Clinical and Pathophysiological Analysis of Atypical Multiple Sclerosis

2016 Fiscal Year Annual Research Report

• Project/Area Number: 26293205
• Research Institution: Tohoku University
• Principal Investigator: 藤原 一男 東北大学, 医学(系)研究科(研究院), 非常勤講師 (70280873)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 多発性硬化症 / 非典型例 / 抗MOG抗体 / 視神経脊髄炎 / 脱髄疾患 / アストロサイトパチー

Outline of Annual Research Achievements

多発性硬化症(MS)の非典型例が典型例といかに異なるかについて臨床、病態などについて種々の検討を行った、
1.非典型例の一型であるミエリンオリゴデンドロサイト糖たんぱく(MOG)抗体陽性症例の中で、“MOG抗体陽性のてんかん発作を伴う一側大脳皮質脳炎”の4例を報告した。成人男性で、一側の大脳皮質がFLAIR画像で高信号病変として描出された。抗てんかん薬のみでは無効でステロイドパルス療法によりてんかんは消失した。このユニークな脳炎は既知の疾患とは異なっており新たな自己免疫性脳炎であると思われ、論文の掲載誌においてEditor’s choiceで紹介され表紙の画像に取り上げられた。
2.MOG抗体陽性例、アクアポリン4(AQP4)抗体陽性視神経脊髄炎(NMO)、MSと対照群の髄液における27種サイトカイン濃度を比較したところ、MOG抗体陽性例のサイトカインプロフィールは、MSとは異なり、AQP4抗体陽性NMOと類似していた。
3.Balo病(同心円硬化症)は特異な病理像を呈する炎症性脱髄疾患である。我々は本疾患のMRI所見と脳病理像を解析し、この病変が経時的に拡大し、最外層では低酸素状態様の状態とそれに対する組織反応(hypoxia-inducible factor 1αの発現)と脱髄に関連するサイトカインの放出が主にグリア細胞で行われていることを見出した。
4. MSの再発にストレスが影響しうることが報告されてきた。昨年度から論文を準備してきた東日本大震災の前後で仙台地区のMS,NMO患者のストレスは有意に上昇したが再発の増加はなかったという結果を国際誌に発表した。

