Journal of Parkinson's Disease - Volume 9, issue 2

Authors: McFarthing, Kevin | Prakash, Neha | Simuni, Tanya

Article Type: Other

DOI: 10.3233/JPD-199001

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 251-264, 2019

Authors: Mohamed, Nguyen-Vi | Larroquette, Frédérique | Beitel, Lenore K. | Fon, Edward A. | Durcan, Thomas M.

Article Type: Review Article

Abstract: Studying Parkinson’s disease (PD) in the laboratory presents many challenges, the main one being the limited availability of human cells and tissue from affected individuals. As PD is characterized by a loss of dopaminergic (DA) neurons in the brain, it is nearly impossible for researchers to access and extract these cells from living patients. Thus, in the past PD research has focused on the use of patients’ post-mortem tissues, animal models, or immortalized cell lines to dissect cellular pathways of interest. While these strategies deepened our knowledge of pathological mechanisms in PD, they failed to faithfully capture key mechanisms at …play in the human brain. The emergence of induced pluripotent stem cell (iPSC) technology is revolutionizing PD research, as it allows for the differentiation and growth of human DA neurons in vitro , holding immense potential not only for modelling PD, but also for identifying novel therapies. However, to reproduce the complexity of the brain’s environment, researchers are recognizing the need to further develop and refine iPSC-based tools. In this review, we provide an overview of different systems now available for the study of PD, with a particular emphasis on the potential and limitations of iPSC as research tools to generate more relevant models of PD pathophysiology and advance the drug discovery process. Show more

Keywords: Stem cells, CRISPR, co-cultures, neuronal organoids, Parkinson’s disease, cell therapy

DOI: 10.3233/JPD-181515

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 265-281, 2019

Authors: Owen, Charlotte L. | Ibrahim, Kinda | Dennison, Laura | Roberts, Helen C.

Article Type: Review Article

Abstract: Background: Falls are common in Parkinson’s disease (PD). Increased involvement of people with Parkinson’s (PwP) in their care has been associated with enhanced satisfaction. Self-management programmes in other long-term conditions (LTCs) have led to improvements in physical and psychological outcomes. These have been more effective when targeted toward a specific behavior. Objective: This paper aimed to identify and review falls self-management interventions for PwP. Methods: A systematic review was conducted. Electronic databases were searched in June 2018. Primary research studies (any design) reporting the delivery of falls self-management interventions to PwP were included. Data was extracted …from each article and synthesised narratively. Results: Six articles were identified, relating to five different self-management interventions. All described a self-management intervention delivered alongside physiotherapy. Intervention delivery was through either group discussion (n  = 3) or falls booklets (n  = 3). Interventions were often incompletely described; the most common components were information about the condition, training/ rehearsal for psychological strategies and lifestyle advice and support. Arising from the design of articles included the effects of self-management and physiotherapy could not be separated. Three articles measured falls, only one led to a reduction. Four articles measured quality of life, only one led to improvement. No articles assessed skill acquisition or adherence to the self-management intervention. Conclusions: Few falls self-management interventions for PwP have been evaluated and reported. The components of an effective intervention remain unclear. Given the benefits of self-management interventions in other LTCs, it is important that falls self-management interventions are developed and evaluated to support PwP. Show more

Keywords: Accidental falls, parkinson’s disease, patient education as topic, review, self care

DOI: 10.3233/JPD-181524

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 283-299, 2019

Authors: Whone, Alan L. | Boca, Mihaela | Luz, Matthias | Woolley, Max | Mooney, Lucy | Dharia, Sonali | Broadfoot, Jack | Cronin, David | Schroers, Christian | Barua, Neil U. | Longpre, Lara | Barclay, C. Lynn | Boiko, Chris | Johnson, Greg A. | Fibiger, H. Christian | Harrison, Rob | Lewis, Owen | Pritchard, Gemma | Howell, Mike | Irving, Charlie | Johnson, David | Kinch, Suk | Marshall, Christopher | Lawrence, Andrew D. | Blinder, Stephan | Sossi, Vesna | Stoessl, A. Jon | Skinner, Paul | Mohr, Erich | Gill, Steven S.

