A Novel Dual-Frequency Deep Brain Stimulation Paradigm for Parkinson's Disease

Neurol Ther. 2019 Dec;8(2):483-489. doi: 10.1007/s40120-019-0140-5. Epub 2019 Jun 26.

Abstract

Introduction: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) using high-frequency (130-185 Hz) stimulation (HFS) is more effective for appendicular than for axial symptoms. Low-frequency stimulation (LFS) of the STN may reduce gait/balance and speech impairment but can result in worsened appendicular symptoms, limiting its clinical usefulness. A novel dual-frequency paradigm (interleave-interlink, IL-IL) was created in order to reduce gait/balance and speech impairment while maintaining appendicular symptom control in Parkinson's disease (PD) patients chronically stimulated with DBS.

Methods: Two overlapping LFS programs are applied to each DBS lead, with the overlapping area focused around the optimal electrode contact. As a result, this area receives HFS, controlling appendicular symptoms. The non-overlapping area receives LFS, potentially reducing gait/balance and speech impairment. Patients were separated into three categories based on their chief complaint(s): gait/balance impairment, speech impairment, and/or incomplete PD symptom control. The Clinical- Global Impression of Change scale (CGI-C) was completed retrospectively based on patient/caregiver feedback in patients who remained on IL-IL (at 3 months and at the last follow-up).

Results: Seventy-six patients were switched from optimized HFS to IL-IL. Fifty-five (72%) patients remained on IL-IL after 22 ± 8.7 months. The median (range) CGI-C for gait was 2 (1-5) at 3 months and 3 (1-4) at last follow-up, for dysarthria it was 4 (1-4) at 3 months and 4 (1-5) at last follow-up, and for PD motor it was 2 (1-3) at 3 months and 2 (1-3) at last follow-up.

Conclusion: A substantial number of patients remained on IL-IL because of subjective improvements in gait/balance, speech, or PD symptoms. A prospective, double-blind, crossover study with objective/quantitative outcome measures is underway.

Keywords: Deep brain stimulation; Freezing of gait; Interleaving stimulation; Low-frequency stimulation; Parkinson’s disease.