Journal of Parkinson's Disease - Volume 5, issue 3

Authors: George, Sonia | Brundin, Patrik

Article Type: Review Article

Abstract: Currently, several α-synuclein immunotherapies are being tested in experimental Parkinson’s disease models and in clinical trials. Recent research has revealed that α-synuclein is not just an intracellular synaptic protein but also exists extracellularly. Moreover, the transfer of misfolded α-synuclein between cells might be a crucial step in the process leading to a progressive increase in deposition of α-synuclein aggregates throughout the Parkinson’s disease brain. The revelation that α-synuclein is present outside cells has increased the interest in antibody-based therapies and opens up for the notion that microglia might play a key role in retarding Parkinson’s disease progression. The objectives of …this review are to describe and contrast the use of active and passive immunotherapy in treating α-synucleinopathies and highlight the likely important role of microglia in clearing misfolded α-synuclein from the extracellular space. Show more

Keywords: alpha synuclein, microglia, immunotherapy, Parkinson’s disease

DOI: 10.3233/JPD-150630

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 413-424, 2015

Authors: Bettiol, Silvana S. | Rose, Tanith C. | Hughes, Clarissa J. | Smith, Lesley A.

Article Type: Review Article

Abstract: Background: The association between Parkinson’s disease and lifestyle exposures such as smoking, coffee and alcohol consumption have been the focus of research for several decades, with varying and often conflicting results. Objective: This paper reviews the key features of observational studies investigating the relationship between alcohol drinking and PD risk, to determine potential sources of variability between the results. Methods: Relevant literature from 2000–2014 was systematically retrieved using three databases. Primary research articles were included if they reported a measure of association between quantity and frequency of alcohol intake and PD risk, …and adjusted at least for the potential confounding factors of smoking and age. Results: Sixteen articles were identified. The seven case-control studies were more likely to report a weak protective association by level of alcohol consumption compared to the studies with prospective designs. Two studies reported the relationship between heavy (harmful to health) drinking and PD. There was weak evidence that associations varied by type of alcoholic beverage. Smoking may modify the association between alcohol intake and PD risk, however, the evidence does not support the theory that a confounder (such as an addiction-avoiding personality trait) produced the inverse associations between smoking, coffee and alcohol intake and PD risk. Methodological weaknesses of the studies, including selection and recall bias, residual confounding and lack of statistical power may in part account for their differences. Conclusion: The weak association between alcohol drinking and PD risk was found in studies at greater risk of selection and recall bias. Show more

Keywords: Alcohol, alcoholic beverages, alcohol drinking, Parkinson’s disease, review, risk factors, case-control studies, cohort studies, epidemiologic methods, lifestyle

DOI: 10.3233/JPD-150533

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 425-442, 2015

Authors: Egan, Sarah J. | Laidlaw, Ken | Starkstein, Sergio

Article Type: Review Article

Abstract: Evidence is reviewed demonstrating that cognitive behavior therapy (CBT) is effective in the treatment of depression and anxiety in Parkinson’s disease. The aims were to review the extant literature, specify a model of cognitive and behavioral maintenance factors in depression and anxiety in Parkinson’s disease and provide a guide to treatment. It is argued that treatment should take into account specific cognitive and behavioral maintaining factors. Symptoms of depression and anxiety are highly prevalent in Parkinson’s disease and therapists should consider how to augment the efficacy of CBT for patients with Parkinson’s disease. Cognitive and behavioral interventions can help people …overcome some of the challenges in living with PD by maximizing wellbeing and overall quality of life. Show more

Keywords: Parkinson’s disease, anxiety, depression, model, CBT

DOI: 10.3233/JPD-150542

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 443-451, 2015

Authors: Domingos, Josefa M. | Godinho, Catarina | Dean, John | Coelho, Miguel | Pinto, Anabela | Bloem, Bastiaan R. | Ferreira, Joaquim J.

Article Type: Review Article

Abstract: Background: There is increasing evidence to suggest a tight relationship between cognitive impairment and falls in Parkinson’s disease (PD). Here, we draw attention to a potentially significant flaw in the existent falls-related research, namely the apparent exclusion of patients with cognitive impairment or dementia. Objective: Our objective was to review all published, on-going or scheduled fall-related intervention studies, in order to investigate the extent to which cognitively impaired individuals with PD were included in these studies. Methods: We analyzed published controlled trials regarding falls and PD in commonly used databases, as well as relevant …ongoing clinical trials registered within the World Health Organization database, clinicaltrials.gov and the European Clinical Trials Database. Results: Fourteen of the fifteen published studies included had explicit cognitive exclusion criteria as part of their study protocol. Most of the 54 on-going PD fall-related studies excluded patients with cognitive impairment. Conclusions: This suggests that individuals with cognitive impairment or dementia are excluded from fall-related research studies. We strongly recommend that future work in this area should include a representative sample of patients with PD, including subjects with cognitive decline. Show more

Keywords: Falls, Parkinson disease, rehabilitation, cognition, clinical trials

DOI: 10.3233/JPD-150590

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 453-469, 2015

Authors: Zach, Heidemarie | Dirkx, Michiel | Bloem, Bastiaan R. | Helmich, Rick C.

