Cephalalgia[JOURNAL]
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200 papers
Post-traumatic headache two to four months after mild traumatic brain injury: A description of phenotypes and treatment patterns.
Nygaard C, Schytz HW, Odgaard L … +10 more , Kinnerup MB, Nicolaisen AB, Hellemose LA, Eggertsen PP, Skandsen T, Thastum MM, Stabel HH, Pedersen CB, Kothari SF, Nielsen JF
Cephalalgia · 2026 Mar · PMID 41804745 · Publisher ↗
AimTo describe headache phenotypes and treatment patterns in adults with moderate to severe post-traumatic headache and a high burden of other post-concussion symptoms two to four months after mild traumatic brain injury...
AimTo describe headache phenotypes and treatment patterns in adults with moderate to severe post-traumatic headache and a high burden of other post-concussion symptoms two to four months after mild traumatic brain injury.MethodsA cross-sectional study was conducted using patient-reported questionnaire data from 218 individuals, aged 18-60 years, with moderate to severe post-traumatic headache, a headache duration between two and four months, and a high burden of other post-concussion symptoms. The study was based on data from a cohort study with a nested randomized controlled trial called Get Going After Concussion 2.0. Individuals were recruited from emergency departments and general practitioners in Central Denmark Region (1.4 million inhabitants). Phenotyping was performed using an algorithm linking the questionnaire data to diagnostic criteria of primary headache disorders.ResultsAmong the 218 individuals, 62% had acute- and 38% had persistent post-traumatic headache. A migraine-like or probable migraine-like phenotype was identified in 88% of the individuals with no significant differences in phenotype distribution between the acute- and persistent headache subgroups (p = 0.414) or between sexes (p = 0.994). Headache frequency of ≥15 days per month was reported by 78% and average headache intensity was moderate or severe in 94% of all individuals. A pressing and/or tightening headache quality was the most frequent (85%). No significant differences were found between the acute- and persistent headache subgroups regarding pharmacological treatment use or efficacy (p = 0.776). Non-opioid analgesics had been used by 88% of all individuals and 81% were still using them; 52% reported lack of efficacy. Triptans had been or were currently used by 4% of all individuals. Preventive medication, used by 7% of the study population, was reported to have lack of efficacy but all continued treatment. Probable medication overuse headache was found in 27% of the individuals. Overall, 33% had tried two or more non-pharmacological treatments, and 6% had tried between four and six.ConclusionA migraine-like phenotype was the most common presentation in adults with moderate to severe post-traumatic headache and a high symptom burden of other post-concussion symptoms two to four months after trauma. Overall, limited effect of both pharmacological and non-pharmacological treatment was reported. Preventive medication and triptans were used by very few individuals, despite being recommended in current treatment guidelines. The study population exhibited a high health care-seeking behavior, and a large proportion had probable medication overuse headache. Consequently, further insights into disease-specific treatment approaches of post-traumatic headache is needed.
Predictive value of preoperative white and gray matter microstructural alterations for microvascular decompression outcome in classical trigeminal neuralgia.
Jiang J, Wang D, Cui S … +11 more , Zhang P, Wang J, Huang W, Cheng Z, Jia F, Wang Z, Lan Z, Han Y, Jiang Y, Liu G, Zhang J
Cephalalgia · 2026 Mar · PMID 41789868 · Publisher ↗
BackgroundClassical trigeminal neuralgia (CTN) is a severe chronic pain disorder. While microvascular decompression (MVD) is an effective treatment, outcomes are variable, and preoperative predictive biomarkers are neede...
