Objective: To evaluate the efficacy of unilateral focused ultrasound subthalamotomy (FUS-STN) in treating patients with Parkinson’s Disease (PD).

Background: PD is a neurodegenerative disorder with a spectrum of clinical presentations, often resulting in various motor and non-motor symptoms [1]. As the disease progresses, PD patients often require increasing doses of levodopa therapy, leading to motor fluctuations, dyskinesia, and dopa resistance [2]. Alternatives such as dopamine agonists and COMT inhibitors may help alleviate symptoms but often cause significant side effects [3]. FUS-STN presents an appealing clinical alternative, offering a cost-effective, minimally invasive approach with low patient commitment [4,5]; however, no meta-analysis has been conducted to evaluate its effects.

Method: We systematically searched four databases, PubMed, Embase, Cochrane Library, and Web of Science, from inception until March 1, 2025, for relevant studies. We included single-arm data from randomized controlled trials (RCTs) and single-arm open-label trials. The primary outcomes were changes in MDS-UPDRS III scores during OFF state, and PDQ-39 scores. Outcome changes from baseline were estimated and pooled to calculate the overall mean change from baseline using R 4.3.2. A random-effects model was done to account for variability and heterogeneity assessed using the I² statistic. In cases of significant heterogeneity in outcomes with 3 or more studies, a meta-regression analysis was performed.

Results: Overall, six studies (N = 91) were included in this meta-analysis. Patients undergoing FUS-STN had improved MDS-UPDRS III from baseline with overall pooled change of -12.73 (95% CI: -15.93; -9.54) at 3 months, -8.72 (95% CI: -12.28; -5.16) at 4 months, -11.54 (95% CI: -13.63; -9.45) at 6 months, and -11.38 (95% CI: -13.44; -9.33) at 12 months. Meta regression analysis at 6 months using gender and age moderators fully explained the resulting heterogeneity (originally, I² = 71%). Particularly, a higher female proportion in studies resulted in significantly decreased overall improvement (β = 13.32, 95% CI: 3.76–22.88, p = 0.0063). Patients had improved PDQ-39 scores from baseline with an overall pooled change of -9.04 (95% CI: -16.98; -1.10) at 6 months.

Conclusion: This meta-analysis demonstrates improvements in motor symptom burden and quality of life following FUS-STN in patients with Parkinson’s Disease.

Figure 1 – MDS-UPDRS Change

Figure 2 – PDQ-39 Change

References: [1] Hauser R A, LeWitt PA, and Comella CL. On demand therapy for Parkinson’s disease patients: Opportunities and choices. Postgrad Med 2021; 133(7): 721–727.

[2] Mishal B, Shetty A, Wadia P. Adverse effects of medications used to treat motor symptoms of Parkinson’s disease: a narrative review. Ann Mov Disord 2023;6:45.

[3] Richmond AM, Lyons KE, Pahwa R. Safety review of current pharmacotherapies for levodopa-treated patients with Parkinson’s disease. Expert Opinion on Drug Safety 2023; 22(7):563–579.

[4] Máñez-Miró JU, Rodríguez-Rojas R, Del Álamo M, et al. Present and future of subthalamotomy in the management of Parkinson’s disease: a systematic review. Expert Rev Neurother 2021;21:533-545.

[5] Mahajan UV, Ravikumar VK, Kumar KK, et al. Bilateral deep brain stimulation is the procedure to beat for advanced Parkinson disease: a meta-analytic, cost-effective threshold analysis for focused ultrasound. Neurosurgery 2021;88:487-496

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MDS Abstracts - https://www.mdsabstracts.org/abstract/efficacy-of-unilateral-focused-ultrasound-subthalamotomy-in-parkinsons-disease-a-systematic-review-and-meta-analysis/