Staged Bilateral Magnetic Resonance-Guided Focused Ultrasound for Treating Essential Tremor: Systematic Review and Meta-Analysis.

BACKGROUND: Unilateral magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy reduces tremor in essential tremor, yet disability often persists on the untreated side. The added benefit and safety of a staged contralateral lesion remain uncertain. OBJECTIVE: The aim was to evaluate the efficacy and safety of staged bilateral MRgFUS thalamotomy for essential tremor. METHODS: We searched MEDLINE, EMBASE, Web of Science, Cochrane CENTRAL, Scopus, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform from inception to April 12, 2026 (PROSPERO CRD420251027624). Eligible studies were staged bilateral MRgFUS with Clinical Rating Scale for Tremor outcomes and adverse events, and at least 3 months of follow up. Two reviewers extracted data per Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The primary outcome was the standardized mean difference (SMD) in tremor severity from pre- to post-second procedure. Safety outcomes were pooled 3-month adverse event proportions using random effects. Risk of bias was assessed with Newcastle-Ottawa Scale and Risk of Bias in Non-randomized Studies of Interventions; certainty was graded with Grading of Recommendations Assessment, Development, and Evaluation. RESULTS: Nine studies were included in the systematic review, of which seven cohorts (n = 149) were included in the meta-analysis. The pooled SMD was -1.91 (95% confidence intervals, -2.19 to -1.63; I2 = 0%), indicating consistent, large-magnitude tremor reduction across all seven cohorts. Three-month adverse events included sensory changes (28.8%), gait disturbance (27.5%), dysarthria (22.0%), taste changes (21.7%), dysphagia (18.4%), and ataxia (11.3%). All studies were single-arm and non-randomized with moderate to serious risk of bias, and certainty was very low. CONCLUSIONS: Staged bilateral MRgFUS yielded clinically meaningful tremor reduction with predominantly mild adverse events at 3 months. Given very low certainty, findings are hypothesis-generating and support-controlled studies with blinded assessment and longer follow-up.