Effects of Repetitive Transcranial Magnetic Stimulation on Motor Symptoms in Parkinson Disease A Systematic Review and Meta-analysis

IMPORTANCE Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that has been closely examined as a possible treatment for Parkinson disease (PD). However, results evaluating the effectiveness of rTMS in PD are mixed, mostly owing to low statistical power or variety in individual rTMS protocols. OBJECTIVES To determine the rTMS effects on motor dysfunction in patients with PD and to examine potential factors that modulate the rTMS effects. DATA SOURCES Databases searched included PubMed, EMBASE, Web of Knowledge, Scopus, and the Cochrane Library from inception to June 30, 2014. STUDY SELECTION Eligible studies included sham-controlled, randomized clinical trials of rTMS intervention for motor dysfunction in patients with PD. DATA EXTRACTION AND SYNTHESIS Relevant measures were extracted independently by 2 investigators. Standardized mean differences (SMDs) were calculated with random-effects models. MAIN OUTCOMES AND MEASURES Motor examination of the Unified Parkinson's Disease Rating Scale. RESULTS Twenty studies with a total of 470 patients were included. Random-effects analysis revealed a pooled SMD of 0.46 (95% CI, 0.29-0.64), indicating an overall medium effect size favoring active rTMS over sham rTMS in the reduction of motor symptoms (P < .001). Subgroup analysis showed that the effect sizes estimated from high-frequency rTMS targeting the primary motor cortex (SMD, 0.77; 95% CI, 0.46-1.08; P < .001) and low-frequency rTMS applied over other frontal regions (SMD, 0.50; 95% CI, 0.13-0.87; P = .008) were significant. The effect sizes obtained from the other 2 combinations of rTMS frequency and rTMS site (ie, high-frequency rTMS at other frontal regions: SMD, 0.23; 95% CI, -0.02 to 0.48, and low primary motor cortex: SMD, 0.28; 95% CI, -0.23 to 0.78) were not significant. Meta-regression revealed that a greater number of pulses per session or across sessions is associated with larger rTMS effects. Using the Grading of Recommendations, Assessment, Development, and Evaluation criteria, we characterized the quality of evidence presented in this meta-analysis as moderate quality. CONCLUSIONS AND RELEVANCE The pooled evidence suggests that rTMS improves motor symptoms for patients with PD. Combinations of rTMS site and frequency as well as the number of rTMS pulses are key modulators of rTMS effects. The findings of our meta-analysis may guide treatment decisions and inform future research.