KEIO RESEARCHERS INFORMATION SYSTEM

Profile 【 Display / hide 】

Profile 【 Display / hide 】

• - Japanese Society of Neurology: 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
  - Japanese Society of Microcirculation: Director
  - Pan-Asian Congress for Treatment and Research in Multiple Sclerosis (PACTRIMS): Executive committee member
  - American Academy of Neurology (AAN): FAAN
  - European Academy of Neurology (EAN): Corresponding Member

Message from the Faculty Member 【 Display / hide 】

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 】

Other Affiliation 【 Display / hide 】

• Guest Professor, Kanazawa University

• Guest Professor, The JIKEI University School of Medicine

• Director, iPS Cell Research Center for Intractable Neurological Diseases, Keio University (KiND)

• Vice Director, Keio University Hospital Stroke Center

Career 【 Display / hide 】

Career 【 Display / hide 】

• 2003.04

  -

  2004.03

  COE Researcher, Keio University

• 2004.04

  -

  2007.03

  JSPS Researcher (DC1), JSPS

• 2007.04

  -

  2008.11

  JSPS Researcher (PD), JSPS

• 2008.12

  -

  2013.03

  Project Assistant Professor, Keio University

• 2013.04

  -

  2018.03

  Instructor, Keio University

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Academic Background 【 Display / hide 】

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 】

Academic Degrees 【 Display / hide 】

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

Licenses and Qualifications 【 Display / hide 】

Licenses and Qualifications 【 Display / hide 】

• Medical License, Japan, 2003.05

• Certified Occupational Physician, The Japan Medical Association, 2011.09

• Board Certified Member, The Japanese Society of Internal Medicine, 2013.09

• Board Certified Neurologist, The Japanese Society of Neurology, 2014.07

• JSIM Appointed Physician for Fellowship Training, The Japanese Society of Internal Medicine, 2017.09

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Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Life Science / Neurology

Research Keywords 【 Display / hide 】

Research Keywords 【 Display / hide 】

• Oligodendrocyte

• Multiple sclerosis

• Neuroimmunology

• Neurology

• Neuromyelitis optica spectrum disorder

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Research Themes 【 Display / hide 】

Research Themes 【 Display / hide 】

• 神経治療学の拠点形成, 

  2018

  -

  Present

• 多発性硬化症の臨床研究, 

  2011

  -

  Present

• 中枢神経系髄鞘再生療法の開発, 

  1999

  -

  Present

Books 【 Display / hide 】

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 】

Papers 【 Display / hide 】

• A case of CD36 deficiency with multiple white matter lesions

  Kizuka Y., Yamakawa H., Iwabuchi Y., Sakai J., Terayama C., Yatabe Y., Arai T., Matsushita H., Ieda M., Nakahara J., Izawa Y.

  BMC Neurology 26 ( 1 )  2026.12

  　View Summary

  Background: CD36 deficiency is associated with abnormal fatty acid metabolism, which may increase the risk of developing atherosclerosis. However, there are few reports on a possible link between CD36 deficiency and cerebral white matter lesions. Case report: We present the case of a 44-year-old woman with heart failure due to CD36 deficiency and multiple white matter lesions. Her comprehensive examination for heart failure, including a single-photon emission computed tomography (SPECT) with ²⁰¹thallium and ¹²³I-β-methyl-p-iodophenyl pentadecanoic acid, revealed a fatty acid metabolism disorder in the myocardium. Flow cytometry confirmed CD36 deficiency, and a subsequent head magnetic resonance imaging (MRI) demonstrated multiple T2-hyperintense lesions in the cerebral white matter. Although the patient had hypertriglyceridemia and a history of smoking, the contribution of CD36 deficiency to the formation of white matter lesions remains unclear. Conclusion: This case suggests a potential association between CD36 deficiency and cerebral small-vessel disease. Further studies in patient cohorts with CD36 deficiency are warranted to clarify the impact of this condition on cerebral microcirculation.

  • Access to Document (DOI)

• Iba1 deficiency impairs microglial synaptic remodeling and neuronal survival after axonal injury

  Sekiguchi K., Shoji H., Shindo T., Sasabe J., Tokuyasu D., Nakahara J., Miyakawa T., Ito D.

