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Epilepsia. 2017 Jun;58(6):1102-1111. doi: 10.1111/epi.13750. Epub 2017 Apr 27.

Plasma cytokines associated with febrile status epilepticus in children: A potential biomarker for acute hippocampal injury.

Author information

1
Department of Pediatrics (Neurology), Duke Children's Hospital, Durham, North Carolina, U.S.A.
2
Departments of Neurology and Pediatrics, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, U.S.A.
3
Department of Epidemiology and GH Sergievsky Center, Columbia University, New York, New York, U.S.A.
4
Department of Neurology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, U.S.A.
5
Department of Pediatrics (Neurology), Children's Hospital Los Angeles, Los Angeles, California, U.S.A.
6
Department of Neurology, Children's Hospital of The King's Daughters and Eastern Virginia Medical School, Norfolk, Virginia, U.S.A.
7
Department of Neurology, Virginia Commonwealth University, Richmond, Virginia, U.S.A.
8
Department of Biostatistics and International Epilepsy Consortium, Virginia Commonwealth University, Richmond, Virginia, U.S.A.

Abstract

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).

KEYWORDS:

Cytokine; Febrile status epilepticus; Hippocampal injury; Interleukin; Mesial temporal lobe epilepsy

PMID:
28448686
PMCID:
PMC5482499
DOI:
10.1111/epi.13750
[Indexed for MEDLINE]
Free PMC Article

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