Febrile infection-related epilepsy syndrome

Febrile infection-related epilepsy syndrome (FIRES), also known as acute encephalitis with refractory, repetitive partial seizures (AERRPS) or devastating epileptic encephalopathy in school-aged children (DESC), is a rare and severe epileptic encephalopathy that primarily affects previously healthy school-aged children. It is characterized by the acute onset of refractory status epilepticus following a nonspecific febrile illness, typically an upper respiratory or gastrointestinal infection. The febrile episode usually precedes seizure onset by 1 to 14 days. The seizures are extremely difficult to control and often require prolonged intensive care management, including multiple antiseizure medications and frequently anesthetic agents. FIRES predominantly affects the central nervous system, with seizures typically originating from the temporal and perisylvian regions of the brain. During the acute phase, patients experience nearly continuous or highly recurrent focal seizures that can evolve into bilateral tonic-clonic seizures, constituting super-refractory status epilepticus that may last weeks to months. MRI imaging may initially appear normal but can later show bilateral mesial temporal and insular cortical signal changes. The acute phase is associated with significant morbidity and mortality, with reported mortality rates of approximately 10-30% during the initial episode. Following the acute phase, the majority of survivors develop chronic drug-resistant epilepsy and significant cognitive impairment, including intellectual disability, behavioral difficulties, and memory deficits. The underlying etiology remains poorly understood, though an immune-mediated or inflammatory mechanism is suspected, as no consistent infectious agent or autoantibody has been identified. Treatment during the acute phase is largely supportive and includes aggressive antiseizure therapy; the ketogenic diet has shown some benefit in reducing seizure frequency during the acute phase and is often initiated early. Immunomodulatory therapies such as high-dose corticosteroids, intravenous immunoglobulin (IVIG), and plasma exchange have been tried with variable results. Anakinra, an interleukin-1 receptor antagonist, has shown promise in case reports and small series. Long-term management focuses on optimizing seizure control and rehabilitation for neurocognitive deficits.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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