PATHOPHYSIOLOGY AND MORTALITY OF STATUS EPILEPTICUS

癫痫持续状态的病理生理学和死亡率

• 批准号: 7148603
• 负责人: ROBERT John DELORENZO
• 金额: $ 54.38万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7148603
• 关键词: clinical research; death

DESCRIPTION (provided by investigator): Status Epilepticus (SE) is associated with significant mortality, yet little is known concerning the pathophysiological basis of death. Furthermore, there are no outcome scales to predict the probability of mortality in SE. This study will investigate predictors of mortality for SE and non convulsive SE (NCSE). Preliminary results (PR) indicate that we developed Outcome Scales for both SE and NCSE that predict mortality with a high degree of specificity and sensitivity. These Outcome Scales will be prospectively validated and improved in this study. Our PR identified After SE Ictal Discharges (ASIDS) as a major predictor of mortality and cardiac abnormalities in SE. Studies are proposed to determine the role of ASIDS in causing cardiac electrophysiological and functional abnormalities. PR indicates that ASIDS can trigger acute cardiac decompensation and death. This study will test our initial observations that increased frequency and duration of ASIDS are associated with increased mortality. We will also determine by continuous EEG and ECG monitoring whether ASIDS are associated in time with cardiac electrophysiological abnormalities and can trigger death. We also propose to conduct postmortem studies on the pathological findings in brain and heart in monitored SE patients and controls. Our PR indicated that SE causes acute ischemic and gliotic changes in the hippocampus and thalamus and is associated with specific cardiac pathology. Hypotheses will be tested in the following 5 Specific Aims. AIM 1: Prospectively validate the NCSE Outcome Scale to predict mortality in NCSE. Aim 2: Determine the effect of frequency and duration of ASIDS on mortality in SE. Aim 3: Determine the temporal relationship of ASIDS and cardiac electrophysiological and/or functional abnormalities and death. AIM 4: Determine CNS and CVS functional abnormalities prior to death and correlate with brain and heart pathologic findings. AIM 5: Prospectively validate the ability of the SE Outcome Scale to predict mortality in SE. This study may provide significant insights into the causes of mortality in SE and also develop Outcome Scales for both SE and NCSE that can be used at the bedside to identify high risk cases. The ability to recognize high risk SE and NCSE cases will offer new hope for the development of new treatment strategies for high risk cases to prevent death in SE and provide guidelines to counsel families regarding prognosis.

描述（由研究者提供）：癫痫持续状态（SE）与显着的死亡率相关，但对于死亡的病理生理学基础知之甚少。此外，没有结果量表来预测 SE 的死亡率概率。本研究将调查 SE 和非惊厥性 SE (NCSE) 死亡率的预测因素。初步结果 (PR) 表明，我们为 SE 和 NCSE 开发了结果量表，可以高度特异性和敏感性地预测死亡率。这些结果量表将在本研究中得到前瞻性验证和改进。我们的 PR 认为 SE 发作后放电 (ASIDS) 是 SE 死亡率和心脏异常的主要预测因素。拟开展研究以确定 ASIDS 在引起心脏电生理和功能异常中的作用。 PR 表明 ASIDS 可引发急性心脏代偿失调和死亡。这项研究将检验我们的初步观察结果，即 ASIDS 的频率和持续时间增加与死亡率增加相关。我们还将通过持续的脑电图和心电图监测来确定 ASIDS 是否与心脏电生理异常相关并可能引发死亡。我们还建议对监测的 SE 患者和对照组的大脑和心脏病理结果进行尸检研究。我们的 PR 表明 SE 会引起海马和丘脑的急性缺血和神经胶质细胞变化，并与特定的心脏病理学相关。假设将在以下 5 个具体目标中得到检验。目标 1：前瞻性验证 NCSE 结果量表以预测 NCSE 死亡率。目标 2：确定 ASIDS 的频率和持续时间对 SE 死亡率的影响。目标 3：确定 ASIDS 与心脏电生理和/或功能异常和死亡的时间关系。目标 4：在死亡前确定 CNS 和 CVS 功能异常，并与大脑和心脏病理结果相关联。目标 5：前瞻性验证 SE 结果量表预测 SE 死亡率的能力。这项研究可以为 SE 的死亡原因提供重要的见解，并开发 SE 和 NCSE 的结果量表，可在床边使用来识别高风险病例。识别高风险 SE 和 NCSE 病例的能力将为开发高风险病例的新治疗策略带来新的希望，以预防 SE 死亡，并为家庭预后提供指导。