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 and Delegate
    - Japanese Society of Internal Medicine: Councilor
    - Japanese Society of Neuroimmunology: Director
    - Japanese Society of Neurological Therapeutics: Councilor
    - Japanese Society for Neuroinfectious Diseases: Councilor
    - Japan Multiple Sclerosis Network: Director
    - Pan-Asian Congress for Treatment and Research in Multiple Sclerosis (PACTRIMS): Central organizing committee member
    - American Academy of Neurology (AAN) and European Academy of Neurology (EAN): 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 Parkinson's Disease Center, Director

  • Center for Parkinson's Disease Research, Keio University, 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

  • CGRP-monoclonal antibodies in Japan: insights from an online survey of physician members of the Japanese headache society

    Takizawa T., Ihara K., Watanabe N., Takemura R., Takahashi N., Miyazaki N., Shibata M., Suzuki K., Imai N., Suzuki N., Hirata K., Takeshima T., Nakahara J.

    Journal of Headache and Pain (Journal of Headache and Pain)  25 ( 1 )  2024.12

    ISSN  11292369

     View Summary

    Background: Anti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) have greatly changed migraine treatment options. In Japan, although CGRPmAb guidelines (≥ 4 monthly migraine days (MMDs) and ≥ 1 previous preventive failure) are well-acknowledged, the actual use of CGRPmAbs and the circumstances of the related headache care are unknown. Methods: We conducted an online survey of Japanese Headache Society members, inquiring about the physicians' experience with CGRPmAbs and how they make decisions related to their use. Results: Of the 397 respondents, 320 had prescribed CGRPmAbs. The threshold number of previous preventive failures for recommending a CGRPmAb was two for the majority of the respondents (n = 170, 54.5%), followed by one (n = 64, 20.5%). The MMD threshold was ≥ 4 for 71 respondents (22.8%), ≥ 6 for 68 (21.8%), ≥ 8 for 76 (24.4%), and ≥ 10 for 81 (26.0%). The respondents tended to assess treatment efficacy after 3 months (episodic migraine: n = 217, 69.6%, chronic migraine: n = 188, 60.3%). The cost of CGRPmAbs was described by many respondents in two questions: (i) any request for a CGRPmAb (27.7%), and (ii) the most frequently reported reason for responders to discontinue CGRPmAbs (24.4%). Conclusions: Most of the respondents recommended CGRPmAbs to patients with ≥ 2 preventive failures, followed by ≥ 1. The MMD threshold ranged mostly from ≥ 4 to ≥ 10. The concern for costs was raised as a major limiting factor for prescribing CGRPmAbs.

  • Real-world management of patients with neuromyelitis optica spectrum disorder using satralizumab: Results from a Japanese claims database

    Nakashima I., Nakahara J., Yasunaga H., Yamashita M., Nishijima N., Satomura A., Nio M., Fujihara K.

    Multiple Sclerosis and Related Disorders (Multiple Sclerosis and Related Disorders)  84 2024.04

