Current Pharmacologic Strategies for Treatment of Intractable Epilepsy in Children

Epileptic encephalopathy (EE) is a devastating pediatric disease that features medically resistant seizures, which can contribute to global developmental delays. Despite technological advancements in genetics, the neurobiological mechanisms of EEs are not fully understood, leaving few therapeutic options for affected patients. In this review, we introduce the most common EEs in pediatrics (i.e., Ohtahara syndrome, Dravet syndrome, and Lennox-Gastaut syndrome) and their molecular mechanisms that cause excitation/inhibition imbalances. We then discuss some of the essential molecules that are frequently dysregulated in EEs. Specifically, we explore voltage-gated ion channels, synaptic transmission-related proteins, and ligand-gated ion channels in association with the pathophysiology of Ohtahara syndrome, Dravet syndrome, and Lennox-Gastaut syndrome. Finally, we review currently available antiepileptic drugs used to treat seizures in patients with EEs. Since these patients often fail to achieve seizure relief even with the combination therapy, further extensive research efforts to explore the involved molecular mechanisms will be required to develop new drugs for patients with intractable epilepsy.

Automated summary

Epileptic encephalopathy is a devastating pediatric disease characterized by medically resistant seizures and global developmental delays, with limited therapeutic options due to incomplete understanding of its neurobiological mechanisms. Common EEs in pediatrics include Ohtahara syndrome, Dravet syndrome, and Lennox-Gastaut syndrome, with molecular mechanisms involving dysregulation of ion channels and synaptic transmission-related proteins. Further research is needed to explore these mechanisms and develop new drugs for patients with intractable epilepsy.