Cephalalgia[JOURNAL]
Sun
200 papers
Cerebrovascular risk with calcitonin gene-related peptide monoclonal antibodies versus onabotulinumtoxinA in patients with migraine: A real-world pharmacoepidemiologic study in the National Institutes of Health All of Us Research Program.
Gül S, Ong B, Trudeau S … +2 more , Thompson N, Yuan H
Cephalalgia · 2026 Jul · PMID 42390441 · Publisher ↗
AimTo evaluate whether initiation of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) was non-inferior to initiation of onabotulinumtoxinA with respect to the hazard of ischemic stroke or transient isc...
AimTo evaluate whether initiation of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) was non-inferior to initiation of onabotulinumtoxinA with respect to the hazard of ischemic stroke or transient ischemic attack (IS + TIA) in a real-world cohort of adults with migraine.MethodsWe conducted a retrospective, active-comparator, new-user pharmacoepidemiology study using the NIH All of Us Research Program Registered Tier Dataset (v8). Adults with migraine initiating CGRP mAbs (erenumab, fremanezumab, galcanezumab, eptinezumab) were compared with initiators of onabotulinumtoxinA from January 2018 through September 2023. The primary outcome was IS + TIA occurring more than 90 days after treatment initiation. Inverse probability of treatment weighting (IPTW) with stabilized propensity scores was used to adjust for 23 baseline covariates. Non-inferiority was assessed on the hazard ratio (HR) scale using a prespecified margin of 1.5, with non-inferiority concluded if the upper bound of the 95% confidence interval (CI) was less than 1.5. Prespecified subgroup analyses included migraine with aura and without aura. Prespecified sensitivity analyses included a per-protocol analysis, a crossover-excluded analysis, and an IS-only analysis. Fracture was used as a negative control outcome.ResultsAmong 16,147 patients with migraine in the cohort, the primary comparison included 1,581 CGRP mAb initiators and 947 onabotulinumtoxinA initiators. IPTW achieved a good covariate balance for the primary comparison (maximum standardized mean difference 0.016). For the primary outcome, 14 IS + TIA events occurred among CGRP mAb initiators and 22 among onabotulinumtoxinA initiators. The hazard ratio for IS + TIA was 0.524 (95% CI 0.263-1.046), which met the prespecified statistical criterion for non-inferiority because the upper confidence bound was below 1.5; however, the estimate was imprecise because of the small number of events. In the migraine with aura subgroup, the estimate also met the non-inferiority criterion (HR 0.419, 95% CI 0.163-1.080), whereas the migraine without aura subgroup, per-protocol analysis, and major adverse cardiovascular events analysis were inconclusive for non-inferiority. For major adverse cardiovascular events the HR was 1.068 (95% CI 0.589-1.935). The fracture negative control was also not significantly different (HR, 1.175; 95% CI, 0.692-1.993; p = 0.551), arguing against systematic healthy-user confounding. A formal adjusted comparison with untreated patients was not feasible due to structural confounding inherent to the stepped-care treatment pathway.ConclusionsIn this real-world diverse cohort, initiation of CGRP mAbs met the prespecified statistical criterion for non-inferiority relative to onabotulinumtoxinA for the primary IS + TIA outcome. However, this finding was based on few events and wide CIs and should be interpreted cautiously as limited evidence against a large relative increase in incident IS + TIA risk, rather than as definitive evidence of equivalent safety, absence of modest harm, or a protective effect. Several secondary, subgroup, and supportive analyses remained inconclusive for non-inferiority. Larger adequately powered comparative safety studies are needed.
Burning mouth syndrome and oral dysaesthetic/perceptual symptoms: Toward clinically actionable boundaries.
Suga T, Tu TTH, Watanabe M … +1 more , Toyofuku A
Cephalalgia · 2026 Jul · PMID 42377410 · Publisher ↗
Abstract loading — click title to view on PubMed.
Effectiveness and clinical predictors of rimegepant for acute vertigo in vestibular migraine: A real-world cohort study.
Li Y, Yu L, Deng D … +3 more , Cao X, Lu X, Bing D
Cephalalgia · 2026 Jul · PMID 42377393 · Publisher ↗
AimIn view of limited evidence-based acute treatments for spontaneous vertigo in vestibular migraine, this real-world cohort study assessed the effectiveness of rimegepant for acute vestibular migraine-related vertigo an...
AimIn view of limited evidence-based acute treatments for spontaneous vertigo in vestibular migraine, this real-world cohort study assessed the effectiveness of rimegepant for acute vestibular migraine-related vertigo and factors associated with treatment response.MethodsClinical data were retrospectively collected from 86 patients with documented vestibular migraine treated with rimegepant 75 mg orally disintegrating tablets for acute attacks at a tertiary referral hospital between March and November 2025. Predictors of 2-h vertigo relief, defined as improvement from moderate or severe baseline vertigo to mild or no vertigo on an 11-point numeric rating scale, and 2-h numeric rating scale scores were analyzed using regression models accounting for within-patient clustering of attacks.ResultsAmong 86 patients, 192 of 252 treated vertigo episodes (76.2%) achieved vertigo relief. At 2 h after dosing, the mean change in vertigo numeric rating scale score was -4.44 (95% CI, -4.65 to -4.23). In adjusted models, age younger than 60 years (OR, 3.45 [95% CI, 1.15 to 10.31]; P = 0.027) and lower baseline numeric rating scale (OR per 1-point increase, 0.56 [95% CI, 0.36 to 0.86]; P = 0.008) were associated with higher odds of vertigo relief. Younger age, lower baseline numeric rating scale score, and better hearing (β, -1.14 [95% CI, -2.02 to -0.26]; P = 0.013) were also associated with lower 2-h numeric rating scale scores.ConclusionRimegepant was effective for vertigo episodes in patients with vestibular migraine, and treatment responsiveness was closely associated with age, baseline vertigo severity, and auditory function. These findings support the early initiation of rimegepant for acute treatment of vestibular migraine, rather than delaying treatment until vertigo exacerbation.
Efficacy of digital therapeutic sinCephalea for personalised nutrition versus control for migraine prevention: A 12-week open-label randomised clinical trial.
