Journal of Parkinson's Disease - Volume 12, issue 6

Authors: Salles, Philippe A. | Liao, James | Shuaib, Umar | Mata, Ignacio F. | Fernandez, Hubert H.

Article Type: Review Article

Abstract: Parkinson’s disease (PD) is in some cases predisposed-or-caused by genetic variants, contributing to the expression of different phenotypes. Regardless of etiology, as the disease progresses, motor fluctuations and/or levodopa-induced dyskinesias limit the benefit of pharmacotherapy. Device-aided therapies are good alternatives in advanced disease, including deep brain stimulation (DBS), levodopa-carbidopa intestinal gel, and continuous subcutaneous infusion of apomorphine. Candidate selection and timing are critical for the success of such therapies. Genetic screening in DBS cohorts has shown a higher proportion of mutation carriers than in general cohorts, suggesting that genetic factors may influence candidacy for advanced therapies. The response of monogenic …PD to device therapies is not well established, and the contribution of genetic information to decision-making is still a matter of debate. The limited evidence regarding gene-dependent response to device-aided therapies is reviewed here. An accurate understanding of the adequacy and responses of different mutation carriers to device-aided therapies requires the development of specific studies with long-term monitoring. Show more

Keywords: Parkinson’s disease, parkinsonian disorders, genetic disorders, apomorphine, levodopa, infusion pumps, deep brain stimulation

DOI: 10.3233/JPD-212986

Citation: Journal of Parkinson's Disease, vol. 12, no. 6, pp. 1703-1725, 2022

Authors: Wang, Jian-Yong | Huang, Jie-Fan | Zhu, Shi-Guo | Huang, Shi-Shi | Liu, Rong-Pei | Hu, Bei-Lei | Zhu, Jian-Hong | Zhang, Xiong

Article Type: Review Article

Abstract: Parkinsonism-hyperpyrexia syndrome (PHS) and dyskinesia-hyperpyrexia syndrome (DHS) are rare but exhibit life-threatening complications in Parkinson’s disease (PD). We herein presented two cases of PD patients and performed a comprehensive and comparative literature review for these two syndromes. The first case was diagnosed as PHS with cerebral salt wasting syndrome caused by abrupt withdrawal of antiparkinsonian medication. Her symptoms were gradually remitted with reinstitution of the medication. The second one was an early-stage PD patient diagnosed as DHS in association with abuse of antiparkinsonian drugs. Her symptoms were gradually remitted with reduced dosage of dopaminergic drugs. Results of literature reviews revealed …a total of 56 and 13 cases of PHS and DHS, respectively, and they were more likely to occur in elderly and long-term PD patients. These two syndromes showed different female-to-male ratio, similar mortality, and different recovery time. There were stark differences between PHS and DHS, including triggers (abrupt drug stoppage versus drug abuse), symptoms (worsened tremor and rigidity versus continuous dyskinesia), and treatment (drug reinstitution versus drug reduction). In summary, our reports and the review provide new insights into PHS and DHS in association with PD and may facilitate rapid discrimination of the syndromes for timely and proper treatment to reduce mortality. Show more

Keywords: Parkinsonism-hyperpyrexia syndrome, dyskinesia-hyperpyrexia syndrome, Parkinson’s disease, emergency, complication

DOI: 10.3233/JPD-223362

Citation: Journal of Parkinson's Disease, vol. 12, no. 6, pp. 1727-1735, 2022

Authors: Chua, Shaun Kai Kiat | Saffari, Seyed Ehsan | Lee, Selene Joon Yan | Tan, Eng-King

