Cephalalgia[JOURNAL]
Sun
200 papers
Real-world achievement of higher standards for migraine prevention with CGRP monoclonal antibodies.
Suzuki K, Suzuki S, Kobayashi S … +5 more , Shioda M, Fujita H, Haruyama Y, Hida R, Hirata K
Cephalalgia · 2026 Jun · PMID 42220267 · Publisher ↗
ObjectiveTo evaluate the achievement of the International Headache Society (IHS) higher standards for migraine prevention in patients treated with calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) in real...
ObjectiveTo evaluate the achievement of the International Headache Society (IHS) higher standards for migraine prevention in patients treated with calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) in real-world practice.MethodsWe retrospectively analyzed 307 migraine patients treated with CGRP mAbs at a single center. Monthly migraine days (MMDs) were assessed at baseline and during follow-up (1-24 months). According to IHS recommendations, migraine control was categorized as optimal (<4 migraine days/month), modest (4-6 days/month), or insufficient (>6 days/month). Patients were further classified by the timing of achieving optimal control.ResultsThe percentage of patients achieving a ≥ 50% reduction in MMDs increased from 36.2% at month 1 to 71.0% at month 24; optimal control increased from 15.0% to 38.8%. Among patients with a ≥ 50% response, 38.7-55.7% achieved optimal control during follow-up. Migraine freedom remained relatively uncommon (1.6-10.1%). Patients who achieved optimal control early (≤3 months) had a lower baseline migraine burden, whereas nonachievers had a higher baseline disease burden and more prior preventive treatment failures.ConclusionsCGRP mAbs were associated with substantial reductions in migraine frequency; however, achieving optimal control and migraine freedom remains challenging in real-world practice, particularly in patients with a higher baseline burden.
Predictors of response to biofeedback-assisted relaxation for migraine: An exploratory analysis.
Szuhany KL, Dorf J, Bostic RC … +2 more , Fanning KM, Minen MT
Cephalalgia · 2026 Jun · PMID 42220255 · Publisher ↗
BackgroundFew studies have examined which patients with migraine might be responders for mind-body interventions. Thus, we examined whether certain baseline mindfulness traits and interest in physical exercise might pred...
BackgroundFew studies have examined which patients with migraine might be responders for mind-body interventions. Thus, we examined whether certain baseline mindfulness traits and interest in physical exercise might predict response to treatment.MethodsThis is a planned exploratory analysis of a phase 2 randomized controlled study ( = 50; 25 per arm) comparing a 6-week physical therapist (PT)-delivered biofeedback-assisted relaxation (BAR) program vs. an Enhanced Usual Care (EUC) migraine self-management program (diary tracking and emailed migraine-related educational materials). We conducted moderation analyses to determine whether the Multidimensional Assessment of Interoceptive Awareness (MAIA), Difficulties in Emotion Regulation Scale (DERS) and Physical Activity Enjoyment Scale (PACES) at baseline influenced the effect of BAR on migraine-related outcomes (Migraine-Specific Quality of Life Role Function Restrictive (MSQv2.1-RFR) and Migraine-Related Disability (MIDAS)) at 6 months.ResultsAmong the = 40 participants (BAR = 19; EUC = 21), the majority were female (95%), non-Hispanic (77.5%) and white (67.5%). Mean (SD) age was 45.6 (11.2) years. For the MAIA Not-Worrying subscale, BAR produced the greatest improvement in 6-month MSQv2.1-RFR scores among participants with low baseline Not-Worrying scores (those who tended to worry about bodily sensations/discomfort more) (BAR = 77.1 ± 6.6 vs. EUC = 48.9 ± 5.0; = 0.002, = 4.75). The benefit diminished at average levels ( = 0.060, = 2.72) and was absent at high baseline Not-Worrying ( = 0.528, = -0.91). For the MAIA Self-Regulation subscale, BAR was most effective among those low in baseline self-regulation (BAR = 71.7 ± 5.3 vs. EUC = 44.3 ± 7.2; = 0.004, = 4.27). The DERS total score showed that BAR demonstrated little benefit among participants with better baseline emotion regulation (i.e. lower DERS score; = 0.907, = 0.17) but was more effective as baseline emotion regulation difficulties increased, showing a moderate benefit at average levels (BAR = 69.2 ± 4.2 vs. EUC = 55.8 ± 4.0, = 0.027, = 3.25) and a large, significant difference at high levels (BAR = 70.6 ± 6.3 vs. EUC = 44.7 ± 5.7; = 0.004, = 4.22). The PACES total score indicated that BAR benefits were strongest among those with low (BAR = 76.1 ± 7.0 vs. EUC = 47.1 ± 5.3, = 0.002, = 4.60) to average (BAR = 71.2 ± 4.2 vs. EUC = 58.6 ± 4.0, = 0.035, = 3.07) enjoyment of physical activity.ConclusionsWe found subgroups of individuals with migraine who may be better responders to PT-delivered BAR, specifically those who tend to worry more about bodily sensations (lower MAIA Not-Worrying score), those with low self-regulation (lower MAIA Self-Regulation score), those with worse emotion regulation (higher DERS score) and those with lower levels of physical activity enjoyment (lower PACES score) at baseline. This may help us determine who may benefit most from BAR.Trial RegistrationClinicalTrials.gov Identifier: NCT06077812.
