, Evangelina V Cores1,2,
Ángeles Merino1,2, Débora Rabinovich3, Javier Toibaro1,
Manuel Firmani 1, Verónica Litvak1, Nélida S Garretto1,2.
1Neurology-Movement
Disorders Section, JM Ramos Mejia Hospital, CABA, Buenos Aires, Argentina
2University Center of Neurology,
University of Buenos Aires, CABA, Buenos Aires, Argentina
3McGill
University, Montreal, QC, Canada.
Objective: Activities such as
exercise programs could be helpful in the management of gait and balance
disorders in Parkinson’s disease patients (PDp). Argentine Tango could be a
good choice of motor rehabilitation of gait in PDp: 1) Specific movement
strategies, 2) External cues for initiation and continuation of movement, and
3) Control of dynamic balance. The objective of this study is to evaluate
changes in motor and emotional aspects in (PDp) that participated in the Dance
Therapy Program using Argentine Tango (DTPAT).
Methods: We recruited 20 PDp, 2 p
dropped out. All were evaluated by a Movement Disorder (MD) specialist at
baseline and at the end with the following scales: UPDRS; MOCA test; Gait and
balance Scale (GABS); Six-Minute-Walk Test (6MWT) and PDQ-39. All p had an
interview with a clinical psychologist. Over 16 weeks, p attended 120 minutes
(min) tango sessions per week: 20 min: breathing, proprioception, and postural
correction; 30 min: basic step of tango; 10 min: break; 30 min: new steps, and
30 min: Tango dance.
Results: Mean age: 65 years;
male:11; years with PD: 5 [3-7]; H&Y II:13p and III:5p; MOCA: ≥ 26:
14p. UPDRS: using Wilcoxon test matched samples we found statistical difference
between baseline and final visit in: part II (p=0.02), part III (p= 0.01), and
total score (p= 0.0005). Other evaluations did not show statistical difference.
In psychological interview p extremely enjoyed the program with high compliance
(assistance >90%). They reported benefits dancing tango and discovered that
their bodies are able to do it beyond the restrictions that PD may present.
Conclusion: DTPAT showed to be useful
improving PD symptoms. Patients felt tango as a valid form of exercise, making
this modality a suitable and interesting rehabilitation tool.
Acknowledgments: We thank
the collaboration of Boehringer Ingelheim-Argentina with an unrestricted grant.
P40.30
Rhythm of Life Cranial Sacral Therapy Explained
Rosemary Craig and Linda Rose
Our Objective is to contribute to the developing dialogue between the
international, medical and alternative health communities as well as
people living with Parkinson’s on the
effectiveness of alternative therapies for Parkinson's Disease.* A review of the
available literature** suggests the current consensus is in the need for more
research about the effectiveness of such healing modalities. We describe the
experience of a Craniosacral Practitioner and a Patient with a 15 year
history of Parkinson's *** from a
serendipitous meeting at a farmers market to significant improvement in the
Parkinson’s Patient’s Quality of Life. By offering experiential evidence of the potential benefits of this therapy, we hope
to capture people's imagination and to inspire them to reach for the potential
relief in other healing modalities.
Cranial
sacral therapy is a method of alternative healing used across the globe.
Working with light pressure and deep patience, the Practitioner guides the
Patient into deep relaxation and awareness of their body. The Therapy sessions
were given at 6-8 week intervals over a three year period, following the
methods of Hugh Milne. **** The Craniosacral
Therapy approach has brought consistent
results, for this patient. After each session the Patient’s posture was
straighter, the arm swing more noticeable, the stride length more even, walking
more fluid and movement easier. These improvements in functional performance ***** have allowed an increase in complex
techniques in the Patient’s hobby of woodcarving. This enhanced function has also led to a General feeling of well being and the sense of knowing her place
in the world.
P40.31
Parkinson en mouvement: evolution
and current focus
Joanabbey Sack1, Maura
Fischer2, Zuzana Sevcikova1, Sarah
Humphrey, Tetiana Lazuk
1Concordia
University, Montréal, QC, Canada
2 McGill
University, Montréal, QC, Canada
Intention: This poster presents the evolution of Parkinson en mouvement Montreal,
Quebec, Canada. The aim of the initial dance classes for people with Parkinson’s
(2007) was to provide an environment of creativity, joy, and movement through
access to professionally taught dance classes designed to meet needs of those
living with Parkinson’s. Classes of 5 grew to 10 and more classes were added
each year. The classes are documented in film, television programs and news
articles; there have been several public performances. A complementary singing
group emerged in 2010. Parkinson en mouvement is now incorporated as a
not for profit organization with a team of teachers with training and
experience in dance therapy, physiotherapy, and medicine. The initial framework
transitioned into a team model of one dancer/dance therapist with a
physiotherapist with dance training; in 2010 the physiotherapist of the team
completed training and certification in LSVT/BIG (an intensive whole body
amplitude-based training protocol for people with P. D.). This added a tool to
the teaching approach; with class warm-ups and choreographies designed around
principals of LSVT BIG. Evidenced based LSVT/BIG was presented to class members
via verbal explanation, example, articles and demonstration; most importantly
it was experienced.
Method: There are
numerous published observations of how dance, movement and exercise classes
affect people with Parkinson’s; few are based on the experience people living
(and dancing) with Parkinson’s. Our research integrates the written and stated
perspective of the dance class members who experience Parkinson’s.
Results: This
process led to the development of a teaching template with the goal of training
more professionals to lead similar classes supporting the development of
classes throughout the Montreal region and to contribute to work across Canada.
Training templates are being formalized and internship opportunities developed.
Please see Parkinsonenmouvement.com
This poster session will be
discussed in English, French, Czech, Ukrainian and Russian by the current
teaching team: Joanabbey Sack (dance therapist), Maura Fisher (physiotherapist),
Zuzana Sevcikova (dance therapist/physiotherapist) and Tetiana Lazuk
(MD/psychotherapist).
P40.32
Parkinson’s Buddy Program: piloting a new support model
for people living with Parkinson’s
Louise Leblanc1 Marjie Zacks2 Barbara
Snelgrove3
1Parkinson Society
Canada, Central & Northern Region, Toronto, ON, Canada
2Chair, World Parkinson
Congress 2013, Communications Committee
3Parkinson Society
Canada, Toronto, ON, Canada
Objective: To pilot the buddies
concept as a model support program for people living with Parkinson’s.
Parkinson’s is a complex condition that impacts people on an individual basis.
Often they feel isolated and search for a way to connect with others who
understand their experience. Support
Groups are one option, but often people are not comfortable discussing problems
in a large group because they are either shy or may be very private people.
There may not be a local support group nearby and transportation may present
challenges. A one-on-one buddy program may address many of the issues that
prevent people attending a Support Group and may lead to ongoing, individual
support.
Methods: World Parkinson
Congress 2013 launched a new Buddies Program matching registrants from around
the world with a Canadian buddy to share experiences about living with
Parkinson’s. Based on the tremendous
response to the Buddies Program, we recognized its potential for ongoing
support beyond the WPC experience. One of the Parkinson Society Canada WPC
Buddies Co-ordinators is interested in piloting the program so there will be
consistency in delivery based on WPC experience.
Results: We
will gather feedback from WPC Buddies on the benefits of the program. As part
of the WPC poster presentation, we will seek ideas and suggestions on how this
model might best work as a support program. Building on the success of the WPC
Buddies Program, we will develop an application similar to the WPC application.
We will create promotional material for over 50 support groups in our region,
using our newsletter and web site. We
will offer appropriate training for the buddies and ongoing educational
support. We plan on piloting this
project after WPC and will share our success with other global partners with
the hope that they would implement the buddies program in their country.
P40.33
Living Well with PD: Vocal Strengthening and Singing
Group
Merrill Tanner1, Lili Liu2
1Glenrose
Rehablilitation Hospital, Edmonton, AB, Canada
2University of Alberta,
Edmonton, AB, Canada
Background: The weekly “Vocal
Strengthening and Singing Group for People with Parkinson’s Disease” provided
in Edmonton, Alberta by Speech Language Pathologist and singer Merrill Tanner
evolved from a research study on the use of singing to improve the vocal skills
and quality of life of people with PD. The treatment portion of the study was
completed in 2010 as a part of a PhD program at the University of Alberta. The
results of the study (presented at the CAG and the GSA in 2012) showed that
physical vocal parameters (loudness range and average pitch during a reading
task) and ‘Quality of Life’ as it relates to voice and communication (Speech
Intelligibility Inventory: Self Assessment Form) both improved as a result of
the six-week intervention. The study participants initiated a weekly group at the
beginning of 2011 led by Merrill Tanner.
Treatment: During the first 45 minutes of each session
participants perform vocal exercises taken from speech and voice therapy and
choral and vocal pedagogy that condition the vocal and breathing mechanisms and
release tension that interferes with optimal voice use. A break of 15 minutes
encourages socialization with an energized voice. The second hour involves
choral and unison singing focused on maximal vocal effort, emotional
expression, body movements to enhance breath support and having fun!
Professional piano accompaniment and improvisation is provided throughout the
session.
Benefits: This ongoing group is
much more than an ordinary sing-along and should be offered in every town! It
is an enjoyable, therapeutic, community-based activity that does not feel like
therapy. It strengthens the support network around those with PD, as relatives,
caregivers, etc. may be present. Participants choose whether or not to attend,
thus contributing to self-empowerment and self-management. No prior musical
knowledge or experience is necessary and all skill levels are easily
accommodated.
P40.34
Creativity and personal story as
a healing modality
Gary Turchin
PD Active, Berkeley, CA, USA
Background: Gary
Turchin is an award-winning poet, performance and visual artist with 40 years
of experience riding his creative edges (see www.garyturchin.net). Diagnosed
with
Parkinson’s in 2004, he has
published three books in the last three years, and wrote and performed a one-man
show, “The Healthiest Man On Earth; A Poet’s Journey With Parkinson’s,”
which is also the title of a documentary film about him (see:
http://youtu.be/craVH8mzpuQ). He says that as long as he remains creative, then
he feels like “the healthiest man on Earth.”
Objectives: The aim of
this session is to inspire a creative practice in PwPs and their caregivers, in
response to their physical and emotional challenges. A creative practice
grounds one in a milieu of hope and excitement. It is the best anti-depressant
on the market. Turn your symptoms into symbols, your Parkinson’s to
poetry.
Methods: Remember
being diagnosed? How did it happen? What did you feel? Everyone’s story is different.
How can you tell yours? Record it? Write it? Sing it? Paint it? Cook it? Through
fun exercises, sharing, and Gary’s keen artistic sensibility and inspired enthusiasm,
we’ll explore our creative edges, and begin to see the arc of story, which is
the connective tissue to the human experience. Let’s give you something to
think about, other than your symptoms, or caring for someone with
symptoms.
Results: Participants
will leave this session with a new curiosity about their creativity and personal
story, and some tools for incorporating that into their lives. They may very
well leave with a seed of what they want to do with their story. They
will definitely leave with a kick in the pants to come home to their
creativity, and with a network of like-minded PwPs to stay connected to.
P40.35
Hamilton City Ballet’s Dance for
Parkinson’s: bringing hope through dance
Jody White, Melania Pawliw
Hamilton City Ballet, Dundas, ON,
Canada
Objective: To provide
a safe and inspiring ballet class for people with Parkinson’s and their
families, with opportunities for nurturing friendships after class with
indulgent cupcakes. Hamilton City Ballet (HCB) is a classical ballet school,
located in Hamilton, Ontario, Canada, founded by Artistic Directors Max
Ratevosian and Melania Pawliw. Jody White, Program Manager has combined her
love of ballet with her career in health sciences to this program.
Methods: HCB offers
Dance for Parkinson’s classes to families living with Parkinson’s.
Classes are based on classical ballet techniques and storylines. with the added
enjoyment and benefits of live classical musical accompaniment. We were
inspired by both the English National Ballet’s Dance for Parkinson’s and
the pioneering, Dance for PD which is reflected in the choreography and
delivery of our classes. HCB spring 2013 session consists of 3 monthly two hour
classes which follow the storyline of Coppelia. The first hour is the
ballet class, followed by Cupcakes & Friendship in the second hour.
Sponsorship was secured from Tiny Cakes who provide cupcakes. The
teachers trained with David Leventhal, of Dance for PD, whose model and
theory provides the framework for the class.
Results: Hope and
joy are the foundation for HCB’s Dance for Parkinson’s. Through the
course of the first hour of class, students appeared to acquire a sense of
belonging and were mindful of their dance movements, instead of the limitations
of having Parkinson’s. These results are achieved through dancing to live
classical music in an environment that is challenging while at the same time,
respectful of limitations. According to Pam, a Dance for Parkinson’s student, “Sometimes when I can’t
walk, I can still dance”. The inaugural class was a success as evidenced by
student’s feedback and registration for further classes. Monthly classes
continue through June and weekly classes begin in September.
P40.36
Dancing for exercise, well-being
and making friends
Richard Windle1, Janet
Roberts1, David Stanfield1
1 Volunteer,
Parkinson’s UK, West Hertfordshire
Objective: To set
up a dance class for people with Parkinson’s. To produce a ‘best practice’
guide that might help other Parkinson’s UK branches to do the same. To examine
how participants benefitted from this activity.
Methods: The
first steps were to find a teacher, someone who could provide live music and a
suitable venue. We worked with the London-based charity Musical Moving who
helped us to find a teacher and provided invaluable advice. A timetable was
agreed and an enrolment form devised. The classes were well publicised and took
place weekly.
Each session began with warm-up
exercises followed by movement, initially sitting, then standing and finally
moving around the room, accompanied by live music. It was noticeable that some
participants seemed to take on a new lease of life and were able to move much
more freely.
We were aiming for up to twenty
participants each week. A few carers took part, others helped out. Two sessions
of six weeks were planned with a gap between them (around Christmas 2012). This
was to enable changes to the programme to be made at the half-way stage.
Results: The
project was evaluated in two ways; by monitoring the numbers attending and by
means of a structured questionnaire that was given to all those who took part.
On average there were sixteen participants each week. Almost all thoroughly
enjoyed the experience and said that they had benefitted from it. It was
apparent from the questionnaire responses that there are three themes running
through these comments that contributed to their enjoyment:
· The dance
movements as a form of exercise
· The ‘inner
peace’ that the activity brought
· That
participants generally got on well and bonded as a group
A practical guide for setting up
dance classes is being written based on everything we learned.
LIVING WITH PARKINSON’S: ADVANCING RESEARCH: FUNDRAISING, TRIALS,
CAMPAIGNS
P41.01
The answer is in all of us: how fox trial finder empowers
patients and powers research
Carey Christensen1, Lily Cappelletti2,
Katie Peabody2, Claire Meunier2, Debi Brooks2
1Person living with
Parkinson’s, Stanwood, WA, USA
2Michael J Fox
Foundation for Parkinson’s Research, New York, NY, USA
Background: PD patients report wanting to participate in
research, but fewer than 10% ever do. Meanwhile, 30% of authorized clinical
trials never happen because they fail to recruit enough participants. Research
progress depends on more patients taking part.
