Large retrospective cohort (n=405) of young-onset Parkinson disease patients shows both GPi and STN deep brain stimulation improve motor symptoms at 1 and 5 years; STN produced greater medication reduction and modest motor benefit while GPi better reduced dyskinesia and motor fluctuations.

This study informs clinical decision-making about DBS target selection in young-onset PD with actionable, long-term outcome data, but it offers limited mechanistic or drug-discovery insights relevant to molecular therapeutic development.

BACKGROUND AND OBJECTIVES: Patients with young-onset Parkinson disease (YOPD) commonly experience early motor complications necessitating deep brain stimulation (DBS), and the subthalamic nucleus (STN) and globus pallidus interna (GPi) are the primary DBS targets used for reducing medication use and addressing dyskinesias. This study leveraged both the University of Florida Fixel Institute high volume of DBS operations and the INFORM database to evaluate motor outcomes in a large cohort of patients with YOPD treated with STN or GPi DBS, and addressed the limited available evidence and paucity of data on the long-term effects of these targets applied to YOPD. METHODS: A single-center retrospective chart review was conducted on a nonrandomized cohort of adult patients with a diagnosis of YOPD treated with STN or GPi DBS between January 1999 and October 2023. Multidisciplinary evaluation was used to choose the anatomical target for each patient. Disease onset, lead location, medications, and mortality were collected and compared between cohorts. Preoperative, 6-month, and 1-, 3-, and 5-year Unified Parkinson's Disease Rating Scale (UPDRS) scores were used to compare motor outcomes. RESULTS: There were 405 patients, and 61.3% received GPi DBS and 37.7% STN DBS. Mean disease duration at surgery was 12.3 (4.2) years for GPi and 11.5 (6.3) years for STN. GPi DBS improved ON UPDRS part 3 scores at 1 year (26.5 [11.84] vs 20.94 [9.09], p = 0.0024), and these scores worsened slightly by 5-year follow-up (20.94 [9.09] vs 24.72 [10.28], p = 0.0491). Unilateral STN DBS showed greater 6-month motor improvement vs unilateral GPi (p < 0.001) and remained stable from 6 months to 3 years (p = 0.3). GPi DBS improved ON UPDRS part 4 scores from baseline to 5 years (8.34 [3.15] vs 4.21 [2.25], p < 0.0001), whereas STN DBS showed no significant change (6.16 [4.21] vs 5.0 [2.98], p = 0.328). Although statistically significant, the changes did not meet the threshold for clinical relevance. DISCUSSION: This large cohort study assessed long-term outcomes of STN vs GPi DBS when used in the setting of YOPD. Both targets improved motor symptoms at 1 and 5 years. STN offered modest motor benefits and greater medication reduction, while GPi DBS better addressed dyskinesia and motor fluctuations. These findings inform preoperative decision-making, although selection bias based on baseline symptoms remains a limitation of the data set.