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Pathophysiology of acute encephalopathy associated with cytokine storm using clinical samples combined with clinical database

Research Project

Project/Area Number 18K15711
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionKobe University

Principal Investigator

Nishiyama Masahiro  神戸大学, 医学部附属病院, 講師 (50741667)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsacute encephalopathy / cytokine / inflammation / status epilepticus / 急性脳症 / 炎症 / サイトカイン / 熱性けいれん / けいれん重積 / 病態
Outline of Final Research Achievements

Acute encephalopathy is a major neurological syndrome characterized by acute onset of severe and long-lasting disturbance of consciousness, which typically occur in previously healthy children. Acute encephalopathy associated with cytokine storm is the most severe syndrome among those syndromes. However, specific treatment strategy for this conditions yet to be established. Therefore, we have researched the pathophysiology of acute encephalopathy associated with cytokine storm using clinical samples combined with clinical database. In this research, we have provided the new insights on the pathophysiology and a detailed clinical picture of acute encephalopathy associated with cytokine by a comprehensive analysis of inflammatory biomarkers. Further, we have suggested that earlier aggressive anti-inflammation treatment might prevent sequelae in these conditions. More comprehensive analysis on pathophysiology and specific treatment strategy for each pathophysiology are needed.

Academic Significance and Societal Importance of the Research Achievements

急性脳症は、生来健康であった乳幼児に認知障害・麻痺・てんかんなどの重篤な後遺症を残す疾患で、年間700人の発症があると推定されている。本研究では、急性脳症における炎症病態のダイナミックな変化が明らかとなった。臨床情報とともに解析できたことで、至適時期に抗炎症治療を行うための重要な知見も得られた。本研究で得られた成果をもとに、急性脳症の治療戦略確立が期待される。予後不良なサイトカインストーム型急性脳症の死亡・後遺症軽減を達成することは、患児本人や家族はもちろん、社会全体にとっても重要である。

Report

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

    (42 results)

All 2021 2020 2019 2018

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 1 results) Presentation (28 results) (of which Invited: 2 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] 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] 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] Thiamylal anaesthetic therapy for febrile refractory status epilepticus in children2020

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

      Seizure

      Volume: 80 Pages: 12-17

    • DOI

      10.1016/j.seizure.2020.03.012

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Seizure prevalence in children aged up to 3 years: a longitudinal population-based cohort study in Japan.2020

    • Author(s)
      Nishiyama M, Yamaguchi H, Ishida Y, Tomioka K, Takeda H, Nishimura N, Nozu K, Mishina H, Iijima K, Nagase H.
    • Journal Title

      BMJ Open

      Volume: 10 Issue: 9 Pages: e035977-e035977

    • DOI

      10.1136/bmjopen-2019-035977

    • NAID

      120006890793

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acute rhabdomyolysis following viral infection with coxsackie A4 in a 50-day-old infant with Fukuyama congenital muscular dystrophy2020

    • Author(s)
      Yamaguchi H, Taniguchi-Ikeda M, Nagase H, Ito Y, Tokumoto S, Toyoshima D, Enkhjargal S, Nishiyama M, Awano H, Kurosawa H, Kasai M, Maruyama A, Iijima K
    • Journal Title

      J Infect Chemother

      Volume: 26 Issue: 5 Pages: 516-519

    • DOI

      10.1016/j.jiac.2019.12.015

    • Related Report
      2019 Research-status 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] 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
      2019 Research-status Report 2018 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] Fibrocartilaginous Embolism of the Spinal Cord in Children: A Case Report and Review of Literature2019

    • Author(s)
      Yamaguchi H, Nagase H, Nishiyama M, Tokumoto S, Toyoshima D, Akasaka Y, Maruyama A, Iijima K
    • Journal Title

      Pediatr Neurol

      Volume: 99 Pages: 3-6

    • DOI

      10.1016/j.pediatrneurol.2019.04.013

    • NAID

      120006846524

    • Related Report
      2019 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] 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
      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] 小児けいれん重積治療ガイドライン改訂に向けて 難治性てんかん重積の治療 ミダゾラムまたはバルビツレートによる麻酔療法2020

    • Author(s)
      西山 将広, 永瀬 裕朗, 丸山 あずさ
    • Organizer
      第62回日本小児神経学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 有熱性けいれんを主訴に入院した小児におけるけいれん時間毎のAESD発症頻度と予後 単一施設の連続症例コホートでの検討2020

