Pathogenetic and etiologic considerations of febrile seizures

Abstract

Febrile seizure (FS), which occurs in febrile children without underlying health problems, is the most common type of seizure disorder in children. The suggested pathogenesis of FS derived from several animal and human studies is multifactorial and debatable. Neuronal hyperexcitability, which develops during inflammatory responses that accompany fever, provokes seizures. However, the exact role of each inflammatory mediator (e.g., cytokines) is undefined in terms of the connection between systemic or local inflammation and the central nervous system, and the mechanisms by which cytokines increase neuronal excitability remain unclear. In contrast, the cause of fever in most children with FS is usually mild respiratory virus infection (e.g., rhinovirus, influenza virus, adenovirus, and enterovirus) rather than severe bacterial infections. In temperate regions, the major causative respiratory viruses seem to mirror seasonally prevalent respiratory viruses in the community. Therefore, vigorous efforts to identify the causative pathogen of fever may not be necessary in children with FS. Genetic factors seem to play a role in neuronal hyperexcitability, and some types of genetic variation have been identified in several genes encoding ion channels of neurons that participate in neuronal excitation. Although most children with FS have benign outcomes, some characteristics such as complex FS, febrile status epilepticus, consecutive afebrile seizures, and the presence of neurodevelopmental disabilities may require further genetic and neurologic evaluations.

Keywords

• cytokine
• febrile seizure
• genetics
• pathogenesis
• viruses