Pediatric Epilepsy Mechanisms: Expanding the Paradigm of Excitation/Inhibition Imbalance.

Affiliation

Division of Pediatric Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. [Email]

Abstract

Mechanisms underlying seizures and epilepsy have traditionally been considered to involve abnormalities of ion channels or synaptic function. Those considerations gave rise to the excitation/inhibition (E/I) imbalance theory, whereby increased excitation, decreased inhibition, or both favor a hyperexcitable state and an increased propensity for seizure generation and epileptogenesis. Several recent findings warrant reconsideration and expansion of the E/I hypothesis: novel genetic mutations have been identified that do not overtly affect E/I balance; neurotransmitters may exert paradoxical effects, especially during development; anti-seizure medications do not necessarily work by decreasing excitation or increasing inhibition; and metabolic factors participate in the regulation of neuronal and network excitability. These novel conceptual and experimental advances mandate expansion of the E/I paradigm, with the expectation that new and exciting therapies will emerge from this broadened understanding of how seizures and epilepsy arise and progress.

Keywords

STXBP1,antiseizure drugs,epilepsy,excitation,genetic mutations,inhibition,ketogenic diet,levetiracetam,metabolism,seizures,synaptic function,