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Repetitive transcranial magnetic stimulation for cognitive dysfunction in multiple sclerosis

Research Project

Project/Area Number 18K10743
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 59010:Rehabilitation science-related
Research InstitutionUniversity of Toyama

Principal Investigator

Nakatsuji Yuji  富山大学, 学術研究部医学系, 教授 (20332744)

Co-Investigator(Kenkyū-buntansha) 野口 京  富山大学, 学術研究部医学系, 教授 (10242497)
高岩 亜輝子  十文字学園女子大学, 人間生活学部, 准教授 (20432114)
小西 宏史  富山大学, 附属病院, 医員 (30816012)
山本 真守  富山大学, 附属病院, 大学院医員 (80816025)
石黒 幸治  富山大学, 附属病院, 理学療法士 (90811258)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords多発性硬化症 / 経頭蓋直流電気刺激療法 / 高次脳機能 / 認知症 / 疲労 / うつ / 経頭蓋磁気刺激療法 / 鬱 / NMOSD / 視神経脊髄炎 / 磁気刺激療法 / fMRI
Outline of Final Research Achievements

Though we originally tried to evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) on non-motor symptoms of patients with multiple sclerosis (MS), we used direct current stimulation (tDCS) due to its safety and convenience. We found that the fatigue was improved by the tDCS therapy, and that the cognitive dysfunction and depression were also tended to be improved. Since there have been no effective treatments for the non-motor dysfunction in patients with MS, tDCS may be a promising therapy.

Academic Significance and Societal Importance of the Research Achievements

MSに対する様々な疾患修飾薬(DMD)が開発・使用可能となり運動障害から見たMSの機能予後は格段に改善された。それに相反して、MSの非運動症状である高次脳機能障害、疲労、うつが社会的にクローズアップされるようになってきた。これらの症状にたいしてはこれまで有効な治療法がなく、早期離職者の増加など社会的に問題となっていたが、本研究で非侵襲的脳刺激療法が新たな治療法となりうることを示すことができたことは大変大きな意義がある。

Report

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

    (38 results)

All 2021 2020 2019 2018

All Journal Article (12 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 12 results,  Open Access: 9 results) Presentation (19 results) (of which Int'l Joint Research: 9 results) Book (7 results)

  • [Journal Article] HLA genotype-clinical phenotype correlations in multiple sclerosis and neuromyelitis optica spectrum disorders based on Japan MS/NMOSD Biobank data2021

    • Author(s)
      Watanabe M. Nakamura Y. Sato S. Niino M. Fukaura H. Tanaka M. Ochi H. et al
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 607-607

    • DOI

      10.1038/s41598-020-79833-7

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Serum neurofilament light chain in chronic inflammatory demyelinating polyneuropathy2021

    • Author(s)
      Hayashi Tomohiro、Nukui Takamasa、Piao Jin‐Lan、Sugimoto Tomoyuki、Anada Ryoko、Matsuda Noriyuki、Yamamoto Mamoru、Konishi Hirofumi、Dougu Nobuhiro、Nakatsuji Yuji
    • Journal Title

      Brain and Behavior

      Volume: - Issue: 5

    • DOI

      10.1002/brb3.2084

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Spinal Cord Uptake of Fluorodeoxyglucose in a Patient with Relapsing Polychondritis2020

    • Author(s)
      Anada Ryoko、Hayashi Tomohiro、Yamamoto Mamoru、Nakatsuji Yuji
    • Journal Title

      Internal Medicine

      Volume: 59 Issue: 10 Pages: 1339-1340

    • DOI

      10.2169/internalmedicine.3660-19

    • NAID

      130007843232

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2020-05-15
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sema4A is implicated in the acceleration of Th17 cell-mediated neuroinflammation in the effector phase2020

    • Author(s)
      Koda Toru、Namba Akiko、Kinoshita Makoto、Nakatsuji Yuji、Sugimoto Tomoyuki、Sakakibara Kaori、Tada Satoru、Shimizu Mikito、Yamashita Kazuya、Takata Kazushiro、Ishikura Teruyuki、Murata Syo、Beppu Shohei、Kumanogoh Atsushi、Mochizuki Hideki、Okuno Tatsusada
    • Journal Title

      Journal of Neuroinflammation

      Volume: 17 Issue: 1 Pages: 1-9

    • DOI

      10.1186/s12974-020-01757-w

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitochondrial DNA enhance innate immune responses in neuromyelitis optica by monocyte recruitment and activation2020

