Current concepts in the pathogenesis of febrile seizures

Abstract

The article reviews current pathophysiological mechanisms underlying febrile seizures, extending beyond the simplified hyperthermic model. Fever is considered a triggering factor for seizure activity that manifests in the setting of age-related functional vulnerability of the central nervous system. Particular emphasis is placed on immaturity of neuronal regulatory systems, imbalance between excitatory and inhibitory processes, and developmental features of GABAergic transmission and chloride homeostasis. The role of temperature-dependent ionic mechanisms, genetic predisposition, and channelopathies in lowering the seizure threshold is analyzed. Special attention is given to neuroinflammation as a modulator of neuronal excitability, as well as to metabolic and mitochondrial disturbances that limit neuronal energy supply during fever. Febrile seizures are regarded as a dynamic functional state with a multilevel pathogenesis.