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Parkinson’s disease (PD) is a progressive neurological disorder characterized by motor and non-motor symptoms for which only symptomatic treatments exist. Exercise is a widely studied complementary treatment option. Aerobic exercise, defined as continuous movement of the body’s large muscles in a rhythmic manner for a sustained period that increases caloric requirements and aims at maintaining or improving physical fitness, appears promising. We performed both a scoping review and a systematic review on the generic and disease-specific health benefits of aerobic exercise for people with PD. We support this by a meta-analysis on the effects on physical fitness (VO2max), motor symptoms (Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) motor section), and health-related quality of life (39-item Parkinson’s disease Questionnaire (PDQ-39)). Aerobic exercise has generic health benefits for people with PD, including a reduced incidence of cardiovascular disease, a lower mortality, and an improved bone health. Additionally, there is level 1 evidence that aerobic exercise improves physical fitness (VO2max) and attenuates motor symptoms (MDS-UPDRS motor section) in the off-medication state, although the long-term effects (beyond 6 months) remain unclear. Dosing the exercise matters: improvements appear to be greater after training at higher intensities compared with moderate intensities. We found insufficient evidence for a beneficial effect of aerobic exercise on health-related quality of life (PDQ-39) and conflicting results regarding non-motor symptoms. Compliance to exercise regimes is challenging for PD patients but may be improved by adding exergaming elements to the training program. Aerobic exercise seems a safe intervention for people with PD, although care must be taken to avoid falls in at-risk individuals. Further studies are needed to establish the long term of aerobic exercise, including a focus on non-motor symptoms and health-related quality of life. Electronic supplementary material The online version of this article (10.1007/s13311-020-00904-8) contains supplementary material, which is available to authorized users.

Contains fulltext : 243907.pdf (Publisher’s version ) (Open Access) Objective: Randomized clinical trials have shown that aerobic exercise attenuates motor symptom progression in Parkinson's disease, but the underlying neural mechanisms are unclear. Here, we investigated how aerobic exercise influences disease-related functional and structural changes in the cortico-striatal sensorimotor network, which is involved in the emergence of motor deficits in Parkinson's disease. Additionally, we explored effects of aerobic exercise on tissue integrity of the substantia nigra, and on behavioral and cerebral indices of cognitive control. Methods: The Park-in-Shape trial is a single-center, double-blind randomized controlled trial in 130 Parkinson's disease patients who were randomly assigned (1:1 ratio) to aerobic exercise (stationary home-trainer) or stretching (active control) interventions (duration: six months). An unselected subset from this trial (exercise: n=25, stretching: n=31) underwent resting-state functional and structural magnetic resonance imaging, and an oculomotor cognitive control task (pro- and anti-saccades), at baseline and at six-month follow-up. Results: Aerobic exercise, but not stretching, led to increased functional connectivity of the anterior putamen with the sensorimotor cortex relative to the posterior putamen. Behaviorally, aerobic exercise also improved cognitive control. Furthermore, aerobic exercise increased functional connectivity in the right frontoparietal network, proportionally to fitness improvements, and it reduced global brain atrophy. Interpretation: MRI, clinical, and behavioral results converge towards the conclusion that aerobic exercise stabilizes disease progression in the cortico-striatal sensorimotor network and enhances cognitive performance. 14 p.

