Epileptogenesis and the Immature Brain

Abstract

Epidemiological studies indicate that the incidence of seizures is highest early in life. This report discusses the experimental data derived from studies of focal epileptogenesis of the immature brain in tandem with ongoing maturational changes. During development, neurons have characteristic neurophysiological properties. Local interictal discharges are long in duration, lack a stereotypic morphology, and have limited fields. Yet the immature brain is very susceptible to the development of bilateral, although asynchronous, seizures and status epilepticus induced by amygdala kindling or by convulsant drugs. This increased seizure susceptibility may be due to a functional immaturity of a substantia nigra, GABA-sensitive output system. The morbidity of convulsions occurring early in life may not be as grave as previously thought in terms of subsequent acquisition of "normal" developmental milestones. The propensity to develop recurrent convulsions in adulthood is not related to the severity of a single seizure in infancy. Although multiple severe seizures may predispose animals to the development of seizures later in life, this is not a unique feature of the immature brain, since it also occurs in the adult brain. Finally, there is evidence that the immature brain may respond to anticonvulsant drugs differently from its mature counterpart; these findings emphasize the need to develop new antiepileptic therapies that take into account the maturational state of the brain.