10-year clinical outcomes of subthalamic nucleus versus pallidal deep brain stimulation for Parkinson’s disease: VA/NINDS CSP #468F

Objective: This study aimed to examine the very long-term effects of globus pallidus interna (GPi) or subthalamic nucleus (STN) deep brain stimulation (DBS) on Parkinson’s disease (PD) in a subset of patients enrolled in the CSP468 VA/NINDS prospective randomized trial. Methods: The primary outcome was the change in off-medication/on-stimulation Unified Parkinson’s Disease Rating Scale III score (UPDRS III) from baseline over time between the two targets at 2, 7, and 10 years. Many secondary outcomes were also explored. Results: A total of 156 patients were enrolled in this substudy, and data were available for 68 GPi/49 STN participants at 7 years and 49 GPi/28 STN participants at 10 years. There was no overall difference in the time trend between the two targets (p < 0.09). UPDRS III improvements from baseline in the GPi cohort at 2, 7, and 10 years were 39.9% (p < 0.001), 16.4%, (p < 0.001), and 22.3%, (p = 0.10), respectively, and in the STN cohort at 2, 7, and 10 years it was 34.9% (p < 0.001), 16.9%, (p < 0.001), and 32.8%, (p < 0.001), respectively. Tremor subscores showed the greatest reduction, followed by rigidity subscores. Initial improvements in bradykinesia and axial subscores were attenuated, and UPDRS I, II, and III on-medication/on-stimulation scores significantly declined. UPDRS IV scores and motor diaries showed significant long-term improvement, and medication reductions were seen regardless of the target. At 7 and 10 years, the PDQ-39 total score no longer showed improvement, and more severe cognitive impairment was seen in both targets. Conclusion: DBS therapy has a significant beneficial effect on overall motor function, dyskinesia, and motor fluctuations over 10 years (regardless of target), though non-motor symptoms progressed. Bradykinesia, axial, and quality-of-life improvement were maintained at 2 years and then declined over time. Clinical trial registration: ClinicalTrials.gov, identifier NCT01022073, NCT00056563, NCT01076452.