The effects of angiotensin receptor blockers as prophylactic migraine treatment: A systematic review and meta-analysis.
Riise HS, Thorvik H, Øie LR … +6 more , Stovner LJ, Tronvik EA, Linde M, Hagen K, Giri S, Wergeland T
Cephalalgia · 2026 May · PMID 42213459 · Publisher ↗
BackgroundThe role of angiotensin II receptor blockers (ARBs) in migraine prophylaxis varies globally, partly due to insufficient evidence from randomized controlled trials (RCTs) supporting their efficacy. We aimed to c...
BackgroundThe role of angiotensin II receptor blockers (ARBs) in migraine prophylaxis varies globally, partly due to insufficient evidence from randomized controlled trials (RCTs) supporting their efficacy. We aimed to conduct a systematic review and meta-analysis of ARBs in migraine prophylaxis.MethodsWe searched PubMed/MEDLINE, Embase, Cochrane, Google Scholar, Clinicaltrials.gov, ITCRP, and EudraCT from database inception to 22 September 2025. The searches were conducted between 19 and 22 September 2025 for controlled trials comparing any ARB to placebo or other preventive migraine drugs in individuals with episodic or chronic migraine. Guidelines, letters, editorials, narrative reviews, case reports, and news were excluded. Summary data were extracted by two reviewers, and random-effects meta-analyses were performed, with heterogeneity assessed using Cochrane I statistic. Primary outcomes were monthly headache/migraine days or attacks, and response rates. Adverse event occurrence was also assessed. The risk of bias was assessed using the Cochrane RoB2 tool and the certainty of evidence was assessed using GRADEpro. The study was pre-registered in Prospero (CRD42023405372) and received no funding.ResultsFour trials published between 2003 and 2025 were included in the meta-analysis: three RCTs on candesartan, and one on telmisartan. All four studies reported the outcomes migraine days and responder (≥50% reduction of migraine days) rates, and three reported headache days. A total of 659 participants were included in the meta-analysis. The combined effect size for migraine days and headache days were reductions of -1.00 (95% CI: -1.51 to -0.49, p<0.001), and -1.21 (95% CI: -1.62 to -0.81, p<0.001) days per month from baseline respectively. The odds ratio for being a responder was 2.68 (95% CI: 1.91 to 3.78, p<0.001). The certainty of evidence was low for migraine days, moderate for responder rates and high for headache days, with heterogeneity between studies categorized as 'might not be important' and no serious risk of bias.DiscussionThe systematic review and meta-analysis provide robust evidence on the effect of ARBs, particularly candesartan, in prevention of episodic migraine, supporting the rationale for reconsidering its position in international guidelines.Trial RegistrationProspero CRD42023405372.
Rethinking Burning Mouth Syndrome: Toward a multidimensional classification of oral dysaesthetic and perceptual disorders in ICHD-4.
Musella G, Adamo D, Caponio VCA … +2 more , Lo Muzio L, Mignogna MD
Cephalalgia · 2026 May · PMID 42187028 · Publisher ↗
Abstract loading — click title to view on PubMed.
Eptinezumab in treatment-resistant chronic migraine: Four-year real-world effectiveness and treatment persistence.
Hsieh WJ, Nicol K, Ng CC … +6 more , Hou TW, Phan P, Keith SW, Heckel B, Marmura MJ, Yuan H
Cephalalgia · 2026 May · PMID 42153799 · Publisher ↗
AimTo evaluate 48-month real-world outcomes of eptinezumab users in chronic migraine (CM), including longitudinal effectiveness, treatment persistence, reasons for discontinuation, and post-discontinuation anti-calcitoni...