    • Author(s)
      Mikito Shimizu, Tatsusada Okuno, Makoto Kinoshita, Hisae Sumi, Harutoshi Fujimura, Kazuya Yamashita, Tomoyuki Sugimoto, Shuhei Sakakibara, Kaori Sakakibara, Toru Koda, Satoru Tada, Teruyuki Ishikura, Hisashi Murata, Shohei Beppu, Naoyuki Shiraishi, Yasuko Sugiyama, Yuji Nakatsuji, Atsushi Kumanogoh & Hideki Mochizuki
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 13274-13274

    • DOI

      10.1038/s41598-020-70203-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Astrocyte metabolism in multiple sclerosis investigated by 1-C-11 acetate PET2020

    • Author(s)
      Kato, H. Okuno, T. Isohashi, K. Koda, T. Shimizu, M. Mochizuki, H. Nakatsuji, Y. Hatazawa, J.
    • Journal Title

      J Cereb Blood Flow Metab

      Volume: 41 Issue: 2 Pages: 369-379

    • DOI

      10.1177/0271678x20911469

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cerebrospinal fluid ATP as a potential biomarker in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke like episodes (MELAS)2020

    • Author(s)
      Nukui Takamasa、Matsui Atsushi、Niimi Hideki、Yamamoto Mamoru、Matsuda Noriyuki、Piao Jin-Lan、Noguchi Kyo、Kitajima Isao、Nakatsuji Yuji
    • Journal Title

      Mitochondrion

      Volume: 50 Pages: 145-148

    • DOI

      10.1016/j.mito.2019.11.001

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single injection of sustained-release prostacyclin analog ONO-1301-MS ameliorates hypoxic toxicity in the murine model of amyotrophic lateral sclerosis.2019

    • Author(s)
      Tada S, Okuno T, Shimizu M, Sakai Y, Sumi-Akamaru H, Kinoshita M, Yamashita K, Sanda E, Choong CJ, Namba A, Sasaki T, Koda T, Takata K, Miyagawa S, Sawa Y, Nakatsuji Y, Mochizuki H.
    • Journal Title

      Sci Rep.

      Volume: 27 Issue: 1 Pages: 5252-5252

    • DOI

      10.1038/s41598-019-41771-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Semaphorin 4A as a biomarker of multiple sclerosis and neuromyelitis optica spectrum disorder.2019

    • Author(s)
      Okuno T, Ishikura T, Kinoshita M, Nakatsuji Y, Kumanogoh A, Mochizuki H.
    • Journal Title

      Clin Exp Neuroimm

      Volume: 10 Pages: 18-26

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Semaphorin 4A as a biomarker of multiple sclerosis and2019

    • Author(s)
      Okuno Tatsusada, Ishikuro Teruyuki, KInoshita Makoto, Nakatsuji Yuji, Kumanogoh Atsushi, Mochizuki Hideki
    • Journal Title

      Clinical & Experimental Neuroimmunology

      Volume: 10 Pages: 18-26

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Beneficial effects of fingolimod in MS patients with high serum Sema4A levels2018

    • Author(s)
      Koda Toru、Namba Akiko、Nakatsuji Yuji、Niino Masaaki、Miyazaki Yusei、Sugimoto Tomoyuki、Kinoshita Makoto、Takata Kazushiro、Yamashita Kazuya、Shimizu Mikito、Fukazawa Toshiyuki、Kumanogoh Atsushi、Mochizuki Hideki、Okuno Tatsusada
    • Journal Title

      PLoS One

      Volume: 13 Issue: 3 Pages: 1-10

    • DOI

      10.1371/journal.pone.0193986

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Transcranial Direct Current Stimulation (tDCS) Over the Frontal Polar Area on Motor and Executive Functions in Parkinson’s Disease; A Pilot Study2018

    • Author(s)
      Ishikuro Koji、Dougu Nobuhiro、Nukui Takamasa、Yamamoto Mamoru、Nakatsuji Yuji、Kuroda Satoshi、Matsushita Isao、Nishimaru Hiroshi、Araujo Mariana F. P.、Nishijo Hisao
    • Journal Title

      Frontiers in Aging Neuroscience

      Volume: 10 Pages: 1-9

    • DOI

      10.3389/fnagi.2018.00231

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 多発性硬化症治療におけるDMD反応性と免疫セマホリンSema4Aの関連の検証2020