Contains fulltext : 207798pos.pdf (Author’s version postprint ) (Open Access) Background: High-intensity aerobic exercise might attenuate the symptoms of Parkinson's disease, but high-quality evidence is scarce. Moreover, long-term adherence remains challenging. We aimed to evaluate the effectiveness of aerobic exercise-gamified and delivered at home, to promote adherence-on relieving motor symptoms in patients with Parkinson's disease with mild disease severity who were on common treatment regimes. Methods: In this single-centre, double-blind, randomised controlled trial (Park-in-Shape), we recruited sedentary patients with Parkinson's disease from the outpatient clinic at Radboudumc, Nijmegen, Netherlands. Patients were made aware of the study either by their treating neurologist or via information in the waiting room. Patients could also contact the study team via social media. We included patients aged 30-75 years with a Hoehn and Yahr stage of 2 or lower, who were on stable dopaminergic medication. Patients were randomly assigned (in a 1:1 ratio) to either aerobic exercise done on a stationary home-trainer (aerobic intervention group) or stretching (active control group) by means of a web-based system with minimisation for sex and medication status (treated or untreated) and permuted blocks of varying sizes of more than two (unknown to study personnel). Patients were only aware of the content of their assigned programme. Assessors were unaware of group assignments. Both interventions were home based, requiring 30-45 min training three times per week for 6 months. Both groups received a motivational app and remote supervision. Home trainers were enhanced with virtual reality software and real-life videos providing a so-called exergaming experience (ie, exercise enhanced by gamified elements). The primary outcome was the between-group difference in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor section at 6 months, tested during the off state (>/=12 h after last dopaminergic medication). The analysis was done on an intention-to-treat basis in patients who completed the follow-up assessment, regardless of whether they completed the assigned intervention. Patients reported adverse events directly to their coach and also after the 6-month visit retrospectively. A between-group difference of 3.5 points or more was deemed a-priori clinically relevant. The study is concluded and registered with the Dutch Trial Registry, NTR4743. Findings: Between Feb 2, 2015, and Oct 27, 2017, 139 patients were assessed for eligibility in person, of whom 130 were randomly assigned to either the aerobic intervention group (n=65) or the active control group (n=65). Data from 125 (96%) patients were available for the primary analysis; five patients were lost to follow-up (four in the intervention group; one in the control group). 20 patients (ten in each group) did not complete their assigned programme. The off-state MDS-UPDRS motor score revealed a between-group difference of 4.2 points (95% CI 1.6-6.9, p=0.0020) in favour of aerobic exercise (mean 1.3 points [SE 1.8] in the intervention group and 5.6 points [SE 1.9] for the control group). 11 patients had potentially related adverse events (seven [11%] in the intervention group, four [6%] in the control group) and seven had unrelated serious adverse events (three in the intervention group [vestibilar disorder, vasovagal collapse, knee injury during gardening that required surgery; 6%], four in the control group [supraventricular tachycardia, hip fracture, fall related injury, severe dyskinesias after suprathreshold dose levodopa in a patient with deep brain stimulation; 7%]). Interpretation: Aerobic exercise can be done at home by patients with Parkinson's disease with mild disease severity and it attenuates off-state motor signs. Future studies should establish long-term effectiveness and possible disease-modifying effects. Funding: Netherlands Organization for Health Research and Development. 11 p.

Exercise is increasingly being recognized as a key element in the overall management of persons living with Parkinson's disease (PD) but various (disease-specific) barriers may impede even motivated patients to participate in regular exercise. We aimed to provide a comprehensive review of the various barriers and motivators for exercise in persons with PD. We scrutinized data on compliance-related factors published in cross-sectional studies, randomized controlled trials and reviews. We classified the barriers and motivators to exercise from a patient perspective according to the International Classification of Functioning, Disability and Health. We present an overview of the large range of potential motivators and barriers for exercise in persons with PD. Healthcare professionals should consider a wide and comprehensive range of factors, in order to identify which specific determinants matter most for each individual. Only when persons with PD are adequately motivated in a way that appeals to them and after all person-specific barriers have been tackled, we can begin to expect their long-term adherence to exercise. Such long-term compliance will be essential if exercise is to live up to its expectations, including the hope that prolonged engagement in regular exercise might help to modify the otherwise relentlessly progressive course of PD. ispartof: JOURNAL OF PARKINSONS DISEASE vol:10 issue:4 pages:1293-1299 ispartof: location:Netherlands status: published