    ISSN  22110348

     View Summary

    Background: Satralizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has been approved globally for the treatment of neuromyelitis optica spectrum disorder (NMOSD), based on positive results from two randomized, double-blind, phase 3 studies: SAkuraSky (NCT02028884) and SAkuraStar (NCT02073279). There remains an unmet need to understand the real-world management of NMOSD, especially in patients undergoing tapering of concomitant therapy. We examined real-world treatment patterns, including concomitant glucocorticoids and immunosuppressants, and relapse in satralizumab-treated patients with NMOSD, using a Japanese administrative hospital claims database. Methods: We used retrospective data from the Medical Data Vision hospital-based administrative claims database. The index date was the date of first satralizumab prescription and the study period was set between August 2018 and March 2022. Patients were included in the overall population if they had a first prescription for satralizumab between August 2020 and March 2022, an International Classification of Disease, Version10 code of G36.0 prior to March 2022, and were observable for ≥90 days prior to the index date. The primary endpoint was the percentage of patients with relapse-free reduction of oral glucocorticoids to 0 mg/day at 360 days of continued satralizumab treatment. Secondary endpoints included time to relapse, number of relapses after the index date while being on continuous satralizumab treatment, annualized relapse rate before and after the index date, and concomitant medication use. Relapse and dose reduction were identified using definition specifically developed for this study. Results: Of the 131 patients included in the overall population, most were female (90.8 %), aged 18–65 years (75.6 %), and were prescribed oral glucocorticoids (93.1 %). Azathioprine (19.1 %) and tacrolimus, a calcineurin inhibitor (18.3 %), were the most common immunosuppressants at index date. Six (4.6 %) patients had a history of biologic use (tocilizumab, 1 [0.8 %]; eculizumab, 5 [3.8 %]). Among 111 patients observable for 360 days pre-index, there were 0.6 ± 0.8 (mean ± SD) relapses during 360 days before the index date. The median (interquartile range) duration of satralizumab exposure was 197.0 (57.0–351.0) days. Most (125/131; 95.4 %) patients were relapse-free post-index; 6 (4.6 %) patients relapsed within 90 days after the index date, of which 2 had the first relapse within 7 days after the index date. Among 21 patients with 360-day follow-up, 6 (28.6 %) patients were on 0 mg/day dose of glucocorticoid prescription without relapse 360 days post-index. Of these 6 patients, 2 had no prescription of oral glucocorticoids at the index date and remained glucocorticoid- and relapse-free 360 days after the index date. Conclusion: These real-world data support the phase 3 clinical trials. Our results, over a median duration of satralizumab exposure of 197.0 days, showed that a majority (125/131, 95.4 %) of patients were relapse-free after initiating satralizumab treatment. The number of glucocorticoid-free patients without relapse increased over time under continuous satralizumab prescription. Further studies are needed to confirm if satralizumab can be used as a potential immunosuppressant- and glucocorticoid-sparing agent.

  • Validation study of the Japanese version of the King's Parkinson's Disease Pain Scale and the King's Parkinson's Disease Pain Questionnaire

    Kurihara K., Fujioka S., Mizutani Y., Watanabe H., Iwaoka K., Maeda T., Seki M., Tezuka T., Nakahara J., Konno T., Ishiguro T., Onodera O., Asano Y., Takahashi K., Rizos A., Chaudhuri K.R., Tsuboi Y.

    Parkinsonism and Related Disorders (Parkinsonism and Related Disorders)  120 2024.03

    ISSN  13538020

     View Summary

    Introduction: The King's Parkinson's Disease Pain Scale (KPPS)/King's Parkinson's Disease Pain Questionnaire (KPPQ) was developed as a tool to quantitatively assess pain in patients with Parkinson's disease (PwPD). Here, we conducted a Japanese multicenter validation study to verify the reliability of KPPS/KPPQ in Japanese PwPD. Methods: PwPD, ≥20 years, with unexplained pain were included; those with a definitive primary cause of pain other than PD were excluded. A total of 151 patients who fulfilled the criteria were analyzed, and test-retest reliability was investigated in 25 individuals. Results: The 151 patients included 101 women (66.9 %); mean age 68.3 ± 9.9 years, mean disease duration 9.2 ± 5.2 years. The most frequent pain type in the KPPS classification was musculoskeletal pain (82.8 %). There was a positive correlation between KPPS total score and the Non-Motor Symptoms Scale (NMSS) total score, NMSS item 27, the Parkinson's disease sleep scale-version 2 (PDSS-2) total score, PDSS-2 item 10, the Parkinson's Disease Questionnaire-8 (PDQ-8) summary index and PDQ-8 item 7. Cronbach's alpha of KPPS was 0.626 (0.562–0.658) and the intraclass correlation coefficient of test-retest reliability was 0.740. Cronbach's alpha of KPPQ was 0.660 (0.617–0.705) and a test-retest reliability of kappa coefficient was 0.593 (0.0–1.0). Conclusions: KPPS correlated well with other scales for assessing pain. KPPS correlated well with patients' quality of life, non-motor symptoms, and sleep disturbances. The reproducibility of KPPS/KPPQ makes it suitable for continuous evaluation of the same patient. On the other hand, the internal consistency of KPPS/KPPQ is rather low.

