Fever, febrile seizures and epileptogenesis

Febrile seizures (FS) are the most common types of seizures in children around the world, yet remarkably little is known about the mechanisms generating these seizures. In addition, long duration or focal FS are associated with increased probability of temporal lobe epilepsy (TLE), but it remains unclear as to whether this relationship is causal. A specific major clinical enigma has centered on whether FS themselves can provoke TLE in individuals without genetic or structural predisposition. In addition, the mechanisms of FS-related epileptogenesis require elucidation. Individuals with TLE and a history of FS have been found to often have a specific pattern of cell loss within the hippocampus, known as mesial temporal sclerosis (MTS). However, if FS cause MTS, or if the cell loss is secondary to the TLE has also been enigmatic. We created and characterized an immature rodent model of FS, which has been useful in defining how fever leads to FS, and if FS lead to epilepsy. Using this rat model, we established that long duration FS cause TLE, and FS duration governed the severity of epilepsy. Epileptogenesis was accompanied, perhaps causally, by ion channel dysfunction and inflammatory changes. Because FS are a prevalent antecedent of TLE, studying the epileptogenesis that follows them provides powerful insights, and may lead to potential therapies for epilepsy.