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: 8763864
• 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/8763864
• 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 该项目拟研究低温作为难治性癫痫持续状态 (RSE) 的治疗方法。 RSE 是 VA 重症监护病房中越来越常见的问题。这可能是由于生命支持系统和 ICU 技术的改进、脑电图记录可用性的提高以及对“微妙”癫痫持续状态 (SE) 和其他因素的认识的提高。 RSE的治疗效果很差，死亡率和发病率很高。需要新的治疗方法。深低温（200℃）临床上用于心脏手术和神经外科手术。中低温（32-330℃）常规用于治疗新生儿缺氧缺血性脑病、心脏骤停后脑病和创伤性脑损伤。事实证明，低温治疗在这些情况下是安全有效的。它还被证明可以抑制癫痫发作。然而，它很少用于治疗 RSE，我们对其适应症和 RSE 有效性缺乏基本了解。我们将测试以下假设：深低温可减少两种实验性癫痫持续状态模型中的癫痫发作活动，这两种模型分别由化学（锂和毛果芸香碱）或电（穿通路径）刺激诱发 大脑。我们将比较深低温和亚低温，并测试不同持续时间的亚低温，以确定较长持续时间的亚低温是否可以与短持续时间深低温一样有效地终止 RSE。我们将比较两种提供低温的方法：全身冷却和头部冷却（“冷帽”）。对于相同水平的顶叶皮层冷却，我们预计全身冷却比“冷却帽”方法更有效地终止 SE。最后，我们将研究低温治疗对 RSE 长期后果的影响：神经元损伤、血脑屏障破坏、细胞介导的炎症、癫痫发生和行为缺陷。我们期望低温治疗能够减少所有这些并发症。在这项研究结束时，我们希望能够确定治疗实验性癫痫持续状态最有效的低温深度、持续时间和方法。