Objectives: The Michael J. Fox Foundation for
Parkinson’s Research (MJFF), wanted to make participation in clinical trials as
easy as possible for patients, and to help clinical trial coordinators find
qualified participants. Another goal was raising awareness and providing
education about the importance of clinical trials.
Methods: Using input from patients, researchers, and
industry, MJFF developed Fox Trial Finder (FTF), an online tool designed to
match patients and controls with clinical trials. FTF lists all ethically
approved PD clinical trials, regardless of funding source. It provides
information about trials in general, informed consent, and patient rights and
responsibilities. Registrants search for trials without commitment, and
communicate securely, directly and anonymously with trial coordinators at the
university or institution conducting the research; they can be notified when a
new trial is posted that matches their profile. FTF also allows registered
trial team members to search the anonymous profiles of PD and control
registrants, and communicate with those who may be a fit for their research.
While created by MJFF, FTF is an independent database; registrants will never
be contacted by MJFF unless they opt-in.
Results: Since its launch in April, 2011, 15, 600+
people have registered (75% PD, 25% control), and 200+ PD trials have been
posted. More than 300 researchers are using FTF to find trial participants. FTF
is now live in the USA, Canada, the UK, Ireland and Australia. In fall 2013,
FTF will be available in 4 additional languages and will list trials in France,
Germany, Spain, Italy and Austria. FTF raises awareness and provides education
through its Ambassadors and Clinical
Trial Recruitment Community Partners programs. FTF Ambassadors receive
toolkits for grassroots outreach; they also use quarterly calls to share ideas.
The Community Partners program
facilitates connection among key stakeholders.
Conclusions: Fox Trial Finder empowers patients to become
directly involved in research, and powers research with the trial participants
needed for success. A cure and better treatment for PD will not be found
without patient participation – the answer is in all of us.
P41.02
Information and support groups
in growth strategy the Run for Parkinson's Brazil
Janette de Melo Franco
Run For Parkinson’s Brasil, Belo Horizonte- Minas Gerais – Brasil
Summary: The Run for Parkinson’s Brasil brought up Parkinson’s disease and the
subjects about it, in an event that mobilized thousands of people and touched
various sections of the society. Although, to make sure this event wouldn’t
happen only on April and its effects would be limited, the benefits out of
social network would be necessary, like the creation support groups in the
countryside, not necessarily linked to any specific Association.
Methods: The information and support group was a path to make sure the
information would get through ailing people and their relatives. The group
brings high quality information at low cost, emotional support with the
similar, exchange of experiences, supported by professional volunteers. If we
can reach the patients and their relatives or helpers in the group, at the
event “Run for Parkinson’s” we will reach more people and various sections of
society besides Parkinson’s people. The search for sponsors for the achievement
of the RUN, always try the locals first with priority of social service
institutions, like nonprofit companies. The goal isn’t to get money, but
benefits forraise awareness and the maintenance of the groups.
Results: In a year, after the event, four support groups had been formed, besides
the group which already worked in Belo Horizonte. Our Parkinson support group
served five or six people, and nowadays we serve close to fifty and these
numbers keep raising. In 2012, only Belo Horizonte city had the RUN, by the
time, counting with four hundred people, and, in 2013, this number had doubled
in participants and a new sportive competition had been added. Before, there
was only one city participating, now, there are seven.
P41.03
Parkinson’s UK
Research Support Network – working together to find a cure
Emily Hughes1,
Ken Bowler1, Geoff Butcher1, Michael Cranfield1,
Richard Hill1, Harry Pearman1, Janice
Russell-Taylor1, Richard Windle1.
1Parkinson’s UK, UK
Objective: Our Research Support Network was set up to
provide opportunities for anyone with an interest in Parkinson’s research to
get involved in the search for a cure and better treatments. We believe that involvement by volunteers
will lead to more and better research. This will be achieved: through awareness-raising, fundraising, increased participation in trials, and
input by people with Parkinson’s and carers into project selection and design.
Methods: The Research Support Network is managed by one
full-time manager, one administrator, and a Development team of 9 volunteers.
The network has over 700 members, many of whom have proactive roles. We support
researchers to encourage them to involve people with Parkinson’s in their work
as well as promoting participation opportunities in their studies. Volunteers
review every application to the Charity for research funding, as one step in
our selection process. We encourage initiatives developed by volunteers across
the UK to support research. These include raising awareness through events;
newsletters and helping other supporters to find out about research; as well as
donations by local volunteer groups to specific research projects.
Results: Through the Research Support Network,
volunteers and supporters from across the UK are involved in research. 100
specific opportunities were promoted to the network in 2012, encouraging
supporters to participate in studies, share their experiences to help
researchers develop projects and information, and raise awareness of
Parkinson’s research. Through the Research Funding Programme, fundraisers from
88 local groups transferred a total of £431,619 to support Parkinson’s UK-funded
projects. Lay grant reviewers submitted 403 reviews of applications for funding
from researchers.
P41.04
A ten-year follow-up analysis of investments made in
Parkinson’s disease research
Beth A. Vernaleo1, Leung-Hang Ma1,2,
and James C. Beck1
1Parkinson’s Disease
Foundation, New York, NY, USA
2New York University
Langone School of Medicine, New York, NY, USA
Objective: To analyze investments made in Parkinson’s
disease research over the past ten years by a non-profit organization.
Background: The Parkinson’s Disease Foundation (PDF) is a
non-profit organization located in the United States whose mission is to
improve the lives of people affected by Parkinson’s disease. PDF works to
achieve this goal through three distinct yet complementary mechanisms:
supporting Parkinson’s disease research, providing educational resources, and
advocating on behalf of those with Parkinson’s. In supporting research, the
Foundation seeks out the most promising ideas to understand and potentially
solve Parkinson’s disease by challenging the scientific community to brainstorm
and develop novel scientific hypotheses for testing. In addition, reflecting
PDF’s long-term commitment to battling Parkinson’s disease, PDF supports the
development of young scientists and clinicians on their path to becoming new
leaders in Parkinson’s disease research. We now seek to ascertain the impact of
the research PDF has funded over the past ten years.
Methods: From 2000 to the present, the Parkinson’s
Disease Foundation has provided over $69 million for Parkinson’s research to
more than 400 individual scientists as part of a comprehensive and multifaceted
approach to support both research and training.
Results: We will provide an analysis of the impact
PDF support has had in the realm of Parkinson’s disease research. Outcomes of
specific projects will be highlighted and how these results may have altered
the research landscape will be subsequently examined. We will also analyze the
success PDF has had in providing “seed” support to enable grant recipients to
compete for larger grants from other sources. PDF will also show how funding
young scientists in their formative years has influenced their ability to stay
within the field of Parkinson’s disease, supporting PDF’s efforts to ensure a
steady pool of talented scientists dedicated to curing this disease. By
utilizing these metrics, it is PDF’s goal to identify potential areas in need
of support and improve upon the Foundation’s existing research programs.
LIVING WITH PARKINSON’S: OTHER
P42.01
Experiencing Parkinson´s disease and the Reward System:
the point of view of an informed patient
Víctor Hugo Alarcón Gómez1, Janeth Mosquera Becerra2, Yoseth Ariza Araújo3
1Physician and Informed patient, Cali, Colombia
2Universidad del Valle, Cali, Colombia
3Univesidad ICESI, Cali, Colombia
Objectives: To explore how the reward system works in an
informed patient and to implement induced behavior strategies to increase
reward sensations.
Methods: It is a case report from an informed patient
living with PD. Using literature review and my own experience, I was able to
identify and implement strategies to increase reward sensations.
Results: I describe my
particular experience as physician living with PD. Because the human biology is
designed for pleasure and both pleasure and displeasure are susceptible of
reframing, I started a process of reframing my personal experiences, moving
other neurotransmitters, in order to influence my lack of dopamine and to
review my reward system. Last year, I started to write reports of my daily
experiences and I developed an exhaustive literature review about the relationship
between anhedonia and PD. I found that there is a research gap between
pathophysiology and quality of life among Parkinsonian
patients. Based on both my own experience and literature review, I identified a
set of strategies to compensation related to: physical activity routine; food
and diet characteristics (taste, nutritive, simple); increasing opportunities
to laugh (seeking for funny experiences); modifying my affective relationships
(pets and reencounter with significant others); redefining my sexual life; and
changing my leisure time activities. Overall, my objective was to revalue my
quotidian activities filling them with hedonic value in order to change my
distorted reward system. This case report suggests that it is necessary to evaluate the reward
system through hedonic enjoy of life and to identify practical and
individualized strategies to balance wellbeing among PD patients. Moreover,
informed Parkinsonian patients can do an important contribution to increase the
understanding of mental health complexities on PD, taking into account that non-motor symptoms are important
factors affecting patient's quality of
life, particularly, in early onset and rapid progression subtypes of PD.
P42.02
Wilson's
disease in southern Brazil: genotype-phenotype correlations and description of
two novel mutations in ATP7B gene
Igor
Barcellos1, Renato P. Munhoz1, Ricardo S. de
Bem2, Salmo Raskin1, Dominique A. Muzzillo1,
Marta M. Degut3, Eduardo L. R. Cançado3, Thiago F. Araújo3,
Maria Cristina Nahle3, Egberto R. Barbosa3, Gabriela
Boschetti1, Hélio A. Teive2
1Pontifical
Catholic University of Paraná, Curitiba, Brazil
2Federal
University of Paraná, Curitiba, Brazil
3University
of São Paulo School of Medicine, São Paulo, Brazil
Objective: Clarify the regional distribution of
ATP7B mutations in Wilson’s disease (WD), genetically analyzing a WD population
of southern Brazil.
Methods: 36 WD subjects were studied and
classified according to their clinical and epidemiological data. In 23 subjects
the ATP7B gene was analyzed.
Results: Mean age at the initial symptom was
23.2+\-9.3(10–41) years. Mean time since the first symptom and the diagnosis
was 27.5+\-41.9(1–194) months. This population presented a high predominance of
an exclusively European origin (74.2%). Nine patients (25%) showed
predominantly neuropsychiatric symptoms, 14 (38.9%) predominantly hepatic
symptoms, 11 (30.6%) mixed presentation and 2 (5.5%) were asymptomatic.
Fourteen distinct mutations were detected in at least one of the alleles. The
c.3207C>A substitution at exon 14 was the most common mutation (allelic
frequency=37.1%) followed by the c.3402delC at exon 15 (allelic
frequency=11.4%). The mutations c.2018-2030del13 at exon 7 and c.4093InsT at exon
20 are being reported for the first time. Subjects homozygous for the most
common mutation (n=5) had a mean age of disease onset of 33.4+\-4.82 years,
compared to 15.7+\-3.21 years for heterozygotes (n=3) and 19.5+\-8.55 years for
the remaining individuals (n=15).
Conclusions: Almost half of the
mutations of the ATP7B gene were located at exons 14 and 15. Identification of
these most prevalent mutations provide basis to design appropriate regional
screening strategies for genetic diagnosis of WD in southern Brazil.
P42.03
Not Only An Old Person’s Disease
Miriam Dixon 1
Emma Partridge 2 Ortiz Michael 3,4
1Parkinson’s NSW Sydney
Australia
2University of
Technology Sydney Australia 3 St Vincents Hospital Clinical School, UNSW,
Sydney NSW Australia 4 Zitro Consulting Services Artarmon, NSW, Australia
Objective: The objective of this research was to assess
the gaps in knowledge about 'younger onset' Parkinson’s Disease (PD) in order
to identify needs for improved support services and information.
‘Stage-of-life’ factors make the challenges faced by 'younger onset' group
(under 65) people particularly significant and worthy of separate
consideration.
Method: An online survey of 38 questions plus focus
groups were used. The project was promoted via a media campaign. The survey
collected a range of demographic, experiential and attitudinal data from
respondents. It also assessed HRQoL using the Assessment of Quality of Life
(AQoL) instrument.
Results: Of the 297 respondents 56% were men diagnosed
between 46 and 65 years. Nearly a quarter had children under 18 living at home.
The following themes emerged from the focus groups :
young onset people face additional challenges relating to the impact of PD on:
a) their ability to continue work or build careers; b) to maintain active
social lives; c) maintain their parenting responsibilities and d) plan for a
secure financial future. TheAQOL results showed the QoL of younger onset
PD patients is severely impaired. The QoL scores of H&Y 4-5 scale people
reflects the worst possible health state being in the bottom 2% of the
Australian population.
Conclusion:
·
This
research supports the need for improved health and support services including:
addressing stage-of-life issues (including counselling related to employment,
retirement, financial and future planning and supporting parents of young
children)
·
PD
community nurses
·
Better
access to neurologists
·
Better
support for those newly diagnosed
P42.04
How the nonprofit sector can help
people living with Parkinson’s receive quality voice treatment: two successful
models
Samantha Elandary
Parkinson Voice Project,
Richardson, TX, USA
Objective: To educate
the rehabilitation community on two new service delivery models that enable
people with Parkinson’s to receive quality voice treatment.
Methods: In 2008,
Parkinson Voice Project, a nonprofit organization dedicated to preserving the
voices of those with Parkinson’s, developed a new service delivery model to
ensure that people with Parkinson’s would receive the treatment they needed to
regain and maintain their speaking skills: Pay It Forward. The challenge with
voice treatment for Parkinson’s is that patients require intensive individual
therapy followed by ongoing maintenance groups; however, Medicare/insurance
limits the number of treatments a patient receives and does not reimburse
“maintenance therapy.” With Pay It Forward, patients receive intensive voice
therapy (SPEAK OUT!®) followed by ongoing group therapy (The LOUD Crowd®) at no
cost. Each patient is given an opportunity to "Pay It Forward"-- make
a donation to help the next patient receive treatment. Through Pay It
Forward, no patient has ever been denied treatment. This unique service
delivery model could be implemented in University Speech Clinics or Nonprofit
Organizations. Since hospitals bill insurance, Parkinson Voice Project
facilitated a second type of service delivery model whereby hospitals partner
with a nonprofit organization to provide quality speech services. Hospitals
provide the services that are covered by insurance, while the nonprofit
organization provides the services and therapy materials not covered.
Results: Pay It
Forward covers 22-25% of the Dallas clinic’s expenses, while fundraising events
cover the remaining budget. Since implementing the Pay It Forward model,
Parkinson Voice Project has treated over 650 patients. The “hospital/nonprofit
partnership” model has been successfully implemented in Oklahoma. In 2012, over
70 patients received SPEAK OUT! and The LOUD Crowd in Oklahoma. By having the
nonprofit sector supplement services provided through hospitals, patients
receive the quality voice treatment they need.