BackgroundClassical trigeminal neuralgia (CTN) is a severe chronic pain disorder. While microvascular decompression (MVD) is an effective treatment, outcomes are variable, and preoperative predictive biomarkers are needed. Furthermore, the relationship between brain microstructural alterations and neurotransmitter systems in CTN is not well understood. This study aimed to characterize these alterations and assess their prognostic value for MVD.MethodsWe evaluated microstructural alterations in both white matter (WM) and gray matter (GM) in 101 CTN patients and 84 healthy controls (HCs) using Neurite Orientation Dispersion and Density Imaging (NODDI). Tract-Based Spatial Statistics (TBSS) and Gray Matter-Based Spatial Statistics (GBSS) were used to identify microstructural differences. Spatial correlations between WM and GM alterations and neurotransmitter distributions were analyzed using JuSpace. Univariate and multivariate logistic regression models with bootstrap validation were employed to identify predictors of pain recurrence after MVD in 58 patients who underwent the surgery.ResultsCompared to HCs, patients with CTN exhibited widespread microstructural disruptions in both WM and GM. These alterations, characterized by neurite injury and elevated free water, were spatially correlated with distributions of key neurotransmitter systems including serotonergic, dopaminergic, and GABAergic pathways. Critically, preoperative free-water accumulation in a specific GM cluster was identified as an independent predictor of MVD failure (AUC = 0.847). This neuroimaging biomarker provided a specificity of 97.92% for predicting poor surgical outcome.ConclusionOur findings indicate neurite injury in both WM and GM of CTN patients that is linked to specific neurotransmitter systems. Critically, preoperative free-water accumulation in GM emerges as a specific neuroimaging biomarker for predicting MVD failure, potentially guiding personalized therapeutic strategies.
Post-traumatic headache phenotypic characteristics and treatment utilization.
Nabity PS, McGeary CA, Eapen BC … +12 more , Houle TT, Resick PA, Moring JC, Reed DE, Jaramillo CA, Penzien DB, Litz BT, Young-McCaughan S, Keane TM, Peterson AL, McGeary DD, Consortium to Alleviate PTSD
Cephalalgia · 2026 Mar · PMID 41789860 · Publisher ↗
BackgroundPost-traumatic headache (PTH) is typically described as migraine- or tension-type-like and treated based on presentation. However, the actual presentations of PTH are not well characterized. The aim of this stu...
BackgroundPost-traumatic headache (PTH) is typically described as migraine- or tension-type-like and treated based on presentation. However, the actual presentations of PTH are not well characterized. The aim of this study is to provide a phenotypic characterization of persistent PTH and co-occurring neurological symptoms from a previously completed clinical trial and characterize PTH treatment utilization.MethodsThis study is a secondary analysis of veterans ( = 193) recruited to participate in a randomized clinical trial of cognitive-behavioral therapy, cognitive processing therapy, or treatment as usual for PTH. Descriptive statistics were examined across characteristics of PTH, including age, gender, neurobehavioral symptoms, headache-related disability, pain characteristics, pain locations, accompanying symptoms, and aura symptoms and treatment utilization.ResultsThe median presentation of PTH in this study was a headache with severe pain, lasting about 4 h, and with about 13 headache episodes per month. About half the participants reported a pulsating quality and/or nausea that accompanied head pain. Most characteristics were uncorrelated to each other. The majority of participants used medication to treat persistent PTH. Neurostimulation was the most common non-pharmacological treatment.ConclusionsThe results of this study show that characteristics associated with migraine are more frequently reported with PTH. Correlations among the migraine characteristics were moderate overall, and there was notable variability among reported characteristics of PTH. Treatment utilization for PTH was not associated with current neurobehavioral symptoms and included both pharmacological and non-pharmacological options.Trial RegistrationClinicalTrials.gov Identifier: NCT02419131.
Where are the men? A systematic review of sex bias in human provocation models of migraine.
Pellesi L, Celik Z, Sari MF … +1 more , Waliszewska-Prosół M
Cephalalgia · 2026 Mar · PMID 41789859 · Publisher ↗
ObjectiveHuman provocation models are widely used to investigate migraine mechanisms and validate therapeutic targets. Despite well-known sex differences in migraine, concerns persist regarding sex representation and rep...
ObjectiveHuman provocation models are widely used to investigate migraine mechanisms and validate therapeutic targets. Despite well-known sex differences in migraine, concerns persist regarding sex representation and reporting in experimental research. This systematic review evaluated sex distribution, sex-specific analyses, and the consideration of female-specific biological factors in randomized, placebo-controlled migraine provocation studies.MethodsPubMed and Embase were systematically searched for randomized, placebo-controlled provocation studies in adults with migraine, following PRISMA 2020 guidelines. Data were extracted on participant sex distribution, sex-stratified outcome reporting, and consideration of female-specific variables, including menstrual cycle, hormonal contraception, and pregnancy status.ResultsFifty-eight studies published between 1972 and 2025 were included. Women represented 82% of participants, while men accounted for 18%. No study performed sex-stratified analyses of provoked headache or migraine outcomes. Sex was rarely discussed as a biological variable or limitation. Female-specific factors were largely overlooked, with menstrual cycle phase unreported in over 90% of studies and inconsistent reporting of hormonal contraception and pregnancy status.ConclusionsMigraine provocation studies show marked sex imbalance and a systematic lack of sex-disaggregated analyses. Although these models have demonstrated substantial translational relevance, particularly in supporting the development of anti-CGRP therapies, the absence of sex-disaggregated analyses and limited consideration of biological sex constrain the assessment of translational applicability across sexes.
