Citations

ABSTRACT Purpose To determine whether quantitative methods could separate golfers with a possible dystonic cause of the “yips” from those that appear to be nondystonic. Methods Twenty-seven golfers completed 10 two-handed and 10 right hand–only putts. Surface EMG assessed forearm muscle co-contraction and motion detectors monitored wrist and putter movements. Based on a videotape review, golfers were grouped into those with yips of dystonic etiology, those with the yips nondystonic, and those with no yips. Results On video review of two-handed putting, five golfers had yips that appeared to be dystonic, nine had yips that did not appear to be dystonic, and 13 had no yips. During two-handed putting co-occurrence of a yipped putt and wrist flexor/extensor and/or pronator/supinator co-contraction was significantly more frequent in those with dystonic yips. The dystonic group had no increase in the number of yipped putts or yips with co-contraction when putting right hand only, whereas the nondystonic group had significantly more yipped putts and more yipped putts with co-contraction with right hand only. Conclusions Quantitative methods were identified that appear to identify golfers with a dystonic etiology for the yips. It is not just the frequency of yips nor just specific motion patterns alone, rather it is also a combination of yips with co-occurring co-contraction when putting with two hands, and then right hand only, that distinguished this possible etiology. Despite being a small study, identifying a dystonic pattern, even in a nonpressure indoor setting, may aid in assessment and possible monitoring of treatment.

ABSTRACTBackground: PD patients often have visual alterations, for example, loss of visual acuity, contrast sensitivity or motion perception, and diminished electroretinogram responses. PD pathology is mainly characterized by the accumulation of pathological α‐synuclein deposits in the brain, but little is known about how synucleinopathy affects the retina.Objective: To study the correlation between α‐synuclein deposits in the retina and brain of autopsied subjects with PD and incidental Lewy body disease.Methods: We evaluated the presence of phosphorylated α‐synuclein in the retina of autopsied subjects with PD (9 subjects), incidental Lewy body disease (4 subjects), and controls (6 subjects) by immunohistochemistry and compared the retinal synucleinopathy with brain disease severity indicators.Results: Whereas controls did not show any phosphorylated α‐synuclein immunoreactivity in their retina, all PD subjects and 3 of 4 incidental Lewy body disease subjects had phosphorylated α‐synuclein deposits in ganglion cell perikarya, dendrites, and axons, some of them resembling brain Lewy bodies and Lewy neurites. The Lewy‐type synucleinopathy density in the retina significantly correlated with Lewy‐type synucleinopathy density in the brain, with the Unified Parkinson's disease pathology stage and with the motor UPDRS.Conclusion: These data suggest that phosphorylated α‐synuclein accumulates in the retina in parallel with that in the brain, including in early stages preceding development of clinical signs of parkinsonism or dementia. Therefore, the retina may provide an in vivo indicator of brain pathology severity, and its detection could help in the diagnosis and monitoring of disease progression. © 2018 International Parkinson and Movement Disorder Society

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).

AbstractObjectiveTo assess the predictive potential of the complete response pattern from the University of Pennsylvania Smell Identification Test for the diagnosis of Parkinson's disease.MethodsWe analyzed a large dataset from the Arizona Study of Aging and Neurodegenerative Disorders, a longitudinal clinicopathological study of health and disease in elderly volunteers. Using the complete pattern of responses to all 40 items in each subject's test, we built predictive models of neurodegenerative disease, and we validated these models out of sample by comparing model predictions against postmortem pathological diagnosis.ResultsConsistent with anatomical considerations, we found that the specific test response pattern had additional predictive power compared with a conventional measure – total test score – in Parkinson's disease, but not Alzheimer's disease. We also identified specific test questions that carry the greatest predictive power for disease diagnosis.InterpretationOlfactory ability has typically been assessed with either self‐report or total score on a multiple choice test. We showed that a more accurate clinical diagnosis can be made using the pattern of responses to all the test questions, and validated this against the “gold standard” of pathological diagnosis. Information in the response pattern also suggests specific modifications to the standard test that may optimize predictive power under the typical clinical constraint of limited time. We recommend that future studies retain the individual item responses for each subject, and not just the total score, both to enable more accurate diagnosis and to enable additional future insights.

Objective The purpose of this review is to describe the recent advances in identifying possible factors involved in the pathogenesis of spasmodic dysphonia. Spasmodic dysphonia is a task‐specific focal laryngeal dystonia characterized by irregular and uncontrolled voice breaks. Pathogenesis of the disorder is poorly understood. Data Sources PubMed, Google Scholar, and Cochrane Library. Review Methods The data sources were searched using the following search terms: ( spasmodic dysphonia or laryngeal dystonia ) and ( etiology, aetiology, diagnosis, pathogenesis , or pathophysiology ). Conclusions Several potential etiological factors have been proposed by epidemiological, genetic, and neuropathological studies. Spasmodic dysphonia is a rare disorder primarily affecting females beginning in their 40s. Vocal tremor co‐occurs in 30% to 60%. Large cohort studies identified risk factors such as a family history of neurological disorders including dystonia and tremor, recent viral illness, and heavy voice use. As none are rare events, a complex interactive process may contribute to pathogenesis in a small proportion of those at risk. Consequences to pathogenesis are neurological processes found in spasmodic dysphonia: loss of cortical inhibition, sensory processing disturbances, and neuroanatomical and physiological differences in the laryngeal motor control system. Implications for Practice Diagnosis of spasmodic dysphonia usually includes speech and laryngoscopic assessment. However, as diagnosis is sometimes problematic, measurement of neurophysiological abnormalities may contribute useful adjuncts for the diagnosis of spasmodic dysphonia in the future.

ObjectiveThe purpose of this review is to describe the recent advances in characterizing spasmodic dysphonia. Spasmodic dysphonia is a task‐specific focal laryngeal dystonia characterized by irregular and uncontrolled voice breaks. The pathophysiology is poorly understood, and there are diagnostic difficulties.Data SourcesPubMed, Google Scholar, and Cochrane Library.Review MethodsThe data sources were searched using the following search terms: (spasmodic dysphonia or laryngeal dystonia) and (etiology, aetiology, diagnosis, pathogenesis, or pathophysiology).ConclusionThe diagnosis of spasmodic dysphonia can be difficult due to the lack of a scientific consensus on diagnostic criteria and the fact that other voice disorders may present similarly. Confusion can arise between spasmodic dysphonia and muscle tension dysphonia. Spasmodic dysphonia symptoms are tied to particular speech sounds, whereas muscle tension dysphonia is not. With the advent of more widespread use of high‐speed laryngoscopy and videokymography, measures of the disruptions in phonation and delays in the onset of vocal fold vibration after vocal fold closure can be quantified. Recent technological developments have expanded our understanding of the pathophysiology of spasmodic dysphonia.Implications for PracticeA 3‐tiered approach, involving a questionnaire, followed by speech assessment and nasolaryngoscopy is the most widely accepted method for making the diagnosis in most cases. More experimental and invasive techniques such as electromyography and neuroimaging have been explored to further characterize spasmodic dysphonia and aid in diagnosing difficult cases.

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.

AbstractIntroductionDepression and neuropsychiatric disorders in individuals with essential tremor (ET) are not well characterized in the literature.MethodsWe 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.ResultsThere 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.ConclusionThere 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.