Article Type: Research Article

Abstract: Background: Intraputamenal glial cell line-derived neurotrophic factor (GDNF), administered every 4 weeks to patients with moderately advanced Parkinson’s disease, did not show significant clinical improvements against placebo at 40 weeks, although it significantly increased [18 F]DOPA uptake throughout the entire putamen. Objective: This open-label extension study explored the effects of continued (prior GDNF patients) or new (prior placebo patients) exposure to GDNF for another 40 weeks. Methods: Using the infusion protocol of the parent study, all patients received GDNF without disclosing prior treatment allocations (GDNF or placebo). The primary outcome was the percentage change from baseline …to Week 80 in the OFF state Unified Parkinson’s Disease Rating Scale (UPDRS) motor score. Results: All 41 parent study participants were enrolled. The primary outcome decreased by 26.7±20.7% in patients on GDNF for 80 weeks (GDNF/GDNF; N = 21) and 27.6±23.6% in patients on placebo for 40 weeks followed by GDNF for 40 weeks (placebo/GDNF, N = 20; least squares mean difference: 0.4%, 95% CI: –13.9, 14.6, p  = 0.96). Secondary endpoints did not show significant differences between the groups at Week 80 either. Prespecified comparisons between GDNF/GDNF at Week 80 and placebo/GDNF at Week 40 showed significant differences for mean OFF state UPDRS motor (–9.6±6.7 vs. –3.8±4.2 points, p  = 0.0108) and activities of daily living score (–6.9±5.5 vs. –1.0±3.7 points, p  = 0.0003). No treatment-emergent safety concerns were identified. Conclusions: The aggregate study results, from the parent and open-label extension suggest that future testing with GDNF will likely require an 80- rather than a 40-week randomized treatment period and/or a higher dose. Show more

Keywords: Glial cell line-derived neurotrophic factor, convection enhanced delivery, Parkinson’s disease, neurorestoration

DOI: 10.3233/JPD-191576

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 301-313, 2019

Authors: Chatterjee, Diptaman | Sanchez, Daniel Saiz | Quansah, Emmanuel | Rey, Nolwen L. | George, Sonia | Becker, Katelyn | Madaj, Zachary | Steiner, Jennifer A. | Ma, Jiyan | Escobar Galvis, Martha L. | Kordower, Jeffrey H. | Brundin, Patrik

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is a synucleinopathy that has multiple neuropathological characteristics, with nigrostriatal dopamine system degeneration being a core feature. Current models of PD pathology typically fail to recapitulate several attributes of the pathogenic process and neuropathology. We aimed to define the effects of combining a mouse model exhibiting multiple PD-like changes with intrastriatal injections of α -synuclein (α -syn) pre-formed fibril (PFFs) aggregates. We employed the heterozygous Engrailed 1 (En1+ /– ) mouse that features several pathophysiological hallmarks of clinical PD. Objective: To test the hypothesis that the neuropathological changes in the En1+ /– …mice will promote formation of α -syn aggregates following intrastriatal injections of pathogenic human α -syn PFFs. Methods: We unilaterally injected PFFs into the striata of 1-month-old En1+ /– and control wild-type mice and euthanized animals at 3 months for post-mortem analysis. Results: Using immunohistochemistry and unbiased stereology, we established that PFF-injected En1+ /– mice exhibited a near-threefold increase in pS129-α -syn-positive neurons in the substantia nigra compared to PFF-injected wild-type mice. The PFF-injected En1+ /– mice also displayed significant increases in pS129-α -syn-positive neurons in the amygdala and ventral tegmental area; regions of known PD pathology with projections to the striatum. Additionally, we observed amplified pS129-α -syn-positive aggregation in En1+ /– mice in multiple cortical regions. Conclusions: Following intrastriatal injection of PFFs, absence of an En1 allele leads to additional aggregation of pathological α -syn, potentially due to En1- loss mediated nigrostriatal impairment. We propose that further development of this double-hit model could result in a PD mouse model that predicts which experimental therapies will be effective in PD. Show more

Keywords: α-Synuclein, Parkinson’s disease, engrailed, proteinopathy, misfolded proteins, propagation, mouse models, neurodegeneration

DOI: 10.3233/JPD-191590

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 315-326, 2019

Authors: Massa, Jason | Chahine, Lana M.

