Details of a Researcher - Takizawa, Tsubasa

Papers - Takizawa, Tsubasa

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Hallmarks of primary headache: part 3 - cluster headache.

Gianluca Coppola, Marco Antônio Arruda, Messoud Ashina, Mads Barloese, Andrea Carmine Belin, Sara Bottiroli, Debashish Chowdhury, Roberto De Icco, Cherubino Di Lorenzo, Giulia Di Stefano, Jacob C A Edvinsson, Stefan Evers, Stefania Ferraro, Rolf Fronczek, David García-Azorín, Peter J Goadsby, Licia Grazzi, Dagny Holle, Julia J Jansen, Raquel Gil-Gouveia, Giorgio Lambru, Michel Lanteri-Minet, Marco Lisicki, Dimos D Mitsikostas, Teshamae Monteith, Danilo Antonio Montisano, Mark Obermann, Li-Ling Hope Pan, Kuan-Po Peng, Mario Peres, Igor Petrušić, Alberto Proietti Cecchini, Marta Vila-Pueyo, Alberto Raggi, Innocenzo Rainero, Giorgio Sandrini, Gabriele Sebastianelli, Tsubasa Takizawa, Surat Tanprawate, Cristina Tassorelli, Andrea Truini, Massimiliano Valeriani, Doga Vuralli, Marta Waliszewska-Prosół, Shuu-Jiun Wang, Yonggang Wang, Tissa Wijeratne, Paolo Martelletti

The journal of headache and pain 26 ( 1 ) 196 - 196 2025.12

ISSN 11292369

BACKGROUND: Cluster headache (CH) is a rare primary headache disorder characterized by recurrent episodes of strictly unilateral excruciating pain accompanied by trigemino-autonomic signs, which significantly impacts the quality of life, social interactions, and occupational functioning of those who are affected. To promote a better understanding of this disabling condition and to foster research on the topic, this review provides a comprehensive description of the hallmarks of CH, including its clinical presentation, diagnostic challenges, pathophysiology, and current and novel therapeutic targets. It concludes by describing the disease burden and advocating for significant improvements in healthcare systems, and promoting health equity, as well as reducing stigma. PRINCIPAL FINDINGS: Despite its distinctive clinical and chronobiological features, CH may be mistaken for other primary headache disorders or different types of orofacial pain. Key pathogenic characteristics include the activation of the trigeminal-autonomic system with the release of several neuropeptides, the involvement of the hypothalamus in regulating the circadian rhythm, genetic variants, and the mesolimbic system. Both invasive and non-invasive neuromodulation treatments have been used to target the trigemino-cervical, parasympathetic, and hypothalamic systems. Additionally, novel therapeutic targets are currently being study. Alongside canonical therapies, several complementary approaches have been explored over the years, with most evidence deriving from uncontrolled research involving individuals who do not respond to standard pharmacological treatments. Despite advancements in our understanding of this complex disease, CH continues to pose considerable social, economic, and psychological challenges. Advocacy is essential and should prioritize early diagnosis, alleviate stigma, provide specialized training for healthcare professionals, and offer support to and through patient associations. CONCLUSIONS: CH is characterised by a complex, multifactorial, pathophysiology that is still not fully understood. Precise diagnosis, additional research studies, and robust psychosocial and institutional support are necessary to improve the quality of life for individuals affected by this debilitating condition.

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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

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.

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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

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.

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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

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.

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Patient–Doctor Communication in Migraine: Results from the OVERCOME (Japan) 2nd Study