Hypersensitivity to phosphodiesterase-5 inhibition in post-traumatic headache: Evidence of cGMP-dependent signaling.
Al-Khazali HM, Christensen RH, Melchior AG … +2 more , Ashina M, Ashina H
Cephalalgia · 2026 Mar · PMID 41789856 · Publisher ↗
BackgroundPhosphodiesterase-5 (PDE-5) inhibition increases intracellular cyclic guanosine monophosphate (cGMP), a second messenger molecule implicated in migraine pathogenesis. Given the clinical overlap between migraine...
BackgroundPhosphodiesterase-5 (PDE-5) inhibition increases intracellular cyclic guanosine monophosphate (cGMP), a second messenger molecule implicated in migraine pathogenesis. Given the clinical overlap between migraine and post-traumatic headache (PTH), we investigated whether pharmacologic elevation of cGMP induces migraine-like headache in individuals with persistent PTH.MethodsAdults with persistent PTH and no pre-trauma history of migraine were enrolled in a randomized, double-blind, placebo-controlled, 2-way crossover study. Each participant received a single 100-mg oral dose of sildenafil or placebo on two experimental days, separated by a 1-week washout interval. Headache outcomes were assessed using structured diaries over 12 h post-ingestion. The primary outcome was the incidence of migraine-like headache during this observation window. The secondary outcome was the baseline-corrected area under the curve (AUC) for headache intensity scores over the same period.ResultsA total of 21 participants (mean age 42.3 years; 57% female) with persistent PTH completed both experimental days. Migraine-like headache occurred in 15 participants (71%) after sildenafil administration, compared with 4 (19%) following placebo ( = 0.003). Headache intensity scores, as quantified by the AUC, were significantly higher after sildenafil than after placebo ( < 0.001).ConclusionsPharmacologic elevation of cGMP via PDE-5 inhibition elicits migraine-like headache in individuals with persistent PTH, despite no pre-trauma history of migraine. These findings provide the first experimental evidence linking intracellular cGMP-dependent signaling to headache provocation in this patient population. The observed response implicates cGMP-dependent mechanisms in the pathogenesis of PTH and identifies this pathway as a potential target for future therapeutic development. ClinicalTrials.gov (Identifier: NCT05669885).
Pan-American migraine prevalence: Findings from the Americas' migraine observatory study (AMIGOS).
Lisicki M, Muñoz-Cerón J, Sarmento EM … +14 more , Ribeiro AP, Dantas ACA, do Prado LL, de Nunes AK, Oliveira AB, Valença MM, de Andrade JR, Vélez-Jiménez K, Rodriguez-Leyva I, Giacomozzi ARE, Bancalari E, Juliet R, Schubaroff P, Peres MFP
Cephalalgia · 2026 Mar · PMID 41789851 · Publisher ↗
IntroductionAnalyzing the epidemiology of headache disorders is fundamental for understanding their behaviour and designing effective public health strategies. Epidemiologic studies conducted in individual countries ofte...