P42.05
Going for the Goal!
William Keith Hall1, Linda J Hall,1
1PDFit, an affiliate of S.C.O.R.E. Power Training,
Marblehead, MA, USA
Objective: A
Parkinson’s diagnosis issues the challenge: you can try to take flight or enter
the fight!
Methods: Our non-profit
foundation is excited to introduce our self-motivated, goal-oriented PDFit
program, which intentionally creates a variety of customized nine-minute
targeted exercise routines, as well as specialized yoga classes and
choreographed PD dance instruction. Designed by ability levels, individualized
sets of balance, stability and strength-training exercises help participants
concentrate on “competing’ against their Parkinson’s symptoms- similar to an
athlete in training. They challenge themselves and fellow members to
consistently increase their endurance and mobility goals through the aid of
boxing, step hurdles, weight, agility ladders, pitch back devices, etc.
Results: Following an initial Parkinson’s diagnosis, everyone eventually
asks: “So, what do I/we do now?” Concerned about future physical and emotional
challenges, many people will diligently seek out physicians who will listen and
guide, join clinical trials, research the Internet and read the newest written
articles, consider whether or not to join a support group, and participate in
Parkinson’s assessment programs, where they learn the importance of regular
exercise to increase endurance, improve balance and mobility, and help injury.
Our vision for presenting the multi-faceted PDFit
program in communities in our area is to educate otherwise healthy individuals
and families affected by Parkinson’s in learning that proactive, resilient
living equates to having confidence in one’s physicians; using medications
correctly and participating in a professional mobility assessment’ establishing
empowering physical goals through consistent, focused exercise; and finding a
welcoming, non-intimidating location for sharing interactive resourcing and
social interaction with others who understand the questions, fears,
frustrations, limitations and triumphs associated with Parkinson’s.
P42.06
Parkinson
disease
in history
Abdul Nasser Kaadan
Aleppo University,
Aleppo, Syria
Objective: It is well known that
Parkinson disease is a very old disease, which was historically mentioned and
discussed by some old civilizations, about 7000 years ago. The aim of this
paper is to provide the historical different stages in which Parkinson disease
developed.
Methods: This paper
accomplished by going back to some historical texts of an old medical books
such as Al-Qanunn book of Avicenna. Some other books related to history of
medicine were reviewed as well to trace this disease.
Results: Symptoms and possible
treatments for Parkinson's disease are discussed in Ayurveda, an ancient Indian
medical practice that has been around since as early as 5000 BC. It is claimed
that there are references to the symptoms of Parkinson’s Disease in both the
old and new testaments of the Bible. In the Illiad, which, along with the
Odyssey are claimed to have been written by Homer in the eighth century B.C.,
the septuagenarian King Nestor describes symptoms that appear to be those of
Parkinson's Disease. Avicenn (c980-1037), discussed the various forms of motor
unrest in his chapter on nervous disorders in the "Qanunn of
Medicine". There is a reference to shaking palsy in the second part of
Henry VI, during an exchange between Dick and Say. Parkinson's disease was
first formally described in modern times in "An Essay on the Shaking
Palsy" published in 1817 by James Parkinson (1755-1824). James Parkinson
systematically described the medical history of six individuals who had
symptoms of the disease that eventually bore his name. It was not until
1861 and 1862 that Jean-Martin Charcot (1825-1893) with Alfred Vulpian
(1826-1887) added more symptoms to James Parkinson's clinical description. The underlying
biochemical changes in the brain were identified in the 1950s, due largely to
the work of Swedish scientist Arvid Carlsson (born 1923). Lastly, Sinemet was
developed by DuPont during the 1970's for the treatment of Parkinson’s disease.
P42.07
The central and essential role of the nurse clinician at
a movement disorder clinic
Nathalie L’Ecuyer¹,
Christiane Lepage¹, Monica Béland¹, Lyne Jean¹, Line Beaudet¹
¹Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada
Context: The Andre Barbeau Movement Disorder Unit of
the University of Montreal Hospital Center is comprised of an interdisciplinary
team that includes a nurse clinician.
Objective: To describe the characteristic role played
by the nurse clinician serving a clientele suffering from Parkinsonism.
Method: Over a period of 3 consecutive months (4
days/week), all interventions performed by the nurse clinician were listed and
documented in detail. Clinical, administrative and telephone interventions were
included.
Results: Based on 534 actions related to 272 patients
and performed by the nurse clinician, the majority (41,2%) were related to the
evaluation of the needs of the patient, changes in disease progression and
overall disease management. Coordinating with other members of the
interdisciplinary team and establishing links with community resources came in
second place with 20,2%. The third role function involved medication review
(19,9%). Lastly, teaching and transmitting information to patients constituted
an important aspect of the role of the nurse clinician (18,7%).
Conclusion: The role of nurse clinician specialized in Parkinson’s
disease is varied and essential. Clinician to the patient, she is also a
pivotal member with neurologists, health care professionals and community
resources. The nurse clinician plays an essential supportive role to the
Parkinson patient and a central role in the interdisciplinary team.
P42.08
Clinical Profile of Parkinson’s
disease Patients with Pneumonia Manor Y1, Shpunt -
Llivshiz D1, Rosenberg A2, Ezra A1 Judith Knaani1, Giladi N1,2, M.
Guttman3, Gurevich T1,2, on behalf of the NPF QII Investigators
1Movement
Disorders Unit, Dept of Neurology, Tel-Aviv Medical Center, Israel
2Sackler
School of Medicine, Tel-Aviv University. Israel
3Division
of Neurology, Dept of Medicine, University of Toronto, Toronto, ON, Canada
Objective: Swallowing
disorders (SD) are a common symptom in Parkinson’s disease (PD) and may cause
pneumonia. A clinical profile of PD patients who experienced pneumonia should
be investigated.
Methods: Data was
obtained from the National Parkinson’s Foundation (NPF) Quality Improvement
Initiative (QII) database an observational, prospective longitudinal study,
conducted at 18 NPF sites. All PD patients are eligible for enrolment into
NPF-QII registry. Dataset filled in retrospectively for the last year includes
demographics, causes of hospital admission including pneumonia, PDQ-39 (quality
of life questionnaire), cognitive status, treatments and medications.
Results: 4907
patients were included in the study. Mean age 67.20±9.91, age of PD onset
58.40±11.04, body mass index (BMI) 26.73 ± 4.61, H&Y 2.41± 0.82. Thirty two
(0.7%) patients self-reported hospital admission due to pneumonia (PWP), 4875 -
had no pneumonia (PNP). The PWP's H&Y was significantly higher than PNP's
(2.88±0.93, 2.41±0.81, p=0.003). PWP had lower scores on verbal fluency test
(14.56±7, 17.78±6.36, p=0.004), PDQ emotional, (7.81±4.94, 6.04±4.85, p=0.039)
cognitive (6.34±3.63, 4.29±3.23, p<0.001), and total scores, (35.18±16.95,
25.32±15.94, p<0.001) than PNP. PWP received significantly more antidepressants,
antipsychotic medications, cognitive enhancers (51.3%, 30.5%, p=0.006, 21.9%,
8.3%, p=0.002, 18.8%, 5.9%, p=0.006) and more speech and physical therapy
(37.5%, 12.9%, p<0.001, 68.8%, 37.3%, p<0.001) than PNP. Logistic
regression revealed the strongest association between PDQ cognitive score and
pneumonia (O.R=1.14, p = 0.016).
P42.09
The effect of STN-DBS's
laterality on voice and perception of speech intelligibility of patients with
Parkinson’s disease
Manor Y1,2,5, Levy M1,3,4,
Meshulam M2, Balash Y1,5,6, Hilel A1,5,
Zifroni Sommer Y1,, Giladi N1,5,6, Fried I3,5,6,
Bergman H4, Gurevich T1,5,6, Cohen JT2,5,6
1Movement
Disorders Unit, Dept of Neurology
2Voice and
Swallowing Disorders Clinic, Department of Otolaryngology Head and Neck Surgery
3Functional
Neurosurgical Unit
4Department
of Neurobiology, Hadassah Medical School, Jerusalem, Israel
5Tel-Aviv
Sourasky Medical Center
6Sackler
School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Objective: To assess and compare
the effect STN-DBS's laterality (bilateral, unilateral-right and left) on voice
and perception of speech intelligibility of patients with PD.
Methods: 48 PD patients with
STN-DBS (unilateral right 8, unilateral left 13, bilateral 27 patients) were
studied. We compared Pre and Post DBS evaluations of objective acoustic
analysis and speech perception ratings by the patients, caregivers, and a
clinician using the voice handicap index (VHI) and voice visual analogue scale
(VVAS) while patients were On-drug. GRBAS (Grade, Roughness, Breathiness,
Asthenia, and Strain) and UPDRS-Speech scores were carried out.
Results: 48 PD patients (19
females, 46 right-handed), age 58±8, PD duration upon surgery 10.5±4.5 years,
total UPDRS score (69±22/36±16, Off/On drugs) were evaluated. Pre-DBS voice and
speech evaluations did not significantly differ between groups
(Bi-STN/Right/Left for VVAS 28/26/28±13, p=0.9, VHI 26/19/15±23, p=0.5 and
UPDRS-Speech1.7/1.2/1.7±1, p=0.5). Post-DBS mean scores tended to worsen
(Pre/Post-DBS clinician evaluation 5.2±0.8/4.5±1, p=0.006; GRBAS-total
1.9±1.6/3.4±3, p=0.03; UPDRS-Speech 1.6±1/2.8±1.8, p<0.001). Post-DBS scores
significantly differ as a function of laterality: deterioration was significant
Post bilateral and left STN-DBS (Bi-STN/Right/Left regarding VVAS 40/20/30±19,
p=0.09, VHI 42/15/24±10, p=0.09 and UPDRS-Speech 3.6/1.1/2±1.8, p=0.0004).
P42.10
La
Salpêtrière’s contribution to the study of Parkinson’s disease
André Parent, Martin Parent
Department of
psychiatry and neuroscience, Faculty of medicine, Université Laval, Quebec
City, QC, Canada
Objective: Jean-Martin Charcot
(1825-1893) and his colleagues at la Salpêtrière in Paris contributed
significantly to our knowledge of Parkinson’s disease (PD). Early in the 1860s,
Charcot provided an enlightening clinical description of PD that greatly helped
to single out this disease from other tremor-associated neurological disorders,
particularly multiple sclerosis.
Methods: Although tremor was a
cardinal feature of PD, Charcot insisted that it was not necessarily present in
all PD patients. Hence, he argued that the term paralysis agitans used by James Parkinson (1818-1892) in his 1817
essay was improper and suggested to change it for Parkinson’s disease.
Results: Charcot
was the first to describe the masked facies and writing problems associated
with PD. In 1867, he introduced treatment with the anti-cholinergic alkaloid
drug hyoscine (scopolamine), which was used until the advent of levodopa a
century later. However, Charcot erred in classifying PD as a névrose, an error was later corrected by
some of Charcot’s students, principally Georges Marinesco (1863-1938) and
Édouard Brissaud (1852-1919). Marinesco’s description
with Paul Oscar Blocq (1860-1896) of a case of parkinsonian tremor due to tumor
in the substantia nigra (SN), in 1893, led Brissaud to propose in 1895 that
parkinsonism occurs as a consequence SN damage. However, it was
Constantin Tretiakoff (1892-1956) who validated Brissaud’s hypothesis in a
remarkable thesis defended at la Salpêtrière in 1919 and which reported highly
convincing evidence of SN cell losses in cases of PD and lethargic
encephalitis. Tretiakoff's findings were definitively confirmed in 1938 by the
German neurologist Rolf Hassler (1914-1984), whose doctoral studies in the
laboratory of Cécile and Oskar Vogt in Berlin elucidated in unprecedented
detail the neuropathology of both PD and post-encephalitic parkinsonism. More
recently, various Canadian clinicians and researchers played a crucial role in
the elucidation of the pathogenesis of this highly incapacitating illness.
P42.11
ParkNC: a referral network for enhanced
Parkinson’s disease care throughout North Carolina
Lindsay Prizer1, Jessica Katz2, Nina Browner2
1Department
of Health Promotion and Behavior, University of Georgia, Athens, GA
2 National Parkinson
Foundation Center of Excellence, University of North Carolina, Chapel Hill, NC
Objective: The complex and chronic nature of Parkinson’s
disease (PD) demands the support from a variety of specialized healthcare
professionals and resources, yet few healthcare settings are able to
accommodate such a wide range of services onsite. As a result, physicians often
refer their PD patients out for additional care, often to nearby allied health
clinicians who may not have the expertise in PD necessary to meet the unique
needs of this population. Aware that it has been found that people with PD
receive higher quality of care from clinicians who have specialized knowledge
in this area, the Movement Disorders Center at UNC Chapel Hill developed a
referral network program to expand specialized PD services throughout North
Carolina.
Methods: This task was implemented through three
primary efforts: 1) creating an on-site, bi-monthly Interdisciplinary PD
Clinic, 2) helping to organize a workshop on clinical presentations of PD and
PD multidisciplinary care in order to increase the number of PD-trained
healthcare professionals in the state, and 3) connecting patients to local
expert allied health clinicians through an online referral network, ParkNC.
Results: The Center worked with multiple stakeholders
within UNC hospital and across the state to execute these efforts. As of April
2013, the UNC Interdisciplinary PD Clinic has served 37 patients from across NC
as well as 4 other states. The ParkNC referral network website currently lists
over 70 Parkinson’s-trained allied health clinicians, and this list is growing.
The process undertaken by the UNC Movement Disorders Center can serve as a
model for healthcare organizations in other states to develop similar programs
and networks, with the goal of enhancing the quality of care for the more than
1 million individuals living with PD in the United States.
P42.12
The science behind
Parkinson's disease: a Wikiversity learning project
John Telford1, Harry Pearman2
1Wikiversity,
Leicester, UK
2Wikiversity, London,
UK
Objective: To enable people affected by Parkinson's (patients,
carers, professionals and others)
* who are keen to follow progress in
research into Parkinson's,
* to share what they have learnt
* by writing about it in accessible
language
* and making it available as a constantly
updateable on-line resource
Methods: The open, global, non-proprietary medium of
Wikiversity has been chosen as the platform for establishing a structured
resource which anyone can add to and amend.
The project aims to attract people already
attempting to follow the progress of Parkinson's research. This includes many
with the ability to explain and write about complex scientific ideas in
language understandable by the non-specialist.
The value of this project is to enable
such people to share what they discover and make it available in a structured
way to the wider Parkinson's community. The wiki format, by which people can
build on the work of others and add fresh material, is an ideal vehicle for
this. A wiki can allow references to be made to source documents and other
background information and thus help to ensure accuracy and scientific
integrity.
