High-Frequency Repetitive Transcranial Magnetic Stimulation Over the Left Dorsolateral Prefrontal Cortex Shortly Alleviates Fatigue in Patients With Multiple System Atrophy: A Randomized Controlled Trial

Background: Fatigue is a common symptom in patients with Multiple system atrophy (MSA), but effective treatments remain elusive. The present study aims to investigate whether high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) could relieve fatigue in patients with MSA. Methods: This is a single-center, randomized and double-blind trial. Twenty-two patients with MSA and fatigue were randomly allocated to receive 10 sessions of either active (N = 11) or sham (N = 11) 10 Hz rTMS over the left DLPFC. The participants were assessed at baseline (T0), after the last session of treatment (T1), and at 2-week (T2), and 4-week (T3) follow-up timepoints. The primary outcomes were Fatigue Severity Scale-9 (FSS-9) scores, with Unified Multiple System Atrophy Rating Scale (UMSARS), 17-item Hamilton Depression Scale (HAMD-17), and Hamilton Anxiety Scale (HAMA) as secondary outcomes. Results: Two-way repeated ANOVAs revealed significant group × time interactions for FSS-9 scores (p < 0.001), HAMD-17 scores (p = 0.01), HAMA scores (p = 0.01), and UMRSA part II (p = 0.05). Post-hoc analyses showed that compared to T0, the active group exhibited remarkable improvements in FSS-9 and UMRSA part II scores at T1 and T2, but not at T3, and also in HAMD-17 and HAMA scores at T1, T2, and T3. No significant improvement was found in the sham group. Conclusion: High-frequency rTMS over the left DLPFC could provide short-term improvements for alleviating fatigue in patients with MSA, but the beneficial effects last no more than 4 weeks.