IntroductionAnalyzing the epidemiology of headache disorders is fundamental for understanding their behaviour and designing effective public health strategies. Epidemiologic studies conducted in individual countries often lack consistent methodologies, limiting broader interpretation. The Americas' Migraine Observatory Study (AMIGOS) is a Pan-American epidemiological study designed to evaluate the burden and access to treatment of migraine and other headache disorders across the Americas. Here, we present data on migraine prevalence and disability.ObjectivesTo describe and compare the prevalence and burden of migraine in the Americas at a specific time point using a unified sampling methodology. Additionally, to identify regional variations and potential factors contributing to differences in prevalence, providing a foundation for targeted public health strategies.Materials and MethodsData were collected online or via telephone from a sample representative of the demographic and social characteristics of each country, with a confidence level of 98% and a margin of error of 5%. We conducted both qualitative and quantitative research on key aspects of headaches among 16,202 individuals in 19 countries from Canada to Chile. Migraine diagnosis was made based on the ICHD-3 criteria.ResultsThe overall prevalence of migraine was 9.7% (13.2% among females, 6.5% among males). The highest prevalence was observed in Brazil (13.8%), Canada (13.2%), and the United States (12.7%), while the lowest prevalence was found in Bolivia (5.5%), Paraguay (7.1%), and Argentina (7.3%). Participants typically experienced 4 headache days per month, and chronic migraine prevalence was estimated at 1.3%. The migraine burden, as measured by Years Lived with Disability (YLDs), was highest in the United States.ConclusionThis is the first comprehensive Pan-American migraine epidemiological study. Findings indicate that migraine is highly prevalent in the Americas, with significant variations among different countries. Genetic, socioeconomic, and environmental factors may explain these observed differences.
Digital and virtual interventions for migraine: A systematic review of randomized controlled trials.
Tana C, Raffaelli B, Moffa L … +2 more , Götz J, Angerhöfer C
Cephalalgia · 2026 Mar · PMID 41776980 · Publisher ↗
BackgroundMigraine is a heterogeneous disorder marked by recurrent attacks and highly variable treatment outcomes, and it continues to impose a substantial personal and societal burden worldwide, underscoring the need fo...
BackgroundMigraine is a heterogeneous disorder marked by recurrent attacks and highly variable treatment outcomes, and it continues to impose a substantial personal and societal burden worldwide, underscoring the need for innovative and accessible therapeutic approaches. Although pharmacological options have expanded in recent years, many patients still experience incomplete response or limited access to specialist care. In this context, digital and virtual technologies-including mobile health applications, remote electrical neuromodulation (REN), virtual reality (VR), biofeedback, and internet-based behavioral therapy-have emerged as promising non-pharmacological tools to enhance self-management and improve clinical outcomes.MethodsWe conducted a systematic review of randomized and quasi-randomized controlled trials (RCTs) evaluating digital or virtual interventions for migraine prevention or acute treatment. Searches were performed in MEDLINE and Embase (via PubMed and Ovid) from database inception to September 4, 2025, following PRISMA guidelines (PROSPERO CRD420251078125). Eligible studies included adults with migraine diagnosed according to the International Classification of Headache Disorders (ICHD). Data were extracted on intervention type, outcomes, adherence, and adverse events. Risk of bias was assessed using the Cochrane RoB 2 tool.ResultsTwelve studies met inclusion criteria, mean age across studies ranged from 35 to 47 years and interventions included digital behavioral therapy (42%), REN (17%), VR (17%), biofeedback (17%), and telemedicine (8%). REN and VR-based interventions demonstrated significant reductions in pain intensity and acute medication use compared with controls (p < 0.01), while sEMG-digital biofeedback was associated with significant improvements in migraine-related disability (p = 0.03) and quality of life (p = 0.003). Behavioral and app-based interventions showed high feasibility but modest effects on headache frequency. No serious adverse events were reported. Risk of bias was judged to be low in only one study, with some concerns identified in two, while the remaining nine were considered at high risk of bias, largely driven by open-label study designs and incomplete outcome data.ConclusionsDigital and virtual therapeutics represent a rapidly evolving and clinically promising frontier in migraine care. REN and VR modalities yield reproducible short-term benefits, while digital behavioral tools enhance feasibility, patient engagement, and continuity of care. Future large-scale, blinded RCTs with standardized endpoints are warranted to confirm efficacy, establish long-term outcomes, and define the role of digital health within integrated, precision-based migraine management.Trial RegistrationPROSPERO, CRD420251078125.
Superior outcomes of candesartan over topiramate in the treatment of migraine: A comparative cohort study.
Oosterlee ASJC, van der Arend BWH, van Veelen N … +6 more , de Boer I, de Groot A, Geuns B, van Zwet E, Pelzer N, Terwindt GM
Cephalalgia · 2026 Mar · PMID 41776970 · Publisher ↗
BackgroundCandesartan and topiramate are both recommended for migraine prevention, but direct comparative data remain limited.AimTo evaluate and compare the tolerability and effectiveness of candesartan versus topiramate...
