FEBRILE INFECTION RELATED EPILEPSY

OVERVIEW

Febrile infection related epilepsy syndrome (FIRES) has previously also been known as fever induced refractory epilepsy in school-aged children, devastating epileptic encephalopathy in school aged children (DESC) and acute encephalitis with refractory repetitive partial seizures (AERRPS). It is a severe post-infectious neurological disorder that presents with intractable status epilepticus in a previously normal child (or less commonly adult) after a febrile illness. If the patient survives, they have intellectual and motor impairment and ongoing intractable seizures.

The pathogenesis of this condition is unknown. Despite extensive investigation for an immune mechanism, anti-neuronal antibody testing on CSF and blood has shown inconsistent findings or been negative. There is no consistent response to immunotherapies such as high dose steroids, immunoglobulin or plasma exchange. Taken together this suggests that the pathogenesis is unlikely to be immune-mediated. Pleocytosis is commonly identified on initial CSF studies of these patients, lending support for an encephalitis, however extensive testing of patients has failed to identify a pathogen. Metabolic encephalopathy has been extensively considered in existing patients, however metabolic testing has been unrevealing.

Clinical context

This syndrome presents with onset of seizures between 2-17 years of age (median 8 years). There is a slight male predominance. A febrile upper respiratory or gastrointestinal illness precedes the onset of seizures by 1-14 days (median 4 days). Seizures rapidly progress to refractory status epilepticus. The condition has a high mortality, surviving patients require prolonged ventilator support and have cognitive and neurological impairment and ongoing seizures. There are limited responses to specific therapies such as the early use of the ketogenic diet.