  • Non-lesional white matter changes depicted by q-space diffusional MRI correlate with clinical disabilities in multiple sclerosis

    Motegi H., Kufukihara K., Kitagawa S., Sekiguchi K., Hata J., Fujiwara H., Jinzaki M., Okano H., Nakamura M., Iguchi Y., Nakahara J.

    Journal of the Neurological Sciences (Journal of the Neurological Sciences)  456 2024.01

    ISSN  0022510X

     View Summary

    Background: We previously developed an optimized q-space diffusional MRI technique (normalized leptokurtic diffusion [NLD] map) to delineate the demyelinated lesions of multiple sclerosis (MS) patients. Herein, we evaluated the utility of NLD maps to discern the white matter abnormalities in normal-appearing white matter (NAWM) and the abnormalities' possible associations with physical and cognitive disabilities in MS. Methods: We conducted a retrospective observational study of MS patients treated at our hospital (Jan. 2012 to Dec. 2022). Clinical and MRI data were collected; Processing Speed Test (PST) data were obtained when possible. For a quantitative analysis of the NLD maps, we calculated the NLD index as GVROI/GVREF, where GV is a mean grayscale value in the regions of interest (ROIs) and the reference area (REF; cerebrospinal fluid). Results: One hundred-one individuals with MS were included. The lower corpus callosum and non-lesional WM NLD index were associated with worse Expanded Disability Status Scale (EDSS) and PST scores. The NLD indexes in the corpus callosum (p < 0.0001) and non-lesional white matter (p < 0.0001) were significantly reduced in progressive MS compared to relapsing-remitting MS. We categorized MS severity as moderate/severe (EDSS score ≥ 4 points) and mild (EDSS score < 4 points). The NLD indexes in the corpus callosum (p < 0.0001) and non-lesional white matter (p < 0.0001) were significantly lower in the moderate/severe MS group compared to the mild MS group. Conclusion: The NLD map revealed abnormalities in the non-lesional white matter, providing valuable insights for evaluating manifestations in MS patients.

  • Improvement of Functional Outcomes in Patients with Stroke who Received Alteplase for Over 15 Years: Japan Stroke Data Bank

    Ishigami A., Toyoda K., Nakai M., Yoshimura S., Wada S., Sasahara Y., Sonoda K., Miwa K., Koge J., Shiozawa M., Iwanaga Y., Miyamoto Y., Nakahara J., Suzuki N., Kobayashi S., Minematsu K., Koga M.

    Journal of Atherosclerosis and Thrombosis (Journal of Atherosclerosis and Thrombosis)  31 ( 1 ) 90 - 99 2024

    ISSN  13403478

     View Summary

    Aim: The nationwide verification of intravenous thrombolysis (IVT) was rarely performed after the extension of the therapeutic time window of alteplase or after the expansion of mechanical thrombectomy (MT). We aimed to examine the long-term change in accurate real-world outcomes of IVT in patients with acute ischemic stroke (AIS) using the Japan Stroke Databank, a representative Japan-wide stroke database. Methods: We extracted all patients with AIS who received IVT with alteplase between October 11, 2005, the approval date for alteplase use for AIS in Japan, and December 31, 2020. Patients were categorized into three groups using two critical dates in Japan as cutoffs: the official extension date of the therapeutic time window for IVT to within 4.5 h of symptom onset and the publication date of the revised guideline, where the evidence level of MT was heightened. We assessed the yearly trend of IVT implementation rates and the secular changes and three-group changes in clinical outcomes at discharge. Results: Of 124,382 patients with AIS, 9,569 (7.7%) received IVT (females, 41%; median age, 75 years). The IVT implementation rate has generally increased over time and plateaued in recent years. The proportion of favorable outcomes (modified Rankin Scale score of 0–2) increased yearly over 15 years. The results of the changes in the outcomes of the three groups were similar to those of the annual changes. Conclusions: We revealed that IVT implementation rates in patients with AIS increased, and the functional outcome in these patients improved over 15 years. Therefore, the Japanese IVT dissemination strategy is considered appropriate and effective.

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

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Reviews, Commentaries, etc. 【 Display / hide

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

  • Precision medicine research for neuromyelitis optica-spectrum disorders


    基盤研究(B), Principal investigator

  • 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

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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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