Five-Year Outcomes from Deep Brain Stimulation of the Subthalamic Nucleus for Parkinson Disease

Authors

Philip A. Starr, Department of Neurosurgery, University of California, San Francisco.
Rajat S. Shivacharan, Division of Neuromodulation, Boston Scientific, Valencia, California.
Edward Goldberg, Division of Neuromodulation, Boston Scientific, Valencia, California.
Alexander I. Tröster, Department of Clinical Neuropsychology, Barrow Neurological Institute, Phoenix, Arizona.
Paul A. House, Neurosurgical Associates LLC, Murray, Utah.
Monique L. Giroux, Movement and Neuroperformance Center of Colorado, Englewood.
Adam O. Hebb, Department of Neurological Surgery, Kaiser Permanente, Denver, Colorado.
Donald M. Whiting, Department of Neurosurgery, Allegheny Health Network, Pittsburgh, Pennsylvania.
Timothy A. Leichliter, Department of Neurology, Allegheny Health Network, Pittsburgh, Pennsylvania.
Jill L. Ostrem, Department of Neurology, University of California, San Francisco.
Leo Verhagen Metman, Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois.
Sepehr Sani, Department of Neurological Surgery, Rush University Medical Center, Chicago, Illinois.
Jessica A. Karl, Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois.
Mustafa S. Siddiqui, Department of Neurology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Stephen B. Tatter, Department of Neurosurgery, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Ihtsham Ul Haq, Department of Neurology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Andre G. Machado, Center for Neurological Restoration Cleveland Clinic, Cleveland, Ohio.
Michal Gostkowski, Center for Neurological Restoration Cleveland Clinic, Cleveland, Ohio.
Michele Tagliati, Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California.
Adam N. Mamelak, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California.
Michael S. Okun, Department of Neurology, College of Medicine, University of Florida, Gainesville.
Kelly D. Foote, Department of Neurosurgery, College of Medicine, University of Florida, Gainesville.
Guillermo Moguel-Cobos, Department of Neurology, Barrow Neurological Institute, Phoenix, Arizona.
Francisco A. Ponce, Department of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona.
Rajesh Pahwa, Department of Neurology, University of Kansas Medical Center, Kansas City.
Kelly Lyons, Department of Neurology, University of Kansas Medical Center, Kansas City.
Cathrin M. Buetefisch, Department of Neurology, Emory University School of Medicine, Atlanta, Georgia.
Robert E. Gross, Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia.
Corneliu C. Luca, Department of Neurology, University of Miami School of Medicine, Miami, Florida.
Jonathan R. Jagid, Department of Neurosurgery, University of Miami School of Medicine, Miami, Florida.
Gonzalo J. Revuelta, Department of Neurology, Medical University of South Carolina, Charleston.

Document Type

Article

Abstract

IMPORTANCE: The Implantable Neurostimulator for the Treatment of Parkinson's Disease (INTREPID) trial was a randomized, double-blind, sham-controlled study of subthalamic nucleus (STN) deep brain stimulation (DBS) for the treatment of Parkinson disease (PD). OBJECTIVE: To evaluate the long-term (5-year) outcomes and safety of STN-DBS for PD. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective, randomized (3:1), 12-week double-blind sham-controlled study at 23 movement disorder centers across the US with an open-label 5-year follow-up. Patients were implanted and followed up with the Vercise DBS system from May 2013 to December 2022. Eligibility required diagnosis of bilateral idiopathic PD with more than 5 years of motor symptoms, more than 6 hours per day of poor motor function, modified Hoehn and Yahr Scale scores higher than 2, Unified Parkinson's Disease Rating Scale (UPDRS-III) score of 30 or higher (medication-off state), and 33% or higher improvement in UPDRS-III medication-on score. INTERVENTION: Bilateral STN-DBS for moderate to advanced PD. MAIN OUTCOMES AND MEASURES: Primary outcomes included changes in UPDRS and dyskinesia scores, quality-of-life measures, and safety assessments. Exploratory analyses included medication reduction and DBS association with motor signs. RESULTS: A total of 313 patients were enrolled with 191 receiving the DBS system, and 137 participants (72%) completed the study. The study population had a mean (SD) age of 60 (7.9) years, with 139 (73%) male participants. Motor function without medication as measured by UPDRS-III improved from a mean (SD) of 42.8 (9.4) to 21.1 (10.6) at year 1 (51%; 95% CI, 49%-53%; P < .001) and 27.6 (11.6) at year 5 (36%; 95% CI, 33%-38%; P < .001). Activities of daily living without medication as measured by UPDRS-II improved from a mean (SD) of 20.6 (6.0) to 12.4 (6.1) at year 1 (41%; 95% CI, 38%-42%; P < .001) and 16.4 (6.5) at year 5 (22%; 95% CI, 18%-23%; P < .001). Dyskinesia scores decreased from 4.0 (5.1) to 1.0 (2.1) at year 1 (75%; 95% CI, 73%-75%; P < .001) and to 1.2 (2.1) at year 5 (70%; 95% CI, 63%-75%; P < .001). The levodopa equivalent dose was reduced by 28% at year 1, remaining stable at year 5 (28%; 95% CI, 26%-31%; P < .001). The most common serious adverse event was infection (9 participants). Ten deaths were reported, none related to the study. CONCLUSIONS AND RELEVANCE: Although STN-DBS outcomes declined slightly, possibly due to the progressive nature of the disease, patients with PD sustained significant improvement in motor and activities of daily living scores, along with a stable reduction in anti-parkinsonian medication over the 5-year follow-up period.

Medical Subject Headings

Humans; Parkinson Disease (therapy, physiopathology); Deep Brain Stimulation (methods, trends, adverse effects); Subthalamic Nucleus (physiology); Male; Female; Middle Aged; Double-Blind Method; Aged; Treatment Outcome; Prospective Studies; Follow-Up Studies

Publication Date

11-1-2025

Publication Title

JAMA neurology

E-ISSN

2168-6157

Volume

82

Issue

11

First Page

1181

Last Page

1190

PubMed ID

40952750

Digital Object Identifier (DOI)

10.1001/jamaneurol.2025.3373

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