Objective:

NA

Background:

Febrile infection-related epilepsy syndrome (FIRES) is a severe subtype of new-onset refractory status epilepticus (NORSE) with unclear pathophysiology and limited treatments. We report a 2-year-old with FIRES who improved following combined immunotherapy with Anakinra (IL-1 receptor antagonist) and intravenous immunoglobulin (IVIG), suggesting therapeutic synergy.

Design/Methods:

A developmentally appropriate 2-year-old male, born outside the U.S. and immigrated a year ago, presented with viral gastroenteritis and discharged with supportive care. Five days later, he developed recurrent full-body stiffening and gaze deviation. Febrile, positive for Rhinovirus/Enterovirus and Streptococcus pneumoniae and a normal head CT, he was diagnosed with complex febrile seizure. The next day, recurrent seizures with desaturations required intubation. Blood, urine, CSF cultures, and meningitis panel were negative. Seizures were refractory to multiple antiseizure agents, high-dose methylprednisolone, ketamine, and pentobarbital coma. Plasmapheresis, pyridoxine challenge, propofol, intrathecal dexamethasone, and ketogenic diet for suspected FIRES were unsuccessful. EEG showed periodic discharges in the right occipito-temporal region evolving to ictal-interictal continuum. Bilateral T2 abnormalities in the extreme capsule–claustrum region on MRI suggested sequelae of status epilepticus or autoimmune etiology. Extensive autoimmune and infectious workups were negative. Whole genome sequencing revealed a maternally inherited SCN3A variant of uncertain significance; mitochondrial testing was negative. Cytokine profiling showed mildly elevated IL-2 receptor; hemophagocytic lymphohistiocytosis was ruled out. Anakinra was started on day 23; IVIG added nine days later, with complete seizure resolution after the first infusion. Recurrence occurred only during Anakinra taper a month after. His discharge regimen following 2 months of hospitalization included clobazam, perampanel, Anakinra, and IVIG. Seizures remain controlled, though developmental regression and behavioral aggression persist.

Results:

NA

Conclusions:

This case highlights a favorable response to combined immunotherapy in FIRES. Seizure recurrence during anakinra taper underscores its pivotal role, while improvement post-IVIG suggests synergistic benefit, emphasizing the need for further research into FIRES immunopathogenesis and combination strategies.