Capture of Longitudinal Change in Real-Life Walking in Cerebellar Ataxia Increases Patient Relevance and Effect Size.

Abstract

BACKGROUND With disease-modifying drugs for degenerative ataxias on the horizon, ecologically valid measures of gait performance that can detect patient-relevant changes in trial-like time frames are highly warranted. OBJECTIVES In this 2-year longitudinal study, we aimed to unravel ataxic gait measures sensitive to longitudinal changes in patients' real lives using wearable sensors. METHODS We assessed longitudinal gait changes of 26 participants with degenerative cerebellar disease (Scale for the Assessment and Rating of Ataxia [SARA]: 9.4 ± 4.1) at baseline, 1-year, and 2-year follow-up using three body-worn inertial sensors in two conditions: (1) laboratory-based walking (LBW); and (2) real-life walking (RLW). In RLW, a context-sensitive analysis was performed by selecting comparable walking bouts according to macroscopic gait characteristics. Gait analysis focused on measures of spatio-temporal variability, particularly stride length variability, lateral step deviation, and a compound measure of spatial variability (SPCmp). RESULTS Gait variability measures showed high test-retest reliability in both walking conditions (intraclass correlation coefficient [ICC], ≥0.82). Cross-sectional analyses revealed high correlations of gait measures with ataxia severity (SARA, effect size ρ ≥ 0.75); and with patients' subjective balance confidence (Activity-specific Balance Confidence scale [ABC]: ρ ≥ 0.71). Although SARA showed longitudinal changes only after 2 years, the gait measure SPCmp revealed changes after 1 year with high effect size (rprb = 0.80). Sample size estimation for the gait measure SPCmp showed a required cohort size of n = 42 participants (n = 38; spinocerebellar ataxias [SCA]1/2/3 subgroup) to detect a 50% reduction in progression at 1 year with a hypothetical intervention, compared to n = 147 for SARA at 2 years. CONCLUSIONS Because of their ecological validity and larger effect sizes, real-life gait characteristics represent promising performance measures as outcomes for future treatment trials. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.