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Attempt to elucidate the pathological mechanisms of myasthenic crisis

Research Project

Project/Area Number 17K09780
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionInternational University of Health and Welfare

Principal Investigator

Murai Hiroyuki  国際医療福祉大学, 医学部, 主任教授 (80325464)

Co-Investigator(Kenkyū-buntansha) 槍澤 公明  公益財団法人総合花巻病院(臨床研究部), 脳神経内科, 脳神経内科部長 (00244913)
松下 拓也  九州大学, 大学病院, 講師 (00533001)
今井 富裕  札幌医科大学, 保健医療学部, 名誉教授 (40231162)
本村 政勝  長崎総合科学大学, 工学研究科, 教授 (70244093)
Project Period (FY) 2017-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords重症筋無力症 / クリーゼ / 臨床疫学 / リスクファクター / メッセンジャーRNA
Outline of Final Research Achievements

The object of this study was to grasp the whole picture of myasthenic crisis and to elucidate the possible mechanisms of it. The first step was the clinico-epidemiological analyses. We analyzed the relationship between crisis and various clinical parameters. We divided generalized MG patients into two groups; with or without crisis. Positivity rate of AChR and MuSK antibodies were higher in crisis group. Early fast-acting treatment (EFT) was performed less frequently in crisis group. This may indicate that EFT contributes in reducing the crisis rate. Secondly, we identify the risk factors of myasthenic crisis applying the statistical procedure. A total of 10 articles were reviewed and meta-analyses identified several risk factors: bulbar symptoms, history of crisis, disease severity, and decreased vital capacity.

Academic Significance and Societal Importance of the Research Achievements

重症筋無力症のクリーゼの病態を解明することは神経筋組織に対する自己免疫疾患である重症筋無力症の重症化を予知することに繋がる。また、クリーゼに陥らないようにすることにより、患者の社会的生産性の低下を防止することも可能となる。

Report

(7 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (44 results)

All 2023 2022 2021 2020 2019 2018 2017

All Journal Article (17 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 17 results,  Open Access: 14 results) Presentation (26 results) (of which Int'l Joint Research: 13 results,  Invited: 9 results) Book (1 results)

  • [Journal Article] Patient-reported burden of myasthenia gravis: baseline results of the international prospective, observational, longitudinal real-world digital study MyRealWorld-MG.2023

    • Author(s)
      Dewilde S, Philips G, Paci S, Beauchamp J, Chiroli S, Quinn C, Day L, Larkin M, Palace J, Berrih-Aknin S, Claeys KG, Muppidi S, Mantegazza R, Sacca F, Meisel A, Bassez G, Murai H, Janssen M.
    • Journal Title

      BMJ Open

      Volume: 13 Issue: 1 Pages: e066445-e066445

    • DOI

      10.1136/bmjopen-2022-066445

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Advances and ongoing research in the treatment of autoimmune neuromuscular junction disorders2022

    • Author(s)
      Verschuuren J, Palace J, Murai H, Tannemaat M, Kaminski H, Bril V
    • Journal Title

      Lancet Neurol

      Volume: 21 Issue: 2 Pages: 189-202

    • DOI

      10.1016/s1474-4422(21)00463-4

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Safety and effectiveness of eculizumab in Japanese patients with generalized myasthenia gravis: Analysis of 1-year postmarketing surveillance.2022

    • Author(s)
      Murai H, Suzuki S, Fukamizu Y, Osawa T, Kikui H, Utsugisawa K:
    • Journal Title

      Clin Exp Neuroimmunol

      Volume: 13 Issue: 4 Pages: 280-289

    • DOI

      10.1111/cen3.12716

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Two-step nationwide epidemiological survey of myasthenia gravis in Japan 20182022

    • Author(s)
      Yoshikawa Hiroaki、Adachi Yumi、Nakamura Yosikazu、Kuriyama Nagato、Murai Hiroyuki、Nomura Yoshiko、Sakai Yasunari、Iwasa Kazuo、Furukawa Yutaka、Kuwabara Satoshi、Matsui Makoto
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 9 September Pages: e0274161-e0274161

