Motor response in monogenic LRRK2 parkinson's disease after deep brain stimulation: A systematic review and metaanalysis

Introduction: Genetic factors are increasingly recognized as crucial contributors to both familial and sporadic forms of Parkinson's disease (PD), including mutations in LRRK2 (Leucine-rich Repeat Kinase 2). Previous studies have indicated that the G2019S variant results in more favorable motor outcomes post-deep brain stimulation (DBS) compared to the R1441G variant. This study was aimed at investigating whether different LRRK2 variants in Parkinson's disease patients with LRRK2 mutations (LRRK2 PD) produce distinct motor responses following DBS. Materials and Methods: A literature search was conducted across three databases using keywords related to Parkinson�s disease, deep brain stimulation, and LRRK2. The inclusion criteria involved studies focusing on LRRK2 PD with DBS intervention, specifically comparing LRRK2 variants, and measuring motor responses pre-and postDBS using the UPDRS III. A meta-analysis was performed to compare motor responses using a random effects model. Results: Out of 325 search results, eleven articles were included in the review. Three LRRK2 PD variants G2019S, R1441G, and G2385R were associated with DBS intervention. The overall effect of DBS in LRRK2 PD compared to idiopathic PD was not statistically significant, with a mean difference (MD) of-3.00 (-8.52; 2.52). High overall heterogeneity was observed (I²=63.1; P < 0.05). Subgroup analysis revealed significant differences (P < 0.05), suggesting that different LRRK2 variants may result in varying motor outcomes post-DBS. Conclusion: LRRK2 PD exhibited diverse motor outcomes depending on the specific mutation variant when subjected to DBS. Patients with LRRK2 variants G2019S and G2385R demonstrated clinically significant improvements in motor responses, while those with the R1441G variant showed inadequate motor response. © 2025, Malaysian Medical Association. All rights reserved.