Seizure-induced damage in the developing human: relevance of experimental models

A considerable amount of money and effort is spent every year investigating the effects of seizure on the developing rodent brain. A critical question is the relevance of these studies to children. The goal of this chapter is to review the relationship between seizures during early development and cognitive impairment in children and rodents. While the majority of children with epilepsy have normal cognitive development, a small group of children with frequent, recurrent seizures show progressive cognitive impairment. Likewise, in rodent models recurrent seizures during early development are associated with cognitive impairment and histological changes including mossy fiber sprouting and reduced neurogenesis. Status epilepticus is associated with a lower morbidity and mortality rate in children than in adults. Status epilepticus in rodent models is associated with less cell loss and cognitive impairment than in adults. While rodent studies can offer a great deal of insight into mechanisms of seizure-induced brain damage, they also have significant limitations. No animal models have yet been developed that mimic human epileptic syndromes, such as infantile spasms, Lennox-Gastaut syndrome, or the severe myoclonic epilepsies. In addition, rodent studies supply only crude measures of learning and memory. Disturbances of language or higher cortical functions such as visual or auditory processing cannot be tested in animal models.