    • Author(s)
      徳元 翔一, 西山 将広, 他
    • 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, 他
    • 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, 他
    • Organizer
      第62回日本小児神経学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] けいれん重積型(二相性)急性脳症の初回けいれん時間による臨床像の比較検討2020

    • Author(s)
      山口 宏, 西山 将広, 他
    • 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, 他
    • Organizer
      第62回日本小児神経学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 発熱に伴うけいれん・意識障害小児患者の長期予後2020

    • Author(s)
      豊嶋 大作, 西山 将広, 他
    • Organizer
      第62回日本小児神経学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 神戸市における熱性けいれんの発症頻度 後期早産であることのリスクの検討2020

    • Author(s)
      西山 将広, 山口 宏, 他
    • Organizer
      第123回日本小児科学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 突然の右片麻痺で発症し、発症4日目からけいれん群発を認めた1例2019

    • Author(s)
      石田悠介、西山将広、他
    • Organizer
      第66回日本小児神経学会近畿地方会
    • Related Report
      2019 Research-status Report
  • [Presentation] てんかん発作の出現により学習障害の原因が判明したECSWS の 1 例2019

    • Author(s)
      本郷裕斗、西山将広、他
    • Organizer
      第15回日本てんかん学会近畿地方会
    • Related Report
      2019 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、西山将広、他
    • 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、他
    • 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、他
    • 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、西山将広、他
    • 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、西山将広、他
    • Organizer
      第61回日本小児神経学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 新規STXBP1変異を認め大田原症候群と診断したSTXBP1脳症2019

    • Author(s)
      山口宏、西山将広、他
    • Organizer
      第53回日本てんかん学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 小児難治てんかん重積状態における急性期の血中サイトカイン推移2019

    • Author(s)
      冨岡和美、西山将広、他
    • Organizer
      第53回日本てんかん学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 在胎週数毎に層別化した熱性けいれんの発生頻度:population-based study2019

    • Author(s)
      西山将広、永瀬裕朗、他
    • Organizer
      第53回日本てんかん学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 急性散在性脳脊髄炎の髄液所見の検討2018

    • Author(s)
      西山将広、永井正志、他
    • Organizer
      第274回日本小児科学会兵庫県地方会
    • Related Report
      2018 Research-status Report
  • [Presentation] 複雑型熱性けいれんの好発時間帯とその重症度2018

    • Author(s)
      山口 宏、西山将広、他
    • Organizer
      第121回日本小児科学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 急性散在性脳脊髄炎24例における発症から軽快までの経時的な臨床経過の特徴2018

    • Author(s)
      西山将広、永瀬裕朗、他
    • Organizer
      第60回日本小児神経学会
    • Related Report
      2018 Research-status Report
  • [Presentation] けいれんの第一選択薬はジアゼパム?それともミダゾラム?2018

    • Author(s)
      西山将広、永瀬裕朗、他
    • Organizer
      第60回日本小児神経学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] サイトカインストームによる急性脳症が予測される小児に対するステロイドパルス療法の有効性2018

    • Author(s)
      石田悠介、西山将広、他
    • Organizer
      第60回日本小児神経学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 小児救急外来における非けいれん性発作を示す小児患者の臨床的特徴2018

    • Author(s)
      山口宏、西山将広、他
    • Organizer
      第60回日本小児神経学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 発熱に伴う難治性けいれん重積状態に対するバルビツレート昏睡療法の最適な鎮静深度に関する多施設共同研究2018

    • Author(s)
      冨岡和美、西山将広、他
    • Organizer
      第60回日本小児神経学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 複雑型熱性けいれんの急性期の臨床経過の特徴2018

    • Author(s)
      田中司、西山将広、他
    • Organizer
      第60回日本小児神経学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 小児におけるカルバマゼピンとレベチラセタムによる血清脂質および甲状腺ホルモンの変化2018

    • Author(s)
      西山将広、高見勇一、他
    • Organizer
      第52回日本てんかん学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 有熱性けいれん重積状態の小児における非けいれん性発作2018

    • Author(s)
      丸山あずさ、西山将広、他
    • Organizer
      第52回日本てんかん学会学術集会
    • Related Report
      2018 Research-status Report

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

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