Abstracts

Rationale: Febrile-Infection Related Epilepsy Syndrome (FIRES) is characterized by explosive onset refractory status epilepticus (RSE) in previously healthy children. Survivors often develop chronic drug-resistant epilepsy and cognitive impairment. Several therapeutic regimens have been reported with limited success.


Methods: We performed a retrospective cohort study of 20 previously healthy children diagnosed with FIRES who were admitted to a free-standing children's hospital over the course of eleven years. Follow-up information was available for 17 patients with a median follow-up of 5.5 years. Clinical, electrographic, and neuroimaging data from the acute and chronic phase were reviewed.


Results: All children were managed with multiple anti-seizure medications (mean number of 4.55 +/- 1.07), anesthetic infusions (mean number of 2.35 +/- 0.72), first and second-line immunotherapy and ketogenic diet in the acute phase (figure 1). The hospital course was complicated by prolonged intubation (80% of patients requiring ventilation greater than 21 days) and prolonged duration of anesthetic coma (mean duration 32.6 +/-26.4 days). The overall survival rate at discharge was 90%.

The evolution into chronic epilepsy occurred without any silent period with all patients being discharged on 3-7 anti-seizure medications. With time, two-thirds of the patients developed poorly controlled drug-resistant epilepsy (~70% with the longest free interval less than three months) and five of whom were treated with vagal nerve stimulation (VNS) and two with responsive neurostimulation (RNS). There was one sudden unexpected death in epilepsy (SUDEP) two years from diagnosis.

All patients had some degree of cognitive decline at discharge. The mean modified Rankin scale (mRS) score at discharge was 3.9 +/- 1.6. However, with rehabilitation and therapy, nearly 60% were able to ambulate but only 25% had a good functional outcome (mRS scores of 0-2). There was no correlation between the degree of seizure control and functional outcomes. Additionally, prolonged intubation and anesthetic coma were not associated with poor outcomes (mRS scores of 3-6). Only five patients underwent formal neuropsychology evaluation at follow-up, of whom 2 were diagnosed with major neurocognitive deficit. No particular second or third-line immunotherapeutic agents were associated with a good neurological or functional outcome. The most common neurobehavioral diagnosis at follow-up was attention deficit hyperactivity disorder (ADHD) in eight patients.

The MRI findings upon admission are represented in Figure 2. All patients had an abnormal MRI at follow-up, with 35% showing diffuse cerebral volume loss and 45% showing bilateral hippocampal sclerosis. Cerebral volume loss did not correlate with poor functional outcome.


Conclusions: FIRES is characterized by high morbidity, chronic epilepsy with high seizure burden, and poor cognitive, functional and behavioral outcomes. Despite a small proportion of patients having a favorable outcome, there is a burning question on whether acute FIRES management is more about "winning the battle, but losing the war".


Funding: N/a