Research Progress Status

28年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

28年度が最終年度であるため、記入しない。

Causes of Carryover

28年度が最終年度であるため、記入しない。

Expenditure Plan for Carryover Budget

28年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] ウイーン医科大学(オーストリア)
  • Country Name: AUSTRIA
  • Counterpart Institution: ウイーン医科大学
• [Int'l Joint Research] ニッテ大学(インド)
  • Country Name: INDIA
  • Counterpart Institution: ニッテ大学
• [Int'l Joint Research] リオグランデドスールカトリック教会大学(ブラジル)
  • Country Name: BRAZIL
  • Counterpart Institution: リオグランデドスールカトリック教会大学
• [Int'l Joint Research] ソウル大学(韓国)
  • Country Name: KOREA (REP. OF KOREA)
  • Counterpart Institution: ソウル大学
• [Journal Article] Impact of the Great East Japan Earthquake in 2011 on MS and NMOSD: a study in Sendai, Japan (2017)
  • Author(s): Kanamori Y, Nakashima I, Takai Y, Misu T, Kuroda H, Nishiyama S, Takahashi T, Sato S, Fujimori J, Higuchi J, Itoyama Y, Aoki M, Fujihara K
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 88 Pages: 362-364
  • DOI: 10.1136/jnnp-2016-313890
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Relapsing optic neuritis and isolated transverse myelitis are the predominant clinical phenotypes for patients with antibodies to myelin oligodendrocyte glycoprotein in India (2017)
  • Author(s): Pandit L, Sato DK, Mustafa S, Takahashi T, D’Cunha A, Malli C, Sudhir A, Fujihara K
  • Journal Title: Multiple Sclerosis Journal: Experimental, Translational and Clinical Volume: 印刷中 Pages: 印刷中
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] MOG-antibody-positive, benign, unilateral, cerebral cortical encephalitis with epilepsy (2017)
  • Author(s): Ogawa R, Nakashima I, Takahashi T, Kaneko K, Akaishi T, Takai Y, Sato DK, Nishiyama S, Misu T, Kuroda H, Aoki M, Fujihara K
  • Journal Title: Neurol Neuroimmunol Neuroinflamm Volume: 16 Pages: e322
  • DOI: 10.1212/NXI.0000000000000322
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Bilateral frontal cortex encephalitis and paraparesis in a patient with anti-MOG antibodies (2017)
  • Author(s): Fujimori J, Takai Y, Nakashima I, Sato DK, Takahashi T, Kaneko K, Nishiyama S, Watanabe M, Tanji H, Kobayashi M, Misu T, Aoki M, Fujihara K
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 印刷中 Pages: 印刷中
  • DOI: 10.1136/jnnp-2016-315094
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Whole brain and grey matter volume of Japanese patients with multiple sclerosis (2017)
  • Author(s): Akaishi T, Nakashima I, Mugikura S, Aoki M, Fujihara K
  • Journal Title: J Neuroimmunol Volume: 15 Pages: 68-75
  • DOI: 10.1016/j.jneuroim.2017.03.009
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Neuromyelitis optica spectrum disorders (2017)
  • Author(s): Akaishi T, Nakashima I, Sato DK, Takahashi T, Fujihara K
  • Journal Title: Neuroimaging Clin N Am Volume: 27 Pages: 251-265
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Differential diagnosis of neuromyelitis optica spectrum disorders (2017)
  • Author(s): Kim SM, Kim SJ, Lee HJ, Kuroda H, Palace J, Fujihara K
  • Journal Title: Ther Adv Neurol Disord Volume: 印刷中 Pages: 印刷中
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Lack of KIR4.1 autoantibodies in Japanese patients with MS and NMO (2016)
  • Author(s): Higuchi O, Nakane S, Sakai W, Maeda Y, Niino M, Takahashi T, Fukazawa T, Kikuchi S, Fujihara K, Matsuo H
  • Journal Title: Neurol Neuroimmunol Neuroinflamm Volume: 3 Pages: e263
  • DOI: 10.1212/NXI.0000000000000263
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hypoxia-like tissue injury and glial response contribute to Balo’s concentric lesion development (2016)
  • Author(s): Takai Y, Misu T, Nishiyama S, Ono H, Kuroda H, Nakashima I, Saito R, Kanamori M, Sonoda Y, Kumabe T, Mugikura S, Watanabe M, Aoki M, Fujihara K
  • Journal Title: Neurology Volume: 87 Pages: 2000-2005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Aquaporin 4-specific T cells and NMO-IgG cause primary retinal damage in experimental NMO/SD (2016)
