Feasibility and Safety of Combined Cerebello-spinal Neuromodulation and Exercise in Spinocerebellar Ataxia Type 3: A 20-session Protocol

Abstract Background Spinocerebellar ataxia type 3 (SCA3) is a hereditary neurodegenerative disorder that progressively impairs balance and gait, without effective pharmacological treatments available. Cerebellar and cerebello-spinal transcranial direct current stimulation (tDCS) have shown neuromodulatory potential. However, extended protocols combined with exercise have not yet been tested in these individuals in a public health service. Objective To assess the feasibility and safety of 20 sessions of cerebello-spinal tDCS combined with exercise in individuals with SCA3 in realworld conditions, and to explore preliminary changes in ataxia severity, balance, and mobility. Methods: In this clinical trial, 39 participants (67% female; mean age 46 years) with mild-to-moderate SCA3 completed 20 sessions over four weeks under realworld publichealth conditions. Feasibility was evaluated through adherence and tolerability, and safety was assessed by monitoring adverse events. Secondary outcomes included disease severity (SARA), balance (Berg Balance Scale), and mobility (Timed Up and Go), assessed at baseline, post-intervention, and one-month follow-up. Analyses included standardized individual differences and multiple linear regression adjusted for baseline values. Results: Adherence was 97.3%, with no serious adverse events. Significant improvements were observed in SARA (P < 0.001), BBS (P < 0.001), and TUG (P = 0.011). Improvements were maintained at one month (P > 0.171). Conclusions: A combination of multiple sessions of cerebello-spinal tDCS and exercise in a public health service was feasible, safe, and may improve ataxia severity, balance, and mobility in individuals with SCA3. Despite the absence of a control group, these findings encourage further investigation of the proposed intervention as a potential rehabilitation strategy for cerebellar neurodegeneration.