Takizawa, Tsubasa

写真a

Affiliation

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

Position

Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)
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Career 【 Display / hide 】

  • 2010
    -
    2012

    Kawasaki Municipal Hospital

  • 2016

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

  • 2016
    -
    2018

    Massachusetts General Hospital, Harvard Medical School

  • 2018
    -
    2020

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

  • 2020
    -
    Present

    Keio University, School of Medicine Department of Internal Medicine (Neurology), Assitant Professor

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Academic Background 【 Display / hide 】

  • 2004
    -
    2010

    Keio University, School of Medicine

  • 2012
    -
    2016

    Keio University, Graduate School of Medicine

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Research Areas 【 Display / hide 】

  • Life Science / General internal medicine

  • Life Science / Neurology

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Research Keywords 【 Display / hide 】

  • Migraine

  • Neurology

  • Cluster Headache

  • Headache

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Papers 【 Display / hide 】

  • Real-world use of over-the-counter medications by patients with migraine in Japan: results from the OVERCOME (Japan) 2nd study

    Ishii R., Takizawa T., Suzuki S., Danno D., Miura M., Tanizawa Y., Osaga S., Hashimoto C., Komori M.

    Journal of Headache and Pain 26 ( 1 ) 107 2025.12

    ISSN  11292369

    　View Summary

    Background: People with migraine may prefer over-the-counter (OTC) drugs because of multiple reasons, but their overuse can cause medication overuse headaches. This analysis of the ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE (OVERCOME [Japan]) 2nd study describes the real-world use of OTC headache drugs and the challenges that potentially prevent people with migraine from accessing appropriate medical management in Japan. Methods: This analysis of the cross-sectional, population-based, nationwide online survey included adults with migraine. Respondents reported their experiences with prescription and OTC drugs for migraine, migraine-specific drug awareness, and attitude towards migraine. Subgroup analyses were performed based on the number of monthly headache days (MHD) and the frequency of OTC drug use/month. Results: The 19,590 respondents with migraine (68.8% female; mean [SD] age 40.5 [13.1] years) had mean (SD) 3.5 (5.2) MHDs; 29.0% consulted doctors in the past year for migraine. OTC drug use in the past year was common (≥ 62.1%) regardless of doctor consultation or number of MHDs. Among respondents who answered that they would usually use prescribed drugs when they have a migraine attack, 35.2% reported that they would typically use OTC drugs too. The frequency of OTC drug use was the same or higher than that of prescribed drugs in 51.3% of the respondents who consulted doctors in the past year. Only 14.6% of respondents discussed OTC drugs with doctors during consultations in the past year. Migraine-specific drug access and awareness were limited even among frequent OTC drug users (≥ 10 days/month); 18.2% used triptans, but 65.5% never heard of it. Among 37.1% of respondents who had hesitated to visit a doctor, ‘I could handle it myself with OTC medicine’ was the most common reason for hesitation (34.9%). Conclusion: OTC drug use is common among people with migraine; however, it is not frequently discussed with doctors. Many respondents, even those with frequent OTC drug use, did not have access or awareness of migraine-specific drugs. To prevent medication overuse for migraine, the use of OTC drugs should also be discussed and managed.

  • The dual impact of ictal and interictal burden in migraine: an analysis from the ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE (OVERCOME) Japan second study.

    Tsubasa Takizawa, Daisuke Danno, Ryotaro Ishii, Shiho Suzuki, Moemi Miura, Yoshinori Tanizawa, Satoshi Osaga, Michio Okada, Chie Hashimoto, Mika Komori