AimTo evaluate 48-month real-world outcomes of eptinezumab users in chronic migraine (CM), including longitudinal effectiveness, treatment persistence, reasons for discontinuation, and post-discontinuation anti-calcitonin gene-related peptide (CGRP) treatment patterns.MethodsWe conducted a retrospective cohort study of 112 CM subjects initiating eptinezumab at a tertiary headache center between 2019 and 2021. Monthly headache days (MHD), migraine disability assessment (MIDAS), and average pain intensity (API) were extracted at baseline and every 6 months for up to 48 months using a predefined outcome form at each visit. Longitudinal changes were analyzed using generalized estimating equations (GEE) with an unstructured correlation matrix, adjusting for age, sex, and body mass index (BMI). Analyses were performed in four predefined analytic cohorts: all initiators, on-treatment, continuation, and discontinuation. Estimated marginal means (EMMs) quantified adjusted mean changes from baseline at each timepoint. No imputation or censoring for treatment discontinuation was applied. Treatment persistence, reasons for discontinuation, factors associated with discontinuation, and post-discontinuation anti-CGRP treatment patterns were summarized descriptively.ResultsAmong 112 patients (mean age 50.2 ± 13.7; 77.7% female; baseline MHD median 30 [IQR 25-30]), most had failed prior anti-CGRP therapies (90.2% ≥ 1 failure; 70.6% ≥ 2 failures). In all-initiators, significant reductions in MHD were observed at 6, 18-42, corresponding to model-estimated reductions of 1.5-1.9 MHD. MIDAS increased at 6 months, corresponding to a 44-point increase, but declined over time. API improved significantly at 24, 36 and 48 months, corresponding to a 0.4-0.6-point reduction. Treatment persistence declined to 55.4%, 39.2%, 35.7%, and 29.5% at 1, 2, 3, and 4 years, respectively; the median time to discontinuation was 8 months. Ineffectiveness (34.2%), loss of effectiveness (19.0%), and insurance-related barriers (16.5%) were the most common reasons for discontinuation. After discontinuation, 54.4% initiated another anti-CGRP therapy, 26.6% stopped anti-CGRP therapy entirely, and 20.3% were lost to follow-up.ConclusionsIn this treatment-resistant CM cohort, eptinezumab produced modest but durable benefit, particularly among patients who continued treatment. Persistence declined substantially over time, and post-discontinuation care followed diverse and often complex pathways. Regular reassessment and timely adjustment of preventive strategies remain essential as clinical responses evolve. Larger prospective studies will help clarify long-term effectiveness and treatment trajectories.
Benefits of eptinezumab on patient-reported disease burden and health-related quality of life in adults with chronic migraine and medication-overuse headache: Results from the placebo-controlled RESOLUTION trial.
Tepper SJ, Schytz HW, Jensen RH … +11 more , Lundqvist C, Terwindt GM, Tassorelli C, Vernieri F, Lantéri-Minet M, Blumenfeld A, Josiassen MK, Jansson G, Ettrup A, Mittoux A, Lipton RB
Cephalalgia · 2026 May · PMID 42142011 · Publisher ↗
AimThe phase 4 RESOLUTION trial showed that, in comparison with placebo, adding eptinezumab-an anti-calcitonin gene-related peptide monoclonal antibody-to a brief educational intervention (BEI) reduced the monthly freque...
