10 Year Clinical Outcomes of Subthalamic Nucleus versus Pallidal Deep Brain Stimulationfor Parkinson’s Disease: VA/NINDS CSP #468F

Jill Louise Ostrem^1*Ping Luo²Frances Weaver²Kenneth Follett³Johannes Rothlind⁴Nicholas B. Galifianakis⁴Eugene Lai⁵Jeff Bronstein⁶John Duda⁷Kathryn Holloway⁸Aliya Sarwar⁹Matt Brodsky¹⁰Meredith Spindler¹¹Kathryn Chung¹²Domenic Reda²Amanda Snodgrass¹³Claudia Moy¹⁴Grant Huang¹⁵Yongliang Wei²William J. Marks¹⁶

• ¹University of California, San Francisco, San Francisco, United States
• ²Edward Hines Junior VA Hospital Cooperative Studies Program, Hines, United States
• ³University of Nebraska Medical Center, Omaha, United States
• ⁴San Francisco VA Health Care System, San Francisco, United States
• ⁵Houston Methodist Neurological Institute, Houston, United States
• ⁶VA Greater Los Angeles Healthcare System, Los Angeles, United States
• ⁷Philadelphia VA Medical center, Philadelphia, United States
• ⁸Virginia Commonwealth University, Richmond, United States
• ⁹Michael E DeBakey VA Medical Center, Houston, United States
• ¹⁰Oregon Health & Science University, Portland, United States
• ¹¹University of Pennsylvania, Philadelphia, United States
• ¹²VA Portland Health Care System, Portland, United States
• ¹³Va cooperative studies program Clinical Research Pharmacy Coordinating Center, Albuquerque, New Mexico, United States
• ¹⁴National Institute of Neurological Disorders and Stroke, Bethesda, United States
• ¹⁵Department of veterans affairs cooperative studies program central office, Washington DC, United States
• ¹⁶Stanford University School of Medicine, Stanford, United States

ABSTRACT Objective: To examine the very long-term effects of globus pallidus interna (GPi) or subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson’s disease (PD) in a subset of patients enrolled in the CSP468 VA/NINDS prospective randomized trial. Methods: The primary outcome was change in off medication/on stimulation Unified Parkinson’s Disease Rating Scale III score (UPDRSIII) from baseline over time between the two targets at 2, 7, and 10 years. Many secondary outcomes were also explored. Results: 156 patients enrolled in this substudy and data was 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 time trend between the two targets (p<0.09). UPDRS III improvement 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) and in the STN cohort at 2, 7, and 10 years were (34.9%, p< 0.001; 16.9%, p<0.001, and 32.8%, p<0.001). Tremor subscores showed the greatest reduction, followed by rigidity subscores. Initial improvements in bradykinesia and axial subscores attenuated and UPDRS I, II, 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 target. At 7 and 10 years, PDQ-39 total score no longer showed improvement, and more severe cognitive impairment was seen in both targets. Conclusion: DBS therapy has a significant 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 two-years and then declined over time.