Cephalalgia最新文献

{"title":"Atogepant for migraine in real-world clinical practice: Insights from a large multicentre study in a treatment-resistant population (GEMA project).","authors":"Ana Beatriz Gago-Veiga, Ana Belen Lopez-Rodriguez, Marina Sanchez Jimenez, Alvaro Iglesias Rubio, Nuria Montes, Javier Camiña Muñiz, Marta Dominguez Gallego, Carlos Calle de Miguel, Germán Latorre, Jaime Rodriguez-Vico, Alex Jaimes, Andrea Gomez Garcia, Sara Urtiaga, Marta Gonzalez Salaices, Michele Dileone, Nuria Gonzalez-García, Jesús Porta-Etessam, María-Luz Cuadrado, Alejandro Herrero San-Martin, Ángel-Luis Guerrero-Peral, Yesica Gonzalez-Osorio, Javier Casas-Limón, Antonio Sánchez-Soblechero, Alberto Lozano-Ros, Javier Díaz-De-Terán, Leonardo Portocarrero-Sánchez, Francisco-José Molina-Martínez, Sonia Santos-Lasaosa, Guillermo Martín-Ávila, Elena Riva, Iris Fernández-Lázaro","doi":"10.1177/03331024261431337","DOIUrl":"10.1177/03331024261431337","url":null,"abstract":"<p><p>AimAtogepant is a novel oral calcitonin gene-related peptide (CGRP) receptor antagonist approved for migraine prevention. This study primarily evaluated its effectiveness and safety in real-world clinical practice, focusing on patients with treatment-resistant migraine, defined according to the European Headache Federation (EHF) criteria as failure of at least three classes of preventive medications, including onabotulinumtoxinA or anti-CGRP monoclonal antibodies (mAbs).MethodsThis prospective multicentre study was conducted across 15 tertiary Headache Units in Spain. Demographic and clinical data, prior preventives, monthly headache days (MHD), monthly migraine days (MMD), and adverse events (AEs) were systematically collected at baseline, 3 months (primary endpoint), and/or 6 months (secondary endpoint).ResultsA total of 513 patients were enrolled (mean age 48 years; 88% women). The 3-month analysis included 455 patients, with median MHD decreasing from 21 (IQR 15-30) to 14 (IQR 6-30) and MMD from 14 (IQR 10-20) to 8 (IQR 3-15) (both p < 0.0001). A ≥ 50% reduction was achieved by 34% (MHD) and 29% (MMD), with ≥75% responses in 16% and 13%. Adverse events were mostly mild, mainly constipation (30%) and nausea (18%), and the 3-month discontinuation rate was 11.8%. Responders had shorter migraine chronicity, less analgesic overuse, and fewer prior preventive failures. Although prior inadequate response to anti-CGRP mAbs reduced the likelihood of improvement, it did not prevent meaningful benefit. At analysis, 151 patients had reached the 6-month visit, showing further improvement (MHD 10 [IQR 5-20]; MMD 6 [IQR 4-12]) and fewer adverse events.ConclusionsAtogepant showed robust real-world effectiveness and good tolerability in a large, treatment-resistant migraine cohort, with clinically meaningful improvement at 3 months and incremental benefit in the subgroup evaluated at 6 months. Lower migraine chronicity and fewer prior preventive failures were associated with better outcomes, supporting the earlier introduction of anti-CGRP therapies in clinical practice.Trial RegistrationClinical Trials.gov NCT06241313.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"46 4","pages":"3331024261431337"},"PeriodicalIF":5.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Migraine attack incidence in relation to the post-ovulatory estrogen decline: A prospective cohort study.","authors":"Britt W H van der Arend, Sally Bakker, Daphne S van Casteren, Iris E Verhagen, Nadine Pelzer, Irene de Boer, Suzanne C Cannegieter, Antoinette MaassenVanDenBrink, Gisela M Terwindt","doi":"10.1177/03331024261436415","DOIUrl":"10.1177/03331024261436415","url":null,"abstract":"<p><p>BackgroundPrevious studies suggest the perimenstrual phase increases migraine without aura risk, attributed to the decline of estrogen in this phase. However, the link to the decline of estrogen in the post-ovulatory phase remains unclear.MethodsWe conducted a longitudinal cohort study among 563 women with migraine and a regular natural menstrual cycle. Participants completed a validated e-headache diary also including menstrual cycle tracking. Of these women, 31 (who participated in our Women Hormones Attacks and Treatment (WHAT)-hormone study) performed urine luteinizing hormone (LH) surge tests during two menstrual cycles to validate the estimation of the post-ovulatory estrogen decline. The association between the post-ovulatory estrogen decline and migraine incidence was assessed using a mixed logistic model with