School of Medicine, Department of Internal Medicine (Neurology) Department of Neurology, Keio University School of Medicine (Shinanomachi)



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Profile 【 Display / hide

  • - Japanese Society of Neurology
    District Representative
    - Japanese Society of Internal Medicine
    - Japanese Society of Neuroimmunology
    - Japanese Society of Neurological Therapeutics
    - Japanese Society for Neuroinfectious Diseases
    - Japan Multiple Sclerosis Network
    - Pan-Asian Congress for Treatment and Research in Multiple Sclerosis (PACTRIMS)
    Central organizing committee member

Message from the Faculty Member 【 Display / hide

  • We aim to develop actual therapeutics by every conceivable means – from advancement of translational research to home care medicine – to improve the quality of life of patients suffering from various neurological diseases.

Other Affiliation 【 Display / hide

  • Keio University Hospital Stroke Center, Director

Career 【 Display / hide

  • 2003.04

    慶應義塾大学, COEプログラム(生命科学), 研究員

  • 2004.04

    独立行政法人日本学術振興会, 特別研究員(DC1)

  • 2007.04

    独立行政法人日本学術振興会, 特別研究員(PD)

  • 2008.12

    慶應義塾大学, 医学部総合医科学研究センター, 特任講師

  • 2013.04

    慶應義塾大学, 医学部内科学教室(神経), 助教

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Academic Background 【 Display / hide

  • 2003.03

    Keio University, School of Medicine

    University, Graduated

  • 2007.03

    Keio University, Graduate School, Division of Medicine, 生理系専攻

    Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide

  • 博士(医学), Keio University, Coursework, 2007.03

Licenses and Qualifications 【 Display / hide

  • Medical license, 2003.05

  • Certified occupational physician, 2011.09

  • Board certified member of the Japanese Society of Internal Medicine, 2013.09

  • Board certified neurologist, 2014.07

  • Fellow of the Japanese Society of Internal Medicine (FJSIM), 2019.12


Research Areas 【 Display / hide

  • Life Science / Neurology

Research Keywords 【 Display / hide

  • Oligodendrocyte

  • Multiple sclerosis

  • Neuroimmunology

  • Neurology

  • Neuromyelitis optica spectrum disorder

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Research Themes 【 Display / hide

  • 神経治療学の拠点形成, 


  • 多発性硬化症の臨床研究, 


  • 中枢神経系髄鞘再生療法の開発, 



Books 【 Display / hide

  • Visualization of Myelin for the Diagnosis and Treatment Monitoring of Multiple Sclerosis

    Nakahara J., Advances in Experimental Medicine and Biology, 2019

     View Summary

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) affecting more than two million people worldwide. As the exact etiology of MS remains elusive, the diagnosis of MS is made by referring to the McDonald diagnostic criteria, which utilizes MRI as a tool to identify “demyelinated” MS lesions. In particular, hyperintense lesions on T2-weighted images (T2WI) or so-called “T2-lesions” are considered to represent demyelinated MS lesions. T2WI, however, lacks myelin specificity, and moreover, remyelination could not be depicted by the use of such modality. For the accurate diagnosis and treatment decision-making, or for the future development of remyelination therapeutics, imaging tools to visualize myelin-specific signals are mandatory. In this chapter, the current use and the limitation of imaging modalities in MS diagnosis and treatment will be reviewed, with the introduction of new imaging method, namely q-space Myelin Map (qMM), to be used for visualization of demyelination and remyelination in MS.

Papers 【 Display / hide

  • Immunodeficiency in patients with thymoma-associated myasthenia gravis

    Ishizuchi K., Takizawa T., Ohnuki Y., Sekiguchi K., Motegi H., Oyama M., Nakahara J., Shiina T., Suzuki S.