Results: This
Wikiversity learning project has been set up at http://en.wikiversity.org/wiki/ParkinsonsScience and already a lot of high quality, interesting and
interlinked material has been amassed by a growing number of active volunteers.
The main section is for tracking Progress
and Prospects in Parkinson's Research and is arranged by topics within
fields of research. There is a Magazine
subsection for standalone articles and a step-wise Introduction to Parkinson's Science. WPC participants including researchers and
health professionals are invited to explore the project and to join the growing
band contributing high quality and accurate material to it.
P42.13
What really matters to people with
Parkinson’s?
Richard Windle1,
Janice Russell Taylor, Simon Cran.McGreehin, Emily Hughes, Stacey Shorey, Mary
Sinnathanmby
1 Volunteer,
Parkinson’s UK
Objective: The
objective is to involve people with Parkinson’s, carers and health professionals
in a wide-reaching consultation that will identify whether there are any gaps
in the coverage of current treatments and research programmes. This information
will be useful in discussions with Government on policy issues and to support
funding applications, as well as giving people with Parkinson’s a voice in the
research process.
Methods: The
methodology is based on a framework developed by the James Lind Alliance (JLA),
a non-profit making body funded by the UK Government. The project will be
managed by a steering group where all the stakeholders are represented and will
include a consultant from the JLA. Questionnaire-based methods are used. The
patient/carer questionnaire seeks to ascertain the symptoms/side-effects that
respondents experience and, via open-ended questions, any new
developments/improvements in existing treatments they would like to see. The
questionnaire for healthcare professionals focuses on their perceptions of what
is needed. Some of the unmet needs identified by respondents may already have
treatments available and this is determined by cross-checking against the UK’s
Database of Uncertainties about the Effects of Treatments (DUETS). The final
part of the process is a ‘priority setting’ meeting where the objective is to
identify a ‘top ten’ of unmet treatment/research needs. This is done in a
workshop where the merits of different suggestions are debated. Specially
adapted techniques based on decision-making theory are used to ensure that all
participants have an equal say and the proceedings are not dominated by those
with the loudest voices.
Results: By October
the consultation will be underway, but it will be too early for results – these
should be available in mid-2014 and can be made available to other WPC
participants for whom this work is of interest. Examples can be given from
priority setting projects carried out in other fields.
Oral Presentations
O144
Overview: Exercise, physical therapy, and
benefits to the brain of Parkinson’s patients
Public
health recommendations endorse sustained activity throughout life because of
its protective effects on health, recommendations that have been extended to
chronic health conditions such as Parkinson’s. In Parkinson’s evidence supports the
role of exercise to manage symptoms with improved symptom severity, muscle
strength and endurance translating to improvements in function. Exercise
targets the effects of deconditioning due to reduced activity and typically
includes advice to engage in endurance training such as cycling, treadmill or
walking, together with strength, co-ordination and flexibility exercise. Most
likely a combination of these types of exercise will provide optimal benefits.
Another area of interest is training of functional
movements and skills which includes complex task practice with dual and
multi-tasking where movements are practiced along with cognitive tasks. Complex
exercise in older adults that engage thinking processes and problem solving
combined with physical exercise may be beneficial to maintain cognitive
function which is also of importance for Parkinson’s. Dancing
could be considered to engage brain activity involved in cognition and
movement. There is also increasing interest in the role of exercise to protect
the brain – so called ‘neuro-protection’. Studies in animal models
suggest that a variety of molecular repair mechanisms restore motor function
and tap into the body’s own mechanisms of neuro-protection with potential for a
neurodegenerative disease such as Parkinson’s, although the neuro-protective
effects of exercise are yet to be demonstrated in humans. Type and dose of
exercise is currently unknown however studies suggest that aerobic forms of
exercise at moderate intensity are required although even less intensive
activities such as walking can be health-protective in older adults and may be
easier to implement. This session will explore the role of different modes of
exercise (physical and mental) and discuss optimal ways people with Parkinson’s
can engage in these types of activities.
Late-Breaking Poster
Presentations
BASIC
SCIENCE: ETIOLOGY, GENETICS, EPIDEMIOLOGY, AND TOXICANTS
LBP01
Neuropsychological
performance in LRRK2 G2019S carriers
and non-carriers with Parkinson’s disease
Roy N. Alcalay1,2, Helen Mejia-Santana1,
Anat Mirelman3,4, Rachel Saunders-Pullman5,
Deborah Raymond5, Laurie Ozelius6, Avi Orr-Urtreger7,8,
Lorraine Clark9,10, Nir Giladi3,7, Susan Bressman5,
Karen Marder1,2
1Department of Neurology, College of
Physicians and Surgeons, Columbia University, NY, USA
2Taub Institute for
Research on Alzheimer's Disease and the Aging Brain
3Movement Disorders Unit, Department of Neurology,
Tel-Aviv Medical Center, Sackler School of Medicine, Tel-Aviv University,
Tel-Aviv, Israel
4School of Health Related Professions,
5The Alan and Barbara Mirken Department of
Neurology,
6Departments of Genetics and Genomic
Sciences and Neurology, Mount Sinai
7Sackler Faculty of Medicine,
8Genetics Institute,
9Department of Pathology and Cell Biology,
10Center for Human Genetics,
Objective: To compare
the cognitive and psychiatric phenotype of Ashkenazi Jews (AJ) with Parkinson’s
disease (PD) with and without LRRK2 G2019S mutations
Methods: We administered a neuropsychological
battery to PD participants in the Michael J Fox AJ consortium. Participants (n=
290, including 86 from
Results: Age at onset, gender, UPDRS-III and GDS
performance did not differ between mutation carriers and non-carriers. Carriers
were older, had a longer disease duration and were taking higher levodopa
equivalent daily doses. In adjusted regression models, carriers performed
better than non-carriers in executive (p=0.014) and attention (p=0.042)
domains. In conclusion: in AJ-PD, LRRK2 G2019S
mutation status is associated with better attention and executive function.
Given the reduced power to detect differences in memory and visuospatial domain
scores, it is possible that LRRK2
carriers perform globally better than non-carriers.
LBP02
Age Specific
Penetrance of the LRRK2 G2019S mutation in the Michael J Fox Ashkenazi Jewish
(AJ) LRRK2 Consortium; Are there gender differences?
Karen Marder1,2,Ming-Xin
Tang1, Roy N. Alcalay1,2 ,Lorraine Clark9,10,
Helen Mejia-Santana1, Deborah Raymond5 , Rachel
Saunders-Pullman5, Laurie Ozelius6, Anat Mirelman3,4,
Avi Orr-Urtreger7,8, Nir Giladi3,7, Susan Bressman5
1Department of
Neurology,
2Taub Institute for
Research on Alzheimer's Disease and the Aging Brain
3Movement Disorders
Unit, Department of Neurology, Tel-Aviv Medical Center, Sackler School of
Medicine, Tel-Aviv University, Tel-Aviv, Israel
4School of Health
Related Professions,
5The Alan and Barbara
Mirken Department of Neurology,
6Departments of
Genetics and Genomic Sciences and Neurology, Mount Sinai
7Sackler Faculty of
Medicine,
8Genetics Institute,
9Department of
Pathology and Cell Biology,
10Center for Human
Genetics,
Objective: Estimates of the
penetrance of LRRK2 G2019S vary widely (24-100%) and may depend on
ascertainment, ethnic group, gender, and other genetic or environmental
modifiers. Using the kin-cohort method, we reported a lifetime penetrance of
26.2% to age 80 (95% CI 16.4-43.0) in 983 relatives of 181 Ashkenazi Jewish
(AJ) cases, similar to the penetrance of 24% (95%CI 13.5-43.7%) in 2975
relatives of 459 AJ and non-AJ Parkinson’s Disease (PD) cases combined (Clark
2006). Here, we estimate the penetrance of the G2019S mutation in the AJ
Consortium .
Methods: PD cases completed a
validated family history interview (FHI) for PD, age at onset (AAO) of PD,
current age, or age at death for each first-degree relative. The kin-cohort
method uses the mutation status in PD cases to infer unobserved genotypes in
relatives and combines this with PD AAO to estimate penetrance of LRRK2 G2019S
in relatives.
Results: 96 G2019S+ probands
(39 Beth Israel (BI), 26 Columbia (CU), 31 Tel Aviv (TA)) and 310 G2019S-
probands (WT) (95 BI, 106 CU, 118 TA) provided FHI on 383 relatives predicted
to be carriers and 1264 predicted to be non-carriers (WT). 74 relatives had PD
based on FHI (45 WT and 29 G2019S). Cumulative risk in predicted WT relatives
to age 80 was 0.057 (0.035-0.080) and 0.218 (0.128-0.311) in predicted G2019S
carriers; RR 3.846 (95%CI 1.990-7.850). Cumulative risk in WT female relatives
was 0.027 (95%CI 0.004-0.051) and 0.249 (95%CI 0.071-0.413) in carrier
relatives; RR 9.12 (1.98-49.92). In male relatives, WT: 0.091 (95% CI:
0.047-0.139) and carrier relatives (0.180 (95% CI: 0.029-0.377) RR: 1.973
(95%CI: 9.226-6.455).
Conclusions:
We confirm that the penetrance of LRRK2 G2019S is low in AJ. The relative
differences in penetrance in female and male relatives, may explain the similar
frequency of male and female LRRK2 G2019S PD cases.
LBP03
The Autonomic profile
of Ashkenazi Jewish Parkinson’s disease patients carriers of the G2019S
mutation in the LRRK2 gene
Tanya Gurevich1,
Roy N Alcalay2, Rachel Saunders-Pullman3, Anat Mirelman1,
Avi Orr-Urtreger1, Karen S Marder2, Susan B Bressman 3
and Nir Giladi 1 on behalf of the AJ LRRK2 consortium
1Tel-Aviv Medical
Center, Tel Aviv, Israel
2Columbia University,
College of Physicians and Surgeons, NY, USA
3Beth Israel Medical
Center, NY, USA
Objective: Autonomic disturbances are common in Parkinson’s disease and are often
manifested early in the disease. The aim of this study was to characterize the
autonomic profile of Ashkenazi Jewish (AJ) patients with PD who carry the
G2019S mutation in the LRRK2 gene.
Methods: 285 Parkinson’s disease patients participating in the Michael J Fox AJ
consortium study (84 from Beth Israel Medical Center, 66 from Columbia
University Medical Center, and 135 from Tel Aviv Medical Center) completed an
in-depth autonomic evaluation. Assessment included completing the Non Motor
Symptoms Questionnaire (NMS), Scale for Outcomes in Parkinson’s
Disease-Autonomic questionnaire (SCOPA-AUT) and the Rapid Eye Movement (REM)
Sleep Behavior Disorder (RBD) questionnaire. Demographics, clinical
characteristics, and autonomic data were compared between carriers and
non-carriers of the G2019S mutation and were adjusted for differences in
disease duration.
Results: 141 patients (mean age 69.6±9.7yrs; 45% females) carried the G2019S
mutation. Age, gender, UPDRS-III, and scores on the Montreal Cognitive
Assessment and Geriatric Depression Scale did not differ between mutation
carriers and non-carriers. Carriers had an earlier age of motor symptoms onset
(58.0±10.2yrs vs. 61.8±11.6yrs; p<0.001) and longer disease duration
(10.9±6.6yrs vs. 7.1±5.2yrs; p<0.001). On the SCOPA-AUT questionnaire,
carriers were less likely to report constipation then non-carriers (34% vs.
43.5%; p=0.038), but reported more urinary incontinence and sweating (0.6±0.9
vs. 0.4± 0.7; p=0.01 and 0.6±0.9 vs. 0.3±0.7; p=0.02 respectively). In
addition, carriers reported less motor expression of RBD (limb movements: 16.5%
vs. 30.3%; p=0.006, shouting 24.5% vs. 40%; p=0.005, hurting of the spouse 7.2%
vs. 18.8%; p=0.004). PD carriers of the G2019S mutation may have a distinctive
autonomic profile to suggest a unique autonomic degenerative process and less
prominent motor manifestations of RBD.
LBP04
Microarray analysis of
differentially deregulated striatal gene expression between striatopallidal and
striatonigral pathways following Deep Brain stimulation in BacTRAP mice
Naomi Vijanji1,
Iman Kamali Sarvestani1,2, Zahra Shams Shoaei1, Clement
Hamani1, Josi Nobunga1 and Lili-Naz Hazrati1
1 University of
Toronto, Toronto, ON, Canada
2 Stockholm Brain
Institute, Stockholm, Sweden
Objective: Deep brain stimulation (DBS) is
arguably the most effective extant treatment for Parkinson’s disease (PD).
Although the major pathology of PD is believed to be degeneration of
nigrostriatal dopaminergic neurons, the neural mechanisms involved in
therapeutic effect of DBS have been explained in pathways sparing the striatum.
In order to investigate the role of striatal pathways in the deep brain
stimulation we analyzed the changes in the striatal gene expression following
DBS in 6-OHDA lesioned mice.
Methods: Two groups of mice,
namely BacTRAP D1 and BacTRAP D2 mice were used. The samples thus represent
differential expression of genes in striatonigral and striatopallidal medium
spiny neurons. Both groups are injected with 6-OHDA to mimic Parkinsonian
state. Operations are performed on all mice to place DBS electrodes in the
subthalamic nucleus (STN). Half of mice in each group received the actual DBS
while the other half kept the electrodes in a sham operation. Samples from each
of the four groups (sham D1, sham D2, stimulated D1 and simulated D2) were
prepared for gene expression analysis. Samples were tested using microarray
technology on an Illumina platform.
Results: Comparison of
expression level between the four groups reveals profound genetic changes in
the striatum following deep brain stimulation in the STN. Significantly altered
genes were grouped into several functional clusters using different
bioinformatics tools. Main gene clusters found to go through significant
changes include those involved in G-protein coupled receptor signal
transduction pathways, chromatin remodeling, inflammatory responses as well as
neuropeptide synthesis, trafficking and release. The results can shed light on
exploring novel striatal therapeutic targets for Parkinson’s disease.
BASIC
SCIENCE: PROTEIN MISFOLDING AND HANDLING
LBP05
Tau oligomers as novel therapeutic target for Parkinson’s
disease and neurodegenerative synucleinopathies
Urmi Sengupta1, Julia Gerson1,
Diana Castillo-Carranza1, 2, Marcos Guerrero-Munoz ,George. Jackson,
1, Rakez Kayed2
1Departments of Neurology, University of
Texas Medical Branch, Galveston, TX, USA
Objective: The accumulation of
tau protein is an important pathogenic factor in Parkinson’s disease (PD) and
other neurodegenerative disorders; still it is less well characterized in PD
and synucleinopathies. Aggregated α-synuclein can induce tau aggregation in vitro and in vivo, which indicate that tau aggregation and the formation of
neurotoxic tau oligomers mediates α-synuclein toxicity. In this study, we
investigated the role of tau oligomers in PD and synucleinopathies and the
effects of anti tau oligomer passive immunotherapy in a well established using
α-synuclein mouse model of PD.
