Inverse associations between cerebellar inhibition and motor impairment in spinocerebellar ataxia type 3

Background: Cerebellar ataxia generally results from a lesion disrupting the corticopontocerebellar or cerebellothalamocortical tract. The cerebellar inhibition (CBI) paradigm represents a dual-coil trans cranial magnetic stimulation protocol that interrogates the integrity of the latter pathway. Whether CBI has clinical relevance in ataxia patients remains largely unknown because associations with pertinent disease severity measures in etiologically homogeneous cohorts have not been previously examined. Objective: To investigate if CBI correlates with clinical and functional indices of disease severity in individuals with spinocerebellar ataxia type 3 (SCA3). Methods: CBI was assessed in fourteen SCA3 patients by paired-pulse cerebellar-motor cortex (M1) stimulation using interstimulus intervals of 3, 5, and 10 ms. Correlation coefficients were determined between CBI and ataxia severity, manual dexterity, and walking speed. Results: Suppression of M1 excitability occurred 5 ms following a contralateral cerebellar conditioning stimulus in SCA3 patients, but, on average, CBI was significantly reduced as compared to a healthy control group from the literature (p < 0.001). A significant association was found between decreased CBI levels and higher Scale for the Assessment and Rating of Ataxia (SARA) scores (r =-0.62, p = 0.019). CBI was negatively correlated with axial, appendicular, and speech subscores, as well as with nine-hole peg test performance (r =-0.69, p = 0.006). No association was observed between CBI and walking speed. As expected, there were no significant clinical-neurophysiological correlations at 3 and 10 ms interstimulus intervals. Conclusion: Our results provide the first neurophysiological evidence for an inverse association between cerebellothalamocortical tract integrity, as reflected by reduced levels of CBI, and ataxia severity in SCA3 patients. Longitudinal studies are required to evaluate if CBI could serve as a marker of disease progression. (c) 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

Reduced levels of cerebellar inhibition (CBI) were found to be inversely associated with ataxia severity and manual dexterity in patients with spinocerebellar ataxia type 3 (SCA3). Additionally, CBI was significantly correlated with Scale for the Assessment and Rating of Ataxia (SARA) scores and nine-hole peg test performance in this cohort.