滝沢　翼 (タキザワ　ツバサ)

Takizawa, Tsubasa

写真a

所属（所属キャンパス）

医学部 内科学教室（神経） （信濃町）

職名

専任講師（有期）
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  • Predicting response to CGRP-monoclonal antibodies in patients with migraine in Japan: a single-centre retrospective observational study

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

    Journal of Headache and Pain （Journal of Headache and Pain)  24 （ 1 ）  2023年12月

    ISSN  11292369

    　概要を見る

    Background: Anti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) are a favourable option for patients with migraine who experience distressful headache disability and fail to respond to traditional preventive treatment options. However, since CGRPmAb has been available for only 2 years in Japan, the difference between good and poor responders remains unknown. We aimed to investigate the clinical characteristics of patients with migraine in Japan who responded well to CGRPmAb based on real-world data. Methods: We analysed patients who visited Keio University Hospital, Tokyo, Japan, between the 12th of August 2021 and 31st of August 2022, and were prescribed one of three CGRPmAbs (erenumab, galcanezumab, and fremanezumab) for more than 3 months. We recorded the patients’ basic migraine characteristics, such as pain quality, monthly migraine days (MMD)/monthly headache days (MHD), and the number of prior treatment failures. We defined good responders as patients whose MMDs decreased by more than 50% after 3 months of treatment and other patients as poor responders. We compared the baseline migraine characteristics between the two groups and performed logistic regression analysis based on the items that showed statistically significant differences. Results: In total, 101 patients were considered eligible for the responder analysis (galcanezumab: 57 (56%), fremanezumab: 31 (31%), and erenumab: 13 (13%)). After 3 months of treatment, 55 (54%) patients achieved ≥ 50% reduction in MMDs. Comparisons between ≥ 50% responders and non-responders revealed that age was significantly higher (p = 0.003), and MHD and total prior treatment failures were significantly lower (p = 0.027, 0.040, respectively), in responders than in non-responders. Age was a positive predictive factor, and the total number of prior treatment failures and past medical history of immuno-rheumatologic diseases were negative predictive factors of CGRPmAb responsiveness in Japanese patients with migraine. Conclusions: Patients with migraine who are older, with fewer prior treatment failures and no past history of immuno-rheumatologic disease, may respond well to CGRPmAbs.

  • Calcitonin Gene-Related Peptide mRNA Synthesis in Trigeminal Ganglion Neurons after Cortical Spreading Depolarization

    Shibata M., Kitagawa S., Unekawa M., Takizawa T., Nakahara J.

    International journal of molecular sciences （International journal of molecular sciences)  24 （ 14 ）  2023年07月

    ISSN  16616596

    　概要を見る

    Migraine is a debilitating neurovascular disorder characterized by recurrent headache attacks of moderate to severe intensity. Calcitonin gene-related peptide (GGRP), which is abundantly expressed in trigeminal ganglion (TG) neurons, plays a crucial role in migraine pathogenesis. Cortical spreading depolarization (CSD), the biological correlate of migraine aura, activates the trigeminovascular system. In the present study, we investigated CGRP mRNA expression in TG neurons in a CSD-based mouse migraine model. Our in situ hybridization analysis showed that CGRP mRNA expression was observed in smaller-sized neuronal populations. CSD did not significantly change the density of CGRP mRNA-synthesizing neurons in the ipsilateral TG. However, the cell sizes of CGRP mRNA-synthesizing TG neurons were significantly larger in the 48 h and 72 h post-CSD groups than in the control group. The proportions of CGRP mRNA-synthesizing TG neurons bearing cell diameters less than 14 μm became significantly less at several time points after CSD. In contrast, we found significantly greater proportions of CGRP mRNA-synthesizing TG neurons bearing cell diameters of 14-18 μm at 24 h, 48, and 72 h post-CSD. We deduce that the CSD-induced upward cell size shift in CGRP mRNA-synthesizing TG neurons might be causative of greater disease activity and/or less responsiveness to CGRP-based therapy.

  • Dysautonomia associated with immune checkpoint inhibitors

    Tezuka T., Okuzumi S., Nakashima C., Ide T., Imai S., Mitsuboshi S., Kuwahara Y., Takizawa T., Seki M., Minematsu N., Aragane N., Nakahara J., Hori S., Nakane S., Suzuki S.