    The journal of headache and pain 26 ( 1 ) 140 - 140 2025.12

    ISSN  11292369

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    BACKGROUND: Migraine adversely affects many aspects of daily life. In addition to burdens during headaches (ictal period), burdens between headaches (interictal period) are increasingly recognized. In this analysis of the ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE in Japan (OVERCOME [Japan]) 2nd study, we evaluated the contribution of interictal burden to daily activities, quality of life, work, family, costs, and medical treatment. METHODS: The OVERCOME (Japan) 2nd study was a cross-sectional, web-based survey of 19,590 adults in Japan with migraine conducted between June and August 2023. Questionnaires included Headache Impact Test-6 (HIT-6), Migraine Interictal Burden Scale-4 (MIBS-4), Migraine Disability Assessment (MIDAS), Allodynia Symptom Checklist-12 (ASC-12), Migraine-Specific Quality-of-Life Questionnaire (MSQ), Impact of Migraine on Partners and Adolescent Children Scale (IMPAC), Work Productivity and Activity Impairment Questionnaire-Migraine (WPAI-M), and Migraine Treatment Optimization Questionnaire-6 (mTOQ-6). Additional questions asked about costs, frequency of migraine concerns between headaches, and experience with medical treatment. Analyses were conducted on subgroups based on HIT-6 and MIBS-4 scores: Severe (HIT-6 ≥ 60, MIBS-4 ≥ 3; n = 6854), High Interictal Burden (HIT-6 < 60, MIBS-4 ≥ 3; n = 2368), High Ictal Burden (HIT-6 ≥ 60, MIBS-4 < 3; n = 4253), and Milder (HIT-6 < 60, MIBS-4 < 3; n = 6115). RESULTS: Number of monthly headache days, total MIDAS score, and pain severity score were higher, and MSQ scores lower, in subgroups with higher HIT-6 (HIT-High) versus subgroups with lower HIT-6 (HIT-Low). Within both HIT-High and HIT-Low subgroups, those with higher MIBS-4 had higher MIDAS and lower MSQ. IMPAC grade, ASC-12 score, and WPAI-M absenteeism were higher in the High Interictal Burden subgroup versus the High Ictal Burden subgroup. Concerns between headaches were more frequent, and costs higher, in subgroups with higher MIBS-4 (MIBS-High) versus subgroups with lower MIBS-4 (MIBS-Low). Acute treatment prescription analgesics were more commonly used in HIT-High versus HIT-Low subgroups, but triptans, lasmiditan, and preventive drugs were more common in the High Interictal Burden subgroup versus the High Ictal Burden subgroup. CONCLUSIONS: These results revealed that high interictal burden negatively affects multiple aspects of daily life in Japanese people with migraine independently of the impact of headaches.

  • Hallmarks of primary headache: part 2- Tension-type headache.

    Li-Ling Hope Pan, Yu-Hsiang Ling, Shuu-Jiun Wang, Linda Al-Hassany, Wei-Ta Chen, Chia-Chun Chiang, Soo-Jin Cho, Min Kyung Chu, Gianluca Coppola, Adriana Della Pietra, Zhao Dong, Esme Ekizoglu, Charl Els, Fatemeh Farham, David Garcia-Azorin, Woo-Seok Ha, Fu-Jung Hsiao, Ryotaro Ishii, Byung-Kun Kim, Najib Kissani, Alejandro Labastida-Ramirez, Kristin Sophie Lange, Ellina Lytvyak, Dilara Onan, Aynur Ozge, Laura Papetti, Lanfranco Pellesi, Bianca Raffaelli, Alberto Raggi, Sebastian Straube, Tsubasa Takizawa, Surat Tanprawate, Derya Uğurlu Uludüz, Kiratikorn Vongvaivanich, Marta Waliszewska-Prosół, Yonggang Wang, Tissa Wijeratne, Jr-Wei Wu, Sophie Merve Yener, Paolo Martelletti

