Plasma cytokines associated with febrile status epilepticus in children: A potential biomarker for acute hippocampal injury.
Journal Article (Journal Article)
OBJECTIVE: Our aim was to explore the association between plasma cytokines and febrile status epilepticus (FSE) in children, as well as their potential as biomarkers of acute hippocampal injury. METHODS: Analysis was performed on residual samples of children with FSE (n = 33) as part of the Consequences of Prolonged Febrile Seizures in Childhood study (FEBSTAT) and compared to children with fever (n = 17). Magnetic resonance imaging (MRI) was obtained as part of FEBSTAT within 72 h of FSE. Cytokine levels and ratios of antiinflammatory versus proinflammatory cytokines in children with and without hippocampal T2 hyperintensity were assessed as biomarkers of acute hippocampal injury after FSE. RESULTS: Levels of interleukin (IL)-8 and epidermal growth factor (EGF) were significantly elevated after FSE in comparison to controls. IL-1β levels trended higher and IL-1RA trended lower following FSE, but did not reach statistical significance. Children with FSE were found to have significantly lower ratios of IL-1RA/IL-1β and IL-1RA/IL-8. Specific levels of any one individual cytokine were not associated with FSE. However, lower ratios of IL-1RA/IL-1β, IL-1RA/1L-6, and IL-1RA/ IL-8 were all associated with FSE. IL-6 and IL-8 levels were significantly higher and ratios of IL-1RA/IL-6 and IL-1RA/IL-8 were significantly lower in children with T2 hippocampal hyperintensity on MRI after FSE in comparison to those without hippocampal signal abnormalities. Neither individual cytokine levels nor ratios of IL-1RA/IL-1β or IL-1RA/IL-8 were predictive of MRI changes. However, a lower ratio of IL-1RA/IL-6 was strongly predictive (odds ratio [OR] 21.5, 95% confidence interval [CI] 1.17-393) of hippocampal T2 hyperintensity after FSE. SIGNIFICANCE: Our data support involvement of the IL-1 cytokine system, IL-6, and IL-8 in FSE in children. The identification of the IL-1RA/IL-6 ratio as a potential biomarker of acute hippocampal injury following FSE is the most significant finding. If replicated in another study, the IL-1RA/IL-6 ratio could represent a serologic biomarker that offers rapid identification of patients at risk for ultimately developing mesial temporal lobe epilepsy (MTLE).
Full Text
Duke Authors
- Bonner, Melanie Jean
- Lewis Jr., Darrell Vincent
- Provenzale, James Michael
- Song, Allen W
- Voyvodic, James T.
Cited Authors
- Gallentine, WB; Shinnar, S; Hesdorffer, DC; Epstein, L; Nordli, DR; Lewis, DV; Frank, LM; Seinfeld, S; Shinnar, RC; Cornett, K; Liu, B; Moshé, SL; Sun, S; FEBSTAT Investigator Team,
Published Date
- June 2017
Published In
Volume / Issue
- 58 / 6
Start / End Page
- 1102 - 1111
PubMed ID
- 28448686
Pubmed Central ID
- PMC5482499
Electronic International Standard Serial Number (EISSN)
- 1528-1167
Digital Object Identifier (DOI)
- 10.1111/epi.13750
Language
- eng
Conference Location
- United States