視神経脊髄炎の新たなアストロサイトパチーの疾患概念の確立と病態、治療に関する研究

2014 Fiscal Year Annual Research Report

• Project/Area Number: 22229008
• Research Institution: International University of Health and Welfare
• Principal Investigator: 糸山 泰人 国際医療福祉大学, 公私立大学の部局等, 教授 (30136428)
• Co-Investigator(Kenkyū-buntansha): 藤原 一男 東北大学, 医学(系)研究科(研究院), 教授 (70280873) ; 中島 一郎 東北大学, 医学(系)研究科(研究院), 准教授 (50333810) ; 三須 建郎 東北大学, 医学(系)研究科(研究院), 助教 (00396491)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: 脳神経疾患 / 視神経脊髄炎 / デビック病

Outline of Annual Research Achievements

I. 臨床解析では、①ミエリンオリゴデンドロサイト糖タンパク(MOG)抗体陽性NMO Spectrum Disorders (NMOSD)では、眼窩部MRIでは視神経に沿った長い病変、両側視神経炎などが特徴で、単相性の経過やステロイドパルス療法への反応性が良好な症例が多かった。OCTでは網膜神経線維層厚の減少がアクアポリン(AQP)4抗体陽性例に比べ軽度だった。②AQP4抗体陽性NMOSDのMRI病変の特徴、光干渉断層計(OCT)所見、またunconventional MRIの所見について国際的な専門家チームで過去の報告のまとめを行い国際誌に総説論文を発表した。
II. 病理病態解析では、①NMOの6型の病理像の分布には一定のパターンは見られなかった。②MOG抗体陽性例では髄液のアストロサイト傷害マーカーであるGFAPの濃度の上昇は見られなかったが、MBPは著明に上昇しており脱髄主体の病態と考えられた。また髄液AQP4抗体値やIL6値とGFAPには優位な相関があり、本自己抗体や炎症によってアストロサイト傷害が起こっていることを支持する所見だった。③フローサイトメーターを用いたAQP4抗体、MOG抗体の測定法を開発し、現在用いているCell-Based Assayとの相関を確認した。
III. ①国際委員会が作成した新たなNMOSDの診断基準の論文が国際誌に掲載予定となった。②AQP4抗体陽性女性は出産後3か月に有意に再発が増加し、妊娠前年の再発や不十分な免疫抑制がリスクを増加させることがわかり、妊娠中も適宜免疫抑制治療を継続することの必要性が示唆された。また新生児は出産後1か月でAQP4抗体が陰転化することなどを明らかにした。③NMOSDの新規治療薬の治験デザイン別(プラセボ対照試験、add-on等)の利点と問題点を詳細にまとめた。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Idiopathic aquaporin-4 antibody negative longitudinally extensive transverse myelitis (2015)
  • Author(s): Hyun JW, Kim SH, Huh SY, Kim W, Yun J, Joung A, Sato DK, Fujihara K, Kim HJ
  • Journal Title: Mult Scler Volume: 未定 Pages: 未定
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Severe demyelination but no astrocytopathy in clinically definite neuromyelitis optica with anti-myelin-oligodendrocyte glycoprotein antibody (2015)
  • Author(s): Ikeda K, Kiyota N, Kuroda H, Sato DK, Nishiyama S, Takahashi T, Misu T, Nakashima I, Fujihara K, Aoki M
  • Journal Title: Mult Scler Volume: 21 Pages: 656-659
  • DOI: 0.1177/1352458514551455
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Acute callosal disconnection syndrome as an initial manifestation of neuromyelitis optica spectrum disorders (2015)
  • Author(s): Kobayashi J, Kuroda H, Ezura M, Sugeno N, Shibui A, Takahashi T, Misu T, Fujihara K, Mori E, Aoki M
  • Journal Title: Neurol Clin Neurosci Volume: 未定 Pages: 未定
  • DOI: 10.1111/ncn3.164
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Multiple Sclerosis in Japan appears to be a milder disease compared to the UK (2015)
  • Author(s): Piccolo L, Kumar G, Nakashima I, Misu T, Kong Y, Wakerley B, Ryan S, Cavey A, Fujihara K, Palace J
  • Journal Title: J Neurol Volume: 262(4) Pages: 831-836
  • DOI: 10.1007/s00415-015-7637-3
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] MRI and retinal abnormalities in isolated optic neuritis with myelin-oligodendrocyte glycoprotein and aquaporin-4 antibodies: a comparative study (2015)
  • Author(s): Akaishi T, Sato DK, Nakashima I, Takeshita T, Takahashi T, Doi H, Kurosawa K, Kaneko K, Kuroda H, Nishiyama S, Misu T, Nakazawa T, Fujihara K, Aoki M
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 未定 Pages: 未定
  • DOI: 10.1136/jnnp-2014-310206
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Pregnancy-related relapse risk factors in women with anti-AQP4 antibody positivity and neuromyelitis optica spectrum disorder (2015)
  • Author(s): Shimizu Y, Fujihara K, Ohashi T, Nakashima I, Yokoyama K, Ikeguch R, Takahashi T, Misu T, Shimizu S, Aoki M, Kitagawa K
  • Journal Title: Mult Scler Volume: 未定 Pages: 未定
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Editorial commentary: MOG-IgG serological status matters in paediatric ADEM (2015)
  • Author(s): Misu T, Sato D, Nakashima I, Fujihara K
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 86 Pages: 242
