The impact of deep brain stimulation of the subthalamic nucleus (STN-DBS) on patients with Parkinson disease (PD) with different genetic risk factors/causes remains uncertain. This study aimed to compare the clinical efficacy of STN-DBS in these patients.

This study compared STN-DBS outcomes in 18 PD patients with mutations in glucosylceramidase beta (GBA) (n = 3), leucine-rich repeat kinase 2 (LRRK2) (n = 9), or Parkin RBR E3 ubiquitin ligase/PTEN-induced kinase 1/DJ1 (n = 6). Clinical measures—levodopa equivalent daily dose, Movement Disorder Society Unified-Parkinson Disease Rating Scale Part III, Parkinson's Disease Questionnaire-39 (PDQ-39), and total electrical energy delivered—were assessed at baseline, programming initiation, 6 months, 1 year, and 2 years postsurgery. Linear mixed models analyzed longitudinal and intergroup differences.

All groups showed significant time-dependent improvements. Levodopa equivalent daily dose dropped sharply post-DBS (maximal reduction at 1 year: β = −577.33, P < 0.001). Movement Disorder Society Unified-Parkinson Disease Rating Scale Part III scores improved by programming initiation (β = −35.00, P < 0.001) and remained stable for 2 years. PDQ-39 scores improved from 6 months onward (β = −27.67, P < 0.001). Total electrical energy delivered increased gradually, with LRRK2 carriers requiring higher stimulation by 2 years (time × gene interaction: β = 94.21, P = 0.043). Main effects revealed GBA carriers had smaller motor improvements (vs. LRRK2: β = −24.94, P = 0.001; vs. Parkin RBR E3 ubiquitin ligase/PTEN-induced kinase 1/DJ1: β = −23.61, P = 0.008) and lesser PDQ-39 gains (β = −22.67, P = 0.018).

STN-DBS demonstrated benefits for patients with PD across all genetic backgrounds, but LRRK2 carriers may require increasing stimulation over time, while GBA carriers show reduced motor and quality-of-life improvements.

Deep brain stimulation

DJ-1 gene

Early-onset Parkinson disease

GBA

Gene mutation

LRRK2

Parkinson disease

Glucosylceramidase beta

Levodopa equivalent daily dose

Leucine-rich repeat kinase 2

Movement Disorder Society Unified-Parkinson Disease Rating Scale Part III

Parkinson's disease Questionnaire-39

PTEN-induced kinase 1

Parkin RBR E3 ubiquitin ligase

Second Affiliated Hospital of Zhejiang University

Deep brain stimulation of the subthalamic nucleus

Total electrical energy delivered

© 2025 The Author(s). Published by Elsevier Inc.