  • Author(s): Zeka B, Hastermann M, Kaufmann N, Schanda K, Pende M, Misu T, Rommer P, Fujihara K, Nakashima I, Dahle C, Leutmezer F, Reindl M, Lassmann H, Bradl M
  • Journal Title: Acta Neuropathol Commun Volume: 4 Pages: 82
  • DOI: 10.1186/s40478-016-0355-y
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Different etiologies and prognoses of optic neuritis in demyelinating diseases (2016)
  • Author(s): Akaishi T, Nakashima I, Takeshita T, Kaneko K, Mugikura S, Sato DK, Takahashi T, Nakazawa T, Aoki M, Fujihara K
  • Journal Title: J Neuroimmunol Volume: 299 Pages: 152-157
  • DOI: 10.1016/j.jneuroim.2016.09.007
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord (2016)
  • Author(s): Oji S, Nicolussi EM, Kaufmann N, Zeka B, Schanda K, Fujihara K, Illes Z, Dahle C, Reindl M, Lassmann H, Bradl M
  • Journal Title: PLoS One Volume: 11 Pages: e0151244
  • DOI: 10.1371/journal.pone.0151244
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Serological markers associated with neuromyelitis optica spectrum disorders in South India (2016)
  • Author(s): Pandit L, Sato DK, Mustafa S, Takahashi T, D'Cunha A, Malli C, Sudhir A, Fujihara K
  • Journal Title: Ann Indian Acad Neurol Volume: 19 Pages: 505-509
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] AQP4-reactive and MOG-reactive NMOSD are mutually exclusive diesases (2017)
  • Author(s): Fujihara K
  • Organizer: 9th Annual International Roundtable Conference on NMO (Guthy-Jackson Charitable Foundation)
  • Place of Presentation: ロサンジェルス(米国)
  • Year and Date: 2017-03-14 – 2017-03-15
  • Int'l Joint Research / Invited
• [Presentation] MS in Asia (2017)
  • Author(s): Fujihara K
  • Organizer: The 4th international Porto Congress of Multiple Sclerosis
  • Place of Presentation: ポルト(ポルトガル)
  • Year and Date: 2017-03-09 – 2017-03-11
  • Int'l Joint Research / Invited
• [Presentation] 多発性硬化症と視神経脊髄炎に関連したバイオマーカー：AQP4抗体とMOG抗体 (2016)
  • Author(s): 藤原一男
  • Organizer: 第56回日本臨床化学会年次学術集会
  • Place of Presentation: くまもと県民交流館パレア(熊本県・熊本市）
  • Year and Date: 2016-12-02 – 2016-12-04
  • Invited
• [Presentation] McDonald criteria in Asian populations (2016)
  • Author(s): Fujihara K
  • Organizer: International Panel on Diagnosis of Multiple Sclerosis
  • Place of Presentation: フィラデルフィア(米国)
  • Year and Date: 2016-11-03 – 2016-11-05
  • Int'l Joint Research / Invited
• [Presentation] Case examples of other MS mimics (2016)
  • Author(s): Fujihara K
  • Organizer: MAGNIMS Teaching Course: Using MRi to diagnose MS and related disorders in the 9th Annual Congress of Pan-Asian Committee on Treatment and Research in Multiple Sclerosis (PACTRIMS)
  • Place of Presentation: バンコク(タイ)
  • Year and Date: 2016-10-28 – 2016-10-28
  • Int'l Joint Research / Invited
• [Presentation] Progressive MS in Asia (2016)
  • Author(s): Fujihara K
  • Organizer: European Charcot Foundation Symposium: Progressive MS in the 9th Annual Congress of Pan-Asian Committee on Treatment and Research in Multiple Sclerosis (PACTRIMS)
  • Place of Presentation: バンコク(タイ)
  • Year and Date: 2016-10-27 – 2016-10-27
  • Int'l Joint Research / Invited
• [Presentation] Aquaporin 4 antibody in neuromyelitis optica spectrum disorders (2016)
  • Author(s): Fujihara K
  • Organizer: The 13th International Wrokshop on Autoantibodies and Autoimmunity
  • Place of Presentation: 京都(日本)
  • Year and Date: 2016-10-11 – 2016-10-13
  • Int'l Joint Research / Invited
• [Presentation] 多発性硬化症の鑑別診断と治療の選択 (2016)
  • Author(s): 藤原一男
  • Organizer: 第28回日本神経免疫学会学術集会
  • Place of Presentation: ブリックホール(長崎県・長崎市)
  • Year and Date: 2016-09-29 – 2016-09-30
  • Invited
• [Presentation] Pathomechanisms of AQP4-Ig+, MOG-IgG+ and Seronegative Diseases (2016)
  • Author(s): Fujihara K
  • Organizer: 32th Congress of European Committee on Treatment and Research in Multiple Sclerosis (ECTRIMS)