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

Neurology and Therapy 14 ( 6 ) 2695 - 2721 2025.12

ISSN 21938253

Introduction: Despite the availability of effective treatments, some patients with migraine in Japan do not receive appropriate medical management and treatment for migraine, potentially due to the lack of effective patient–doctor communication. This analysis of the ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE (OVERCOME [Japan)] 2nd study described the current state and challenges of patient–doctor communication in migraine treatment in Japan. Methods: This analysis included adults with migraine who consulted doctors for headaches/migraine and reported details of their first consultation: their experiences with doctors regarding migraine diagnosis and treatments, migraine-related topics, and treatment goals discussed, and challenges in communication. Results: Among the 6762 included respondents, 55.1% (3729/6762) consulted a general practitioner (GP) first for headaches. Of the 3192 respondents diagnosed with migraine and reported the diagnosing doctor’s specialty (as GP, specialist, or non-headache specialist), specialists (64.0%; 2044/3192), followed by GPs (31.4%; 1001/3192), mostly commonly diagnosed migraine. In the first consultation, doctors told 48.0% (3249/6762) of respondents they had migraine. In the past year, 3854 respondents discussed migraine-related topics with doctors; most commonly, the use and effectiveness of prescription drugs, and headache symptoms, severity, and frequency [48.9% (1885/3854) to 67.8% (2612/3854)]. Specialists most commonly discussed migraine-related topics with respondents, but non-headache specialists, i.e., obstetricians and gynecologists, most commonly discussed menstrual-related migraine. A total of 1978 respondents had migraine-related topics they wanted to but could not discuss with doctors in the past year. Among them, 32.9% (651/1978) of respondents did not discuss the topics because the doctor did not ask. Although 96.6% (3724/3854) of respondents had treatment goals in mind, 36.0% (1388/3854) never discussed it with doctors. Conclusion: Open and considerate patient–doctor communication and appropriate medical judgment are needed for timely and adequate medical management of migraine. Training doctors in effective communication techniques and considering a migraine diagnosis during consultations may be associated with better patient outcomes.

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Clinical characteristics and social burden of menstrual migraine in Japan: an online-based cross-sectional questionnaire study.

Takizawa T, Ihara K, Yoshikawa R, Togo K, Kitano T, Iijima M

The journal of headache and pain 2025.11

ISSN 1129-2369

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Effect of Galcanezumab on PHQ-9 and GAD-7 in Patients with Migraine: A Real-world Study in Japan

Oshima Kota, Hattori Yuna, Ihara Keiko, Watanabe Narumi, Takemura Ryo, Ishizuchi Kei, Takahashi Nobuyuki, Sekiguchi Koji, Nakahara Jin, Takizawa Tsubasa

Internal Medicine (The Japanese Society of Internal Medicine) advpub ( 0 ) 2025.08

ISSN 0918-2918

Objective Patients with migraine are at increased risk of developing psychiatric comorbidities, particularly depression and anxiety. Recently, anti-calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) have been suggested to be effective not only for migraine but also for comorbid depression. However, their effectiveness in depression and anxiety remains inconclusive, particularly in Asian populations. This study evaluated the effect of galcanezumab on depressive and anxiety symptoms in patients with migraine. Methods We conducted a single-center, retrospective, real-world study of 27 Japanese patients with migraine who received galcanezumab at Keio University Hospital, using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scores at two time points (baseline and 3-5 months after initiating galcanezumab) to evaluate depressive and anxiety symptoms. Results During galcanezumab treatment, the mean monthly migraine days (MMD) significantly decreased from 13.6±8.2 to 8.5±9.3 (p<0.001). PHQ-9 scores significantly decreased from 5.8±4.4 to 4.5±4.2 (p=0.010) and GAD-7 scores from 4.0±3.9 to 3.1±3.5 (p=0.030). No significant correlation was observed between changes in PHQ-9/GAD-7 scores and changes in MMD, numerical rating scale scores, or associated symptoms. Furthermore, Fisher's exact tests showed no significant association between improvements in PHQ-9/GAD-7 scores and MMD reduction. Conclusion Galcanezumab improved PHQ-9 and GAD-7 scores in Japanese patients with migraine. These improvements may be partly attributable to the direct effects of galcanezumab, independent of its effect on migraine frequency.

第1土曜特集頭痛診療の新潮流--神経科学の進歩がもたらす治療戦略片頭痛の病態・診断・治療片頭痛の新規治療薬

滝沢翼, 井原慶子

医学のあゆみ (医歯薬出版) 294 ( 5 ) 373 - 380 2025.08

ISSN 00392359

A Structured Myofascial Pain Management Program for Chronic Headache Including Medication-Refractory Cases.