    • DOI

      10.1371/journal.pone.0274161

    • URL

      https://localhost/en/publications/5e66c4dc-d73c-44d6-9a2e-0f6d6de6d9b6

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunotherapy for ocular myasthenia gravis: an observational study in Japan2022

    • Author(s)
      Narita Tomoko; Nakane Shunya, Nagaishi Akiko, Minami Naoya, Niino Masaaki, Kawaguchi Naoki, Murai Hiroyuki, Kira Jun-Ichi, Shimizu Jun, Iwasa Kazuo, Yoshikawa Hiroaki, Hatanaka Yuki, Sonoo Masahiro, Shimizu Yuko, Matsuo Hidenori
    • Journal Title

      Therapeutic advances in neurological disorders

      Volume: 16 Pages: 1-12

    • DOI

      10.1177/17562864231163819

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Safety and effectiveness of eculizumab in Japanese patients with generalized myasthenia gravis: Interim analysis of post-marketing surveillance2021

    • Author(s)
      Murai H, Suzuki S, Hasebe M, Fukamizu Y, Rodrigues E, Utsugisawa K
    • Journal Title

      Ther Adv Neurol Disord

      Volume: 14

    • DOI

      10.1177/17562864211001995

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Zilucoplan: an investigational complement C5 inhibitor for the treatment of acetylcholine receptor autoantibody- positive generalized myasthenia gravis2021

    • Author(s)
      Howard JF, Vissing J, Gilhus NE, Leite MI, Utsugisawa K, Duda PW, Farzaneh-Far R, Murai H, Wiendl H
    • Journal Title

      Expert Opin Investig Drugs

      Volume: 30 Issue: 5 Pages: 483-493

    • DOI

      10.1080/13543784.2021.1897567

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Efficacy, Safety, and Tolerability of Efgartigimod in Patients with Generalized Myasthenia Gravis (gMG): Analysis of the Randomized Phase 3 ADAPT Study2021

    • Author(s)
      Howard JF, Bril V, Vu T, Karam C, Peric S, Margania T, Murai H, Bilinska M, Shakarishvili R, Smilowski M, Guglietta A, Ulrichts P, Vangeneugden T, Utsugisawa K, Verschuuren J, Mantegazza R, ADAPT Investigator Study Group
    • Journal Title

      Lancet Neurol

      Volume: 20 Issue: 7 Pages: 526-536

    • DOI

      10.1016/s1474-4422(21)00159-9

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The patient-reported impact of myasthenia gravis in the real world: protocol for a digital observational study (MyRealWorld MG)2021

    • Author(s)
      Berrih-Aknin S, Claeys KG, Law N, Mantegazza R, Murai H, Sacca F, Dewilde S, Janssen MF, Bagshaw E, Kousoulakou H, Larkin M, Beauchamp J, Leighton T, Paci S
    • Journal Title

      BMJ Open

      Volume: 11 Issue: 7 Pages: e048198-e048198

    • DOI

      10.1136/bmjopen-2020-048198

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] International Consensus Guidance for Management of Myasthenia Gravis: 2020 Update2021

    • Author(s)
      Narayanaswami P, Sanders DB, Wolfe GI, Benatar M, Cea G, Evoli A, Gilhus NE, Illa I, Kuntz N, Massey JM, Melms A, Murai H, Nicolle M, Palace J, Richman DP, Verschuuren J
    • Journal Title

      Neurology

      Volume: 96 Issue: 3 Pages: 114-122

    • DOI

      10.1212/wnl.0000000000011124

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Response to eculizumab in patients with myasthenia gravis recently treated with chronic IVIg: a subgroup analysis of REGAIN and its open-label extension study2020

    • Author(s)
      Jacob S, Murai H, Utsugisawa K, Nowak RJ, Wiendl H, Fujita KP, O’Brien F, Howard JF
    • Journal Title

