MEDICAL COLLEGE OF VIRGINIA EPILEPSY RESEARCH CENTER

弗吉尼亚医学院癫痫研究中心

• 批准号: 6629259
• 负责人: ROBERT John DELORENZO
• 金额: $ 101.94万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-01-01 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6629259
• 关键词: epilepsy; nervous system disorder epidemiology

Status epilepticus (SE) is a major medical emergency, causing more than 35,000 deaths each year in the United States. The four research projects of this Epilepsy Research Center (ERC) at the Medical College of Virginia of Virginia Commonwealth University are focused on the CENTRAL THEME of studying SE. These projects compliment each other and the interaction of multi-disciplined investigators around a common theme greatly enhances the development of new insights and research productivity. The four projects will test specific hypotheses developed to investigate clinical aspects and basic mechanisms of SE are: SE: A Clinical and Epidemiological Study; Pathophysiology and Mortality of SE; Genetic Preponderance of SE in Twin Kindreds; and SE Duration- Dependent Modulation of GABAA Receptor Function. The clinical projects will offer important new insights into the epidemiology of SE in the elderly, the neonatal period, the young child, and different ethnic groups. This research will also produce a SE Outcome Scale for identifying high risk patients that can be used for clinical assessment and future therapeutic interventions. The intensive cardiac and central nervous system (CNS) physiological monitoring will test preliminary evidence that persistent CNS excitability predicts HIGH RISK patients for cardiac abnormalities that may ultimately lead to death in SE. In addition, this research effort has identified non-convulsive SE as a major cause of morbidity and mortality and has developed a prospective data base to evaluate this under recognized form of SE in the comatose patient. Utilizing one of the largest twin registries in the world, studies are proposed that provide the first direct evidence that the development of SE in man is controlled in part by a genetic predisposition. Animal models of SE demonstrate that there is a modulation of the GABAA receptor function that underlies the development of SE intractability and resistance to treatment. Studies indicate that alterations in the gamma amino butyric acid (GABA) receptor function play a major role in the pathogenesis of SE. The accomplishments of this research program are enhanced by the collaboration between committed investigators and research projects. The results from this study will ultimately develop new strategies to offer insights into the pathophysiology of SE and improve the diagnosis and treatment of this severe neurological condition.

癫痫持续状态(SE)是一种重大的医疗紧急情况，在美国每年导致超过3.5万人死亡。弗吉尼亚联邦大学弗吉尼亚医学院癫痫研究中心(ERC)的四个研究项目集中在研究癫痫的中心主题上。这些项目相辅相成，多学科调查人员围绕一个共同主题的互动极大地增强了新见解的发展和研究生产率。这四个项目将测试为研究SE的临床方面和基本机制而开发的特定假说：SE：临床和流行病学研究；SE的病理生理学和死亡率；SE在双亲中的遗传优势；以及SE对GABAA受体功能的持续时间调节。这些临床项目将为老年人、新生儿期、幼儿和不同种族群体的SE流行病学提供重要的新见解。这项研究还将产生一种用于识别高危患者的SE结果量表，可用于临床评估和未来的治疗干预。密集的心脏和中枢神经系统(CNS)生理监测将测试初步证据，即持续的CNS兴奋性预示着心脏异常的高危患者，这些心脏异常可能最终导致SE死亡。此外，这项研究确定了非惊厥性SE是发病率和死亡率的主要原因，并开发了一个前瞻性数据库来评估昏迷患者中这种公认的SE形式。利用世界上最大的双胞胎注册表之一，提出了第一项研究，提供了第一个直接证据，表明人类SE的发育部分由遗传易感性控制。SE的动物模型表明，存在GABAA受体功能的调节，这是SE难治性和治疗耐药性发展的基础。研究表明，γ-氨基丁酸(GABA)受体功能的改变在SE的发病机制中起重要作用。这一研究计划的成就通过致力于研究人员和研究项目之间的合作而得到加强。这项研究的结果最终将开发新的策略，为SE的病理生理学提供见解，并改善这种严重神经疾病的诊断和治疗。