Digital Gait Biomarkers Allow to Capture 1‐Year Longitudinal Change in Spinocerebellar Ataxia Type 3
Winfried Ilg, Björn Müller, Jennifer Faber, Judith van Gaalen, Holger Hengel, Ina R. Vogt, Guido Hennes, Bart P.C. van de Warrenburg, Thomas Klockgether, Lüdger Schöls, Matthis Synofzik
Abstract
ABSTRACT 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 r prb = 0.66; lateral sway: P = 0.007, r prb = 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