Progression of corticospinal tract dysfunction in pre-ataxic spinocerebellar ataxia type 2: A two-years follow-up TMS study

Objective Corticospinal tract (CST) dysfunction is common in the pre-ataxic stage of spinocerebellar ataxia type 2 (SCA2) but quantitative assessment of its progression over time has not been explored. The aim of this study was to quantify the progression of CST dysfunction in pre-ataxic SCA2 using transcranial magnetic stimulation (TMS). Methods Thirty-three pre-ataxic SCA2 mutation carriers and a 33 age- and gender-matched healthy controls were tested at baseline and 2-years follow-up by standardized clinical exams, validated clinical scales, and TMS. Results Pre-ataxic SCA2 mutation carriers showed a significant increase of resting motor thresholds (RMT) to abductor pollicis brevis (APB) and tibialis anterior (TA) muscles, and of central motor conduction time (CMCT) to TA at 2-years follow-up, over and above changes in healthy controls. The changes in the pre-ataxic SCA2 mutation carriers were independent of the presence of clinical signs of CST dysfunction at baseline, and independent of conversion to clinically definite SCA2 at 2-years follow-up. Conclusions TMS markers of CST dysfunction progress significantly during the pre-ataxic stage of SCA2. Significance TMS measures of CST dysfunction may provide biomarkers of disease progression prior to clinical disease expression that have potential utility for monitoring neuroprotective therapies in future clinical trials.