Evers S, Grube HCB, Gendolla A … +9 more , Gaul C, Ewald K, Witt O, Voggel J, Nitschke M, Sina C, Thaçi D, König IR, Schröder T
Cephalalgia · 2026 Jul · PMID 42377084 · Publisher ↗
BackgroundLow-glycaemic diet may alleviate migraine; however, individual blood glucose variability can affect efficacy. In this open-label randomised controlled trial in Germany, we assessed whether the digital therapeut...
BackgroundLow-glycaemic diet may alleviate migraine; however, individual blood glucose variability can affect efficacy. In this open-label randomised controlled trial in Germany, we assessed whether the digital therapeutic (DTx) sinCephalea, which delivers personalised low-glycaemic nutritional recommendations supported by intermittent continuous glucose monitoring (CGM), reduces migraine frequency compared with a design-matched control application.MethodsThis open-label trial in Germany assessed the DTx sinCephalea for migraine prevention. Adults aged 18-65 years with episodic migraine were randomised 1:1 (in addition to standard treatment) to the digital therapeutic (intervention) or a design-matched control application. Patients completed a daily headache and medication diary, and 4-weekly patient-reported outcome questionnaires. Adherence to nutritional recommendations was monitored. Primary endpoint (Week 12): change from baseline in monthly migraine days (every 4 weeks) for intervention versus control. Secondary endpoints: change from baseline in monthly migraine days in patients with ≥50% adherence to nutritional recommendations, 30% response rates, migraine- and headache-related impairment, quality-of-life, and acute medication use for intervention versus control. Adverse events were recorded.Results842 patients were randomised between July 2021 and August 2023 (full analysis set: intervention = 416; control = 419). There were significantly greater reductions in monthly migraine days at week 12 for intervention versus control (mean [SD] change: 1.7 [3.4] versus 1.2 [3.2] days; between-group difference estimate: -0.53 [95% CI -0.98 to -0.09]; p = 0.0195) with similar monthly migraine days reductions observed in adherent patients (p = 0.0062; adjusted α = 0.05). Response rate was 54.9% (185/337) in intervention versus 42.9% (168/392) in control (odds ratio: 1.63 [95% CI 1.21-2.19]; p = 0.0012; adjusted α = 0.0125). Migraine- and headache-related impairment were lower at week 12 for intervention versus control (p = 0.0247, adjusted α = 0.0167and p = 0.0001, adjusted α = 0.01, respectively). There was no significant difference in quality-of-life or acute medication use and no digital therapeutic-related adverse events.ConclusionPersonalised nutrition, supported by intermittent CGM, via the DTx sinCephalea, was efficacious for migraine prevention without DTx-related adverse events. This study provides evidence in support of the link between diet and migraine frequency and symptoms. Additionally, as this is a non-pharmacological treatment with no DTx-related side effects, it may be an attractive option for patients. DTx could also reduce the burden of migraine on healthcare systems by providing a scalable, remote, non-invasive and convenient treatment option.
SafeTy and effectiveness of Atogepant accoRding to the IHS outcome categories: A multicentric, prospective observational study in real life (the 24-week STAR study).
Altamura C, Iannone LF, Castro FL … +36 more , Sebastianelli G, Marcosano M, Santis F, Corrado M, Ornello R, Grazzi L, Montisano DA, Cesaris F, Munafò A, Avino G, Trimboli M, Albanese M, Russo A, Silvestro M, Volta GD, Romozzi M, Calabresi P, Boccalini A, Merlo P, Prudenzano MP, Valente MR, Rainero I, Giuliani G, Altieri M, Fofi L, Doretti A, Vaghi G, Pistoia F, Ferrandi D, Battistini S, Coppola G, Guerzoni S, Sacco S, Tassorelli C, Vernieri F, Italian Headache Registry (RICe) Study Group
Cephalalgia · 2026 Jun · PMID 42360082 · Publisher ↗
BackgroundThe improved prevention of migraine, driven by the introduction of calcitonin gene-related peptide (CGRP)-targeted therapies, has prompted the International Headache Society (IHS) to propose new goals in migrai...
BackgroundThe improved prevention of migraine, driven by the introduction of calcitonin gene-related peptide (CGRP)-targeted therapies, has prompted the International Headache Society (IHS) to propose new goals in migraine management. This study aimed to evaluate the safety and effectiveness of atogepant for migraine prevention over 24 weeks, in accordance with the IHS-defined goals.MethodsThis is a multicenter, prospective, observational, real-world study on patients starting atogepant 60 mg for migraine prevention. We describe efficacy and safety outcomes at weeks 9-12 (T3) and 21-24 (T6) relative to baseline (T0) from the initiation of atogepant treatment. We also report the proportion of patients achieving migraine freedom, optimal, modest or insufficient control according to the IHS position paper categories.ResultsOne hundred twenty-eight ( = 128) patients (63 (49.2%) with chronic migraine, 115 (89.9%) female, aged 48.3 ± 13.3 years) from 17 centers were analyzed. Monthly migraine days decreased from 16.5 ± 8.5 at T0 to 8.0 ± 8.4 at T3 ( < 0.001 vs. T0) and 8.6 ± 9.2 at T6 ( < 0001 vs. T0, = 0.265 compared to T3). Overall, 64.8% of patients were responders (at least 50% reduction in monthly migraine days from T0) at T3 and 61.7% at T6; 81.9% of responders at T3 maintained the responder status at T6, while 24.4% of patients among non-responders at T3 became responders at T6. At T3 and T6, 39.1% of the entire cohort achieved at least optimal migraine control (20.6% in chronic migraine and 56.9% in episodic migraine).ConclusionsThe STAR study demonstrates, in a real-world setting, the safety and the sustained effectiveness of atogepant 60 mg over 24 weeks and indicates that more than one-third of treated patients can achieve at least optimal disease control, with markedly better outcomes in episodic than in chronic migraine.Trial RegistrationThe study was preregistered on clinicaltrial.gov, NCT06414044.
