Simultaneous low-frequency deep brain stimulation of the substantia nigra pars reticulata and high-frequency stimulation of the subthalamic nucleus to treat levodopa unresponsive freezing of gait in Parkinson's disease: A pilot study

• Published in: Parkinsonism & related disorders 2019-03, Vol.60, p.153-157
• Main Authors: Valldeoriola, Francesc, Muñoz, Esteban, Rumià, Jordi, Roldán, Pedro, Cámara, Ana, Compta, Yaroslau, Martí, María José, Tolosa, Eduardo
• Format: Article
• Language: English
• Subjects: Aged; Cross-Over Studies; Deep Brain Stimulation - methods; Dopamine Agents - pharmacology; Female; Follow-Up Studies; Freezing of gait; Gait Disorders, Neurologic - drug therapy; Gait Disorders, Neurologic - etiology; Gait Disorders, Neurologic - therapy; Humans; Levodopa - pharmacology; Low frequency stimulation; Male; Middle Aged; Outcome and Process Assessment, Health Care; Parkinson Disease - complications; Parkinson Disease - drug therapy; Parkinson Disease - therapy; Parkinson's disease; Pilot Projects; Single-Blind Method; Substantia Nigra; Substantia nigra reticulata; Subthalamic Nucleus
• ISSN: 1353-8020; 1873-5126
• DOI: 10.1016/j.parkreldis.2018.09.008

Experimental studies suggest that low-frequency (LF) (63 Hz) deep brain stimulation (DBS) of the substantia nigra pars reticulata (SNr) could be useful to regulate gait disorders refractory to medical treatment in Parkinson's disease (PD). The SNr neurons could act as high-frequency (HF) pacemakers within locomotor control systems. Currently, no specific therapies can treat gait disorders in PD with insufficient response to dopaminergic treatment. To investigate whether LF-SNr-DBS combined with standard HF stimulation of the subthalamic nucleus (STN) is clinically relevant in improving gait disorders that no longer respond to levodopa in PD patients, compared with HF-STN or LF-SNr stimulation alone. Patients received LF-SNr or HF-STN stimulation alone or combined (COMB) stimulation of both nuclei (crossover design). The nucleus to be stimulated was randomly assigned and clinical evaluations performed by a blinded examiner after three months follow-up for each. Clinical assessment included the Freezing of Gait questionnaire, Tinetti Balance and Walking Assessing tool, and Unified Parkinson's Disease Rating. We included six patients (mean age 59.1 years, disease duration 16.1 years). All patients suffered motor fluctuations and dyskinesias. The best results were obtained with COMB in four patients (who preferred and remained with COMB over 3 years of follow-up) and with HF-STN in two patients. SNr stimulation alone did not produce better results than COMB or STN in any patient. COMB and HF-STN stimulation improved PD-associated gait disorders in this preliminary case series, sustained over time. Further multicenter investigations are required to better explore this therapeutic option. •Freezing during the “on” period in Parkinson's disease is very difficult to treat pharmacollogically or with conventional DBS.•Low frequency stimulation of the substantia nigra reticulata could regulate gait disorders in Parkinson's disease.•Simultaneous DBS in the subthalamus and SNr at different frequencies showed substained improvement of “on” freezing in PD.