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.

项目摘要/摘要 中风是一种在工业化世界中流行的疾病，也是长期致病的主要原因。 残疾人士。三分之一的中风患者长期存在严重的运动障碍，足以致残， 尽管有康复的努力。我们提出了齿状核脑深部刺激(dn-dbs)作为一种治疗方法。 目的：促进缺血性中风所致慢性上肢偏瘫患者的运动功能恢复。我们的 工作假说是，低频率的DN-DBS增加了兴奋性的牙齿皮质输出；因此 增强大脑皮层兴奋性和促进皮质区功能重组 这支持了进一步的运动恢复。我们的支持数据表明，促进运动恢复可以 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 大脑皮层皮层兴奋性持续增强，周围区运动重组 长时程增强和突触发生的标志物的表达增加。我们的 临床前数据已经达到了人工翻译的程度，基于这些数据，我们已经获得了FDA 批准进行首例人糖尿病肾病-DBS临床试验，以评估糖尿病肾病患者应用糖尿病肾病-DBS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偏瘫 卒中。本研究中提出的实验将建立在这个临床提供的机会之上。 审判。具体地说，我们将从受试者那里获得和分析行为和生理数据，以 推进下一代系统的开发和评估，该系统将专门为 卒中后康复强化。这些研究将由一个调查小组进行， 多项长期合作，旨在开发DN-DBS技术和治疗 中风后的运动障碍；该团队在临床试验、神经学、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 食品和药物管理局的安全和可行性试验的研究设备豁免是 于2015年12月获得批准，IRB正在等待批准。