Repeated sessions of cerebellar anodal
transcranial direct current stimulation (
tDCS) have been suggested to modulate cerebellar-motor cortex (M1) connectivity and decrease
ataxia severity. However, therapeutic trials involving etiologically homogeneous groups of
ataxia patients are lacking. The objective of this study was to investigate if a two-week regimen of daily cerebellar
tDCS sessions diminishes
ataxia and non-motor symptom severity and alters cerebellar-M1 connectivity in individuals with
spinocerebellar ataxia type 3 (SCA3). We conducted a randomized, double-blind,
sham-controlled trial in which twenty mildly to moderately affected SCA3 patients received ten sessions of real or
sham cerebellar
tDCS (i.e., five days per week for two consecutive weeks). Effects were evaluated after two weeks, three months, six months, and twelve months. Change in Scale for the Assessment and Rating of
Ataxia (SARA) score after two 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. 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 six or even twelve months, indicating interindividual variability in treatment response. CBI, which reflects the functional integrity of the cerebellothalamocortical tract, remained unchanged after ten
tDCS sessions. Albeit exploratory, there was some indication for between-group differences in SARA speech score after six and twelve months and in the number of extracerebellar signs after three and six months. Taken together, our study does not provide evidence that a two-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.