AimThe phase 4 RESOLUTION trial showed that, in comparison with placebo, adding eptinezumab-an anti-calcitonin gene-related peptide monoclonal antibody-to a brief educational intervention (BEI) reduced the monthly frequency of migraine, headache, and acute medication use in participants with chronic migraine (CM) and medication-overuse headache (MOH). Herein, we report data from multiple patient-reported outcomes (PROs) evaluating treatment impact on disease burden and health-related productivity and quality of life in the RESOLUTION trial.MethodsRESOLUTION was a multi-national (conducted at 76 sites across 11 countries), double-blind, randomized, placebo-controlled trial. The trial comprised a 4-week screening period; a 12-week, double-blind, placebo-controlled period; a 12-week, open-label, extension period; and an 8-week, safety follow-up period, with results of the placebo-controlled period presented in this paper. Adults diagnosed with CM and MOH received a BEI and were randomized 1:1 to intravenous infusion with either eptinezumab 100 mg or placebo. Several PROs were assessed at baseline, Week 4, and Week 12, including the six-item Headache Impact Test (HIT-6), modified Migraine Disability Assessment (mMIDAS), Migraine-specific Work Productivity and Activity Impairment questionnaire (WPAI:M), Patient Global Impression of Change (PGIC; assessed only at follow-up), patient-identified most bothersome symptom (PI-MBS; assessed only at follow-up), Migraine-Specific Quality-of-Life questionnaire version 2.1 (MSQ v2.1), EQ-5D-5L visual analogue scale, and nine-item Treatment Satisfaction Questionnaire for Medication (TSQM-9; assessed only at follow-up). analyses included responder rates for HIT-6 (i.e., participants with ≥5-point reduction from baseline), as well as for PGIC and PI-MBS (i.e., participants who reported "much improved" or "very much improved").ResultsOf 608 participants randomized, the full-analysis set included 302 participants in the eptinezumab arm and 300 in the placebo arm. Eptinezumab with BEI was associated with more favorable PRO scores compared to placebo with BEI, starting at Week 4 ( < 0.05 for all comparisons) and up to Week 12 ( < 0.01 for all comparisons except WPAI:M absenteeism). Responder rates for HIT-6, PGIC, and PI-MBS also favored eptinezumab versus placebo.ConclusionsIn participants with CM and MOH who also received patient education, eptinezumab treatment resulted in greater reductions in headache impact and migraine disability than placebo, with greater improvements in productivity, quality of life, overall disease status, and treatment satisfaction starting from Week 4 and sustained to Week 12. Eptinezumab in combination with patient education is an effective treatment for reducing disease burden and improving overall quality of life in people with CM and MOH.Trial registrationClinicalTrials.gov Identifier: NCT05452239 (https://clinicaltrials.gov/study/NCT05452239); EudraCT Number: 2021-003049-40 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=2021-003049-40).
Magnetic resonance spectroscopy during migraine attacks: A systematic review.
Radutiu DI, Szabo E, Christensen RH … +5 more , Ratai EM, Hadjikhani N, Al-Khazali HM, Ashina M, Ashina H
Cephalalgia · 2026 May · PMID 42135598 · Publisher ↗
BackgroundThe neurobiological basis of migraine remains incompletely understood. Magnetic resonance spectroscopy (MRS) allows non-invasive quantification of neurochemical and metabolic patterns in the brain, offering uni...
BackgroundThe neurobiological basis of migraine remains incompletely understood. Magnetic resonance spectroscopy (MRS) allows non-invasive quantification of neurochemical and metabolic patterns in the brain, offering unique insights into biochemical processes during distinct migraine phases. This systematic review provides a critical appraisal of existing evidence describing MRS-derived neurochemical and metabolic alterations during spontaneous and experimentally provoked migraine attacks.MethodsA systematic review was conducted in accordance with the PRISMA statement and prospectively registered in PROSPERO. Comprehensive searches of PubMed, Embase, and Scopus were performed from database inception through August 1, 2025. Eligible studies included observational or interventional investigations acquiring H-MRS or P-MRS data during the ictal phase in adults with migraine, incorporating either non-ictal comparisons or healthy controls. Considerable variability in study design, brain regions, and metabolite outcomes precluded quantitative synthesis, necessitating a structured qualitative analysis organized by MRS technique and anatomical region.ResultsEight studies published between 1988 and 2022 met inclusion criteria, comprising five H-MRS investigations and three P-MRS studies, some of which derived from overlapping participant cohorts. Brain regions examined included occipital cortex, pons, frontal cortex, basal ganglia, and parieto-occipital areas. In individual H-MRS studies, occipital cortex analyses demonstrated ictal elevations in total choline and total N-acetyl aspartate, while lower glutathione concentrations were observed. A single H-MRS study targeting the pons identified ictal increases in total creatine and total N-acetyl aspartate. Findings from P-MRS studies indicated altered cerebral energy metabolism during migraine attacks.ConclusionsAvailable MRS evidence suggests that migraine attacks are associated with altered cerebral energy metabolism, particularly within visual cortical and brainstem regions. However, existing studies differ substantially in design, acquisition parameters, regions of interest, and analytical approaches, such that few directly address comparable questions. Thus, the reproducibility of reported findings remains uncertain. Establishing reliable attack-related metabolic signatures will require well-designed longitudinal MRS investigations capable of directly probing ictal dynamics.
Patient reported trigger, not the speed of transition to continuous headache, is associated with headache-related disability in children: Results of a cross-sectional clinic-based study.
