Epileptic sudden death: Animal models

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Simon R(1997) Epileptic sudden death: Animal models. Epilepsia 38:S11 S35–37.

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Abstract: The pathologic hallmark of sudden unexpected death in epilepsy (SUDEP) in humans is pulmonary edema. In an animal model of seizures, pulmonary vascular pressure, but not systemic pressure, increases in proportion to seizure duration. The induced pulmonary vascular hypertension drives fluid out of the vascular compartment into the lung parenchyma. Blocking intra-ictal pulmonary vascular pressure elevations prevents changes in the observed doubling of the pulmonary transcapillary fluid flux. In this animal model, the main difference between surviving animals and those that die during the seizure is apnea, with a precipitous fall in the partial pressure of oxygen (pO(2)) and a parallel elevation in the partial pressure of carbon dioxide (pCO(2)) recorded in nonsurvivors. Pulmonary artery and left atrial pressures in animals that die are double those of surviving animals, with a resultant increase in extra-vascular lung water at postmortem examination. The pulmonary edema is due to the combined effects of seizure- and hypoxia-induced pulmonary vascular hypertension. This animal model reproduces both death during epilepsy and pulmonary edema at postmortem examination. The etiology of the pulmonary edema appears to be that of pulmonary vascular hypertension, and the etiology of sudden death appears to be that of centrally induced apnea.

Keywords: SUDEP, Epilepsy, Seizures, Pulmonary edema, Apnea


This study investigate the role of seizures on the pulmonary circuit within the sheep model. Simon found that with electroconvulsive shocks there was a 200% increase in vascular pressure within the aorta regardless of seizure detection through EEG. With induced seizure through injections with bicuculline, the pulmonary artery and left atrial pressues were nearly double in SUDEP sheep. Also there was a drastic increase of CO2 levels within four minutes of seizure induction. These results coincide with studies by Johnston et al who saw similar effects due to central apnea within the sheep model.


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