  • Place of Presentation: ロンドン(イギリス)
  • Year and Date: 2016-09-14 – 2016-09-17
  • Int'l Joint Research / Invited
• [Presentation] New trial designs and treatment approach for NMO (2016)
  • Author(s): Fujihara K
  • Organizer: 32th Congress of Eurpean Committee on Treatment and Research in Multiple Sclerosis (ECTRIMS)
  • Place of Presentation: ロンドン(イギリス)
  • Year and Date: 2016-09-14 – 2016-09-17
  • Int'l Joint Research / Invited
• [Presentation] Classic MS: Update on Pathogenesis (2016)
  • Author(s): Fujihara K
  • Organizer: 15th Axsian and Oceanian Congress of Neurology (AOCN)
  • Place of Presentation: クアラルンプール(マレーシア)
  • Year and Date: 2016-08-19 – 2016-08-21
  • Int'l Joint Research / Invited
• [Presentation] Implications of The New Diagnostic Criteria of NMOSD (2015) (2016)
  • Author(s): Fujihara K
  • Organizer: 15th Axsian and Oceanian Congress of Neurology (AOCN)
  • Place of Presentation: クアラルンプール(マレーシア)
  • Year and Date: 2016-08-19 – 2016-08-21
  • Int'l Joint Research / Invited
• [Presentation] The Diagnostic Challenge of Multiple Sclerosis (2016)
  • Author(s): Fujihara K
  • Organizer: APAC MS Summit
  • Place of Presentation: ソウル韓国()
  • Year and Date: 2016-07-16 – 2016-07-17
  • Int'l Joint Research / Invited
• [Presentation] Optic Neuritis: Pathology and Differential Diagnosis (2016)
  • Author(s): Fujihara K
  • Organizer: European Charcot Foundation Symposium, 17th Annual Meeting of Brazilian Committee on Treatment and Research in Multiple Sclerosis (BCTRIMS)
  • Place of Presentation: サンパウロ(ブラジル)
  • Year and Date: 2016-06-24 – 2016-06-24
  • Int'l Joint Research / Invited
• [Presentation] Epidemiology of Multiple Sclerosis in Asia: An Overview (PACTRIMS) (2016)
  • Author(s): Fujihara K
  • Organizer: 17th Annual Meeting of Brazilian Committee on Treatment and Research in Multiple Sclerosis (BCTRIMS)
  • Place of Presentation: サンパウロ(ブラジル)
  • Year and Date: 2016-06-22 – 2016-06-25
  • Int'l Joint Research / Invited
• [Presentation] Critical Comparative Analysis of the Revised 2006 Criteria and the International Consensus Criteria (2015) for Diagnosis of NMOSD (2016)
  • Author(s): Fujihara K
  • Organizer: 17th Annual Meeting of Brazilian Committee on Treatment and Research in Multiple Sclerosis (BCTRIMS)
  • Place of Presentation: サンパウロ(ブラジル)
  • Year and Date: 2016-06-22 – 2016-06-25
  • Int'l Joint Research / Invited
• [Presentation] International consensus diagnostic criteria of NMOSD. In Session V: NMO/NMO Spectrum Diseases (in honor of Eugene Devic) (2016)
  • Author(s): Fujihara K
  • Organizer: IX. Clinical Neuroimmunology Symposium
  • Place of Presentation: クシャダス(トルコ)
  • Year and Date: 2016-06-03 – 2016-06-04
  • Int'l Joint Research / Invited
• [Presentation] Neuromyelitis optica spectrum disorders (NMOSD) and MOG-IgG (2016)
  • Author(s): Fujihara K
  • Organizer: The 2nd Chinese International Summit Meeting of Neuroinfection, Immunity and Cerebrovascular Diseases
  • Place of Presentation: 北京(中国)
  • Year and Date: 2016-05-20 – 2016-05-21
  • Int'l Joint Research / Invited
• [Presentation] 視神経脊髄炎の新しい診断基準 (2016)
  • Author(s): 藤原一男
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸国際会議場(兵庫県・神戸市)
  • Year and Date: 2016-05-18 – 2016-05-21
  • Invited
• [Book] Pocket Drugs 2017 (2017)
  • Author(s): 藤原一男
  • Total Pages: 6
  • Publisher: 医学書院
• [Book] Dynamic diagnosisに必要な脊椎脊髄の神経症候学 (2017)
  • Author(s): 藤原一男
  • Total Pages: 3
  • Publisher: 三輪書店
• [Book] Dynamic diagnosisに必要な脊椎脊髄の神経症候 (2017)
  • Author(s): 藤原一男
  • Total Pages: 2
  • Publisher: 三輪書店
• [Book] 神経疾患最新の治療 2018-2020 (2017)
  • Author(s): 黒田 宙、藤原一男
  • Total Pages: 印刷中
  • Publisher: 南江堂
• [Book] 神経内科clinical questions and pearls「中枢脱髄性疾患」 (2017)
  • Author(s): 7.高井良樹、藤原一男
  • Total Pages: 印刷中
  • Publisher: 中外医学社
• [Book] 臨床神経内科学(改訂6版) (2016)
  • Author(s): 藤原一男
  • Total Pages: 13
  • Publisher: 南山堂