Deep Brain Stimulation of the Posterior Subthalamic Area and the Subthalamic Nucleus in Tremor‐Dominant Parkinson's Disease: A Randomized, Crossover Trial

Abstract

Abstract

BACKGROUND: The posterior subthalamic area (PSA) is a familiarized target for Parkinson's disease (PD) in the lesioning era and has recently been reconsidered for deep brain stimulation (DBS). OBJECTIVE: The aim of this study was to compare the therapeutic efficacy of PSA versus subthalamic nucleus (STN) DBS in tremor-dominant Parkinson's disease (TD-PD). METHODS: This single-center, randomized, crossover trial was conducted at Ruijin Hospital, Shanghai, China, from June 2022 to August 2025. Patients with TD-PD received bilateral DBS implants via a single trajectory targeting both PSA and STN. Participants received 2 months of PSA stimulation followed by 2 months of STN stimulation or vice versa, with blinded programming and evaluation. The primary outcome was the difference in off medication improvement from baseline to the end of each stimulation period in the tremor subscore of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Part III (MDS UPDRS-III; ClinicalTrials.gov, NCT05382858). RESULTS: Of the 40 patients assessed for eligibility, 27 were randomly assigned and 19 completed the randomized crossover phase. Both PSA-DBS and STN-DBS significantly reduced the MDS UPDRS-III tremor subscore (baseline, 17.5 [3.3]; PSA, 4.5 [2.8]; STN, 8.0 [5.3]; P < 0.001 for both). PSA-DBS achieved greater tremor suppression than STN-DBS (adjusted mean difference -3.3; 95% confidence interval [CI]: -5.4 to -1.3; P = 0.004). STN-DBS led to greater balance improvement (adjusted mean difference -1.7; 95% CI: -2.6 to -0.7; P = 0.002). Three cases of abnormal impedance occurred. Other adverse effects were mostly stimulation related and could be resolved with reprogramming. CONCLUSIONS: Given the limited sample size and study attrition, these findings should be considered hypothesis generating. Nonetheless, PSA-DBS appears to be a safe and effective alternative or complementary target to STN in treating TD-PD and warrants further investigation in larger, definitive trials. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.