Despite the significant mortality associated with status epilepticus (SE), little is known concerning the exact pathophysiological basis of death. A major aim of this proposal is to investigate the effects of SE on the central nervous system (CNS) and cardiovascular system (CVS) and determine the causes of mortality associated with SE. Preliminary data from this study have provided the first electrophysiological data on SE patients just prior to and at the time of death, and data on the effects of SE on CVS function. These findings identified two distinct cardiovascular patterns of mean arterial pressure and rate preceding death in SE. Our research also demonstrated that previously unrecognized CNS and CVS hyper- excitability occurs after SE in a significant percent of patients. We have identified After SE Ictal Discharges (ASIDS) and abnormal evoked potentials (EPs) as electrophysiological high risk markers for a hyper- excitable CNS state. Non-convulsive SE were also demonstrated in up to 10% of comatose patients without overt seizure activity. Preliminary results from this study suggested that ASIDS is a predictive indicator of abnormal cardiac function and are associated with increased cardiac arryhythmogenicity. This research project is focused on critically evaluating the pathophysiology of SE by obtaining carefully controlled physiological data on SE in humans. CENTRAL HYPOTHESES will be tested by accomplishing the following Specific Aims. 1. Develop optimal criteria for detecting and evaluating the temporal occurrence of ASIDS; 2. Determine the temporal relationship of ASIDS and cardiac conduction and/or functional abnormalities that can precipitate cardiac arrest or injury; 3. Evaluate the role of EPS in predicting SE patients at high risk of cardiac death. 4. Determine CNS and CVS functional abnormalities prior to death and correlate with pathologic findings; 5. Determine the frequency of occurrence and the clinical presentation of unrecognized non-convulsive SE (NCSE) in comatose patients; 6. Establish a prospective data base of clinical CNS and CVS data in a large population of adult SE patients and correlate the functional state of the CNS and CVS with other clinical and laboratory values. By coordinating neurologic and cardiac electrophysiological monitoring with pathological, laboratory, and clinical evaluations in a controlled, prospective, population-based data base, this study may provide the first insights into the causes of death and morbidity from SE in man.
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