Methods: We performed systematic
biochemical and immunohistochemical analyses of human tissues and brains
extracted from different synuclein animal models using a number of novel
antibodies.
Then we specifically targeted tau oligomer in an α-synuclein mouse model
of PD by passive immunotherapeutic approach a novel
tau oligomer specific antibody-TOMA- which was administered,
intravenously, to aged animals and its effects on the PD-like phenotypes were
assessed by multiple approaches. After the final behavioral evaluation, animals
were sacrificed and are being systematically analyzed.
Results: We discovered that the
synergy between synuclein and tau is dependent on the formation of synuclein
oligomers which cause tau aggregation and oligomerization. Moreover, we
established that tau oligomer levels in fractions of
brain tissues from PD patients are elevated compared to the age-matched
controls, and tau oligomers formation coincide with behavioral deficits in the
synuclein mouse models. Finally, passive
immunotherapy using TOMA reversed the phenotypes in aged synuclein
animals. Collectively, these results argue that
oligomers represent a potential target for a disease-modifying immunotherapy,
either alone or in combination with anti α-synuclein immunotherapeutic
approaches.
BASIC
SCIENCE: MITOCHONDRIA, OXIDATIVE STRESS, INFLAMMATION, PATHOGENESIS
LBP06
LRRK2 and oxidative stress: can we turn
genotypes into phenotypes?
Elizabeth Abdel-Messih1, Maxime W. Rousseaux2,
Yasmilde Rodriguez Gonzalez1, Sameera Abuaish1, Yi Zhang1,
Jerzy Kulczycki3, Youren Tong4, Ruth S. Slack1,
Hymie Anisman3, Robin J. Parks5, Jie Shen4,
David S. Park1*.
1Department of Cellular
& Molecular Medicine, University of Ottawa, Ottawa, ON, Canada
2Department of
Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA
3Institute of
Neurosciences, Carleton University, Ottawa, ON, Canada
4Brigham Women’s
Hospital, Harvard Medical School, Boston, MA, USA
5Division of
Regenerative Medicine, Ottawa Hospital Research Institute, Ottawa, ON, Canada
Objective: As most of the LRRK2-linked animal
models of Parkinson’s disease (PD) fail to recapitulate the clinically relevant
symptoms and pathology, we set out to evaluate whether coupling a genetic
susceptibility with an environmental toxin could illicit changes in cell
viability. We tested whether an oxidative stress insult could manifest a
LRRK2-induced cell survival phenotype in
vitro and in vivo, using various
mammalian models of LRRK2.
Methods: Primary,
embryonic neuronal cultures harvested from LRRK2 R1441C Knock In (KI) mice, the WT
and R1441G-hLRRK2 (WT and RG-hLRRK2) over-expressing animals, and the LRRK2
Knock Out (KO) animals were treated with the active neurotoxic metabolite of
MPTP (MPP+) and cell survival was assessed in
vitro. Simultaneously, we performed in
vivo MPTP neurotoxin studies on 10-week-old male LRRK2 KI, WT and RG-hLRRK2
expressing mice and their respective wild-type littermate controls. Animals
were exposed to sub-chronic and/or acute MPTP treatment paradigms and the brain
tissue was collected for sectioning and immunohistochemistry. Dopaminergic cell
survival was assessed at the level of the striatum, via optical densitometry of
dopamine transporter (DAT) staining, and at the substantia nigra pars compacta (SNc) region, using
stereological quantification of the surviving tyrosine hydroxylase
(TH)–positive neurons.
Results: Our results
illustrate that the presence of mutant LRRK2 does not sensitize neurons to
death induced by the Parkinsonism-related neurotoxin MPTP. These results
suggest that traditional PD-linked oxidative stress insults may not be a major
contributing factor in the pathogenesis of LRRK2-linked PD.
LBP07
Deciphering the mechanisms of action of parkin during
mitophagy using a structure-based FRET-reporter system
Matthew Y. Tang1, Jean-François Trempe1,
and Edward A. Fon1
1Montreal Neurological
Institute, McGill University, Montréal, QC, Canada
Objective: To understand the
structural basis of parkin’s function and to gain insight on its mechanism of
activation, Gehring and coworkers have determined the structure of parkin using
X-ray crystallography in collaboration with our group. The structure reveals that
parkin exists in an auto-inhibited state and its activation must be associated
with conformational changes at the C-terminal domain. We investigated the
structural changes of parkin during the activation of parkin using fluorescent
probes, and set out to characterize the activity of parkin in mitochondrial
autophagy (mitophagy) based on insights obtained from the structure of parkin.
Methods: Time-lapse
fluorescent microscopy was used to examine the kinetics of wild-type and mutant
parkin recruitment to the mitochondria after their depolarization with carbonyl
cyanide m-chlorophenyl hydrazone (CCCP). To monitor conformational changes in
parkin during the course of mitophagy, we used a Förster Resonance Energy
Transfer (FRET) -reporter, consisting of the Cerulean fluorescent protein fused
to the N-terminus of parkin, and a tetracysteine motif that binds with high
affinity to the biarsenical dye FlAsH at the C-terminus.
Results: Wild-type parkin was found to recruit to the
mitochondria beginning at 30 mins after CCCP treatment, with half of the cells
showing recruitment at 45 mins, whereas no recruitment of the catalytically
inactive mutant was observed during the first hour. In contrast, the W403A
mutation that releases the auto-inhibition of parkin predisposes parkin for
mitochondrial recruitment, and recruits earlier (10 min) than wild-type.
Preliminary experiments with the FRET reporter constructs show that labelling
at specific positions does not interfere with parkin’s function, and that a
FRET signal is detected. Thus, it is possible to use FRET to monitor
conformational changes in parkin.
LBP08
Balanced ubiquitination and deubiquitination
of MFN regulates mitophagy and affects cell viability
E. Ziviani1, A. Nardin, A. Whitworth and L.
Scorrano
1Department of Cell
Physiology and Metabolism, University
of Geneva Medical School, Geneva, Switzerland
Parkin, an E3
ubiquitin ligase and a Parkinsons's disease related gene, translocates to
impaired mitochondria upon mitochondria intoxication and drives their
elimination via autophagy, a process known as mitophagy. Mitochondrial
pro-fusion protein Mitofusin (Mfn) was found to be a target for Parkin mediated
ubiquitination. In the absence of Parkin, Mfn fails to be ubiquitinated,
affecting mitochondria dynamic. We found that under
stressful conditions, the pattern of Mfn ubiquitination changes, leading to the
disappearance of the ubiquitinated Mfn isoforms and the concomitant increase in
the steady state levels of Mfn. This process is dependent on the activity of
deubiquitination enzyme Usp8, which, in our model, is opposing Parkin in the
ubiquitination of Mfn, ultimately impinging on mitophagy. We therefore
identified a novel pathway where balanced ubiquitination and deubiquitination
of Mfn regulates mitophagy and affects cell survival.
BASIC
SCIENCE: ANIMAL AND CELLULAR MODELS OF PARKINSONISMS
LBP09
Translational profiling reveals novel gene
expression changes in the direct and indirect pathways in a mouse model of
L-DOPA-induced dyskinesia.
Naomi P. Visanji1, Mahdi Ghani2, Carl Virtanen3
& Lili-Naz Hazrati2
1Morton and
Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, Toronto,
ON, Canada
2Tanz Centre for Research
In Neurodegenerative Disease. University of Toronto, Toronto, ON, Canada
3 University Health Network Microarray
Centre, The Toronto Medical Discovery Tower, Toronto, ON, Canada
Objective: The molecular
mechanisms underlying the response of the direct and indirect pathway to
chronic L-DOPA that underlie dyskinesia are poorly understood. Here we employ
two novel transgenic mouse lines, combining translating ribosomal affinity
purification (TRAP) with bacterial artificial chromosome expression (Bac), to
selectively isolate RNA from either D1-expressing striatonigral or
D2-expressing striatopallidal neurons and study changes in translational gene
expression following repeated L-DOPA treatment.
Methods: 6-OHDA lesioned D1
and D2 bacTRAP mice were treated with either saline or L-DOPA/benseraside
(6/15mg/kg) bi-daily for 21d over which time they developed abnormal
involuntary movements reminiscent of dyskinesia. On day 22 all animals received
L-DOPA/benseraside (6/15mg/kg) 1 hour prior to sacrifice. The striatum of the
lesioned hemisphere was dissected and subject to TRAP assay. Purified ribosomal
RNA was amplified (Nugen), purified (Quiagen) and gene expression was
quantified using microarray (Mouse WG-6 v2.0 BeadChip, Illumina).
Results: 195 significantly
varying transcripts were identified among the 4 treatment groups (1-way ANOVA
with a Benjamini-Hochberg FDR of p<0.05). Pathway analysis revealed an overrepresentation of
calcium signaling (HSA04020; Enrichr p value 0.0012) and long term potentiation
(LTP) (HSA04720; Enrichr p value 0.0171) in the direct pathway, with
significant involvement of long term depression (LTD) (HSA04730; Enrichr p
value 0.04) in the indirect pathway following chronic treatment with L-DOPA.
Several MAPK associated genes (Nr4a1, Gadd45g, Stmn1, Fos, Dusp1, and Pak1)
were upregulated in the direct pathway after chronic L-DOPA treatment.
Strikingly the MAPK pathway activator PAK1 was downregulated in the indirect
pathway but upregulated in the direct pathway strongly suggesting a role for
PAK1 in regulating the opposing effects of L-DOPA on these two pathways in
dyskinesia.
Future studies will assess the potential of
targeting these genes and pathways to prevent the development of L-DOPA-induced
dyskinesia.
BASIC SCIENCE: BRAIN PHYSIOLOGY
AND CIRCUITRY
LBP10
Impairment of cerebral auto-regulation in multiple system
atrophy and Parkinson’s disease
Young Jin Kim, Mi-Jung Kim, Sung Reul Kim, Sun Ju Chung,
Department of
Neurology, Asian Medical Center, University of Ulsan College of Medicine,
Seoul, South Korea
Objective: To investigate the characteristics of
cerebral auto-regulation in multiple system atrophy (MSA) and Parkinson’s
disease (PD).
Methods: 23 patients with probable MSA (MSA group) and
15 patients with PD (PD group) were studied. Additionally, 16 patients with
orthostatic hypotension (OH) without neurodegenerative diseases (OH group) and
15 normal controls (control group) were recruited for comparison. All subjects
underwent tilt test with transcranial Doppler (TCD) monitoring. Blood pressure
(BP), heart rate (HR) and blood flow velocity in middle cerebral artery
(MCA-FV) were measured at supine position and at an angle of 70o
from supine on the tilt table. Pulsatility index (PI) and cerebrovascular
resistance (CVR) were also calculated. We used the orthostatic subsection (9
items) of composite autonomic symptom scale (COMPASS) for investigating
symptoms of orthostatic hypotension (Suarez GA, et al., 1999).
Results: Of 23 MSA patients, 10 patients (43.5%) are
classified as MSA-parkinsonian (MSA-P) subtype. Between MSA-P and PD, there was
no significant difference in levodopa equivalent dose and Hoehn-Yahr stage. OH
group had DM, HTN, cardiac disease and peripheral neuropathy more frequently
than other groups. OH was detected in 15 subjects (65.2%) in MSA group and 7
subjects (46.7%) in PD group by tilt test. In COMPASS orthostatic subsection,
there was no significant difference between MSA (16.26 ± 14.52) and PD (11.29 ±
10.52) groups. In tilt test, significant differences were found in supine PI
and CVR, post-tilt systolic MCA-FV, PI and CVR between MSA, PD and OH groups.
In MSA group, positional change of systolic BP showed a significant positive
correlation with the alteration of mean MCA-FV (r=0.468, p=0.024), and COMPASS
score (r=0.527, p=0.010), while COMPASS score was not correlated with change of
mean MCA-FV.
Conclusions: The pattern of cerebral vasomotor control between
MSA/PD and OH group was different, resulting from the change of CVR.
BASIC
SCIENCE: DOPAMINE, RECEPTORS AND OTHER NEUROTRANSMITTERS
LBP11
Striatal and extrastriatal dopamine correlates with
cognition in Lewy body disorders: an 11C altropane PET study
Marta Marquie1, Joseph J. Locascio1,
Dorene M. Rentz1, Trey Hedden1, Keith A.
Johnson1, John H. Growdon1, and Stephen N.
Gomperts1
1Massachusetts General
Hospital, Boston, MA, USA
Objective: The biological
basis of cognitive impairment in Parkinson disease is believed to be
multifactorial, including dopaminergic loss, degeneration of basal forebrain
cholinergic nuclei, cortical Lewy-related pathology, and amyloid deposition. We
investigated the contribution of dopamine deficiency to cognition in Lewy body
disorders (Parkinson Disease (PD), Parkinson disease with dementia (PDD) and
Dementia with Lewy bodies (DLB)) with dopamine transporter (DAT) imaging.
Methods: We
performed MRI and PET with 11C altropane in 19 nondemented subjects
with PD, 14 with parkinsonism and dementia (PDem, including PDD and DLB)
and 17 healthy control subjects (HCS). We analyzed DAT concentration in
putamen, caudate, anterior cingulate (AC), orbitofrontal and prefrontal regions,
using the Standardized Uptake Volume Ratio with partial volume correction, and
we related DAT concentration and global cortical thickness (GCT) to
neuropsychological performance.
Results: DAT concentration in putamen and caudate was similar in PD and
PDem groups and lower than in HCS. Adjusting for putamen DAT concentration, as
a measure of severity of motor disease, caudate DAT concentration was lower in
PDem than in PD. Diagnostic group, adjusted for putamen DAT, GCT, and their
interactions, related to AC DAT concentration (p=0.03), and this association
was modified by both putamen DAT and GCT. In PDem but not PD, lower putamen DAT
concentration related to higher AC DAT concentration. In PDem, loss of caudate
DAT concentration was associated with worse CDR-SB scores and visuospatial
function, while higher AC DAT concentration related to greater impairment in
semantic memory and language. In conclusion, striatal and extrastriatal
dopamine dysfunction both contribute to cognitive impairment in the Lewy body
dementias.
CARE
DELIVERY & QUALITY OF LIFE: CAREGIVING, RELATIONSHIPS, RESPITE CARE,
FAMILIES
LBP12
Experiencing Parkinson’s disease: A PhotoVoice Story
Joyce Bredesen1, Kerry Keenan2
1Metropolitan State
University, St. Paul, MN, USA
2Century College, White Bear Lake, MN,
USA
Objective: The intent of this
research project is to better understand how Parkinson’s disease affects a care
partner’s everyday life. The PhotoVoice methodology used in the study empowered
these care partners to share, through photographs they take, their perceptions
and views of how the disease affects their day-to-day living environment. The
broader aim of this research project is to raise awareness of Parkinson’s
disease with community and health care providers, potentially improving the
delivery of care and services to these and other families.
