Effects of globus pallidus internus deep brain stimulation on freezing of gait in Parkinson's disease: a prospective short-term single-arm study

BACKGROUND: Freezing of gait (FoG) is a debilitating symptom in Parkinson's disease (PD), often resistant to medication. Deep brain stimulation (DBS) has emerged as an effective treatment for advanced PD, while its effect on FoG remains inconsistent. Specifically, the effect of globus pallidus internus deep brain stimulation (GPi-DBS) against FoG is inconclusive, and relevant studies are scarce. OBJECTIVE: To describe the post-operative effect of GPi-DBS on FoG and identify pre-operative predictors of improvement. METHODS: Forty-six PD patients undergoing GPi-DBS were assessed pre-operatively and at short-term follow-up (a median of 11 months) using the Gait and Falls Questionnaire (GFQ) and a comprehensive Timed Up and Go (TUG) test that quantified five FoG-related TUG indices. The primary outcome was the within-individual change in TUG total time, computed as the pre-operative med-off value minus the DBS-on med-off value. The secondary outcomes were changes of pre-operative med-off vs. med-on (the acute levodopa response) and pre-operative med-off vs. DBS-off med-off (a within-subject negative control for disease progression). Pre-operative predictors of FoG were assessed to predict the within-individual change in the TUG indices by performing forward stepwise Akaike Information Criterion (AIC) regression analysis. RESULTS: At short-term follow-up, FoG measures (the TUG-derived indices and the self-reported GFQ) improved after GPi-DBS. TUG total time decreased by a median of 5.0 s (95% CI 1.5-14.5; FDR = 0.003), and the longest FoG duration by 1.0 s (95% CI 0-3.5; FDR = 0.030); the other three TUG indices improved in the same direction but did not survive correction (FDR 0.064-0.080). Additionally, GFQ total score decreased from a baseline median of 24 to 17 (Hodges-Lehmann median difference 4.0 points; 95% CI 0-8; n = 46; p = 0.036). In the forward-stepwise AIC regression (n = 40), the pre-operative axial levodopa response was the only pre-operative variable retained for the TUG changes; among the four motor components, only the DBS- related change in the axial subscore was significantly correlated with TUG improvement (Spearman ρ = 0.431, 95% CI 0.138-0.654, p = 0.006). CONCLUSIONS: Within this single-arm cohort, FoG measures improved over short-term follow-up after GPi-DBS, and greater pre-operative axial levodopa-responsiveness was associated with greater TUG improvement.