      Ther Adv Neurol Disord

      Volume: 13 Pages: 1-8

    • DOI

      10.1177/1756286420911784

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Suitable indications of eculizumab for patients with refractory generalized myasthenia gravis2020

    • Author(s)
      Oyama M, Okada K, Masuda M, Shimizu Y, Yokoyama K, Uzawa A, Kawaguchi N, Ikeguchi R, Hoshino Y, Hatano T, Ozawa Y, Nakahara J, Aizawa H, Kitagawa K, Hattori N, Kuwabara S, Murai H, Suzuki S
    • Journal Title

      Therapeutic Advances in Neurological Disorders

      Volume: 13 Pages: 1-9

    • DOI

      10.1177/1756286420904207

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term safety and efficacy of eculizumab in generalized myasthenia gravis.2019

    • Author(s)
      Muppidi S, Utsugisawa K, Benatar M, Murai H, Barohn RJ, Illa I, Jacob S, Vissing J, Burns TM, Kissel JT, Nowak RJ, Andersen H, Casasnovas C, de Bleecker JL, Vu TH, Mantegazza R, O'Brien FL, Wang JJ, Fujita KP, Howard JF Jr; Regain
    • Journal Title

      Muscle Nerve.

      Volume: - Issue: 1 Pages: 14-24

    • DOI

      10.1002/mus.26447

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Long-term efficacy and safety of eculizumab in Japanese patients with generalized myasthenia gravis: A subgroup analysis of the REGAIN open-label extension study2019

    • Author(s)
      Murai H, Uzawa A, Suzuki Y, Imai T, Shiraishi H, Suzuki H, Okumura M, O’Brien F, Wang JJ, Fujita KP, Utsugisawa K
    • Journal Title

      Journal of the Neurological Sciences

      Volume: 407 Pages: 116419-116419

    • DOI

      10.1016/j.jns.2019.08.004

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clinical burden and healthcare resource utilization associated with myasthenia gravis: assessments from a Japanese claims database2019

    • Author(s)
      Murai H, Hasebe M, Murata A, Utsugisawa K
    • Journal Title

      Clin Exp Neuroimmunol

      Volume: 10 Issue: 1 Pages: 61-68

    • DOI

      10.1111/cen3.12495

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rationale for the clinical guidelines for myasthenia gravis in Japan2018

    • Author(s)
      Murai H, Utsugisawa K, Nagane Y, Suzuki S, Imai T, Motomura M
    • Journal Title

      Annals of the New York Academy of Sciences

      Volume: 1413 Issue: 1 Pages: 35-40

    • DOI

      10.1111/nyas.13544

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oral corticosteroid dosing regimen and long-term prognosis in generalised myasthenia gravis: a multicentre cross-sectional study in Japan2018

    • Author(s)
      Imai Tomihiro、Utsugisawa Kimiaki、Murai Hiroyuki、Tsuda Emiko、Nagane Yuriko、Suzuki Yasushi、Minami Naoya、Uzawa Akiyuki、Kawaguchi Naoki、Masuda Masayuki、Konno Shingo、Suzuki Hidekazu、Akaishi Tetsuya、Aoki Masashi
    • Journal Title

      J Neurol Neurosurg Psychiatry

      Volume: in press Issue: 5 Pages: 513-517

    • DOI

      10.1136/jnnp-2017-316625

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Long-Term Safety, Tolerability, and Efficacy of Efgartigimod in Patients With Generalized Myasthenia Gravis: Interim Results of the ADAPT+ Study.2022

    • Author(s)
      Howard JF, Bril V, Vu T, Karam C, Peric S, De Bleecker JL, Murai H, Meisel A, Beydoun S, Pasnoor M, Guglietta A, Ulrichts P, T’joen C, Utsugisawa K, Verschuuren J, Mantegazza R:
    • Organizer
      74th Annual Meeting of American Academy of Neurology
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Real-world effectiveness of eculizumab in generalized myasthenia gravis in Japan: 1-year post-marketing surveillance data2022

