Adler, C H

AbstractBackgroundADS‐5102 (amantadine) extended release capsules (GOCOVRI™) are a treatment for dyskinesia in patients with Parkinson's disease (PD). ADS‐5102 reduced dyskinesia and OFF time in phase 3 controlled trials of up to six months. Amantadine immediate release (IR) is used for dyskinesia, but suboptimal durability and tolerability limit its clinical utility.MethodsIn an ongoing, open‐label, phase 3 study in the US and Western Europe (NCT02202551), patients with PD received 274 mg of ADS‐5102 (equivalent to 340 mg amantadine HCl) once daily at bedtime for up to two years. Study outcomes included safety and assessment of motor complications, as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Part IV. This manuscript focuses on those patients switched to ADS‐5102 from amantadine IR. Results in two groups of patients who previously completed a randomized controlled trial (EASE LID or EASE LID 3) are also presented according to use of ADS‐5102 or placebo in that study before enrollment in the open‐label study.ResultsChange in MDS‐UPDRS Part IV at week 8 was –0.3 in the previous ADS‐5102 subgroup (n = 61), –3.4 in the previous placebo subgroup (n = 79), and –3.4 in the previous amantadine IR subgroup (n = 32). Effects were maintained to week 64. In the previous amantadine IR subgroup (mean treatment duration, 2.5 years), mean amantadine IR dose was 221 mg. Safety data were consistent with previous randomized controlled trials of ADS‐5102.ConclusionThese open‐label data suggest ADS‐5102 provides incremental reduction from baseline in MDS‐UDPRS Part IV score in patients switched directly from amantadine IR, without exacerbating adverse events.

AbstractBackgroundClinical diagnostic criteria for PD rely on rest tremor, bradykinesia, and rigidity. These features are non‐specific and neuropathological confirmation remains the gold standard for diagnosis. This study presents data on clinical certainty ratings in autopsy‐proven PD.MethodsSubjects were assessed annually by a movement disorders specialist and assigned to a clinical certainty group for PD based on multiple clinical features before autopsy. The three groups considered for analysis are as follows: Group I 0–49% certainty, Group II 50‐89% certainty, and Group III 90–100% certainty. All subjects were autopsied and had a standardized neuropathological assessment.Results275 subjects were assigned a PD certainty at their last visit before death. Group I had 80 subjects, Group II 56 subjects, and Group III 139 subjects. The clinical features recorded in Group I, II, and III, were as follows: rest tremor, bradykinesia, rigidity, postural instability, asymmetric onset, persistent asymmetry, current response to dopaminergic treatment, motor fluctuations, and dyskinesia. Rigidity, postural instability, asymmetric onset, current response to dopaminergic treatment, motor fluctuation, and dyskinesia were more likely to be present in the group which was rated with higher certainty. The final diagnosis of PD was confirmed by neuropathological assessment in 85% of the patients in Group III as compared to 30% in Group II and 5% in Group I.ConclusionsHigh certainty (90–100%) had strong positive predictive value (85%) for autopsy‐proven PD as compared to either lower certainty groups (0–49% and 50–89%) which had lower predictive value (5% and 30% respectively).

Background and purpose Mutations in the glucocerebrosidase ( GBA ) gene are known to be a risk factor for Parkinson's disease ( PD ). Data on clinicopathological correlation are limited. The purpose of this study was to determine the clinicopathological findings that might distinguish PD cases with and without mutations in the GBA gene. Methods Data from the Arizona Study of Aging and Neurodegenerative Disorders were used to identify autopsied PD cases that did or did not have a GBA gene mutation. Clinical and neuropathological data were compared. Results Twelve PD cases had a GBA mutation and 102 did not. The GBA mutation cases died younger (76 vs. 81 years of age) but there was no difference in disease duration or clinical examination findings. No neuropathological differences were found in total or regional semi‐quantitative scores for Lewy‐type synucleinopathy, senile plaques, neurofibrillary tangles, white matter rarefaction or cerebral amyloid angiopathy scores. Conclusions In longitudinally assessed, autopsied PD cases, those with GBA mutations had a younger age at death but there was no evidence for clinical or neuropathological differences compared to cases without GBA mutations. Due to the small GBA group size, small differences cannot be excluded.