Pathophysiology of developmental epilepsies

Epilepsy in children often has unique characteristics that differentiate it from adult-onset epilepsy. The immature brain exhibits an increased susceptibility to seizures, resulting in a peak incidence of epilepsy in the first year of life. Most of the common idiopathic epilepsy syndromes typically have their onset in childhood. Other prominent seizure disorders, such as febrile seizures and infantile spasms, also exhibit a distinct predilection for the pediatric years. Furthermore, many causes of symptomatic epilepsies are relatively specific to the pediatric population, such as certain types of malformations of cortical development. Significant advances have recently been made in understanding the neurobiological mechanisms that cause developmental differences in seizures and account for the unique properties of many childhood epilepsies. Developmental processes that guide the growth and maturation of the nervous system under normal conditions may contribute to the increased seizure susceptibility of the immature brain. Genetic, biochemical, and structural abnormalities may initially become symptomatic or have distinctive effects in the developing brain, manifesting as specific pediatric epilepsy syndromes. Both clinical studies and animal models of epilepsy have helped contribute to our understanding of the developmental characteristics of seizures in the immature brain. Most importantly, many of these findings are beginning to be applied to the development of novel, more effective therapies for pediatric epilepsies. This chapter summarizes our understanding of some of these concepts by examining various epilepsy syndromes in a chronological fashion across the pediatric years. Particular attention is focused on how our understanding of these syndromes is translating into potential therapies.