  Journal of Neuroinflammation 23 ( 1 )  2026.12

  　View Summary

  Background: Microglia remodel neuronal circuits in pathological conditions; however, the molecular requirements for these responses and their consequences for motoneuron survival remain unclear. Methods: Aif1 (Iba1) knockout mice were generated using CRISPR/Cas9-mediated deletion, and baseline phenotypes and responses to unilateral facial nerve axotomy were assessed using immunohistochemistry, transmission electron microscopy, and single-nucleus RNA sequencing of the facial motor nucleus. Motoneuron survival and nuclear γH2AX foci were evaluated 28 days post-axotomy. Findings: Under baseline conditions, Iba1^−/− mice had reduced body weights and mild behavioral abnormalities compared to wild-type mice. After axotomy, microglial ensheathment of ChAT-positive facial motoneurons was reduced, with fewer neurons showing extensive perisomatic microglial coverage than in Iba1^+/+ mice. Ultrastructurally, somatic synapse loss observed after injury in wild-type mice was not detected in Iba1^−/− mice, and fewer injured motoneurons were in contact with microglial processes. Single-nucleus transcriptomics showed an exaggerated expansion of an interferon-responsive microglial state in Iba1−/− mice after axotomy, whereas injured motoneurons displayed altered transcriptional programs related to synapse organization and neurotransmission. At 28 days, Iba1−/− mice showed reduced motoneuron survival, lower ChAT expression, and increased nuclear γH2AX foci. Interpretation: Iba1 supports microglia-neuron cross-talk that enables effective perisomatic remodefling after axonal injury; disruption of this response is accompanied by inflammatory-state shifts and compromised motoneuron survival.

  • Access to Document (DOI)

• Differential impact of smoking on intracerebral haemorrhage based on cerebral microbleed status: a case-control study

  Kuroda T., Tanaka T., Saito S., Bhaskar S., Ishiyama H., Inui R., Shiomi Y., Nakaoku Y., Ogata S., Morita Y., Ozaki E., Kuriyama N., Nishimura K., Koga M., Nakahara J., Toyoda K., Ihara M.

  BMJ Open 16 ( 6 )  2026.06

  　View Summary

  Objectives: While smoking is a well-established risk factor for various cardiovascular diseases, its association with intracerebral haemorrhage (ICH) remains controversial. Cerebral microbleeds (CMBs) are markers of haemorrhage-prone small vessel disease, but ICH can also occur without detectable CMBs. Therefore, we investigated the association between smoking and ICH according to CMB status. Design: Single-centre retrospective case-control study. Setting: A tertiary stroke centre in Osaka, Japan (2017–2021). Participants: 487 patients with ICH as their first stroke (female sex 41.5%) and 322 controls with non-stroke neurological conditions (female sex 47.5%) were included. Patients with missing CMB evaluation or smoking status data were excluded. Primary and secondary outcome measures: The primary outcome was ICH status, analysed according to CMB status, with current smoking as the primary exposure. Secondary analyses evaluated the association between smoking cessation duration and the odds of ICH, using current smoking as the reference. Results: Patients with ICH (median age, 70.0 years; presence of CMBs, 53.6%) and controls (median age, 71.0 years; presence of CMBs, 13.4%) were analysed. Among individuals without CMBs, current smoking was more frequently observed in patients with ICH than in controls (25.7% vs 14.0%, p<0.001) and was independently associated with ICH following adjustment for potential confounders (adjusted OR (aOR) 1.84, 95% CI 1.02 to 3.31, p=0.042). Long-term smoking cessation (>10 years) was associated with lower odds of ICH than current smoking (aOR 0.31, 95% CI 0.14 to 0.67, p=0.003), whereas short-term cessation (≤10 years) showed no significant difference. Among individuals with CMBs, no significant association was observed between smoking status and ICH. Conclusions: Current smoking was associated with higher odds of ICH among individuals without CMBs, whereas long-term cessation was associated with lower odds. These findings suggest that the absence of CMBs should not be interpreted as the absence of modifiable ICH risk, highlighting the clinical relevance of smoking history in this population. Trial registration number: NCT02251665.

  • Access to Document (DOI)

• Impact of Basal Ganglia Perivascular Spaces on Ischemic and Hemorrhagic Risks in Patients Taking Antithrombotic Therapies

  Iwamoto S., Miwa K., Koga M., Yoshimura S., Tanaka K., Yakushiji Y., Sasaki M., Hoshino H., Shiozawa M., Yagita Y., Kudo K., Nagakane Y., Ihara M., Nishiyama K., Nakahara J., Hirano T., Toyoda K.

