Beta burst-driven adaptive deep brain stimulation for gait impairment and freezing of gait in Parkinson's disease.

Abstract

Freezing of gait is a debilitating symptom of Parkinson's disease that is often refractory to medication. Prolonged beta bursts within the subthalamic nucleus are associated with worse impairment and freezing, which are improved with deep brain stimulation. The goal of the study was to investigate the feasibility, safety and tolerability of beta burst-driven adaptive deep brain stimulation for gait impairment and freezing of gait in Parkinson's disease. Seven individuals with Parkinson's disease were implanted with the investigational Summit™ RC + S deep brain stimulation system (Medtronic, PLC, Dublin, Ireland). A PC-in-the-loop architecture adjusted stimulation in real-time based on beta burst durations in the subthalamic nucleus. A rigorous calibration procedure was employed to find participant-specific adaptive deep brain stimulation parameters. In a double-blind design, participants performed a harnessed stepping-in-place task, a free walking turning and barrier course, instrumented measures of bradykinesia and clinical motor assessments in four conditions: OFF stimulation, on adaptive, continuous or randomly adapting deep brain stimulation. Adaptive deep brain stimulation was successfully implemented and deemed safe and tolerable in all participants. Gait metrics such as overall percent time freezing and mean peak shank angular velocity improved on adaptive deep brain stimulation compared to OFF and showed similar efficacy as continuous deep brain stimulation. Similar improvements were also seen for overall clinical motor impairment, including tremor and quantitative metrics of bradykinesia. The current pilot study demonstrated initial safety, tolerability, and feasibility of adaptive deep brain stimulation for freezing of gait in Parkinson's disease in the acute laboratory setting, supporting the future investigation of its longer-term efficacy in the at-home setting.