慢性植入式皮质-丘脑闭环深部脑刺激治疗特发性震颤

Chronic embedded cortico-thalamic closed-loop deep brain stimulation for the treatment of essential tremor.

作者信息

Opri Enrico, Cernera Stephanie, Molina Rene, Eisinger Robert S, Cagle Jackson N, Almeida Leonardo, Denison Timothy, Okun Michael S, Foote Kelly D, Gunduz Aysegul

机构信息

J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611, USA.

Electrical and Computer Engineering, University of Florida, Gainesville, FL 32603, USA.

出版信息

Sci Transl Med. 2020 Dec 2;12(572). doi: 10.1126/scitranslmed.aay7680.

Abstract

Deep brain stimulation (DBS) is an approved therapy for the treatment of medically refractory and severe movement disorders. However, most existing neurostimulators can only apply continuous stimulation [open-loop DBS (OL-DBS)], ignoring patient behavior and environmental factors, which consequently leads to an inefficient therapy, thus limiting the therapeutic window. Here, we established the feasibility of a self-adjusting therapeutic DBS [closed-loop DBS (CL-DBS)], fully embedded in a chronic investigational neurostimulator (Activa PC + S), for three patients affected by essential tremor (ET) enrolled in a longitudinal (6 months) within-subject crossover protocol (DBS OFF, OL-DBS, and CL-DBS). Most patients with ET experience involuntary limb tremor during goal-directed movements, but not during rest. Hence, the proposed CL-DBS paradigm explored the efficacy of modulating the stimulation amplitude based on patient-specific motor behavior, suppressing the pathological tremor on-demand based on a cortical electrode detecting upper limb motor activity. Here, we demonstrated how the proposed stimulation paradigm was able to achieve clinical efficacy and tremor suppression comparable with OL-DBS in a range of movements (cup reaching, proximal and distal posture, water pouring, and writing) while having a consistent reduction in energy delivery. The proposed paradigm is an important step toward a behaviorally modulated fully embedded DBS system, capable of delivering stimulation only when needed, and potentially mitigating pitfalls of OL-DBS, such as DBS-induced side effects and premature device replacement.

摘要

深部脑刺激(DBS)是一种已获批准的治疗难治性严重运动障碍的疗法。然而,大多数现有的神经刺激器只能进行持续刺激[开环DBS(OL-DBS)],忽略了患者行为和环境因素,从而导致治疗效率低下,进而限制了治疗窗口。在此,我们针对三名患有特发性震颤(ET)的患者,在一项纵向(6个月)的受试者自身交叉方案(DBS关闭、OL-DBS和CL-DBS)中,确立了一种完全嵌入慢性研究性神经刺激器(Activa PC + S)的自我调节治疗性DBS[闭环DBS(CL-DBS)]的可行性。大多数ET患者在目标导向运动期间会出现肢体不自主震颤,但在休息时不会出现。因此,所提出的CL-DBS模式探索了基于患者特定运动行为调节刺激幅度的疗效,基于检测上肢运动活动的皮层电极按需抑制病理性震颤。在此,我们展示了所提出的刺激模式如何能够在一系列运动(够杯子、近端和远端姿势、倒水和书写)中实现与OL-DBS相当的临床疗效和震颤抑制,同时能量传递持续减少。所提出的模式是朝着行为调制的完全嵌入式DBS系统迈出的重要一步,该系统能够仅在需要时提供刺激,并有可能减轻OL-DBS的缺陷,如DBS引起的副作用和过早更换设备。

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