Placebo or active comparator in chronic migraine trials: Balancing evidence and practicality.
van Veelen N, Ornello R, Terwindt GM … +1 more , Sacco S
Cephalalgia · 2026 Jun · PMID 42345571 · Publisher ↗
This debate addresses the choice of placebo versus active comparator in randomized controlled trials (RCTs) for chronic migraine (CM), a disabling condition with high global burden. Placebo-controlled designs have tradit...
This debate addresses the choice of placebo versus active comparator in randomized controlled trials (RCTs) for chronic migraine (CM), a disabling condition with high global burden. Placebo-controlled designs have traditionally been considered the gold standard for new treatments, allowing quantification of placebo and pharmacological effects, ensuring internal validity, smaller sample sizes, and regulatory acceptance. Yet, ethical concerns arise from the possibility that participants may be denied effective treatments. The emergence of migraine-specific therapies targeting the calcitonin gene-related peptide (CGRP) pathway has prompted calls for active comparator designs. Such trials may enhance clinical relevance, support recruitment, and better mirror clinical practice compared with placebo-controlled RCTs. However, defining a universal standard of care may be challenging given global disparities in access, cost, and treatment preferences, limiting the feasibility of RCTs with active comparators. Placebo-controlled trials remain valuable, but alternative strategies, including short placebo phases with open-label extensions, add-on designs, or three-arm trials (investigational treatment, placebo, active comparator) may reconcile scientific rigor with ethical considerations. Ultimately, the optimal trial design depends on the research question, regulatory requirements, and evolving definitions of standard care in CM prevention.
Impaired bone status in high frequency episodic or chronic migraine women: A case-control study with blood and densitometric parameters.
Haro M, Muñoz-San Martín M, Gárate G … +8 more , De La Guerra L, González-Quintanilla V, Madera J, Pérez-Pereda S, Valero C, Olmos JM, Hernández JL, Pascual J
Cephalalgia · 2026 Jun · PMID 42340335 · Publisher ↗
Background/AimMigraine and osteoporosis are highly prevalent in women and represent a substantial socio-health burden. We aimed to comprehensively assess bone status in women with frequent migraine.Patients and MethodsAd...
Background/AimMigraine and osteoporosis are highly prevalent in women and represent a substantial socio-health burden. We aimed to comprehensively assess bone status in women with frequent migraine.Patients and MethodsAdult women with high-frequency episodic migraine (HFEM) or chronic migraine (CM) were recruited and compared with age- and body mass index-matched female controls. Serum parameters of bone metabolism, including 25-hydroxyvitamin D (25[OH]D), calcium and parathyroid hormone (PTH), as well as bone turnover markers (procollagen type 1 N-terminal propeptide [P1NP] and C-terminal telopeptide of type I collagen [CTX]), were measured. Bone mineral density (BMD), T-scores and trabecular bone score (TBS) were assessed by dual-energy X-ray absorptiometry.ResultsA total of 108 women with CM/HFEM and 129 matched controls were included. Compared with controls, women with migraine had lower serum 25(OH)D and calcium levels (p ≤ 0.001) and higher adjusted CTX levels (p = 0.039). Densitometric assessment revealed significantly reduction in BMD at femoral neck (g/cm and T-score) and total hip (T-score) in the migraine group (p < 0.001). Lumbar TBS was also lower in CM/HFEM patients (p < 0.001). After multivariable adjustment, TBS remained independently associated with migraine status. These alterations remained in women with HFEM and in those younger than 50 years, and were associated with reduced physical activity and sun exposure.ConclusionsWomen with frequent migraine exhibit impaired bone health, characterized by alterations in bone mass and trabecular microarchitecture. TBS appears to be a sensitive marker of early skeletal involvement in this population. The presence of bone impairment in HFEM and in premenopausal women supports early assessment of bone status and reinforcement of lifestyle interventions, including adequate physical activity and sun exposure.
Distribution of intranasal lidocaine and its effect on electrically-evoked calcium signals in mouse trigeminal ganglion neurons.
Tiebl L, Solinski HJ, Belejova S … +7 more , Soares S, Pitzer C, Palkovacs R, Poschet G, Schmelz M, Oehler B, Carr R
Cephalalgia · 2026 Jun · PMID 42340327 · Publisher ↗
BackgroundLidocaine applied intranasally has shown promise in treating post-dural puncture headache and has been explored as a potential treatment for cluster headache and migraine. However, the mechanisms underlying its...
BackgroundLidocaine applied intranasally has shown promise in treating post-dural puncture headache and has been explored as a potential treatment for cluster headache and migraine. However, the mechanisms underlying its analgesic effects remain unclear. This study aimed to determine the concentration of lidocaine that reaches target tissues after intranasal application and its impact on the excitability of trigeminal ganglion neurons.MethodsA mouse model was used to examine lidocaine (10%) distribution after intranasal administration, employing liquid chromatography-mass spectrometry (LC-MS). Fluorescence calcium imaging with electrical field stimulation on acutely cultured murine trigeminal ganglion cells was applied to determine the effects of the pre-determined lidocaine concentrations on their excitability.ResultsAfter intranasal application, lidocaine concentrations ranged from approximately 2.5 μM in plasma to 7 μM in trigeminal ganglia. Calcium imaging revealed that 100 μM lidocaine was required to decrease electrical responses in capsaicin-unresponsive trigeminal ganglion neurons. In capsaicin-responsive nociceptive neurons such an inhibition was already observed at 10 μM lidocaine and these neurons also displayed a sustained increase in calcium that failed to return to baseline levels.ConclusionsThese findings suggest that intracranial lidocaine concentrations after intranasal administration are sufficiently high to selectively affect depolarized trigeminal nociceptors with ongoing activity, providing a potential mechanism for the analgesic effects of intranasally applied lidocaine. These results have implications for the use of intranasal lidocaine as a treatment for headache.
Treatment outcomes in new daily persistent headache in children and adolescents.
Abuhalaweh N, Gelfand AA, Evans M … +5 more , Marquez de Prado B, Patterson Gentile C, Raj N, Hershey AD, Szperka CL
Cephalalgia · 2026 Jun · PMID 42318710 · Publisher ↗
BackgroundNew daily persistent headache (NDPH) is a primary headache disorder that often presents in adolescence. Presently, there is no effective treatment for NDPH and a paucity of clinical trials exploring therapeutic...
