Febrile infection–related epilepsy syndrome (FIRES): A nonencephalitic encephalopathy in childhood

Abstract

SUMMARYEncephalitis is generally presumed, even when seizures follow banal febrile infection, and pathogen detection in cerebrospinal fluid fails. This retrospective multicenter case series reports on 22 previously healthy children aged 3-15 years (median 6.5 years) with prolonged or recurrent seizures occurring 2-14 days (median 5 days) after fever onset (19 children with respiratory or nonspecific infections). Cerebrospinal fluid studies revealed 2-42 cells/ll (median 5 cells/ll) and no pathogens. Electroencephalography showed diffuse slowing or multifocal discharges. Neuroimaging demonstrated normal findings in 10 children. Brain biopsies were performed in seven children showing gliosis but no inflammation. Anesthetic barbiturates were used in 14 children with refractory status epilepticus, and immunotherapy in 9. Two children died, eight remained in a state of impaired consciousness, eight developed therapy-refractory epilepsies, two had behavioral disturbances, and two recovered. The lack of evidence for encephalitis suggests another infectionrelated pathogenesis of this disastrous epileptic encephalopathy. Therefore, we propose the term ''febrile infection-related epilepsy syndrome'' (FIRES).

Cognitive Outcomes in Febrile Infection-Related Epilepsy Syndrome Treated With the Ketogenic Diet

“…[1][2][3] At presentation, SE lasts for weeks and may result in death 4 or evolve into treatment-resistant epilepsy with associated severe intellectual disabilities. 1 The underlying pathophysiology may be immune-mediated, but adjunctive therapies to anticonvulsant medications, including immunotherapy with intravenous immunoglobulin, steroids, and plasmapheresis, have been used with limited success.…”

Febrile Infection-Related Epilepsy Syndrome (Fires) in Schoolchildren: Literature Review and Own Observations

“…• «острый энцефалит с устойчиво повторяю-щимися парциальными приступами» (acute encephalitis with refractory repetitive partial seizures -AERRPS) [24]; • «эпилептический статус с упорной лихорад-кой ввиду предполагаемого энцефалита» (severe refractory status epilepticus due to presumed encephalitis) [18]; • «идиопатическая злокачественная эпилепти-ческая энцефалопатия» (idiopathic catastrophic epileptic encephalopathy) [17]; • «первичный рефрактерный эпилептический статус» (new-onset refractory status epilepticus -NORSE) [2]; • «разрушительная эпилептическая энцефало-патия у детей школьного возраста» (devastating epileptic encephalopathy in school-aged children -DESC) [17]; • «синдром эпилепсии, индуцированный феб-рильной инфекцией» (febrile infection-related epilepsy syndrome -FIRES) [11]; • «эпилептическая энцефалопатия, индуциро-ванная лихорадкой, у детей школьного возра-ста» (fever-induced refractory epileptic encephalopathy of school-age children) [21]. На территории Европы чаще используется термин FIRES, а врачи Японии предпочитают AERRPS [6].…”

“…У части пациентов в ЦСЖ опре-деляли повышение неоптерина, которое наблюдается при цитотоксическом иммунном ответе (острые ви-русные инфекции, аутоиммунные заболевания и др.) [21]. Также в некоторых случаях отмечалось повыше-ние таких антител, как анти-GluR2 (антитело к субъе-динице NMDA-рецептора) и анти-GAD [8,24].…”

Epileptic Syndromes With Possible Immunological Mechanisms (Rasmussen Encephalitis, FIRES, West Syndrome, Landau-Kleffner Syndrome)

“…[44] Hastaların yaklaşık yarısında ilk nöbet geliştiğinde ateş kaybolmuştur. [39] Nöbet-lerde baş deviasyonu gibi fokal başlangıç ve otonom bulgular olabilir.…”

“…[40][41][42][43][44][45][46][47][48] Bu özgün sendrom, günümüze kadar, yeni-başlangıçlı dirençli status epileptikus (New-Onset Refractory Status Epilepticus (NORSE)), okul çağı çocuklarının yıkıcı epileptik ensefalopatisi (Devastating Epileptic Encephalopathy in School Aged Children (DESC)), dirençli, tekrarlayıcı parsiyel nöbetlerle seyreden akut ensefalit (Acute Encephalitis with Refractory Repetitive Partial Seizures (AERRPS)), ateşli enfeksiyonla ilişkili epilepsi sendromu (febrile infection-related epilepsy syndrome (FIRES)) ve okul çağı çocuklarının ateşle tetiklenen dirençli epileptik ensefalopatisi (Fever-Induced Refractory Epileptic Encephalopathy of School-Age Children (FIRES) olmak üzere çok çeşitli başlıklar altında tartışılmıştır. [39,42,44,47,49,50] Son yıllarda FIRES en çok kullanılan ve kabul gören tanım olmuştur.…”