Staged Bilateral FUS-STN Safely Improves Motor Features in Parkinsonism

A study published in the JAMA Neurology suggests that unilateral magnetic resonance imaging (MRI)–guided focused ultrasound subthalamotomy (FUS-STN) improves cardinal motor features among patients with asymmetrical Parkinson's disease (PD). The feasibility of bilateral FUS-STN is as yet unexplored. A study was done to assess the safety and effectiveness of staged bilateral FUS-STN to treat Parkinson's disease.

This prospective, open-label, case series study was conducted between June 18, 2019, and November 7, 2023, at HM-CINAC, Puerta del Sur University Hospital, Madrid, Spain, and included 6 patients with Parkinson's disease who had been treated with unilateral FUS-STN contralateral to their most affected body side and whose parkinsonism on the untreated side had progressed and was not optimally controlled with medication.

Primary Outcomes

Primary outcomes were assessed 6 months after the second treatment and included:

• Safety (incidence and severity of adverse events after the second treatment)
• Effectiveness in terms of motor change (measured with the Movement Disorders Society Unified Parkinson’s Disease Rating Scale part III [MDS-UPDRS III]) in the off-medication state (ie, after at least 12 hours of antiparkinsonian drug withdrawal) compared with baseline (ie, prior to the first side ablation)

Secondary Outcomes

Secondary outcomes included:

• Motor change in patients in the on-medication state (ie, after usual antiparkinsonian medication intake)
• Motor complications (measured with the MDS-UPDRS IV)
• Daily living activities (measured with the MDS-UPDRS I-II)
• Quality of life (measured with the 39-item Parkinson’s Disease Questionnaire)
• Change in dopaminergic treatment
• Patient’s global impression of change (measured with the Global Impression of Change [PGI-C] scale)
• Long-term (24-month) follow-up

Results

Of 45 patients previously treated with unilateral FUS-STN, 7 were lost to follow-up, and 4 were excluded due to adverse events. Of the remaining 34 patients, 6 (median age at first FUS-STN, 52.6 years [IQR, 49.0-57.3 years]; 3 women [50%]) experienced progression of parkinsonism on the untreated body side and were included. At the time of the first FUS-STN, patients’ median duration of disease was 5.7 years (IQR, 4.7-7.3 years).

The median time between procedures was 3.2 years (IQR, 1.9-3.5 years). After the second FUS-STN, 4 patients presented with contralateral choreic dyskinesia, which resolved by 3 months. Four patients developed speech disturbances, which gradually improved but remained in a mild form for 2 patients at 6 months; 1 patient experienced mild imbalance and dysphagia during the first week after treatment, which subsided by 3 months. No behavioural or cognitive disturbances were found on neuropsychological testing.

For patients in the off-medication state, MDS-UPDRS III scores improved by 52.6% between baseline and 6 months after the second FUS-STN (from 37.5 [IQR, 34.2-40.0] to 20.5 [IQR, 8.7-24.0]; median difference, 23.0 [95% CI, 7.0-33.7]; P = .03). The second treated side improved by 64.3% (MDS-UPDRS III score, 17.0 [IQR, 16.0-19.5] prior to the second treatment vs 5.5 [IQR, 3.0-10.2]; median difference, 9.5 [95% CI, 3.2-17.7]; P = .02). After the second procedure, all self-reported PGI-C scores were positive.

Findings of this pilot study suggest that staged bilateral FUS-STN was safe and effective for the treatment of PD, although mild but persistent speech-related adverse events were observed among a small number of patients.

Reference

Martínez-Fernández R, Natera-Villalba E, Rodríguez-Rojas R, et al. Staged Bilateral MRI-Guided Focused Ultrasound Subthalamotomy for Parkinson Disease. JAMA Neurol. Published online May 13, 2024. doi:10.1001/jamaneurol.2024.1220