Sho Usuda, Satoru Morikawa, Hironori Saisu, Takazumi Yasui, Tsubasa Takizawa, Taneaki Nakagawa, Wataru Muraoka

Cureus 17 ( 8 ) e91095 2025.08

ISSN 2168-8184

Background and objective Musculoskeletal factors, such as myofascial pain, are often overlooked in chronic headaches. This study aimed to evaluate the effectiveness of a structured self-care program, myofascial pain management (MPM), for patients with chronic headaches. Methods This single-arm observational study involved 37 patients with chronic headaches who were referred from a neurology clinic. The patients were categorized into two groups: suspected myofascial pain (n=19) and medication-refractory (n=18). All patients underwent the MPM program, which included instructions for self-massage and stretching techniques. Treatment effectiveness was evaluated using the pain item in the Integrated Palliative Care Outcome Scale (IPOS), with a score of ≤1 indicating improvement. Results The overall improvement rate in the patients was 76%, with significant improvements observed in the myofascial (84%; p=0.00017) and refractory (67%; p=0.00038) groups. Of the 28 patients who demonstrated improvements, 25 (89%) achieved this outcome without changing their prescribed headache medications. Conclusions The MPM program was effective for patients with chronic headache, including those with medication-refractory headache. Evaluation of the masticatory and pericranial muscles, along with the introduction of a structured self-care program, could prove to be a valuable nonpharmacological strategy for headache management.

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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

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.

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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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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, Shin-Pin Chen, Keiko Ihara, Narumi Watanabe, Yoshikane Izawa, Jin Nakahara, Satoko Hori, Tsubasa Takizawa

BMC Neurology (Springer Science and Business Media LLC) 25 ( 1 ) 1 - 1 2025.01

Abstract

Background

Migraine is associated with cervical artery dissection (CeAD). Calcitonin gene-related peptide (CGRP) is a multifunctional neuropeptide with vasodilatory effects. The use of anti-CGRP monoclonal antibodies (CGRP mAb) may affect cerebrovascular disease risk; however, no reports have associated CGRP mAb with CeAD.

Case presentation and FAERS database analysis

We report a case of vertebral artery dissection in a 39-year-old woman with migraine treated with galcanezumab. We searched the number of cases where cerebral and cervical artery dissection were reported as adverse effects of CGRP mAb using the FDA Adverse Event Reporting System (FAERS) database. Six and ten such cases were reported regarding galcanezumab and CGRP mAbs use, respectively. The reporting odds ratios for galcanezumab and CGRP mAbs were elevated.

Conclusion

Although migraine is reported to be associated with CeAD, the use of CGRP mAb might be related to CeAD and warrant further investigation.

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片頭痛の発作間欠期の負担とその評価の現状について　文献レビュー

滝沢翼, 竹村亮, 五十嵐久佳, 松森保彦, 佐藤美奈子, 植田要

臨床神経学 ((一社)日本神経学会) 65 ( 1 ) 8 - 15 2025.01

ISSN 0009-918X

片頭痛の発作間欠期の患者負担に関するtargeted literature reviewを実施した.文献レビューの結果,(1)片頭痛の随伴症状や患者負担は発作時のみではなく,発作間欠期にも存在すること,(2)発作間欠期には,繰り返し出現する頭痛発作に対する恐怖や不安などが日常活動への支障や生活の質(Quality of Life:QOL)の低下をもたらすこと,(3)カルシトニン遺伝子関連ペプチド(calcitonin gene-related peptide:CGRP)関連抗体薬による予防治療は,発作間欠期の負担を軽減する可能性があることなどが明らかとなった.これらのことから,片頭痛治療では,発作間欠期の負担を含めた患者のアンメットニーズを確認したうえで,患者個人の負担に合わせた適切な治療法を選択することが重要である.(著者抄録)

Efficacy and Safety of Switching Between Anti-CGRP Monoclonal Antibodies: A Detailed Monthly and Long-term Follow-up Study and Literature Review

Oshima Kota, Ihara Keiko, Watanabe Narumi, Takemura Ryo, Ishizuchi Kei, Takahashi Nobuyuki, Shibata Mamoru, Nakahara Jin, Takizawa Tsubasa

Internal Medicine (The Japanese Society of Internal Medicine) advpub ( 0 ) 2114 - 2123 2025

