Gabriella Abou-El-Kheir, B.S.
Medical Student
Baylor College of Medicine, United States
Disclosure information not submitted.
Thao Nguyen, M.D.
Instructor
Baylor College of Medicine, United States
Disclosure information not submitted.
Margo Hanerhoff, Pharm.D.
Clinical Pharmacist
Texas Children's Hospital, United States
Disclosure information not submitted.
James Riviello, M.D.
Professor
Baylor College of Medicine, United States
Disclosure information not submitted.
Eyal Muscal, M.D.
Associate Professor
Baylor College of Medicine, United States
Disclosure information not submitted.
Title: Clinical characteristics of anakinra-responsive febrile-infection related epilepsy syndrome
Introduction: Febrile-infection related epilepsy syndrome (FIRES), characterized by refractory status epilepticus (RSE), has significant ICU mortality and long-term disability. Anakinra is increasingly utilized to dampen neuroinflammation thought to contribute to the FIRES pathology. However, clinical characteristics associated with anakinra response is not well understood.
Methods: We collected patient demographics, PRISM III score and seizure evolution of 10 children with FIRES whom were treated with anakinra. The anti-seizure medication (ASM) regimen and seizure frequency over a 24-h period for the following epochs were also collected: 24 hrs prior to, 1 wk and 3 wks following anakinra therapy. Additionally, we collected serial serum CRP and cytokine profiles. Descriptive statistics was used for patient demographics, clinical and laboratory data. Wilcoxon rank sum test was used for continuous variables. We evaluated whether CRP or cytokine profiles were associated with anakinra response using logistic regression analyses accounting for multiple observations by patients.
Results: There were 2 initial seizure evolutions: A) Rapid progression to RSE requiring rapid escalation of anesthetic infusions (n=5), B) Gradual increases in seizure frequency with matching anesthetic infusion increase (n=5). PRISM III scores were higher for children with rapid RSE progression (median [25%-75%]: 14 [5-20] vs. 3 [3-4], p = 0.06). Following 1 wk of anakinra, 4 children had decreased seizures; anesthetic infusions were decreased in 5 children. Three children remained on pentobarbital infusions with 3 wks of anakinra and were categorized as non-responders. All had initial rapid RSE progression. Nine children had abnormal CRP absent a confirmed infection. Responders had higher odds for normal CRP with longer anakinra therapy (OR 1.03 95% CI: 1.01-1.05, p< 0.05). Additionally, the responders had increased odds for elevated IL-6 levels (OR 4.4, 95% CI: 1.4-13.3, p< 0.01); and decreased odds for elevated IL-10 levels (OR 0.03, 95% CI: 0.002-0.39, p< 0.01), adjusting for the time to anakinra initiation.
Conclusions: Children with gradual RSE progression, elevated serum IL-6, and normal IL-10 levels may have best response to anakinra. Full determination of response may require 3 wks of treatment, aided by normalization of CRP.