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.

项目总结/摘要 中风是工业化世界中流行病学比例的疾病，并且是长期脑卒中的主要原因。 残疾。三分之一的中风患者长期存在严重到致残的运动缺陷， 尽管康复的努力。我们提出了齿状核脑深部电刺激（DN-DBS）作为一种治疗方法， 促进缺血性中风所致慢性上肢轻偏瘫患者的运动恢复。我们 工作假设是，低频，DN-DBS增加兴奋性齿状丘脑皮质输出;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 在缺血啮齿动物模型中用单电极系统实现，这些变化伴随着 病灶周围区域大脑皮层兴奋性持续增加，运动神经元的病灶周围重组 代表，并增加长期增强和突触发生的标志物的表达。我们 临床前数据已经达到了人类翻译的程度，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用于患有以下疾病的患者的安全性和可行性： 继发于大脑中动脉缺血的持续性中重度上肢轻偏瘫 中风本研究中提出的实验将建立在本临床研究提供的机会基础上。 审判具体来说，我们将获得和分析人类受试者的行为和生理数据， 推进下一代系统的开发和评估，该系统将专门为 脑卒中后康复治疗这些研究将由一个调查小组进行， 多个，长期的合作，旨在开发DN-DBS技术和治疗 中风后的运动障碍;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、放射学和计算建模。一个 美国食品药品监督管理局（FDA）对安全性和可行性试验的试验用器械豁免是 2015年12月批准，IRB批准正在等待。