Background/Purpose: Febrile-illness related epilepsy syndrome (FIRES), characterized by the emergence of super refractory status epilepticus (SRSE) in previously healthy children following a febrile illness, is a devastating neurological condition with significant morbidity and mortality. Dysregulated innate immunity has been implicated as a potential etiology. MRI findings of children with FIRES include early evidence of cytotoxicity and neuronal damage. Despite improvements in pediatric intensive care support and encouraging results from early initiation of ketogenic diet for the treatment of SRSE, there are no definitive immunomodulatory treatments to thwart damage and improve outcome of FIRES. Anakinra usage has been described in case reports in both acute and chronic phases of this condition. We describe MRI findings in one of the largest single center cohorts of children with FIRES who received anakinra.

Methods: After obtaining IRB approval we abstracted data on clinical presentation, MRI findings, anakinra usage, and outcomes of children diagnosed with FIRES treated with anakinra.

Results: Six children with FIRES were treated with anakinra per institutional best care practices adopted by a multi-disciplinary work group (ICU, neurology, and rheumatology). Demographic characteristics: 4 boys (66.7%), all from minority populations (50% Hispanic, 33.3% South East Asian, and 16.7% African-American), median age at presentation 7.5 years (IQR 5.7-14.3). Anakinra was started after a median 22.5 days of illness (IQR 12-32.5) with a maximum median anakinra dose of 7 mg/kg (IQR 3.8-7.9). Anakinra was added after other etiologies were ruled out and children did not respond to other agents. Anakinra was maintained for a median of 226 days (IQR 159.8-307.5)

Children were ventilated for a median of 42.5 days (IQR 29.5-94.5). Median ICU length of stay (LOS) was 45 days (IQR 31.5-116.3) and hospital LOS 106 days (IQR 45.8-162.3). All but one patient had chronic epilepsy at follow up (median 389 days, IQR 303-447.5) and all suffered cognitive deficits.  At last follow up all children had disability [mild (50%), moderate (33.3%) and severe (16.7%)].

MRI findings approximated reports of children with FIRES who had not received anakinra. Initial imaging was near normal but rapidly revealed volume loss, thinning of the Corpus collosum, and even ex-vacuo dilatation of the ventricular system. There was no breakdown of the blood brain barrier in any case. Gray (GM) and white matter (WM) lesions developed in all cases. GM involvement most commonly affected hippocampi. Children with more severe disease (increased seizures, longer anesthetic usage) had more pronounced findings. Findings at last MRI were at times discordant with functional outcomes.

Conclusion: Clinical outcomes in our single institution anakinra cohort were more robust then historical cohorts. Yet, all patients were found to have early and persistent imaging evidence of cytoxicity and neuronal damage. It is unclear if earlier introduction of anakinra in children with FIRES may dampen neuronal damage and improve outcomes. Larger retrospective and prospective projects are underway to elucidate the role of anakinra on FIRES disease course.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/does-anakinra-dampen-neuronal-damage-in-children-with-febrile-infection-related-epilepsy-syndrome-fires-a-single-center-review-of-neuroimaging/