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 #
5P50NS025630-09
Application #
6243628
Study Section
Project Start
1997-06-01
Project End
1998-05-31
Budget Start
1996-10-01
Budget End
1997-09-30
Support Year
9
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Type
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
Deshpande, Laxmikant S; Sombati, Sompong; Blair, Robert E et al. (2007) Cannabinoid CB1 receptor antagonists cause status epilepticus-like activity in the hippocampal neuronal culture model of acquired epilepsy. Neurosci Lett 411:11-6
Deshpande, Laxmikant S; Blair, Robert E; Nagarkatti, Nisha et al. (2007) Development of pharmacoresistance to benzodiazepines but not cannabinoids in the hippocampal neuronal culture model of status epilepticus. Exp Neurol 204:705-13
Falenski, K W; Blair, R E; Sim-Selley, L J et al. (2007) Status epilepticus causes a long-lasting redistribution of hippocampal cannabinoid type 1 receptor expression and function in the rat pilocarpine model of acquired epilepsy. Neuroscience 146:1232-44
Deshpande, Laxmikant S; Blair, Robert E; Ziobro, Julie M et al. (2007) Endocannabinoids block status epilepticus in cultured hippocampal neurons. Eur J Pharmacol 558:52-9
Carter, Dawn S; Haider, S Naqeeb; Blair, Robert E et al. (2006) Altered calcium/calmodulin kinase II activity changes calcium homeostasis that underlies epileptiform activity in hippocampal neurons in culture. J Pharmacol Exp Ther 319:1021-31
Blair, Robert E; Deshpande, Laxmikant S; Sombati, Sompong et al. (2006) Activation of the cannabinoid type-1 receptor mediates the anticonvulsant properties of cannabinoids in the hippocampal neuronal culture models of acquired epilepsy and status epilepticus. J Pharmacol Exp Ther 317:1072-8
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
Penberthy, L T; Towne, A; Garnett, L K et al. (2005) Estimating the economic burden of status epilepticus to the health care system. Seizure 14:46-51
Delorenzo, Robert J; Sun, David A; Deshpande, Laxmikant S (2005) Cellular mechanisms underlying acquired epilepsy: the calcium hypothesis of the induction and maintainance of epilepsy. Pharmacol Ther 105:229-66

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