    • Author(s)
      Murai H, Suzuki S, Fukamizu Y, Osawa T, Kikui H, Utsugisawa K:
    • Organizer
      第63回日本神経学会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Long-Term Safety and Efficacy of Efgartigimod in Patients With Generalized Myasthenia Gravis: Interim Results of the ADAPT+ Study2022

    • Author(s)
      Meisel A, Bril V, Vu T, Karam C, Peric S, De Bleecker JL, Murai H, Beydoun S, Pasnoor M, Guglietta A, Ulrichts P, T’joen C, Utsugisawa K, Verschuuren J, Mantegazza R, Howard JF:
    • Organizer
      8th Congress of the European Academy of Neurology
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Efficacy of Efgartigimod in Generalized Myasthenia Gravis: Myasthenia Gravis Composite Score Analysis From ADAPT.2022

    • Author(s)
      De Bleecker JL, Meisel A, Howard JF, Vu T, Bril V, Ulrichts P, Guglietta A, T’joen C, Murai H, Utsugisawa K, Mantegazza R:
    • Organizer
      17th International Congress on Neuromuscular Diseases
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] LUMINESCE: Phase 3 study of satralizumab, a therapeutic recycling antibody targeting the IL-6 receptor, in patients with generalised myasthenia gravis.2022

    • Author(s)
      Kaminski H, Zhao C, Meyer zu Horste G, O’Connor KC, Klingelschmitt G, Krumova P, Bolt S, Vodopivec I, Lennon-Chrimes S, Murai H:
    • Organizer
      27th Annual Congress of the World Muscle Society
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis of Efgartigimod Efficacy Across Patient Populations and Myasthenia Gravis Specific Scales2021

    • Author(s)
      Murai H, Bril V, Vu T, Karam C, Peric S, Imai T, Takahashi M, Uzawa A, Guglietta A, Ulrichts P, Vangeneugden T, Utsugisawa K, Mantegazza R, Howard J
    • Organizer
      第62回日本神経学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Real-world experience with refractory generalized myasthenia gravis2021

    • Author(s)
      Murai H
    • Organizer
      16th International Congress on Neuromuscular Diseases
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] COVID-19時代におけるMGのマネージメント2021

    • Author(s)
      村井弘之
    • Organizer
      第33回日本神経免疫学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 抗補体薬ソリリスの位置づけ2021

    • Author(s)
      村井弘之
    • Organizer
      第33回日本神経免疫学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] エクリズマブ投与時の全身型重症筋無力症患者の病態生理特性に関する多施設共同臨床研究(中間解析)2021

    • Author(s)
      村井弘之, 鈴木靖士, 永田栄一郎, 望月秀樹, 横山和正, 大崎康史, 関口兼司, 玉岡晃, 中嶋秀人, 丹羽淳一,野村恭一, 阪田麻友美, 増田眞之, 南尚哉, 岡村和美, 深水裕二, 小原崇史, 鈴木重明
    • Organizer
      第33回日本神経免疫学会
    • Related Report
      2021 Research-status Report
  • [Presentation] REAL-WORLD PATIENT-REPORTED IMPACT OF MYASTHENIA GRAVIS: INITIAL DATA FROM THE MYREALWORLD MG STUDY2021

    • Author(s)
      Murai H, Claeys K, Friconneau M, Larkin M, Shao J
    • Organizer
      第39回日本神経治療学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 難治性重症筋無力症に対するエクリズマブの適応2020

    • Author(s)
      大山宗徳、岡田健佑、増田真之、清水優子、横山和正、川口直樹、鵜沢顕之、中原仁、村井弘之、鈴木重明
    • Organizer
      第117回日本内科学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 日本におけるエクリズマブの全身型重症筋無力症に関する製造販売後調査の中間解析2020

    • Author(s)
      村井弘之、鈴木重明、長谷部美紀、深水裕二、ロドリゲスエマ、槍澤公明
    • Organizer
      第61回日本神経学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Safety and effectiveness of eculizumab for patients with generalized myasthenia gravis in Japan: Interim analysis of post-marketing surveillance2020

