Pozo-Rosich P, López JAG, Lisewski P
… +7 more, Aslan AN, Seehra H, Thiry A, Abraham L, Ramirez LM, Fountaine R, Fullerton T
Cephalalgia
· 2025 Nov · PMID 41255098
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AimThis study aimed to evaluate the efficacy and tolerability of rimegepant for the prevention of episodic migraine in participants with a documented history of inadequate response to 2-4 categories of traditional oral p...AimThis study aimed to evaluate the efficacy and tolerability of rimegepant for the prevention of episodic migraine in participants with a documented history of inadequate response to 2-4 categories of traditional oral preventive medication (OPM).MethodsThis multinational phase 4 trial consisted of an untreated 28-day observational phase (OP) and a 12-week double-blind treatment (DBT) phase. Participants with 4-14 monthly migraine days (MMDs), <15 monthly headache days (<7 non-migraine) and documented previous inadequate response to 2-4 traditional OPM categories were enrolled. Participants were randomized to rimegepant 75 mg orally disintegrating tablet (ODT) or placebo every other day (EOD). The primary endpoint was mean change from the OP in MMDs through the 12-week DBT phase. Key secondary endpoints were tested hierarchically to control type I errors. Tolerance and safety were assessed throughout the DBT phase.ResultsIn total, 328 participants received rimegepant and 324 received placebo. The most common OPM categories with prior inadequate response were anticonvulsants (61%), beta-blockers (56%) and amitriptyline (51%). The mean ± SD number of MMDs in the OP was 8.4 ± 2.4 and 8.3 ± 2.3, respectively, in the rimegepant (n = 324) and placebo (n = 319) groups. Across the DBT phase, participants who received rimegepant had a significantly larger mean change from the OP in MMDs than those who received placebo (-2.1 vs. -0.5 days; difference = -1.6 days; 95% confidence interval (CI) = -2.1 to -1.2; < 0.0001). All key secondary endpoints favored rimegepant: (i) percentage of participants with ≥50% reduction from the OP in MMDs with moderate or severe pain intensity across the DBT phase (difference: 20.1%; 95% CI = 13.7 to 26.5; < 0.0001); (ii) mean change from the OP in MMDs in the first month of the DBT phase (difference: -1.7 days; 95% CI = -2.3 to -1.2; < 0.0001); (iii) mean change from the OP in MMDs in the last month of the DBT phase (difference: -1.4 days; 95% CI = -2.1 to -0.8; < 0.0001); (iv) mean change from baseline in Migraine-Specific Quality-of-Life Questionnaire v2.1 Restrictive Role Function domain score at week 12 of the DBT phase (difference: 6.6 points; 95% CI = 3.6 to 9.5; < 0.0001); and (v) mean change from baseline in Migraine Interictal Burden Scale score at week 12 of the DBT phase (difference: -0.9 points; 95% CI = -1.4 to -0.4; = 0.0006). Rimegepant was well tolerated with a safety profile not notably different from placebo.ConclusionsRimegepant 75 mg ODT EOD is efficacious and well tolerated for the prevention of episodic migraine in participants with a documented history of inadequate response to 2-4 categories of traditional OPM.Trial RegistrationClinicalTrials.gov, NCT05518123 (https://clinicaltrials.gov/study/NCT05518123).
