Objective: To investigate if a 2-week regimen comprising daily sessions of cerebellar anodal transcranial direct current stimulation (tDCS) 1) diminishes ataxia and non-motor symptom severity and 2) alters cerebellar-motor cortex (M1) connectivity in individuals with spinocerebellar ataxia type 3 (SCA3).

Background: Repeated sessions of cerebellar tDCS have been suggested to modulate cerebellar-M1 connectivity and decrease ataxia severity. However, therapeutic trials involving etiologically homogeneous groups of ataxia patients are lacking.

Method: We conducted a randomized, double-blind, sham-controlled trial in which 20 mildly to moderately affected SCA3 patients received 10 sessions of real or sham cerebellar tDCS (i.e., 5 days per week for 2 consecutive weeks). Effects were evaluated after 2 weeks, 3 months, 6 months, and 12 months. Change in Scale for the Assessment and Rating of Ataxia (SARA) score after 2 weeks was defined as the primary endpoint. Static posturography, SCA Functional Index tests, various patient-reported outcome measures, the cerebellar cognitive affective syndrome scale, and paired-pulse transcranial magnetic stimulation to examine cerebellar brain inhibition (CBI) served as secondary endpoints.

Results: Absolute change in SARA score did not differ between both trial arms at any of the time points. We observed significant short-term improvements in several motor, cognitive, and patient-reported outcomes after the last stimulation session in both groups but no treatment effects in favor of real tDCS. Nonetheless, some of the patients in the intervention arm showed a sustained reduction in SARA score lasting 6 or even 12 months, indicating interindividual variability in treatment response. CBI, which reflects the functional integrity of the cerebellothalamocortical tract, remained unchanged after 10 tDCS sessions. Albeit exploratory, there was some indication for a decrease in SARA speech score after 6 and 12 months and in the number of extracerebellar signs after 3 and 6 months.

Conclusion: This study does not provide evidence that a 2-week treatment with daily cerebellar tDCS sessions reduces ataxia severity or restores cerebellar-M1 connectivity in early-to-middle-stage SCA3 patients at the group level. In order to potentially increase therapeutic efficacy, further research is warranted to identify individual predictors of symptomatic improvement.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cerebellar-transcranial-direct-current-stimulation-in-spinocerebellar-ataxia-type-3-a-randomized-double-blind-sham-controlled-trial/