AUTHOR=Cheng Bo , Luo Zhang-hong , Xiao Xiao , Che Cheng-fa , Zhu Tao , Zhang Shu-shan TITLE=Effectiveness and safety of magnetic resonance–guided unilateral focused ultrasound subthalamotomy for Parkinson’s disease: a systematic review and meta-analysis of prospective studies JOURNAL=Frontiers in Neuroscience VOLUME=Volume 19 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1693035 DOI=10.3389/fnins.2025.1693035 ISSN=1662-453X ABSTRACT=BackgroundPatients with asymmetric, medication-refractory Parkinson’s disease (PD) often continue to experience disabling motor symptoms despite optimized pharmacological management. Magnetic resonance–guided focused ultrasound subthalamotomy (FUS-STN) has recently emerged as a promising, non-invasive alternative for improving motor function. However, its overall clinical efficacy and long-term safety remain the subject of active investigation.MethodsWe systematically searched PubMed, Cochrane Library, Embase, Web of Science, and ClinicalTrials.gov from their inception to 30 November 2024. Prospective studies that assessed unilateral FUS-STN in patients with PD were included. Data were pooled using RevMan 5.3 for mean differences (MD) with 95% confidence intervals (CIs).ResultsFour prospective studies (n = 69) were included. Unilateral FUS-STN significantly reduced the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III scores for the treated hemibody in both the off-medication [MD = −11.01, 95% CI (−12.23, −9.80), p < 0.001] and on-medication states [MD = −6.51, 95% CI (−7.57, −5.42), p < 0.001]. The MDS-UPDRS II (MD = −3.05, p < 0.01) and 39-item Parkinson’s disease questionnaire summary index (PDQ-39SI) scores (MD = −6.99, p < 0.01) also improved. Levodopa equivalent daily dose (LEDD) was reduced in the short term (MD = −149.5 mg, p < 0.001), although it was attenuated at 12 months (p = 0.09). No significant improvement was observed in MDS-UPDRS IV scores (MD = −3.29, p = 0.64). In all included studies, adverse events (AEs) were frequent during and after the procedure, such as postoperative gait and speech disturbance, facial asymmetry, and dyskinesia. However, the majority of AEs were resolved during the 6–12 month follow-up period.ConclusionUnilateral FUS-STN may offer symptomatic benefits and a general safety profile in selected patients with asymmetric PD. Future investigations should emphasize large-scale, longitudinal, multicenter, and symptom-specific randomized controlled trials to assess the long-term benefits and risks of unilateral FUS-STN in PD patients.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251002754, identifier PROSPERO (CRD420251002754).