Ashina M, McAllister P, Gaul C
… +7 more, Leyva-Rendon A, Ramirez LM, Nalpas C, Thiry A, Abraham L, Fountaine RJ, Fullerton T
Cephalalgia
· 2025 Nov · PMID 41255093
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BackgroundA subset of individuals with migraine are unsuitable for triptans due to intolerance, lack of efficacy, or contraindications. This phase 4 study assessed the efficacy and tolerability of a single 75-mg dose of...BackgroundA subset of individuals with migraine are unsuitable for triptans due to intolerance, lack of efficacy, or contraindications. This phase 4 study assessed the efficacy and tolerability of a single 75-mg dose of rimegepant orally disintegrating tablet (ODT) for acute treatment of migraine in adults with documented triptan unsuitability.MethodsParticipants (aged ≥18 years with 4-14 migraine days per month) with documented history of (A) intolerance and/or lack of efficacy to ≥2 triptans or (B) contraindication to triptans were randomized (1:1) to rimegepant 75 mg ODT or placebo to treat a single migraine attack of moderate or severe pain intensity. Randomization was stratified by history of clinically relevant cardiovascular disease. The primary endpoint was the percentage of participants with migraine pain relief (no or mild pain) at 2 h post dose. Key secondary endpoints, tested using a hierarchal approach to control type 1 error, included the percentage of participants with migraine pain freedom at 2 h, rescue medication use within 24 h, return to normal function at 2 h, sustained return to normal function from 2-24 h and from 2-48 h, sustained migraine pain relief from 2-24 h and from 2-48 h, sustained migraine pain freedom from 2-24 h and from 2-48 h, and most bothersome symptom freedom at 2 h. Safety was assessed via adverse events (AEs) and laboratory tests.ResultsOverall, 585 participants (89.1% were female, mean age was 42.9 years) received study medication (rimegepant, = 295; placebo, = 290). Participants analyzed for efficacy (rimegepant, = 286; placebo, = 284) had documented failure to ≥2 triptans with ≥1 reason due to prior intolerance (30.5%) and/or ≥1 reason due to lack of efficacy (84.9%); 9.1% had a contraindication. Rimegepant demonstrated superiority over placebo for the primary endpoint of migraine pain relief at 2 h (55.9% vs 32.7%; difference [95% CI]: 23.2% [15.3-31.1%]; < 0.0001) and all 10 alpha-protected key secondary endpoints including pain freedom at 2 h (all ≤ 0.0005). AE rates were similar across treatments (12.5% vs 12.1%), with no severe AEs, serious AEs, or clinically significant laboratory test abnormalities reported in the rimegepant group.ConclusionsA single 75-mg dose of rimegepant ODT was efficacious and well tolerated for acute treatment of migraine in adults unsuitable for triptans. This first prospective trial of a gepant in this population supports calcitonin gene-related peptide antagonism as a valuable option when triptans are unsuitable.Trial RegistrationClinicaltrials.gov NCT05509400.
Tang Y, Li H, Dong B
… +3 more, Sha L, Yang R, Chen L
Cephalalgia
· 2025 Nov · PMID 41252278
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BackgroundMenstrually-related migraine (MRM) is a subtype of migraine associated with the ovarian cycle that imposes a significant burden on female patients. Although MRM and non-menstrual migraine (NMM) differ in clinic...BackgroundMenstrually-related migraine (MRM) is a subtype of migraine associated with the ovarian cycle that imposes a significant burden on female patients. Although MRM and non-menstrual migraine (NMM) differ in clinical presentation and treatment response, their distinct neural mechanisms remain unclear. Emerging evidence suggests that alterations in intrinsic functional connectivity (FC) within and between large-scale brain networks may underlie the phenotypic heterogeneity of migraine subtypes. This study investigated FC alterations between patients with MRM and NMM, explored their correlations with clinical characteristics, and assessed the preliminary utility of FC in subtype differentiation.MethodsResting-state functional magnetic resonance imaging (MRI) with independent component analysis was used to examine whole-brain FC in 50 patients with MRM, 50 with NMM and 50 age-balanced healthy controls (HC). We analyzed within- and between-network connectivity across major resting-state networks, including the frontoparietal, default mode, salience and dorsal attention networks, and applied logistic regression to test whether FC values could classify migraine subtypes. Correlation analyses were further performed between FC measures and clinical indices, including disease duration, headache frequency, visual analog scale scores and Headache Impact Test (HIT-6) scores.ResultsBoth MRM and NMM groups showed weaker within-network connectivity compared to HCs, primarily in the right frontoparietal, default mode and salience networks. Compared with NMM, the MRM group exhibited significantly stronger connectivity in the left frontoparietal network and weaker between-network connectivity between the dorsal attention and default mode networks. In the women with migraine, FC within the dorsal attention network (DAN) was negatively correlated with disease duration (r = -0.200, p = 0.046) and HIT-6 score (r = -0.183, p = 0.049). Furthermore, FC between the DAN and auditory network was inversely associated with disease duration ( = -0.225, = 0.025). The logistic regression model achieved an area under the receiver operating characteristic curve of 0.73 (sensitivity = 0.70; specificity = 0.64) in distinguishing MRM from NMM.ConclusionsOur findings reveal both shared and distinct alterations in large-scale brain networks in MRM and NMM, potentially explaining differences in clinical presentation and treatment response. This enhanced understanding of migraine pathophysiology supports the development of subtype-specific diagnostic tools and targeted therapies and underscores the value of resting-state fMRI as a non-invasive tool for migraine phenotyping and personalized care.Registration NumberChiCTR2200065586.