    • Author(s)
      甲田亨、奥野龍禎、木下允、望月秀樹、宮本勝一、新野正明、清水優子、山本真守、熊ノ郷淳、中辻裕司
    • Organizer
      第32回日本神経免疫学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] MSおよびNMOSD患者における髄液dsDNAの検討2020

    • Author(s)
      山本真守、奥野龍禎、朴今蘭、清水幹人、温井孝昌、甲田亨、木下允、宮本勝一、林 智宏、小西宏史、道具伸浩、中辻裕司
    • Organizer
      第32回日本神経免疫学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 視神経脊髄炎及び多発性硬化症患者のアストロサイト代謝と認知機能との関連~11C-酢酸PETを用いた検討~2020

    • Author(s)
      奥野龍禎、加藤弘樹、甲田亨、木下允、畑澤順、中辻裕司、望月秀樹
    • Organizer
      第32回日本神経免疫学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 第5回全国調査が示す多発性硬化症・視神経脊髄炎総患者数の増加2020

    • Author(s)
      磯部紀子、新野正明、松下拓也、中村優理、中島一郎、渡邉充、酒井康成、迫田礼子、中原仁、河内泉、越智博文、中辻裕司、福元尚子、林史恵、中村好一、中村幸志、坂田清美、嶋田莉奈子、松井真、吉良潤一
    • Organizer
      第32回日本神経免疫学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Serum Sema4A levels correlate with distinct clinical phenotype in patients with NMOsd2020

    • Author(s)
      別府祥平、奥野龍禎、木下允、甲田亨、石倉照之、村田尚、中辻裕司、望月秀樹
    • Organizer
      第32回日本神経免疫学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] CIDP患者における血清ニューロフィラメントLの検討2020

    • Author(s)
      林智宏、朴今蘭、田中遼、廣澤宏昭、松田憲幸、穴田涼子、山本真守、小西宏史、温井孝昌、道具伸浩、中辻裕司.
    • Organizer
      第32回日本神経免疫学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] CONTINUED INCREASE OF MULTIPLE SCLEROSIS AND NEUROMYELITIS OPTICA IN JAPAN: UPDATES FROM THE 5TH NATIONWIDE SURVEY2020

    • Author(s)
      Noriko Isobe, Masaaki Niino, Takuya Matsushita, Yuri Nakamura, Ichiro Nakashima, Mitsuru Watanabe,Yasunari Sakai, Ayako Sakoda, Jin Nakahara, Izumi Kawachi, Hirofumi Ochi, Yuji Nakatsuji et al.
    • Organizer
      145th annual meeting of the American Neurological association
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Continued increase of multiple sclerosis and neuromyelitis optica and the north-south gradient in Japan; updates from the 5th nationwide survey2020

    • Author(s)
      Noriko Isobe, Masaaki Niino, Takuya Matsushita, Yuri Nakamura, Ichiro Nakashima, Mitsuru Watanabe, Yasunari Sakai, Ayako Sakoda, Jin Nakahara, Izumi Kawachi, Hirofumi Ochi, Yuji Nakatsuji et al.
    • Organizer
      8th JOINT ACTRIMS-ECTRIMS MEETING
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Continued increase of multiple sclerosis and neuromyelitis optica in Japan; updates from the 5th nationwide survey2020

    • Author(s)
      Noriko Isobe, Masaaki Niino, Takuya Matsushita, Yuri Nakamura, Ichiro Nakashima, Mitsuru Watanabe, Yasunari Sakai, Ayako Sakoda, Jin Nakahara, Izumi Kawachi, Hirofumi Ochi, Yuji Nakatsuji et al.
    • Organizer
      28th European Charcot Foundation
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Astrocytic metabolism in the patients with multiple sclerosis investigated by 1-C-11 acetate PET.2019

    • Author(s)
      T Okuno, Y Nakatsuji, H Kato, T Koda, M Shimizu,J Hatazawa, H Mochizuki.
    • Organizer
      The 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Identification of innate immunity activation in the pathogenesis of NMO.2019

    • Author(s)
      M Shimizu, M Kinoshita, T Koda, K Yamashita, T Ishikura, K Miyamoto, Y Nakatsuji, H Mochizuki, T Okuno.
    • Organizer
      The 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pathogenic role of mitochondrial DNA through NLRP3 inflammasome in vitro and in vivo mouse model of neuromyelitis optica spectrum disorder.2019

