Effect of deep brain stimulation on early-onset Parkinson’s disease with mutations in a Han Chinese Mainland population

BACKGROUND: The influence of genetic factors on the efficacy of deep brain stimulation (DBS) remains unclear. This study aimed to analyze the effects of DBS in Han Chinese patients with early-onset Parkinson’s disease (EOPD) across various genetic backgrounds and to explore the differences in DBS responsiveness among patients EOPD with and distinct genetic profiles. METHODS: This retrospective study examined 48 patients with EOPD who underwent DBS. Patients were divided into mutation-positive (Mut+) and mutation-negative (Mut-) groups. Clinical evaluations were performed before and 24 months after DBS using the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale, Non-Motor Symptoms Scale for Parkinson’s Disease, and levodopa-equivalent daily dose (LEDD). RESULTS: In the Mut + group, 16 patients with EOPD carried gene mutations: seven in PRKN, four in GBA, three in PLA2G6, one in LRRK2, and one in PINK1. Fifteen patients had no detectable pathogenic mutations (Mut- group). The two groups had similar baseline demographic characteristics and preoperative clinical features, except for a younger age at onset in the Mut + group. Both the groups derived benefits from DBS surgery, with no statistically significant differences observed between them in terms of motor symptoms improvement and LEDD reduction at 24 months post-DBS. Furthermore, DBS responses varied according to genetic subtype, with the PLA2G6 subgroup demonstrating relatively poor outcomes, especially in terms of non-motor symptoms and axial symptoms. Regarding non-motor symptoms, DBS showed no significant differences in non-motor symptom improvement between the two groups or among the various genetic subgroups. CONCLUSIONS: DBS is effective in improving motor symptoms and reducing the LEDD in patients with EOPD, regardless of their genetic background. However, patients with genetic mutations, especially in PLA2G6, may show a weaker response to DBS, highlighting the need for personalized approaches in DBS therapy for EOPD.