Subthalamic and Nigral Stimulation for Freezing of Gait in Parkinson disease: randomized pilot trial

Background: Freezing of gait (FoG) is a debilitating symptom of Parkinson’s disease (PD) with limited response to dopa- minergic medication and subthalamic deep brain stimulation (STN-DBS). Substantia nigra pars reticulata (SNr) stimulation could improve FoG. Objective: To analyze the effect of combined STN-SNr stimulation at different frequencies on FoG. Methods: We performed a double-blind, cross-over, randomized pilot trial involving STN-DBS treated PD patients with FoG. Participants received: high-frequency (HF) STN-DBS (S), combined HF-STN and SNr stimulation (C1), and com- bined HF-STN and low-frequency (LF) SNr stimulation (C2), for one month each. The primary endpoint was the score change in the New-Freezing-of-Gait-Questionnaire (NFOG-Q). Secondary analyses were performed on motor complications, axial symptoms, daily living activities, psychiatric symptoms, sleep, and patient preference. Results: Fifteen patients received at least one combined stimulation. No signi cant difference in NFOG-Q scores was found between S, C1, and C2; one-third of patients showed a clinically signi cant improvement (≥8 points) with combined stimulations. Motor complications improved signi cantly with C1 and C2 (C1-S: 3.6 ± 3.8 vs. 4.9 ± 3.8, p= 0.046; C2-S: 2.7 ± 3.1 vs. 4.9 ± 3.8, p= 0.005). 80% of patients preferred the combined STN-SNr stimulation while blinded. All adverse events were manageable. Conclusions: Our study did not prove a statistically signi cant improvement in NFOG-Q with STN-SNr stimulation; however, one-third of patients experienced a clinically meaningful FoG improvement, and the majority preferred to main- tain STN-SNr stimulation. STN-SNr stimulation was both safe and effective in addressing motor complications and improving sleep quality, highlighting the importance of further exploration into the effects of combined STN-SNr stimulation.