Vagus Nerve Stimulation to Augment Recovery from Traumatic Brain Injury

迷走神经刺激可促进脑外伤的恢复

• 批准号: 8466794
• 负责人: Uzma Samadani
• 金额: --
• 依托单位: VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-10-01 至 2013-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8466794
• 关键词: Animal Experimentation; Animal Model; Arousal; Atmospheric Pressure; Atrophic; Behavioral; Blast Cell; Blast Injuries; Blinded; Brain; Brain Injuries; Caregivers; Cerebrovascular Circulation; Cerebrum; Clinical; Cognition; Cognitive Therapy; Coma; Conscious; Cross-Over Studies; Devices; Diffuse Axonal Injury; Electroencephalography; Employee Strikes; Enrollment; Epilepsy; Frequencies; Genetic Crossing Over; Head; Injury; Lead; Liquid substance; Magnetic Resonance Imaging; Measures; Medical; Memory; Mental Depression; Metabolism; Midbrain structure; Military Personnel; Minimally Conscious States; Moods; Morbidity - disease rate; Motion; Neurons; Occupational Therapy; Outcome; Outcome Assessment; Outcome Measure; Patients; Percussion; Persistent Vegetative State; Physical therapy; Pilot Projects; Population; Positron-Emission Tomography; Prosencephalon; Quality of life; Randomized; Rattus; Recovery; Reporting; Reticular Formation; Seizures; Severities; Slow-Wave Sleep; Soldier; Solid; Speech Therapy; Thalamic structure; Traumatic Brain Injury; United States; Vagus nerve structure; cognitive recovery; disability; falls; fluorodeoxyglucose positron emission tomography; glucose metabolism; implantation; improved; injured; instrument; mortality; primary outcome; prospective; public health relevance; randomized trial; secondary outcome; success; vagus nerve stimulation; vehicular accident

DESCRIPTION (provided by applicant): Summary: Traumatic brain injury has a high morbidity and mortality in both civilian and military populations. Blast and other mechanisms of traumatic brain injury damage the brain by causing neurons to disconnect and atrophy. Such traumatic axonal injury can lead to persistently vegetative and minimally conscious states, for which extremely limited treatment options exist, including physical, occupational, speech and cognitive therapies. More than 50,000 patients have received vagus nerve stimulation for epilepsy and depression. In addition to decreased seizure frequency and severity, patients report enhanced mood, reduced daytime sleepiness independent of seizure control, increased slow wave sleep, and improved cognition, memory, and quality of life. Vagus nerve stimulation has not yet been performed in traumatic brain injured patients, however, animal experimentation has shown promising results. Early stimulation of the vagus nerve accelerates the rate and extent of behavioral and cognitive recovery after fluid percussion brain injury in rats. The purpose of this study is to demonstrate objective improvement in clinical outcome by placement of a vagus nerve stimulator in patients who are recovering from severe traumatic brain injury. Our hypothesis is that stimulation of the vagus nerve results in increased cerebral blood flow and metabolism in the forebrain, thalamus and reticular formation, which promotes arousal and improved consciousness, thereby improving outcome after traumatic brain injury resulting in minimally conscious or persistent vegetative states. If this study demonstrates that vagus nerve stimulation can safely and positively impact outcome, then a larger randomized prospective crossover trial will be proposed. We will achieve this objective by evaluating whether vagus nerve stimulation impacts clinical recovery from minimally conscious or persistent vegetative states caused by traumatic brain injury as assessed by the FIM" instrument and Functional Assessment Measure (FIM+FAM) as well as the JFK Coma Recovery Scale Score. We will also evaluate whether vagus nerve stimulation alters cerebral glucose metabolism as assessed by fluorodeoxyglucose positron emission tomography. Twelve patients will be enrolled in this initial crossover pilot study. These patients will have sustained a severe traumatic brain injury (Disability Rating Scale score of 22 to 29) between four and ten months from starting the study, and have no other concurrent active severe medical problems. Baseline EEG and magnetic resonance imaging (MRI) will be performed prior to vagus nerve stimulation implantation. Patients will be randomized to alternating three month periods with the device on or off. Outcomes will be assessed at three month intervals with the FIM" instrument and Functional Assessment Measure (FIM+FAM) and JFK Coma Recovery Scale by a neuropsychologist blinded to the status of the device. Positron emission tomography will also be performed. Patients will continue crossing over each three months and be followed for at least 18 months after enrollment. If vagus nerve stimulation is found to impact recovery, then a multicenter randomized prospective trial will be proposed to evaluate its efficacy.

描述（由申请人提供）： 摘要：创伤性脑损伤在平民和军人中都有很高的发病率和死亡率。爆炸和创伤性脑损伤的其他机制通过导致神经元断开和萎缩来损害大脑。这种创伤性轴突损伤可导致持续的植物人和最低意识状态，对此存在极其有限的治疗选择，包括物理、职业、言语和认知疗法。 超过 50,000 名患者接受了迷走神经刺激治疗癫痫和抑郁症。除了癫痫发作频率和严重程度降低外，患者还报告情绪改善、白天嗜睡减少（与癫痫控制无关）、慢波睡眠增加以及认知、记忆和生活质量改善。 迷走神经刺激尚未在脑外伤患者中进行，但动物实验已显示出有希望的结果。早期刺激迷走神经可加速大鼠液体冲击脑损伤后行为和认知恢复的速度和程度。 本研究的目的是证明通过在严重创伤性脑损伤中恢复的患者中放置迷走神经刺激器可以客观地改善临床结果。我们的假设是，刺激迷走神经会导致前脑、丘脑和网状结构的脑血流量和新陈代谢增加，从而促进觉醒和改善意识，从而改善导致最低意识或持续植物人状态的创伤性脑损伤后的结果。如果这项研究证明迷走神经刺激可以安全、积极地影响结果，那么将提出更大规模的随机前瞻性交叉试验。 我们将通过评估迷走神经刺激是否影响由创伤性脑损伤引起的最低意识或持续植物人状态的临床恢复来实现这一目标，并通过 FIM" 仪器和功能评估测量 (FIM+FAM) 以及 JFK 昏迷恢复量表进行评估我们还将通过氟脱氧葡萄糖正电子发射断层扫描评估迷走神经刺激是否会改变大脑葡萄糖代谢，并将招募 12 名患者。这些患者在研究开始后四到十个月内遭受严重的创伤性脑损伤（残疾评定量表评分为 22 至 29），并且没有其他并发的活动性严重医疗问题。 ) 将在迷走神经刺激植入之前进行，患者将被随机分为三个月，每隔三个月使用 FIM” 仪器和功能评估测量 (FIM+FAM) 评估一次结果。和肯尼迪昏迷恢复量表，由神经心理学家对设备状态不知情。还将进行正电子发射断层扫描。患者将每三个月继续交叉一次，并在入组后随访至少 18 个月。 如果发现迷走神经刺激影响恢复，那么将提出一项多中心随机前瞻性试验来评估其疗效。