Article Type: Research Article

Abstract: Background: In patients with early parkinsonism, misdiagnosis may occur in >30% of cases. This can have detrimental consequences clinically and in clinical trials. Dopamine transporter (DAT) SPECT imaging can help improve diagnostic accuracy. Objective: To describe characteristics of individuals initially diagnosed with idiopathic Parkinson’s disease (iPD) and with abnormal DAT SPECT imaging who had a change in diagnosis on follow-up. Methods: Data were obtained from the biomarker study Parkinson’s Progression Markers Initiative (PPMI). PPMI is a multicenter, observational study that enrolled 423 individuals with a diagnosis of iPD of ≤2 years duration and with abnormal DAT …SPECT imaging. Participants were assessed at least annually, and diagnosis was documented by the site neurologist. Characteristics of those that had a change in diagnosis were compared to those with stable diagnosis. Results: 390 subjects were included. Eight (2%) had a change in diagnosis. The diagnosis was changed to multiple system atrophy in 5 cases, dementia with Lewy bodies in 2, and corticobasal degeneration in 1. Revision of diagnosis occurred 2–5.2 years from enrollment. Mean motor score was higher (26.9 vs 20.6; p  = 0.01), DAT binding lower (1.056 vs 1.406; p  = 0.01), genetic risk score lower (–0.016 vs –0.022; p  = 0.0470), and olfaction score higher (28.75 vs 22.05; p  = 0.03) in those whose diagnosis changed compared to those who did not. Conclusion: Diagnosis remained stable in most individuals with early parkinsonism diagnosed with iPD and with abnormal DAT imaging. A small number had a revision in diagnosis. Clinical and biomarker abnormalities were greater at baseline in those whose diagnosis changed. Show more

Keywords: Parkinson’s disease, parkinsonism, movement disorders, SPECT, DAT scan, multiple system atrophy, atypical parkinsonism

DOI: 10.3233/JPD-181517

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 327-334, 2019

Authors: Kalyani, H.H.N | Sullivan, Karen | Moyle, Gene | Brauer, Sandy | Jeffrey, Erica Rose | Roeder, Luisa | Berndt, Sara | Kerr, Graham

Article Type: Research Article

Abstract: Dance-based interventions have been proposed for the management of Parkinson’s disease (PD) symptoms. This review critically appraises and synthesises the research on the effects of dance interventions on gait, cognition and dual-tasking in PD, through a meta-analysis of peer-reviewed literature from seven databases. Eligible studies included people with PD, used a parallel-group or cohort design with a dance-based intervention, reported outcome measures of gait, cognition or dual-tasking, and were published in English up until September 2017. Of the initial 1079 articles, 677 articles were reviewed for eligibility, and 25 articles were retained. Only 12 articles had sufficient common assessment items …for meta-analysis. Two independent reviewers extracted the data and assessed the risk of bias of each study using the Cochrane risk-of-bias tool. Based on pre-post change scores, gait speed, Timed Up and Go (TUG) test performance, freezing of gait questionnaire, and six-minute walk test times significantly improved after a dance intervention compared to controls. Global cognition assessed with Montreal Cognitive Assessment, and cognitive dual-tasking measured using dual-task TUG, also exhibited greater improvement in dance groups. There was limited evidence to determine the most effective intensity, frequency, duration of dance interventions or the most beneficial music. Findings must be interpreted cautiously because of the lack of randomised control trials, and the moderate to high risk of bias of studies. However, the results of papers with level-I and level-II.1 evidence suggest that dance may have the potential to ameliorate PD symptoms, particularly gait, global cognition and cognitive dual-tasking. Show more

DOI: 10.3233/JPD-181516

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 335-349, 2019

Authors: Sleeman, Isobel | Lawson, Rachael A. | Yarnall, Alison J. | Duncan, Gordon W. | Johnston, Fionnuala | Khoo, Tien K. | Burn, David J.