    The journal of headache and pain 26 ( 1 ) 164 - 164 2025.12

    ISSN  11292369

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    BACKGROUND AND AIM: Tension-type headache is the most prevalent primary headache disorder. While the episodic subtype is more common, chronic tension-type headache significantly impacts health-related quality of life and contribute to increased healthcare utilization and disability. Despite considerable advances in the understanding of tension-type headache, critical gaps persist. This paper aims to provide a comprehensive review of the hallmarks of tension-type headache, from its pathophysiology, comorbidities, treatment options, to psychosocial impact. MAIN RESULTS: Multiple factors are associated with tension-type headache, including peripheral mechanisms (increased muscle tenderness and myofascial trigger points), central sensitization, genetic predisposition, and psychological comorbidities such as anxiety and depression. Neuroimaging and neurophysiological studies demonstrated altered pain processing in cortical and subcortical regions in patients with tension-type headache. Regarding treatment strategy, in addition to pharmacological treatment, novel insights into non-pharmacological interventions such as cognitive behavioral therapy, neuromodulation techniques, physical therapy, mindfulness, lifestyle management, and patient education were highlighted as valuable components of comprehensive management strategies. CONCLUSIONS: A complex interplay between peripheral and central mechanisms and psychosocial stressors underpins tension-type headache. Integrated multidisciplinary approaches combining pharmacological and non-pharmacological interventions are critical for optimal patient outcomes. Further research should continue to refine the understanding of these mechanisms to improve targeted therapeutic strategies and reduce the global burden of tension-type headache.

  • Effect of lacosamide on cortical spreading depolarization in mice.

    Chisato Iba, Miyuki Unekawa, Keiko Ihara, Yoshikane Izawa, Jin Nakahara, Tsubasa Takizawa

    The journal of headache and pain 26 ( 1 ) 163 - 163 2025.07

    ISSN  1129-2369

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    BACKGROUND: Antiseizure medications are often used as preventive treatment of migraine in appropriate cases; however, the efficacy of lacosamide (LCM), a sodium channel blocker, in preventing migraine attacks remains unclear. Cortical spreading depolarization (CSD) refers to a wave of slowly propagating depolarization across the cerebral cortex. CSD animal models have been extensively used to investigate migraine attacks and evaluate the effects of migraine medication. Herein, we examined the effects of single dose LCM (40 mg/kg) on CSD sensitivity in a mouse model. FINDINGS: Thirty-two C57BL/6 mice (male, n = 16; female, n = 16) were intraperitoneally injected with either LCM (40 mg/kg) or saline before CSD sensitivity testing. Potassium chloride (KCl) was administered to induce CSD, and the CSD threshold, frequency, and propagation velocity were determined. The average CSD frequency induced by 1 M KCl was significantly lower (p = 0.030) and the CSD propagation velocity tended to be lower in the female LCM group than in the saline group. However, no significant differences were observed in any of the three CSD parameters in male mice. CONCLUSIONS: In female mice, single dose LCM treatment significantly reduced CSD frequency induced by KCl. Further investigations are warranted to assess the clinical potential of LCM in preventing migraine.

  • Correction: Vertebral artery dissection in a patient with migraine treated with calcitonin gene-related peptide monoclonal antibody: a case report and FAERS database analysis.

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

    BMC neurology 25 ( 1 ) 40 2025.01

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

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Reviews, Commentaries, etc. 【 Display / hide 】

  • Correction: Vertebral artery dissection in a patient with migraine treated with calcitonin gene-related peptide monoclonal antibody: a case report and FAERS database analysis.

    Daiki Tokuyasu, Shungo Imai, Shih-Pin Chen, Keiko Ihara, Narumi Watanabe, Yoshikane Izawa, Jin Nakahara, Satoko Hori, Tsubasa Takizawa

    BMC neurology 25 ( 1 ) 40 - 40 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.

  • 片頭痛の薬物治療の最前線　CGRP関連抗体薬の登場によるパラダイムシフト

    滝沢 翼, 井原 慶子

    日本女性医学学会雑誌 ((一社)日本女性医学学会)  32 ( 3 ) 597 - 599 2025.04

    ISSN  2185-8861

  • 【「失敗」から学ぶ脳神経内科学】失敗から学ぶ頭痛学

    滝沢 翼, 柴田 護

    脳神経内科 ((有)科学評論社)  102 ( 3 ) 310 - 316 2025.03

    ISSN  2434-3285

  • 【「失敗」から学ぶ脳神経内科学】失敗から学ぶ頭痛学

    滝沢 翼, 柴田 護

    脳神経内科 ((有)科学評論社)  102 ( 3 ) 310 - 316 2025.03

    ISSN  2434-3285

  • 頭痛診療とライフワークバランス

    渡邊 成美, 滝沢 翼

    Japanese Journal of Headache (The Japanese Headache Society)  51 ( 3 ) 202 - 203 2025.02

