P3C267: Febrile Infection-related Epilepsy Syndrome in a Previously Healthy Child: A Case Report

Introduction: Febrile infection-related epilepsy syndrome (FIRES) is a rare but devastating neurological condition characterized by the sudden onset of refractory seizures in previously healthy individuals, typically children, following brief febrile illnesses.

Case Description: A previously healthy 8-year-old boy was hospitalized with altered mental status after 1 day of fever, headache, and rash. Shortly thereafter, he developed intractable seizures resistant to maximum doses of multiple anti-seizure medications. A broad work-up for potential infectious, inflammatory, metabolic, toxic, and structural etiologies was unremarkable. An operating diagnosis of FIRES was implemented. Burst suppression was obtained after the patient was placed in a pentobarbital coma. He completed multiple courses of plasmapheresis, IVIG, and methylprednisolone without significant improvement. A ketogenic diet was trialed but stopped due to difficulty maintaining ketosis. After an episode of status epilepticus lasting > 60 minutes, additional labs were significant for elevated IL-8 in both CSF (2,041; normal <= 181) and serum (18; normal <= 9) as well as elevated serum IL-6 (45; normal <=8).

After obtaining negative PPD skin test, the IL-1 receptor antagonist Anakinra was started on hospital day 43. Subsequently, he experienced marked improvement with only 2 additional clinical seizures on prior to discharge on hospital day 58. He continues to thrive as an outpatient on Anakinra, Keppra, Onfi, Vimpat, and Epidiolex. Approximately 6 months since his first seizure, he is back in school, playing baseball, and has only mild lingering cognitive difficulties.

Discussion: FIRES is a rare but severe epileptic syndrome with significant morbidity and mortality. The exact cause of FIRES is unknown but thought to be related to an immune-mediated response following a viral or bacterial infection. FIRES has a slight male predominance and typically follows a biphasic pattern with an acute phase followed by chronic refractory epilepsy. Diagnosis is difficult due to the rarity of FIRES and lack of definitive biomarkers. No standardized treatment guidelines exist and treatment often consists of multiple antiepileptic drugs, immunomodulatory therapies, and ketogenic diets. Even with aggressive treatment, outcomes remain poor with a mortality rate of 10-30% and lasting intellectual disability and/or refractory epilepsy in up to 87% of survivors. This report discusses a rare case of a patient with FIRES who achieved significant seizure control with only mild neurocognitive deficits following treatment with Anakinra.

Conclusion: FIRES is an increasingly recognized neurological condition that causes severe, refractory epilepsy in previously healthy patients. Little is known about the etiology and pathogenesis of FIRES. Despite aggressive treatment, the prognosis remains poor with most patients experiencing long-term neurological deficits. Further research is needed to understand the pathophysiology of FIRES and to develop more effective treatments for this devastating condition.