ISSN 09182918

Objective Switching from one anti-calcitonin gene-related peptide monoclonal antibody (CGRP mAb) to another can be beneficial for treating patients with migraine who do not respond well to the first CGRP mAb. However, detailed and long-term follow-up reports of both efficacy and safety remain insufficient. We conducted a case-series analysis of patients with migraine who switched from galcanezumab to erenumab, both belonging to the class of CGRP mAbs. Methods We conducted a single-center retrospective real-world study. Patients with migraine who first received galcanezumab for ≥3 months and then switched to erenumab at Keio University Hospital were enrolled to investigate changes in monthly migraine days (MMD), response rate, and adverse effects (e.g., injection-site reactions). Additionally, we performed a narrative review of the literature on switching CGRP mAbs. Results Among the nine patients enrolled, the 50% response rate for MMD was 33% at 3 months after switching. Two patients (22%) initially responded at the 3-month assessment, but later reverted to baseline MMD levels. Switching from galcanezumab to erenumab increased the frequency of constipation, which was typically managed using laxatives. Participants who experienced injection-site reactions tended to exhibit similar reactions regardless of the type of CGRP mAb used. Five patients (56%) demonstrated an improvement in satisfaction after erenumab initiation at least once. A literature review revealed that the characteristics of the cohorts varied among studies. Conclusions Switching from galcanezumab to erenumab was effective in some patients, while it was associated with some tolerable side effects, and it improved patient satisfaction in approximately half of the patients, despite interindividual diversity in responses and fluctuating responses after switching, which warrants further investigation.

Treatment patterns and characteristics of patients with migraine: results from a retrospective database study in Japan.

Tsubasa Takizawa, Takahiro Kitano, Masahiro Iijima, Kanae Togo, Naohiro Yonemoto

The journal of headache and pain (Journal of Headache and Pain) 25 ( 1 ) 19 - 19 2024.12

ISSN 11292369

BACKGROUND: Clinical characteristics and treatment practice of patients with migraine in Japan in real-world setting have not been fully investigated. We conducted a retrospective cohort study using claims database to understand the clinical practice of migraine in recent years and to characterize patients potentially not managed well by current treatment options. METHODS: Our study used data from the large claims database maintained by JMDC Inc. Patients with diagnosis of headache or migraine between January 1, 2018, and July 31, 2022, were defined as the headache cohort, and those with migraine diagnosis and prescription of migraine treatments among the headache cohort were included in the migraine cohort. In the headache cohort, characteristics of medical facilities and status of imaging tests to distinguish secondary headache were examined. Treatment patterns and characteristics of patients potentially not managed well by acute/preventive treatment were described in migraine cohort. RESULTS: In the headache cohort, 989,514 patients were included with 57.0% females and mean age of 40.3 years; 77.0% patients visited clinics (with ≤ 19 bed capacities) for their primary diagnosis, and 30.3% patients underwent imaging tests (computed tomography and/or magnetic resonance imaging). In the migraine cohort, 165,339 patients were included with 65.0% females and mean age of 38.8 years. In the migraine cohort, 95.6% received acute treatment while 20.8% received preventive treatment. Acetaminophen/non-steroidal anti-inflammatory drugs were most common (54.8%) as the initial prescription for migraine treatment followed by triptan (51.4%). First treatment prescription included preventive treatment in 15.6%, while the proportion increased to 82.2% in the fourth treatment prescription. Among patients with more than 12 months of follow-up, 3.7% had prescription patterns suggestive of risk of medication-overuse headache, and these patients were characterized by a higher percentage of females and a higher prevalence of comorbidities. CONCLUSIONS: This study revealed that approximately one-fifth of the patients with migraine visiting medical facilities use preventive drugs. The presence of potential patients at risk of medication-overuse headache and the role of clinics in migraine treatment were also described.

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

Tsubasa Takizawa, Keiko Ihara, Narumi Watanabe, Ryo Takemura, Nobuyuki Takahashi, Naoki Miyazaki, Mamoru Shibata, Keisuke Suzuki, Noboru Imai, Norihiro Suzuki, Koichi Hirata, Takao Takeshima, Jin Nakahara

The journal of headache and pain (Journal of Headache and Pain) 25 ( 1 ) 39 - 39 2024.12

ISSN 11292369

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.

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The impact of primary headaches on disability outcomes: a literature review and meta-analysis to inform future iterations of the Global Burden of Disease study.

