Children with
epilepsy present unique challenges to the clinician. In addition to having differences in clinical and EEG phenomena, children differ from adults in regard to etiological factors, response to
antiepileptic drugs (AEDs), and outcome. It is now recognized that the immature brain also differs from the mature brain in the basic mechanisms of epileptogenesis and propagation of
seizures. The immature brain is more prone to
seizures due to an imbalance between excitation and inhibition.
gamma-Aminobutyric acid (
GABA), the major CNS inhibitory
neurotransmitter in the mature brain, can lead to depolarization in the hippocampal CA3 region in very young rats. There are also age-related differences in response to
GABA agonists and antagonists in the substantia nigra, a structure important in the propagation of
seizures. These age-related differences in response to
GABAergic agents provide further evidence that the pathophysiology of
seizures in the immature brain differs from that in the mature brain. Although prolonged
seizures can cause brain damage at any age, the extent of brain damage after prolonged
seizures is highly age dependent. Far less histological damage and fewer disturbances in cognition result from prolonged
seizures in the immature brain than from
seizures of similar duration and intensity in mature animals. However, detrimental effects of AEDs may be greater in the immature brain, than in the mature brain. These lessons from the animal laboratory raise questions about the appropriateness of current therapeutic approaches to childhood
seizure disorders.