Methods: Twelve adult care partners living with
someone diagnosed with Parkinson’s disease were invited to participate in the
project. Using PhotoVoice methodology, participants were asked to photograph
images or situations that illustrate the day-to-day realities and challenges of
living with someone with Parkinson’s disease.
The PhotoVoice
methodology enables individuals to use photography to self-select issues of
importance to them. A semi-structured interview is conducted with each
participant using their photographs to guide the interview. Content analysis is
used to identify themes among the interviews.
Results: The PhotoVoice methodology has three main
outcomes: empowerment of the participant, awareness-raising, and the potential
to bring about dialogue and change. At the time of this submission, both
researchers are conducting post-photography interviews. By August 2013, the
research project will be completed. The photos, stories, and themes will be
shared with health care providers and the community at public events in August
and September 2013. Elements of this PhotoVoice project will be incorporated
into nursing curriculum to further educate nurses on evidenced based research
for improved care delivery for families living with Parkinson’s disease.
CARE DELIVERY & QUALITY OF LIFE: DAILY LIFE ACTIVITIES
INCLUDING WORKING & DRIVING
LBP13
Living with Parkinson’s: Impact and
importance of ‘on’ and ‘off time’
Cicely Kerr1,
Charlotte E. Howard1, Emily Lloyd2, James A. Cooper2,
Karissa Johnston3, Emma McIntosh4, Andrew J. Lloyd1
1Oxford
Outcomes, An ICON plc Company, Oxford, Oxfordshire, UK
2GlaxoSmithKline,
Brentford, UK
3Oxford
Outcomes, An ICON plc Company, Vancouver, Canada
4Health
Economics and Health Technology Assessment, University of Glasgow, Glasgow, UK,
(Parkinson’s UK Research Fellow)
Objective: This study aimed
to develop understanding of the experience of living with Parkinson’s, in
particular the impact and importance of ‘on’ and ‘off time’.
Methods: This
two-stage study was conducted using mixed methods. Semi-structured interviews
were conducted with People with Parkinson’s (PwP) (n=20), informal carers (n=6)
and physicians (n=6) in UK and Spain. Qualitative analysis of interview
transcripts informed development of an online stated preference discrete choice
experiment (SPDCE) and survey that was completed by PwP experiencing ≥ 2
hours ‘off time’ daily. Participants were from Spain (n=100), UK (n=98), France
(n=57) and Italy (n=50). The survey, completed with assistance from informal
carers if needed, explored PwP’s experience of ‘on’ and ‘off time’; including
the impact on health-related quality of life (HRQL, using EQ-5D-5L) and
important usual activities (mapped to those covered by UPDRS and PDQ-39). The
relative value to PwP of increasing ‘on time’ and the ability to predict the
start of ‘off time’ was quantified using SPDCE.
Results: PwP reported considerably worse
HRQL during ‘off’ compared to ‘on time’. Activity limitations during ‘off time’
that were of most concern to PwP were self-care (washing and dressing
themselves), mobility at home and communicating effectively. PwP relied heavily
on informal carers for help with ‘off time’ activity limitations. Treatments
offering increased daily duration of ‘on time’ and ability to predict the start
of ‘off time’ to within 1 hour of symptoms returning were valued most highly by
PwP.
Study findings
highlight and quantify the relatively greater impact of Parkinson’s during ‘off
time’ and the value to PwP of increasing daily ‘on time’ and the predictability
of ‘off time’. These findings have relevance for considering PwP’s priorities
in treatment selection and meaningful measurement of treatment benefit. The
study also increases awareness of the broader impact of informal carers
supporting PwP.
Financial Disclosure: Funded by GSK (Study HO-11-802). The views expressed are those of the
authors and not the funding body.
CLINICAL SCIENCES: SYMPTOMS, SIGNS, FEATURES & NON-MOTOR
MANIFESTATIONS
LBP14
The clinical features
of asymptomatic, first degree relatives of Ashkenazi Jewish Parkinson patients,
carriers of the G2019S mutation in the LRRK2 gene
Anat Mirelman1,
Rachel Saunders-Pullman2, Roy N Alcalay3, Avi
Orr-Urtreger1, Lorraine N Clark3, Laurie J Ozelius4,
Karen S Marder3 , Nir Giladi1 and Susan B Bressman2
on behalf of the AJ LRRK2 consortium.
1Tel-Aviv Medical
Center, Tel Aviv, Israel,
2 Beth Israel Medical
Center, NY USA
3Columbia University,
College of Physicians and Surgeons, NY, USA
4Mount Sinai Medical
School of Medicine, NY USA
Objective: To assess differences
between healthy non-manifesting carriers and non-carriers of the G2019S
mutation in the LRRK2 gene.
Methods: 264 Ashkenazi
asymptomatic first degree relatives of Parkinson’s disease (PD) patients,
carriers of the G2019S mutation in the LRRK2 gene participated in this
double blind observational cross sectional study (58 from Beth Israel, 50 from
Columbia University and 156 from Tel Aviv Medical Center). Participants
underwent a battery of tests including the Montreal Cognitive Assessment
(MoCA), neuropsychological tests, the Unified Parkinson’s Disease Rating Scale
(UPDRS), the Spielberg State and Trait Inventory, the University of Pittsburg Smell
Identification Test (UPSIT), the Geriatric Depression Scale (GDS) and the
non-motor symptoms (NMS) questionnaire. Mixed
procedures were used to assess differences between carriers and non-carriers.
Differences between carriers and non-carriers were also assessed based on age
(older and younger than the median age of the cohort=48yrs). Analyses were
adjusted for age, sex, pedigree, years of education and site.
Results: A total of 139 individuals (mean age
51.3±15.2yrs; 54% males) carried the G2019S mutation. Genetic groups were
similar in age, gender, UPDRS-III, MoCA, GDS, and UPSIT . Carriers tended to
have slightly higher scores on the NMS questionnaire than non-carriers (3.1±3.0
vs. 2.2±2.1; p=0.07). Carriers also tended to perform worse on the Stroop
color-word test (49.6±11.5 vs. 52.9±10.8 number of words; p=0.06). 42 carriers
and 31 non-carriers were in the “older group”. Carriers in the ‘older’ group
showed more interference effect during the Stroop than the ‘older’ non-carriers
(p= 0.04) and presented more trait anxiety than non-carriers (p=0.05). Subtle
differences in non-motor symptoms can be detected between non manifesting
carriers and non-carriers of the G2019S mutation in the LRRk2 gene.
These subtle differences are more apparent in older age and may perhaps be
related to changes in the prodromal phase of the disease.
LBP15
Crucial
contribution for asymmetric reduction of arm and leg swing in Parkinson’s
disease: Rigidity versus Bradykinesia?
Kyum-Yil Kwon,
Minjik Kim, Seon-Min Lee, Sung Hoon Kang, Hye Mi Lee, Seong-Beom Koh
Department of
Neurology, Korea University College of Medicine, Seoul, Rep. of Korea
Objective: Asymmetric reduction
of arm and leg swing during gait has been investigated in the field of
Parkinson’s disease (PD). Although it has been shown that rigidity and
bradykinesia are related to the reduction of arm and leg swing representing
gait hypokinesia, the precise pathogenic mechanism of such abnormality remains
to be unknown.
Methods: Through visual
analysis of video clips recording normal walking and standing, we compared
dominant side of rigidity/bradykinesia with more affected side in arm swing, leg
swing, low shoulder, and laterally rotated foot, respectively. Nineteen
patients showing discordance between severe rigidity and bradykinesia as well
as 21 patients revealing concordance between both were enrolled in the current
study.
Results: More rigid limb is
significantly and moderately agreed to more reduction in arm swing (p<0.001, k=0.592) as well as in leg swing (p=0.011, k=0.432).
However, severe bradykinetic limb is not related with arm swing (p=1, k=0.014)
or with leg swing (p=1, k=-0.036). Taken together, our results
indicate that decreased arm and leg swing is more connected with rigidity than
bradykinesia. In addition, both lower shoulder position and external foot
rotation were not significantly associated with rigidity or bradykinesia,
implying that asymmetric posture might be affected by more complicated factors.
We suspect that our findings will contribute to the future research elucidating
gait hypokinesia for the pathophysiology of PD.
LBP16
Impaired perception of facial expressions of emotion and
its link to facial masking in Parkinson’s disease
Michelle Marneweck1, Romina Palermo12,
Geoff Hammond1
1University of Western
Australia, Australia
2ARC Centre of
Excellence in Cognition and its Disorders, Australia
Objective: There is evidence that the ability to label
facial expressions of emotion is impaired in Parkinson’s disease (PD). An
embodied simulationist account of perception of emotion would predict a link
between the ability to perceive expressions of emotion and facial masking
symptoms, the ability to voluntarily contract facial musculature. The
experimental objectives were to investigate basic abilities involved in
perception of facial expressions of emotion and its relationship to facial
masking symptoms.
Methods: Across two experiments (Experiment 1: PD n = 34, control n = 32; Experiment 2: PD n
= 25, controls n = 24) we took
psychophysical measures of (1) the ability to discriminate graded intensities
of facial expressions of emotion from neutral expressions and (2) the ability
to discriminate emotional expressions of graded intensity for each of the four
commonly expressed emotions, anger, disgust, happiness and sadness. We also
explored the relationship between measures of discrimination of emotion and
measures of facial masking, the ability to extract other information from
faces, and overall disease severity.
Results: Those with PD were as a group impaired in
discrimination of all facial expressions of emotion. However, some with PD
performed as well as some of the best-performing controls. In support of
embodied simulation, we found a strong, positive relationship between measures
of discrimination of emotional facial expressions and measures of facial
masking. We also found strong correlations between discrimination of emotion,
the ability to extract other information from faces, and overall disease
severity. The results indicate a broader impairment in extracting from faces
emotional and non-emotional information where impairment in extracting
emotional information is in part contributed by a reduced ability to
voluntarily contracting facial musculature.
LBP17
Olfaction in LRRK2 G2019S Mutation Carriers
Rachel Saunders-Pullman1,2, Anat Mirelman3,
Roy Alcalay4, Cuiling Wang2, Robert Ortega1,
Helen Mejia-Santana2, Avi Orr-Urtreger3, Nir Giladi3,
Karen Marder2, Susan Bressman1,2 and the LRRK2 AJ
Consortium
1Beth Israel Medical
Center, NY, USA
2Albert Einstein
College of Medicine, NY, USA
3Tel Aviv Medical Center,
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
4Columbia University
Medical Center, College of Physicians and Surgeons, Columbia University, NY,
USA
Objective: Olfaction is not impaired in all genetic
forms of PD, and the relative impairment in PD due to LRRK2 G2019S mutations
(manifesting carriers, MC) is disputed. It is also not clear whether there is
an olfactory endophenotype in mutation carriers without PD (non-manifesting
carriers, NMC).
Methods: 126 PD non-carriers(PD-NC), 132 MC, 131
NMC, 106 relative non-carriers(NC-Family) and 35 controls from the MJFF LRRK2
Ashkenazi Jewish Consortium (Tel Aviv Medical Center, Columbia, Beth Israel)
completed University of Pennsylvania Smell Identification Tests(UPSITs). Mixed effects models, including family as the
random effect, and adjusting for age, gender, Montreal Cognitive
Assessment(MoCA) score, site and ever a regular smoker assessed differences in
UPSIT; GEE, accounting for correlated data within clusters of families, and adjusting
for the other co-variates were used to assess odds of hyposmia (≤15th percentile) Simple mixture models were
used to identify subgroups based on olfaction status.
Results: Lower UPSIT score and hyposmia were
associated with male gender, older age, worse MoCA, and testing site (all
p<0.05). All PD had impaired olfaction, however LRRK2 carriers had better
UPSIT (difference 3.5, p<0.001) and reduced odds of hyposmia (OR 0.44,
p=0.01) than PD-NC. NMC did not differ from NC-F or controls. NC-F had worse olfaction
than controls (difference -2.30, p=0.03), although the odds of hyposmia were
not different. Three latent classes were identified in the MC and three in the
NMC. In conclusion, olfactory differences between LRRK2 PD and other PD are
confirmed in our sample. The existence of subgroups of MC suggests that there
may be pathophysiologic heterogeneity in the LRRK2 PD group. Mixture models
might be utilized to facilitate identification of clusters of NMC with
olfactory phenotypes. Site differences in UPSIT should be
considered in cross-cultural comparisons.
CLINICAL SCIENCES: PROGRESSION & PROGNOSIS
LBP18
Modifiable Cardiovascular Risk Factors and Axial Motor
Impairments in Parkinson disease
Vikas Kotagal1, Roger L. Albin1,2,
Martijn L.T.M Müller3, Robert A Koeppe3, Kirk A. Frey1,3
& Nicolaas I. Bohnen1,2,3
1 Department of
Neurology, University of Michigan, Ann Arbor, MI, USA
2 Neurology Service and GRECC, VAAAHS, Ann
Arbor, MI, USA
3 Department of Radiology, University of
Michigan, Ann Arbor, MI, USA
Introduction: Cerebral changes attributable to
cardiovascular comorbidities may aggravate clinical morbidity in various
age-related neurodegenerative disorders, including Parkinson disease (PD).
Cardiovascular risk factors may contribute to extranigral pathologies, which
are thought to associate with dopamine resistant (DR) features including axial
motor impairments in PD.
Methods: In this cross-sectional study, we explored
differences in the estimated rate of axial motor feature accrual between PD
subjects with and without elevated cardiovascular risk factors as estimated by
the Framingham General Cardiovascular Disease risk-scoring algorithm. All
subjects underwent motor evaluations with the Movement Disorders Society
revised Unified Parkinson’s disease Rating Scale (MDS-UPDRS), [11C]dihydrotetrabenazine
(DTBZ) monoaminergic brain PET imaging, and
MRI imaging.
Results: PD subjects with
elevated Framingham risk (FR) scores (n=63, 74.1%) showed higher unadjusted rates
of total MDS-UPDRS (t=3.60,p=0.0006) and axial motor scores (t=3.98,p=0.0001)
per year of motor symptoms compared to subjects with normal risk scores (n=22,
25.9%). After controlling for gender, Montreal Cognitive Assessment score,
frontal leukoaraiosis severity, and striatal DTBZ activity, elevated risk
factor status associated with the rate of accrual of axial motor impairments (t
= 2.62, p =0.011) but not with total MDS-UPDRS motor score (t = 1.51, p =
0.135). Frontal leukoaraiosis associated with the rate of axial and total
MDS-UPDRS scores per year of symptoms and also associated with elevated
systolic blood pressure (t=2.54, p=0.0132) in a separate risk-factor model.
