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

FEBSTAT Investigator Team

Research output: Contribution to journalArticle

18 Citations (Scopus)

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).

Original languageEnglish (US)
Pages (from-to)1102-1111
Number of pages10
JournalEpilepsia
Volume58
Issue number6
DOIs
StatePublished - Jun 1 2017

Fingerprint

Status Epilepticus
Interleukins
Fever
Biomarkers
Cytokines
Wounds and Injuries
Interleukin-8
Interleukin-6
Interleukin-1
Magnetic Resonance Imaging
Febrile Seizures
Temporal Lobe Epilepsy
Epidermal Growth Factor

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

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

In: Epilepsia, Vol. 58, No. 6, 01.06.2017, p. 1102-1111.

Research output: Contribution to journalArticle

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title = "Plasma cytokines associated with febrile status epilepticus in children: A potential biomarker for acute hippocampal injury",
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",
author = "{FEBSTAT Investigator Team} and Gallentine, {William B.} and Shlomo Shinnar and Hesdorffer, {Dale C.} and Leon Epstein and Nordli, {Douglas R.} and Lewis, {Darrell V.} and Frank, {L. Matthew} and Syndi Seinfeld and Shinnar, {Ruth C.} and Karen Cornett and Binyi Liu and Moshe, {Solomon L.} and Shumei Sun and Jacqueline Bello and Bello, {Jacqueline A.} and Gomes, {William A.} and Sharyn Katz and Ann Mancini and David Masur and Ruth Shinnar and Erica Weiss and Weiss, {Erica F.} and Stephen Chan and Darrell Lewis and Melanie Bonner and William Gallentine and James MacFall and James Provenzale and Allen Song and James Voyvodic and Yuan Xu and Joanne Andy and Terrie Conklin and Susan Grasso and Powers, {Connie S.} and David Kushner and Susan Landers and {Van de Water}, Virginia and Bush, {Brian J.} and Davis, {Lori L.} and Xiaoyan Deng and Christiane Rogers and Sabo, {Cynthia Shier} and John Curran and Epstein, {Leon G.} and Andrew Kim and Julie Rinaldi and Emilia Bagiella and Tanya Brazemore and James Culbert",
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T1 - Plasma cytokines associated with febrile status epilepticus in children

T2 - A potential biomarker for acute hippocampal injury

AU - FEBSTAT Investigator Team

AU - Gallentine, William B.

AU - Shinnar, Shlomo

AU - Hesdorffer, Dale C.

AU - Epstein, Leon

AU - Nordli, Douglas R.

AU - Lewis, Darrell V.

AU - Frank, L. Matthew

AU - Seinfeld, Syndi

AU - Shinnar, Ruth C.

AU - Cornett, Karen

AU - Liu, Binyi

AU - Moshe, Solomon L.

AU - Sun, Shumei

AU - Bello, Jacqueline

AU - Bello, Jacqueline A.

AU - Gomes, William A.

AU - Katz, Sharyn

AU - Mancini, Ann

AU - Masur, David

AU - Shinnar, Ruth

AU - Weiss, Erica

AU - Weiss, Erica F.

AU - Chan, Stephen

AU - Lewis, Darrell

AU - Bonner, Melanie

AU - Gallentine, William

AU - MacFall, James

AU - Provenzale, James

AU - Song, Allen

AU - Voyvodic, James

AU - Xu, Yuan

AU - Andy, Joanne

AU - Conklin, Terrie

AU - Grasso, Susan

AU - Powers, Connie S.

AU - Kushner, David

AU - Landers, Susan

AU - Van de Water, Virginia

AU - Bush, Brian J.

AU - Davis, Lori L.

AU - Deng, Xiaoyan

AU - Rogers, Christiane

AU - Sabo, Cynthia Shier

AU - Curran, John

AU - Epstein, Leon G.

AU - Kim, Andrew

AU - Rinaldi, Julie

AU - Bagiella, Emilia

AU - Brazemore, Tanya

AU - Culbert, James

PY - 2017/6/1

Y1 - 2017/6/1

N2 - 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).

AB - 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).

KW - Cytokine

KW - Febrile status epilepticus

KW - Hippocampal injury

KW - Interleukin

KW - Mesial temporal lobe epilepsy

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