Bsteh G, Pemp B, Marik W
… +5 more, Novak K, Leutner M, Leis S, Broessner G, Austrian network for idiopathic intracranial hypertension (AN4IH)
Cephalalgia
· 2025 Nov · PMID 41223050
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BackgroundThe diagnosis, treatment and monitoring of patients with idiopathic intracranial hypertension (IIH) are highly complex processes that require interdisciplinary collaboration with respect to neurology, ophthalmo...BackgroundThe diagnosis, treatment and monitoring of patients with idiopathic intracranial hypertension (IIH) are highly complex processes that require interdisciplinary collaboration with respect to neurology, ophthalmology, neuroradiology, neurosurgery and endocrinology. Accordingly, there is a consensus among international guidelines that the management of these aspects of care should be the responsibility of specialized centers that are equipped with appropriate facilities. The objective of the Austrian Network for Idiopathic Intracranial Hypertension (AN4IH) is to establish a national network of excellence and to provide comprehensive recommendations for the structure and operation of specialized IIH centers (AN4IH centers), including an integrated, interdisciplinary diagnostic and treatment pathway.MethodsThis consensus was developed by an interdisciplinary panel of experts convened by Austrian neurologists, (neuro)ophthalmologists, neuroradiologists, neurosurgeons and endocrinologists. The process adhered to a formal consensus methodology.ResultsThe AN4IH consensus provides a comprehensive, integrated, interdisciplinary framework addressing care infrastructure, urgency stratification, diagnostics, treatment and monitoring, as well as considerations related to family planning and pregnancy in patients with IIH. The AN4IH consensus is explicitly intended as a supplement and extension to existing international guidelines.ConclusionsThe management of IIH necessitates a structured, interdisciplinary approach to optimize patient outcomes. Through formal consensus methodology, the AN4IH provides expert - and where available evidence - based recommendations for specialized care centers, emphasizing standardized diagnostic pathways, urgency stratification and tailored treatment protocols. By fostering collaboration and institutionalizing best practices, the AN4IH model represents a significant advancement in delivering comprehensive, patient-centered care for this complex neurological disorder and encourages participants to create a secure, quality-controlled shared database for the collection of all clinical and paraclinical data, alongside the establishment of a biobank for the storage of biosamples.
Lin C, Li Y, Wang Z
… +10 more, Duan C, Liu G, Guo Z, Li X, Xiong Z, Chen T, Zhang M, Gao T, Sui B, Wang Y
Cephalalgia
· 2025 Nov · PMID 41223010
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BackgroundNeurovascular coupling (NVC) reflects the interaction between cerebral blood flow (CBF) and functional activity. However, the relationship between NVC and migraine chronification remains unclear. This study inv...BackgroundNeurovascular coupling (NVC) reflects the interaction between cerebral blood flow (CBF) and functional activity. However, the relationship between NVC and migraine chronification remains unclear. This study investigated the state of NVC in migraine patients and evaluated its potential as an imaging feature for migraine chronification using arterial spin labeling (ASL) combined with resting-state functional magnetic resonance imaging (rs-fMRI).MethodsThis was a cross-sectional study. Thirty-nine episodic migraine (EM), 61 chronic migraine (CM) patients (25 with medication overuse headache, MOH) and 42 healthy controls (HCs) were recruited in the same period. Imaging data were acquired using a 3.0 T MRI. Regional homogeneity (ReHo) represented functional activity, whereas CBF was quantified via ASL. Correlation coefficient between CBF and ReHo values of each participant in voxel level represented the whole-brain NVC status, whereas the CBF/ReHo ratio represented regional NVC status. Correlations between NVC metrics and clinical characteristics were analyzed in CM patients. Exploratory mediation analysis was conducted to identify mediators between NVC alterations and the clinical characteristics of CM patients. Finally, receiver operating characteristic (ROC) curve was generated to evaluate the diagnostic performance of NVC metrics for migraine chronification.ResultsCompared to HCs, both EM and CM patients presented significantly reduced whole-brain CBF-ReHo coupling. Compared to EM patients, CM patients presented a decreased CBF/ReHo ratio in the right precuneus. Correlation analysis revealed that z value of the CBF/ReHo ratio in the right precuneus was negatively correlated with both HIT-6 score and PHQ-9 score; HIT-6 score was positively correlated with PHQ-9 score in CM group. Exploratory mediation analysis indicated that depression mediated the relationship between abnormal NVC and clinical characteristics in CM patients. Finally, ROC curve indicated that the CBF/ReHo ratio in the right precuneus (AUC = 0.75) exhibited high sensitivity and specificity in distinguishing CM from EM patients.ConclusionAbnormal NVC in the precuneus was involved in migraine chronification, with depression potentially serving as a mediator in this process. NVC metric may serve as an imaging feature for migraine chronification in the future.