  Neurology 106 ( 7 )  2026.04

  ISSN  00283878

  　View Summary

  BACKGROUND AND OBJECTIVES: Enlarged perivascular spaces (ePVSs) are considered to increase the risk of stroke. However, data regarding the benefits and risks of antithrombotic therapy in patients with ePVSs are currently limited. This study assessed the association between ePVSs and the risks of hemorrhagic or ischemic events in patients taking antithrombotic agents. METHODS: This prospective, multicenter observational study enrolled patients with cerebrovascular or cardiovascular diseases who had newly started or were continuing to take oral antithrombotic agents at 52 hospitals across Japan between 2016 and 2019. Baseline multimodal MRI was performed for all of the study participants. The images were then centrally evaluated for cerebral small vessel disease (SVD), including white matter hyperintensities, cerebral microbleeds, lacunes, and basal ganglia-enlarged perivascular spaces (BGPVSs). BGPVSs were categorized as 0, 1-10, 11-20, or ≥21. Outcomes included major bleeding, intracranial hemorrhage, ischemic events, ischemic stroke, and mortality. Multivariable Cox proportional hazards models were used for the BGPVSs (in categorical and ordinal forms), adjusted for patient demographics, vascular risk factors, and other SVD markers. RESULTS: Of the total 5,065 patients (1,663 women; median age 74 [interquartile range 67-81] years), antiplatelets and anticoagulants were administered at the baseline to 3,820 (75.4%) and 1,502 (29.7%) patients, respectively. Their BGPVS distributions were as follows: 0, 475 (9.4%); 1-10, 2,615 (51.6%); 11-20, 1,267 (25.0%); and 21+, 708 patients (14.0%). Over a median follow-up period of 2.0 (interquartile range 1.8-2.0) years, we noted 266 ischemic events, 188 ischemic strokes, 92 major bleeding events, 54 intracranial hemorrhages, and 198 deaths. Higher BGPVS was associated with an increased risk of major bleeding (BGPVS ≥21: adjusted hazard ratio [aHR] 4.04, 95% CI 1.17-13.92; per-unit increase: aHR 1.38, 95% CI 1.07-1.77) and ischemic stroke (BGPVS ≥21: aHR 2.58, 95% CI 1.21-5.50; per-unit increase: aHR 1.28, 95% CI 1.07-1.53) but was not significantly associated with higher risks of ischemic events, intracranial hemorrhage, or mortality. DISCUSSION: Higher BGPVS burdens are associated with higher risks of ischemic stroke and major bleeding in patients receiving antithrombotic therapy. BGPVSs may serve as useful imaging biomarkers for vascular risk assessment and personalized therapy.

  • Access to Document (DOI)

• Long-term efficacy and disease-specific responsiveness to protirelin in patients with spinocerebellar degeneration: A retrospective study

  Okusa S., Tezuka T., Nakahara J., Seki M.

  Parkinsonism and Related Disorders 145 2026.04

  ISSN  13538020

  　View Summary

  Introduction: The thyrotropin-releasing hormone (TRH) analog protirelin has short-term benefits for cerebellar ataxia (CA), but its long-term efficacy and the subtype-specific responsiveness of spinocerebellar degeneration (SCD) patients remain unclear. Methods: We retrospectively reviewed the records of 92 SCD patients (273 courses) treated with protirelin between July 2011 and October 2025, including patients with idiopathic CA (IDCA), multiple system atrophy with predominant CA (MSA-C) or parkinsonism (MSA-P), and genetic subtypes including spinocerebellar ataxia (SCA) type 6, SCA31 and dentatorubral-pallidoluysian atrophy (DRPLA). Responders were defined as showing ≥1-point improvement on the Scale for the Assessment and Rating of Ataxia (SARA). Results: Protirelin was effective in 64.1% of subjects, with significant improvement overall (p < 0.001) and significant SARA gains in MSA-C (p = 0.047), IDCA (p = 0.02), and SCA31 (p = 0.01). Change in SARA score (ΔSARA) correlated negatively with age and positively with total protirelin dose in IDCA, and negatively with age and disease duration and positively with baseline SARA score in SCA31. Several IDCA and DRPLA patients maintained clinical benefit for more than 10 years. All MSA-P discontinued protirelin within 2 years and all MSA-C within 5 years; some SCA6, and SCA31 patients continued for ≥5 years. Adverse effects were infrequent (2/92, 2.2%). Conclusion: Protirelin is efficacious in SCD patients and well-tolerated, particularly in slow-progressing phenotypes (IDCA and SCA31); its benefit in rapidly progressing ataxias (MSA-C) may be confined to early disease stages. Prospective studies with standardized dosing and long-term follow-up are warranted to establish evidence-based protocols for TRH-related therapy for CA.

