Supplementary motor area stimulation for Parkinson disease

Objective: To explore the efficacy and stimulation frequency dependence of repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA) in Parkinson disease (PD). Methods: In this randomized, double-blind, sham-controlled, multicenter study with a parallel design, a weekly intervention was performed 8 times. The effects were monitored up to 20 weeks. By central registration, participants were assigned to 1 of 3 arms of the study: low-frequency (1-Hz) rTMS, high-frequency (10-Hz) rTMS, and realistic sham stimulation. The primary end point was the score change of the Unified Parkinson's Disease Rating Scale (UPDRS) part III from the baseline. Several nonmotor symptom scales such as the Hamilton Rating Scale for Depression, apathy score, and nonmotor symptoms questionnaire were defined as secondary end points. Results: Of the 106 patients enrolled, 36 were allocated to 1-Hz rTMS, 34 to 10-Hz rTMS, and 36 to realistic sham stimulation. Results show 6.84-point improvement of the UPDRS part III in the 1-Hz group at the last visit of the 20th week. Sham stimulation and 10-Hz rTMS improved motor symptoms transiently, but their effects disappeared in the observation period. Changes in nonmotor symptoms were not clear in any group. No severe adverse event was reported. Conclusions: The 1-Hz rTMS over the SMA was effective for motor, but not nonmotor, symptoms in PD. Level of evidence: This study provides Class I evidence that 1-Hz rTMS over the SMA is effective for motor symptoms in PD.