Article Type: Research Article

Abstract: Background: Urate and homocysteine are potential biomarkers for disease progression in Parkinson’s disease (PD). Baseline serum urate concentration has been shown to predict motor but not cognitive decline. The relationship between serum homocysteine concentration and cognitive and motor impairment is unknown. Objectives: The aim of this study was to examine the association between baseline serum urate and homocysteine, and prospective measures of disease progression and cognition over 54 months in early PD. Methods: 154 newly diagnosed PD participants and 99 age-matched controls completed a schedule of assessments at baseline, 18, 36 and 54 months. The Movement …Disorders Society Unified Parkinson’s Disease Scale Part III (MDS-UPDRS III) was used to assess motor severity. The Montreal Cognitive Assessment (MoCA) was used to assess global cognition. Serum samples drawn at baseline were analysed for urate, homocysteine, red cell folate and vitamin B12 concentrations. Results: Baseline urate was 331.4±83.8 and 302.7±78.0μ mol/L for control and PD participants, respectively (p  = 0.015). Baseline homocysteine was 9.6±3.3 and 11.1±3.8μ mol/L for controls and PD participants, respectively (p  < 0.01). Linear mixed effects modelling showed that lower baseline urate (β = 0.02, p  < 0.001) and higher homocysteine (β = 0.29, p  < 0.05) predicted decline in motor function. Only higher homocysteine concentrations at baseline, however, predicted declining MoCA scores over 54 months (β = 0.11, p  < 0.01). Conclusions: Lower serum urate concentration is associated with worsening motor function; while higher homocysteine concentration is associated with change in motor function and cognitive decline. Therefore, urate and homocysteine may be suitable biomarkers for predicting motor and cognitive decline in early PD. Show more

Keywords: Parkinson’s disease, urate, homocysteine, disease progression, prospective study

DOI: 10.3233/JPD-181535

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 351-359, 2019

Authors: Markaki, Ioanna | Klironomos, Stefanos | Svenningsson, Per

Article Type: Research Article

Abstract: Background: Cerebral small vessel disease (SVD), often manifesting as white matter lesions (WMLs), and Parkinson’s disease (PD) are common disorders whose prevalence increases with age. Vascular risk factors contribute to SVD, but their role in PD is less clear. Objectives: The study objective was to investigate the frequency and grade of WMLs in PD, and their association with clinical and biochemical parameters. Methods: In total, 100 consecutive patients with available magnetic resonance imaging were included. Vascular risk factors including smoking, hypertension, diabetes type 2, atrial fibrillation, heart insufficiency and hypercholesterolemia were assessed. In 50 patients that …had underwent lumbar puncture, cerebrospinal fluid (csf) levels of beta-amyloid1-42 , tau and phospho-tau were measured. Results: WMLs were present in 86 of 100 patients. Increasing WML severity was independently associated with increased age and lower csf beta-amyloid1-42 . Conclusions: In our study, WMLs were very common in patients with PD, and were associated with low levels of csf beta-amyloid1-42 . Longitudinal studies would increase understanding of the interplay between WMLs and amyloid pathology in PD. Show more

Keywords: Parkinson’s disease, cerebral small vessel disease, amyloid-beta, cerebrospinal fluid

DOI: 10.3233/JPD-181486

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 361-367, 2019

Authors: Fründt, Odette | Grashorn, Wiebke | Buhmann, Carsten | Forkmann, Katarina | Mainka, Tina | Bingel, Ulrike | Schmidt, Katharina

Article Type: Research Article

Abstract: Background: Pain is highly prevalent in patients with Parkinson’s disease (PD), but underlying pathophysiological mechanisms are largely unclear. Alterations in somatosensory processing might contribute to sensory abnormalities in PD. Objective: This study investigated sensory processing in PD patients. Methods: We used the standardized “Quantitative Sensory Testing” (QST) protocol (German Research Network on Neuropathic Pain) to investigate 13 somatosensory parameters in 19 PD patients naïve to dopaminergic medication and 19 healthy controls matched for age, gender, and handedness. We tested for differences in sensory parameters between i) drug-naïve PD patients and healthy controls, ii) patients’ more and …less affected body side, and iii) for an association of somatosensory parameters with disease-specific factors. Results: We did not observe any significant group differences in somatosensory parameters between PD patients and healthy subjects. In PD patients, QST mean z-scores did not differ between the predominantly and the less affected body side, PD patients with and without PD-specific chronic pain or between different PD subtypes. Age, but not PD disease severity, was associated with a greater loss of function in thermal and mechanical detection thresholds. Conclusions: Somatosensory processing, as assessed with the well-established QST protocol, was normal in drug-naïve PD patients. Thus, somatosensory abnormalities previously reported in medicated PD patients might rather be a result of dopaminergic medication, or may occur later in the course of the disease or with increasing age. Show more