BackgroundNew daily persistent headache (NDPH) is a primary headache disorder that often presents in adolescence. Presently, there is no effective treatment for NDPH and a paucity of clinical trials exploring therapeutic options. In this study, we explored the relative benefit of currently used treatments to help inform future trials and clinical decision-making.MethodsIn this retrospective chart review study, patients aged 5-17 years with abrupt onset continuous headache and headache duration of at least one month (constituting NDPH or probable NDPH) were identified based on responses to a Headache Questionnaire in child neurology clinic and confirmed with chart review. We included all treatments (transitional therapy, preventive supplement, preventive medication and preventive non-medication therapy) started during continuous headache until both break in continuous headache and sustained improvement in headache were achieved. For treatments tried by at least 10 patients and for the first treatment tried in each category, we calculated proportions of any documented benefit, including "Significant" (≥30% improvement lasting ≥4 weeks) and "Some improvement" (all other improvement) and proportions of negative outcome (those with worsened headaches or side effects warranting discontinuation), as well as median time to treatment. We used multivariable regression modeling to examine for factors associated with headache outcomes. Treatments may have overlapped.ResultsOf the 165 patients, the largest proportion of patients experienced benefit with the first transitional therapy (62/108; 57%), which was usually intravenous medications ± oral corticosteroids. The first supplement tried, usually riboflavin ± magnesium, offered benefit in (36/118; 31%), with few negative outcomes (3/118; 3%). The first prescription preventive tried, usually amitriptyline or topiramate, offered similar benefit (37/106; 35%) as the first supplement, but with more negative outcomes (25/106; 24%). Despite being tried after oral preventives, onabotulinumtoxinA injections offered benefit to the largest proportion of patients (14/20; 70%) without negative outcomes (0%). Overall, the time to first therapy was weeks to months into continuous headache: shortest for transitional therapies (median = 49 days, interquartile range = 17-92 days), and longest for non-medication therapies (median = 144 days, interquartile range = 61-381 days). Increased time to any first treatment was associated with decreased odds of headache improvement at one-year follow-up (odds ratio = 0.823, 95% confidence interval = 0.715-0.946, = 0.006).ConclusionsChildren and adolescents with new onset continuous headache experience treatment delays which are associated with worse outcomes. Clinicians should consider use of transitional therapies in combination with preventive treatments as early as possible. Prospective natural history studies and trials are needed to improve treatment outcomes for pediatric patients with NDPH.
Is achieving higher standards in real-world migraine care feasible with anti-CGRP monoclonal antibodies preventive therapies?: Insights from the EUREkA cohort.
Caronna E, Mas-de-Les-Valls R, Egeo G … +114 more , Vázquez MM, Castellanos CN, Membrilla JA, Vaghi G, Rodríguez-Montolio J, Fabra NF, Caballero FS, Jaimes A, Muñoz-Vendrell A, Oliveira R, Gárate G, Osorio YG, Guisado-Alonso D, Ornello R, Thunstedt C, Fernández-Lázaro I, Sánchez-Soblechero A, Husøy AK, Vicente BN, Basedau H, Riesco Pérez NP, Pina BF, Fernandes C, Andrés-López A, Martins-Silva E, Budrewicz S, Arlanzón PR, Caetano A, Gallardo VJ, Gómez-Dabó L, Torres-Ferrús M, Alpuente A, Torelli P, Aurilia C, Zapata S, Pérez RL, Ruiz Castrillo MJ, Icco R, Sances G, Broadhurst S, Ong HC, Winstanley J, Aranceta S, Zubizarreta IK, Urabayen AE, García AG, Campoy S, Marques I, Parreira E, González-Quintanilla V, Guerrero-Peral ÁL, Miró I, Peris-Subiza J, Caponnetto V, Straube A, Gonzalez-Martinez A, Quintas S, Sánchez-Del-Río M, Tronvik E, Pérez BV, Durán AO, Rodrigues M, Ramos AF, Esteban YV, Cevoli S, Colombo B, Trimboli M, Frediani F, d'Onofrio F, Aguggia M, Salerno A, Carnevale A, Zucco M, Albanese M, Finocchi C, Ranieri A, Zoroddu F, Autunno M, Sanahuja J, Cabral G, Blasco IB, Waliszewska-Prosół M, Pereira L, Layos-Romero A, Luzeiro I, Dorado L, Álvarez Escudero MR, May A, López-Bravo A, Martins IP, Sundal C, Irimia P, Ros AL, Gago-Veiga AB, Juanes FV, Ruscheweyh R, Sacco S, Cuadrado-Godia E, García-Azorín D, Pascual J, Gil-Gouveia R, Huerta-Villanueva M, Rodriguez-Vico J, Romero JV, Obach V, Santos-Lasaosa S, Ghadiri-Sani M, Tassorelli C, Díaz-de-Terán J, Insa SD, Oria CG, Barbanti P, Pozo-Rosich P, EUREkA study group
Cephalalgia · 2026 Jun · PMID 42318706 · Publisher ↗
BackgroundThe International Headache Society has proposed new treatment goals for migraine prevention in real world, as a way to set higher standards of care. This study provides the first assessment of the proportion of...
