Published papers

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.

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.

INTRODUCTION: The impact of migraine on patients' lives, including challenges they face before getting access to appropriate medical management, is not well understood. The ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE [OVERCOME (Japan)] 2nd study was conducted to provide information regarding burden and experience with migraine throughout the life course. METHODS: This cross-sectional, population-based, nationwide online survey was conducted in adults with or without migraine. The migraine group reported their headache features and experiences in medical management since headache onset. Migraine's burden and impact were assessed with various PRO instruments. Migraine and non-migraine groups reported their experiences in life events and answered questions on self-esteem. Subgroup analyses by the number of monthly headache days (MHD) were performed. RESULTS: The migraine group (n = 19,590) was numerically younger [mean (SD) age 40.5 (13.1) years vs. 53.1 (17.8) years] and included more females (68.8% vs. 52.1%) than the non-migraine group (n = 2219). The migraine group had mean (SD) 3.5 (5.2) MHDs; 24.2-56.7% had moderate-to-very severe disease burden per various PRO instruments. Headaches started when respondents with migraine were 17.8 years old; 86.7% started over-the-counter medications at 19.4 years of age. Only 46.4% self-reported migraine diagnosis by a physician and 25.1% received an oral preventive drug, almost a decade after headache onset. Up to 16.8% reported poor support/lack of understanding from either teachers or parents during school life. The migraine group had numerically more frequent job changes and divorce, and lower self-esteem, than the non-migraine group. Across assessments, increased MHDs tended to worsen outcomes. CONCLUSION: Migraine affected many individuals from an early stage, but timely support and medical intervention were insufficient. This may negatively impact important life events, cause long-term impairment, and decrease self-esteem. Hence, improving the social understanding and medical environment for migraine to provide timely support is essential.

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.

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.

Headache disorders are among the most disabling neurological conditions, affecting over 1.5 billion people globally. Despite advances in pharmacological therapies, major inequities persist due to underdiagnosis, undertreatment and limited access to effective care, particularly in low- and middle-income countries. Social determinants of health, including cultural meanings, language and health beliefs, are increasingly recognized as key drivers of disparities in burden, diagnosis and treatment outcomes. Traditional medicine, used by more than 80% of the global population, remains first-line care in many regions and continues to influence therapeutic choices in high-income settings. Major systems such as Ayurveda, Traditional Chinese Medicine, Unani and Tibetan medicine, as well as diverse indigenous traditions, emphasize holistic approaches that integrate mental and physical symptoms into diagnosis and management. Additionally, religious and spiritual practices are commonly used to relieve suffering and pain. These culturally grounded explanatory models not only strongly shape health-seeking behavior, treatment adherence and patient narratives, but also may delay biomedical care when misconceptions or unsafe practices predominate. This paper introduces Transcultural Headache Medicine as an emerging framework that integrates cultural contexts, linguistic diversity and traditional practices into headache research, clinical care and policy. We review global traditions and therapeutic modalities including herbal, physical, mental and spiritual approaches, and propose a research agenda combining ethnography, culturally adapted diagnostic tools, experimental studies and clinical trials to evaluate benefits, risks, and contextual effects. We conclude with a call to action from the International Headache Society, aiming to map and evaluate culturally embedded practices, strengthen rigorous evidence and build a global learning network that supports culturally safe integration of effective, affordable and safe headache care.

PURPOSE OF REVIEW: Despite the established efficacy and safety of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) worldwide, evidence from East Asian countries remains limited and may differ from that in Western countries. RECENT FINDINGS: This narrative review comprehensively summarises clinical trials and real-world studies on CGRP mAbs in East Asian populations. A total of 12 clinical trials and 23 real-world studies on galcanezumab, fremanezumab, and erenumab in East Asia were identified through MEDLINE and manual searches. After reviewing each country’s regulations on CGRP mAb usage, we summarised the findings across several categories and compared them with reports from Western countries: effectiveness, adverse events, patient-reported outcome measures, associated symptoms, patient satisfaction, switching, responder characteristics, and discontinuation. Although effectiveness and safety were comparable, notable differences regarding evidence on switching and responder characteristics were observed, likely attributable to variations in inclusion criteria and study design. Overall, the effectiveness and safety profiles of CGRP mAbs in Japan, South Korea, and Taiwan are comparable to those reported in Western countries. However, differences in regulatory policies significantly influenced the findings of real-world reports, highlighting the importance of region- and country-specific evidence.

＜ココがポイント!＞▼二次性頭痛を疑う問診のポイントとしてSNNOOP10がある。▼くも膜下出血(subarachnoid hemorrhage;SAH)の患者はwalk-inで来院することもありうる。▼脳動脈解離を疑った場合は,MRIの撮像法を工夫する。▼可逆性脳血管攣縮症候群(reversible cerebral vasoconstriction syndrome;RCVS)におけるMRA,3D-CTAでの血管攣縮像は,臨床症状の発症早期においては検出できないこともしばしばある。▼jolt accentuation of headacheが陰性であっても,髄膜炎は否定できない。▼適宜,専門医にコンサルトする。(著者抄録)

＜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.

＜Key Points＞◎抗CGRP抗体および抗CGRP受容体抗体は、片頭痛の予防療法に特化して開発された初めての治療薬である。◎抗CGRP抗体としてガルカネズマブ、fremanezumab、eptinezumab、抗CGRP受容体抗体としてerenumabがある。◎臨床試験において片頭痛日数の減少、50%反応率や生活支障度の改善などが示されており、片頭痛の新規治療として期待されている。(著者抄録)