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Elucidation of the pathophysiology of refractory status epilepticus by comprehensive inflammation analysis and development of new diagnosis and treatment methods

Research Project

Project/Area Number 18K08918
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55060:Emergency medicine-related
Research InstitutionKobe University

Principal Investigator

Nagase Hiroaki  神戸大学, 医学研究科, 特命教授 (80571968)

Co-Investigator(Kenkyū-buntansha) 森岡 一朗  日本大学, 医学部, 教授 (80437467)
篠原 正和  神戸大学, 医学研究科, 准教授 (80437483)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords熱性けいれん / てんかん重積状態 / 急性脳症 / 炎症 / サイトカイン / GDF-15 / てんかん重積 / けいれん重積 / 炎症性サイトカイン
Outline of Final Research Achievements

Febrile status epilepticus (FSE) and refractory FSE (fRSE) are common in pediatric emergency, and are often diagnosed as acute encephalopathy with serious outcomes such as death and sequelae. In this study, we found that in pediatric patients with fRSE, inflammatory cytokines peaked within 24 hours of onset and then decreased, regardless of the final diagnosis or outcome. We also revealed that the inflammation-related protein GDF15 reported as an excellent pathological and prognostic markers such as sepsis was also significantly elevated in FSE, peaked out within 12 hours of onset. Furthermore, the peak value of GDF-15 within 6 hours of onset was shown to be associated with the neurological sequelae in children with FSE.

Academic Significance and Societal Importance of the Research Achievements

FSE, fRSEと炎症性サイトカインが関連することはこれまでにも報告されており,抗炎症治療が行われているが,発症24時間以内にはすでにピークアウトしていることが本研究で初めて明らかになった.さらに炎症関連蛋白であるGDF-15は発症12時間以内にピークアウトしていること,発症6時間以内の値が転帰と関連することも今回初めて明らかとなった.炎症のピークとなる時間が6-12時間であることが明らかになったことで,今後fRSEに対する抗炎症治療の有効性、ゴールデンタイムの解明につながる成果であると考えた。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (27 results)

All 2021 2020 2019 2018

All Journal Article (15 results) (of which Peer Reviewed: 15 results) Presentation (12 results)

  • [Journal Article] Elevated cytokine, chemokine, and growth and differentiation factor-15 levels in hemorrhagic shock and encephalopathy syndrome: A retrospective observational study2021

    • Author(s)
      Yamaguchi Hiroshi、Nishiyama Masahiro、Tokumoto Shoichi、Ishida Yusuke、Tomioka Kazumi、Aoki Kazunori、Seino Yusuke、Toyoshima Daisaku、Takeda Hiroki、Kurosawa Hiroshi、Sakuma Hiroshi、Tada Hiroko、Nozu Kandai、Maruyama Azusa、Tanaka Ryojiro、Iijima Kazumoto、Nagase Hiroaki
    • Journal Title

      Cytokine

      Volume: 137 Pages: 155324-155324

    • DOI

      10.1016/j.cyto.2020.155324

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prediction of AESD and neurological sequelae in febrile status epilepticus2021

    • Author(s)
      Nishiyama M, Ishida Y, Yamaguchi H, Tokumoto S, Tomioka K, Hongo H, Toyoshima D, Maruyama A, Kurosawa H, Tanaka R, Nozu K, Iijima K, Nagase H
    • Journal Title

      Brain Dev

      Volume: 43 Issue: 5 Pages: 616-625

    • DOI

      10.1016/j.braindev.2021.01.004

    • NAID

      120007028964

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Early non-convulsive seizures are associated with the development of acute encephalopathy with biphasic seizures and late reduced diffusion2021

    • Author(s)
      Maruyama A, Tokumoto S, Yamaguchi H, Ishida Y, Tanaka T, Tomioka K, Nishiyama M, Fujita K, Toyoshima D, Nagase H
    • Journal Title

      Brain Dev

      Volume: 43 Issue: 4 Pages: 548-555

    • DOI

      10.1016/j.braindev.2020.11.012

    • NAID

      120007002555

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detailed characteristics of acute encephalopathy with biphasic seizures and late reduced diffusion: 18-year data of a single-center consecutive cohort.2020

    • Author(s)
      Yamaguchi H, Nishiyama M, Tokumoto S, Ishida Y, Tomioka K, Aoki K, Seino Y, Toyoshima D, Takeda H, Kurosawa H, Nozu K, Maruyama A, Tanaka R, Iijima K, Nagase H.
    • Journal Title

      J Neurol Sci.

