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Purkinje Cell Cytoplasmic Antibody (PCA-2)-related Chorea–Dystonia Syndrome
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A Consensus Set of Outcomes for Parkinson's Disease from the International Consortium for Health Outcomes Measurement
Background: Parkinson's disease (PD) is a progressive neurodegenerative condition that is expected to double in prevalence due to demographic shifts. Value-based healthcare is a proposed strategy to improve outcomes and decrease costs. To move towards an actual value-based health care system, condition-specific outcomes that are meaningful to patients are essential. Objective: Propose a global consensus standard set of outcome measures for PD. Methods: Established methods for outcome measure development were applied, as outlined and used previously by the International Consortium for Health Outcomes Measurement (ICHOM). An international group, representing both patients and experts from the fields of neurology, psychiatry, nursing, and existing outcome measurement efforts, was convened. The group participated in six teleconferences over a six-month period, reviewed existing data and practices, and ultimately proposed a standard set of measures by which patients should be tracked, and how often data should be collected. Results: The standard set applies to all cases of idiopathic PD, and includes assessments of motor and non-motor symptoms, ability to work, PD-related health status, and hospital admissions. Baseline demographic and clinical variables are included to enable case mix adjustment. Conclusions: The Standard Set is now ready for use and pilot testing in the clinical setting. Ultimately, we believe that using the set of outcomes proposed here will allow clinicians and scientists across the world to document, report, and compare PD-related outcomes in a standardized fashion. Such international benchmarks will improve our understanding of the disease course and allow for identification of 'best practices', ultimately leading to better informed treatment decisions.This project was funded by the International Consortium for Health Outcome Measurement.S
Effects of Gocovri (Amantadine) Extended Release Capsules on Non-Motor Symptoms in Patients with Parkinson's Disease and Dyskinesia.
Backward Protective Stepping During Dual-Task Scenarios in People With Parkinson’s Disease: A Pilot Study
Effects of Gocovri (Amantadine) Extended Release Capsules on Non-Motor Symptoms in Patients with Parkinson's Disease and Dyskinesia.
IntroductionGocovri (amantadine) extended release capsules are approved for treatment of dyskinesia and as a levodopa adjunct for OFF episodes in patients with Parkinson's disease (PD). We report treatment-related effects on non-motor symptoms (NMS) assessed as secondary outcomes in two trials using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I.MethodsEASE LID and EASE LID 3 enrolled levodopa-treated patients with PD and ≥ 1 h/day ON time with troublesome dyskinesia. Patients were randomized to Gocovri (274 mg) or placebo taken daily at bedtime. Treatment differences from baseline to week 12 in MDS-UPDRS Part I were evaluated for the pooled population (N = 196) from both trials. Correlation analyses of NMS (MDS-UPDRS Part I) with dyskinesia using Unified Dyskinesia Rating Scale (UDysRS) scores were performed.ResultsFor changes in the MDS-UPDRS Part I items, the treatment difference favored Gocovri in daytime sleepiness (P = 0.006) and depression (P = 0.049) scores, but favored placebo in cognitive impairment (P = 0.038), and hallucinations and psychosis (P < 0.001) scores. The treatment difference for the changes in total Part I score was -0.8, favoring Gocovri (P = 0.22). At baseline, MDS-UPDRS Part I modestly correlated with UDysRS score (r +0.25, P < 0.001), and improvement in NMS correlated with improvement in dyskinesia at week 12 for Gocovri (r +0.39, P < 0.001) but not placebo (r +0.12, P = 0.29). The most commonly reported adverse events for Gocovri were hallucination (21%); dizziness, dry mouth, and peripheral edema (16% each); and constipation, falls, and orthostatic hypotension (13% each).ConclusionThis post hoc analysis shows potential benefit with Gocovri treatment for the NMS of daytime sleepiness and depression in dyskinetic PD patients. Overall, improvement in NMS scores correlated with improvement in dyskinesia.Trial registrationClinicalTrials.gov identifiers: NCT02136914 and NCT02274766
Essential Tremor and Depression
Introduction: Depression and neuropsychiatric disorders in individuals with essential tremor (ET) are not well characterized in the literature. Methods: We compared 104 ET subjects with 481 non-ET controls involved in the Arizona Study of Aging and Neurodegenerative Disorders. An analysis of baseline depression scales and neuropsychiatric inventory (NPI) was done between the two groups. Additionally, comparisons were made within the ET group based on tremor severity, duration of tremor, and age of onset. Results: There were no significant differences between the ET and non-ET groups. There were no significant differences in the ET group above and below the median tremor duration. Additionally, no differences were found in the ET group based on objective measures of tremor severity, age of onset, or those with subjectively distressing tremor compared with those without. Conclusion: There were no significant differences in depressive symptoms between ET and non-ET groups. Furthermore, no correlation was found between depressive symptoms in ET groups based on tremor severity, duration, or age of onset