    • Author(s)
      Murai H, Suzuki S, Hasebe M, Fukamizu Y, Rodriguez E, Utsugisawa K
    • Organizer
      The 6th European Academy of Neurology
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] ADAPT: A Randomized Phase 3 Study of the FcRn antagonist, Efgartigimod, in Myasthenia Gravis2020

    • Author(s)
      Howard JF, Vu T, Bril V, De Bleecker J, Verschuuren J, Mantegazza R, Meisel A, Peric S, de Haard H, Parys W, Guglietta A, Ulrichts P, Murai H.
    • Organizer
      AANEM 2020 Annual Meeting (American Association of Neuromuscular & Electrodiagnostic Medicine)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 重症筋無力症に対するエクリズマブ治療:これまでにわかったこと、わからないこと2019

    • Author(s)
      村井弘之
    • Organizer
      第60回日本神経学会学術大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Response to eculizumab in patients with myasthenia gravis recently treated with chronic intravenous immunoglobulin2019

    • Author(s)
      Genge A, Jacob S, Murai H, Utsugisawa K, Nowak RJ, Wiendl H, Fujita KP, O’Brien F, Howard JF
    • Organizer
      The 54th Canadian Neurological Sciences Federation Congress
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Relieving the burden of myasthenia gravis: eculizumab reduces exacerbation, hospitalization and rescue therapy rates2019

    • Author(s)
      Siddiqi Z, Howard JF, Jacob S, Guptill JT, Meisel A, Wiendl H, Murai H, Utsugisawa K, Nowak RJ, Fujita KP, O’Brien F, Patra K, Muppidi S
    • Organizer
      The 54th Canadian Neurological Sciences Federation Congress
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 重症筋無力症:新時代の治療戦略2019

    • Author(s)
      村井弘之
    • Organizer
      第60回日本神経病理学会総会学術研究会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 重症筋無力症の新しい分類と治療戦略2019

    • Author(s)
      村井弘之
    • Organizer
      第37回日本神経治療学会学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Response to eculizumab in patients with AChR+ refractory myasthenia gravis recently treated with chronic IVIg2018

    • Author(s)
      Jacob S, Murai H, Utsugisawa K, Nowak RJ, Wiendl H, Fujita KP, O’Brien F, Howard JF
    • Organizer
      The 15th International Congress on Neuromuscular Diseases
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] MGクリーゼに遭遇したら2018

    • Author(s)
      村井弘之
    • Organizer
      第36回日本神経治療学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 重症筋無力症の診断から治療までの最前線2018

    • Author(s)
      村井弘之
    • Organizer
      第30回日本神経免疫学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Updates on antibodies in myasthenia gravis2017

    • Author(s)
      Murai H
    • Organizer
      Asean Neurological Association Biennial Convention 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Early fast-acting treatment strategy against generalized myasthenia gravis2017

    • Author(s)
      Utsugisawa K, Nagane Y, Akaishi T, Suzuki Y, Imai T, Tsuda E, Minami N, Uzawa A, Kawaguchi N, Masuda M, Konno S, Suzuki H, Murai H, Aoki M
    • Organizer
      The 23rd World Congress of Neurology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Open label extension trial of REGAIN to evaluate the safety and efficacy of eculizumab in patients from Japan with refractory generalized myasthenia gravis2017

    • Author(s)
      Murai H, Uzawa A, Suzuki Y, Imai T, Shiraishi H, Tsuda E, Suzuki H, Okumura M, Utsugisawa K
    • Organizer
      The 23rd World Congress of Neurology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Book] 今日の処方(改訂第6版)2019

    • Author(s)
      浦部 晶夫、島田 和幸、川合 眞一
    • Total Pages
      904
    • Publisher
      南江堂
    • ISBN
      9784524251193
    • Related Report
      2019 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2024-01-30  

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