Despite the significant mortality associated with status epilepticus (SE), little is known concerning the exact pathophysiological basis of death. Although in some cases of SE mortality can be attributed to the underlying etiology, there are a substantial number of cases of unexpected and sudden death that cannot be explained. This project proposes, by the use of intensive physiological and electrophysiological monitoring, to identify and characterize the cause(s) of death secondary to prolonged seizures and developed predictive indicators of mortality. The CENTRAL HYPOTHESIS to be tested by our studies are that 1) specific physiological parameters are associated with subsequent mortality in status epilepticus and 2) that by continuous monitoring of electrophysiological data up to the time of death will assist in elucidating the cause of sudden death associated with SE and may provide specific predictors of outcome. To test the central hypothesis, we will: 1) evaluate preceding death if there is any alteration in the functioning of the cerebral cortex, brainstem, cardiovascular and autonomic nervous system by intensive monitoring; 2) evaluate whether duration and degree of coma following status epilepticus is related to mortality; 3) identify possible predictive variables associated with mortality from the evaluation of physiological and electrophysiological monitoring. Preliminary results indicate that seizure duration is associated with coma. We have identified a """"""""high risk"""""""" group of status epilepticus patients with a greater than 34% chance of mortality. In addition, our results suggest that specific electroencephalogram (EEG) and evoked potential (EP) changes associated with prolonged status epilepticus are significant predictors of mortality. The project will expand these initial observations and evaluate them with multivariate regression analysis. By intensive physiological and electrophysiological monitoring of SE following prolonged SE, it may be possible to identify and characterize the cause of death secondary to prolonged seizures. The results of this study may provide an insight into the causes of death in status epilepticus and develop predictive indicators to identify a """"""""high risk"""""""" group of patients with a high mortality. It is hoped that identifying specific predictors of outcome may lead to the development of new clinical treatments to prevent or minimize mortality.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
5P50NS025630-08
Application #
5215260
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
1996
Total Cost
Indirect Cost
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DeLorenzo, Robert J; Sun, David A; Deshpande, Laxmikant S (2006) Erratum to ""Cellular mechanisms underlying acquired epilepsy: the calcium hypothesis of the induction and maintenance of epilepsy."" [Pharmacol. Ther. 105(3) (2005) 229-266] Pharmacol Ther 111:288-325
DeLorenzo, Robert J (2006) Epidemiology and clinical presentation of status epilepticus. Adv Neurol 97:199-215
Singleton, Michael W; Holbert 2nd, William H; Ryan, Matthew L et al. (2005) Age dependence of pilocarpine-induced status epilepticus and inhibition of CaM kinase II activity in the rat. Brain Res Dev Brain Res 156:67-77
Singleton, Michael W; Holbert 2nd, William H; Lee, Anh Tuyet et al. (2005) Modulation of CaM kinase II activity is coincident with induction of status epilepticus in the rat pilocarpine model. Epilepsia 46:1389-400

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