Marta Waliszewska-Prosół, Danilo Antonio Montisano, Mariola Antolak, Federico Bighiani, Francescantonio Cammarota, Ilaria Cetta, Michele Corrado, Keiko Ihara, Regina Kartamysheva, Igor Petrušić, Maria Magdalena Pocora, Tsubasa Takizawa, Gloria Vaghi, Paolo Martelletti, Barbara Corso, Alberto Raggi

The journal of headache and pain (Journal of Headache and Pain) 25 ( 1 ) 27 - 27 2024.12

ISSN 11292369

BACKGROUND: The burden and disability associated with headaches are conceptualized and measured differently at patients' and populations' levels. At the patients' level, through patient-reported outcome measures (PROMs); at population level, through disability weights (DW) and years lived with a disability (YLDs) developed by the Global Burden of Disease Study (GBD). DW are 0-1 coefficients that address health loss and have been defined through lay descriptions. With this literature review, we aimed to provide a comprehensive analysis of disability in headache disorders, and to present a coefficient referring to patients' disability which might inform future GBD definitions of DW for headache disorders. METHODS: We searched SCOPUS and PubMed for papers published between 2015 and 2023 addressing disability in headache disorders. The selected manuscript included a reference to headache frequency and at least one PROM. A meta-analytic approach was carried out to address relevant differences for the most commonly used PROMs (by headache type, tertiles of medication intake, tertiles of females' percentage in the sample, and age). We developed a 0-1 coefficient based on the MIDAS, on the HIT-6, and on MIDAS + HIT-6 which was intended to promote future DW iterations by the GBD consortium. RESULTS: A total of 366 studies, 596 sub-samples, and more than 133,000 single patients were available, mostly referred to cases with migraine. Almost all PROMs showed the ability to differentiate disability severity across conditions and tertiles of medication intake. The indexes we developed can be used to inform future iterations of DW, in particular considering their ability to differentiate across age and tertiles of medication intake. CONCLUSIONS: Our review provides reference values for the most commonly used PROMS and a data-driven coefficient whose main added value is its ability to differentiate across tertiles of age and medication intake which underlie on one side the increased burden due to aging (it is likely connected to the increased impact of common comorbidities), and by the other side the increased burden due to medication consumption, which can be considered as a proxy for headache severity. Both elements should be considered when describing disability of headache disorders at population levels.

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Hallmarks of primary headache: part 1 - migraine.

Alberto Raggi, Matilde Leonardi, Marco Arruda, Valeria Caponnetto, Matteo Castaldo, Gianluca Coppola, Adriana Della Pietra, Xiangning Fan, David Garcia-Azorin, Parisa Gazerani, Lou Grangeon, Licia Grazzi, Fu-Jung Hsiao, Keiko Ihara, Alejandro Labastida-Ramirez, Kristin Sophie Lange, Marco Lisicki, Alessia Marcassoli, Danilo Antonio Montisano, Dilara Onan, Agnese Onofri, Lanfranco Pellesi, Mario Peres, Igor Petrušić, Bianca Raffaelli, Eloisa Rubio-Beltran, Andreas Straube, Sebastian Straube, Tsubasa Takizawa, Claudio Tana, Michela Tinelli, Massimiliano Valeriani, Simone Vigneri, Doga Vuralli, Marta Waliszewska-Prosół, Wei Wang, Yonggang Wang, William Wells-Gatnik, Tissa Wijeratne, Paolo Martelletti

The journal of headache and pain 25 ( 1 ) 189 - 189 2024.12

ISSN 11292369

BACKGROUND AND AIM: Migraine is a common disabling conditions which, globally, affects 15.2% of the population. It is the second cause of health loss in terms of years lived with disability, the first among women. Despite being so common, it is poorly recognised and too often undertreated. Specialty centres and neurologists with specific expertise on headache disorders have the knowledge to provide specific care: however, those who do not regularly treat patients with migraine will benefit from a synopsis on the most relevant and updated information about this condition. This paper presents a comprehensive view on the hallmarks of migraine, from genetics and diagnostic markers, up to treatments and societal impact, and reports the elements that identify migraine specific features. MAIN RESULTS: The most relevant hallmark of migraine is that it has common and individual features together. Besides the known clinical manifestations, migraine presentation is heterogeneous with regard to frequency of attacks, presence of aura, response to therapy, associated comorbidities or other symptoms, which likely reflect migraine heterogeneous genetic and molecular basis. The amount of therapies for acute and for prophylactic treatment is really wide, and one of the difficulties is with finding the best treatment for the single patient. In addition to this, patients carry out different daily life activities, and might show lifestyle habits which are not entirely adequate to manage migraine day by day. Education will be more and more important as a strategy of brain health promotion, because this will enable reducing the amount of subjects needing specialty care, thus leaving it to those who require it in reason of refractory condition or presence of comorbidities. CONCLUSIONS: Recognizing the hallmarks of migraine and the features of single patients enables prescribing specific pharmacological and non-pharmacological treatments. Medical research on headaches today particularly suffers from the syndrome of single-disease approach, but it is important to have a cross-sectional and joint vision with other close specialties, in order to treat our patients with a comprehensive approach that a heterogeneous condition like migraine requires.

