Laterality and frequency settings of subthalamic nucleus DBS for Parkinson's disease: A systematic review and network meta-analysis

Introduction: Deep Brain Stimulation (DBS) is an effective treatment for the motor symptoms of Parkinson's Disease. The targeted physiological structure for lead location is commonly the subthalamic nucleus (STN). The efficacy of DBS for improving motor symptoms is assessed via the Unified Parkinson's Disease Rating III Scale (UPDRS-III). In this study, we sought to compare the efficacy of different parameters utilized for STN-DBS. Methods: Following PRISMA Guidelines, a search on PUBMED and MEDLINE was performed to include full-length randomized controlled trials evaluating STN-DBS. Laterality and frequency stimulation parameters were extracted in the search. High frequency stimulation (HFS) was defined as ≥130 Hz and low-frequency stimulation (LFS) was defined as <130 Hz. A frequentist network meta-analysis was performed with odds ratios (OR) and pooling performed using the Mantel-Haenszel method. Statistics are presented as OR [95% CI]. Results: 16 studies consisting of 318 patients were included for analysis. Bilateral HFS (−0.31 [-1.34; 0.72]) was associated with better UPDRS-III scores compared to bilateral LFS. Unilateral HFS (0.19 [-0.06; 0.45]) had better UPDRS-III outcomes compared to unilateral LFS. On the other hand, bilateral LFS with meds was significantly favored over bilateral HFS with meds (−0.55 [-0.98; −0.12]). Discussion: STN is a common target for DBS, and the laterality and parameters of the stimulation need to be investigated. The outcomes suggest that unilateral or bilateral HFS has better utility for those with no response to medication, while LFS has additive benefits to medication by improving unique symptoms via different neurophysiological mechanisms.