Epileptogenesis after prolonged febrile seizures: Mechanisms, biomarkers and therapeutic opportunities

Epidemiological and recent prospective analyses of long febrile seizures (FS) and febrile status epilepticus (FSE) support the idea that in some children, such seizures can provoke temporal lobe epilepsy (TLE). Because of the high prevalence of these seizures, if epilepsy was to arise as their direct consequence, this would constitute a significant clinical problem. Here we discuss these issues, and describe the use of animal models of prolonged FS and of FSE to address the following questions: Are long FS epileptogenic? What governs this epileptogenesis? What are the mechanisms? Are there any predictive biomarkers of the epileptogenic process, and can these be utilized, together with information about the mechanisms of epileptogenesis, for eventual prevention of the TLE that results from long FS and FSE.

► Febrile seizure (FS) duration is an important parameter for epileptogenesis.
► T2 MRI indicates no acute cell loss after FS; sclerosis may be a result of epilepsy.
► Inflammation is important; IL-1B levels are up only in rats that develop epilepsy.
► Coordinate expression changes in sets of genes contribute to epileptogenesis.
► Biomarkers and identification of epileptogenic mechanisms are crucial for treatment.