Article Type: Research Article

Abstract: Background: The relationship between Parkinson’s disease (PD) and coronary artery disease (CAD) is unclear. Objective: This study aims to investigate whether PD and CAD are associated through systematic review and meta-analysis of observational studies. Methods: Electronic database search of PubMed, EMBASE, and Web of Science for observational studies published from 1 January 2010 to 1 August 2021 was conducted using terms related to PD and CAD. Unadjusted risk ratios (RR) and odds ratios (OR) of included cohort and case-control studies respectively were used to ascertain the association between PD and CAD. Study heterogeneity was evaluated using …the I2 test. Results: Forty-one full-text studies were initially retrieved for eligibility assessment. Five studies that satisfied the inclusion criteria, consisting of three cohort and two case-control studies, were eventually included in this meta-analysis. The five studies enrolled 35,237 PD patients and 650,866 non-PD patients. PD and CAD were found to be significantly associated in cohort studies (RR = 2.23, 95% CI = 1.08–4.59, p  = 0.03; Fig. 2 ), which held after sensitivity analysis (RR = 1.45, 95% CI = 1.31–1.60, p  < 0.001; Fig. 3 ). Case-control studies found a trend towards association of PD and CAD approaching significance (OR = 1.47, 95% CI = 0.84–2.56, p  = 0.18; Fig. 2 ). Conclusion: Overall, this meta-analysis suggests that PD is associated with CAD. The underlying mechanisms, as well as the role of ethnicity and other comorbidities on the relationship between PD and CAD should be further explored. Show more

Keywords: Coronary artery disease, meta-analysis, observational studies, Parkinson’s disease, systematic review

DOI: 10.3233/JPD-223291

Citation: Journal of Parkinson's Disease, vol. 12, no. 6, pp. 1737-1748, 2022

Authors: Liebermann-Jordanidis, Hannah | Roheger, Mandy | Boosfeld, Lukas | Franklin, Jeremy | Kalbe, Elke

Article Type: Systematic Review

Abstract: Background: Visuo-cognitive impairment is common in patients with Parkinson’s disease with mild cognitive impairment (PD-MCI) and constitutes a prognostic factor for the conversion to Parkinson’s disease dementia (PDD). However, systematic analyses on which neuropsychological tests are most suitable to assess visuo-cognition in PD-MCI and PDD and to differentiate these cognitive stages are lacking. Objective: To review neuropsychological tests used to assess visuo-cognition including visuo-perceptual and visuo-spatial processing, visuo-constructive copying and drawing on command abilities; and to identify the visuo-cognitive subdomain as well as tests most suitable to discriminate between PD-MCI and PDD. Methods: MEDLINE, PsycINFO, Web …of Science Core Collection, and CENTRAL were systematically searched for relevant studies assessing visuo-cognitive outcomes in patients with PD-MCI and PDD. Risk of bias was assessed using a customized form based on well-established tools. Random-effect meta-analyses were conducted. Results: 33 studies were included in the systematic review. Data of 19 studies were entered in meta-analyses. Considerable heterogeneity regarding applied tests, test versions, and scoring systems exists. Data indicate that visuo-constructive command tasks are the subdomain best suited to discriminate between PD-MCI and PDD. Furthermore, they indicate that the Rey-Osterrieth-Complex-Figure Test (ROCF), Corsi Block-Tapping Test, Judgment of Line Orientation (JLO), and Clock Drawing Test (CDT) are tests able to differentiate between the two stages. Conclusion: We provide suggestions for suitable visuo-cognitive tests (Corsi Block-Tapping Test, or JLO, ROCF, CDT) to improve diagnostic accuracy. Methodological challenges (e.g., heterogeneity of definitions, tests) are discussed and suggestions for future research are provided. Registration: https://www.crd.york.ac.uk/prospero/ , ID: CRD42018088244 Show more

Keywords: Parkinson’s disease, cognition, cognitive aging, spatial learning, spatial processing, neuropsychological tests

DOI: 10.3233/JPD-223238

Citation: Journal of Parkinson's Disease, vol. 12, no. 6, pp. 1749-1782, 2022

Authors: Gollan, Romina | Ernst, Moritz | Lieker, Emma | Caro-Valenzuela, Julia | Monsef, Ina | Dresen, Antje | Roheger, Mandy | Skoetz, Nicole | Kalbe, Elke | Folkerts, Ann-Kristin

