L'Italien Gilbert J, Oikonomou Evangelos K, Khera Rohan, Potashman Michele H, Beiner Melissa W, Maclaine Grant D H, Schmahmann Jeremy D, Perlman Susan, Coric Vladimir
Biohaven Pharmaceuticals, Inc., 215 Church Street, New Haven, CT, 06510, USA.
Yale School of Medicine, New Haven, CT, USA.
Neurol Ther. 2024 Aug;13(4):1287-1301. doi: 10.1007/s40120-024-00625-6. Epub 2024 May 30.
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.
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.
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)].
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.
NCT03701399.
传统的运动质量评估方法依赖于主观标准化量表和临床专业知识。这一局限性给评估脊髓小脑共济失调（SCA）患者带来了挑战，因为这些患者的运动能力变化可能很细微且各不相同。我们假设机器学习分析系统可能会补充传统的临床医生评定的步态测量方法。我们的目标是使用基于视频的步态离散度评估来比较曲鲁唑与安慰剂对成年SCA患者步态质量的影响。
SCA患者在曲鲁唑的一项3期双盲、安慰剂对照试验（NCT03701399）中接受步态评估。视频通过深度学习姿态提取算法进行处理，随后估计一种新的步态稳定性测量指标——姿态离散度指数，该指标量化了自然行走和串联行走任务期间逐帧的对称性、平衡和稳定性。在混合线性模型、参与者水平分组以及根据年龄、性别、基线改良共济失调评估和评分功能量表（f-SARA）以及诊断后的时间进行调整的治疗组×访视周交互作用中评估曲鲁唑治疗的效果。
在218名随机分组的参与者中，分别有67名和56名参与者有可解释的串联行走和自然行走尝试的视频。在第48周时，与安慰剂相比，接受曲鲁唑治疗的个体在串联行走姿态离散度指数方面有显著改善（p = 0.010）{调整后的交互系数：0.584 [95%置信区间（CI）0.137至1.031]}。在自然行走评估中观察到类似但不显著的趋势[系数：1.198（95% CI -1.067至3.462）]。此外，自然行走期间较低的基线姿态离散度指数与随后跌倒的较高风险显著相关（p = 0.041）[调整后的泊松系数：-0.356 [95% CI -0.697至-0.014]]。
使用这种新方法，与安慰剂相比，接受曲鲁唑治疗的受试者在串联行走时步态有改善。应用于视频捕捉的步态参数的机器学习可以补充成年SCA患者临床医生报告的运动评估。姿态离散度指数可能会在未来研究中加强评估。试验注册 - 临床试验。
NCT03701399。