Deep brain stimulation and cognitive outcomes among patients with Parkinson’s disease: A historical cohort study
© 2019, American Psychiatric Association. All rights reserved. Objective: Deep brain stimulation (DBS) is an effective treatment for motor symptoms of Parkinson’s disease; however, there is conflicting literature about the effect of DBS on cognitive function. The authors conducted a historical cohort study involving patients with Parkinson’s disease who underwent DBS of the globus pallidus pars interna (GPi; N=12) or subthalamic nucleus (STN; N=17). Methods: The authors i nvesti gated di fferences i n four neuropsychol ogi cal test scores at 6 months post-DBS (follow-up) as compared with baseline (i.e., Boston Naming Test, WAIS Verbal Comprehension Index [WAIS-VCI], Working Memory Index [WAIS-WMI], and Processing Speed Index [WAIS-PSI]). Results: GPi DBS patients showed no difference between baseline and follow-up on any neuropsychological test. STN DBS patients had lower scores indicating decreased performance at follow-up as compared with baseline on WAIS-PSI (mean [SD], 91.47 [10.42] versus 81.65 [12.03]; p=0.03). There was a significant (p=0.008) difference between the change in baseline to follow-up scores on the WAIS-VCI for the STN DBS and GPi DBS groups (i.e., STN DBS patients scored lower at the 6-month follow-up compared with baseline, whereas GPi DBS patients scored higher). Conclusions: GPi may be a preferred target for DBS in patients with Parkinson’s disease when considering cognitive outcomes
Brain Lewy-Type Synucleinopathy Density is Associated With a Lower Prevalence of Atherosclerotic Cardiovascular Disease Risk Factors in Patients With Parkinson\u27s Disease
Background: Some epidemiology studies suggest that atherosclerotic cardiovascular disease (ASCVD) risk factors increase the risk of developing Parkinson\u27s disease (PD). However, conflicting data suggest lower rates of ASCVD in PD. Objective: The objective of this study is to determine, with data from a longitudinal clinicopathological study, whether ASCVD risk factors are associated with a PD diagnosis and/or increased brain or peripheral load of Lewy-type synucleinopathy (LTS). Methods: All subjects were followed to autopsy and neuropathological examination in the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Multivariable regression models, including age, gender, and smoking history, were used to investigate the association of a PD diagnosis or brain or submandibular gland LTS load with ASCVD risk factors. Results: 150 subjects were included (PD n=60, controls n=90). Univariable comparisons and regression models showed a general trend to inverse associations. The multivariable odds ratio (OR) of brain LTS load for carotid artery disease was 0.93 (95% CI: 0.86 to 0.98; p=0.02), for anticoagulant use 0.95 (95% CI: 0.90 to 0.99; p=0.04) and for abnormal heart weight 0.96 (95% CI: 0.92 to 0.99; p=0.01). Composite clinical and overall (clinical + pathology composite risk scores) composite risk scores were also significantly lower in the PD subjects (p=0.0164 and 0.0187, respectively). Submandibular gland LTS load was not significantly related to ASCVD conditions. Conclusions: This study shows associations of higher brain LTS with lower prevalence of both clinical and pathological indices of ASCVD in PD subjects versus age-similar controls. We suggest that this is due to α-synuclein pathology-induced sympathetic denervation in PD
Comparison of neuropathology in Parkinson\u27s disease subjects with and without deep brain stimulation
Background: The aim of this postmortem study was to compare, in Parkinson\u27s disease subjects with and without bilateral subthalamic nucleus deep brain stimulation (STN-DBS), the loss of pigmented neurons within the substantia nigra and pathological alpha-synuclein density within the SN and other brain regions. Methods: PD subjects were identified from the Arizona Study of Aging and Neurodegenerative Disorders database (STN-DBS = 11, non-DBS = 156). Pigmented neuron loss scores within the substantia nigra as well as alpha-synuclein density scores within the substantia nigra and 9 other brain regions were compared, the latter individually and in summary as the Lewy body brain load score. Results: DBS subjects had higher alpha-synuclein density scores within the substantia nigra, olfactory bulb, and locus ceruleus, as well as higher total Lewy body brain load scores when compared with non-DBS subjects. No differences in substantia nigra pigmented neuron loss scores were found. Conclusions: STN-DBS subjects tend to have higher alpha-synuclein density scores, but do not have a differential loss of substantia nigra pigmented neurons. © 2016 International Parkinson and Movement Disorder Society