Symptomatic neonatal seizures followed by febrile status epilepticus: The two-hit hypothesis for the subsequent development of epilepsy

Neonatal seizures have been associated with the later development of postneonatal epilepsy, mainly beginning within the first year of life. Mechanisms of epileptogenesis in the immature brain still need to be fully elucidated but a two-hit hypothesis, showing that an early insult heightens later susceptibility to seizure-induced brain damage, has been demonstrated in animal models. We describe 2 cases of preterm babies sustaining recurrent neonatal seizures in the context of a severe perinatal brain damage who presented with symptomatic epilepsy only after the occurrence of an episode of febrile status epilepticus. In the context of preexisting perinatal brain damage, febrile status epilepticus acted as a second hit for developing epilepsy, confirming animal evidence.