Article Type: Systematic Review

Abstract: Background: Previous reviews indicated positive effects of resistance training (RT) on motor outcomes in Parkinson’s disease (PD). However, inconsistencies between the included studies exist, and non-motor outcomes have only scarcely been considered in a review on RT in PD. Objective: To analyze the RT effects on motor- and non-motor outcomes in PD patients compared to passive and physically active control groups (i.e., other structured physical interventions). Methods: We searched CENTRAL, MEDLINE, EMBASE, and CINAHL for randomized controlled trials of RT in PD. After identifying 18 studies, a meta-analysis was conducted for the outcomes muscle strength, motor …impairment, freezing of gait (FoG), mobility and balance, quality of life (QoL), depression, cognition, and adverse events. Meta-analyses with random models were calculated using mean differences (MD) or standardized mean differences (SMD) with 95% confidence intervals (CI). Results: When comparing RT with passive control groups, the meta-analyses showed significant large effects on muscle strength (SMD = –0.84, 95% CI –1.29––0.39, p  = 0.0003), motor impairment (SMD = –0.81, 95% CI –1.34––0.27, p  = 0.003), mobility and balance (MD = –1.81, 95% CI –3.13––0.49, p  = 0.007), and small significant effects on QoL (SMD = –0.48, 95% CI –0.86––0.10, p  = 0.01). RT compared with physically active control groups reached no significant results for any outcome. Conclusions: RT improves muscle strength, motor impairment, mobility and balance, QoL, and depression in PD patients. However, it is not superior to other physically active interventions. Therefore, exercise is important for PD patients but according to this analysis, its type is of secondary interest. Show more

Keywords: Parkinson’s disease, resistance training, muscle strength, motor outcomes, non-motor outcomes

DOI: 10.3233/JPD-223252

Citation: Journal of Parkinson's Disease, vol. 12, no. 6, pp. 1783-1806, 2022

Authors: van Munster, Marlena | Stümpel, Johanne | Thieken, Franziska | Ratajczak, Florin | Rascol, Olivier | Fabbri, Margherita | Clemens, Timo | Czabanowska, Katarzyna | Mestre, Tiago A. | Pedrosa, David J.

Article Type: Systematic Review

Abstract: Background: Quality of life (QoL) of persons with Parkinson’s disease (PD) is diminished by (non-)motor symptoms, that require personalized care. Parkinson Nurses (PN) may be pivotal promoting tailored care offerings. This systematic review and meta-analysis investigates PD care models and aims at furnishing current concepts of PN to offer personalized care. Objective: The purpose of this study is to identify the various roles and functions that PN may hold for personalized PD care. Methods: We performed a systematic literature review, utilizing: PubMed, Web of Science, The Cochrane Library, and PsycINFO. The review qualitatively evaluated articles, which …described personalized care models involving PNs and was guided by the personalized care management model. A meta-analysis compared patient-reported QoL (quantified using the 39-item Parkinson’s Disease Questionnaire) between personalized care interventions involving PN versus standard care with. Results: Twenty-seven publications were identified, including six randomized, controlled trials ascertaining with health related QoL (n  = 1830 PwPs). The qualitative evaluation revealed that PN contribute to all aspects of personalized care. The meta-analysis showed no improved QoL in personalized care models compared to standard care, thought a great heterogeneity among study design and interventions was outlined (Standardized Mean Difference = –0.8935; 95% Confidence Interval, –2.1177 to 0.3307; z = –1.43, p  = 0.1526). Conclusion: PN fulfil important functions in personalized PD care. For the future, a clear role definition will be necessary to adjust training for PN across healthcare systems and care settings but especially to realize their full potential for PD care. Show more

Keywords: Parkinson’s disease, Parkinson nurse, role of specialized care nurse, personalized care, quality of life, PDQ-39

DOI: 10.3233/JPD-223215

Citation: Journal of Parkinson's Disease, vol. 12, no. 6, pp. 1807-1831, 2022

Authors: Ellis, Penelope K. | Davies, Matthew L. | Gray, William K. | Barber, Margaret | Bolnykh, Ifkov | Sadler, Molly | Walker, Richard W.