    • Author(s)
      K Yamashita, M Kinoshita, K Miyamoto, A Namba, M Shimizu, T Koda, T Ishikura, Y Nakatsuji, A Kumanogoh, S Kusunoki, H Mochizuki, T Okuno.
    • Organizer
      The 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 当院における抗AQP4抗体陰性、抗MOG抗体陰性NMOSD症例の検討2019

    • Author(s)
      山本真守、松田憲幸、穴田涼子、林智宏、小西宏史、温井孝昌、道具伸浩、高橋利幸、朴金蘭、中辻裕司.
    • Organizer
      第31回 日本神経免疫学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 当院で経験した橋本脳症を疑った3症例の検討2019

    • Author(s)
      穴田涼子、松田憲幸、山本真守、林智宏、小西宏史、温井孝昌、道具伸浩、朴金蘭、中辻裕司.
    • Organizer
      第31回 日本神経免疫学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 結晶性検査と流動性検査のディスクレパンシー分析による軽度認知機能障害の検出方法2018

    • Author(s)
      髙岩亜輝子, 桑山直也, 秋岡直樹, 柏崎大奈, 黒田敏, 小西宏史, 田口芳治, 中辻裕司
    • Organizer
      日本神経学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Cerebrospinal fluid mitochondrial DNA elicits innate immune response in NMO spectrum disorder2018

    • Author(s)
      南波明子, 奥野龍禎, 甲田亨, 山下和哉, 清水幹人, 木下允, 熊ノ郷淳, 宮崎雄生, 新野正明, 宮本勝一, 中辻裕司, 望月秀樹
    • Organizer
      日本神経学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Sema4A expressed on hematopoietic cells determines interferon-beta response in Th17 autoimmunity2018

    • Author(s)
      M Kinoshita, T Okuno, A Namba, T Koda, M Shimizu, A Kumanogoh, Y Nakatsuji, H Mochizuki
    • Organizer
      Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Oral administration of succinate exacerbates an animal model of multiple sclerosis2018

    • Author(s)
      M Shimizu, K Takata, M Kinoshita, T Ishikura, T Koda, Y Nakatsuji, H Mochizuki, T Okuno
    • Organizer
      Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Cerebrospinal fluid mitochondrial DNA elicits innate immune response in neuromyelitis optica spectrum disorder2018

    • Author(s)
      K Yamashita, M Kinoshita, K Miyamoto, A Namba, M Shimizu, T Koda, Y Nakatsuji, A Kumanogoh, S Kusunoki, H Mochizuki, T Okuno
    • Organizer
      Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Book] 脱髄疾患における免疫細胞・グリア・ニューロン相互作用2020

    • Author(s)
      奥野龍禎、杉山靖子、中辻裕司.
    • Total Pages
      8
    • Publisher
      科学評論社
    • Related Report
      2020 Annual Research Report
  • [Book] 免疫性神経疾患とセマフォリン2020

    • Author(s)
      中辻裕司、甲田亨、木下允、奥野龍禎
    • Total Pages
      6
    • Publisher
      日本臨床社
    • Related Report
      2020 Annual Research Report
  • [Book] 多発性硬化症(MS)・視神経脊髄炎(NMO)、免疫・炎症病態x治療 Update2020

    • Author(s)
      中辻裕司. 奥野龍禎.
    • Total Pages
      8
    • Publisher
      南山堂
    • Related Report
      2019 Research-status Report
  • [Book] 多発性硬化症、視神経脊髄炎 今日の処方2019

    • Author(s)
      中辻裕司.
    • Total Pages
      4
    • Publisher
      南江堂
    • Related Report
      2019 Research-status Report
  • [Book] NMO-SDにおける血清LDH2019

    • Author(s)
      温井孝昌、中辻裕司.
    • Total Pages
      3
    • Publisher
      科学評論社
    • Related Report
      2019 Research-status Report
  • [Book] NMO-SDにおける血清Sema4A2019

    • Author(s)
      奥野龍禎、木下允、中辻裕司、望月秀樹.
    • Total Pages
      5
    • Publisher
      科学評論社
    • Related Report
      2019 Research-status Report
  • [Book] 急性散在性脳脊髄炎 acute disseminated encephalomyelitis (ADEM) 今日の治療指針2019

    • Author(s)
      中辻裕司
    • Total Pages
      1
    • Publisher
      医学書院
    • Related Report
      2019 Research-status Report

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

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