Article Type: Research Article

Abstract: Parkinson’s disease harbours many different tremors that differ in distribution, frequency, and context in which they occur. A good clinical tremor assessment is important for weighing up possible differential diagnoses of Parkinson’s disease, but also to measure the severity of the tremor as a basis for further tailored treatment. This can be challenging, because Parkinson’s tremor amplitude is typically very variable and context-dependent. Here, we outline how we investigate Parkinson’s tremor in the clinic. We describe a simple set of clinical tasks that can be used to constrain tremor variability (cognitive and motor co-activation, several specific limb postures). This may help …to adequately characterize the tremor(s) occurring in a patient with Parkinson’s disease. Show more

Keywords: Parkinson’s disease, clinical examination, tremor

DOI: 10.3233/JPD-150650

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 471-474, 2015

Authors: Cattaneo, Carlo | Ferla, R. La | Bonizzoni, Erminio | Sardina, Marco

Article Type: Research Article

Abstract: Background: Safinamide is a novel α-aminoamide with dopaminergic and non-dopaminergic properties developed as adjunctive therapy for patients with PD. Results from a 24-month double-blind controlled study suggested that as add-on to levodopa (and other PD medications) the benefits of safinamide on dyskinesia may be related to severity of dyskinesia at baseline. Objective: This post-hoc analysis further characterized the effects of safinamide on dyskinesia in mid- to late-stage PD patients. Methods: Patients were stratified by the presence or absence of dyskinesia at baseline, and by whether or not the dose of levodopa …had been changed during the 24-month treatment period. Differences between safinamide and placebo were evaluated using the Wilcoxon rank-sum test. Results: For the overall treated population (with or without baseline dyskinesia), safinamide 100 mg/day significantly improved the dyskinesia rating scale score, compared with placebo, in the subgroup of patients with no change in levodopa dose (p  = 0.0488). For patients with baseline dyskinesia, improvements over placebo were also significant (p  = 0.0153) in patients with or without changes in levodopa dose, and nearly significant (p  = 0.0546) in patients with no change in levodopa dose, suggesting that these improvements were not due to levodopa dose reductions. Conclusions: While no statistically significant difference in mean DRS scores was seen between safinamide and placebo in the original study population, the present post-hoc analysis helps to provide a meaningful interpretation of the long-term effects of safinamide on dyskinesia. These results may be related to safinamide state- and use-dependent inhibition of sodium channels and stimulated glutamate release, and are unlikely due to reduced dopaminergic stimulation. Show more

Keywords: Parkinson’s disease, levodopa, safinamide, dyskinesia

DOI: 10.3233/JPD-150569

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 475-481, 2015

Authors: Ughratdar, Ismail | Samuel, Michael | Ashkan, Keyoumars

Article Type: Research Article

Abstract: Functional and stereotactic neurosurgery has always been regarded as a subspecialty based on and driven by technological advances. However until recently, the fundamentals of deep brain stimulation (DBS) hardware and software design had largely remained stagnant since its inception almost three decades ago. Recent improved understanding of disease processes in movement disorders as well clinician and patient demands has resulted in new avenues of development for DBS technology. This review describes new advances both related to hardware and software for neuromodulation. New electrode designs with segmented contacts now enable sophisticated shaping and sculpting of the field of stimulation, potentially allowing …multi-target stimulation and avoidance of side effects. To avoid lengthy programming sessions utilising multiple lead contacts, new user-friendly software allows for computational modelling and individualised directed programming. Therapy delivery is being improved with the next generation of smaller profile, longer-lasting, re-chargeable implantable pulse generators (IPGs). These include IPGs capable of delivering constant current stimulation or personalised closed-loop adaptive stimulation. Post-implantation Magnetic Resonance Imaging (MRI) has long been an issue which has been partially overcome with ‘MRI conditional devices’ and has enabled verification of DBS lead location. Surgical technique is considering a shift from frame-based to frameless stereotaxy or greater role for robot assisted implantation. The challenge for these contemporary techniques however, will be in demonstrating equivalent safety and accuracy to conventional methods. We also discuss potential future direction utilising wireless technology allowing for miniaturisation of hardware. Show more

Keywords: Deep brain stimulation, technology, advances, innovations

DOI: 10.3233/JPD-150579

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 483-496, 2015

Authors: Westbay, Lauren C. | Cao, Lishan | Burnett-Zeigler, Inger | Reizine, Natalie | Barton, Brandon | Ippolito, Dolores | Weaver, Frances M. | Stroupe, Kevin T.

