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.
Keywords: Biomarker; Central motor conduction time; Corticospinal tract; Disease progression; Pre-ataxic disease stage; Spinocerebellar ataxia type 2; Transcranial magnetic stimulation.
Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.