Interleukin-1 in Febrile Infection-Related Epilepsy Syndrome

Abstract

Febrile infection-related epilepsy syndrome (FIRES) characteristically affects previously healthy children, who experience a sudden and explosive onset of super-refractory status epilepticus preceded by febrile infection and accompanied by fulminant neurogenic inflammation. FIRES, however, can affect individuals of all ages and is a subcategory of new-onset refractory status epilepticus. This definition of FIRES excludes febrile status epilepticus in infants. FIRES is a rare type of epileptic encephalopathy with rapidly progressive onset of seizures and a devastating prognosis, as drug-resistant epilepsy often follows without a latency period. Although the exact pathogenesis of FIRES has not been elucidated, a functional deficiency in the endogenous interleukin-1 receptor antagonist has been implicated in a genetic predisposition to FIRES. Dysregulation of the interleukin-1β–interleukin-1 receptor 1 (IL-1β–IL-1R1) signaling pathway appears to be involved in the pathogenesis of FIRES. In this review, the authors summarize the definition of FIRES, IL-1β–IL-1R1 signaling, the nucleotide-binding oligomerization domain the NLRP3 inflammasome, and IL-1 targeted therapy for FIRES.

New onset refractory status epilepticus: Summary of the NORSE Institute roundtable during the 2023 American Epilepsy Society meeting, Orlando, Florida

“…3 Given the compromised IL1 receptor antagonist (IL1ra) function reported in febrile infection-related epilepsy syndrome (FIRES), 4 a subset of NORSE with a prior febrile infection, 1 an in vivo murine model of FIRES was developed utilizing juvenile IL1radeficient mice. 5 Status epilepticus was induced by intrahippocampal kainic acid (IHKA), with or without LPS plus hyperthermia. The experimental fever followed by IHKA at P30 led to recurrent spontaneous subclinical status epilepticus and replicated salient clinical features of FIRES.…”