  • DOI: 10.1136/jnnp-2014-308723
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Editorial: AQP4 in biopsied demyelinating lesions as a diagnostic clue to NMOSD and MS (2015)
  • Author(s): Fujihara K, Misu T
  • Journal Title: Neurology Volume: 84 Pages: 110-111
  • DOI: 10.1212/WNL.0000000000001135
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] MRI characteristics of neuromyelitis optica spectrum disorder: an international update (2015)
  • Author(s): Kim, HJ, Paul F, Lana-Peixoto MA, Tenembaum S, Asgari N, Palace J, Klawiter EC, Sato DK, de Seze J, Jens Wuerfel J, Banwell BL, Villoslada P, Saiz A, Fujihara K, Kim SH
  • Journal Title: Neurology Volume: 84 Pages: 1165-1173
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Challenges and opportunities in designing clinical trials for neuromyelitis optica (2015)
  • Author(s): Weinshenker BG, Barron G, Behne JM, Bennett JL, Chin PS, Cree B, de Seze J, Armando Flor, Fujihara K, Greenberg BM, Higashi S, Holt W, Khan OA, Knappertz V, Levy M, Melia AT, Palace J, Smith TJ, Sormani MP, Van Herle K, VanMeter SA, Villoslada P, Walton MK, Wasiewski W, Wingerchuk D, Yeaman M
  • Journal Title: Neurology Volume: 84(17) Pages: 1805-1815
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] International consensus diagnostic criteria for neuromyelitis optica spectrum disorders (2015)
  • Author(s): Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, de Seze J, Fujihara K, Greenberg B, Jacob A, Jarius S, Lana-Peixoto M, Levy M, Simon JH, Tenembaum S, Traboulsee AL, Waters P, Wellik KE, Weinshenker BG
  • Journal Title: Neurology Volume: 未定 Pages: 未定
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cerebrospinal fluid aquaporin-4 antibody levels in neuromyelitis optica attacks (2014)
  • Author(s): Sato DK, Callegaro D, MD, PhD2; Jorge FMdH, Nakashima I, Nishiyama S, Takahashi T, Simm RF, Apostolos-Pereira SL, Misu T, Steinman L, Aoki M, Fujihara K
  • Journal Title: Ann Neurol Volume: 76 Pages: 305-309
  • DOI: 10.1002/ana.24208
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Anti-N-methyl-aspartate receptor encephalitis with multiphasic demyelination (2014)
  • Author(s): Kaneko K, Sato, DK, Misu T Kurosawa K, Nakashima I, Fujihara K, Aoki M
  • Journal Title: Ann Neurol Volume: 76 Pages: 462-464
  • DOI: 10.1002/ana.24224
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Editorial: Secondary progression and innate immunity in NMO: a possible link to alemtuzumab (2014)
  • Author(s): Fujihara K, Nakashima I
  • Journal Title: Neuroimmunology & Neuroinflammation Volume: 1(3) Pages: e38
  • DOI: 10.1212/NXI.0000000000000038
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Toward more-accurate diagnosis in neuromyelitis optica (2014)
  • Author(s): Fujihara K, Palace J
  • Journal Title: Nat Rev Neurol Volume: 10 Pages: 679-681
  • DOI: 10.1038/nrneurol.2014.216
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Pain- prevalence, pathogenesis and therapy in neuromyelitis optica (2014)
  • Author(s): Bradl M, Kanamori Y, Nakashima I, Misu T, Fujihara K, Lassmann H, Sandkuhler J
  • Journal Title: Nat Rev Neurol Volume: 10 Pages: 529-536
  • DOI: 10.1038/nrneurol.2014.129
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The investigation of optic neuritis: a review and proposed protocol (2014)
  • Author(s): Petzold A, Wattjes M, Costello F, Rivera JF, Fraser C, Fujihara K, Leavitt J, Marignier R, Paul F, Schippling S, Sindic C, Villoslada P, Weinshenker B, Plant G
  • Journal Title: Nat Rev Neurol Volume: 10 Pages: 447-458
  • DOI: 10.1038/nrneurol.2014.108
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Symposium on Neuromyelitis Optica Spectrum Disorders: Seronegative NMO Spectrum Disorders and MOG-IgG (2014)
