Transcranial Alternating Current Stimulation for Treatment of Multiple System Atrophy Cerebellar Type: A Randomized Controlled Trial.

BACKGROUND: No disease-modifying treatments exist for the cerebellar subtype of multiple system atrophy (MSA-C). Because transcranial alternating current stimulation (tACS) has demonstrated safety and efficacy in spinocerebellar ataxia type 3, a cerebellar disorder, we tested whether tACS improves clinical outcomes in MSA-C. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of tACS in MSA-C. Participants received daily 40-minute sessions of 70 Hz, 2 mA tACS or sham stimulation, 5 days/week for 2 weeks. The primary outcome was the change from baseline to 2 weeks in the Unified Multiple System Atrophy Rating Scale (UMSARS) total score. Secondary assessments included the Scale for the Assessment and Rating of Ataxia (SARA), Scales for Outcomes in Parkinson's Disease-Autonomic Dysfunction (SCOPA-AUT), MSA quality of life (MSA-QoL), gait analysis, and fMRI. RESULTS: The primary endpoint-the change from baseline in UMSARS scores-favored active stimulation: A-tACS -4.48 (4.64) versus S-tACS 0.30 (3.98), with a mean difference of -4.78 (95% CI -6.61 to -2.94), P < 0.001. No treatment-related serious adverse events were reported. Active tACS also improved SARA and gait outcomes but not SCOPA-AUT or MSA-QoL. In exploratory fMRI analyses, no between-group effects survived FDR correction at the whole-connectome edgewise or network-pair level. A subsequent post hoc seed-based screen identified comparatively extensive connectivity-change patterns for Left Frontal Control (ContB.PFClv) and Default Mode (DefaultB.PFCd) parcels; because the seed screen was not corrected across the full 400-seed search space, these findings are hypothesis-generating rather than confirmatory. CONCLUSION: Our results show that tACS produced a statistically significant clinical improvement in MSA-C and was well tolerated. The underlying mechanisms may include enhanced brain network function.