Wilkins Kevin B, Petrucci Matthew N, Lambert Emilia F, Melbourne Jillian A, Gala Aryaman S, Akella Pranav, Parisi Laura, Cui Chuyi, Kehnemouyi Yasmine M, Hoffman Shannon L, Aditham Sudeep, Diep Cameron, Dorris Hannah J, Parker Jordan E, Herron Jeffrey A, Bronte-Stewart Helen M
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94304, USA.
Department of Bioengineering, Stanford Schools of Engineering & Medicine, Stanford, CA 94305, USA.
Brain Commun. 2025 Jul 9;7(4):fcaf266. doi: 10.1093/braincomms/fcaf266. eCollection 2025.
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.
冻结步态是帕金森病的一种致残症状，通常对药物治疗无效。丘脑底核内的长时间β波爆发与更严重的功能障碍和冻结步态相关，而深部脑刺激可改善这些症状。本研究的目的是探讨β波爆发驱动的适应性深部脑刺激治疗帕金森病步态障碍和冻结步态的可行性、安全性和耐受性。7名帕金森病患者植入了研究性的Summit™ RC + S深部脑刺激系统（美敦力公司，爱尔兰都柏林）。一种基于计算机的回路架构根据丘脑底核中的β波爆发持续时间实时调整刺激。采用了严格的校准程序来确定参与者特定的适应性深部脑刺激参数。在双盲设计中，参与者在四种情况下进行了一项系安全带的原地踏步任务、一次自由行走转弯和障碍课程、运动迟缓的仪器测量以及临床运动评估：关闭刺激、开启适应性、连续或随机适应性深部脑刺激。适应性深部脑刺激在所有参与者中均成功实施，且被认为是安全且可耐受的。与关闭刺激相比，适应性深部脑刺激改善了步态指标，如总体冻结时间百分比和平均峰值小腿角速度，并且显示出与连续深部脑刺激相似的疗效。在包括震颤和运动迟缓定量指标在内的总体临床运动障碍方面也观察到了类似的改善。当前的初步研究证明了在急性实验室环境中，适应性深部脑刺激治疗帕金森病冻结步态的初步安全性、耐受性和可行性，为未来在家中环境下对其长期疗效的研究提供了支持。
