A promising animal model demonstrates course of epilepsy

A promising animal model of epilepsy became even more valuable with the demonstration that the course of the disorder closely parallels that of one of the most common forms of epilepsy in humans.

In an article published online June 6, 2005, in the Annals of Neurology, researchers at St. Justine Hospital at the University of Montreal in Canada report that prolonged fever-related seizures in rat pups with underlying brain malformations lead to epilepsy in the rats in adulthood. The article is available via Wiley InterScience.

Fever-related, or 'febrile,' seizures are not uncommon in young children and usually have no apparent lasting consequences. However, researchers have noted for a long time that people with temporal lobe epilepsy are more likely to have experienced atypical childhood febrile seizures--ones that occur at lower fever temperatures and last for a long time.

"Our results stress the importance of a careful evaluation of children with atypical febrile seizures. Early identification of children at risk of developing epilepsy could lead to neuroprotective treatments that could prevent the development of later epilepsy," said senior author Lionel Carmant, M.D., of the Sainte-Justine Hospital at the University of Montreal in Canada.

Doctors have long debated whether atypical childhood febrile seizures lead to epilepsy later in life. Researchers have had to consider the alternate possibility that these seizures are merely another manifestation of an underlying disease process that will lead to epilepsy with or without atypical febrile seizures.

The answer to this conundrum has profound treatment implications. Only with a better understanding of the relationship between febrile seizures and adult epilepsy would doctors be able to take aggressive measures to arrest or even prevent the consequences of febrile seizures in children at risk of temporal lobe epilepsy.

An important development in recent years is the discovery that some people with epilepsy have subtle brain malformations that arose during the early development of the brain. Carmant and his group have hypothesized that such abnormalities might remain harmless unless a child experiences atypical febrile seizures.

They have been able to test this hypothesis by creating brain malformations just after birth in rat pups. "In earlier studies, we showed that that atypical febrile seizures occur only in rat pups with an underlying subtle cortical malformation," said Carmant.

In the current study, the researchers found that when these rats reach adulthood, almost all develop temporal lobe epilepsy. Furthermore, they have deficits in learning and memory, problems noted in some patients with temporal lobe epilepsy.

The next step in this research--which Carmant's team has already begun--is to understand the mechanisms that transform a predisposed brain into an epileptic one, and to search for ways to prevent atypical febrile seizures from triggering these processes.