Prospective open-label study (n=45, 32 at 5 years) showing unilateral focused‑ultrasound subthalamotomy gives sustained, side-specific motor improvement (54% off‑med MDS‑UPDRS‑III improvement for treated side; overall 27% reduction) with increased LEDD, stable QoL/function, and no late adverse…

Demonstrates durable, noninvasive, clinically actionable symptomatic benefit of STN‑FUS as a long‑term alternative to invasive neurosurgical approaches, informing therapeutic strategy and device development despite lacking disease‑modifying mechanistic insight.

BACKGROUND: Unilateral focused ultrasound subthalamotomy (STN-FUS) improves motor features of Parkinson's disease (PD) for up to 3 years. OBJECTIVES: To assess the efficacy of unilateral STN-FUS in PD 5 years post-procedure. METHODS: Prospective, open-label study including PD patients treated with STN-FUS. PRIMARY OUTCOME: change from baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-Part III (MDS-UPDRS-III) off-medication for the treated side. SECONDARY OUTCOMES: global motor state, motor complications, functional disability, quality of life, medication, and safety. RESULTS: Forty-five patients were included; 32 completed 5 years of follow-up. While off-medication, the MDS-UPDRS-III on the treated side showed 54% improvement from baseline (19.0 [95% CI 17.9-20.1] to 8.8 [7.5-10.1], P < 0.001). The total MDS-UPDRS-III was reduced by 27% (37.1 [34.9-39.3] to 27.1 [24.3-29.9], P < 0.001). At 5 years, motor complications, quality of life, and functional disability were equivalent to baseline. Levodopa equivalent daily dose (LEDD) increased from 739.2 (650.1-828.4) to 1053.3 (946.3-1160.3) milligrams (P < 0.001). Mild-to-moderate levodopa-induced dyskinesias (n = 7) were reported. No late adverse events occurred. CONCLUSION: Unilateral STN-FUS for PD may provide sustained motor benefits after 5 years. © 2026 International Parkinson and Movement Disorder Society.