Towards ecologically valid biomarkers: real-life gait assessment in cerebellar ataxia

Abstract BACKGROUND With disease-modifying drugs on the horizon for degenerative ataxias, motor biomarkers are highly warranted. While ataxic gait and its treatment-induced improvements can be captured in laboratory-based assessments, quantitative markers of ataxic gait in real life will help to determine ecologically meaningful improvements. OBJECTIVES To unravel and validate markers of ataxic gait in real life by using wearable sensors. METHODS We assessed gait characteristics of 43 patients with degenerative cerebellar disease (SARA:9.4±3.9) compared to 35 controls by 3 body-worn inertial sensors in three conditions: (1) laboratory-based walking; (2) supervised free walking; (3) real-life walking during everyday living (subgroup n=21). Movement analysis focussed on measures of movement smoothness and spatio-temporal step variability. RESULTS A set of gait variability measures was identified which allowed to consistently identify ataxic gait changes in all three conditions. Lateral step deviation and a compound measure of step length categorized patients against controls in real life with a discrimination accuracy of 0.86. Both were highly correlated with clinical ataxia severity (effect size ρ=0.76). These measures allowed detecting group differences even for patients who differed only 1 point in the SARA p&g subscore, with highest effect sizes for real-life walking ( d =0.67). CONCLUSIONS We identified measures of ataxic gait that allowed not only to capture the gait variability inherent in ataxic gait in real life, but also demonstrate high sensitivity to small differences in disease severity - with highest effect sizes in real-life walking. They thus represent promising candidates for quantitative motor markers for natural history and treatment trials in ecologically valid contexts.