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

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 SARAposture&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.