Sehgal R, Szperka CL, Hershey AD … +1 more , Patterson Gentile C
Cephalalgia · 2026 May · PMID 42100972 · Publisher ↗
ObjectiveTo investigate the relationship between the evolution of continuous headache and headache-related disability in children.MethodsThis was a single site cross-sectional study using patient-entered questionnaires f...
ObjectiveTo investigate the relationship between the evolution of continuous headache and headache-related disability in children.MethodsThis was a single site cross-sectional study using patient-entered questionnaires from children aged 6-17 who presented to neurology clinic between November 2022-May 2024 with continuous headache. Participants were categorized as sudden onset (no evolution), rapidly evolved (< 3 months), or gradually evolved (≥ 3 months) continuous headache. Analysis examined the relationship between the pattern of headache evolution and headache-related disability (PedMIDAS score), accounting for demographic, headache characteristic, and onset factors.ResultsOf 751 respondents, 42.5% reported sudden onset, 35.0% rapid evolution, and 22.5% gradual evolution to continuous headache. There was no significant difference in PedMIDAS score in children who reported sudden onset compared to children with rapid (6.9 [-2.7, 16.4], p = 0.159) or gradual evolution (10.3 [-0.8, 21.3], p = 0.068) of headache onset. Older age (3.3 per year [1.8, 4.8], p < 0.001) and patient reported trigger (17.1 [8.8, 25.5], p < 0.001) at the onset of continuous headache were both associated with greater headache-related disability, accounting for other covariates.ConclusionChildren transitioned to continuous headache quickly, consistent with prior studies. Older children and those who associated onset of continuous headache with a trigger reported higher rates of headache-related disability.
Environmental and psychological risk factors for migraine chronification in China: A multicenter prospective cohort study.
Ma L, Liu L, Ran Y … +16 more , Han X, Su H, Zhang M, Wang X, An X, Zhang L, Xu S, Gu W, Zuo S, Wu Y, Li Y, Zhang Y, Dong M, Tian Q, Yu S, Dong Z
Cephalalgia · 2026 May · PMID 42084558 · Publisher ↗
BackgroundPreventing migraine chronification is a key treatment goal, yet environmental and lifestyle contributors remain understudied in Asian populations. We investigated predictors of the transition from episodic migr...
BackgroundPreventing migraine chronification is a key treatment goal, yet environmental and lifestyle contributors remain understudied in Asian populations. We investigated predictors of the transition from episodic migraine (EM) to chronic migraine (CM) in a prospective Chinese clinical-based cohort.MethodsThis multicenter, prospective study involved 1642 participants with EM meeting ICHD-3 criteria. Baseline characteristics, including environmental factors and psychological scales, were captured via a Clinical Decision Support System (CDSS). Longitudinal follow-up was conducted using a web-based mini-program. Risk factors were identified using multi-variable Cox proportional hazards models, validated by LASSO and stepwise regression.ResultsDuring a median 6-month follow-up, 47 (2.9%) patients progressed to CM. Multivariable analysis identified anxiety symptoms [Generalized Anxiety Disorder-7 (GAD-7) score: Hazard Ratio (HR) 1.15, 95% Confidence Interval (CI) 1.06-1.25], baseline analgesic use frequency (HR 1.07, 95% CI 1.01-1.14), and age (HR 1.04, 95% CI 1.01-1.06) as independent risk factors. Conversely, weekly physical activity duration emerged as a significant protective factor (HR 0.66, 95% CI 0.45-0.98).ConclusionAnxiety and higher frequency of analgesic use are independent risk factors of migraine chronification in this Chinese cohort, while regular physical activity offers protection. These findings support an integrated management strategy combining psychological intervention, medication education, and exercise therapy.
Perception of headache-related disability in individuals with and without headache disorders working in a municipal government in the Tokyo Metropolitan Area.
Shibata M, Shimizu T, Takemura R … +1 more , Sakai F
Cephalalgia · 2026 May · PMID 42080841 · Publisher ↗
AimThe discrepancy in headache perception between people with and without headache disorders remains poorly studied. We aimed to gain insights into the factors that determine headache perception in individuals with and w...
