Febrile infection-related epilepsy syndrome (FIRES): pathogenesis, treatment, and outcome: a multicenter study on 77 children.

Purpose: To explore the correlations between treatment modalities and selected disease parameters with outcome in febrile infection-related epilepsy syndrome (FIRES), a catastrophic epileptic encephalopathy with a yet undefined etiology.

Methods: We conducted a retrospective multicenter study on children who had been included in eight studies published between November 2001 and July 2010. Additional data were retrieved from six of the eight participating centers.

Key Findings: The 77 enrolled patients presented with prolonged refractory status epilepticus. A preceding febrile infection had been reported in 96% of them. Treatment modalities included antiepileptic drugs (a median of six), intravenous immunoglobulin (IVIG, 30 patients), steroids (29 patients), burst-suppression coma (BSC, 46 patients), and other less conventional agents. There was no evidence of efficacy for those treatment modalities except for IVIG (two patients), a ketogenic diet (one patient), and a prolonged cycle of barbiturate anesthesia coma (one patient). Nine patients (11.7%) died during the acute phase of FIRES. Only 12 of the 68 surviving patients (18%) retained normal cognitive level, but most of them had learning disabilities. Sixty-three patients (93%) had refractory epilepsy at follow-up. Cognitive levels at follow-up were significantly associated with duration of BSC (p = 0.005) and younger age at FIRES onset (p = 0.02).

Significance: The outcome of FIRES is poor. No therapeutic agent was efficacious in shortening the acute phase, with the possible exception of a ketogenic diet. Treatment by inducing a prolonged BSC was associated with a worse cognitive outcome.