    ISSN  1345-6547

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

  • HANAC症候群におけるiPS細胞樹立とβ１インテグリンシグナル作動薬による治療法の確立

    2025.04
    -
    2028.03

    Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), No Setting

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    一部の遺伝性脳小血管病では、基底膜を構成するアミノ酸が他のアミノ酸に置換され、コラーゲンの三重らせん構造が崩れることが原因でラクナ梗塞、白質病変など脳小血管病変をきたす。ただし、その機序の詳細は解明されていない。我々はこれまでに、コラーゲンIVの受容体であるβ１インテグリンの機能阻害やコンディショナルノックアウトにより、遺伝性脳小血管病と同様の血栓形成、出血性変化、白質病変の原因となる血液脳関門の破綻が惹起される現象とその機序を報告した。本研究はコラーゲンIV変異による血液脳関門の障害機序を評価するとともに、血管内皮細胞内シグナルの調節に基づく遺伝性脳小血管病の治療確立を目標とする。

  • Effects of changes in barometric pressure on mood fluctuations and somatisation: Basic and clinical approaches

    2024.04
    -
    2028.03

    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (A), No Setting

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    我が国で頭痛やめまいの症状を持つ患者数は3,000万人を超えると言われており，それに伴う気分の揺らぎに伴うパフォーマンスの低下は，社会全体の活動低下を招いている．これらの患者のなかには，心的ストレスが原因となって身体の不調を訴える症例が多く含まれているが，なぜそのような身体化の症状が生じるかは十分に解明されていない．本研究では，健常者・身体症状症・片頭痛・メニエール病の患者を対象として，自律神経活動，身体状態の変化を感知する内受容感覚，予測的情報処理に基づく信念形成の特性に着目し，気圧変化に対する身体・認知特性を明らかにする．そして，症状改善に向けたプロトコルの開発に取り組む．

  • Investigation of the Current Epidemiology and Biomarkers of Migraine

    2024.04
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    2027.03

    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), No Setting

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    CGRP関連抗体薬が2021年に上市され、片頭痛診療は大きな変革期を迎えている。そのような中、わが国における頭痛・片頭痛の最新の疫学を明らかにすることは重要と考える。
    片頭痛について、有用なバイオマーカーは確立されていない。
    本研究では、頭痛・片頭痛についての疫学調査を実施する。さらには片頭痛のバイオマーカーの検索などを試みる。

  • Investigation of anti-CGRP monoclonal antibodies and novel therapeutics for migraine

    2022.04
    -
    2024.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists, Principal investigator

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    片頭痛の病態で重要なカルシトニン遺伝子関連ペプチド（Calcitonin gene-related peptide; CGRP）あるいはその受容体を標的とした抗体治療（CGRP関連抗体薬）が、わが国において2021年に新たに承認となった。
    本研究では、CGRP関連抗体薬を含めた片頭痛の最新治療の実態を明らかにしつつ、今後に向けての新規治療についても検討する。
    慶應義塾大学病院の頭痛外来にてCGRP関連抗体薬のリアルワールドエビデンスを検討した。まず、CGRP関連抗体薬の一つであるガルカネズマブが3回以上投与された片頭痛患者について効果と安全性を検討した。50%反応率（片頭痛日数がベースラインから半分以下になった患者の割合）は62%、100%反応率（片頭痛日数が消失した患者の割合）は10%であった。片頭痛日数のみではなく、随伴症状である光過敏、音過敏、悪心/嘔吐についても65%、50%、64%の患者で改善を認めていた。最も多い有害事象は注射部位反応で、35%の患者で認めていた（Takizawa T et al. BMC Neurology 2022）。
    次に、CGRP関連抗体薬が3回以上投与された片頭痛患者について、どのような臨床的特徴がCGRP関連抗体薬の効果に関連しているのか検討した。治療開始3ヶ月後に、50%反応率を達していた患者をレスポンダー、達していなかった患者をノンレスポンダーと定義した。CGRP関連抗体薬が投与された半数以上の患者がレスポンダーであった。年齢や体重、既往歴、ひと月あたりの片頭痛日数、痛みの程度・性質、予防薬失敗数などのデータを基に解析を行ったところ、①年齢が高く、②予防薬失敗数が少なく、③免疫系疾患の既往がない患者ほどCGRP関連抗体薬のレスポンダーになりやすいことが明らかとなった（Ihara K et al. The Journal of Headache and Pain 2023）。
    その他、わが国におけるCGRP関連抗体薬の学会報告をまとめた総説（大谷星也、井原慶子（co-1st）ら．日本頭痛学会誌 2023）、片頭痛領域の最新治療薬についての総説なども執筆した（Begasse de Dhaem O, Takizawa T (co-1st) et al. Cephalalgia 2023）。
    CGRP関連抗体薬について臨床現場からのリアルワールドデータを基に日本から有効性や安全性、レスポンダーの特徴について初めて英文論文として報告することができた。当初の計画以上に進展していると考えられた。
    CGRP関連抗体薬について、さらに新規を含めた頭痛の治療についても検討を進めていく予定である。

