P2.C049: Outcome of a 4-Year-Old Male with Febrile Infection-Related Epilepsy Syndrome: A Case Report

Introduction: Febrile Infection-Related Epilepsy Syndrome (FIRES) is a subtype of New-Onset Refractory Status Epilepticus (NORSE). Both are exceedingly rare clinical presentations that present with the onset of refractory status epilepticus (RSE) without a clearly identifiable cause such as an active structural, metabolic, or toxic etiology. Diagnosis of FIRES requires a previous febrile infection starting between 24 hours and up to 2 weeks before onset of RSE.

Case Description: A 4-year-old, previously healthy boy presented with altered mental status and unsteady gait 5 days after having an upper respiratory infection and fever of 102°F. Physical exam and basic labs were unremarkable, as were an initial MRI and CSF studies. An electroencephalogram (EEG) showed generalized slowing. 5 days after admission to the hospital, the patient began to have repetitive focal seizures with evolution to bilateral tonic-clonic seizures. Despite multiple anti-seizure medications, steroids, and IVIG, the patient continued to have refractory seizures, and his condition progressed to status epilepticus. Care was escalated to the ICU where he was intubated, continued on multiple anti-seizure medications, and started on a midazolam infusion, requiring 0.4 mg/kg/hr in an attempt to control seizures, but he continued to have breakthrough seizures. Repeat CSF studies continued to reveal no abnormalities with extensive negative infectious workup; however, a repeat MRI showed symmetric hyperintensities within the bilateral external capsule, periventricular and deep white matter, indicating a potential toxic-metabolic etiology. At this time, the patient met criteria for FIRES and was placed on a ketogenic diet and anakinra, an IL-1 inhibitor. Induction of a barbiturate coma was avoided due to association with worse outcomes in FIRES. Seizures resolved and the patient was successfully extubated after 2 weeks. He was downgraded and started intensive inpatient rehabilitation. Labs were significant for elevated serum levels of IL-6 and IL-10. After spending 68 days in the hospital, the patient was discharged. He remains on anakinra, a ketogenic diet, Epidiolex, lacosamide, clonazepam, levetiracetam, perampanel, and tetrabenazine. Since discharge, he has been having approximately 0-1 seizure-like events per day lasting about 1 minute, and occasionally will have up to 7 seizure-like events per day. Events include full movement of the mouth, twitching and pulling of the face, and behavioral arrest.

Discussion: NORSE and FIRES are uncommon, but difficult diagnoses to manage clinically. Etiology, course, and treatment is poorly understood. These diagnoses are associated with a high morbidity and mortality; therefore, clinicians must have a high index of suspicion for new-onset seizures that are refractory to standard antiepileptics.

Conclusion: Febrile Infection-Related Epilepsy Syndrome is a rare diagnosis with high morbidity and mortality but may respond to immunomodulators such as IL-1 inhibitors and a ketogenic diet.