patient as random effect, and the post-ovulatory and menstrual window as fixed effects. Secondary analyses included a case-crossover model and a self-controlled case series (SCCS) model to strengthen robustness and control for time-invariant confounders.ResultsE-diary data from 2627 menstrual cycles, including 58 from the WHAT-hormone subgroup, were analyzed. Across all three statistical models, the post-ovulatory window showed no higher incidence of migraine (with or without aura) than other menstrual cycle days (mixed logistic model: OR 0.95, 95% CI 0.89-1.02; WHAT-hormone subgroup: OR 0.68, 95% CI 0.38-1.16). The perimenstrual window had the highest migraine incidence (SCCS model with luteal phase as reference: OR 1.67, 95% CI 1.60-1.75), followed by the follicular phase (OR 1.31, 95% CI 1.26-1.37).DiscussionIn contrast to what many women with migraine believe, there is no increased incidence of migraine attacks (with or without aura) during the post-ovulatory window, but a higher incidence during the follicular phase compared to the luteal phase was confirmed.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"46 4","pages":"3331024261436415"},"PeriodicalIF":5.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and tolerability of pharmacological prophylaxis in migraine patients with prior preventive treatment failure: A systematic review and network meta-analysis of randomized controlled trials.","authors":"Malahat Khalili, Faraidoon Haghdoost, Amin Liaghatdar, Kian Torabiardakani, Fatemeh Mahdian, Tariq Atkin-Jones, Tal Levit, Sara Moradi, Ehsan Hedayati, Farzaneh Ahmadi, Sahar Khademioore, Ahmad Sofi-Mahmudi, Vivek Patil, Fatemeh Mirzayeh Fashami, Soheil Mehmandoost, Rachel J Couban, Kameshwar Prasad, Seyed-Mohammad Fereshtehnejad, Behnam Sadeghirad","doi":"10.1177/03331024261441287","DOIUrl":"10.1177/03331024261441287","url":null,"abstract":"<p><p>BackgroundDespite advances in migraine management, some patients fail to respond to preventive treatments for migraine. We aimed to assess the comparative effects of available pharmacological prophylaxis in adults with a treatment failure history.MethodsWe searched Medline, Embase, Cochrane Central, PsycINFO, Web of Science, and Scopus up to July 2025. Pairs of reviewers independently screened titles, abstracts, and full-text articles to identify randomized controlled trials of prophylactic pharmacological interventions that enrolled adults diagnosed with chronic or episodic migraine and a prior preventive treatment failure. We performed a frequentist random-effects network meta-analysis and used the GRADE approach to assess the certainty of evidence.ResultsWe included 18 randomized trials (7281 participants). Compared to placebo, low certainty evidence suggest fremanezumab [mean difference (MD) -3.30 (95% CI: -4.11 to -2.49)], eptinezumab [MD -3.35 (95% CI: -4.38 to -2.32)], galcanezumab [MD -2.73 (95% CI: -3.43 to -2.03)], atogepant [MD -2.30 (95% CI: -3.47 to -1.13)], and erenumab [MD -2.20 (95% CI: -2.72 to -1.68)] may be among the most effective in reducing the monthly migraine headache days. Low to moderate certainty evidence suggests that, compared with placebo, galcanezumab [relative risk (RR) 1.94 (95% CI: 1.52 to 2.48)], fremanezumab [RR 3.98 (95% CI: 2.40 to 6.59)], atogepant [RR 2.80 (95% CI: 1.73 to 4.54)], erenumab [RR 2.56 (95% CI: 2.01 to 3.26)], and eptinezumab [RR 2.35 (95% CI: 1.61 to 3.42)] may increase the likelihood of achieving a 50% response rate.ConclusionEvidence for migraine patients with prior preventive treatment failure is limited. Low- to moderate-certainty data suggest that CGRP-targeted therapies may provide some benefit and are generally tolerable, but the available evidence is driven by a few industry-sponsored trials. Additional independent, well-powered studies with longer follow-up are needed to strengthen the evidence base.Registration numberPROSPERO (CRD42024547860).</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"46 4","pages":"3331024261441287"},"PeriodicalIF":5.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcultural headache medicine: A framework for integrating cultural contexts into headache science and care - a call to action from the International Headache Society.","authors":"Mario F P Peres, Giancarlo Lucchetti, Homero Vallada, Ivy L Riso, Georgia K Westenhofen, Marcelo Moraes Valença, Juliana Ramos de Andrade, K C Brennan, Morris Levin, Tsubasa Takizawa, Zhao Dong, Yonggang Wang, Wanakorn Rattanawong, Henry Riyanto Sofyan, Massimo Leone, Freda Dodd-Glover, Hsiangkuo Yuan, Abdulrazaq Albilali, Taoufik Alsaadi, Leonardo Caixeta, Anna P Andreou, Peter J Goadsby, Antoinette MaassenVanDenBrink, Sait Ashina, Rami Burstein, Patricia Pozo-Rosich, Fayyaz Ahmed, Shuu-Jiun Wang","doi":"10.1177/03331024261432929","DOIUrl":"10.1177/03331024261432929","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"46 4","pages":"3331024261432929"},"PeriodicalIF":5.