AimThe discrepancy in headache perception between people with and without headache disorders remains poorly studied. We aimed to gain insights into the factors that determine headache perception in individuals with and without headache disorders.MethodsA questionnaire-based headache survey was administered to municipal employees in the Tokyo Metropolitan Area. The participants were divided into four groups: Group A, individuals with current headache; Group B, individuals with a history of headache; Group C, individuals without headache and without nearby individuals with headaches; and Group D, individuals without headache but with nearby individuals with headaches. In Groups A and B, migraine without aura (MO), migraine with aura (MA), probable MO (pMO), and tension-type headache (TTH) were classified according to the International Classification of Headache Disorders, 3rd edition (ICHD-3). All participants were asked about their perceptions of headaches.ResultsThe response rate was 52.3% (1156 males and 764 females). There were 518 individuals in Group A (MO, 116; MA, 93; pMO, 95; TTH, 214) and 137 in Group B (MO, 24; MA, 24; probable MO, 29; TTH, 60). In Group A, headache severity (headache intensity, duration, and frequency), visual aura, and throbbing pain contributed to the perception of headaches as disabling. Individuals with MA were more likely to consider their headaches disabling than those with TTH ( = 0.0003). However, there were no differences in the proportion of respondents who perceived headaches as disabling across headache disorders in Group B. The perception of headaches as disabling was more common in individuals without headaches (Groups C and D combined) than in those with headaches ( < 0.0001 vs. Group A; = 0.0078 vs. Group B). However, 9.7% of them responded that headaches were not a disease. In individuals without headaches, males were more likely than females to consider headaches life-threatening ( = 0.0037). Among females, more individuals considered headaches disabling in Group D than in Group C ( = 0.0306).ConclusionHeadache severity, visual aura, and throbbing pain appear to be key therapeutic targets for attenuating headache-related disability. Headache perception varied between individuals with and without headaches, and these differences were further modified by sex among those without headaches. These findings suggest that males without headaches are more likely to perceive headaches as a serious condition, whereas females without headaches appear to be influenced by the presence of nearby individuals with headaches.
Toward quantifying disability in spontaneous intracranial hypotension: A patient-derived disability weight.
Volz F, Omer M, Overstijns M … +9 more , Rahal AE, Hohenhaus M, Klingler JH, Lützen N, Urbach H, Zander C, Carroll I, Beck J, Wolf K
Cephalalgia · 2026 Apr · PMID 42037515 · Publisher ↗
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 framewor...
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.
Physical activity in migraine: Identifying an engagement threshold and patient clusters in a population-based cohort.
Peles I, Sharvit S, Novack V … +1 more , Ifergane G
Cephalalgia · 2026 Apr · PMID 42033407 · Publisher ↗
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...
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.
Proposed changes to current definitions of ICHD-3 regarding headache and facial pain attributed to the disorder of the nose or paranasal sinuses.
Straburzyński M, Agius AM, Hopkins C … +7 more , Luong AU, De Corso E, May A, Smith TL, Zwetsloot CP, Orlandi RR, Fokkens W
Cephalalgia · 2026 Apr · PMID 42033402 · Publisher ↗
BackgroundClinicians encounter difficulties in differentiating between headache/facial pain of true sinogenic origin, and clinically similar pain related to primary headache disorders, such as migraine. The International...
BackgroundClinicians encounter difficulties in differentiating between headache/facial pain of true sinogenic origin, and clinically similar pain related to primary headache disorders, such as migraine. The International Classification of Headache Disorders and International Classification of Orofacial Pain, together with clinical definitions of acute and chronic rhinosinusitis as refined by the European Position Paper on Rhinosinusitis and Nasal Polyps, have produced a unique opportunity to improve the current diagnostic criteria of headache/facial pain attributed to rhinosinusitis.MethodsAn international multidisciplinary panel reviewed clinical evidence regarding the overlap of primary headaches and rhinosinusitis in order to harmonize and clarify diagnostic frameworks.ResultsThe proposal integrates validated rhinologic definitions into headache and facial pain classifications. Key suggestions include the removal or adjustment of non-specific criteria (e.g., headache exacerbated by pressure applied over the paranasal sinuses) which also frequently occur in primary headache disorders. To enhance specificity, evidence-based negative predictors - such as the absence of nausea, osmophobia or photophobia and phonophobia - are introduced. Only for chronic rhinosinusitis, it has been proposed to include endoscopic or radiological evidence of inflammation, as necessary to confirm the diagnosis.ConclusionAligning ICHD-4 with contemporary rhinologic guidelines through the use of positive and negative predictors may help improve diagnostic accuracy, ensure appropriate therapy and increase the reliability of trial design.
Visually-induced hemodynamic response and white matter hyperintensities in middle-aged women with ischemic stroke or migraine with aura.
van der Weerd N, Ali M, van Harten TW … +10 more , Ma AM, Holswilder G, Wilms AE, van Zwet EW, Kruit MC, van den Maagdenberg AMJM, Terwindt GM, van Osch MJP, van Os HJA, Wermer MJH
Cephalalgia · 2026 Apr · PMID 42024133 · Publisher ↗
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, poten...