BackgroundThe International Headache Society has proposed new treatment goals for migraine prevention in real world, as a way to set higher standards of care. This study provides the first assessment of the proportion of individuals achieving them after 6 months of migraine-specific treatment with anti-CGRP monoclonal antibodies (MAbs).MethodsThis was a prospective, real-world, European multicenter study, including adults with migraine treated with anti-CGRP MAbs (EUREkA cohort). We assessed the proportions of individuals in each treatment goal category-migraine freedom (no monthly migraine days [MMD]); optimal control (< 4 MMD), modest control (4-6 MMD); insufficient control (>6 MMD)-after 6 months of treatment. We also assessed the proportion of individuals with ≥50% reduction in MMD in the insufficient control group.ResultsOf the 5818 individuals in the EUREkA cohort, 4963 had 6 months data. Of these, 82.3% (4086/4963) were females and the median age was 48.0 [40.0-55.0] years. At baseline, the median monthly headache days [MHD] and MMD were 20.0 [13.3-28.0] and 15.0 [10.0-20.0], respectively. All participants were classified as having insufficient headache control (>6 MMD) at baseline. At month 6, 6.9% (342/4963) had migraine freedom, 22.9% (1137/4963) optimal control, 24.6% (1223/4963) modest control and 45.6% (2261/4963) insufficient control. In the insufficient control group, 27.1% (613/2261) had ≥50% reduction in MMD.ConclusionsHigh standards of care, defined as optimal disease control or even migraine freedom, are achieved in real-world settings with anti-CGRP MAbs in approximately 30% of individuals with a high migraine burden. These findings highlight the need to expand global access to these treatments. Future studies should explore whether initiating migraine-specific preventive treatments earlier could further reduce residual migraine days in responders, enabling a larger proportion of patients to achieve optimal disease control.
Weekend headache in migraine - fact or fiction? An observational study from DMKG-app data.
Ruscheweyh R, Dresler T, Gossrau G … +5 more , Kraya T, Neeb L, Raffaelli B, Ruschil V, Scheidt J
Cephalalgia · 2026 Jun · PMID 42312356 · Publisher ↗
BackgroundIt has long been proposed that some individuals with migraine are especially prone to experience headache on weekends, however, results have been contradictory. Electronic headache diaries offer the possibility...
BackgroundIt has long been proposed that some individuals with migraine are especially prone to experience headache on weekends, however, results have been contradictory. Electronic headache diaries offer the possibility to analyze this question more thoroughly in larger populations.MethodsTwo non-overlapping samples of individuals with migraine from the DMKG-App electronic headache diary were investigated. Cluster analysis and logistic regression were performed to study existence, prevalence and predictive factors of weekend headache.ResultsWe included 1793 and 5840 patients with ≥35 headache day entries in the two samples ("registry sample" and "app-only sample"), respectively. In both samples, cluster analysis identified a cluster of patients with headache occurring preferably on weekends, accounting for 14-15% of all patients, and 18% of individuals with episodic migraine. Compared to the three other clusters identified (an early week cluster, a midweek cluster and a flat cluster without preference for a specific day), the weekend cluster was more frequent in working patients (p < 0.001, OR = 3.57 to 3.97) and in patients with lower headache frequencies (p < 0.001, OR = 0.86). A small association with older age (p < 0.001, OR = 1.01) was limited to the app-only sample. Longitudinal analysis showed that headache patterns of single patients were variable over time.ConclusionsResults from two large samples corroborate that there is a subgroup of individuals with migraine prone to weekend headache. Association with working status supports the notion that release from stress could be a trigger factor in these patients, although change in sleep, caffeine and alcohol intake and other factors might also contribute.
CGRP, VIP and PACAP plasmatic levels in migraine patients before and after anti-CGRP(R) monoclonal antibodies treatment.
Chiasserini D, Bellotti A, Megaro A … +9 more , Tringali G, Corbelli I, Cresta E, Teti V, Fruttini D, Calabresi P, Navarra P, Parnetti L, Sarchielli P
Cephalalgia · 2026 Jun · PMID 42307444 · Publisher ↗
AimCalcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) play a crucial role in migraine pathophysiology. In recent years, anti-CGRP(R) mon...
AimCalcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) play a crucial role in migraine pathophysiology. In recent years, anti-CGRP(R) monoclonal antibodies (mAbs) have emerged as the first targeted and highly effective therapy for migraine. This study aimed to assess any changes in plasma CGRP levels following prophylactic treatment with anti-CGRP(R) mAbs and to compare CGRP dynamics between anti-receptor (erenumab) and anti-ligand (galcanezumab, fremanezumab) therapies. Secondary objectives were: (i) to evaluate changes in VIP and PACAP plasma levels following treatment with anti-CGRP(R) mAbs and (ii) to investigate whether baseline or post-treatment plasma levels of CGRP, VIP and PACAP were associated with clinical response to anti-CGRP(R) monoclonal antibody therapy.MethodsBetween February 2022 and February 2023, we enrolled 56 migraine patients who initiated prophylaxis with either erenumab (26 patients), galcanezumab (16 patients) or fremanezumab (14 patients). Responders were defined as those achieving a ≥50% reduction in monthly migraine days after six months. Blood samples were collected at baseline and at each follow-up visit (baseline, T0; three months, T1; six months, T2; 12 months, T3). Plasma levels of CGRP, VIP and PACAP were measured using a validated radioimmunoassay and commercially available enzyme-linked immunosorbent assay kits.ResultsOverall, 80.3% (45 out of 56) of patients responded to anti-CGRP(R) mAbs. No correlation was found between baseline CGRP, VIP and PACAP plasma levels and clinical response to anti-CGRP(R) mAbs therapy. Regarding CGRP trend, significant differences were found between patients treated with the anti-receptor monoclonal antibody (erenumab) and those receiving anti-ligand therapies. In patients treated with erenumab, CGRP levels did not show a significant change over the treatment period (T1-T3), whereas, in the galcanezumab group, CGRP levels significantly decreased as early as T1 ( < 0.01). CGRP longitudinal assessment of the fremanezumab group were excluded due to assay interference with the drug. VIP and PACAP plasma levels remained stable over time for all treatments, with no significant differences between responders and non-responders.ConclusionsGalcanezumab reduced CGRP plasmatic levels already after three months, whereas erenumab did not affect significantly CGRP plasmatic levels. VIP and PACAP levels were not influenced by the therapy.
Methodological limitations of anxiety screening tools used in migraine studies -a narrative review.
Hoang Pham MY, Asheer J, Ali F … +3 more , Hilker R, Videbech P, Schytz HW
Cephalalgia · 2026 Jun · PMID 42307416 · Publisher ↗
BackgroundAnxiety is commonly reported among patients with migraine, and anxiety questionnaires are frequently used to assess anxiety symptoms. This narrative review examines how common anxiety screening tools are applie...