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific orchestration of morphometric similarity networks in children and adolescents with migraine.","authors":"Laura Papetti, Alessia Guarnera, Daniela Longo, Antonio Napolitano, Giulia Baldassari, Greta Pirani, Giorgia Sforza, Gabriele Monte, Fabiana Ursitti, Francesco Dellepiane, Maria Vaccaro, Alessia Carboni, Maria Camilla Rossi-Espagnet, Giulia Moltoni, Carlo Gandolfo, Massimiliano Valeriani","doi":"10.1177/03331024261416494","DOIUrl":"10.1177/03331024261416494","url":null,"abstract":"<p><p>BackgroundMigraine accounts for most primary headaches in children and adolescents and is related to cortical and connectivity changes. However, the underlying mechanisms remain unclear. Morphometric similarity mapping has not yet been applied to children and adolescents with migraine.MethodsEighty-three patients (6-17 years) with migraine without aura and 81 age- and sex-matched controls were retrospectively included. High-resolution 3D T1-weighted and diffusion-weighted magnetic resonance imaging scans were processed to extract cortical morphometric parameters and compute morphometric similarity networks (MSN). Global and regional MSN differences were assessed between patients and controls, and across subgroups defined by sex, attack frequency and migraine-associated symptoms.ResultsPatients showed significant MSN alterations, particularly in temporal and cingulate regions. Sex emerged as the strongest factor influencing MSN architecture, with additional modulations linked to attack frequency and clinical symptoms. Affected pathways encompassed the executive control, nociceptive and default mode networks.ConclusionsMigraine in children and adolescents is associated with widespread MSN abnormalities, likely reflecting cortical reorganization mechanisms. Male and female patients appear to engage distinct neural \"orchestras\", each emphasizing different network sections (sensory-affective in males and cognitive-attentive in females) to produce a shared clinical experience. These findings highlight sex as a key determinant of migraine neurobiology in developmental age.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"46 4","pages":"3331024261416494"},"PeriodicalIF":5.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147622047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and outcomes of pharmacological treatments for headaches after traumatic brain injury: A systematic review.","authors":"Shirin Saleh, Elizabeth M Sanford, Donald D McGeary, Melissa M Cortez, Matt Hayward, Erin D Bouldin, Jacob Kean, Mary Jo V Pugh","doi":"10.1177/03331024261441563","DOIUrl":"10.1177/03331024261441563","url":null,"abstract":"<p><p>BackgroundHeadache following traumatic brain injury (TBI) is a common, yet disabling, disorder with diverse mechanisms and treatment needs that remain poorly defined. Pharmacological regimens are the primary source of remedies for individuals with post-traumatic headaches (PTH). The main objective of this review is to describe the efficacy of pharmacological medications for the treatment of PTH with a specific focus on the effect of these medications on headache characteristics and headache-related quality of life (QoL).MethodsThis systematic review (CRD42024537719) followed PRISMA and SWiM guidelines. PubMed, CINAHL, Scopus, PsycINFO and the Cochrane Library were searched in April 2024 for peer-reviewed articles published in English between 2009 and 2024. Eligible studies included randomized controlled trials, controlled cohort studies, and systematic reviews or meta-analyses evaluating pharmacological treatments for PTH in adults. Studies were excluded if they did not assess outcomes related to PTH pain, only included pediatric populations, used animal models, investigated only non-pharmacological interventions, were case reports, narrative reviews, editorials or conference abstracts, or did not involve human participants with TBI-related headache. Risk of bias was assessed using RoB-2 for Randomized controlled trials (RCTs) and