Digital Gait Measures Capture 1‐Year Progression in Early‐Stage Spinocerebellar Ataxia Type 2.

Background: With disease‐modifying drugs in reach for cerebellar ataxias, fine‐grained digital health measures are highly warranted to complement clinical and patient‐reported outcome measures in upcoming treatment trials and treatment monitoring. These measures need to demonstrate sensitivity to capture change, in particular in the early stages of the disease. Objective: Our aim is to unravel gait measures sensitive to longitudinal change in the—particularly trial‐relevant—early stage of spinocerebellar ataxia type 2 (SCA2). Methods: We performed a multicenter longitudinal study with combined cross‐sectional and 1‐year interval longitudinal analysis in early‐stage SCA2 participants (n = 23, including nine pre‐ataxic expansion carriers; median, ATXN2 CAG repeat expansion 38 ± 2; median, Scale for the Assessment and Rating of Ataxia [SARA] score 4.8 ± 4.3). Gait was assessed using three wearable motion sensors during a 2‐minute walk, with analyses focused on gait measures of spatio‐temporal variability that have shown sensitivity to ataxia severity (eg, lateral step deviation). Results: We found significant changes for gait measures between baseline and 1‐year follow‐up with large effect sizes (lateral step deviation P = 0.0001, effect size rprb = 0.78), whereas the SARA score showed no change (P = 0.67). Sample size estimation indicates a required cohort size of n = 43 to detect a 50% reduction in natural progression. Test–retest reliability and minimal detectable change analysis confirm the accuracy of detecting 50% of the identified 1‐year change. Conclusions: Gait measures assessed by wearable sensors can capture natural progression in early‐stage SCA2 within just 1 year—in contrast to a clinical ataxia outcome. Lateral step deviation represents a promising outcome measure for upcoming multicenter interventional trials, particularly in the early stages of cerebellar ataxia. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]