Digital Gait Biomarkers Allow to Capture 1-Year Longitudinal Change in Spinocerebellar Ataxia Type 3.

Measures of step variability and body sway during gait have shown to correlate with clinical ataxia severity in several cross-sectional studies. However, to serve as a valid progression biomarker, these gait measures have to prove their sensitivity to robustly capture longitudinal change, ideally within short time frames (eg, 1 year). We present the first multicenter longitudinal gait analysis study in spinocerebellar ataxias. We performed a combined cross-sectional (n = 28) and longitudinal (1-year interval, n = 17) analysis in Spinocerebellar Ataxia type 3 subjects (including seven preataxic mutation carriers). Longitudinal analysis showed significant change in gait measures between baseline and 1-year follow-up, with high effect sizes (stride length variability: P = 0.01, effect size rprb  = 0.66; lateral sway: P = 0.007, rprb  = 0.73). Sample size estimation for lateral sway indicates a required cohort size of n = 43 for detecting a 50% reduction of natural progression, compared with n = 240 for the clinical ataxia score Scale for the Assessment and Rating of Ataxia (SARA). These measures thus present promising motor biomarkers for upcoming interventional studies. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.