BackgroundCandesartan and topiramate are both recommended for migraine prevention, but direct comparative data remain limited.AimTo evaluate and compare the tolerability and effectiveness of candesartan versus topiramate for migraine prevention using systematically collected real-world data.MethodsThis longitudinal cohort study included patients treated at the Leiden Headache Center (LHC), with data collected using our validated E-headache diary. The 28 days preceding treatment initiation served as the baseline period. The primary endpoint was the proportion of participants that discontinued candesartan or topiramate within the 6-month follow-up. Secondary endpoints included ≥50%-response rate, change in monthly migraine days (MMD), headache days (MHD), acute medication days (MAMD), and HIT-6 from baseline to the last 28-day period with the highest achieved dosage of candesartan (ranging 4-32 mg daily) or topiramate (25-100 mg daily). Patients were assigned a propensity score based on baseline MHD, MMD, HADS, and number of failed preventive treatments. The primary analysis looked at discontinuation rates of candesartan and topiramate by using a Kaplan-Meier curve with Cox regression, adjusting for group differences by including the propensity score as a covariate. Secondary endpoint regressions were adjusted for propensity score and time to reach the highest dosage month. The primary and secondary outcomes were also investigated in a sensitivity analysis by applying optimal matching based on the propensity score.ResultsIn total 661 migraine participants were included. In the candesartan group less participants discontinued medication within 6-months follow-up compared to the topiramate group (29.7% versus 67.3%; HR 2.5 [95% CI: 1.9-3.3], p < 0.001). Candesartan had higher ≥50% response rates than topiramate (47% versus 29%, OR 0.6 [95% CI: 0.4-0.8], p = 0.004) and greater reduction in MHD (difference -1.1 days [95% CI: -2.2 to -0.01], p = 0.04). No differences were observed between treatments in reduction of MMD, MAMD, or HIT-6 scores after adjustment. These findings were confirmed in the sensitivity analysis using optimal matching.ConclusionsCandesartan demonstrates a favorable tolerability and effectiveness profile compared to topiramate. Therefore, (inter)national treatment guidelines for migraine prevention should be revised to spare patients from being prescribed medications that have a low tolerability profile, as demonstrated by this study.
PET and fMRI insights into experimentally-induced premonitory symptoms in migraine: A systematic review.
Christensen RH, Vashchenko N, Eigenbrodt AK … +3 more , Iljazi A, Ashina M, Ashina H
Cephalalgia · 2026 Mar · PMID 41776969 · Publisher ↗
BackgroundMigraine attacks are believed to unfold through discrete but interrelated phases, among which the premonitory phase has garnered increasing attention. This early phase, occurring hours to days before pain onset...
BackgroundMigraine attacks are believed to unfold through discrete but interrelated phases, among which the premonitory phase has garnered increasing attention. This early phase, occurring hours to days before pain onset, might reflect neurobiological processes that promote subsequent headache generation. Neuroimaging of experimentally induced attacks enables controlled investigation of the brain mechanisms underlying these early symptoms. This systematic review synthesizes and critically appraises current neuroimaging evidence on the experimentally induced premonitory phase in individuals with migraine.MethodsA systematic literature search of MEDLINE and Embase was performed from database inception through June 1, 2025, using predefined terms related to migraine and premonitory symptoms. Studies were eligible if they reported original neuroimaging findings on experimentally induced migraine attacks and specifically addressed the premonitory phase. Two independent reviewers screened all titles, abstracts, and full-text articles and extracted relevant data. Due to methodological heterogeneity in study design, a narrative synthesis was applied to summarize findings and assess the consistency of reported brain activity patterns across included studies.ResultsSeven studies met the inclusion criteria, all of which used glyceryl trinitrate to induce migraine attacks and applied either positron emission tomography or magnetic resonance imaging to assess brain changes. Across studies, reported alterations in cerebral perfusion and functional connectivity-used as surrogates for neural activity-during the premonitory phase were inconsistent and lacked replication. While some investigations suggested involvement of the thalamus and pons, these findings were derived exclusively from exploratory or uncorrected analyses. Hypothalamic involvement-a hypothesized migraine generator-was only sporadically observed, and reproducibility not investigated. The inconsistencies across studies likely reflect small sample sizes (ranging from 5 to 21 participants), suboptimal definitions of the premonitory phase, absence of appropriate controls, and unconventional use of neuroimaging statistics.ConclusionsNeuroimaging studies investigating the experimentally induced premonitory phase of migraine have largely produced inconsistent findings, likely due to small sample sizes, non-standardized symptom definitions, and exploratory imaging analyses lacking statistical rigor. Current evidence offers limited support for specific neural correlates of this phase, and its translatability to spontaneous migraine remains uncertain. To improve interpretability and clinical relevance, future research should prioritize standardized definitions, adequate control groups, and use of appropriate neuroimaging statistics.Trial RegistrationPROSPERO - Identifier: CRD42023415959.