Article Type: Research Article

Abstract: Background: People with Parkinson’s disease (PD) have higher rates of hospitalisation and healthcare utilisation compared to the general population. The COVID-19 pandemic caused significant changes in admissions to hospital and access to healthcare. People with PD are some of the most vulnerable to such changes. There is no pre-existing data on the cause and duration of admission to hospital of people with PD during the COVID-19 pandemic. Objective: To determine the cause, duration, and outcome of hospital admissions to Northumbria Healthcare NHS Foundation Trust (NHCFT) for people with idiopathic Parkinson’s disease (IPD) in 2020. Methods: All …people with IPD who had an emergency admission to NHCFT between 01/01/2020 and 31/12/2020 were identified. Demographic and disease characteristics, the number, duration, cause of admission and the location prior to admission were collected from an audit of medical notes. Results: 271 people with IPD had one or more emergency admissions to NHCFT between 01/01/2020 and 31/12/2020. There was a total of 453 emergency admissions, with a median duration of 5 (IQR 2-13) days. The most common causes of admission to hospital were PD-related motor dysfunction (includes falls with no other underlying cause or associated injury) and injury (includes falls with fracture), at 78 (17.2%) and 70 (15.5%) respectively. Conclusions: People with IPD had a short duration but high number of emergency admissions to hospital. Our chronological data on number of admissions shows a peak in admissions during August 2020. As a result of these findings and emerging data we suggest that individuals with PD deconditioned during 2020. Show more

Keywords: Parkinson’s disease, COVID-19, admissions

DOI: 10.3233/JPD-223173

Citation: Journal of Parkinson's Disease, vol. 12, no. 6, pp. 1833-1840, 2022

Authors: O’Day, Chelsea | Finkelstein, David Isaac | Diwakarla, Shanti | McQuade, Rachel Mai

Article Type: Review Article

Abstract: Constipation afflicts many patients with Parkinson’s disease (PD) and significantly impacts on patient quality of life. PD-related constipation is caused by intestinal dysfunction, but the etiology of this dysfunction in patients is unknown. One possible cause is neuron loss within the enteric nervous system (ENS) of the intestine. This review aims to 1) Critically evaluate the evidence for and against intestinal enteric neuron loss in PD patients, 2) Justify why PD-related constipation must be objectively measured, 3) Explore the potential link between loss of enteric neurons in the intestine and constipation in PD, 4) Provide potential explanations for disparities in …the literature, and 5) Outline data and study design considerations to improve future research. Before the connection between intestinal enteric neuron loss and PD-related constipation can be confidently described, future research must use sufficiently large samples representative of the patient population (majority diagnosed with idiopathic PD for at least 5 years), implement a consistent neuronal quantification method and study design, including standardized patient recruitment criteria, objectively quantify intestinal dysfunctions, publish with a high degree of data transparency and account for potential PD heterogeneity. Further investigation into other potential influencers of PD-related constipation is also required, including changes in the function, connectivity, mitochondria and/or α-synuclein proteins of enteric neurons and their extrinsic innervation. The connection between enteric neuron loss and other PD-related gastrointestinal (GI) issues, including gastroparesis and dysphagia, as well as changes in nutrient absorption and the microbiome, should be explored in future research. Show more

Keywords: Parkinson’s disease, α-synuclein, constipation, enteric neuron, degeneration, dysfunction, gastrointestinal, microbiome, mitochondria, neurodegeneration

DOI: 10.3233/JPD-223262

Citation: Journal of Parkinson's Disease, vol. 12, no. 6, pp. 1841-1861, 2022

Authors: Yin, Dong Xu | Toyoda, Hiroki | Nozaki, Kazunori | Satoh, Keitaro | Katagiri, Ayano | Adachi, Kazunori | Kato, Takafumi | Sato, Hajime