  • Author(s): Fujihara K
  • Organizer: 8th Annual Academic Sessions of Sri Lankan Medical Association (ASN)
  • Place of Presentation: コロンボ(スリランカ)
  • Year and Date: 2014-11-14 – 2014-11-16
  • Invited
• [Presentation] Symposium on Pediatric Neurology: Central Demyelinating Disorders (2014)
  • Author(s): Fujihara K
  • Organizer: 8th Annual Academic Sessions of Sri Lankan Medical Association (ASN)
  • Place of Presentation: コロンボ(スリランカ)
  • Year and Date: 2014-11-14 – 2014-11-16
  • Invited
• [Presentation] Differential Diagnosis of Longitudinally Extensive Transverse Myelitis (2014)
  • Author(s): Fujihara K
  • Organizer: Sri Lankan Medical Association (SLMA) Symposium on NMO and NMO Spectrum Disorders
  • Place of Presentation: コロンボ(スリランカ)
  • Year and Date: 2014-11-13 – 2014-11-13
  • Invited
• [Presentation] International Consensus Diagnostic Criteria of NMOSD (2014)
  • Author(s): Fujihara K
  • Organizer: Sri Lankan Medical Association (SLMA) Symposium on NMO and NMO Spectrum Disorders
  • Place of Presentation: コロンボ(スリランカ)
  • Year and Date: 2014-11-13 – 2014-11-13
  • Invited
• [Presentation] Therapeutic Update of NMOSD (2014)
  • Author(s): Fujihara K
  • Organizer: Sri Lankan Medical Association (SLMA) Symposium on NMO and NMO Spectrum Disorders
  • Place of Presentation: コロンボ(スリランカ)
  • Year and Date: 2014-11-13 – 2014-11-13
  • Invited
• [Presentation] Personalized Treatment in MS, Algorithms (2014)
  • Author(s): Fujihara K
  • Organizer: European Charcot Foundation Symposium, The 7th Annual Congress of PACTRIMS
  • Place of Presentation: 台北(台湾)
  • Year and Date: 2014-11-06 – 2014-11-06
  • Invited
• [Presentation] Workshop 10: Updates on Demyelinating Diseases, Demyelination after discovery of aquaporin 4 (multiple sclerosis, neuromyelitis optica) (2014)
  • Author(s): Fujihara K
  • Organizer: The 18th International Congress of Neuropathology (ICN2014)
  • Place of Presentation: リオデジャネイロ(ブラジル)
  • Year and Date: 2014-09-17 – 2014-09-17
  • Invited
• [Presentation] Parallel Session 2: MS subpopulations and disease variants, (PS2.2) Neuromyelitis Optica Spectrum Disorders: Evolution and Current Concept (2014)
  • Author(s): Fujihara K
  • Organizer: Joint 2014 ACTRIMS-ECTRIMS Meeting (MSBoston2014)
  • Place of Presentation: ボストン（米国）
  • Year and Date: 2014-09-11 – 2014-09-11
  • Invited
• [Presentation] Teaching Course 6: Neuromyelitis Optica (NMO), AQP4-Antibody-Seronegative NMOSD, the Clinical Dilemma (2014)
  • Author(s): Fujihara K
  • Organizer: Joint 2014 ACTRIMS-ECTRIMS Meeting (MSBoston2014)
  • Place of Presentation: ボストン（米国）
  • Year and Date: 2014-09-10 – 2014-09-10
  • Invited
• [Presentation] Neuromyelitis optica (NMO), an update (2014)
  • Author(s): Fujihara K
  • Organizer: Neurology Lecture, The Drum Tower Hospital, Nanjing Medical University
  • Place of Presentation: 南京（中国）
  • Year and Date: 2014-07-29 – 2014-07-29
  • Invited
• [Presentation] Neuromyelitis optica (NMO), an update (2014)
  • Author(s): Fujihara K
  • Organizer: Neurology Seminar, Tianjin Neurological Institute, Tianjin Medical University
  • Place of Presentation: 天津（中国）
  • Year and Date: 2014-07-28 – 2014-07-28
  • Invited
• [Presentation] Pathology and pathophysiology, Astrocytopathy (2014)
  • Author(s): Fujihara K
  • Organizer: European NMO Meeting 2014
  • Place of Presentation: ロンドン（英国）
  • Year and Date: 2014-06-20 – 2014-06-20
  • Invited
• [Presentation] Syndrome that mimic NMO: OSMS (2014)
  • Author(s): Fujihara K
  • Organizer: European NMO Meeting 2014
  • Place of Presentation: ロンドン（英国）
  • Year and Date: 2014-06-19 – 2014-06-19
  • Invited
• [Book] Pocket Drugs 2015 (2015)
  • Author(s): 藤原一男
  • Total Pages: 5
  • Publisher: 医学書院
• [Remarks] 東北大学大学院医学系研究科多発性硬化症治療学寄附講座
  • URL: http://www.ms.med.tohoku.ac.jp/index.html