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.
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.
Khalili M, Haghdoost F, Liaghatdar A … +16 more , Torabiardakani K, Mahdian F, Atkin-Jones T, Levit T, Moradi S, Hedayati E, Ahmadi F, Khademioore S, Sofi-Mahmudi A, Patil V, Fashami FM, Mehmandoost S, Couban RJ, Prasad K, Fereshtehnejad SM, Sadeghirad B
Cephalalgia · 2026 Apr · PMID 42011527 · Publisher ↗
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...
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).
Efficacy and outcomes of pharmacological treatments for headaches after traumatic brain injury: A systematic review.
Saleh S, Sanford EM, McGeary DD … +5 more , Cortez MM, Hayward M, Bouldin ED, Kean J, Pugh MJV
Cephalalgia · 2026 Apr · PMID 41995457 · Publisher ↗
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 re...
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 ( = 7), non-randomized prospective ( = 4) and randomized controlled trials ( = 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.
Reducing light sensitivity during and between migraine attacks: A prospective study investigating spectral tuning of white light.
Fani M, Sharp N, Schwedt TJ
Cephalalgia · 2026 Apr · PMID 41983992 · Publisher ↗
BackgroundPhotophobia is experienced by most individuals with migraine, and it is frequently the most bothersome symptom other than headache. Light is not perceived uniformly; spectral composition and intensity influence...
BackgroundPhotophobia is experienced by most individuals with migraine, and it is frequently the most bothersome symptom other than headache. Light is not perceived uniformly; spectral composition and intensity influence discomfort and can exacerbate symptoms. While monochromatic green light shows therapeutic potential, it appears visually unnatural and is impractical for daily use. This study aimed to determine whether spectrally tailored white light, more visually acceptable in everyday environments, reduces light sensitivity among those with migraine.MethodsTwenty adults (18-44 years) with episodic migraine completed two research sessions: one during an acute migraine attack and one between migraine attacks. Participants were exposed to four spectrally distinct white light conditions (red-, green-, cyan-, and blue-enriched) in a randomized order delivered at ten intensity levels (50-590 lux). After each exposure, visual discomfort was rated on a 0-10 scale. Pupil size was measured using a pupillometer. Repeated-measures ANOVAs examined the effects of light spectrum, intensity, and migraine state on visual discomfort and pupil response.ResultsMigraine attack status significantly increased visual discomfort ((1,19) = 25.84, < .001, η = .576). White light spectrum ((3,57) = 12.47, < .001, η = .396) and light intensity ((9171) = 124.30, < .001, η = .867) were associated with intensity of visual discomfort. Post-hoc analyses indicated that visual discomfort increased with increasing light intensity, especially at higher light intensities. Among all tested spectra, green-enriched white light resulted in the least visual discomfort; blue-, red-, and cyan-enriched white light produced significantly higher discomfort (all p < .001). Pupil size varied by spectrum ((3,57) = 14.13, < .001, η = .426), with green-enriched white light producing the largest pupil size.ConclusionSpectral composition, light intensity, and migraine state jointly influence both subjective and physiological responses to light. Across lighting spectra, lower light intensity was consistently associated with reduced visual discomfort, indicating greater visual comfort at lower intensities. These results identify green-enriched white light at lower intensities as a visually acceptable, migraine-conscious lighting option with potential for real-world application.
How do we facilitate individuals with recurrent headache and migraine receiving evidence-based behavioral treatment?
Martin PR
Cephalalgia · 2026 Apr · PMID 41972924 · Publisher ↗
Abstract loading — click title to view on PubMed.
Spinal trigeminal nucleus lesions in trigeminal zoster-associated neuralgia: A retrospective cohort study on diagnostic value and prognostic factors.
Wang L, Chen Y, Li M … +3 more , Dong Y, Wang JN, Sun T
Cephalalgia · 2026 Apr · PMID 41967869 · Publisher ↗
BackgroundTrigeminal zoster-associated neuralgia (TZAN) is a refractory intractable craniofacial neuropathic pain with a high risk of progressing to postherpetic neuralgia. Abnormal T2-weighted magnetic resonance imaging...
