Proposal to optimize evaluation and treatment of Febrile infection‐related epilepsy syndrome (FIRES): A Report from FIRES workshop

Abstract

Febrile infection‐related epilepsy syndrome (FIRES) is a rare catastrophic epileptic encephalopathy that presents suddenly in otherwise normal children and young adults causing significant neurological disability, chronic epilepsy, and high rates of mortality. To suggest a therapy protocol to improve outcome of FIRES, workshops were held in conjunction with American Epilepsy Society annual meeting between 2017 and 2019. An international group of pediatric epileptologists, pediatric neurointensivists, rheumatologists and basic scientists with interest and expertise in FIRES convened to propose an algorithm for a standardized approach to the diagnosis and treatment of FIRES. The broad differential for refractory status epilepticus (RSE) should include FIRES, to allow empiric therapies to be started early in the clinical course. FIRES should be considered in all previously healthy patients older than two years of age who present with explosive onset of seizures rapidly progressing to RSE, following a febrile illness in the preceding two weeks. Once FIRES is suspected, early administrations of ketogenic diet and anakinra (the IL‐1 receptor antagonist that blocks biologic activity of IL‐1β) are recommended.

Sevoflurane as bridge therapy for plasma exchange and Anakinra in febrile infection–related epilepsy syndrome

“…18 In our case, anakinra was efficacious in maintaining seizure control after sevoflurane withdrawal, thus supporting its efficacy in FIRES. 10 The brain MRI revealed a diffuse cortical-subcortical brain atrophy, as is often reported in FIRES patients. 19 Whether brain atrophy is due to prolonged intractable seizures or the disease entity itself is still uncertain.…”

“… 5 , 6 , 9 Increasing evidence indicates anakinra, an IL‐1 receptor antagonist, as a safe and efficacious therapy in FIRES. 10 Anakinra efficacy has also been reported in improving recovery and long‐term outcomes; its early administration has therefore recently been recommended in children with suspected FIRES. 10 The efficacy of inhalational anesthetics has been reported in the treatment of RCSE.…”

“… 10 Anakinra efficacy has also been reported in improving recovery and long‐term outcomes; its early administration has therefore recently been recommended in children with suspected FIRES. 10 The efficacy of inhalational anesthetics has been reported in the treatment of RCSE. 11 Isoflurane is the only inhaled anesthetic recommended and is preferred over desflurane, xenon, and sevoflurane because of its higher rate of tolerability and hypothetical lower toxicity.…”

Transport study of interleukin-1 inhibitors using a human in vitro model of the blood-brain barrier

“…Likewise, traumatic brain injury (TBI) has a large inflammatory component, where both acute and long-lasting inflammation are present ( Kumar et al., 2015 ; Webster et al., 2017 ). Also, growing evidence suggests an important role for inflammatory pathways in refractory seizure disorders and epileptogenesis ( Koh et al., 2021 ; Vezzani et al., 2011 ; Webster et al., 2017 ).…”

“…Anti-IL-1 molecules are an emerging treatment approach for selected CNS disorders, including stroke, TBI and seizure disorders ( Helmy et al., 2014 ; Galea et al., 2018 ; Kenney-Jung et al., 2016 ; Koh et al., 2021 ). Therapeutic monoclonal antibodies targeting IL-1β (canakinumab) and IL-1α (bermekimab) have been developed.…”