Deep cerebellar electrical stimulation for post-stroke motor recovery

深部小脑电刺激促进中风后运动恢复

• 批准号: 10058307
• 负责人: KENNETH B BAKER
• 金额: $ 16万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10058307
• 关键词: Activities of Daily Living; Acute; Advanced Development; Adverse event; Affect; Area; Behavioral; Cerebral cortex; Cerebrum; Chronic; Clinical Trials; Collaborations; Computer Models; Data; Deep Brain Stimulation; Dentate nucleus; Development; Device Designs; Devices; Disease; Electric Stimulation; Electrodes; Epidemiology; Evaluation; Event; Exhibits; FDA approved; Family; Frequencies; Funding; Future; Goals; Grant; Human; Implant; Implantation procedure; Incidence; Individual; Industrialization; Institutional Review Boards; Intervention; Investigation; Ischemic Stroke; Lead; Limb structure; Location; Long-Term Potentiation; Maps; Mission; Morphology; Motor; Movement; National Institute of Neurological Disorders and Stroke; Nature; Neurology; Neuropsychology; Operative Surgical Procedures; Outcome; Output; Pathway interactions; Patients; Performance; Phase II Clinical Trials; Phase III Clinical Trials; Physiologic pulse; Physiological; Public Health; Quality of life; Radiology Specialty; Recovery; Rehabilitation therapy; Research; Residual state; Rodent Model; Role; Safety; Secondary to; Serious Adverse Event; Signal Transduction; Site; Societies; Stroke; Survivors; System; Task Performances; Techniques; Technology; Therapeutic; Therapeutic Effect; Therapeutic Intervention; Time; Tissues; Transcranial magnetic stimulation; Translations; Treatment Efficacy; United States; United States Food and Drug Administration; Upper Extremity; Work; algorithm development; base; biophysical model; daily functioning; design; disability; experimental study; feasibility trial; first-in-human; hemiparesis; human data; human subject; implantation; improved; middle cerebral artery; motor behavior; motor deficit; motor function recovery; motor impairment; motor recovery; neurological rehabilitation; neurophysiology; neurosurgery; next generation; novel; post stroke; pre-clinical; primary endpoint; prospective; relating to nervous system; response; safety and feasibility; stroke patient; stroke rehabilitation; synaptogenesis; therapy development; treatment strategy; trial design

PROJECT SUMMARY/ABSTRACT Stroke is a disease of epidemiological proportions in the industrialized world and a leading cause of long-term disabilities. One third of stroke patients maintain long-term motor deficits severe enough to be disabling, despite rehabilitative efforts. We have proposed dentate nucleus deep brain stimulation (DN-DBS) as a therapy to facilitate motor recovery for patients with chronic upper extremity hemiparesis due to ischemic stroke. Our working hypothesis is that low-frequency, DN-DBS increases excitatory dentatothalamocoritical output; thereby enhancing cerebral cortical excitability and facilitating functional reorganization in perilesional cortical areas that support further motor recovery. Our supporting data demonstrate that motor recovery facilitation can be achieved with a single electrode system in the ischemic rodent model, with those changes accompanied by sustained increments in cerebral cortical excitability in perilesional regions, perilesional reorganization of motor representation, and increased expression of markers of long-term potentiation and synaptogenesis. Our preclinical data has reached the point of human translation and, based on these data, we have obtained FDA approval for a first-in-man DN-DBS clinical trial to assess the safety and feasibility of DN-DBS for patients with persistent, moderate-to-severe upper-extremity hemiparesis secondary to middle cerebral artery ischemic stroke. The experiments proposed in the present study will build upon the opportunities provided by this clinical trial. Specifically, we will obtain and analyze behavioral and physiological data from human subjects to advance the development and evaluation of a next-generation system that will be specifically designed for post-stroke rehabilitation enhancement. These studies will be carried out by an investigative team with multiple, long-standing collaborations aimed at the development of DN-DBS technologies and treatment of motor impairments following stroke; the team spans expertise in clinical trials, neurology, neurosurgery, neurophysiology, neurorehabilitation, neuropsychology, radiology, and computational modeling. An Investigational Device Exemption with the Food and Drug Administration for the safety and feasibility trial was granted in December of 2015 and IRB approval is pending.

项目概要/摘要 中风是工业化国家的一种流行病学疾病，也是长期导致中风的主要原因。 残疾。三分之一的中风患者长期存在运动缺陷，严重程度足以致残， 尽管进行了康复努力。我们提出了齿状核深部脑刺激（DN-DBS）作为一种治疗方法 促进缺血性中风导致的慢性上肢偏瘫患者的运动恢复。我们的 工作假设是低频 DN-DBS 增加了兴奋性齿丘脑皮层输出；从而 增强大脑皮层兴奋性并促进病灶周围皮层区域的功能重组 支持进一步的运动恢复。我们的支持数据表明，运动恢复促进可以 在缺血性啮齿动物模型中通过单电极系统实现，这些变化伴随着 病灶周围区域大脑皮质兴奋性持续增加，病灶周围运动重组 代表，并增加长时程增强和突触发生标记的表达。我们的 临床前数据已经达到了人类翻译的程度，并且基于这些数据，我们已经获得了FDA 批准首次人体 DN-DBS 临床试验，以评估 DN-DBS 对患有以下疾病的患者的安全性和可行性 大脑中动脉缺血继发的持续性中度至重度上肢偏瘫 中风。本研究中提出的实验将建立在该临床提供的机会的基础上 审判。具体来说，我们将获取并分析人类受试者的行为和生理数据，以 推进下一代系统的开发和评估，该系统将专门设计用于 中风后康复增强。这些研究将由一个调查小组进行 旨在开发 DN-DBS 技术和治疗 中风后运动障碍；该团队涵盖临床试验、神经病学、神经外科、 神经生理学、神经康复、神经心理学、放射学和计算模型。一个 美国食品和药物管理局的安全性和可行性试验研究设备豁免 于 2015 年 12 月获得批准，目前正在等待 IRB 批准。