PATHOPHYSIOLOGY AND MORTALITY OF STATUS EPILEPTICUS

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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.