      Volume: 411 Pages: 116684-116684

    • DOI

      10.1016/j.jns.2020.116684

    • NAID

      120006846525

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Detailed clinical course of fatal acute encephalopathy in children.2019

    • Author(s)
      Tomioka K, Nishiyama M, Nagase H, Ishida Y, Tanaka T, Tokumoto S, Yamaguchi H, Toyoshima D, Maruyama A, Fujita K, Aoki K, Seino Y, Nozu K, Nishimura N, Kurosawa H, Iijima K.
    • Journal Title

      Brain Dev.

      Volume: 41 Issue: 8 Pages: 691-698

    • DOI

      10.1016/j.braindev.2019.04.012

    • NAID

      120006894043

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Predicting the outcomes of targeted temperature management for children with seizures and/or impaired consciousness accompanied by fever without known etiology2019

    • Author(s)
      Tanaka Tsukasa、Nagase Hiroaki、Yamaguchi Hiroshi、Ishida Yusuke、Tomioka Kazumi、Nishiyama Masahiro、Toyoshima Daisaku、Maruyama Azusa、Fujita Kyoko、Nozu Kandai、Nishimura Noriyuki、Kurosawa Hiroshi、Tanaka Ryojiro、Iijima Kazumoto
    • Journal Title

      Brain and Development

      Volume: 印刷中 Issue: 7 Pages: 604-613

    • DOI

      10.1016/j.braindev.2019.03.007

    • NAID

      120006733176

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Acute encephalopathy with biphasic seizures and late reduced diffusion accompanied by Takotsubo cardiomyopathy2019

    • Author(s)
      Yamaguchi Hiroshi、Nagase Hiroaki、Yoshida Shinobu、Tokumoto Shoichi、Hayashi Ken、Toyoshima Daisaku、Kurosawa Hiroshi、Tanaka Toshikatsu、Maruyama Azusa、Iijima Kazumoto
    • Journal Title

      Brain and Development

      Volume: 41 Issue: 3 Pages: 305-309

    • DOI

      10.1016/j.braindev.2018.10.002

    • NAID

      120006846523

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lipid and thyroid hormone levels in children with epilepsy treated with levetiracetam or carbamazepine: A prospective observational study2019

    • Author(s)
      Nishiyama Masahiro、Takami Yuichi、Ishida Yusuke、Tomioka Kazumi、Tanaka Tsukasa、Nagase Hiroaki、Nakagawa Taku、Tokumoto Shoichi、Yamaguchi Hiroshi、Toyoshima Daisaku、Maruyama Azusa、Nozu Kandai、Nishimura Noriyuki、Iijima Kazumoto
    • Journal Title

      Epilepsy & Behavior

      Volume: 90 Pages: 15-19

    • DOI

      10.1016/j.yebeh.2018.11.003

    • NAID

      120006599198

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nonconvulsive Seizure Detection by Reduced-Lead Electroencephalography in Children with Altered Mental Status in the Emergency Department2019

    • Author(s)
      Yamaguchi Hiroshi、Nagase Hiroaki、Nishiyama Masahiro、Tokumoto Shoichi、Ishida Yusuke、Tomioka Kazumi、Tanaka Tsukasa、Fujita Kyoko、Toyoshima Daisaku、Nishimura Noriyuki、Kurosawa Hiroshi、Nozu Kandai、Maruyama Azusa、Tanaka Ryojiro、Iijima Kazumoto
    • Journal Title

      The Journal of Pediatrics

      Volume: 207 Pages: 213-219

    • DOI

      10.1016/j.jpeds.2018.11.019

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical time course of pediatric acute disseminated encephalomyelitis2019

