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 Global Research Institute (KGRI), Deputy Director

  • 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

  • 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.

  • Comprehensive and long-term surveys of COVID-19 sequelae in Japan, an ambidirectional multicentre cohort study: Study protocol

    Nakagawara K., Namkoong H., Terai H., Masaki K., Tanosaki T., Shimamoto K., Lee H., Tanaka H., Okamori S., Kabata H., Chubachi S., Ikemura S., Kamata H., Yasuda H., Kawada I., Ishii M., Ishibashi Y., Harada S., Fujita T., Ito D., Bun S., Tabuchi H., Kanzaki S., Shimizu E., Fukuda K., Yamagami J., Kobayashi K., Hirano T., Inoue T., Kagyo J., Shiomi T., Ohgino K., Sayama K., Otsuka K., Miyao N., Odani T., Oyamada Y., Masuzawa K., Nakayama S., Suzuki Y., Baba R., Nakachi I., Kuwahara N., Ishiguro T., Mashimo S., Minematsu N., Ueda S., Manabe T., Funatsu Y., Koh H., Yoshiyama T., Saito F., Ishioka K., Takahashi S., Nakamura M., Goto A., Harada N., Kusaka Y., Nakano Y., Nishio K., Tateno H., Edahiro R., Takeda Y., Kumanogoh A., Kodama N., Okamoto M., Umeda A., Hagimura K., Sato T., Miyazaki N., Takemura R., Sato Y., Takebayashi T., Nakahara J., Mimura M., Ogawa K., Shimmura S., Negishi K., Tsubota K., Amagai M., Goto R., Ibuka Y., Hasegawa N., Kitagawa Y., Kanai T., Fukunaga K.

    BMJ Open Respiratory Research (BMJ Open Respiratory Research)  8 ( 1 )  2021.11

     View Summary

    Introduction The rapid spread of COVID-19 posed a global burden. Substantial number of people died of the disease in the acute phase of infection. In addition, a significant proportion of patients have been reported to suffer from post-acute phase symptoms, sequelae of COVID-19, which may negatively influence the quality of daily living and/or socioeconomic circumstances of the patients. However, no previous study has comprehensively and objectively assessed the quality of life of patients by using existing international scales. Further, evidence of socioeconomic consequences among patients with COVID-19 is scarce. To address the multidimensional issues from sequelae of COVID-19, evidence from comprehensive surveys beyond clinical perspectives is critical that investigates health, and social determinants of disease progression as well as socioeconomic consequences at a large scale. Methods and analysis In this study, we plan to conduct a nationwide and comprehensive survey for the sequelae of COVID-19 in a total of 1000 patients diagnosed at 27 hospitals throughout Japan. This study will evaluate not only the health-related status of patients from clinical perspectives but also the Health-related Quality of Life (HRQoL) scores, socioeconomic status and consequences to discuss the sequelae of the disease and the related risk factors. The primary endpoint is the frequency of long-term complications of COVID-19 infection. The secondary endpoints are risk factors for progression to sequelae of COVID-19 infection. The study will provide robust and important evidence as a resource to tackle the issues from the sequelae of COVID-19 from the multi-dimensional perspectives. Ethics and dissemination This trial was approved by the Keio University School of Medicine Ethics Committee (20200243, UMIN000042299). The results of this study will be reported at a society meeting or published in a peer-reviewed journal.

  • Meningitis caused by Listeria monocytogenes in a locally advanced cervical cancer patient with pyometra: A case report

    Matoba Y., Nishio H., Sekiguchi K., Uno S., Masuda K., Hiramatsu M., Takahashi M., Oishi M., Uwamino Y., Uchida S., Daté Y., Morisada T., Banno K., Nakahara J., Aoki D.

