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Pathophysiology and treatment in enterovirus D68-associated acute flaccid myelitis

Research Project

Project/Area Number 17K16266
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pediatrics
Research InstitutionYamaguchi University

Principal Investigator

MATSUSHIGE Takeshi  山口大学, 医学部附属病院, 講師 (60528941)

Research Collaborator SHIRABE Komei  
DOI Kazuteru  
CUI Dan  
IKEDA Eiji  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords急性弛緩性麻痺 / エンテロウイルスD68 / サイトカイン / 病理 / 急性弛緩性脊髄炎 / 脳神経疾患 / 感染症 / ウイルス
Outline of Final Research Achievements

Acute flaccid myelitis (AFM) is a recent issue that causes permanent flaccid paralysis in healthy children. Although enterovirus D68 (EV-D68) is assumed as one of the causes of AFM, the pathophysiology is not fully understood. The following two main results were obtained in this study.
1) We found that the inflammatory cytokines, interferon-gamma (IFN-γ) and interleukin 6 (IL-6), in cerebrospinal fluid were markedly elevated in the acute phase. 2) Pathological analysis of peripheral nerves was performed during nerve transfer surgery, and atrophic changes in nerves and EV-D68 positive findings were observed, which will be confirmed in several ways.
Also, in parallel, we are preparing for analysis using a mouse model.

Academic Significance and Societal Importance of the Research Achievements

ヒトでは脳脊髄液からEV-D68が検出されない。そのため、本病態がウイルスの脊髄への直接感染によるものか、二次的な免疫反応による神経障害なのかが不明であった。脳脊髄液のIFN-γ上昇を認めたことは、ウイルスによる直接感染を示唆する。したがって、急性期において過度な免疫抑制療法はマイナスに働く可能性がある。また、長期にわたって神経にEV-D68が感染することは過去に知られていないため、他の手法も含めて慎重に判断されるべきである。持続感染によって神経回復が妨げられているかどうかは現時点で明らかでないものの、抗ウイルス薬の治療適応は急性期だけではない可能性もあり、開発が望まれる。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (1 results)

All 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] Cytokine Profile in a Patient With Enterovirus D68-Associated Acute Flaccid Myelitis2019

    • Author(s)
      Ippei Hidaka, Takeshi Matsushige, Hirofumi Inoue, Madoka Hoshide, Komei Shirabe, Shunji Hasegawa
    • Journal Title

      Pediatr Neurol

      Volume: 印刷中

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access

URL: 

Published: 2017-04-28   Modified: 2020-03-30  

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