Artusi, Carlo Alberto (CA);Ledda, Claudia (C);Gallo, Silvia (S);Rinaldi, Domiziana (D);Campisi, Corrado (C);Rousseau, Vanessa (V);Thalamas, Claire (C);Barbosa, Raquel (R);Ory-Magne, Fabienne (F);Brefel-Courbon, Christine (C);Rascol, Olivier (O);de Barros, Amaury (A);Harroch, Estelle (E);Zibetti, Maurizio (M);Rizzone, Mario Giorgio (MG);Romagnolo, Alberto (A);Imbalzano, Gabriele (G);Lopiano, Leonardo (L);Houeto, Jean Luc (JL);Fabbri, Margherita (M);

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J Parkinsons Dis.2025 Jan 17;14(8):1602-1613.doi:10.1177/1877718X241292315

Abstract

BACKGROUND: Freezing of gait (FoG) is a debilitating symptom of Parkinson's disease (PD) with limited response to dopaminergic 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 combined 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 significant difference in NFOG-Q scores was found between S, C1, and C2; one-third of patients showed a clinically significant improvement (≥8 points) with combined stimulations. Motor complications improved significantly 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 significant improvement in NFOG-Q with STN-SNr stimulation; however, one-third of patients experienced a clinically meaningful FoG improvement, and the majority preferred to maintain 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.