    Journal of Neuroimmunology (Journal of Neuroimmunology)  371 2022.10

    ISSN  01655728

     View Summary

    Thymoma with immunodeficiency is sometimes accompanied by myasthenia gravis (MG), but the clinical characteristics have not been elucidated. This study aimed to characterize its clinical and immunological features. Of the 132 thymoma-associated MG patients, 9 patients presented with immunodeficiency. All suffered from severe pneumonia, and most had invasive thymoma and autoimmune disorders. DRB1*08:03 and DQB1*06:01 alleles were frequently detected. Compared to group without immunodeficiency, they showed no significant differences in the severity of MG, significantly lower IgG concentrations and higher mortality rate. Thymoma-associated MG with immunodeficiency is a distinct subset requiring special attention to prevent infection during the follow-up period.

  • Close association between spreading depolarization and development of infarction under experimental ischemia in anesthetized male mice

    Unekawa M., Tomita Y., Masamoto K., Kanno I., Nakahara J., Izawa Y.

    Brain Research (Brain Research)  1792 2022.10

    ISSN  00068993

     View Summary

    Clinical and experimental evidence suggests that spreading depolarizations (SD) usually occur in patients with ischemic or hemorrhagic stroke when the gray matter of the brain is affected. In this study, we evaluated spatiotemporal changes of cerebral blood flow (CBF) during middle cerebral artery (MCA) occlusion and examined the relationship between SD occurrence and cerebral infarct development. In male isoflurane-anesthetized C57BL/6J mice, CBF changes over the ipsilateral parietal bone were recorded by laser speckle flowgraphy during and after transient (45 min, n = 22) or permanent occlusion (n = 22) of the distal MCA. Infarct volume was evaluated 24 hr after the operation. Upon MCA occlusion, CBF decreased by −55.6 ± 8.5 % in the lowest CBF and linearly recovered with increasing distance from the region. At 1–10 min after onset of occlusion, SD occurred and concentrically propagated from the core region, showing a decrease of CBF in the whole observed area along with a transient hyperemia and oligemia in the normal region. SD spontaneously re-occurred and propagated around the ischemic area in 37 % of mice, accompanied with a marked decrease of CBF in the core or a marked increase of CBF in the normal region. The CBF response to SDs gradually changed from the core to the normal area, depending upon the distance from the core region. Infarction was not observed in transiently (n = 2) or permanently (n = 4) occluded mice without SD. The infarct area tended to be larger with increasing number of SDs in transiently occluded mice. In conclusion, our findings suggest that the occurrence of SD during ischemia might elicit infarct formation and/or influence infarct development.

  • History and prospects of multiple sclerosis treatment

    Nakahara J.

    Rinsho shinkeigaku = Clinical neurology (Rinsho shinkeigaku = Clinical neurology)  62 ( 7 ) 517 - 523 2022.07

    ISSN  0009918X

     View Summary

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system of unknown etiology. Based on a hypothesis that MS is caused by certain viral infections, the efficacy of interferon β was examined in patients and it became the first disease-modifying drug (DMD) approximately 30 years ago. Through the series of research utilizing experimental autoimmune encephalomyelitis, many other DMDs were later developed. With emerging insights on limitation of the animal model, newer treatment strategies are being developed based on pathological findings from MS patients. In the current article, the history of MS treatment and its future prospects will be reviewed and discussed.

  • The questionnaire survey regarding the impact of COVID-19 pandemic on Parkinson's disease patients

    Tezuka T., Osada T., Terayama Y., Kubota M., Okusa S., Shiihashi G., Kubo S.I., Suzuki N., Nakahara J., Seki M.

    Rinsho shinkeigaku = Clinical neurology (Rinsho shinkeigaku = Clinical neurology)  62 ( 1 ) 8 - 14 2022.01

    ISSN  0009918X

     View Summary

    We conducted the multicenter questionnaire survey targeting patients with Parkinson's disease (PD) in order to investigate the impacts on their daily lives and their requests to hospitals in the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Mainly using open-ended questionnaire, we asked their anxiety, troubles they are facing, and requests toward hospitals in the pandemic of SARS-CoV-2. Two hundred fifth-eight PD patients answered the questionnaire. There were various opinions about anxiety such as "PD patients are susceptible and vulnerable to SARS-CoV-2" (36.8%). Concerning the troubles in the pandemic, the most frequent answer was that they couldn't participate in the rehabilitation and elderly day care (38.4%). Relatively many PD patients requested telemedicine (29.5%), whereas some people hoped face-to-face medical care (8.1%). There were demands about the delivery of medications (50.0%), the establishment of telephone consultations (43.8%), resources for rehabilitation at home (43.8%). The medical care adapted to the anxiety, trouble and requests of PD patients will be required in the era when we have to live with SARS-CoV-2.