    Journal of Neurology （Journal of Neurology)  270 （ 7 ） 3413 - 3423 2023年07月

    ISSN  03405354

    　概要を見る

    Objective: The purpose of this study is to report the clinical characteristics of dysautonomia associated with immune checkpoint inhibitors (ICIs). Methods: We reported two patients with autoimmune autonomic ganglionopathy (AAG) occurring as immune-related adverse events (irAEs). We also performed a review of previous case reports presenting dysautonomia during ICI therapy. Moreover, we conducted pharmacovigilance analyses using the US Food and Drug Administration Adverse Events Reporting System (FAERS) to investigate dysautonomia associated with ICI. Results: Two patients in our care developed both AAG and autoimmune encephalitis following ICI therapy for lung cancers. We comprehensively reviewed 13 published cases (M:F = 11:2, mean onset age of 53 years) with ICI-associated dysautonomia including AAG (n = 3) and autonomic neuropathy (n = 10). Of these, ICI monotherapy was performed in seven and combination ICI use in six. In 6 of 13 patients, dysautonomia appeared within one month after the start of ICIs. Orthostatic hypotension was observed in 7 and urinary incontinence or retention in five. All patients except three showed gastrointestinal symptoms. Anti-ganglionic acetylcholine receptor antibodies were undetectable. All but two patients received immune-modulating therapy. Immuno-modulating therapy was effective in three patients with AAG and two patients with autonomic neuropathy, but ineffective in the others. Five patients died, of either the neurological irAE (n = 3) or cancer (n = 2). The pharmacovigilance analyses using FAERS showed that ipilimumab monotherapy and the combination of nivolumab and ipilimumab constituted significant risks for developing dysautonomia, consistent with the review of literature. Conclusion: ICIs can cause dysautonomia including AAG, and autonomic neuropathy is a neurological irAE.

  • Anti-N-methyl-D-aspartate receptor encephalitis with concurrent human herpes virus-6A deoxyribonucleic acid detection: An autopsy case

    Shimohama S., Iizuka T., Takizawa T., Watanabe N., Tezuka T., Matsuda K., Yamanoi K., Kanazawa N., Kawamura Y., Yoshikawa T., Suzuki T., Takao M., Nakahara J., Izawa Y.

    Neuropathology （Neuropathology)  43 （ 3 ） 257 - 261 2023年06月

    ISSN  09196544

    　概要を見る

    We report an autopsy case of anti-N-methyl-D-aspartate (NMDA) receptor (NMDAR) encephalitis with concurrent human herpes virus-6 (HHV-6) A deoxyribonucleic acid (DNA) detection in cerebrospinal fluid (CSF). A 38-year-old previously healthy Japanese man presented with a generalized seizure. Brain magnetic resonance imaging (MRI) findings were unremarkable, but CSF revealed pleocytosis. On Day 11, HHV-6 DNA was detected in CSF, and IgG antibodies against the NR1 subunit of the NMDAR (GluN1) were subsequently detected. Since HHV-6 encephalitis was initially suspected, the patient was treated with foscarnet and ganciclovir, but the HHV-6A copy number increased from 200 (Day 22) to 2000 copies/mL (Day 47), and the therapy was ineffective. As typical symptoms of anti-NMDAR encephalitis developed, we changed the patient's treatment to combat anti-NMDAR encephalitis. He was repeatedly treated with first-line immunotherapy, and GluN1 antibody titer decreased. He was not treated with second-line immunotherapy because of recurrent infections; he died on Day 310. Postmortem examinations did not show systemic tumors. Microscopic examination of the brain revealed only severe neuronal rarefaction in the hippocampal cornu ammonis (CA) 3–4 areas with gliosis. Early initiation of aggressive immunotherapy may be required in a refractory case of anti-NMDAR encephalitis, even with HHV-6A DNA detection, because the significance of this concurrent detection in autoimmune encephalitis remains unclear.

  • COVID-19 vaccination elicited de novo and recurrence of cluster headache: A case series

    Chen S.P., Takizawa T., Sekiguchi K., Nakahara J., Wang S.J.

