Test–retest reliability of the Friedreich’s ataxia rating scale

The modified Friedreich Ataxia Rating Scale (mFARS) is a disease specific, exam-based neurological rating scale commonly used as a outcome measure in clinical trials. While extensive clinimetric testing indicates it’s validity in measuring disease progression, formal test–retest reliability was lacking. To fill this gap, we acquired results from screening and baseline visits of several large clinical trials and calculated intraclass correlation coefficients, coefficients of variance, standard error, and the minimally detectable changes. This study demonstrated excellent test–retest reliability of the mFARS, and it’s upright stability subscore.Fil: Rummey, Christian. Clinical Data Science Gmbh; SuizaFil: Zesiewicz, Theresa A.. University of South Florida; ArgentinaFil: Perez Lloret, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Farmer, Jennifer M.. Friedreich Ataxia Research Alliance; Estados UnidosFil: Pandolfo, Massimo. Université Libre de Bruxelles; BélgicaFil: Lynch, David R.. Children’s Hospital of Philadelphia; Estados Unido

Clinical characteristics of patients with spinocerebellar ataxias 1, 2, 3 and 6 in the US; a prospective observational study

Background: All spinocerebellar ataxias (SCAs) are rare diseases. SCA1, 2, 3 and 6 are the four most common SCAs, all caused by expanded polyglutamine-coding CAG repeats. Their pathomechanisms are becoming increasingly clear and well-designed clinical trials will be needed. Methods: To characterize the clinical manifestations of spinocerebellar ataxia (SCA) 1, 2, 3 and 6 and their natural histories in the United States (US), we conducted a prospective multicenter study utilized a protocol identical to the European consortium study, using the Scale for the Assessment and Rating of Ataxia (SARA) score as the primary outcome, with follow-ups every 6 months up to 2 years. Results: We enrolled 345 patients (60 SCA1, 75 SCA2, 138 SCA3 and 72 SCA6) at 12 US centers. SCA6 patients had a significantly later onset, and SCA2 patients showed greater upper-body ataxia than patients with the remaining SCAs. The annual increase of SARA score was greater in SCA1 patients (mean ± SE: 1.61 ± 0.41) than in SCA2 (0.71 ± 0.31), SCA3 (0.65 ± 0.24) and SCA6 (0.87 ± 0.28) patients (p = 0.049). The functional stage also worsened faster in SCA1 than in SCA2, 3 and 6 (p = 0.002). Conclusions: The proportions of different SCA patients in US differ from those in the European consortium study, but as in the European patients, SCA1 progress faster than those with SCA2, 3 and 6. Later onset in SCA6 and greater upper body ataxia in SCA2 were noted. We conclude that progression rates of these SCAs were comparable between US and Europe cohorts, suggesting the feasibility of international collaborative clinical studies

Prospective Home-use Study on Non-invasive Neuromodulation Therapy for Essential Tremor.

Highlights: This prospective study is one of the largest clinical trials in essential tremor to date. Study findings suggest that individualized non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction and improves quality of life for many essential tremor patients. Background: Two previous randomized, controlled, single-session trials demonstrated efficacy of non-invasive neuromodulation therapy targeting the median and radial nerves for reducing hand tremor. This current study evaluated efficacy and safety of the therapy over three months of repeated home use. Methods: This was a prospective, open-label, post-clearance, single-arm study with 263 patients enrolled across 26 sites. Patients were instructed to use the therapy twice daily for three months. Pre-specified co-primary endpoints were improvements on clinician-rated Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) and patient-rated Bain & Findley Activities of Daily Living (BF-ADL) dominant hand scores. Other endpoints included improvement in the tremor power detected by an accelerometer on the therapeutic device, Clinical and Patient Global Impression scores (CGI-I, PGI-I), and Quality of Life in Essential Tremor (QUEST) survey. Results: 205 patients completed the study. The co-primary endpoints were met (p≪0.0001), with 62% (TETRAS) and 68% (BF-ADL) of \u27severe\u27 or \u27moderate\u27 patients improving to \u27mild\u27 or \u27slight\u27. Clinicians (CGI-I) reported improvement in 68% of patients, 60% (PGI-I) of patients reported improvement, and QUEST improved (p = 0.0019). Wrist-worn accelerometer recordings before and after 21,806 therapy sessions showed that 92% of patients improved, and 54% of patients experienced ≥50% improvement in tremor power. Device-related adverse events (e.g., wrist discomfort, skin irritation, pain) occurred in 18% of patients. No device-related serious adverse events were reported. Discussion: This study suggests that non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction in many essential tremor patients

Methods of treating disease-induced ataxia and non-ataxic imbalance

Methods for treatment of disease-induced ataxia and non-ataxic imbalance are disclosed. The methods involve treating a patient with a compound having nicotinic acetylcholine receptor activity

Depressive Symptoms in Parkinson Disease: Degree of Association and Rate of Agreement of Clinician-Based and Self-Report Measures

Depression in Parkinson disease (PD) is associated with faster disease progression, lower activities of daily living, and more severe cognitive impairment. Even mild symptoms of depression may impact outcomes in patients with PD. Nevertheless, a low rate of agreement has been reported between patient and clinician ratings of depression, suggesting that clinicians may underestimate depression in patients with PD. However, to accurately compare the rates of agreement, comparable estimates are needed so that patient and clinician ratings have similar meaning (eg, mild, moderate, severe, etc). The purpose of this study was to examine this question by investigating the degree of association and rate of agreement of levels of symptom severity among self-report and clinician ratings using established cutoffs that correspond to more comparable estimates of these levels for both patient and clinician. Our findings suggest that patient\u27s self-report of depressive symptoms was significantly correlated with clinician-based report irrespective of the stage of disease. Moreover, patients demonstrated a 72% rate of agreement with clinicians in classifying symptoms as asymptomatic, mildly symptomatic, or fully symptomatic, a rate significantly higher than the rate of 35% previously reported. This difference in rate of agreement may be accounted for using varying criteria for severity levels across the studies. Findings suggest that clinician and patient reports show a high rate of agreement across a range of depressive symptoms and that self-report measures may provide a relatively efficient means of detecting depressive symptoms especially if patients are disinclined to initiate their report