Objective:

To evaluate the safety and clinical efficacy of staged, bilateral magnetic resonance-guided focused ultrasound (MRgFUS) pallidothalamic tractotomy (PTT) in advanced Parkinson’s disease (PD) with motor complications.

Background:

Motor fluctuations and dyskinesia are common in advanced PD and often persist despite optimized medical therapy. MRgFUS is an incisionless technique that enables precise targeting of the pallidothalamic tract at the H1/Field of Forel. This multicenter, phase III study investigates outcomes following staged, bilateral MRgFUS PTT, recently approved by the FDA for advanced PD.

Design/Methods:

This prospective, open-label, single-arm trial (NCT04728295) enrolled 84 participants (≥30 years old) across nine international centers. Those eligible underwent unilateral MRgFUS PTT, with eligibility for contralateral treatment assessed after at least 6 months. Primary efficacy was measured by change in MDS-UPDRS Part III OFF (bilateral upper/lower extremity score) at 3 months post-bilateral treatment. Secondary endpoints included MDS-UPDRS Part IV and total Part III OFF scores. Safety was assessed throughout by related adverse events.

Results:

Of 84 enrolled, 54 received unilateral treatment; 40 proceeded to bilateral. At 3 months post-unilateral treatment, Part III OFF (treated side) improved by 50% (20.9 ± 5.3 to 10.0 ± 5.4), and Part IV by 56.3% (10.5 ± 3.5 to 4.6 ± 3.7). Following bilateral treatment, bilateral extremity scores improved by 34%, total Part III OFF by 32% (51.3 ± 12.4 to 33.4 ± 11.4), and Part IV by 68% (10.7 ± 3.2 to 3.6 ± 2.9), all statistically significant (p < 0.0001). Improvements were sustained through at least 12 months. Adverse events were mostly mild, with imbalance, dysarthria, and fatigue being most common.

Conclusions:

Staged, bilateral MRgFUS PTT offers a safe and effective incisionless option for patients with advanced PD and motor complications.