Age-dependent consequences of seizures: relationship to seizure frequency, brain damage, and circuitry reorganization

Seizures in the developing brain pose a challenge to the clinician. In addition to the acute effects of the seizure, there are questions regarding the impact of severe or recurrent seizures on the developing brain. Whether provoked seizures cause brain damage, synaptic reorganization, or epilepsy is of paramount importance to patients and physicians. Such questions are especially relevant in the decision to treat or not treat febrile seizures, a common occurrence in childhood. These clinical questions have been addressed using clinical and animal research. The largest prospective studies do not find a causal connection between febrile seizures and later temporal lobe epilepsy. The immature brain seems relatively resistant to the seizure-induced neuronal loss and new synapse formation seen in the mature brain. Laboratory investigations using a developmental rat model corresponding to human febrile seizures find that even though structural changes do not result from hyperthermic seizures, synaptic function may be chronically altered. The increased understanding of the cellular and synaptic mechanisms of seizure-induced damage may benefit patients and clinicians in the form of improved therapies to attenuate damage and changes induced by seizures and to prevent the development of epilepsy.