Ailani J, Tomaschek I, Stark-Inbar A
… +3 more, Shmuely S, Ironi A, Lax DN
Cephalalgia
· 2025 Oct · PMID 41195499
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AimTo evaluate the effect of treatment onset-time on the effectiveness of remote electrical neuromodulation (REN) for acute treatment of migraine.MethodsA real-world evidence study on migraine patients who treated with R...AimTo evaluate the effect of treatment onset-time on the effectiveness of remote electrical neuromodulation (REN) for acute treatment of migraine.MethodsA real-world evidence study on migraine patients who treated with REN . REN treatments initiated within one hour of migraine attack onset (headache or aura) were classified as "early"; those initiated after one hour were classified as "late". Treatments with baseline and two-hour reports were termed "evaluable" and analyzed.ResultsAmong 55,261 patients (37.9 ± 18.5 years, 83.4% female) who conducted 586,981 treatments, 56.5% were administered early. Effectiveness was calculated from "evaluable" treatments, varying between 6413 and 35,581 treatments depending on the outcome. Early treatments yielded higher responder-rates than late ( < 0.001, significant following Bonferroni correction for multiple comparisons) for pain relief (65.1% vs. 46.6%; Δ = 18.5%), pain freedom (28.8% vs. 14.5%; Δ = 14.3%), functional disability relief (58.1% vs. 49.3%; Δ = 8.8%), functional disability freedom (35.4% vs. 20.9%; Δ = 14.5%), and freedom from photophobia (26.9% vs. 19.0%; Δ = 7.9%), phonophobia (34.0% vs. 25.9%; Δ = 8.1%) and nausea/vomiting (51.5% vs. 38.7%; Δ = 12.8%). Similarly, patients consistently treating early with REN (in 50% or more of their treatments) experienced higher efficacy ( < 0.001). Similar effects were seen in youths.ConclusionsEarly acute treatment with REN enhanced patient outcomes by up to two-fold compared to late treatment onset. Educating providers and patients to "treat as early as possible" boosts clinical and patient-centered results.
Cephalalgia
· 2025 Nov · PMID 41190900
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BackgroundAlthough guidelines for clinical trials have proposed a definition for a migraine day, randomised clinical trials tend to vary in their definition used.MethodsDefinitions of a migraine day in phase III trials w...BackgroundAlthough guidelines for clinical trials have proposed a definition for a migraine day, randomised clinical trials tend to vary in their definition used.MethodsDefinitions of a migraine day in phase III trials with monoclonal antibodies and small molecules targeting the calcitonin gene-related peptide pathway for the preventive treatment of migraine were compared.ResultsTwelve different definitions were found across 23 trials. Variation in headache duration, the inclusion or exclusion of probable migraine and the inclusion or exclusion of a treated migraine attack with a specific or non-specific drug were most subject to debate. No single criterium or set of criteria was common to all definitions used. The most common single criterium used was a minimal headache duration of at least 30 minutes where only two clinical trials allowed for a headache with a shorter duration to be included.ConclusionThere is a pressing need for a standardised accepted definition of a migraine day both from a clinical and research perspective.