Article Type: Research Article

Abstract: Background: The subthalamic nucleus (STN) and the globus pallidus internus (GPi) are both effective targets for deep brain stimulation (DBS) to relieve motor symptoms of Parkinson’s disease. However, studies have reported varied effects on mental health-related adverse events and depressed mood following DBS. Objective: The current observational study sought to compare mental health healthcare utilization and costs for three years following STN or GPi DBS. Methods: For a cohort of Veterans (n  = 161) with Parkinson’s disease who participated in a larger multi-site randomized trial, we compared mental health outpatient visits, medication use, …inpatient admissions, and associated costs by DBS target site (STN vs. GPi). Results: Neither group nor time differences were significant for mental health outpatient or inpatient utilization following DBS. Overall costs associated with mental health visits and medications did not differ by time or by group. However, the percentage of patients with mental health medication use increased in the 6-month and 6 to 12 month periods post-surgery. The STN group had significantly greater increase in medication use at 6 to 12 months post-surgery compared to the GPi group (p  <  0.05). Conclusion: Despite a brief increase in medication use following surgery, this study suggests that mental health healthcare use and costs are stable over time and similar between DBS targets. Prior research findings of mental health-related adverse events and mood following DBS did not translate to greater mental health service utilization in our cohort. The changes seen in the year following surgery may reflect temporary adjustments with stabilization over time. Show more

Keywords: Deep brain stimulation, Parkinson’s disease, mental health, utilization

DOI: 10.3233/JPD-140512

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 497-504, 2015

Authors: Dorsey, E. Ray | Wagner, Joseph D. | Bull, Michael T. | Rizzieri, Ashley | Grischkan, Justin | Achey, Meredith A. | Sherer, Todd | Chowdhury, Sohini | Meunier, Claire | Cappelletti, Lily | Rocker, Charlotte | Richard, Irene H. | Schwarz, Heidi | Kang, Gail | Ahmad, Stacy H. | Biemiller, Rachel A. | Biglan, Kevin M.

Article Type: Research Article

Abstract: Background: Fox Trial Finder is an online registry for individuals with and without Parkinson disease (PD) interested in participating in PD research. However, distance or disability could prevent such individuals from participating in traditional, clinic-based research at major centers. Objective: Use videoconferencing to connect participants to specialists to: (1) demonstrate feasibility of virtual research visits within this population (2) collect phenotypic data of the participants, (3) validate self-reported diagnosis, and (4) gauge interest in virtual research visits. Methods: We solicited volunteers throughout the United States through Fox Trial Finder. Interested individuals with …PD provided consent, were given web cameras if needed, completed baseline surveys, and downloaded videoconferencing software remotely. Participants had a test connection and assessment appointment which included the Montreal Cognitive Assessment (MoCA), then a virtual research visit with a neurologist who reviewed their history and assessed their PD using a modified Movement Disorders Society Unified Parkinson’s Disease Rating Scale. Neurologists assessed PD diagnosis and symptomatology. Physicians and participants were surveyed about their experience. Results: Of 204 individuals who consented, 166 (81% ) individuals from 39 states completed all visits. The mean age was 62 and mean disease duration was 8.0 years. Mean MoCA score was 26.5, and mean modified MDS-UPDRS motor score was 22.8 (out of a possible 124). Neurologists judged PD as the most likely diagnosis in 97% of cases. Overall satisfaction with the visits was 79% (satisfied or very satisfied) among neurologists and 93% among participants. Conclusions: Through virtual research visits, neurologists engaged, characterized, and validated self-reported diagnosis in individuals with PD over a broad geography. This model may facilitate future research participation. Show more

Keywords: Parkinson disease, telemedicine

DOI: 10.3233/JPD-150549

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 505-515, 2015

Authors: Silbergleit, Alice K. | LeWitt, Peter A. | Peterson, Edward L. | Gardner, Glendon M.

Article Type: Research Article

Abstract: Background: Characteristic features of hypokinetic dysarthria develop in Parkinson disease (PD). We hypothesized that quantified acoustic changes of voice might provide a correlate of disease severity. Objective: To determine if there are significant differences in acoustic measures of voice between mild and moderate PD; 2) To evaluate correlations between acoustic parameters of voice and subtests of the UPDRS in mild and moderate PD. Methods: Twenty six participants with PD underwent vocal acoustic testing while off PD medication, for comparison to 22 healthy controls. Participants with PD were divided into two groups based upon UPDRS activities …of daily living (ADL) ratings: summed scores were used to define mild and moderate PD. Participants voiced /i/ (“ee”) at comfort, high, and low pitch (3 trials/pitch). The CSpeech Waveform Analysis Program was used to analyze cycle-to-cycle frequency (“jitter”) and amplitude (“shimmer”) irregularities of the vocal signal, signal-to-noise ratio, and maximum phonation frequency range converted to semitones. Sections of UPDRS scores were correlated to acoustic variables of voice. Results: Key findings included a significant difference between the semitone range of the control subjects and the moderate PD group (p  = 0.036). Further analyses revealed significant differences in semitone range for males between the controls vs. mild PD (p  = 0.014), and controls vs. moderate PD (p  = 0.005). Significant correlations were also found between acoustic findings and both the ADL and motor portions of the UPDRS. Conclusions: Acoustic analysis of voice, particularly frequency range, may provide a quantifiable correlate of diseaseprogression in PD. Show more

Keywords: Voice, phonation, motor function, Parkinson disease

DOI: 10.3233/JPD-140526

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 517-524, 2015