Differential effects of deep brain stimulation target on motor subtypes in Parkinson's disease

Abstract

Objective: The VA Cooperative Studies Program (CSP) #468, a multicenter study that randomized Parkinson's disease (PD) patients to either subthalamic nucleus (STN) or globus pallidus internus (GPi) deep brain stimulation (DBS), found that stimulation at either target provided similar overall motoric benefits. We conducted an additional analysis of this dataset to evaluate if PD motor subtypes responded differently to the two stimulation targets. Methods: We classified 235 subjects by motor subtype: Tremor Dominant (TD), Intermediate (I), or Postural Instability Gait Difficulty (PIGD), based on pre‐DBS baseline Unified Parkinson's Disease Rating Scale (UPDRS) scores, off‐medication. The primary outcome was change in UPDRS part III (UPDRS‐III) off‐medication scores from baseline to 24 months post‐DBS, compared among subjects with particular PD motor subtypes and by DBS target (STN vs. GPi). Changes in tremor, rigidity, akinesia, and gait scores were also assessed using the UPDRS. Results: TD patients had greater mean overall motor improvement, measured by UPDRS‐III, after GPi DBS, compared to STN DBS (17.5 ± 13.0 vs. 14.6 ± 14.9, p = 0.02), with improvement in gait accounting for this difference. Regardless of stimulation target, PIGD subjects had lower mean overall improvement in UPDRS‐III scores compared with I or TD subjects (8.7 ± 12.2 vs. 21.7 ± 11.2 vs. 16.3 ± 13.8, p=<0.001) Interpretation: Our results suggest that responsiveness to both GPi and STN DBS is similar among different PD motor subtypes, although the TD motor subtype may have a greater response to GPi DBS with respect to gait. PIGD patients obtained less overall benefit from stimulation.