BackgroundAnxiety is commonly reported among patients with migraine, and anxiety questionnaires are frequently used to assess anxiety symptoms. This narrative review examines how common anxiety screening tools are applied in migraine studies and whether they are applied and interpreted appropriately.MethodA PubMed search included studies using the Hospital Anxiety Depression Scale (HADS), Generalized Anxiety Disorder 7-Items (GAD-7) or Beck Anxiety Inventory (BAI). The search also included studies using the Hamilton Anxiety Rating Scale (HAM-A) or State Anxiety Inventory (STAI). Eligible patients were diagnosed with migraine according to the International Classification of Headache Disorders (ICHD-2 or ICHD-3).ResultsNinety-eight studies met the inclusion criteria. In 42 studies (41%), an anxiety score above the cut-off was interpreted as an anxiety diagnosis. This approach was used in 52%, 44%, 41%, 29% and 38% of studies using HADS-A, GAD-7, BAI, HAM-A and STAI. Only three studies confirmed the diagnosis through a structured clinical interview. Data presentation and interpretation across the studies were heterogeneous. Only a few of the scales are validated in a population of migraine patients.ConclusionThis study shows that anxiety screening tools are commonly used in migraine studies but with considerable variation in cut-off scores and interpretation. Such methodological differences and limited validation of these tools may make it difficult to determine the true prevalence of anxiety in migraine studies. Further studies are needed to validate these instruments and to establish clear guidelines for their use in migraine research.
Beyond ICHD-3 criteria: Diagnostic challenges in headache in pediatric age.
Papetti L, Borrelli A, Granata C … +4 more , Monte G, Ursitti F, Sforza G, Valeriani M
Cephalalgia · 2026 Jun · PMID 42300745 · Publisher ↗
BackgroundDiagnosing headache in children and adolescents is challenging because clinical features vary with age, primary and secondary forms may overlap and the use of investigations is often inconsistent.MethodsWe cond...
BackgroundDiagnosing headache in children and adolescents is challenging because clinical features vary with age, primary and secondary forms may overlap and the use of investigations is often inconsistent.MethodsWe conducted a scoping review following PRISMA guidelines. PubMed, Ovid MEDLINE, Scopus and the Cochrane Library were searched for studies on headache diagnosis in individuals aged 1-18 years (2018-2025). Of 126 records identified, 36 met eligibility criteria and were included.ResultsSeveral studies indicate that ICHD-3 criteria, developed mainly in adults, may not fully reflect paediatric presentations, contributing to diagnostic uncertainty. Evidence clarifies the value of some red flags while challenging others. Neuroimaging demonstrates low diagnostic yield except in selected cases. Common pitfalls include overdiagnosis of sinusitis, inappropriate EEG use and unnecessary ophthalmologic or allergologic testing.ConclusionsAccurate diagnosis relies on careful history taking, recognition of age-specific patterns and judicious use of investigations. Paediatric-focused diagnostic pathways are needed. Emerging digital tools and biomarkers may support earlier and more precise diagnosis.
Beyond headache: Cognitive improvement in patients with migraine responding to anti-CGRP monoclonal antibodies or botulinum toxin.
Martins IP, Taveira MC, Couto M … +5 more , Velasco S, Rato R, Costa A, Martins B, Dourado Sotero F
Cephalalgia · 2026 Jun · PMID 42294952 · Publisher ↗
BackgroundCognitive functioning worsens during migraine attacks and in the interictal period, especially in chronic migraine. This study aims to evaluate whether preventive treatment with anti-CGRP monoclonal antibodies...
BackgroundCognitive functioning worsens during migraine attacks and in the interictal period, especially in chronic migraine. This study aims to evaluate whether preventive treatment with anti-CGRP monoclonal antibodies (mAbs) or botulinum toxin (BoNT) improves interictal cognitive performance in migraine patients, and to compare cognitive changes between treatment responders and non-responders, controlling for treatment type.MethodsA two-center prospective longitudinal comparative study of patients with Episodic (EM) or Chronic (CM) migraine receiving either mAbs or BoNT. Participants underwent two comprehensive cognitive evaluations targeting attention/processing speed, executive functions, episodic memory, and language, at baseline (visit 1) and after three to six months of treatment (visit 2). The primary end point was the degree of improvement measured by the z scores of each cognitive domain (adjusted for age and education), from baseline to follow-up, assessed using repeated-measures analysis with time as the within-subject factor and treatment response as the between-subject factor, controlling for treatment group. Treatment response was defined as a decrease in monthly moderate-to-severe headache days of ≥30% in CM or ≥50% in EM at follow-up.ResultsOne hundred patients were included, and 90 completed the study (median age = 42 years, 96.7% women, 58 (64.4%) with CM, 64 (71.1%) treated with mAbs, and 26 (28.8%) with BoNT. Forty-seven (52.2%) were responders (59.4% in the mAbs group and 34.6% in the BoNT group) after a mean follow-up time of 4.5 months. Improvement in a measure of executive functions (comprising tests of working memory, alternating attention, and phonological fluency) was significantly higher in responders than in non-responders, independently of treatment group. No significant differences between responders and non-responders were observed in episodic memory, language, or processing speed. Among responders, the change in executive function score was not associated with the reduction in monthly moderate-severe headache days or the final number of monthly headache-free days.ConclusionsPerformance on measures of executive capacities, may improve in migraine patients after a few months of effective migraine treatment with mAbs or BoNT, regardless of the treatment group. Further research is needed to determine whether this effect augments over time, is associated to the reduction of pre-ictal and post-ictal days and /or to brain networks reorganization.
A retrospective cohort study comparing treatment persistence between rimegepant and lasmiditan for the acute treatment of migraine in the US.
Tepper SJ, Jenkins A, Dagenais S … +5 more , Henriksen C, Abraham L, Dai F, Hygge Blakeman K, Gendolla A
Cephalalgia · 2026 Jun · PMID 42273779 · Publisher ↗
BackgroundThis study compared treatment persistence of individuals newly initiating treatment with rimegepant or lasmiditan for the acute treatment of migraine.MethodsA retrospective cohort analysis was conducted on indi...