ROBINS-I for the non-randomized studies of the effects of interventions.ResultsSixteen studies were included in the final review, comprising retrospective observational (<i>n</i> = 7), non-randomized prospective (<i>n</i> = 4) and randomized controlled trials (<i>n</i> = 5). Most studies reported some improvements in headache frequency and intensity following pharmacological treatment, although findings for headache-related QoL were inconsistent. Erenumab showed potential benefits for persistent PTH in small, uncontrolled studies of civilian samples. However, findings on its impact on headache-related QoL should be interpreted with caution, given the high discontinuation rate observed. Prazosin demonstrated similar benefits in military populations, with minimal side effects. In the acute care setting, metoclopramide, co-administered with diphenhydramine to minimize side effects, was associated with short-term relief of headache symptoms. Of the RCTs, only two had a low risk of bias, of which only one specifically focused on PTH.ConclusionsPharmacological treatments for PTH may provide improvements in headache frequency and intensity; however, evidence for their efficacy is limited and inconsistent. Given the limited high-quality evidence overall, no specific clinical recommendations can be made at this time. Future research should prioritize rigorous, controlled studies, particularly comparative effectiveness trials, and explore holistic, personalized approaches that incorporate treatment of psychiatric comorbidities and consider patient context.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"46 4","pages":"3331024261441563"},"PeriodicalIF":5.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visually-induced hemodynamic response and white matter hyperintensities in middle-aged women with ischemic stroke or migraine with aura.","authors":"Nelleke van der Weerd, Mariam Ali, Thijs W van Harten, Ay-Min Ma, Ghislaine Holswilder, Annelise E Wilms, Erik W van Zwet, Mark C Kruit, Arn M J M van den Maagdenberg, Gisela M Terwindt, Matthias J P van Osch, Hendrikus J A van Os, Marieke J H Wermer","doi":"10.1177/03331024261439256","DOIUrl":"10.1177/03331024261439256","url":null,"abstract":"<p><p>BackgroundMigraine, especially with aura (MA), increases the risk of brain white matter hyperintensities (WMH) and ischemic stroke. Altered microvascular function has been proposed as a shared underlying mechanism, potentially involving endothelial dysfunction. Visually-induced hemodynamic response describes the process by which cerebral blood flow is locally increased to meet the metabolic demands of neuronal activity and may serve as a surrogate measure of cerebral endothelial function. We investigated the relationship between visually-induced hemodynamic responseand WMH volume in middle-aged women with ischemic stroke or MA.MethodsWe cross-sectionally measured hemodynamic response using blood-oxygen-level-dependent (BOLD) fMRI upon visual stimulation on 7T-MRI, and WMH volume on 3T-MRI, in three groups of women aged 40-60 with: (I)ischemic stroke, (II)MA, and (III)no history of stroke or migraine. We assessed the associations between BOLD parameters in the posterior circulation (amplitude, time-to-peak [TTP], and time-to-baseline [TTB]) and WMH volume using multivariable linear regression within each group.ResultsWe included 87 women (mean age 51 years): (I)25 with ischemic stroke, (II)25 with MA, and (III)37 without stroke or migraine. Visually-induced hemodynamic response was similar across groups and not associated with WMH volume overall. However, lower amplitude was associated with higher deep WMH volume in those without stroke or migraine (adjusted-β= -0.28;95%CI = -0.53 to -0.02 mL), shorter TTB with greater periventricular WMH volume in women with MA (adjusted-β= -0.12;95%CI = -0.21 to -0.02 mL), and longer TTP with increased periventricular WMH volume in women with stroke (adjusted-β=0.22;95%CI = 0.06 to 0.40 mL).ConclusionsNo overall association was observed between visually-induced hemodynamic response and WMH volume. Exploratory findings suggest potential differences in hemodynamic response in the posterior circulation across groups, which require replication in larger datasets and confirmation in longitudinal studies to clarify their temporal or mechanistic relevance to WMH development.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"46 4","pages":"3331024261439256"},"PeriodicalIF":5.