Cephalalgia
· 2025 Nov · PMID 41182862
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BackgroundThis study investigates the therapeutic potential of a combined dose of cannabidiol (CBD) and tetrahydrocannabinol (THC) at a 100:1 ratio (100 mg/kg CBD and 1 mg/kg THC) in mitigating central calcitonin gene-re...BackgroundThis study investigates the therapeutic potential of a combined dose of cannabidiol (CBD) and tetrahydrocannabinol (THC) at a 100:1 ratio (100 mg/kg CBD and 1 mg/kg THC) in mitigating central calcitonin gene-related peptide (CGRP)-induced migraine symptoms in a mouse model.MethodsThe 100:1 ratio of CBD to THC was administered intraperitoneally, 60 minutes prior to starting all the assays, followed by intracerebroventricular CGRP administration, 30 minutes later, with behavior assays conducted 30 minutes after CGRP injection. To determine whether pretreatment of CBD:THC could counteract CGRP-induced light aversion, we utilized the light/dark assay, which also recorded motility behavior. To investigate whether CBD:THC pretreatment could alleviate CGRP-induced spontaneous pain, we used the automated squint assay.ResultsOur findings show that pretreatment with 100:1 CBD:THC rescued light aversion caused by centrally administered CGRP in CD1 mice. Additionally, CBD:THC pretreatment rescued the increased resting time in darkness, decreased transitions between light and dark zones, and partially rescued the decreased rearing behavior induced by centrally administered CGRP. Moreover, an open field assay confirmed that centrally administered CGRP did not induce anxiety in a light independent assay. Finally, our findings from the automated squint assay indicate that pretreatment with 100:1 CBD:THC partially rescued centrally administered CGRP-induced spontaneous pain.ConclusionsCollectively, these results demonstrate that a combination of CBD and THC can alleviate light aversion and pain symptoms induced by a centrally-acting migraine trigger.
Cephalalgia
· 2025 Nov · PMID 41182861
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BackgroundThis narrative review establishes the current state of the art of machine learning approaches for prediction of migraine attacks. Related concepts are highlighted including the identification of triggers or pre...BackgroundThis narrative review establishes the current state of the art of machine learning approaches for prediction of migraine attacks. Related concepts are highlighted including the identification of triggers or premonitory symptoms and methods for evaluating prediction models. Existing efforts at machine learning prediction of individual migraine headaches and attacks are reviewed in detail. Challenges in this task are discussed.ResultsA variety of input data and modeling approaches have been used. It is consistently found that individualized models provide better results compared to a generalized model and achievable performance varies considerably between individuals. Patient needs should be assessed to discover what a valuable prediction looks like. The field should develop common standards for evaluating migraine prediction algorithms.Conclusions/InterpretationsWhile the problem is far from solved there is great potential and reason to believe that feasible solutions that improve the quality of life of those with migraine are within our grasp.
Herekar AA, Ahmad A, Uqaili UL
… +6 more, Ahmed B, Effendi J, Alvi SZU, Herekar AD, Steiner TJ, Husøy AK
Cephalalgia
· 2025 Oct · PMID 41148124
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BackgroundIn Pakistan, we have shown that both migraine (one-year prevalence of 22.5%) and tension-type headache (TTH: 44.6%) are more common among the adult population than reported globally. Here, to inform local healt...BackgroundIn Pakistan, we have shown that both migraine (one-year prevalence of 22.5%) and tension-type headache (TTH: 44.6%) are more common among the adult population than reported globally. Here, to inform local health policy and add to knowledge of the global burden of headache, we estimate the lost health and other burdens attributable to headache in this populous Eastern Mediterranean Region country.MethodsIn a cross-sectional survey using cluster-randomized sampling, we visited households unannounced in Punjab, Sindh, Khyber Pakhtunkhwa and Baluchistan. We randomly selected and interviewed one adult member (aged 18-65 years) of each household, using a validated Urdu version of the HARDSHIP (i.e. Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation) structured questionnaire. Burden enquiry was in multiple domains.ResultsIn total, there were 4223 participants. Those with headache spent on average 6.4% of their time with headache of moderate intensity, with females worse affected than males. Participants with migraine were worse affected than those with TTH. Those with probable medication-overuse headache or other headache on ≥15 days/month spent 39.7% and 30.2% of their total time with headache. Quality of life, productivity and participation in social or leisure activities were impaired. Factoring in prevalence and adjusting for age and gender, we estimated that 4.9-5.9% of all time in this population was spent with headache, and, on average, 3.1 and 3.8 days were lost from paid and household work in the preceding three months. Over half (57.5%) of the population were assessed as needing care, but education promoting effective self-care might reduce this to 28.7% in need of professional care.ConclusionsThe burdens of headache in Pakistan are therefore very substantial in terms of health and productivity losses. These findings are important to national health and economic policies. The benefits in health gain from nationwide implementation of structured headache services, cost-effective in themselves, should be accompanied by enhancements in productivity, offsetting the cost of these services.