BackgroundThis study compared treatment persistence of individuals newly initiating treatment with rimegepant or lasmiditan for the acute treatment of migraine.MethodsA retrospective cohort analysis was conducted on individuals from MarketScan (commercial and managed Medicare) newly initiating treatment with rimegepant or lasmiditan between March 2020 and December 2022. Treatment persistence was defined as the proportion of individuals with ≥1 medication refill within 12 months of the index prescription. Subgroups included individuals with chronic migraine, index lasmiditan dose (50 and 100 mg) and individuals with a history of two or more uses of controlled substances (prior repeated use of controlled substances [PRUCS] defined here as opioids, butalbital, nausea medications with central nervous system action). Treatment persistence was compared between inverse probability of treatment weighting (IPTW)-adjusted cohorts using odds ratios (ORs) and 95% confidence intervals (CIs).ResultsThe primary analysis included 16,603 rimegepant and 716 lasmiditan users. A significantly higher proportion of individuals in the rimegepant cohort were treatment persistent compared with the lasmiditan cohort (OR 3.79 [95% CI 3.23-4.41]). This finding remained consistent across lasmiditan dosages (50 mg: 5.05 [3.87-6.60]; 100 mg: 3.33 [2.78-4.00]), chronic migraine diagnosis (3.89 [3.21-4.71]), or PRUCS (ORs ranged from 2.78 to 4.63; all statistically significant).ConclusionRimegepant users demonstrated higher treatment persistence over 12 months compared to lasmiditan users, which could reflect better real-world treatment satisfaction.
Diagnostic tests and headache misdiagnoses in individuals with resistant and refractory migraine - data from the REFINE study.
De Santis F, Rosignoli C, Onofri A … +28 more , Braschinsky M, Sved O, Gil-Gouveia R, Oliveira R, Lampl C, Paungarttner J, Martelletti P, Wells-Gatnik WD, Martins IP, Mitsikostas DD, Apostolakopoulou L, Ozge A, Narin DB, Pozo-Rosich P, Munoz-Vendrell A, Prudenzano MP, Gentile M, Ryliskiene K, Vainauskiene J, Sanchez-Del-Rio M, Vernieri F, Iaccarino G, Waliszewska-Prosół M, Budrewicz S, Carnovali M, Katsarava Z, Sacco S, Ornello R
Cephalalgia · 2026 Jun · PMID 42244176 · Publisher ↗
BackgroundIndividuals with difficult-to-treat migraine, including resistant migraine (ResM) and refractory migraine (RefM), might experience treatment delays, undergo unnecessary diagnostic tests and receive misdiagnoses...
BackgroundIndividuals with difficult-to-treat migraine, including resistant migraine (ResM) and refractory migraine (RefM), might experience treatment delays, undergo unnecessary diagnostic tests and receive misdiagnoses, which might influence treatment outcomes. For this reason, we hypothesized that individuals with ResM and RefM might report more diagnostic tests and misdiagnoses in their medical history compared with those with non-resistant/non-refractory migraine (NRNRM).MethodsThis analysis used baseline, cross-sectional data from the REFINE study, a multicenter, prospective observational study conducted in 15 European tertiary headache centers. Adults with episodic or chronic migraine were classified into RefM, ResM, or NRNRM groups. Baseline data were analyzed to assess the frequency of previous diagnostic tests and misdiagnoses.ResultsOverall, 689 participants were included with a median age of 46 years (interquartile range 36-53); 570 participants (82.7%) were female; 355 (51.5%) had NRNRM, 261 (37.9%) ResM, and 73 (10.9%) RefM. Referring to diagnostic tests, 335 participants (48.7%) had one and 237 (34.4%) multiple brain magnetic resonance imaging scans. ResM and RefM participants underwent more diagnostic tests than NRNRM. Overall, 193 participants (28.0%) had at least one prior headache misdiagnosis, most commonly cervical spine disorders and sinusitis; misdiagnoses were more frequent in NRNRM and ResM than in RefM (31.1%, 28.5%, and 15.1%, respectively; p = 0.025). Misdiagnosis rates were not influenced by age, sex, disease duration, or comorbidities.ConclusionsDiagnostic tests use and misdiagnoses are highly prevalent in all the three groups of individuals with ResM, RefM, and NRNRM with some differences across the three groups that may depend on multiple factors. Our findings emphasize a need for better diagnostic accuracy and care pathway across the entire spectrum of migraine, to avoid unnecessary diagnostic tests and misdiagnoses.
Optimized and validated clinical diagnostic criteria for burning mouth syndrome.
El-Rubaiy M, List T, Truedsson A … +3 more , Goulet JP, Svensson P, Alstergren P
Cephalalgia · 2026 Jun · PMID 42244168 · Publisher ↗
ObjectivesBurning mouth syndrome (BMS) is defined as a chronic intraoral burning sensation occurring in the absence of identifiable local or systemic causes. Several classification systems have proposed diagnostic criter...
ObjectivesBurning mouth syndrome (BMS) is defined as a chronic intraoral burning sensation occurring in the absence of identifiable local or systemic causes. Several classification systems have proposed diagnostic criteria for BMS, including the International Classification of Headache Disorders (ICHD-3), the International Classification of Diseases (ICD-11), the International Classification of Orofacial Pain (ICOP-1), and the World Congress of Oral Medicine (WCOM). However, none of these have been validated. This study aims to evaluate the diagnostic performance of ICHD-3, ICD-11, ICOP-1, and WCOM criteria for BMS and to suggest optimized diagnostic criteria.MethodsWe assessed 76 consecutive patients referred for burning oral pain. Of these, 34 (28 women) were diagnosed with BMS according to the reference standard, and 42 (37 women) had other oral mucosal pain conditions. Two control groups were also recruited: 31 TMD patients (28 women) and 30 pain-free participants (26 women). Assessment involved self-report questionnaires and comprehensive clinical examinations. All patients with burning oral pain underwent additional laboratory tests. Consensus-based diagnosis constituted the reference standard, and a blinded examiner applied each set of different diagnostic criteria as the index tests. We calculated sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and positive and negative likelihood ratios (LR + and LR-), and the area under the ROC curve for each index tests. Because some ICHD-3 criteria were ambiguously defined, we created operational definitions and tested three versions of the criteria.ResultsNo significant group differences were found in age, sex, or smoking status. None of the criteria exhibited both high sensitivity and specificity. WCOM showed the highest sensitivity (91.2%), NPV (99.2%), LR- (0.14), and AUC (0.717). In contrast, ICHD-3 definition 3 showed the highest specificity (93.2%), PPV (8.2%), and LR + (5.2), but the lowest sensitivity (35.3%). Based on these findings, we developed an optimized version of the ICOP criteria. The new criteria showed the highest sensitivity (94.1%), NPV (99.9), LR- (0.07), and AUC (0.874), while maintaining acceptable specificity (79.6%), PPV (7.4%), and LR + (4.4).ConclusionSubstantial variation exists in the diagnostic performance of current BMS criteria, with each set showing either high sensitivity or specificity. This study provides the first data-driven proposal for modified diagnostic criteria for BMS, offering a foundation for improving future versions of ICHD and ICOP.
