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

Abstract

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. MRDD Research Reviews 2000;6:242–252. © 2000 Wiley‐Liss, Inc.

The Neurodevelopmental Impact of Childhood‐onset Temporal Lobe Epilepsy on Brain Structure and Function

“…It is widely appreciated that animal studies have shown the pathophysiologic consequences of seizures in the developing brain to differ from those in the mature brain. Whereas the immature brain is far more prone to seizures than is the mature brain, developing neurons appear less vulnerable to neuronal damage and cell loss, with different consequences of seizures in the mature compared with the immature brain (see 57–60 for reviews). However, there is animal research to support the hypothesis that early‐onset seizures may affect cerebral white matter.…”

Convulsing toward the pathophysiology of autism

“…Animal studies demonstrate differences in seizure-induced injury which are dependent on age [36], with the immature brain being more prone to seizures but more resistant to seizure-induced damage, especially hippocampal pathology [37]. Despite lack of cell loss, specific processes affected by early onset seizures include synaptic reorganization, a decrease in neurogenesis in the hippocampal dentate gyrus [38], and a permanent increase in epileptic potential that persists into adulthood [39–42].…”

Lessons From the Laboratory: The Pathophysiology, and Consequences of Status Epilepticus

“…Although the number of studies in which murine models have been used to study the outcome of early life SE is relatively small when compared to studies performed using adult animals (as reviewed by 18), it is evident that outcome at the neuropathological and behavioral levels in these models also reflects a unique interaction between developmental stage and model (as reviewed by 70–73). A summation of age and model dependence of the long term outcomes of SE based on a representative sample of the published literature is provided in Table 2.…”