    • Author(s)
      Nishiyama Masahiro、Nagase Hiroaki、Tomioka Kazumi、Tanaka Tsukasa、Yamaguchi Hiroshi、Ishida Yusuke、Toyoshima Daisaku、Fujita Kyoko、Maruyama Azusa、Sasaki Kaori、Oyazato Yoshinobu、Nakagawa Taku、Takami Yuichi、Nozu Kandai、Nishimura Noriyuki、Nakashima Ichiro、Iijima Kazumoto
    • Journal Title

      Brain and Development

      Volume: 41 Issue: 6 Pages: 531-537

    • DOI

      10.1016/j.braindev.2019.02.011

    • NAID

      120006645705

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Acute focal bacterial nephritis characterized by acute encephalopathy with biphasic seizures and late reduced diffusion2018

    • Author(s)
      Yamaguchi Hiroshi、Nagase Hiroaki、Ito Yusuke、Matsunoshita Natsuki、Mizutani Makoto、Matsushige Takeshi、Ishida Yusuke、Toyoshima Daisaku、Kasai Masashi、Kurosawa Hiroshi、Maruyama Azusa、Iijima Kazumoto
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 24 Issue: 11 Pages: 932-935

    • DOI

      10.1016/j.jiac.2018.04.007

    • NAID

      120006846522

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Early risk factors for mortality in children with seizure and/or impaired consciousness accompanied by fever without known etiology2018

    • Author(s)
      Tomioka Kazumi、Nagase Hiroaki、Tanaka Tsukasa、Nishiyama Masahiro、Yamaguchi Hiroshi、Ishida Yusuke、Toyoshima Daisaku、Maruyama Azusa、Fujita Kyoko、Taniguchi-Ikeda Mariko、Nozu Kandai、Morioka Ichiro、Nishimura Noriyuki、Kurosawa Hiroshi、Uetani Yoshiyuki、Iijima Kazumoto
    • Journal Title

      Brain and Development

      Volume: 印刷中 Issue: 7 Pages: 552-557

    • DOI

      10.1016/j.braindev.2018.02.015

    • NAID

      120006629313

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Diurnal occurrence of complex febrile seizure and their severity in pediatric patients needing hospitalization2018

    • Author(s)
      Yamaguchi Hiroshi、Nagase Hiroaki、Ishida Yusuke、Toyoshima Daisaku、Maruyama Azusa、Tomioka Kazumi、Tanaka Tsukasa、Nishiyama Masahiro、Fujita Kyoko、Mariko Taniguchi-Ikeda、Nozu Kandai、Morioka Ichiro、Nishimura Noriyuki、Kurosawa Hiroshi、Takada Satoshi、Uetani Yoshiyuki、Iijima Kazumoto
    • Journal Title

      Epilepsy & Behavior

      Volume: 80 Pages: 280-284

    • DOI

      10.1016/j.yebeh.2018.01.015

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Infantile spasms related to a 5q31.2-q31.3 microdeletion including PURA2018

    • Author(s)
      Shimojima Keiko、Okamoto Nobuhiko、Ohmura Kayo、Nagase Hiroaki、Yamamoto Toshiyuki
    • Journal Title

      Human Genome Variation

      Volume: 5 Issue: 1 Pages: 18007-18007

    • DOI

      10.1038/hgv.2018.7

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fosphenytoin vs. continuous midazolam for pediatric febrile status epilepticus2018

    • Author(s)
      Nishiyama Masahiro、Nagase Hiroaki、Tomioka Kazumi、Tanaka Tsukasa、Yamaguchi Hiroshi、Ishida Yusuke、Toyoshima Daisaku、Fujita Kyoko、Maruyama Azusa、Kurosawa Hiroshi、Uetani Yoshiyuki、Nozu Kandai、Taniguchi-Ikeda Mariko、Morioka Ichiro、Takada Satoshi、Iijima Kazumoto
    • Journal Title

      Brain and Development

      Volume: 40 Issue: 10 Pages: 884-890

    • DOI

      10.1016/j.braindev.2018.08.001

    • NAID

      120006599197

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 急性脳症の予測基準の有用性の検証(第1報) AESD予測のために開発された基準の別コホートにおける再検証2020