Keywords: QST, quantitative sensory testing, Parkinson’s disease, drug-naïve

DOI: 10.3233/JPD-181513

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 369-378, 2019

Authors: Khedr, Eman M. | Al-Fawal, Bastawy | Abdel Wraith, Ahmed | Saber, Mostafa | Hasan, Asmaa M. | Bassiony, Ahmed | Nasr Eldein, Ahmed | Rothwell, John C.

Article Type: Research Article

Abstract: Background: There is evidence that both high and low frequency rTMS may have therapeutic effects on motor performance of Parkinson’s disease. Objective: The aim of the study was to conduct the first direct comparison of the two approaches. Methods: 52 PD patients were randomly classified into two groups. The first group received 20 Hz and the 2nd group received 1 Hz rTMS with a total of 2000 pulses over M1of each hemisphere for ten days. Effects were assessed with the Unified Parkinson’s Disease Rating Scale part III (UPDRS), Instrumental Activity of Daily Living (IADL), and a self-assessment score …(SA) before, after the last session, and one month later. Cortical excitability was measured before and after the end of sessions. Results: There was a significant improvement on all rating scales after either 1 Hz or 20 Hz rTMS, but the effect persisted for longer after 20 Hz (treatment X time interaction for UPDRS and IADL (P  = 0.075 and 0.04, respectively). Neither treatment affected motor thresholds, but 20 Hz rTMS increased MEP amplitude and the duration of transcallosal inhibition. In an exploratory analysis, each group was subdivided into akinetic-rigid and tremor dominant subgroups and the effects of 1 Hz and 20 Hz treatment recalculated. There was weak evidence that patients with an akinetic-rigid presentation may respond better than those with predominant tremor. Conclusion: Both 20 Hz and 1 Hz rTMS improve motor function in PD, but 20 Hz rTMS is more effective. Show more

Keywords: ClinicalTrials.gov Identifier: NCT03342846

DOI: 10.3233/JPD-181540

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 379-387, 2019

Authors: Chuang, Yu-Hsuan | Lu, Ake T. | Paul, Kimberly C. | Folle, Aline D. | Bronstein, Jeff M. | Bordelon, Yvette | Horvath, Steve | Ritz, Beate

Article Type: Research Article

Abstract: Background: DNA methylation studies in Parkinson’s disease (PD) thus far have focused on disease susceptibility but not progression. Objective: In this epigenome-wide association study (EWAS), we aim to identify methylation markers associated with faster cognitive decline or motor progression in PD. Methods: We included 232 PD patients from the Parkinson’s Environment and Gene follow-up study who provided blood samples at enrolment. Information on cognitive and motor function was collected using the Mini-Mental State Examination (MMSE) and Unified Parkinson’s Disease Rating Scale (UPDRS). For EWAS analyses, we used a robust measure of correlation: biweight midcorrelations, t -tests, …and Cox proportional hazard models. We also conducted weighted correlation network analysis (WGCNA) to identify CpG modules associated with cognitive decline or motor progression in PD. Results: Among 197 individuals of European ancestry, with our EWAS approach we identified 7 genome-wide significant CpGs associated with a MMSE 4-point decline and 8 CpGs associated with faster motor progression (i.e., rate of UPDRS increase ≥5-point/year). The most interesting CpGs for cognitive decline include cg17445913 in KCNB1 (cor = 0.36, p  = 6.85×10–7 ) and cg02920897 in DLEU2 (cor = 0.34, p  = 3.23×10–6 ), while for motor progression it was cg01754178 in PTPRN2 (cor = – 0.34, p  = 2.07×10–6 ). In WGCNA, motor progression related modules were enriched for genes related to neuronal synaptic functions, Wnt signaling pathway, and mitochondrial apoptosis. Conclusions: Our study provides the first epigenetic evidence that differential methylation in genes previously identified as being associated with cognitive impairment, neuronal synaptic function, Wnt signaling pathway, and mitochondrial apoptosis is associated with cognitive and motor progression in PD. Show more