Migraine as a primary care-sensitive condition: Building pathways to accessible care.
Oliveira WS, Dos Santos ERR, Peixoto PM … +4 more , Grassi V, Pedrosa MVS, Burstein R, Peres MFP
Cephalalgia · 2026 Feb · PMID 41773569 · Publisher ↗
ObjectiveTo evaluate the eligibility of migraine for classification as a Primary Care-Sensitive Condition (PCSC), and to discuss the public health, clinical, and economic implications of this designation in enhancing acc...
ObjectiveTo evaluate the eligibility of migraine for classification as a Primary Care-Sensitive Condition (PCSC), and to discuss the public health, clinical, and economic implications of this designation in enhancing access to care across different healthcare systems.BackgroundPrimary Care-Sensitive Conditions are health issues for which timely and effective management in primary care can reduce the need for hospitalization and specialist care. Although migraine is a leading cause of disability worldwide and frequently results in emergency visits and productivity loss, it remains underrecognized in PCSC classifications. This narrative review explores whether migraine fulfills the criteria for PCSC designation and how such recognition may contribute to improved outcomes and system efficiency, particularly in low- and middle-income countries.MethodsWe conducted a narrative review based on the five criteria established by Solberg and Weissman for defining PCSCs: (1) existence of evidence supporting primary care management; (2) public health relevance; (3) diagnostic clarity at the primary care level; (4) potential to avoid hospitalizations through early intervention; and (5) the possibility of hospitalization in severe cases. Global data on migraine epidemiology, diagnosis, treatment, and health system impact were analyzed in this framework.ResultsMigraine fulfills all five criteria for classification as a PCSC. It is highly prevalent and disabling, with substantial economic and social impacts. Diagnosis can be reliably established in primary care using the International Classification of Headache Disorders (ICHD-3) and screening tools like ID-Migraine™, while management is feasible through patient education and preventive strategies. Despite this, underdiagnosis, lack of provider training, and limited access to effective therapies - especially in resource-constrained settings - continue to drive unnecessary hospitalizations. Integrating migraine care into primary care has shown promising outcomes in pilot initiatives globally. Structured interventions, such as professional training and non-pharmacological strategies, have demonstrated cost-effectiveness and improved patient outcomes. Classifying migraine as a PCSC could guide policy reforms, enhance early intervention, and reduce reliance on emergency services.ConclusionMigraine meets criteria for a PCSC and recognizing that offers an opportunity to reframe policy, guide resource allocation and reduce avoidable hospitalizations decreasing the global burden of the disease by promoting timely diagnosis and improving equitable access to care. Strengthening primary care systems and embedding migraine management into routine practice are critical for achieving better health outcomes and more sustainable healthcare delivery.
A missing piece in the puzzle of chronic dizziness: Dysautonomia.
Masoud F, Blitshteyn S
Cephalalgia · 2026 Feb · PMID 41755715 · Publisher ↗
Abstract loading — click title to view on PubMed.
Classification of solitary pontine lesion-related trigeminal neuralgia.
Benoliel R
Cephalalgia · 2026 Feb · PMID 41736629 · Publisher ↗
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Recognizing solitary pontine lesion-related trigeminal neuralgia as a distinct entity: The need for an updated ICHD classification.
Di Stefano G, De Stefano G, Kristt MH … +2 more , Sekula RF, Truini A
Cephalalgia · 2026 Feb · PMID 41736624 · Publisher ↗
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Management of migraine in children and adolescents: A systematic review of guidelines and practice recommendations.
