Safety and efficacy of staged, bilateral magnetic resonance-guided focused ultrasound pallidothalamic tractotomy for motor complications of Parkinson's disease: a prospective, multicentre, single-arm trial.
Safety and efficacy of staged, bilateral magnetic resonance-guided focused ultrasound pallidothalamic tractotomy for motor complications of Parkinson's disease: a prospective, multicentre, single-arm trial.
Where did the research take place?
Possible study sites were matched from the text; these need review.
ES · Possible study site · country only
4 score ≥2) were enrolled at nine investigational centres (six in the USA, two in Spain, and one in Taiwan).Location evidence
TW · Possible study site · country only
4 score ≥2) were enrolled at nine investigational centres (six in the USA, two in Spain, and one in Taiwan).Location evidence
US · Possible study site · country only
4 score ≥2) were enrolled at nine investigational centres (six in the USA, two in Spain, and one in Taiwan).Location evidence
Boynton Beach, US · Author affiliation
Comprehensive Movement Disorders Center, Palm Beach Neuroscience Institute, Boynton Beach, FL, USA.Location evidence
Baltimore, US · Author affiliation
Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: heisenberg@som.umaryland.edu.Location evidence
TW · Author affiliation · country only
Department of Neurology, Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan.Location evidence
Delray Beach, US · Author affiliation
Brain and Spine Center South Florida, Delray Beach, FL, USA.Location evidence
New York City, US · Author affiliation
Department of Neurology, Parkinson's Disease and Movement Disorders Institute, Weill Cornell Medicine, New York, NY, USA.Location evidence
Palo Alto, US · Author affiliation
Department of Neurosurgery, Stanford School of Medicine, Palo Alto, CA, USA.Location evidence
Centro, ES · Author affiliation
HM CINAC (Centro Integral de NeurocienciasAbarca Campal), Instituto de Investigación Sanitaria HM Hospitales, CIBERNED, Instituto Carlos III, Madrid, Spain.Location evidence
Madrid, ES · Author affiliation
HM CINAC (Centro Integral de NeurocienciasAbarca Campal), Instituto de Investigación Sanitaria HM Hospitales, CIBERNED, Instituto Carlos III, Madrid, Spain.Location evidence
Universidad, ES · Author affiliation
Neurology Department, Clínica Universidad de Navarra, Navarra Institute for Health Research (IdiSNA), Pamplona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.Location evidence
Pamplona, ES · Author affiliation
Neurology Department, Clínica Universidad de Navarra, Navarra Institute for Health Research (IdiSNA), Pamplona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.Location evidence
Chicago, US · Author affiliation
Department of Neurosurgery, Rush University Medical Center, Chicago, IL, USA.Location evidence
Follow the study behind this paper
Evaluation of the Safety and Effectiveness of Bilateral Exablate Ablation of the Pallidothalamic Tract (PTT) for the Treatment of the Motor Complications of Parkinson's Disease (PD)
The registry links this paper to the study.
A plain-language reading has not been prepared for this paper yet.
Original abstract
BACKGROUND: Parkinson's disease management is often complicated by motor fluctuations and dyskinesia. Although deep brain stimulation addresses these symptoms, its use is limited by invasiveness, potential device failure, and the need for ongoing maintenance. Magnetic resonance-guided focused ultrasound (MRgFUS) provides incisionless, image-guided ablation as an alternative. However, the benefits and harms of staged, bilateral MRgFUS pallidothalamic tractotomy have not been evaluated systematically in prospective multicentre studies. METHODS: In this prospective, multicentre, single-arm study, adults with idiopathic, levodopa-responsive Parkinson's disease and motor complications (Movement Disorders Society Unified Parkinson's Disease Rating Scale [MDS-UPDRS] part IV item 4.2 or 4.4 score ≥2) were enrolled at nine investigational centres (six in the USA, two in Spain, and one in Taiwan). Participants underwent unilateral MRgFUS pallidothalamic tractotomy to the symptom-dominant side. Contralateral pallidothalamic tractotomy followed a minimum of 6 months later for participants meeting prespecified criteria. The primary efficacy endpoint was percent change from baseline to 3 months after the second procedure in the summed MDS-UPDRS part III off-medication upper and lower extremity (ULE) motor scores. Safety outcomes were incidence, severity, and persistence of treatment-related adverse events in the 12 months after each procedure. Safety and efficacy of unilateral treatment were evaluated in the unilateral intention-to-treat (ITT) and safety populations, defined as all patients receiving one or more sonications during the first procedure. The primary outcome and safety of bilateral treatment were evaluated in the bilateral modified ITT (mITT) and safety populations, which required one or more sonications during the second procedure, a baseline motor assessment, and at least one post-bilateral motor assessment. This trial is registered at ClinicalTrials.gov, NCT04728295 and is active, not recruiting. FINDINGS: Between July 12, 2021, and Nov 1, 2023, 54 patients received unilateral treatment and 40 proceeded to bilateral treatment (63 [67%] were male and 31 [33%] were female) and were included in the primary analysis; 36 completed 12-month follow-up after the second procedure. Median bilateral ULE motor scores decreased from 33·0 points (IQR 28·0-40·5) at baseline to 21·0 points (15·0-25·5) at month 3 post-bilateral treatment, a median within-patient change of 10·5 points (5·7-20·0), representing a 32% (18-52) improvement (p<0·0001). Benefits became apparent within 1 month of the first procedure and lasted through to 12 months after the second procedure. Treatment-related adverse events occurred in 21 (39%) of 54 patients after unilateral treatment; one (2%) had a persistent moderate adverse event at 6 months. After bilateral treatment, 22 (55%) of 40 patients had treatment-related adverse events; ten (25%) had persistent moderate or severe adverse events at 12 months, mainly affecting speech, gait, and balance. One (3%) patient developed severe persistent anarthria. INTERPRETATION: Unilateral MRgFUS pallidothalamic tractotomy demonstrated safety and efficacy for Parkinson's disease motor complications; however, bilateral treatment offered small motor gains while increasing persistent moderate or severe adverse events. Post-bilateral treatment complications in speech, gait, and balance are consistent with historical data for bilateral ablative procedures for movement disorders. Although unilateral MRgFUS pallidothalamic tractotomy was beneficial in our study, bilateral procedures demand rigorous patient selection and counselling regarding cumulative risks. FUNDING: Insightec.