Keywords: Parkinson’s disease, disease progression, longitudinal studies, cognitive decline, MMSE, UPDRS, DNA methylation

DOI: 10.3233/JPD-181549

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 389-400, 2019

Authors: Spear, Kelsey L. | Auinger, Peggy | Simone, Richard | Dorsey, E. Ray | Francis, Jessica

Article Type: Research Article

Abstract: Background: Telemedicine is increasingly used for Parkinson disease, but the perspectives of persons with Parkinson disease have not been systematically assessed. Methods: We therefore conducted a national online survey, and 781 individuals with Parkinson disease responded. Results: Of these, 76% indicated high interest, and 29% reported prior telemedicine experience. The top advantages included access to specialists (62%), convenience (60%), and time savings (59%). The most common disadvantages were the lack of hands-on care (69%), lack of intimacy (43%), and technical difficulties (37%). Conclusions: In this non-representative sample, interest in telemedicine was high but tempered …by the concern for loss of high touch care. Show more

Keywords: Movement disorders, Parkinson disease, telehealth, telemedicine

DOI: 10.3233/JPD-181557

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 401-404, 2019

Authors: Yoo, Sang-Won | Kim, Joong-Seok | Oh, Yoon-Sang | Ryu, Dong-Woo | Lee, Kwang-Soo

Article Type: Research Article

Abstract: Background: Trouble concentrating during orthostasis is one symptom of orthostatic hypotension (OH), but it is often ignored in clinical practice because OH incorporates many nonspecific symptoms. Blunted cognition during orthostasis may affect various aspects of the clinical status of patients with Parkinson’s disease (PD), but its impact on drug-naïve, early PD patients is not clear. Objective: This study investigated the association between trouble concentrating during orthostasis and orthostatic blood pressure changes and the influence of trouble concentrating during orthostasis on other non-motor symptoms and health-related quality of life in de novo PD. Methods: A total …of 124 patients with early PD were enrolled and received a structured clinical interview, physical examination, and validated questionnaires to evaluate motor and non-motor symptoms and quality of life. Disturbed concentration was evaluated with question 5 of the Orthostatic Hypotension Questionnaire system assessment (part I). Supine blood pressure and blood pressure change during tilt table testing were recorded, and any association was analyzed. Results: Among the study population, 76 (61.3%) patients had trouble concentrating. Patients with blunted concentration had a steeper decrease in blood pressure during orthostasis. The score for trouble concentrating was positively associated with non-motor symptoms and quality of life scores. Conclusions: Trouble concentrating when standing was a frequent finding in early, drug-naïve PD patients. It was positively associated with non-motor burden, mood and quality of life in patients with PD. OH was correlated with the incidence of trouble concentrating. Such findings complicate treatment but provide valuable information for managing early PD. Show more

Keywords: Orthostatic hypotension, Parkinson’s disease, quality of life, trouble concentrating

DOI: 10.3233/JPD-191578

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 405-411, 2019

Authors: Gaßner, Heiko | Steib, Simon | Klamroth, Sarah | Pasluosta, Cristian F. | Adler, Werner | Eskofier, Bjoern M. | Pfeifer, Klaus | Winkler, Jürgen | Klucken, Jochen

