Fighting autoinflammation in FIRES: The role of interleukins and early immunomodulation

Febrile infection-related epilepsy syndrome (FIRES) is a challenging condition with unfavorable outcome in most cases. Preliminary evidence suggests that some interleukins, in particular IL-1 Receptor Antagonist (IL-1RA), could be elevated due to a functional deficiency of anti-inflammatory pathways. Therefore, treatment strategies acting on innate immunity could represent a targeted treatment. We describe the case of an 11-year-old child with super-refractory status epilepticus (SE), lasting more than two months. After being treated aggressively with antiseizure medications, anesthetics and empiric treatment for autoimmune encephalitis without success, she responded to anakinra and ketogenic diet. Escalation of the therapy was supported by the finding of a very high serum level of IL-1RA. This immunomodulatory approach allowed to discharge the child from intensive care 48 days after the SE onset. After more than one year follow-up the patient has moderate intellectual disability but with good language skills; she is seizure free and without motor deficits. This case suggests that serum IL-1RA serum levels may help to support treatment escalation. Moreover, anakinra and ketogenic diet represent encouraging immunomodulatory strategies which deserve further studies and could potentially have a synergistic effect. Finally, structured neuropsychological testing is an important outcome measure that will help to define the effectiveness of different treatment strategies. (C) 2022 The Authors. Published by Elsevier Inc.

Automated summary

Febrile infection-related epilepsy syndrome (FIRES) is a challenging condition with unfavorable outcome in most cases. Preliminary evidence suggests that elevated levels of certain interleukins may be related to a functional deficiency in anti-inflammatory pathways. Therefore, targeting innate immunity in treatment strategies may be effective. This case study describes a successful treatment approach using anakinra and a ketogenic diet for a patient with super-refractory status epilepticus (SE). High levels of IL-1RA in the patient's serum supported the escalation of therapy. After more than one year follow-up, the patient is seizure-free with moderate intellectual disability but good language skills. This case suggests that serum IL-1RA levels could be helpful in guiding treatment escalation and that anakinra and ketogenic diet show promise as immunomodulatory strategies.