Mascarella D, Zhuang ZA, Gliga O
… +9 more, Santis F, Rosignoli C, Daputke A, Njohjam MN, Mazzotta E, Adewinle FE, Caronna E, Pozo-Rosich P, International Headache Academy of the International Headache Society (IHS-iHEAD)
Cephalalgia
· 2025 Oct · PMID 41147997
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BackgroundMigraine is a common neurological disorder with a strong genetic component, yet the precise mechanisms underlying its genetic susceptibility remain largely unknown. Genome-wide association studies (GWAS) have i...BackgroundMigraine is a common neurological disorder with a strong genetic component, yet the precise mechanisms underlying its genetic susceptibility remain largely unknown. Genome-wide association studies (GWAS) have identified multiple risk loci, but monogenic forms of migraine, particularly Familial Hemiplegic Migraine (FHM), have provided deeper insights into the pathophysiology of migraine. Studying monogenic disorders that present migraine as a symptom could help identify novel therapeutic targets by uncovering shared molecular pathways.MethodsA narrative literature review was conducted using a stepwise approach in the PubMed database. Reviewers were divided into three groups, each focusing on different aspects of migraine genetics. The first group analyzed monogenic migraine syndromes, including FHM and related ion-channelopathies. The second group examined clinical manifestations and phenotypic spectrum of FHM-related genes. The third group expanded the search to other monogenic disorders associated with migraine, such as Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), and Familial Advanced Sleep Phase Syndrome (FASPS). Additional searches were conducted using the Compendium of Causative Genes for Monogenic Disorders.ResultsThe review identified multiple monogenic disorders associated with migraine, revealing distinct but interconnected mechanisms. Ion-channel dysfunction (, , ), vascular impairment (, ), mitochondrial dysfunction (), and circadian dysregulation () emerged as critical contributors to migraine pathophysiology. These findings highlight the roles of neuronal excitability, cortical spreading depression, trigeminal sensitization, and neurovascular dysfunction in migraine.ConclusionsMonogenic migraine disorders offer valuable insights into migraine pathogenesis, emphasizing the importance of ion homeostasis, vascular function, and circadian regulation. Although genetic studies have not yet directly translated into new therapeutic targets, the study and knowledge of these rare conditions is pivotal for neurologists and migraine specialists, as it might improve diagnosis and care, and provide new insights into migraine pathophysiology that may ultimately inform future treatments.