CLINICAL
SCIENCES: COGNITION/ MOOD/ MEMORY
LBP19
The roles of dorsal and ventral striatum in
stimulus-response learning: implications for Parkinson’s disease
Nole Hiebert1,2, Andrew Vo1,3,
Ken Seergobin1, Adam Hampshire1,3, Stephanie Solcz1,
Adrian Owen1,2,3, Allison Partridge1, & Penny
MacDonald1,2,3,4
1Brain and Mind
Institute, University of Western Ontario, London, ON, Canada
2Department
of Physiology and Pharmacology, University of Western Ontario, London, ON,
Canada
3Department
of Psychology, University of Western Ontario, London, ON, Canada
4Department
of Clinical Neurological Sciences, University of Western Ontario, London, ON,
Canada
Objective: Dorsal striatum (DS)
function is impaired whereas ventral striatum (VS) processes are relatively
spared in Parkinson’s disease (PD). These brain regions are also differentially
affected by dopaminergic medication in PD. Our aim was to increase our
understanding of the cognitive functions associated with DS and VS to better
anticipate, explain, and treat cognitive symptoms arising in PD.
Method: Young, healthy adults
performed a task during which they learned to associate abstract images with
one of three button-press responses while in a functional magnetic resonance
imaging (fMRI) machine. During Session 1 (i.e., learning phase), feedback was
provided after each response, facilitating learning through trial and error.
Participants then performed Session 2 where they provided previously learned,
button-press responses for abstract images. Feedback was not provided in this
session to preclude further learning.
Results: DS activation was
seen when participants selected a response (i.e., during decision making) in
Sessions 1 and 2 but not when they received feedback (i.e., during learning) in
Session 1. DS activation increased across the learning phase, opposite to the
learning pattern observed in behavioural data, and correlated with response
accuracy, not learning efficiency. In contrast, VS activity occurred during the
feedback phase, peaked early and decreased over Session 1, mirroring learning
behaviour, and correlated with learning efficiency. These data suggest that DS
is implicated in decision-making, whereas VS mediates learning
stimulus-response associations. In PD, DS-mediated functions are impaired at
baseline and improved with dopaminergic therapy, whereas VS-mediated operations
are normal at baseline and worsened by dopamine replacement. We anticipated
impaired decision-making but not learning in PD, with improvements in
decision-making versus impairment in learning owing to dopaminergic therapy.
The implications of this study inform cognitive complaints and medication
strategies in PD. Understanding striatum-mediated cognition can guide
medication titration in PD, considering individualized motor and cognitive
symptoms.
LBP20
Associations of cognitive domain impairments and gait
disturbance in Parkinson’s disease
Valerie E. Kelly1, Catherine Johnson2,
Ellen L. McGough1, Anne Shumway-Cook1, Fay Horak3,
Alberto J. Espay5, Fredy J. Revilla5, Johnna Devoto5,
Kathy A. Chung3,4, Karen Edwards1,2, Joseph F. Quinn3,4,
Cyrus P. Zabetian1,2, James B. Leverenz1,2
1 University of
Washington, Seattle, WA, USA
2 VA-Puget Sound Health
Care System, Seattle, WA, USA
3 Oregon Health and
Science University, Portland, OR, USA
4 Portland VA Medical
Center, Portland, OR, USA
5University of
Cincinnati, Cincinnati, OH, USA
Objective: Cognitive impairments are prevalent among
people with Parkinson’s disease (PD),but the relationship between gait
impairments and specific cognitive deficits is poorly understood. This study
examined associations between gait and cognitive function, both global and
within specific cognitive domains, in a large, well-characterized sample of
persons with PD.
Methods: A standardized neuropsychological battery
was administered based on published consensus guidelines. Neuropsychological
testing included assessment of global cognition, executive function (including
attention and working memory), language, memory, and visuospatial function.
Multiple linear regression analysis was used to examine the relationship
between cognitive domains and gait disturbance after adjusting for age, sex,
education, disease duration, and motor symptom severity (MDS-UPDRS III).
Separate models were used to examine associations between cognitive domains and
gait outcomes determined from the MDS-UPDRS, Part III: (1) score on the
individual gait items; and (2) postural instability gait disturbance (PIGD)
sub-score, calculated as the sum of gait, freezing of gait, and postural
stability items. Significance was set at α = 0.001 to adjust for multiple
comparisons.
Results: The sample included 635 individuals with PD
who met the UK Brain Bank criteria for PD. Average age was 68 years, and 69% of
the participants were male. In fully adjusted models (for age, gender,
education, disease duration, and MDS-UPDRS III), single-item gait scores were
associated with global cognitive function and executive function, but not
memory or visuospatial function. In fully adjusted models, PIGD scores were
associated with global cognitive function and executive function (i.e., Digit
Symbol scores). More severe gait and PIGD scores were significantly associated
with worse scores on tests of global cognition and tests of executive function,
even after adjusting for covariates. An improved understanding of the
relationship between gait and cognition can inform the development of more
targeted rehabilitation strategies for people with PD.
LBP21
The Montreal Cognitive Assessment across English and
Hebrew
Timothy P. Quinn1, Roy N. Alcalay1,2,
Rachel Saunders-Pullman5, Anat Mirelman3,4, Helen
Meija-Santana1, Deborah Raymond5, Laurie Ozelius10,
Avi Orr-Urtreger6,7, Lorraine Clark8,9, Nir Giladi3,6,
Susan Bressman5, Karen Marder1,2
1Department of Neurology, College of
Physicians and Surgeons, Columbia University, NY, USA
2Taub Institute for
Research on Alzheimer's Disease and the Aging Brain, Columbia University, NY,
USA
3Movement Disorders Unit, Department of
Neurology, Tel-Aviv Medical Center, Sackler School of Medicine, Tel-Aviv
University, Tel-Aviv, Israel
4School of Health Related Professions, Ben
Gurion University, Beer Sheba, Israel
5The Alan and Barbara Mirken Department of
Neurology, Beth Israel Medical Center, NY, USA
6Sackler Faculty of Medicine, Tel Aviv
University, Tel Aviv, Israel.
7Genetics Institute, Tel Aviv Sourasky
Medical Center, Israel
8Department of Pathology and Cell Biology,
College of Physicians and Surgeons, Columbia University, NY, USA
9Center for Human Genetics, College of
Physicians and Surgeons, Columbia University, NY, USA
10Departments of Genetics and Genomic
Sciences and Neurology, Mount Sinai School of Medicine, NY, USA
Objective: The Montreal Cognitive Assessment (MoCA) is
a cognitive screening instrument recommended by the Movement Disorders Society
task force for cognitive screening in Parkinson Disease (PD). The
MoCA is validated in 21 languages including Hebrew and English, however,
it remains unknown whether scores in different languages are comparable. Here,
we compare the Hebrew and English versions of the MoCA.
Methods: The MoCA was administered to 528 Ashkenazi
Jewish (AJ) PD patients in three sites, one in Tel-Aviv and two in New York.
Participants were further evaluated by the Unified Parkinson’s Disease Rating
Scale (UPDRS). Each section of the MoCA was compared between the English and
Hebrew versions. Linear regression models were used to test the association
between MoCA performance (outcome) and language, adjusted for gender, PD
duration, UPDRS-III and levodopa equivalent daily dose. We repeated analyses
restricted to participants with post-secondary education and those with total
scores ≥28/30.
Results: Total MoCA scores were lower in Hebrew than
in English (24.09, SD=3.89 versus 25.19, SD=3.49; p=0.001), even after
adjustment for gender, PD duration, UPDRS-III and levodopa equivalent dose in a
linear model (beta=1.19 ; p<0.001). However, when language tests (sentence
repetition, two points, and fluency, one point) were removed from the total
scores, scores were similar between the languages (Hebrew 22.46, SD=3.44, English
22.61, SD=3.20, p=0.598). When individual questions were compared, percent
correct in Hebrew was significantly lower in sentence repetition (40.8% versus
75.8%, p<0.001) and verbal fluency (41.4% versus 84.6%, p<0.001). Similar
differences were noted when analysis included only those with post-high school
education and those with scores ≥28/30. We conclude that the
language section of the MoCA is more difficult in the Hebrew version than the
English version. Attention should be directed to comparability of items across
languages.
LBP022
Recasting the role of dorsal striatum in learning and
decision-making: A study in Parkinson’s disease
Andrew Vo1,2, Nole Hiebert1,3, Ken
N. Seergobin1, Stephanie Solcz1, Adrian M. Owen1,2,3,
Allison Partridge1, Penny A. MacDonald1,2,3,4
1Brain and Mind
Institute, University of Western Ontario, London, ON, Canada
2Department of
Psychology, University of Western Ontario, London, ON, Canada
3Department of
Physiology and Pharmacology, University of Western Ontario, London, ON, Canada
4Department of Clinical
Neurological Sciences, University of Western Ontario, London, ON, Canada
Objective: Changes to cognitive
functions are now recognized in Parkinson’s disease (PD). Our aim was to
investigate learning and decision-making in PD, as well as the effect of
dopaminergic medication on these separate cognitive processes.
Methods: In Session 1, 36 PD patients and 36
age-matched, healthy control participants learned to associate abstract images
to key-press responses through trial-and-error based on feedback. Half of the
PD patients learned these stimulus-response relations ON medication whereas the
other half learned associations OFF medication. In Session 2, on a separate
day, patients and controls were asked to select key-press responses associated
with abstract images learned in Session 1. No feedback was provided, precluding
new learning. Half of the PD patients performed response selections ON whereas
the other half performed selections OFF medication. For each ON and OFF group
in Session 2, an equal number of participants had learned stimulus-response
relations ON as OFF medication, to reduce carry-over effects from learning
efficiency in Session 1.
Results: PD patients learned stimulus-response associations
significantly more poorly ON relative to OFF medication in Session 1. Further,
learning was impaired in PD patients ON medication relative to controls, though
no differences in learning arose between PD patients OFF medication and
controls. In contrast, PD patients ON and OFF medication performed key-press
responses based on previous learning equally well in Session 2. ON medication
PD patients performed equivalently to controls, however, OFF medication PD
patients performed these decisions more poorly than controls. In PD, learning
is unimpaired but decision-making seems deficient at baseline. Dopaminergic
medication worsens learning stimulus-response associations. At present there is
incomplete understanding of cognitive impairments in PD and the effect of
dopaminergic medication on cognition. Our results help to anticipate these
concerns and guide medication strategies, taking into account motor and
cognitive symptoms, and individual patient priorities.
CLINICAL SCIENCES: DIAGNOSIS (DIFFERENTIAL, ACCURACY)
LBP23
Metrics to analyze micrographia using signature samples
Naiqian Zhi1, Beverly Kris Jaeger1,
Andrew Gouldstone1, Samuel Frank2, Rifat Sipahi1
1Northeastern
University, Boston, MA, USA
2Boston University
Medical Center, Boston, MA, USA
Objective: As a result of the
increased aging population, the total prevalence rates for Parkinson’s disease
(PD) will increase. The debilitating nature of this medical condition involving
hand tremors can negatively impact use of upper limbs for tasks such as
handwriting, potentially resulting in reduced sense of independence, identity
and well-being. More than 75 percent of people with PD have issues with
abnormally small, cramped writing that tends to taper to smaller size (micrographia).
An objective method is sought after here for analyzing micrographia from
individuals’ signatures.
Methods: Here, we apply a
series of metrics on previously published signature samples of patients for
analyzing their micrographia status and the effect on their signature
legibility. The series of metrics measure the global features and local
features of signature samples to detect micrographia progression in different
aspects.
Results: With
micrographia progression, either global features or local features have been
detected to show similar changing trends. The studied metrics could therefore
correlate with the general trends of
how micrographia progresses. Further experimental data needs to be collected in
order to generalize the approach and its statistical reliability.
Financial Disclosure: The authors
gratefully acknowledge funding from US National Science Foundation,
CBET1133992.
CLINICAL SCIENCES: REHABILITATION SCIENCES (PT, OT, SLP)
LBP024
The effect of dopaminergic medication on muscle performance
in people with Parkinson’s disease-related fatigue
Dimitrios Katsavelis, Sam K. Morton, Terry L. Grindstaff,
A. Joseph Threlkeld
Rehabilitation Science
Research Laboratory, Department of Physical Therapy, Creighton University,
Omaha, NE, USA
Objective: Excessive fatigue is a major cause of
disability and activity limitation in people with Parkinson’s disease (PD).
Additionally, withdrawal of dopaminergic medication (DMed) has been reported to
reduce muscle contractile force in people with PD. The underlying mechanisms of
PD fatigue, the response to DMed and the effects of normal aging are poorly
understood. The purpose of this study was to assess thigh muscle performance of
people with PD-fatigue whilst on and off DMEd compared to younger and older
control subjects.
Methods: Eight PD-fatigue (6M, 2F; age=63.4±6; UPDRS
III=4.0±3.8; Parkinson’s Fatigue Scale=10.7±1.6), 10 younger unimpaired (6M,
4F; age=25.1±3) and 4 older (3M, 1F; age=56.0±3) volunteers were assessed.
Subjects with PD-fatigue were tested twice (minimum of 4 days apart), on and
off DMed. Maximum voluntary isometric knee extensor and flexor torque was
determined while monitoring quadriceps and hamstring surface EMG. Superimposed
electrical stimulation was applied to the quadriceps to determine percent
voluntary activation via twitch interpolation (%Activation). The primary
outcome was peak torque (extension and flexion) normalized to body weight
(nPT). Secondary outcome measures included %Activation and EMG co-activation
index of the quadriceps and hamstrings.
Results: DMed withdrawal produced a significant
decrease in quadriceps knee extension nPT (-14%; p=0.02) and a 7% decrease (not
statistically significant; p=0.35) in
knee flexion nPT (Figure 1). Younger controls produced statistically higher nPT
for both muscle groups (Younger vs PD-ON p<0.01;
Younger vs PD-OFF p<0.01; Younger
vs Older p<0.01). The older
controls produced nPT comparable with the ON medication state of the
PD-fatigue. A significant difference in %Activation of the quadriceps
activation was present between younger and older groups (p=0.03). There was no difference in %Activation comparing
PD-Fatigue On vs OFF (Figure 2). EMG co-activation of knee flexors/extensors
was not significantly different between groups although PD-fatigue tended to
have higher co-activation.
Figure
1.
Figure
2.
LBP25
The role of optic flow
on locomotion in young adults during overground walking
Xiaolin Ren1,
Robert C. Wagenaar,1, Cheng-Chieh Lin,1, Alice
Cronin-Golomb,2
1College of Health and
Rehabilitation Sciences: Sargent College, Boston University, Boston, MA, USA
2Department of Psychology,
Boston University, Boston, MA, USA
Objective: This study serves as
the first that investigates the effects of optic flow speed and texture density
on gait patterns during overground comfortable speed walking.