Hassan A, Elmazny A, Elgenidi A … +8 more , Dahshan A, Abu-Arafeh I, Magdy R, Tassorelli C, Prieto Peres MF, Puledda F, Ozge A, Hussein M
Cephalalgia · 2026 Feb · PMID 41699419 · Publisher ↗
BackgroundHigh-quality research studies on therapeutic approaches for migraine management in pediatrics are scarce. Therefore, we conducted a systematic review of current clinical practice guidelines for the diagnosis an...
BackgroundHigh-quality research studies on therapeutic approaches for migraine management in pediatrics are scarce. Therefore, we conducted a systematic review of current clinical practice guidelines for the diagnosis and management of migraine in children and adolescents to identify areas of consensus and disagreement, as well as critical gaps, paving the way for future updates and improvements.MethodsWe searched PubMed, WOS, and SCOPUS for guidelines published in the English language in the last 10 years focused on the diagnosis and management of migraine in children and adolescents.ResultsFollowing a systematic search, eight eligible guidelines were identified. These guidelines were authored by the American Academy of Neurology (AAN), the European Headache Federation/European Academy of Neurology (EHF/EAN), the International Headache Society (IHS), National Institute for Health and Care Excellence (NICE), the Danish Headache Society, and the German Migraine and Headache Society and the German Society of Neurology. There was a broad consensus on considering the International Classification of Headache Disorders-3rd edition as the diagnostic reference. As regards management, paracetamol and ibuprofen were considered first line in the acute management of migraine, with sumatriptan and zolmitriptan nasal sprays rated as second line. Injectable medications for acute management were overlooked in most guidelines. On the other hand, targeted age groups, dosing, and preventive treatment choices showed areas of variability. Various non-pharmacological measures gained attention in all guidelines. Notably, CGRP antagonists and non-invasive neuromodulation techniques were identified as major gaps.ConclusionThe current systematic review highlights areas of agreement and disagreement between existing guidelines on the management of childhood and adolescent migraine and emphasizes the current gaps and opportunities, thus offering a solid foundation for future studies and guidelines.
Differentiating episodic migraine from healthy controls using fractal dimension analysis of MRI cortical morphology.
Jao CW, Chen WH, Wu YT … +3 more , Yeh JH, Walsh V, Lau CI
Cephalalgia · 2026 Feb · PMID 41699416 · Publisher ↗
BackgroundThe diagnosis of migraine currently relies on clinical criteria based on expert consensus. Despite advances in neuroimaging, a sensitive and reliable morphological biomarker for episodic migraine (EM) remains e...
BackgroundThe diagnosis of migraine currently relies on clinical criteria based on expert consensus. Despite advances in neuroimaging, a sensitive and reliable morphological biomarker for episodic migraine (EM) remains elusive. Fractal dimension (FD), a novel morphometric metric, offers promise for detecting minor cortical alterations and may offer more precise quantification of cerebral folding than conventional cortical thickness (CT) analysis.MethodsThis study compared 50 EM patients and 50 matched healthy controls (HC) using both FD and CT analyses of magnetic resonance imaging (MRI) across hemispheres, cerebral lobes and 68 cortical regions. After evaluating data normality, group differences were assessed using false discovery rate-corrected -tests and validated through permutation testing. Unsupervised -means clustering was applied to evaluate classification performance.ResultsFD showed lower variance and narrower data distribution, revealing more significant cortical alterations than CT, especially in the temporal lobe. Notably, FD uniquely identified structural changes in the insula, a region implicated in high-frequency migraine attacks, where CT showed no differences. The FD-based classifier achieved 81.62% accuracy in distinguishing EM from HC, significantly outperforming CT (54.03%).ConclusionsFD-based analysis of structural MRI shows greater sensitivity than conventional method in detecting migraine-related cortical changes, effectively distinguishing EM from HC, even in low-frequency cases with minor alterations previously undetectable by MRI. This approach may hold promise for supporting clinical diagnosis and enabling future automated screening.
2025 Highlights in sex and gender differences in migraine.
de Boer I, Kopruszinski CM
Cephalalgia · 2026 Feb · PMID 41685540 · Publisher ↗
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Levels of migraine controls following International Headache Society (IHS) recommendations with eptinezumab: Effectiveness and tolerability in a 24-week, prospective multicenter study (the TACHIS study).