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Effects of passive smoking on cortical spreading depolarization in male and female mice.

Tsubasa Takizawa, Keiko Ihara, Miyuki Unekawa, Chisato Iba, Shizuko Kagawa, Narumi Watanabe, Shingo Nakayama, Kaori Sakurai, Naoki Miyazaki, Noriyuki Ishida, Ryo Takemura, Mamoru Shibata, Yoshikane Izawa, Shotaro Chubachi, Koichi Fukunaga, Jin Nakahara

The journal of headache and pain 25 ( 1 ) 162 - 162 2024.12

ISSN 11292369

BACKGROUND: Patients with migraine are typically advised to avoid passive smoking because it may aggravate headaches and other health conditions. However, there is insufficient high-quality evidence on the association between passive smoking and migraine, which warrants further investigation using animal models. Therefore, using a mouse model, we examined the effect of passive smoking on susceptibility to cortical spreading depolarization (CSD), the biological basis of migraine with aura. FINDINGS: Fifty C57BL/6 mice (25 males and 25 females) were exposed for one hour to cigarette smoke or room air. Subsequently, potassium chloride (KCl) was administered under isoflurane anesthesia to induce CSD, and the CSD threshold, frequency of induction, and propagation velocity were determined. The threshold to induce CSD (median [interquartile range (IQR)]) was significantly lower in female mice (adjusted p = 0.01) in the smoking group (0.05 [0.05, 0.088]) than in the sham group (0.125 [0.1, 0.15]); however, there was no significant difference in the male mice (adjusted p = 0.77). CSD frequency or propagation velocity did not differ significantly between the two groups for either sex. CONCLUSIONS: Female mice in the smoking group showed lower CSD threshold compared to the sham group, suggesting a potential sex-specific difference in the effect of smoking on the pathogenesis of CSD and migraine with aura. This finding may contribute to the understanding of migraine pathophysiology in association with passive smoking and sex difference.

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Clinical practice for migraine treatment and characteristics of medical facilities and physicians treating migraine: Insights from a retrospective cohort study using a Japanese claims database.

Tsubasa Takizawa, Takahiro Kitano, Kanae Togo, Reiko Yoshikawa, Masahiro Iijima

PloS one 19 ( 12 December ) e0315610 2024.12

The real-world treatment patterns at medical facilities and their physicians' specialties treating migraine have not been fully investigated in Japan. Therefore, a retrospective cohort study aimed to describe real-world clinical practice and treatment patterns in Japanese patients with migraine according to medical facilities and physicians' specialties. Anonymized claims data of patients with migraine was obtained from JMDC Inc (January 2018-June 2023). Patient characteristics and treatment pattern according to medical facilities and physicians' specialties treating migraine were evaluated. Of 231,156 patients with migraine (mean age [SD], 38.8 [11.8] years; females, 65.3%), 81.8% had the first prescription at clinics (CPs), 42.5% underwent imaging tests, 44.4% visited general internal medicine, and 25.9% consulted neurosurgery at initial diagnosis. Imaging tests were carried out at CPs with specialists (59.4%), hospitals (HPs) with specialists (59.1%), HPs (32.9%), and CPs (26.9%) without specialists. Overall, 95.6% received acute treatment while 21.8% received preventive treatment. At facilities with specialists compared to without specialists, triptans were more frequently prescribed (67.9% vs 44.9%) whereas acetaminophen and nonsteroidal anti-inflammatory drugs were less frequently prescribed (52.4% vs 69.2%). Preventive treatment use was higher at facilities with specialists (27.4%) than without specialists (15.7%) and increased annually regardless of the type of medical institution. In Japan, only half of patients with migraine visited facilities with specialists at their first diagnosis, and specialists are more likely use migraine-specific and preventive drugs than nonspecialists. Therefore, there is a need for awareness among migraine patients that they should consult specialists and for enhancement of medical collaboration between specialists and nonspecialists.

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