ReviewSearching for new targets for treatment of pediatric epilepsy

The highest incidence of seizures in humans occurs during the first year of life. The high susceptibility to seizures in neonates and infants is paralleled by animal studies showing a high propensity to seizures during early life. The immature brain is highly susceptible to seizures because of an imbalance of excitation and inhibition. While the primary outcome determinant of early-life seizures is etiology, there is evidence that seizures which are frequent or prolonged can result in long-term adverse consequences, and there is a consensus that recurrent early-life seizures should be treated. Unfortunately, seizures in many neonates and children remain refractory to therapy. There is therefore a pressing need for new seizure drugs as well as antiepileptic targets in children. In this review, we focus on mechanisms of early-life seizures, such as hypoxia-ischemia, and novel molecular targets, including the hyperpolarization-activated cyclic nucleotide-gated channels. This article is part of a Special Issue entitled “The Future of Translational Epilepsy Research”.

► Current antiepileptic therapy for neonates is suboptimal. ► Flupirtine is a promising drug for neonatal seizures. ► Targeting HCN channels may provide novel therapeutics.