Article Type: Research Article

Abstract: Background: Taste impairments are often accompanied by olfactory impairments in the early stage of Parkinson’s disease (PD). The development of animal models is required to elucidate the mechanisms underlying taste impairments in PD. Objective: This study was conducted to clarify whether the intranasal administration of rotenone causes taste impairments prior to motor deficits in mice. Methods: Rotenone was administrated to the right nose of mice once a day for 1 or 4 week(s). In the 1-week group, taste, olfactory, and motor function was assessed before and after a 1-week recovery period following the rotenone administration. Motor …function was also continuously examined in the 4-weeks group from 0 to 5 weeks. After a behavioral test, the number of catecholamine neurons (CA-Nos) was counted in the regions responsible for taste, olfactory, and motor function. Results: taste and olfactory impairments were simultaneously observed without locomotor impairments in the 1-week group. The CA-Nos was significantly reduced in the olfactory bulb and nucleus of the solitary tract. In the 4-week group, locomotor impairments were observed from the third week, and a significant reduction in the CA-Nos was observed in the substantia nigra (SN) and ventral tegmental area (VTA) at the fifth week along with the weight loss. Conclusion: The intranasal administration of rotenone caused chemosensory and motor impairments in an administration time-period dependent manner. Since chemosensory impairments were expressed prior to the locomotor impairments followed by SN/VTA CA neurons loss, this rotenone administration model may contribute to the clarification of the prodromal symptoms of PD. Show more

Keywords: Parkinson’s disease, pesticides, rotenone, taste disorders, olfaction disorders, catecholamines, experimental animal models

DOI: 10.3233/JPD-223273

Citation: Journal of Parkinson's Disease, vol. 12, no. 6, pp. 1863-1880, 2022

Authors: Elabi, Osama F. | Pass, Rachel | Sormonta, Irene | Nolbrant, Sara | Drummond, Nicola | Kirkeby, Agnete | Kunath, Tilo | Parmar, Malin | Lane, Emma L.

Article Type: Research Article

Abstract: Background: First-in-human studies to test the efficacy and safety of human embryonic stem cells (hESC)-derived dopaminergic cells in the treatment of Parkinson’s disease (PD) are imminent. Pre-clinical studies using hESC-derived dopamine neuron transplants in rat models have indicated that the benefits parallel those shown with fetal tissue but have thus far failed to consider how ongoing L-DOPA administration might impact on the graft. Objective: To determine whether L-DOPA impacts on survival and functional recovery following grafting of hESC-derived dopaminergic neurons. Methods: Unilateral 6-OHDA lesioned rats were administered with either saline or L-DOPA prior to, and for …18 weeks following surgical implantation of dopaminergic neural progenitors derived from RC17 hESCs according to two distinct protocols in independent laboratories. Results: Grafts from both protocols elicited reduction in amphetamine-induced rotations. Reduced L-DOPA-induced dyskinesia preceded the improvement in amphetamine-induced rotations. Furthermore, L-DOPA had no effect on overall survival (HuNu) or dopaminergic neuron content of the graft (TH positive cells) but did lead to an increase in the number of GIRK2 positive neurons. Conclusion: Critically, we found that L-DOPA was not detrimental to graft function, potentially enhancing graft maturation and promoting an A9 phenotype. Early improvement of L-DOPA-induced dyskinesia suggests that grafts may support the handling of exogenously supplied dopamine earlier than improvements in amphetamine-induced behaviours indicate. Given that one of the protocols will be employed in the production of cells for the European STEM-PD clinical trial, this is vital information for the management of patients and achieving optimal outcomes following transplantation of hESC-derived grafts for PD. Show more

Keywords: L-dopa-induced dyskinesia, 6-OHDA lesioned rat, Parkinson’s disease, abnormal involuntary movements, transplantation, human embryonic stem cells

DOI: 10.3233/JPD-212920

Citation: Journal of Parkinson's Disease, vol. 12, no. 6, pp. 1881-1896, 2022