    • Author(s)
      石田 悠介, 西山 将広, 徳元 翔一, 山口 宏, 冨岡 和美, 豊嶋 大作, 丸山 あずさ, 飯島 一誠, 永瀬 裕朗
    • Organizer
      第62回日本小児神経学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 急性脳症の予測基準の有用性の検証(第2報) 後遺症またはAESD予測のために開発された基準の比較2020

    • Author(s)
      西山 将広, 石田 悠介, 徳元 翔一, 冨岡 和美, 山口 宏, 豊嶋 大作, 丸山 あずさ, 飯島 一誠, 永瀬 裕朗
    • Organizer
      第62回日本小児神経学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 有熱時けいれん/意識障害の発症6時間以内のサイトカインによる予後予測 血清IL-1RA,IL-10の可能性2020

    • Author(s)
      冨岡 和美, 西山 将広, 山口 宏, 石田 悠介, 徳元 翔一, 豊嶋 大作, 丸山 あずさ, 服部 有香, 親里 嘉展, 中川 卓, 高見 勇一, 多田 弘子, 佐久間 啓, 飯島 一誠, 永瀬 裕朗
    • Organizer
      第62回日本小児神経学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 小児けいれん重積に対する脳波モニタリング下ミダゾラム昏睡療法の有効性と安全性2019

    • Author(s)
      石田悠介、冨岡和美、田中 司、西山将広、 永瀬裕朗、徳元翔一、山口 宏、豊嶋大作、丸山あずさ、黒澤寛史、飯島一誠
    • Organizer
      第61回日本小児神経学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 時間単位で評価した急性脳症のサイトカイン動態解析:第1報2019

    • Author(s)
      冨岡和美、西山将広、永瀬裕朗 、石田悠介、田中司、徳元翔一、山口宏、豊嶋大作、丸山あずさ、黒澤寛史、多田弘子、佐久間啓、飯島一誠
    • Organizer
      第61回日本小児神経学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 時間単位で評価した急性脳症のサイトカイン動態解析:第2報2019

    • Author(s)
      西山将広、冨岡和美、永瀬裕朗 、石田悠介、田中司、徳元翔一、山口宏、豊嶋大作、丸山あずさ、起塚庸、親里嘉展 、高見勇一、多田弘子、佐久間啓、飯島一誠
    • Organizer
      第61回日本小児神経学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 出血性ショック脳症症候群(HSES)7 症例の詳細な臨床経過の検討2019

    • Author(s)
      山口宏、徳元翔一、西山将広、豊嶋大作、永瀬裕朗 、丸山あずさ、飯島一誠
    • Organizer
      第61回日本小児神経学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 有熱性難治性けいれん重積の治療プロトコル変遷による短期的予後の検討2019

    • Author(s)
      徳元翔一、山口宏、豊嶋大作、丸山あずさ、石田悠介、冨岡和美、田中司、西山将広、永瀬裕朗、飯島一誠
    • Organizer
      第61回日本小児神経学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 出血性ショック脳症症候群(HSES)7症例の詳細な臨床経過の検討2019

    • Author(s)
      山口宏,徳元翔一,西山将広,豊嶋大作,永瀬裕朗,丸山あずさ,飯島一誠
    • Organizer
      第61回日本小児神経学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 時間単位で評価した急性脳症のサイトカイン動態解析:第1報2019

    • Author(s)
      冨岡和美,西山将広,永瀬裕朗,石田悠介,田中司,徳元翔一,山口宏,豊嶋大作,丸山あずさ,黒澤寛史,多田弘子,佐久間啓,飯島一誠
    • Organizer
      第61回日本小児神経学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 小児けいれん重積に対する脳波モニタリング下ミダゾラム昏睡療法の有効性と安全性2019

    • Author(s)
      石田悠介,冨岡和美,田中司,西山将広,永瀬裕朗,徳元翔一,山口宏,豊嶋大作,丸山あずさ,黒澤寛史,飯島一誠
    • Organizer
      第61回日本小児神経学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 有熱性難治性けいれん重積の治療プロトコル変遷による短期的予後の検討2019

    • Author(s)
      徳元翔一,山口宏,豊嶋大作,丸山あずさ,石田悠介,冨岡和美,田中司,西山将広,永瀬裕朗,飯島一誠
    • Organizer
      第61回日本小児神経学会学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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