    Cephalalgia （Cephalalgia)  43 （ 5 ）  2023年05月

    ISSN  03331024

    　概要を見る

    Background: Recent pharmacovigilance studies suggested that cluster headache could be a potential adverse effect after coronavirus disease-2019 (COVID-19) vaccination; however, the possibility of coincidence could not be excluded. Detailed case studies might help elucidate their potential link and implicate potential pathogenic mechanisms. Methods: Patients who developed cluster headache in close temporal relationship to COVID-19 vaccination were identified from two tertiary medical centers in Japan and Taiwan respectively through 2021–2022. Detailed characteristics of the headaches and time between the onset of the index cluster episode and antecedent COVID-19 vaccination were reported. In patients with previous cluster headaches, the duration from previous bout was also recorded. Results: Six patients with new cluster headache bout 3–17 days after COVID-19 vaccination were identified. Two of them were de novo cases. The others either had been attack-free for a long time or developed new cluster bout in seasons atypical to prior bouts. The vaccines included mRNA, viral vector, or protein subunit vaccines. Conclusions: COVID-19 vaccines, regardless of vaccine types, may elicit de novo or relapse of cluster headache. Future studies are needed to confirm the potential causality and explore the potential pathogenic mechanism.

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  • 【頭痛の臨床(その1)】頭痛研究の現状と展望

    滝沢 翼, 井原 慶子

    脳神経内科 ((有)科学評論社)  98 ( 3 ) 318 - 324 2023年03月

    ISSN  2434-3285

  • 免疫チェックポイント阻害剤関連の自律神経障害

    手塚 俊樹, 奥隅 真一, 中島 千穂, 今井 俊吾, 峰松 直人, 荒金 尚子, 滝沢 翼, 関 守信, 中原 仁, 鈴木 重明

    日本内科学会雑誌 ((一社)日本内科学会)  112 ( 臨増 ) 188 - 188 2023年02月

    ISSN  0021-5384

  • 【令和の頭痛診療-プライマリ・ケア医のためのガイド】頭痛診療Start-Up　頭痛患者の問診と身体診察のコツ

    石鎚 啓, 滝沢 翼

    Medicina ((株)医学書院)  59 ( 13 ) 2350 - 2353 2022年12月

    ISSN  0025-7699

    　概要を見る

    ＜文献概要＞Point　◎問診と身体診察は,一次性頭痛と二次性頭痛の鑑別,診断を行ううえで非常に重要である.◎問診票を用いて網羅的に問診することが理想だが,患者の容態次第で臨機応変に情報収集する.◎まずはバイタル,意識レベルを確認する.異常を認める場合には適切な対応を行ったうえで,一般身体所見,神経学的所見の確認を行う.◎診療のうえで問診および身体診察は最も重要であるが,重篤な疾患を否定しきれない場合には検査も組み合わせて診断を進める.

  • 【頭痛診療はここまで進歩した】新たな片頭痛治療薬　CGRP関連抗体薬

    滝沢 翼, 大谷 星也

    日本医師会雑誌 ((公社)日本医師会)  151 ( 9 ) 1577 - 1580 2022年12月

    ISSN  0021-4493

  • 再発性非小細胞肺癌が疑われ、ニボルマブ、イピリムマブを投与したのち脳炎と自律神経障害を発症した61歳男性例

    手塚 俊樹, 奥隅 真一, 峰松 直人, 滝沢 翼, 関 守信, 中原 仁, 鈴木 重明

    臨床神経学 ((一社)日本神経学会)  62 ( 12 ) 972 - 972 2022年12月

    ISSN  0009-918X

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競争的研究費の研究課題 【 表示 ／ 非表示 】

  • 片頭痛に対するCGRP関連抗体薬および新規治療についての検討

    2022年04月
    -
    2024年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 滝沢 翼, 若手研究, 補助金,  研究代表者

  • 片頭痛のトリガーの実態調査と解明

    2019年04月
    -
    2022年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 滝沢　翼, 若手研究, 補助金,  研究代表者

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担当授業科目 【 表示 ／ 非表示 】

  • 先端医科学研究

    2023年度

  • 内科学（神経）講義

    2023年度

  • 先端医科学研究

    2022年度

  • 内科学（神経）講義

    2022年度

  • 医学概論（ヒトの構造・機能・病態概論）

    2021年度

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