Digital gait measures capture 1-year progression in early-stage spinocerebellar ataxia type 2

Abstract

AbstractBACKGROUNDWith 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.OBJECTIVETo unravel gait measures sensitive to longitudinal change in the - particularly trial-relevant- early stage of spinocerebellar ataxia type 2 (SCA2).METHODSMulti-center longitudinal study with combined cross-sectional and 1-year interval longitudinal analysis in early-stage SCA2 participants (n=23, including 9 pre-ataxic expansion carriers; medianATXN2CAG repeat expansion 38±2; median SARA [Scale for the Assessment and Rating of Ataxia] score 4.83±4.31). Gait was assessed using three wearable motion sensors during a 2-minute walk, with analyses focusing on gait measures of spatiotemporal variability shown sensitive to ataxia severity, e.g. lateral step deviation.RESULTSWe 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.CONCLUSIONSGait measures assessed by wearable sensors can capture natural progression in early-stage SCA2 within just one year – in contrast to a clinical ataxia outcome. Lateral step deviation thus represents a promising outcome measure for upcoming multi-centre interventional trials, particularly in the early stages of cerebellar ataxia.