Monitoring the Progression of Pre-Ataxic Gait in SCA2 with Inertial Sensors Over Four Years

The search for digital biomarkers of gait ataxia is a key research priority in spinocerebellar ataxias (SCAs), especially in the early stages when traditional clinical scales are less effective. Despite existing evidence supporting the effectiveness of suitable digital biomarkers, their use in assessing early disease progression remains limited. This study was aimed to evaluate the progression of digitally measured gait ataxia features in preclinical SCA2. Twenty-seven preclinical carriers of the SCA2 mutation were monitored four times over four years. Participants completed a 10-meter walking test (back and forth) using six body-worn inertial measurement units. We assessed stride-to-stride means and variability of eight gait features indicative of subtle abnormalities in SCA2 carriers, alongside the Scale for the Assessment and Rating of Ataxia (SARA). Mean stride-to-stride variables demonstrated significant progression more frequently than variability measures, with means primarily exhibiting non-linear patterns and variability metrics showing mainly linear trajectories. Significant progression of mean stride-to-stride variables was also observed in unconverted carriers. CAG repeat length significantly influences progression of some gait kinematics in preclinical SCA2 carriers. Notably, several digitally measured gait parameters required smaller sample sizes to detect progression in hypothetical clinical trials than the SARA clinical scale. This study confirmed the progressive deterioration of subtle gait function in preclinical SCA2 and highlighted the clinical utility of digitally derived metrics for tracking longitudinal changes at early disease stages. These digital measures may provide more sensitive and reliable biomarkers of disease progression than conventional clinical rating scales, supporting their potential use in future clinical trials.