Parkinson’s disease (PD) is a complex neurodegenerative disorder characterised by disabling motor and non-motor signs. Current medical therapies can partially alleviate these symptoms, but are also accompanied by dose-limiting side effects. Moreover, their therapeutic window narrows with disease progression, leaving the patient with increasing disability. Complementary non-pharmacological approaches, such as aerobic exercise, have been evaluated for over two decades. The heterogeneity of the interventions and outcomes used hinders the interpretation of the effect of exercise in PD.1 Several systematic reviews and meta-analyses have pooled the results, but their conclusions depend greatly on the diversity of the included exercise modalities. Nevertheless, a beneficial effect of exercise on motor symptoms of PD as well as a general health benefit (physical fitness) seems likely from these studies. A beneficial effect on non-motor symptoms in PD is also conceivable, but not yet proven.2 To strengthen the evidence on symptomatic benefits, we need methodologically sound randomised controlled trials (RCTs) with large sample sizes, clinically relevant outcomes for both motor and non-motor signs, long-term interventions and prolonged follow-up.3 Additionally, there is a need for pragmatic home-based or community-based studies, aiming to test the feasibility and efficacy of exercise therapies in real life. Several semi-supervised home-based studies were performed in PD before. These included low-intensity therapies that were delivered only briefly. 4. Although these home-based studies reported some positive results, it appears that more intensive exercise therapies (ie, resistance …

Contains fulltext : 165751.pdf (Publisher’s version ) (Open Access) Progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the brain, is typically diagnosed in immunocompromised persons. Here, we describe the diagnostic challenge of PML in an apparently immunocompetent patient. Thorough analyses, including cytokine release assays and whole exome sequencing, revealed a deficit in the antiviral interferon gamma production capacity of this patient and compound heterozygous mutations in BCL-2-associated athanogene 3. Interestingly, both factors are associated with reduced expression of John Cunningham virus T-antigen, a protein that plays a key role in viral replication in infected cells. After validation in other patients, our findings may contribute to novel insights into the etiology and possibly treatment of PML.

Contains fulltext : 154960.pdf (Publisher’s version ) (Open Access) BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder with a wide range of motor and non-motor symptoms. Despite optimal medical management, PD still results in a high disability rate and secondary complications and many patients lead a sedentary lifestyle, which in turn is also associated with a higher co-morbidity and mortality. Exercise has been explored as a strategy to reduce secondary complications and results suggests that it not only provides general health benefits, but may also provide symptomatic relief. If this holds true exercise would be a very attractive addition to the therapeutic arsenal in PD. The supportive evidence remains incomplete. Here, we describe the design of the Park-in-Shape study, which primarily aims to evaluate whether aerobic exercise affords clinically relevant improvements in motor symptoms in sedentary PD patients. A specific new element is the introduction of gaming to optimize compliance to the exercise intervention. METHODS/DESIGN: The Park-in-Shape study is a randomized controlled, assessor- and patient-blinded single center study. Two parallel groups will include a total of 130 patients, receiving either aerobic exercise on a home trainer equipped with gaming elements ("exergaming"), or a non-aerobic intervention (stretching, flexibility and relaxation exercises). Both groups are supported by a specifically designed motivational app that uses gaming elements to stimulate patients to exercise and rewards them after having completed the exercise. Both interventions are delivered at home at least 3 times a week for 30-45 minutes during 6 months. Eligible patients are community-dwelling, sedentary patients diagnosed with mild-moderate PD. The primary outcome is the MDS-UPDRS motor score (tested in the off state) after 6 months. Secondary outcomes include various motor and non-motor symptoms, quality of life, physical fitness, and adherence. DISCUSSION: This Park-in-Shape study is anticipated to answer the question whether high intensity aerobic exercise combined with gaming elements ("exergaming") provides symptomatic relief in PD. Strong elements include the double-blinded randomized controlled trial design, the MDS-UPDRS as valid primary outcome, the large sample size and unique combination of home-based pure aerobic exercise combined with gaming elements and motivational aspects. TRIAL REGISTRATION: Dutch trial register NTR4743. 12 p.