Neurology and Therapy (May 2024)

Video-Based Kinematic Analysis of Movement Quality in a Phase 3 Clinical Trial of Troriluzole in Adults with Spinocerebellar Ataxia: A Post Hoc Analysis

  • Gilbert J. L’Italien,
  • Evangelos K. Oikonomou,
  • Rohan Khera,
  • Michele H. Potashman,
  • Melissa W. Beiner,
  • Grant D. H. Maclaine,
  • Jeremy D. Schmahmann,
  • Susan Perlman,
  • Vladimir Coric

DOI
https://doi.org/10.1007/s40120-024-00625-6
Journal volume & issue
Vol. 13, no. 4
pp. 1287 – 1301

Abstract

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Abstract 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.

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