Article Type: Research Article

Abstract: Background: Impaired gait and postural stability are cardinal motor symptoms in Parkinson’s disease (PD). Treadmill training improves gait characteristics in PD. Objective: This study investigates if postural perturbations during treadmill training improve motor performance and particularly gait and postural stability in PD. Methods: This work presents secondary outcome measures of a pilot randomized controlled trial. PD patients (n  = 43) recruited at the University Hospital Erlangen were randomly allocated to the experimental (perturbation treadmill training, PTT, n  = 21) or control group (conventional treadmill training, CTT, n  = 22). Outcome measures were collected at baseline, after 8 weeks of …intervention, and 3 months follow-up. Motor impairment was assessed by the Unified Parkinson Disease Rating Scale part-III (UPDRS-III), Postural Instability and Gait Difficulty score (PIGD), and subitems ‘Gait’ and ‘Postural stability’ by an observer blinded to the randomization. Intervention effects were additionally compared to progression rates of a matched PD cohort (n  = 20) receiving best medical treatment (BMT). Results: Treadmill training significantly improved UPDRS-III motor symptoms in both groups with larger effect sizes for PTT (–38%) compared to CTT (–20%). In the PTT group solely, PIGD –34%, and items ‘Gait’ –50%, and ‘Postural stability’ –40% improved significantly in comparison to CTT (PIGD -24%, ‘Gait’ –22%, ‘Postural stability’ –33%). Positive effects persisted in PTT after 3 months and appeared to be beneficial compared to BMT. Conclusions: Eight weeks of PTT showed superior improvements of motor symptoms, particularly gait and postural stability. Sustainable effects indicate that PTT may be an additive therapy option for gait and balance deficits in PD. Show more

Keywords: Gait analysis, parkinson’s disease, postural stability, treadmill training

DOI: 10.3233/JPD-181534

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 413-426, 2019

Authors: Borm, Carlijn D.J.M. | Smilowska, Katarzyna | de Vries, Nienke M. | Bloem, Bastiaan R. | Theelen, Thomas

Article Type: Short Communication

Abstract: Visual disorders like double vision, dry eyes, and visual field deficits are common but frequently missed in Parkinson’s disease. Here, we aim to increase awareness for these visual disorders in Parkinson patients by discussing several common problems that can be easily diagnosed using comprehensive history taking and a basic neuro-ophthalmological examination. We offer practical guidance for the patient interview and physical exam that can facilitate a timelier recognition of visual disorders. Such recognition has immediate therapeutic relevance, because Parkinson patients are strongly dependent on an adequate vision, for example to optimally benefit from visual cueing strategies.

Keywords: Neuro-ophthalmology, parkinson’s disease, vision

DOI: 10.3233/JPD-181523

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 427-435, 2019

Authors: Radder, Danique L.M. | Tiel Groenestege, Andreas T. | Boers, Inge | Muilwijk, Eline W. | Bloem, Bastiaan R.

Article Type: Case Report

Abstract: We present a 48-year-old woman with Parkinson’s disease in whom carbidopa was added to Mucuna pruriens, resulting in marked motor improvement (documented on video and using MDS-UPDRS motor scores). This case report shows that adding a dopa-decarboxylase inhibitor (DDCI) to Mucuna pruriens could fit well in a personalized approach for patients who are reluctant to start levodopa. Meanwhile, larger trials with a longer follow-up are needed to establish the true effects and tolerability of Mucuna pruriens plus a DDCI.

Keywords: Dopa-decarboxylase inhibitor, Mucuna pruriens, Parkinson’s disease, personalized medicine

DOI: 10.3233/JPD-181500

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 437-439, 2019

Authors: Kho, Kuan H. | Leijten, Quinten H. | Dorresteijn, Lucille D. A.

Article Type: Case Report

Abstract: The authors report of a patient with Parkinson’s disease in whom imaging revealed a complete agenesis of the corpus callosum. Although this co-occurrence is probably coincidental, this finding suggests that the bilateral degenerative changes in Parkinson’s disease may occur independent of the interhemispheric connections.

Keywords: Agenesis of corpus callosum, corpus callosum, Parkinson’s disease, Parkinsonian disorders

DOI: 10.3233/JPD-191599

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 441-442, 2019

Authors: Polymeropoulos, Mihael H.

Article Type: Letter

DOI: 10.3233/JPD-191569

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 443-444, 2019

Authors: Nussbaum, Robert L.

Article Type: Letter

DOI: 10.3233/JPD-190001

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 445-445, 2019

Authors: Rosqvist, Kristina | Odin, Per | Hagell, Peter | Iwarsson, Susanne | Nilsson, Maria H. | Storch, Alexander

Article Type: Correction

DOI: 10.3233/JPD-189380

Citation: Journal of Parkinson's Disease, vol. 9, no. 2, pp. 447-448, 2019