The long-term effects of neonatal seizures

Abstract

The highest incidence of seizures occurs during the first hours to days after birth. The immature brain is prone to seizures because of reduced inhibition. GABA, which is the primary inhibitory neurotransmitter in the mature brain, is depolarizing and excitatory in the immature brain. Seizures are an ominous sign, indicating either an acquired brain insult or a genetic abnormality. While the primary outcome determinant of neonatal seizures is etiology, whether seizures can result in long-term adverse consequences independently is not clear. While the clinical data is uncertain, there is now a considerable body of evidence indicating that in animals, neonatal seizures can adversely alter the developing brain. Animal data indicates that the sequelae of seizures are strongly age dependent; seizures will affect the developing and plastic neuronal circuitry much differently than the fixed circuitry of the mature brain. Seizures at an early developmental stage can dramatically affect the construction of networks, resulting in severe and permanent handicaps in some patients. In the young brain, the long-lasting detrimental consequences of seizures are caused by an alteration of developmental programs rather than by neuronal cell loss, as occurs in adults. In animal models, neonatal seizures result in decreases in neurogenesis, sprouting of mossy fibers, and long-standing changes in signaling properties. Seizures in rat pups are also associated with abnormalities in firing patterns of single cells in the hippocampus. Furthermore, these anatomic and physiologic changes correlate well with behavioral dysfunction.