Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Aug;13(4):1287-1301.
doi: 10.1007/s40120-024-00625-6. Epub 2024 May 30.

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  1 , Evangelos K Oikonomou  2 , Rohan Khera  2 , Michele H Potashman  3 , Melissa W Beiner  1 , Grant D H Maclaine  4 , Jeremy D Schmahmann  5 , Susan Perlman  6 , Vladimir Coric  1
Affiliations

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 et al. Neurol Ther. 2024 Aug.

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.

Keywords: Artificial intelligence; Kinematic analysis; Pose dispersion index; Spinocerebellar ataxia; Troriluzole; Video.

PubMed Disclaimer

Conflict of interest statement

Evangelos Oikonomou receives support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (under award 1F32HL170592) outside the submitted work. He is an academic co-founder of Evidence2Health LLC, a co-inventor in patent applications (US17/720,068, 63/177,117, 63/580,137, 63/606,203, WO2018078395A1, WO2020058713A1) and has been an ad hoc consultant for Caristo Diagnostics Ltd. Rohan Khera is an Associate Editor of JAMA. He receives support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (under award K23HL153775) and the Doris Duke Charitable Foundation (under award, 2022060) outside the submitted work. He also receives research support, through Yale, from Bristol-Myers Squibb and Novo Nordisk. He is a coinventor of U.S. Provisional Patent Applications 63/177,117, 63/428,569, 63/346,610, 63/484,426, 63/508,315, 63/580,137 and 63/606,203, and an academic co-founder of Evidence2Health, LLC and ENSIGHT-AI, Inc. Jeremy Schmahmann has served on the editorial board for The Cerebellum, Editorial Board,1999. Consultancy: Biohaven Pharmaceuticals. Site PI: Biohaven clinical Trials in ataxia and multiple system atrophy. Research Support, Commercial Entities: Biohaven Pharma support of clinical trials. Research Support, Academic Entities: National Ataxia Foundation. Research Support, Foundations and Societies: National Ataxia Foundation, 2019, PI License fee payments, Technology or Inventions: Brief Ataxia Rating Scale (BARS), and Brief Ataxia Rating Scale revised (BARS2). Copyright held by The General Hospital Corporation. Cerebellar Cognitive Affective/Schmahmann syndrome Scale. Copyright held by The General Hospital Corporation. Patient-Reported Outcome Measure of Ataxia. Copyright held by The General Hospital Corporation. Cerebellar Neuropsychiatric Rating Scale. Copyright held by The General Hospital Corporation. Susan Perlman has nothing to disclose. Gilbert L’Italien, Michele Potashman, Melissa Beiner, Grant Maclaine and Vladimir Coric are employed by and own stock and stock options in Biohaven, Ltd.

Figures

Fig. 1
Fig. 1
Change in the Pose Dispersion Index during a tandem walk task and a natural walk task at week 48
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Hekman KE, Gomez CM. The autosomal dominant spinocerebellar ataxias: emerging mechanistic themes suggest pervasive Purkinje cell vulnerability. J Neurol Neurosurg Psychiatry. 2015;86(5):554–61. 10.1136/jnnp-2014-308421. 10.1136/jnnp-2014-308421 - DOI - PMC - PubMed
    1. Robinson KJ, Watchon M, Laird AS. Aberrant cerebellar circuitry in the spinocerebellar ataxias. Front Neurosci. 2020;14:707. 10.3389/fnins.2020.00707. 10.3389/fnins.2020.00707 - DOI - PMC - PubMed
    1. Prestori F, Moccia F, D’Angelo E. Disrupted calcium signaling in animal models of human spinocerebellar ataxia (SCA). Int J Mol Sci. 2019. 10.3390/ijms21010216. 10.3390/ijms21010216 - DOI - PMC - PubMed
    1. Sullivan R, Yau WY, O’Connor E, Houlden H. Spinocerebellar ataxia: an update. J Neurol. 2019;266(2):533–44. 10.1007/s00415-018-9076-4. 10.1007/s00415-018-9076-4 - DOI - PMC - PubMed
    1. Chuang CY, Yang CC, Soong BW, Yu CY, Chen SH, Huang HP, et al. Modeling spinocerebellar ataxias 2 and 3 with iPSCs reveals a role for glutamate in disease pathology. Sci Rep. 2019;9(1):1166. 10.1038/s41598-018-37774-2. 10.1038/s41598-018-37774-2 - DOI - PMC - PubMed

Associated data