Methods: Fourteen healthy young
adults were instructed to walk straight forward under two visual conditions:
eyes-open, blindfolded. Subsequently, optic flow speed (OS) and dot density
(DD) manipulations were implemented. A virtual hallway consisting of two
sidewalls with random white dots on a black background was displayed via a
head-mounted display. Individual comfortable walking speed (CWS) was estimated
while walking through the virtual hallway. OS manipulations included forward
flow of equal velocity at the CWS, zero OS and backward flow 1, 2 and 3 times
faster than the CWS, with a DD of 50 dots/m2. The DD conditions were 10, 30,
50, 70, and 90 dots/m2 with backward flow equal to the CWS. All the orders were
randomized.
Results: Significant effects of
visual conditions were observed for walking speed, stride frequency, stride
length, and the phase and frequency relations between arm and leg movements.
There was a significant effect of OS on the relative phase between left arm and
leg but not on other variables. Walking speed and stride length increased with
increasing DD from 10 to 70 dots/m2, and slightly decreased from 70 to 90
dots/m2. These findings suggest that the richness of texture embedded in the
optical array influenced the coordination of overground walking, with participants
being more responsive to the changes in DD than OS. These outcomes testified
the important role of visual input in modulating gait patterns which could lay
the foundation for the prospective development of treatments for movement
abnormalities on Parkinson’s disease (PD) patients. Currently, we are
investigating the effects of visual cues displayed on the walking path on gait
regulation in PD patients.
LBP26
Long-term observation
of speech and language in patients with Parkinson’s disease under continuous
Levodopa/Carbidopa intestinal gel therapy
A. Tautscher-Basnett1, V.
Tomantschger1, M. Freimueller1
1Gailtal-Klinik
Hermagor, Neurorehabilitation, Austria
Objective: The investigators’ subjective
impression combined with reports from carers suggest that some patients with
Parkinson’s Disease (PD) benefit from Levodopa/Carbidopa intestinal gel (LCIG)
therapy in terms of intelligibility of speech and verbal expression of
language. Our objective was to analyze audio-recorded speech samples post-hoc
to either refute or confirm this impression.
Methods: 15 patients with LCIG therapy were recorded during a
picture description task at 5 different times (before switching from oral to
LCIG therapy and 6, 12, 18, 24 months with LCIG therapy).
As cognitive decline
over time cannot be ruled out, these results are discussed in the light of the
Mini Mental State Examination (MMSE), which was conducted at the times of
investigation.
The speech samples
were analyzed in terms of number of meaningful units per minute (MUM). In
addition all samples where judged regarding intelligibility of speech by a
student of speech and language therapy using the intelligibility scale of the
Lee Silverman Voice Treatment (LSVT). These scores were summed up with the
judgments of investigator and carers and the arithmetic average scores were
determined.
Results: The following differences in scores before the
switch and with LCIG therapy after 24 months were observed: in 5 patients the cognitive function according to MMSE improved, in 3 it
remained unchanged over time. The verbal expression in 4 of the 5 patients did
not correlate, only one of them improved his rate of MUM, the 3 patients with
constant MMSE scores correlated positively in their MUM scores and 3 patients
improved their MUM score while decreasing slightly (1-2 points) in their MMSE
score. Overall intelligibility of speech improved slightly in 8 patients over
two years, 3 remained stable.
LBP27
Central components of quadriceps fatigue are dopamine
dependent
A. Joseph Threlkeld, Sam K. Morton, Dimitrios Katsavelis,
Terry L. Grindstaff
Rehabilitation Science
Research Lab, Dept. of Physical Therapy, Creighton Univ., Omaha, NE, USA
Objective: Excessive fatigue is a major cause of
disability and activity limitation in ~58% of people with Parkinson’s disease
(PD). Additionally, withdrawal of dopaminergic medication (DMed) has been
reported to reduce muscle contractile force in people with PD. The purpose of
this study was to compare the effects of DMed on the ability of people with
PD-fatigue to maximally activate the un-fatigued vs fatigued quadriceps muscle.
Methods: Eight volunteers with
PD-fatigue were assessed (6M, 2F; age=63.4±6.4; UPDRS III=4.0 ±3.8; Parkinson’s
Fatigue Scale=10.7±1.6). Two testing sessions were conducted > 4 days
apart: one ON prescribed DMed (ON-med) and another session OFF DMed (OFF-med).
The order of ON- vs OFF-med testing was alternated between subjects to minimize
the effect of testing order. Using superimposed electrical stimulation of the
quadriceps and the twitch interpolation technique, percent activation
(%Activation) of the quadriceps muscles was measured prior to (Tpre) and
immediately after (Tpost) a fatiguing-inducing exercise protocol. The fatiguing
exercise consisted of repeated 7-second maximum voluntary knee extension
contractions followed by 3 seconds of rest. The 7-3 contract-relax cycle was
repeated until reaching >35% decrement of each subject’s pre-fatigue
peak torque.
Results:
At
Tpre, the %Activation was not different between the ON- vs OFF-med state
(ON-med=87.7+9.7; OFF-med=84.0+10.3; p=0.35). At Tpost,
%Activation was significantly different between the ON- vs OFF-med
(ON-med=84.7±12.8; OFF-med=73.8±11.5; p=0.022). The reduction in %Activation in
the OFF-med state following exercise-induced fatigue implies a strong
dopamine-dependent central component of exercise-induced fatigue. This finding
has implications for disability, activity limitation and community
participation related to DMed fluctuations over time. Further studies are
underway to discern the interaction of aging and the effects of disease
sub-type (people with and without PD-fatigue).
LBP28
To explore the experiences of people with Parkinson’s
disease of the treatment and care received from a specialist multidisciplinary
team at a particular Parkinson’s Unit
Bharti Udeshi
Edgware Parkinson’s
Unit (EPU), London, UK
Objective: The primary purpose of the study is to
understand the experiences of patients with Parkinson’s disease of the
treatment and care received from a specialist health care team at a particular
Parkinson’s Unit, rather than from separate places.
The secondary purpose
is to inform managers and commissioners of the value of the treatment received
form the specialist healthcare team at the particular Parkinson’s Unit, rather
than from separate places.
Methods: A qualitative study using phenomenological
approach and semi–structured interviews was conducted. Purposive sampling by
third party was carried out using a cross-sectional design. A digital
dictaphone was used for recording the data that was analysed using framework
analysis.
Results: Eight people with Parkinson’s disease and
one carer were interviewed for this study. People recognised that the care
received at the large teaching hospitals was impersonal and dealt “purely” with
their medical needs. They acknowledged the value of receiving coordinated care
at the EPU. Participants appreciated that their progressive needs were being
met with continuing support from the integrated multidisciplinary team at the
EPU. Participants adopted their own specific strategies for coping with limitations.
Thus the findings suggest that the multidisciplinary team at the EPU is meeting
the holistic disease-specific needs of people with Parkinson’s disease compared
to the care received at the large teaching hospitals. The findings also
demonstrate that the disease-specific care management by the multidisciplinary
team at the EPU may promote self-efficacy for individuals with Parkinson’s
disease. However, participants highlighted a need for ongoing psychological
support onsite as this is currently lacking.
CLINICAL SCIENCES: RATING SCALES
LBP29
Olfactory Capability
in Patients with Parkinson’s disease
V. Tomantschger1, A.
Tautscher-Basnett1, M. Freimueller1
1Gailtal-Klinik
Hermagor, Neurorehabilitation, Austria
Objective: Using the „Sniffin’ Sticks
Screening 12“ in assessing patients with Parkinson’s disease (PD) during their
in-patient neurorehabilitation we investigated:
a)
olfactory capability (anosmia, hyposmia, normosmia)
amongst patients with Idiopathic PD (IPD) and patients with Atypical or
Secondary Parkinson Syndromes
b)
correlation of olfactory capability and disease
progression
c)
self perception of olfactory dysfunction
d)
changes in olfactory capability over time
e)
differences in identification between odors.
Methods: Case series comprising 298 patients (60% male, 40%
female) who were assessed during routine care in our neurorehabilitation clinic
over a period of 30 months with „Sniffin’ Sticks Screening 12“. Idiopathic PD:
94%, Atypical Parkinson Syndromes: 5%, Secondary Parkinson Syndromes: 1%.
Analyses in terms of type of PD, time since diagnosis (1-5 years, 6-10 years,
11 and more years), self perception of olfactory dysfunction, differences
between odors and changes in olfactory capability over time.
Results:
a)
IPD (n=280): anosmia: 36%, hyposmia: 55%, normosmia:
9%; Atypical and Secondary Parkinson Syndromes (n=18): anosmia: 27,8%,
hyposmia: 27,8%, normosmia: 44,4%.
b)
Date of diagnosis was known for 276 IPS patients: as
expected, the proportion of normosmia decreased while hyposmia and anosmia
increased steadily over time.
c)
Of 100 IPD anosmics 30% did not judge their olfactory
capacity as impaired; of 154 IPD hyposmics 52% did not realize they had
impaired olfactory capability. Of 18 patients with Atypical or Secondary PD 10
were anosmic or hyposmic and of these 7 (70%) did not think they had olfactory
dysfunction.
d)
38 patients with IPS were assessed at different times:
consistent normosmia: 3; consistent hyposmia: 17; consistent anosmia: 10;
normosmia changed to hyposmia: 3; hyposmia changed to anosmia: 3; hyposmia
changed to normosmia: 1; anosmia changed to hyposmia: 1.
e)
More than 50% misidentifications: cinnamon (53,9%),
lemon (62,5%), licorice (65%), pineapple (60%). Highest correct identification:
orange (73,6%).
LIVING WITH PARKINSON’S: PUBLIC EDUCATION OR AWARENESS PROGRAMS
LBP30
The impact of Parkinson’s disease on community-dwelling
Canadians
Asako Bienek1, Catherine Pelletier1,
Sulan Dai1
1Public Health Agency
of Canada, Ottawa, ON, Canada
Objective: A national population-based survey was
conducted to assess the impact of neurological conditions, including
Parkinson’s disease (PD), on community-dwelling Canadians.
Methods: The 2011 Survey on Living with Neurological
Conditions in Canada was administered to 4,409 respondents age 15+. Targeting
18 neurological conditions, questions covered diagnosis, social support,
changes to work/daily living, and general wellbeing. Data specific to people
with Parkinson’s disease (PwP) were analysed using SAS 9.3; estimates were
weighted to represent the Canadian population, and bootstrapping methods were
used to estimate variance.
Results: A total of n=356 (unweighted) respondents
had PD, representing over 47,000 PwP in Canada. One quarter (27.5%) of
responses was by proxy on behalf of PwP. The majority of respondents with PD
were men (65.2%) and age 65+ (77.8%). Mean age of symptom onset was 63.8
(range= 12 to 89)(no difference by sex). Mean age of diagnosis was 65 (range =
21 to 89). The majority of PwP experienced limitations in at least one usual
activity (79.4%). Only 8.8% were working at the time of survey; 67.1% were not
working and a further 23.4% were permanently unable to work. Of PwP who did
work, 80.3% reported experiencing changes to their work activities because of
their PD. The sense that some people felt uncomfortable around them was the
most frequently reported experience of stigma (80.3%). A lower yet considerable
proportion of PwP reported feeling embarrassed by their condition (45.4%),
perceiving that they were left out of things (34.4%), or perceiving that some
people avoided them (24.1%).
Conclusion: The SLNCC
is being used to identify the impacts of conditions such as PD on Canadians.
This information may support federal and provincial governments, as well as
non-government organizations, to better plan policies, health services, and
awareness strategies for community-dwelling PwP.
LIVING WITH PARKINSON’S: LIVING WELL WITH PD
LBP31
Young Onset Parkinson’s Support Group improves our Quality
of Life
Anne Dowling
Objective: To inform others of how connecting with a
support group made a difference in coping with the disease.
Method: In January 2005 two people with Parkinson’s disease
made a commitment to forming a support group for those with young onset
Parkinson’s. George and Norma found a venue: a small library in White Plains
Hospital and advertised through their doctors and on Parkinson’s websites. For
months they showed up at the designated time and sat alone. Gradually the group
expanded to 4, then 6. By 2006 there were 10 members. Now in 2013, we are proud
to say that our mailing list contains 40 names! We meet once a month; our
current location is Burke Rehabilitation in White Plains New York. We invite
guest speakers to inform us and allow time to share and support each other. We
also organize social activities such as holiday parties, dining out and
attending Parkinson’s symposiums and workshops. We participate in the annual
Parkinson’s Unity walk and this year raised over $21,000.
Results: We encourage anyone who has recently been
diagnosed to connect with a support group. Parkinson’s is a lonely disease.
People with Parkinson’s exert a great deal of energy attempting to minimize the
symptoms to appear “normal”. No one understands this but someone else with
Parkinson’s.
LBP32
Achieving the Impossible Together
Hope Young1, A.J. Hernandez2,
Earl Dumitru2
1Center for Music Therapy, Inc., USA
2Team Dopamine, USA
Objective: To change the environment of fitness programs,
events and trainings to facilitate Parkinson’s patients of all levels to
successfully participate.
Methods: The creation of teams which use
neurologically based training techniques for Parkinson’s patients. Examples of
techniques used are music therapy to improve timing and synchronization of
movements and treadmills with harness support systems for indoor higher speed
cardio training. Personalized tempo music, including tango and other favorites,
is very effective with treadmill and body weight support system (if
appropriate) for gait training, aerobic exercise, and quality of life
enjoyment. Each team member has the goal to participate a minimum of two times
yearly in a 10k event with the Team as a relay member. Each team member must
agree to focus 60% or more of their thoughts on what they can do.
Results: Team I am / I can was formed in 2005.
In October of 2006, five people with moderate to advanced stages of Parkinson’s
disease successfully participated in their first 5k event. Since this time that
Team has successfully competed in 11/10k events. The team size has grown to 40
participants incorporating those who have all stages of Parkinson’s disease as
well as other neurologic movement disorders. Team Dopamine was formed for early
onset Parkinson’s disease? Many who were using walkers now use only canes or
walking sticks. All have decreased the frequency of their falls. All have
slowed the rapid decline of quality of life and decreased the prominence of the
symptoms of their disease. The creation of these Teams has energized its team
members to regularly exercise at a level that demands higher cardio
performance.
Discussion: Although research
supports exercise as beneficial to Parkinson’s patients of all stages very
little has been done to fund or organize fitness programs for Parkinson’s
patients. Most programs that do exist are targeted only to early stage
patients. Team I am/I can provides a safe model to empower living healthier.
Note: Earl Dumitru was
unable to present in Glasgow due to an aortic dissection in August 2010.