Treatment of status epilepticus: a translational proposal.

癫痫持续状态的治疗：一项转化建议。

• 批准号: 8543421
• 负责人: CLAUDE G WASTERLAIN
• 金额: --
• 依托单位: VA GREATER LOS ANGELES HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2017-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8543421
• 关键词: Behavioral; Blood - brain barrier anatomy; Brain; Cardiac Surgery procedures; Cells; Chemicals; Complication; Conscious; Cool-X-A; Data; Drug Combinations; Effectiveness; Electroconvulsive Shock; Electroencephalography; Encephalopathies; Epilepsy; Epileptogenesis; Experimental Models; Exposure to; Grant; Head; Heart Arrest; Hippocampus (Brain); Inflammation; Intensive Care; Intensive Care Units; Life Support Systems; Lithium; Measures; Mediating; Methodology; Methods; Midazolam; Modeling; Monitor; Morbidity - disease rate; Neonatal; Neuronal Injury; Operative Surgical Procedures; Outcome; Parietal Lobe; Pathology; Patients; Perforant Pathway; Pharmaceutical Preparations; Pharmacotherapy; Pilocarpine; Recovery; Recurrence; Refractory; Seizures; Series; Severities; Status Epilepticus; Surface; Technology; Temperature; Testing; Time; Traumatic Brain Injury; Veterans; alternative treatment; cell mediated immune response; cooperative study; improved; morris water maze; mortality; natural hypothermia; neonatal hypoxic-ischemic brain injury; neurosurgery; prevent; public health relevance

DESCRIPTION (provided by applicant): PROJECT SUMMARY This project proposes to study hypothermia as a treatment of refractory status epilepticus (RSE). RSE is an increasingly common problem in VA Intensive Care Units. This may be due to improvement in life support systems and ICU technology, to increased availability of EEG recordings and increased recognition of "subtle" status epilepticus (SE) and other factors. The results of treatment of RSE are very poor, with high mortality and morbidity. New treatments are needed. Deep hypothermia (200 C) is used clinically during cardiac surgery and neurosurgery. Moderate hypothermia (32-330 C) is used routinely in the treatment of neonatal hypoxic- ischemic encephalopathy, of post-cardiac arrest encephalopathy and of traumatic brain injury. Hypothermia has proved safe and effective in those conditions. It has also been shown to inhibit seizure activity. Yet, it is rarely used to treat RSE, and we lack a basic understanding of its indications and effectiveness in RSE. We will test the hypothesis that deep hypothermia reduces seizure activity in two models of experimental status epilepticus induced respectively by chemical (lithium and pilocarpine) or by electrical (perforant path) stimulation of the brain. We will compare deep and mild hypothermia, and will test different durations of mild hypothermia, to find out whether longer durations of mild hypothermia can be as effective in terminating RSE as short durations of deep hypothermia. We will compare two methods for delivering hypothermia: whole body cooling and head cooling ("cool cap"). For the same level of cooling of parietal cortex, we expect whole body cooling is more effective than the "cool cap" method in terminating SE. Finally, we will study the effect of hypothermia treatment on the long-term consequences of RSE: neuronal injury, blood-brain barrier breakdown, cell-mediated inflammation, epileptogenesis and behavioral deficits. We expect hypothermia treatment to reduce all of these complications. At the end of this study, we expect to be able to define the depth, duration and method of hypothermia that is most effective in the treatment of experimental status epilepticus.

描述（由申请人提供）： 项目摘要本项目建议研究体温过低，以作为对癫痫持续状态（RSE）的治疗。在VA重症监护病房中，RSE是一个日益普遍的问题。这可能是由于生命支持系统和ICU技术的改善，增加了脑电图记录的可用性以及对“微妙”状态癫痫持续状态（SE）和其他因素的识别。 RSE的治疗结果非常差，死亡率和发病率很高。需要新的治疗方法。深层体温过低（200 C）在心脏手术和神经外科手术期间临床使用。中度低温（32-330 C）通常用于治疗新生儿缺氧 - 缺血性脑病，后心骤停脑病和创伤性脑损伤。在这种情况下，体温过低已证明是安全有效的。它也已显示出抑制癫痫发作的活性。但是，它很少被用来治疗RSE，我们对RSE中的迹象和有效性缺乏基本的理解。我们将检验以下假设：深度体温过低会降低两种通过化学（锂和毛钙磷）或通过电（穿孔路径）刺激的实验状态癫痫持续状态癫痫持续性癫痫的癫痫发作活性。 大脑。我们将比较深度和温和的体温过低，并将测试不同的温和体温过低持续时间，以找出较长的轻度体温过低持续时间是否可以像较短的深度体温过低时间一样有效地终止RSE。我们将比较两种输送体温过低的方法：全身冷却和头部冷却（“酷盖”）。对于顶叶皮层的相同水平的冷却，我们预计全身冷却比终止SE的“冷帽”方法更有效。最后，我们将研究体温过低治疗对RSE长期后果的影响：神经元损伤，血脑屏障分解，细胞介导的炎症，癫痫生成和行为缺陷。我们预计低温治疗可以减少所有这些并发症。在这项研究结束时，我们希望能够定义在治疗实验状态癫痫症中最有效的体温过低的深度，持续时间和方法。