  • Anemia in female patients with myasthenia gravis

    Sekiguchi K., Ishizuchi K., Takizawa T., Motegi H., Oyama M., Nakahara J., Suzuki S.

    PloS one (PloS one)  17 ( 9 )  2022

     View Summary

    Myasthenia gravis (MG) is the most common autoimmune neuromuscular disorder, and is more common in women than in men. Anemia is also more common in women. The purpose of this study was to investigate factors associated with anemia and the negative impact of anemia in female MG patients. We investigated factors related to MG and anemia in 215 female patients with MG, who were attending the MG clinic of Keio Hospital between January and December 2021. We statistically evaluated clinical factors related to anemia in patients with and without anemia. Eighty-five patients (40%) had anemia in the past, and 130 patients did not have anemia in the past. There were no significant differences in age at study, age at MG onset, body mass index, or frequency of autoantibodies between the anemia and non-anemia groups. MG severity evaluated by the MG Foundation of America classification was greater in the anemia group than in the non-anemia group. History of anemia was associated with immunosuppressive treatment, such as prednisolone and calcineurin inhibitor treatment. There was a correlation between hemoglobin levels and the MG-quality of life score. Long term immunosuppressive therapy can cause anemia in female MG patients. Anemia may negatively affect the quality of life of female MG patients.

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Papers, etc., Registered in KOARA 【 Display / hide

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Reviews, Commentaries, etc. 【 Display / hide

Research Projects of Competitive Funds, etc. 【 Display / hide

  • ミエリンマップ法を用いた多発性硬化症における髄鞘病理の画像解析


    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • 髄鞘を標的とした神経変性疾患・脊髄損傷に対する新規治療戦略に関する研究


    文部科学省, Grant-in-Aid for Scientific Research, Principal investigator

  • 髄鞘の可視化技術による多発性硬化症の病型分類に関する研究


    文部科学省, Grant-in-Aid for Scientific Research, Principal investigator

  • アストロサイトによるin vivoケトン体生合成機構の解明


    文部科学省, Grant-in-Aid for Scientific Research, Principal investigator

  • 内在性オリゴデンドロサイト前駆細胞の分化誘導を基盤とする中枢神経系髄鞘再生医薬の開発


    独立行政法人医薬基盤研究所, -, Principal investigator

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Intellectual Property Rights, etc. 【 Display / hide

  • Drug delivery system toward demyelinating lesion and biochemical marker of demyelinating lesions

    Date applied: 8252540  2012.08 

    Date issued: 8252540  2012.08

    Patent, Joint

  • Medicinal compositions containing Fc receptor γ chain activator

    Date applied: 7901678  2011.03 

    Date issued: 7901678  2011.03

    Patent, Joint

  • Fc受容体γ鎖活性化物質を含有する医薬組成物

    Date applied: 4214249  2008.11 

    Date issued: 4214249  2008.11

    Patent, Joint

Awards 【 Display / hide

  • Best Presentation Award

    2017, Sendai Conference

  • MSJ-PACTRIMS investigator award

    2014, Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS)

  • 優秀指導教官賞

    2014, 日本内科学会

  • MSJ-PACTRIMS Investigator Award

    2014, PACTRIMS

  • 優秀指導教官賞

    2014, 内科学サミット2014

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Courses Taught 【 Display / hide











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Memberships in Academic Societies 【 Display / hide

  • 日本内科学会

  • 日本神経学会

  • 日本神経免疫学会

  • 日本神経治療学会

  • 日本脳卒中学会


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