Achieving International Headache Society-aspired optimal migraine control in fremanezumab-treated patients: A post-hoc analysis of a real-world, prospective study from the GRASP study group.
Argyriou AA, Dermitzakis EV, Rikos D … +9 more , Chondrogianni M, Foska A, Soldatos P, Mavraki E, Xiromerisiou G, Litsardopoulos P, Tsivgoulis G, Vikelis M, Greek Research Alliance for the Study of Headache and Pain (GRASP) Study Group
Cephalalgia · 2026 Jun · PMID 42237864 · Publisher ↗
ObjectiveTo evaluate whether the conventional ≥50% reduction in monthly migraine days (MMDs) accurately reflects clinically meaningful benefit compared with IHS-aspired migraine control definitions in difficult-to-treat...
ObjectiveTo evaluate whether the conventional ≥50% reduction in monthly migraine days (MMDs) accurately reflects clinically meaningful benefit compared with IHS-aspired migraine control definitions in difficult-to-treat high-frequency episodic migraine (HFEM).MethodsIn this post-hoc analysis of a prospective, real-world registry, conducted by the Greek Research Alliance for the Study of Headache and Pain (GRASP), 114 HFEM patients who had failed ≥3 preventive therapies and achieved a sustained ≥50% reduction in MMDs with monthly fremanezumab over 24 months, were included. Treatment response (≥50% and ≥75% MMD reduction) and IHS-defined control states (freedom, optimal, modest, insufficient control) were assessed using headache diaries at baseline (T0), month 12 (T1), and month 24 (T2). Secondary outcomes included headache intensity, analgesic use, and migraine-related disability.ResultsAt T1, fremanezumab significantly improved all efficacy and disability outcomes (p < 0.001), with mean MMDs reduced from 11.9 at baseline to 5.1 at T1. While 78.1% achieved ≥50% MMD reduction, only 19.3% reached optimal control (<4 MMDs), highlighting a mismatch between relative response and true disease control. At T2, MMDs further declined to 4.3, while optimal control increased to 29.8% and insufficient control declined to 7.8%. Overall, most patients remained moderately controlled (60.6%) with residual 4-6 MMDs. Non-prior exposure to other anti-CGRP therapies emerged as the only independent predictor of optimal long-term control (OR:2.1; p = 0.03).ConclusionAchieving a ≥ 50% MMD reduction with CGRP-targeted therapies may not always correspond to clinically-meaningful benefit. More ambitious outcome measures are essential for more accurately evaluating treatment effectiveness and achieving clinically-meaningful reduction of migraine's disability.
Smoking and medication-overuse headache: Exploring the potential link between nicotine dependence and analgesic overuse.
Hussein M, Hassan A, Magdy R … +11 more , Dahshan A, Yacoub O, Abdelghaffar M, Taha NA, Essmat A, Fayez MM, Merghany N, Elgenidi A, Moustafa RR, Nasser AMA, Elmazny A
Cephalalgia · 2026 Jun · PMID 42227209 · Publisher ↗
BackgroundDespite consistent epidemiological evidence identifying smoking as a risk factor for medication-overuse headache (MOH), the mechanisms underlying this association remain incompletely elucidated. The aim of this...
BackgroundDespite consistent epidemiological evidence identifying smoking as a risk factor for medication-overuse headache (MOH), the mechanisms underlying this association remain incompletely elucidated. The aim of this work was to explore the relationship between the severity of analgesic dependence, headache-related disability, nicotine dependence, psychological distress, and addiction-related personality traits in patients with MOH.MethodsThis multicenter cross-sectional study was conducted on 442 patients with primary headache disorders. Participants underwent structured face-to-face interviews and were asked to fill out the following questionnaires: Headache Impact Test-6 (HIT-6), Severity of Dependence Scale (SDS), Depression Anxiety Stress Scales-12 (DASS-12), and Substance Use Risk Profile Scale (SURPS). Smoking status was documented for all participants. Current smokers were asked to complete Fagerström Test for Nicotine Dependence questionnaire (FTND).ResultsThis study included 442 patients with primary headache disorders, of whom 150 had MOH and 292 did not. Patients with MOH (n = 150) reported significantly higher monthly headache days (MHD), acute medication days (AMD), HIT-6, DASS-12, and SURPS scores than those without MOH (n = 292) (all P-values < 0.001). Smoking prevalence and FTND scores were significantly higher among MOH patients than those without MOH (all P-values < 0.001). Smokers demonstrated higher MHD, AMD, prevalence of MOH, DASS-12, and SURPS scores than non-smokers (all P-values < 0.05). Among smokers, FTND correlated positively with MHD, AMD, HIT-6, DASS-12, and SURPS (all P-values < 0.001). In patients with MOH, SDS scores showed positive correlations with AMD, HIT-6, DASS-12, and SURPS (all P-values < 0.05).ConclusionSeverity of dependence on analgesics in patients with MOH is strongly associated with headache burden, nicotine dependence, psychological distress, and addiction-related personality traits.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe