The Case for Subspecialization in Neurology: Movement Disorders

Within the world of medicine, the advent of new treatments and new technology has resulted in an increase in the number of specialties and subspecialties. This is especially true in neurology. A widely quoted article has demonstrated that 74 % of neurology residents will do a fellowship (Larson et al., 2000), and given that the survey was done over 10 years ago, the number increased, as the most recent AAN resident survey gives a number of almost 78 % (Resident Survey, 2008). Movement disorders is one of the many neurology fellowships that is non-accredited. On the AAN webpage there are currently 44 programs listed in the United States and Canada that offer a movement disorders fellowship (Directory fo

A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease

Objective: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. Methods: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach. Results: An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study. Conclusions: These data do not justify use of CoQ as a treatment to slow functional decline in HD

Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease A Randomized Clinical Trial

Importance Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. Objective To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. Design, Setting, and Participants Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. Interventions Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. Main Outcomes and Measures Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form– physical functioning subscale score (SF-36), and the change in the Berg Balance Test. Results Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was –2.5 units (95% CI, –3.7 to –1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, –0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. Conclusions and Relevance Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety

A 12-month, dose-level blinded safety and efficacy study of levodopa inhalation powder (CVT-301, Inbrija) in patients with Parkinson\u27s disease

INTRODUCTION: CVT-301 (Inbrija®) is a levodopa inhalation powder for on-demand treatment of OFF episodes in Parkinson\u27s disease patients treated with carbidopa/levodopa. Safety and efficacy results of a 12-month, dose-level blinded extension study of a phase 3 trial (SPAN℠-PD) of CVT-301 are presented. METHODS: Patients were receiving oral carbidopa/levodopa and adjunctive CVT-301 treatment, blinded to dose (60 mg or 84 mg, N = 325). Study visits occurred every 3 months. Pulmonary function was assessed by spirometry. Other safety assessments included dyskinesia and adverse events (AEs). Secondary objectives of the study included maintenance of improvement assessments for occurrence of an ON state during the 60-min post-dose period, change in total daily OFF time, and Patient Global Impression of Change (PGIC). RESULTS: Most frequent AEs (≥5%) were cough (15.4%), fall (13.1%), upper respiratory tract infection (7.1%), and dyskinesia (5.1%). Severe AEs (\u3e1 event) were cough (1.9%) and dyskinesia (0.6%). Twelve-month mean changes from baseline for FEV(1), FVC, and DL(CO) were -0.092 L, -0.097 L, and -0.922 mL/min/mmHg, respectively. At 12 months, 73.0% of patients on 84 mg achieved an ON state within 60 min. Total daily OFF time was reduced by 0.55 h (month 1) and 0.88 h (month 12) for the 84 mg dose. Percentage of patients self-reported as improved by PGIC was 65.5-91.9% over 12 months. CONCLUSION: CVT-301 was generally well-tolerated. Twelve-month decline in pulmonary function was consistent with a prior PD control group. Exploratory efficacy results showed CVT-301 maintained improvement at achieving ON states in patients experiencing OFF episodes, decreasing daily OFF time, and maintaining improvement in PGIC

Longitudinal Change in Quality of Life in Neurological Disorders Measures Over 3 Years in Patients With Early Parkinson's Disease

BackgroundThe Quality of Life in Neurological Disorders (Neuro- QoL) is a publicly available health- related quality- of- life measurement system.ObjectiveThe aim of this study was to evaluate the utility of Neuro- QoL item banks as outcome measures for clinical trials in Parkinson’s disease.MethodsAn analysis of Neuro- QoL responsiveness to change and construct validity was performed in a multicenter clinical trial cohort.ResultsAmong 310 participants over 3- years, changes in five of eight Neuro- QoL domains were significant (P <- 0.05) but very modest. The largest effect sizes were seen in the cognition and mobility domains (0.35- 0.39). The largest effect size for change over the year in which levodopa was initiated was - 0.19 for lower extremity function- mobility. For a similarly designed clinical trial, estimated sample size required to demonstrate a 50% reduction in worsening ranged from 420 to more than 1000 participants per group.ConclusionsMore sensitive tools will be required to serve as an outcome measure in early Parkinson’s disease. © 2021 International Parkinson and Movement Disorder SocietyPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/169296/1/mds28641.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/169296/2/mds28641_am.pd

Longitudinal Change in Quality of Life in Neurological Disorders Measures Over 3- Years in Patients with Early Parkinson’s Disease

BackgroundThe Quality of Life in Neurological Disorders (Neuro- QoL) is a publicly available health- related quality- of- life measurement system.ObjectiveThe aim of this study was to evaluate the utility of Neuro- QoL item banks as outcome measures for clinical trials in Parkinson’s disease.MethodsAn analysis of Neuro- QoL responsiveness to change and construct validity was performed in a multicenter clinical trial cohort.ResultsAmong 310 participants over 3- years, changes in five of eight Neuro- QoL domains were significant (P <- 0.05) but very modest. The largest effect sizes were seen in the cognition and mobility domains (0.35- 0.39). The largest effect size for change over the year in which levodopa was initiated was - 0.19 for lower extremity function- mobility. For a similarly designed clinical trial, estimated sample size required to demonstrate a 50% reduction in worsening ranged from 420 to more than 1000 participants per group.ConclusionsMore sensitive tools will be required to serve as an outcome measure in early Parkinson’s disease. © 2021 International Parkinson and Movement Disorder SocietyPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/169296/1/mds28641.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/169296/2/mds28641_am.pd