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 (r(prb) = 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.