  • Access to Document (DOI)

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

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

• Imaging analysis of myelin pathologies in multiple sclerosis using q-Space myelin map method

  Nakahara, Jin

  科学研究費補助金研究成果報告書 2022

• Designing Asian platform for neuroimmunology

  Nakahara, Jin

  学事振興資金研究成果実績報告書 (慶應義塾大学)  2020

• International collaborative study on novel MRI modality "Myelin map"

  Nakahara, Jin

  福澤諭吉記念慶應義塾学事振興基金事業報告集 (福澤基金運営委員会)  2020

• Platform development for neuro-immunological therapeutics in the Asian region.

  Nakahara, Jin

  学事振興資金研究成果実績報告書 (慶應義塾大学)  2019

• Novel therapeutic strategy against ischemic stroke based on glial cell interaction by ketone bodies

  Nakahara, Jin

  科学研究費補助金研究成果報告書 2017

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Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• Reply: Intention-to-treat analysis, MOH remission, and mechanistic insights: Reframing the 12-month CGRP mAb experience

  Imai S., Ihara K., Takahashi N., Ohtani S., Watanabe N., Iba C., Ishizuchi K., Takemura R., Nakahara J., Hori S., Takizawa T.

  Journal of the Neurological Sciences 486 2026.07

  ISSN  0022510X

  • Access to Document (DOI)

• Reply: Pathophysiological, methodological, and statistical considerations in CGRP monoclonal antibody therapy: A comment on Imai et al

  Imai S., Ihara K., Takahashi N., Ohtani S., Watanabe N., Iba C., Ishizuchi K., Takemura R., Nakahara J., Hori S., Takizawa T.

  Journal of the Neurological Sciences 483 2026.04

  ISSN  0022510X

  • Access to Document (DOI)

• Correction to: Vertebral artery dissection in a patient with migraine treated with calcitonin gene-related peptide monoclonal antibody: a case report and FAERS database analysis (BMC Neurology, (2025), 25, 1, (1), 10.1186/s12883-024-04009-z)

  Tokuyasu D., Imai S., Chen S.P., Ihara K., Watanabe N., Izawa Y., Nakahara J., Hori S., Takizawa T.

  BMC Neurology 25 ( 1 )  2025.12

  　View Summary

  Following publication of the original article [1], the authors identified an error in the author name of Shih-Pin Chen. The incorrect author name is: Shin-Pin Chen The correct author name is: Shih-Pin Chen The author group has been updated above and the original article [1] has been corrected.

  • Access to Document (DOI)

• A Cautionary Note on the Indication for Deep Brain Stimulation in Parkinsonism Patients With SLC9A6 Gene Mutations

  Okusa S., Tezuka T., Kosugi K., Yamamoto Y., Takahata K., Higuchi M., Akiyama T., Kobayashi M., Toda M., Ito D., Nakahara J., Seki M.

  Journal of Movement Disorders 18 ( 3 ) 268 - 270 2025.07

  ISSN  2005940X

  • Access to Document (DOI)

• Levodopa Pharmacokinetics in Switching From Levodopa/Carbidopa Intestinal Gel to Continuous Subcutaneous Foslevodopa/Foscarbidopa Infusion in a Patient With Parkinson’s Disease: A Case Report

  Nukariya T., Tezuka T., Okusa S., Okochi R., Sakai Y., Nihei Y., Nakahara J., Seki M.

  Journal of Movement Disorders 18 ( 2 ) 179 - 181 2025.04

  ISSN  2005940X

  • Access to Document (DOI)

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

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

• Precision medicine research for neuromyelitis optica-spectrum disorders

  2023.04

  -

  2028.03

  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

  2018.04

  -

  2023.03

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

  2013.04

  -

  2016.03

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

  2013.04

  -

  2016.03

  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

  2010.04

  -

  2013.03

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

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Intellectual Property Rights, etc. 【 Display / hide 】

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 】

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 】

Courses Taught 【 Display / hide 】

• INTERNAL MEDICINE: PRACTICE

  2026

• INTERNAL MEDICINE: SEMINAR

  2026

• INTERNAL MEDICINE

  2026

• ADVANCED INTERNAL MEDICINE

  2026

• CLINICAL CLERKSHIP IN NEUROLOGY

  2026

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Memberships in Academic Societies 【 Display / hide 】

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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