OBJECTIVES: With disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid motor biomarkers are highly warranted. In this observational study, we aimed 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 spatio-temporal step variability and movement smoothness.

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 with a discrimination accuracy of 0.86 in real life. 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 clinical SARA_posture&gait 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 motor markers for natural history and treatment trials in ecologically valid contexts.

Walking movements were recorded in three different conditions, namely: (i) Lab-based walking (LBW condition): walking was constrained by a specified walking distance of 50m in a specific quiet non-public indoor floor within an institutional setting (hospital), and supervised by a study assessor watching the walking performance; patients were instructed to walk normally at a self-selected speed;  (ii) Supervised Free Walking (SFW condition): unconstrained walking in public indoor floor and outdoor spaces  on an institutional (hospital) compound where subjects were free to choose and change the floors and indoor and outdoor spaces where they wished to walk (complete walking time: 5 minutes) with all spaces being open to public, but still supervised by a study assessor watching subject’s walking performance;   (iii)  Real-Life Walking (RLW condition): unconstrained walking during subjects’ everyday living where subjects where free to move how they wanted and were used to in their  individual daily life, without supervision by any study personnel (total recording time: 4-6 hours).