Staged Bilateral MRI-Guided Focused Ultrasound Subthalamotomy for Parkinson Disease

Neurology Biophysics Medical Imaging Life Sciences Neurosurgery Medicine
Parkinson's disease Focused ultrasound Subthalamic nucleus Motor function Safety Effectiveness

MRI-Guided Staged Bilateral Focused Ultrasound Subthalamotomy for Parkinson’s Disease

Background

Parkinson’s Disease (PD) is a common neurodegenerative disorder, characterized mainly by motor symptoms such as tremor, rigidity, and bradykinesia. Traditionally, treatments for PD include medication and surgical interventions such as Deep Brain Stimulation (DBS) and radiofrequency procedures. However, unilateral MRI-guided focused ultrasound subthalamotomy (FUS-STN) has been shown to improve contralateral motor symptoms in patients with asymmetric PD. The feasibility of bilateral FUS-STN has not yet been explored. Unilateral treatment may not provide overall symptom control, especially as untreated body sides can experience motor deterioration and axial symptoms such as gait disturbances. Therefore, this study aims to assess the safety and efficacy of staged bilateral FUS-STN in treating Parkinson’s disease.

Source Introduction

The authors of this study include Raúl Martínez-Fernández and others. The research was conducted by HM-CINAC, Puerta del Sur University Hospital, and several Spanish research institutions. The paper was published in JAMA Neurology on May 13, 2024.

Study Design and Methods

This prospective, open-label case series study included 6 PD patients who had undergone prior unilateral FUS-STN and experienced aggravated symptoms on the untreated body side, which could not be optimally controlled with medication. The study was conducted from June 18, 2019, to November 7, 2023, at HM-CINAC and Puerta del Sur University Hospital in Madrid, Spain.

Study Procedures

  1. Patient Screening: From 45 patients who had previously undergone unilateral FUS-STN, 6 eligible patients were selected. Inclusion criteria included worsening symptoms on the untreated body side that could not be controlled by medication.

  2. Treatment Process: Each patient underwent two FUS-STN treatments, with an interval of 3.2 years (IQR, 1.9-3.5 years). Patients received the second treatment no less than six months after the first one.

  3. Assessment Methods: Follow-ups were conducted at 1, 3, 6, 12, and 24 months after the second treatment. Primary outcomes included safety (adverse events following the second treatment) and motor changes in the off-medication state (MDS-UPDRS III score). Secondary outcomes included motor changes in the on-medication state, motor complications (MDS-UPDRS IV), activities of daily living (MDS-UPDRS I-II), quality of life (PDQ-39), etc.

Data Analysis

Data analysis was conducted using JASP version 0.16.4.0 software. Clinical outcomes for continuous variables were expressed as medians and interquartile ranges, and stepwise comparisons were conducted using Friedman and Conover tests with a significance level set at p<0.05.

Results

Safety Evaluation

Following the second FUS-STN treatment, 4 patients experienced contralateral choreiform involuntary movements which resolved within 3 months. 4 patients had speech impairments, with symptoms persisting in 2 patients at 6 months. One patient experienced mild imbalance and swallowing difficulties within a week after treatment, which resolved within 3 months. No patient showed behavioral or cognitive impairment in neuropsychological tests.

Efficacy Evaluation

In the off-medication state, the MDS-UPDRS III score improved by 52.6% at 6 months post second FUS-STN treatment (from 37.5 to 20.5, p=0.03), and improvement was 64.3% in the contralateral treated side (from 17.0 to 5.5, p=0.02). Patients’ self-assessed global impression scores were all positive.

Secondary outcomes showed significant improvements in motor scores in the on-medication state, quality of life scores, and daily living activities, though these were not statistically significant. The daily levodopa equivalent dose decreased after 6 months, but not significantly.

Discussion and Conclusion

This study preliminarily demonstrates the safety and efficacy of staged bilateral FUS-STN in treating PD. Despite mild but persistent speech-related adverse events, overall motor improvement was significant, and all patients reported notable global improvement. This suggests that bilateral FUS-STN may be a viable and safe option for improving PD motor features.

Further technical refinements, experience accumulation, and comparisons with other treatments like DBS are needed to better define the role of bilateral FUS-STN in PD treatment and identify the most suitable patient populations.

Study Significance

This study provides first-line evidence for bilateral FUS-STN treatment for PD, laying a foundation for future large-scale clinical trials and treatment guidelines, and holds significant scientific and clinical application value.