    Gynecologic Oncology Reports (Gynecologic Oncology Reports)  37 2021.08

     View Summary

    Locally advanced cervical cancer occasionally induces pyometra, but there have been no reports of meningitis where pyometra is the cause of infection. Here, we report a case of Listeria monocytogenes meningitis related to pyometra during concurrent chemoradiotherapy (CCRT) in a cervical cancer patient. The patient, a 77-year-old woman, was diagnosed with Stage IIB (FIGO 2018) cervical adenocarcinoma, and CCRT was initiated. Pyometra was exacerbated during CCRT, and after her first brachytherapy, she presented at our hospital with fever and decreased consciousness level. After admission to the Intensive Care Unit, the patient lost consciousness and experienced frequent seizures; tracheal intubation was required. Whole-body computed tomography revealed pyometra; therefore, transvaginal removal of the abscess was performed. Laboratory tests and vital signs indicated septic shock, and meropenem was administered. L. monocytogenes was detected in the abscess from the uterine cavity and the blood cultures on the third day of hospitalization. A lumbar puncture was performed on the same day to investigate whether the patient had meningitis. A FilmArray meningitis/encephalitis panel test of the spinal fluid revealed L. monocytogenes. After the diagnosis of meningitis with L. monocytogenes, ampicillin and gentamicin were started, and the blood test results gradually improved. Five months after the initial episode, her consciousness recovered, however she still received mechanical ventilatory support. L. monocytogenes infections can occur in patients undergoing chemotherapy, even without the use of steroids or immunosuppressive agents. In cases with pyometra, intrauterine manipulation can increase the risk of severe infection.

  • Effect of ofatumumab versus placebo in relapsing multiple sclerosis patients from Japan and Russia: Phase 2 APOLITOS study

    Kira J.I., Nakahara J., Sazonov D.V., Kurosawa T., Tsumiyama I., Willi R., Zalesak M., Pingili R., Häring D.A., Ramanathan K., Kieseier B.C., Merschhemke M., Su W., Saida T.

    Multiple Sclerosis Journal (Multiple Sclerosis Journal)   2021

    ISSN  13524585

     View Summary

    Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, has been developed as a treatment for relapsing multiple sclerosis (RMS) which can be self-administered at home. Objective: To investigate the efficacy and safety of ofatumumab in RMS patients from Japan and Russia. Methods: APOLITOS included a 24-week, double-blind, placebo-controlled core-part followed by an open-label extension-part. Patients were randomized (2:1) to subcutaneous ofatumumab 20 mg or placebo. Primary outcome was the number of gadolinium-enhancing (Gd+) T1 lesions per scan over 24 weeks. Results: Sixty-four patients were randomized (ofatumumab, n = 43; placebo, n = 21). Primary endpoint was met; ofatumumab reduced Gd + T1 lesions versus placebo by 93.6% (p < 0.001) and the results were consistent across regions (Japan/Russia). Ofatumumab reduced annualized T2 lesion and relapse rate versus placebo by week 24. Both groups showed benefit from ofatumumab in the extension-part. Incidence of adverse events was lower with ofatumumab versus placebo (69.8% vs 81.0%); injection-related reactions were most common. No deaths, opportunistic infections, or malignancies were reported. Conclusion: Ofatumumab demonstrated superior efficacy versus placebo, with sustained effect through 48 weeks in RMS patients from Japan/Russia. Switching to ofatumumab after 24 weeks led to rapid radiological and clinical benefits. Safety findings were consistent with pivotal trials.

  • Mechanisms of myelin repair, MRI techniques and therapeutic opportunities in multiple sclerosis

    Sommer R.C., Hata J., Rimkus C.d.M., Klein da Costa B., Nakahara J., Sato D.K.

    Multiple Sclerosis and Related Disorders (Multiple Sclerosis and Related Disorders)  58 2021

    ISSN  22110348

     View Summary

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). The remyelination process requires the activation, migration and differentiation of oligodendrocyte progenitor cells (OPC) in demyelinated areas. The metabolic dysfunction in chronic demyelinating lesions impairs the activation of OPCs, the myelin debris clearance by microglia decreases with age, along with diminished secretion of factors promoting OPC differentiation. Conventional magnetic resonance imaging (MRI) sequences have limited ability to differentiate unmyelinated and remyelinated lesions. Advanced MRI sequences based on magnetization transfer ratio (MTR), myelin water fraction (MWF) and diffusion tensor imaging (DTI) have been used to evaluate remyelination in clinical trials. More recently, the q-space myelin map (qMM) has been used on experimental and exploratory clinical studies. The improvement of myelin-specific MRI sequences with high reliability and standardization among centers will allow a more accurate evaluation of new therapies to improve remyelination. These new remyelination promoting treatments alone or in combination with current options may reduce the risk of long-term disability in MS.

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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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