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward quantifying disability in spontaneous intracranial hypotension: A patient-derived disability weight.","authors":"Florian Volz, Mazin Omer, Manou Overstijns, Amir El Rahal, Marc Hohenhaus, Jan-Helge Klingler, Niklas Lützen, Horst Urbach, Charlotte Zander, Ian Carroll, Jürgen Beck, Katharina Wolf","doi":"10.1177/03331024261444662","DOIUrl":"10.1177/03331024261444662","url":null,"abstract":"<p><p>IntroductionSpontaneous intracranial hypotension (SIH) due to a spinal CSF leak is associated with substantial health loss. However, SIH is not represented as a distinct condition in the Global Burden of Disease framework, and no disease specific disability weight has been reported. A disability weight is the fundamental basis for comparative analyses of disease burden. The objective of this study was to estimate a patient-derived disability weight for SIH based on pre-treatment health-related quality of life data and to contextualize this estimate relative to published values for other conditions.MethodsWe conducted a retrospective observational study of consecutive patients with confirmed spinal CSF leaks treated at a tertiary referral center between October 2020 and October 2025. Pre-treatment quality of life and headache burden were assessed using the EQ-5D-5L and HIT-6 questionnaires. After calculating the EQ-Index using the German value set, the mean disability weight and its 95% confidence interval were derived using a linear transformation. For contextual interpretation, the newly estimated disability weight was compared descriptively with published values for deliberately selected neurological, headache- or pain-related, and chronic conditions.ResultsA total of 321 patients with confirmed spinal CSF leaks before targeted treatment were included (60.4% female; median age 47 years [IQR 37-56.). Most patients had a ventral leak (192/321, 60%), followed by CSF-venous fistulas (67/321, 21%) and lateral leaks (62/321, 19%). The mean EQ-Index was 0.568 (95% CI 0.533-0.603), the median EQ-VAS was 45.5 (IQR 30-65). The median HIT-6 score was 65 (IQR 59-68). All scores showed no significant differences between the three leak types. Based on EQ-5D-5L data, the resulting mean disability weight for SIH was 0.432 (95% CI 0.40-0.47).ConclusionThis study provides a first patient-derived disability weight estimate of 0.432 for ongoing SIH. This indicates a substantial non-fatal health loss that is comparable to or exceeding that of other chronic conditions. This estimate enables contextual comparison with other conditions and provides a foundation for future burden-of-disease assessments of this curable condition.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"46 4","pages":"3331024261444662"},"PeriodicalIF":5.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, tolerability, and efficacy of atogepant added to onabotulinumtoxinA for the preventive treatment of chronic migraine: A phase 3, multicenter, 24-week, open-label study.","authors":"John Rothrock, Umer Najib, Jessica Ailani, Sait Ashina, Jia Bao, Jonathan H Smith, Aubrey M Adams, Brett Dabruzzo, Kimberly Pfleeger, Andrew Blumenfeld","doi":"10.1177/03331024261429118","DOIUrl":"10.1177/03331024261429118","url":null,"abstract":"<p><p>BackgroundTreatment with onabotulinumtoxinA is effective in reducing migraine day frequency and duration in individuals with chronic migraine (CM), but given the severity of the disease, those with CM often need additional treatment to achieve optimal outcomes. Combining preventive treatments with distinctly different physiological targets may yield greater benefit than monotherapy. This study evaluated the safety, tolerability, and efficacy of adding atogepant to onabotulinumtoxinA for preventive treatment of CM.MethodsIn this 24-week, Phase 3, open-label, single arm, multicenter study (NCT05216263), 75 participants on a stable dose of onabotulinumtoxinA (155-200U) with baseline mean monthly migraine days (MMDs) of 8-23 (inclusive) received add-on atogepant 60 mg once daily. Primary safety endpoints included treatment-emergent adverse events (TEAEs), and exploratory efficacy endpoints included changes in MMDs, changes in mean monthly headache days (MHDs) and responder rates (RRs) (≥50%, ≥75%, and 100% MMDs) over Weeks 1-12, Weeks 13-24, and at each 4-week interval.ResultsThe mean age of study participants was 48 (13.68) years (mean (SD)); 89% were women, and 97% were white. Participants had an established CM diagnosis for 15 (13.27) years (mean (SD)) and had been treated with onabotulinumtoxinA for 4 (3.45) years (mean (SD)). In the safety population (n = 75), the incidence of TEAEs was 65.3%. TEAEs occurring in ≥5% of participants were constipation (n = 12, 16.0%), nausea (n = 10, 13.3%), and urinary tract infection (n = 6, 8.0%). An AE was considered the primary reason for drug discontinuation in 2 (2.7%) participants. Treatment-emergent serious AEs (TESAEs) occurred in 2 participants; neither were considered treatment-related by the investigators. In the modified intention-to-treat population (n = 72), the least squares (LS) mean change from baseline of 14.34 MMDs was -6.45 MMDs (95% CI: -7.7, -5.1) at Weeks 1-4, -6.89 MMDs (95% CI: -8.1, -5.6) across Weeks 1-12, and -7.20 MMDs (95% CI: -8.4, -5.9) across Weeks 13-24. The least square mean change from baseline of 17.00 MHDs was -6.57 MHDs (95% CI: -7.8, -5.3) at Weeks 1-4, -7.33 MHDs (95% CI: -8.6, -6.0) across Weeks 1-12 and -8.15 MHDs (95% CI: -9.4, -6.8) across Weeks 13-24. A ≥ 50% RR in MMD was achieved by 54.2% and 61.9% of participants across Weeks 1-12 and Weeks 13-24 of combined treatment, respectively. A ≥ 75% RR was achieved by 30.6% and 38.1% of participants.ConclusionsIn this study, combination preventive treatment for CM with onabotulinumtoxinA and atogepant was safe and generally well-tolerated. Furthermore, the addition of atogepant to those stable on onabotulinumtoxinA resulted in clinically meaningful reductions in migraine days and improvement in responder rates, suggesting a benefit of combining treatments with distinct and complementary mechanisms of action for suppression of CM.Trial RegistrationClinical Trials.gov NCT05216263.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"46 4","pages":"3331024261429118"},"PeriodicalIF":5.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical activity in migraine: Identifying an engagement threshold and patient clusters in a population-based cohort.","authors":"Ido Peles, Shaked Sharvit, Victor Novack, Gal Ifergane","doi":"10.1177/03331024261426569","DOIUrl":"10.1177/03331024261426569","url":null,"abstract":"<p><p>BackgroundPhysical activity (PA) has been associated with reduced migraine burden, but patients with frequent or comorbid migraine often report difficulty sustaining regular activity. We examined the association between minimal PA and migraine-related outcomes, and explored whether a disease burden threshold limits PA engagement.MethodsWe analyzed data from 550 participants with migraine in the Negev Migraine Cohort in southern Israel who completed a questionnaire assessing PA (≥2 h/week), migraine-related disability (MIDAS), depressive symptoms (DASS-21), and psychosocial functioning. Between-group comparisons and multivariable linear regression models were conducted to assess the independent associations of PA with key outcomes, adjusting for demographic characteristics. We also explored the probability of engaging in PA by migraine frequency, and conducted unsupervised clustering based on migraine days, depressive symptoms, and PA status to identify patient profiles.ResultsPhysically active participants (46%) reported significantly fewer migraine days per month (median 3.0 vs. 5.0), lower use of triptans per month (mean 2.6 vs. 4.1 pills), and reduced migraine-related disability (median MIDAS score 26.0 vs. 36.0). They also reported fewer days of presenteeism per month (median 3.5 vs. 5.0). In addition, they experienced less impairment in overall life satisfaction (mean 4.49 vs. 5.14). In fully adjusted models, PA remained independently associated with reduced disability (β = -0.14, 95% CI -0.28 to -0.1) and improved life satisfaction (β = -0.46, 95% CI -0.9 to -0.1). Probability modeling showed that individuals with more than three migraine days per month had less than 50% likelihood of meeting PA targets. Clustering analysis identified three subgroups: a high-burden and low-activity group, an intermediate group, and an active and well-functioning group.ConclusionsMinimal PA was associated with lower migraine-related disability and better life satisfaction. The identification of an activity engagement threshold and distinct patient clusters suggests a staged care model where pharmacologic stabilization enables PA, which may itself serve as a marker of recovery.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"46 4","pages":"3331024261426569"},"PeriodicalIF":5.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}