  • 脳血管内皮透過性制御機構の解明による新規神経疾患治療法の確立

    2021.04
    -
    2024.03

    日本学術振興会, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), No Setting

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    脳血管障害は要介護状態となる原因疾患の第一位を占め、2018年に成立した「脳卒中・循環器病対策基本法」の基本理念である、健康寿命延伸の観点から大きな社会的問題となっている。血管内治療など超急性期脳梗塞治療の進歩は目覚ましいが、脳梗塞の発症予防は、いまだ抗血栓療法と血圧管理などに依存し、新規治療法は久しく開発されていない。抗血栓療法は脳出血発症リスクと表裏一体であるなど、脳血管障害の治療で解決すべき課題は多く、脳血管性認知症に至っては治療法が存在しない。安全性と有効性を両立した脳血管障害、さらには脳血管性認知症に対する治療の確立は喫緊の課題である。
    本研究は、内皮に血栓が生じる機序、血管が破綻する機序、神経組織が機能低下する機序の解明を目的とし、脳血管透過性亢進モデルマウスを用いて、血管透過性調節による脳血管障害・血管性認知症の新たな治療概念確立を目指すものである。これにより実臨床で用いられる各抗血栓薬の有効性と安全性の違いや特徴を統一的に説明する理論の確立も目指す。 2021年度は本研究の先行研究結果をまとめた共著論文が提出され、血栓形成（止血）作用を持つトロンビンが脳微小血管障害（血管透過性亢進作用）により脳出血リスクを上昇させる可能性を示したが、これは直感的に想定されるトロンビン作用と真逆の視点を提唱するものである。また、トロンビンが脳微小血管の透過性を上昇させる様子をin vivo、生存下で連続（経時）的に捉えることに成功した。2020年度までの研究成果報告書では統計解析上は、本研究の実験仮説が誤りである可能性も否定できない状況であったが、実験手法改善により、仮説からの予測と一致する結果が蓄積され、統計的評価にも頑健であった。このように、本研究が目標とする「血管透過性制御機構」の解明という観点から、提唱する理論的仮説が真である蓋然性が一定程度高まるデータが得られた。

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Awards 【 Display / hide 】

  • Young Investigator Award, Keio University School of Medicine Alumni Association (Sanshikai)

    2024, Keio University School of Medicine, Sanshikai

  • Frontiers in Headache Research Scholarship

    2018, American Headache Society

  • Kitamura Award

    2014, The Japanese Headache Society

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Courses Taught 【 Display / hide 】

  • RESEARCH FRONTIERS IN BIOMEDICAL SCIENCE

    2025

  • LECTURE SERIES, INTERNAL MEDICINE (NEUROLOGY)

    2025

  • RESEARCH FRONTIERS IN BIOMEDICAL SCIENCE

    2024

  • LECTURE SERIES, INTERNAL MEDICINE (NEUROLOGY)

    2024

  • RESEARCH FRONTIERS IN BIOMEDICAL SCIENCE

    2023

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