A multicenter retrospective case series of 22 children (16 male, 6 female) aged 3-15 years (median 6.5 yrs) with prolonged or recurrent seizures occurring 2-14 days (median 5 days) after a febrile respiratory (59%) or nonspecific infection is reported from Kiel University, Germany. The early clinical course was biphasic in 68%, the acute period of high seizure activity lasting 1-12 weeks (median 3 weeks). Despite enteral and parenteral anticonvulsant drugs, barbiturate-induced coma (64%), pyridoxine (18%), folinic acid (9%), and adjuvant immunotherapy (46%) for suspected cerebral inflammation, the outcome was uniformly poor. CSF revealed 2-42 cells/mcl (median 5 cells/mcl) and no pathogens. Serological and PCR tests for pathogens were negative. Inborn errors of metabolism, mitochondrial disease, including Alpers syndrome (POLG disease), were excluded. EEG showed diffuse slowing (41%) or multifocal discharges (59%). MRI or CT during acute phase was normal in 41% and showed altered signal intensities in hippocampus or temporal lobe in 41%. Follow-up MRI showed brain atrophy in 10 (50%) of surviving patients. Brain biopsies performed in 7 children (32%) showed gliosis but no evidence of inflammation. The median follow-up was 5 years (range 1-14 years). Two children died, 8 had persistent impaired consciousness, 8 had refractory epilepsy, 2 had behavior disorders, and 2 recovered. The authors propose the term “febrile infection-related epilepsy syndrome” (FIRES). [1]

COMMENT. Under different terminologies, this syndrome has been described in various case series, and was first reported in Brain [2] as “acute encephalopathies of obscure origin” by Lyons, Dodge, and Adams. “Lyons-Dodge-Adams syndrome” would be a suitable eponym. Further research concerning the etiology suggested by the current authors includes immune and nonimmune mechanisms (eg.channelopathies, antibodies against ion channels and receptors, and infection-triggered alterations of receptor expression). A special issue on acute encephalopathy/encephalitis in childhood appears in Brain Dev June 2010.