Semin Neurol 2020; 40(02): 263-272
DOI: 10.1055/s-0040-1708503
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Extinguishing Febrile Infection-Related Epilepsy Syndrome: Pipe Dream or Reality?

Eric T. Payne
1  Section of Neurology, Department of Pediatrics, Alberta Children's Hospital, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Sookyong Koh
2  Division of Neurology, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
Elaine C. Wirrell
3  Division of Epilepsy, Department of Neurology, Mayo Clinic, Rochester, Minnesota
4  Division of Child and Adolescent Neurology, Department of Neurology, Mayo Clinic, Rochester, Minnesota
› Author Affiliations
Further Information

Publication History

Publication Date:
17 March 2020 (online)


Febrile infection-related epilepsy syndrome (FIRES) is a rare and devastating epileptic encephalopathy with historically abysmal neurocognitive outcomes, including a high incidence of mortality. It tends to affect children and young adults and is characterized by superrefractory status epilepticus following a recent febrile illness. Growing evidence suggests a heterogeneous etiology resulting in fulminant nonantibody-mediated neuroinflammation. For some children with FIRES, this aberrant neuroinflammation appears secondary to a functional deficiency in the endogenous interleukin-1 receptor antagonist. A precise etiology has not been identified in all FIRES patients, and current treatments are not always successful. Limited treatment evidence exists to guide choice, dosing, and duration of therapies. However, the ketogenic diet and certain targeted immunomodulatory treatments, including anakinra, appear safe and have been associated with relatively excellent clinical outcomes in some FIRES patients. Future prospective multicenter collaborative studies are needed to further delineate the FIRES heterogeneous disease pathophysiology and to determine the safety and efficacy of treatment strategies through a robust measurement of neurocognitive outcomes.