BackgroundTrigeminal zoster-associated neuralgia (TZAN) is a refractory intractable craniofacial neuropathic pain with a high risk of progressing to postherpetic neuralgia. Abnormal T2-weighted magnetic resonance imaging (MRI) hyperintensity in the spinal trigeminal nucleus (STN) has been reported in TZAN patients, but its diagnostic value, influencing factors and association with prognosis remain insufficiently explored. This study aimed to investigate the correlation between STN lesions and TZAN and identify factors affecting STN signal characteristics and TZAN therapeutic efficacy.MethodsThis retrospective cohort study included 105 TZAN patients, 105 non-TZAN normal controls (NC) and 287 classical trigeminal neuralgia (CTN) patients who underwent cranial MRI at Shandong Provincial Hospital Affiliated to Shandong First Medical University between September 2018 and March 2024. Propensity score matching (1:1, caliper = 0.1) was used to balance baseline differences between the TZAN and CTN groups. STN lesions were evaluated in a blinded manner by two radiologists, and clinical data (pain Numeric Rating Scale scores, pregabalin dosage) were collected via medical records and 6-month telephone follow-up. Multivariate logistic regression analyzed factors associated with STN hyperintensity and TZAN efficacy (pain relief ≥ 80% defined as "excellent response").ResultsSTN lesion detection rate was significantly higher in TZAN than in NC (62.9% vs. 1.0%, < 0.001) and matched CTN (68.9% vs. 0%, < 0.001), with 62.9% sensitivity, 99.0% specificity and 81.0% accuracy for TZAN diagnosis. Age (odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.006-1.116, = 0.030) and subacute phase (vs. acute: OR = 32.01; vs. chronic: OR = 46.40, both < 0.001) independently predicted STN hyperintensity. STN-normal patients had better short-term efficacy (discharge Numeric Rating Scale = 2 (1, 3) vs. 3 (2, 4), = 0.042; excellent response rate: 38.5% vs. 19.7%, = 0.036) but no long-term difference (3 and 6 months post-discharge, > 0.05). Chronic phase predicted poor prognosis (vs. acute: OR = 6.55, = 0.005; vs. subacute: OR = 5.39, = 0.017).ConclusionsSTN lesions are highly specific for TZAN and may serve as an auxiliary diagnostic indicator. STN hyperintensity is most prominent in elderly TZAN patients in the subacute phase, potentially acting as a subacute-phase imaging marker. Early intervention in subacute TZAN may be critical for improving prognosis.
Genetic variability within molecular core clock genes in cluster headache.
Sanches CD, Spulber S, Olofsgård FJ … +10 more , Fourier C, Sundholm A, Lantz M, Sjöstrand C, Waldenlind E, Steinberg A, Houlden H, Matharu M, Ran C, Belin AC
Cephalalgia · 2026 Apr · PMID 41967867 · Publisher ↗
Background / HypothesisHeadache attacks are reported to occur with circadian rhythmicity by 2/3 of individuals with cluster headache, hinting to potential dysfunctions of the molecular clock. The aim of this study was to...
Background / HypothesisHeadache attacks are reported to occur with circadian rhythmicity by 2/3 of individuals with cluster headache, hinting to potential dysfunctions of the molecular clock. The aim of this study was to investigate the contribution of genetic markers in core clock genes, alone or in combinations, to the genetic risk for cluster headache.MethodsSeven markers in core clock genes and were genotyped using TaqMan qPCR in 707 individuals with cluster headache and 682 controls. Genetic data from eleven additional markers located in six other core clock genes (, , and ) was obtained from the database of the Centre for Cluster Headache at Karolinska Institutet. Genotype analysis was applied for risk analysis for combinations of up to three markers. For validation we used a cluster headache cohort from the National Hospital for Neurology and Neurosurgery, London, UK.Results and interpretationSingle marker analysis of the newly genotyped markers in and found rs3789327 and rs3768984 more frequently among individuals with cluster headache (p < 0.01 and p < 0.05 respectively). Multiallelic analysis revealed that the median number of risk alleles was eight for controls and nine for individuals with cluster headache, which justifies the analysis of combinations of markers. The analysis of combinations of up to three markers identified 258 out of 897 combinations to be associated with significant risk. Further investigation starting from the function of genes in the molecular clock transcription-translation feedback loop (TTFL) found that 80% of the combinations had >50% markers located in the positive arm of the TTFL. The comparison between Swedish and UK cohorts identified 39 concordant combinations, which confirmed the risk associated with rs3768984 (), as well as the enrichment in markers in , , and in combinations associated with significant risk.ConclusionOur data points to molecular clock dysfunction playing a central role in the manifestation of cluster headache.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe