Corticospinal tract involvement in Spinocerebellar ataxias type 1, 2 and 3 characterized by motor evoked potential and diffusion MRI

Background Spinocerebellar ataxia (SCA) type 1, 2, and 3 are the most frequent spinocerebellar ataxia, characterized by brainstem, basal ganglia and cerebellar damage. To date, no studies have investigated damage in the corticospinal tract using neurophysiological and neuroimaging approaches. The objective was to investigate the clinical features, neurophysiological and imaging aspects of SCA subtypes. Methods A total of 23 SCA1, 21 SCA2, 40 SCA3 patients and 27 healthy controls were enrolled. All subjects underwent neurologic examinations and motor evoked potential (MEP) recordings. Additionally, SCA3 patients completed MRI acquisition. Association between CMCT value and corticospinal tract diffusion kurtosis imaging (DKI) metrics, counts of corticospinal tract streamlines and clinical parameters were analyzed. Results MEP abnormality observed in 95.7% of SCA1, followed by 87.5% of SCA3 and 66.7% of SCA2. SCA1 demonstrated significantly higher resting motor threshold (RMT) than both controls and other subtypes. Furthermore, all SCA cohorts showed prolonged CMCT of both upper and lower limbs relative to controls. Meanwhile, in SCA3 patients, CMCT of lower limb demonstrated significant correlations with DKI metrics (fractional anisotropy: r = -0.4815, P  < 0.05; mean kurtosis: r = -0.4411, P  < 0.05) of corticospinal tract, while showing no significant association with tractography-derived streamlines counts. In addition, lower limb CMCT value correlated positively with clinical severity (r = 0.4616, P  = 0.004) and disease duration (r = 0.5647, P  = 0.0003) in SCA3 patients. Conclusions Our study provide significant neurophysiological and imaging characteristics of corticospinal tract involvement in SCA cohorts. The identified correlation between CMCT value and DKI parameters of corticospinal tract, clinical severity and disease duration suggests that CMCT may become relevant biomarkers to monitor disease progression and therapeutic responses in potential future clinical trials.