Oliveira AB, Barbosa F, Santos IS
… +4 more, Peres MFP, Lotufo PA, Benseñor IM, Goulart AC
Cephalalgia
· 2025 Oct · PMID 41147994
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BackgroundEmerging evidence suggests a link between migraine and selenium (Se). Se is related to systemic low-grade inflammation and thyroid function, which in their turn are also linked to migraine. Thus, we aimed to ex...BackgroundEmerging evidence suggests a link between migraine and selenium (Se). Se is related to systemic low-grade inflammation and thyroid function, which in their turn are also linked to migraine. Thus, we aimed to explore these relationships and hypothesized that higher Se levels would be related to decreased risk of migraine with an influence of systemic low-grade inflammation and thyroid function.MethodsIn a prospective analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), measurements of serum Se levels, dietary Se intake, high-sensitivity C-reactive protein (hs-CRP) and thyroid function hormones at baseline (2008-2010) and migraine incidence (2013-2014) were assessed. Serum Se was quantified by inductively coupled plasma mass spectrometry, a validated Food Frequency Questionnaire estimated dietary Se intake and hs-CRP was measured by the quantitative nephelometry method. Diagnosis of migraine without aura (MWO) and migraine with aura (MWA) followed International Classification of Headache Disorders, 3rd edition, criteria, while chronic migraine (CM) was defined according to headache attack frequency. Modified Poisson regression models estimated risk ratios (RR) for migraine subtypes, along with 95% confidence intervals, according to serum Se levels (continuous or quartiles).ResultsAmong 2355 adults (mean age: 52.4 ± 9.1 years, 48.8% female), 20.0% were diagnosed with overall migraine between 2013-14. The mean ± SD follow-up time was 4.1 ± 0.37 years. Compared to no migraine, the overall migraine group had significantly lower median (interquartile range) serum Se levels (70.8 μg/l (60.4-82.8) . 177.0 μg/l (149.0-220.7), = 0.017) and dietary Se intake (170.9 μg/l (147.4-200.3) . 177.0 μg/l (149.0-220.7), = 0.018), while no between-group differences for hs-CRP and thyroid function hormones was found. There was a significant positive association between Se levels and dietary Se intake, while both were negatively associated with hs-CRP levels. Compared to the lowest quartile of serum Se levels, the highest quartile was associated with a lower risk of overall migraine (RR = 0.56 (0.31-0.99), = 0.046) in the models adjusted for sex, age, body mass index, race, household income, schooling, marital status, smoking status, alcohol consumption, and use of migraine prophylactic medication, thyroid function hormones and hs-CRP. In the sex-stratified analysis considering the same confounders, a decreased risk of MWO was observed among males (RR =0.53 (0.29-0.94), = 0.026) and CM among females (RR = 0.71 (0.51-0.98), = 0.038) within the highest quartile of serum Se.ConclusionsIn the ELSA-Brasil Study, diet-related higher Se levels were associated with a lower risk of migraine regardless of systemic low-grade inflammation and thyroid hormones, with migraine type- and sex-specific associations. Further studies are warranted to confirm the involvement of Se in the risk of migraine and migraine progression.
Pozo-Rosich P, Caronna E, Sacco S
… +13 more, Peres MFP, Ashina S, Özge A, Ahmed F, Velez-Jimenez MK, Jenkins B, Wang SJ, Schwedt TJ, Sakai F, Levin M, Burstein R, Terwindt GM, Tassorelli C
Cephalalgia
· 2025 Oct · PMID 41134822
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Migraine is one of the most disabling diseases worldwide, especially when it transforms into chronic migraine, which is often associated with medication overuse and can become resistant or even refractory to treatments....Migraine is one of the most disabling diseases worldwide, especially when it transforms into chronic migraine, which is often associated with medication overuse and can become resistant or even refractory to treatments. Molecular, neuroimaging and neurophysiological changes have been described in chronic migraine, some of which might not be fully reversible with preventive treatment. For these reasons, we should aim to prevent this transition, and initiate preventive treatment before disease becomes refractory and burden increases. Preventive migraine treatments are often delayed because of access to care, stigma leading to undertreatment and patients' reluctance as a result of fear of side effects and, in some cases, fear of being labeled as chronically ill. With the availability of effective and well-tolerated preventive treatments, we must shift our mindset and take advantage of new opportunities to initiate preventive treatment earlier. In this International Headache Society position statement, we propose a migraine preventive strategy under the idea of shifting from reactive treatment once disability is established (prevention of attacks), to proactive, individualized prevention initiated early with safe, effective and tolerable therapies (prevention of disease progression). This approach is based on 1) promoting the early initiation of effective and tolerable preventive therapies, starting from two to four monthly migraine days in line with the majority of current guidelines and recommendations and 2) fostering longitudinal studies to gather more evidence on the potential benefit of early prevention, with the final goal of improving patient outcomes, promoting excellent migraine care, enhancing individual and social well-being, and, ultimately, preventing migraine progression and preserving brain health.