RESUMEN
INTRODUCTION: Traditional methods for assessing movement quality rely on subjective standardized scales and clinical expertise. This limitation creates challenges for assessing patients with spinocerebellar ataxia (SCA), in whom changes in mobility can be subtle and varied. We hypothesized that a machine learning analytic system might complement traditional clinician-rated measures of gait. Our objective was to use a video-based assessment of gait dispersion to compare the effects of troriluzole with placebo on gait quality in adults with SCA. METHODS: Participants with SCA underwent gait assessment in a phase 3, double-blind, placebo-controlled trial of troriluzole (NCT03701399). Videos were processed through a deep learning pose extraction algorithm, followed by the estimation of a novel gait stability measure, the Pose Dispersion Index, quantifying the frame-by-frame symmetry, balance, and stability during natural and tandem walk tasks. The effects of troriluzole treatment were assessed in mixed linear models, participant-level grouping, and treatment group-by-visit week interaction adjusted for age, sex, baseline modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA), and time since diagnosis. RESULTS: From 218 randomized participants, 67 and 56 participants had interpretable videos of a tandem and natural walk attempt, respectively. At Week 48, individuals assigned to troriluzole exhibited significant (p = 0.010) improvement in tandem walk Pose Dispersion Index versus placebo {adjusted interaction coefficient: 0.584 [95% confidence interval (CI) 0.137 to 1.031]}. A similar, nonsignificant trend was observed in the natural walk assessment [coefficient: 1.198 (95% CI - 1.067 to 3.462)]. Further, lower baseline Pose Dispersion Index during the natural walk was significantly (p = 0.041) associated with a higher risk of subsequent falls [adjusted Poisson coefficient: - 0.356 [95% CI - 0.697 to - 0.014)]. CONCLUSION: Using this novel approach, troriluzole-treated subjects demonstrated improvement in gait as compared to placebo for the tandem walk. Machine learning applied to video-captured gait parameters can complement clinician-reported motor assessment in adults with SCA. The Pose Dispersion Index may enhance assessment in future research. TRIAL REGISTRATION-CLINICALTRIALS. GOV IDENTIFIER: NCT03701399.
RESUMEN
Ataxia rating scales are observer administered clinical outcome assessments (COAs) of the cerebellar motor syndrome. It is not known whether these COAs mirror patient experience of their disease. Here we test the hypothesis that ataxia COAs are related to and reflect patient reported symptoms and impact of illness. A concept library of symptoms and activities impacted by ataxia was created by reviewing (a) concept elicitation data from surveys completed by 147 ataxia patients and 80 family members and (b) cognitive debrief data from focus groups of 17 ataxia patients used to develop the Patient Reported Outcome Measure of Ataxia. These findings were mapped across the items on 4 clinical measures of ataxia (SARA, BARS, ICARS and FARS). Symptoms reported most commonly related to balance, gait or walking, speech, tremor and involuntary movements, and vision impairment. Symptoms reported less frequently related to hand coordination, loss of muscle control, dizziness and vertigo, muscle discomfort or pain, swallowing, and incontinence. There was a mosaic mapping of items in the observer-derived ataxia COAs with the subjective reports by ataxia patients/families of the relevance of these items to their daily lives. Most COA item mapped onto multiple real-life manifestations; and most of the real-life impact of disease mapped onto multiple COA items. The 4 common ataxia COAs reflect patient reported symptoms and impact of illness. These results validate the relevance of the COAs to patients' lives and underscore the inadvisability of singling out any one COA item to represent the totality of the patient experience.
