The efficacy and limits of magnetic resonance-guided focused ultrasound pallidotomy for Parkinson's disease: a Phase I clinical trial

OBJECTIVE Recently, MR-guided focused ultrasound (MRgFUS) has emerged as an innovative treatment for numerous neurological disorders, including essential tremor, Parkinson's disease (PD), and some psychiatric disorders. Thus, clinical applications with this modality have been tried using various targets. The purpose of this study was to determine the feasibility, initial effectiveness, and potential side effects of unilateral MRgFUS pallidotomy for the treatment of parkinsonian dyskinesia. METHODS A prospective, nonrandomized, single-arm clinical trial was conducted between December 2013 and May 2016 at a single tertiary medical center. Ten patients with medication-refractory, dyskinesia-dominant PD were enrolled. Participants underwent unilateral MRgFUS pallidotomy using the Exablate 4000 device (InSightec) after providing written informed consent. Patients were serially evaluated for motor improvement, neuropsychological effects, and adverse events according to the 1-year follow-up protocol. Primary measures included the changes in the Unified Parkinson's Disease Rating Scale (UPDRS) and Unified Dyskinesia Rating Scale (UDysRS) scores from baseline to 1 week, 1 month, 3 months, 6 months, and 1 year. Secondary measures consisted of neuropsychological batteries and quality of life questionnaire (SF-36). Technical failure and safety issues were also carefully assessed by monitoring all events during the study period. RESULTS Unilateral MRgFUS pallidotomy was successfully performed in 8 of 10 patients (80%), and patients were followed up for more than 6 months. Clinical outcomes showed significant improvements of 32.2% in the "medication-off" UPDRS part III score (p = 0.018) and 52.7% in UDysRS (p = 0.017) at the 6-month follow-up, as well as 39.1% (p = 0.046) and 42.7% (p = 0.046) at the 1-year follow-up, respectively. These results were accompanied by improvement in quality of life. Among 8 cases, 1 patient suffered an unusual side effect of sonication; however, no patient experienced persistent aftereffects. CONCLUSIONS In the present study, which marks the first Phase I pilot study of unilateral MRgFUS pallidotomy for parkinsonian dyskinesia, the authors demonstrated the efficacy of pallidal lesioning using MRgFUS and certain limitations that are unavoidably associated with incomplete thermal lesioning due to technical issues. Further investigation and long-term follow-up are necessary to validate the use of MRgFUS in clinical practice.