Febrile Infection-Related Epilepsy Syndrome: Clinical Review and Hypotheses of Epileptogenesis

Febrile infection-related epilepsy syndrome (FIRES, AERRPS, or DESC) is one of the most severe, mostly irreversible, and presumably immune-mediated epileptic encephalopathies affecting healthy children. Refractory status epilepticus or a cluster of seizures start a few days after the onset of an acute febrile illness; however, encephalitis cannot be proved. Sequelae of FIRES are drug-resistant epilepsy and neuropsychological impairments occurring without latency. Clinical knowledge is limited because FIRES is sporadic and extremely rare. Therefore, based on literature and our data, this review includes clinical features, terminology, epidemiology, diagnostic criteria and procedures, differential diagnoses, acute and chronic therapeutic options, and outcome data. Particular attention is paid to the epileptogenesis. We hypothesize that FIRES is an immune but not an autoimmune disease and discuss GABAergic therapy at high doses, avoidance of burst-suppression coma, and early introduction of enteral or even parenteral ketogenic diet as the most promising treatment. The lack of evidence requires both a network and a multinational web-based clinical registry to define the clinical spectrum for improving diagnosis and treatment and at the very least, to clarify the cause of FIRES. We conclude that the term "fulminant inflammatory response epilepsy syndrome" may be more appropriate.