Iannone LF, Piella EM, Montisano DA … +39 more , Fasano C, Sebastianelli G, Coppola G, Ferrandi D, Lanni C, Prudenzano MP, de Tommaso M, Merlo P, De Cesaris F, Chiarugi A, Munafò A, Pistoia F, Ornello R, Doretti A, Grazzi L, Lo Castro F, De Icco R, Vaghi G, Avino G, Romozzi M, Calabresi P, Battistini S, Rufa A, Albanese M, Trimboli M, Carlucci G, Silvestro M, Russo A, Rainero I, Valente MR, Fofi L, Marcosano M, Geppetti P, Altamura C, Vernieri F, Tassorelli C, Sacco S, Guerzoni S, Italian Headache Registry (RICe) Study Group
Cephalalgia · 2026 Feb · PMID 41684106 · Publisher ↗
AimThe TACHIS study (from the ancient Greek adjective "" meaning rapid) aimed to evaluate eptinezumab effectiveness and tolerability in routine clinical practice, integrating patient-reported outcomes and use of Internat...
AimThe TACHIS study (from the ancient Greek adjective "" meaning rapid) aimed to evaluate eptinezumab effectiveness and tolerability in routine clinical practice, integrating patient-reported outcomes and use of International Headache Society (IHS)-endorsed categories of migraine control by treatment.BackgroundEptinezumab is the only intravenous anti-calcitonin gene related peptide (CGRP) monoclonal antibody (mAb) approved for migraine prevention. While its efficacy has been demonstrated in RCTs, real-world evidence in patients with prior preventive treatment failures is still limited.MethodsTACHIS is a prospective, multicenter, observational study conducted in Italy. Adults with episodic or chronic migraine initiating eptinezumab were followed for 24 weeks. Primary outcomes included change from baseline in monthly migraine days (MMDs) and ≥50% responder rate. Secondary outcomes included changes from baseline in acute medication use, Migraine Disability Assessment (MIDAS) and Headache Impact Test-6 (HIT-6) and IHS-defined residual burden categories. Logistic regression identified factors of response status.ResultsA total of 128 patients were included (82% female; 82% chronic migraine). MMDs decreased overall by 5.7 days (95% CI: -7.2 to -4.3) at week 12 and 6.9 (95% CI: -8.5 to -5.2) at week 24 (p < 0.001). A ≥ 50% response was achieved in 43.8% and 48.2% of patients at weeks 12 and 24, respectively. Over 40% of patients achieved optimal or modest migraine control. CGRP targeted therapy-naïve patients experienced significant greater benefit, though non-naïve patients also improved. Female sex and chronic migraine diagnosis were independently associated with response at 12 weeks. Adverse events were infrequent (4.7%) and mild, with no discontinuations due to safety concerns.ConclusionsEptinezumab demonstrated effectiveness and tolerability in a real-world population of patients with migraine and prior preventive treatment failures. The integration of migraine control metrics provides a comprehensive evaluation of therapeutic impact and supports eptinezumab use in routine care.Trial RegistrationThe TACHIS study was preregistered on clinicaltrial.gov, NCT06409845.
Cortical microstructure in persistent post-traumatic headache, migraine and healthy controls: A quantitative magnetic resonance imaging study.
Christensen RH, Al-Khazali HM, Ashina M … +1 more , Ashina H
Cephalalgia · 2026 Feb · PMID 41622925 · Publisher ↗
AimTo compare cortical microstructural features in people with persistent post-traumatic headache (PPTH), migraine and healthy controls (HCs) using quantitative magnetic resonance imaging (qMRI).MethodsThis cross-section...
AimTo compare cortical microstructural features in people with persistent post-traumatic headache (PPTH), migraine and healthy controls (HCs) using quantitative magnetic resonance imaging (qMRI).MethodsThis cross-sectional study included 103 participants with PPTH, 296 with migraine and 155 HCs. All underwent 3.0 Tesla qMRI using standardized sequences to generate quantitative T2 (qT2), quantitative T1 (qT1) and apparent diffusion coefficient (ADC) maps. Intracortical voxel values were projected onto the cortical surface for surface-based analysis. Group comparisons were adjusted for age and sex, with correction for multiple comparisons. Associations with clinical variables were explored in regions showing significant group differences.ResultsCompared with HCs, participants with PPTH showed elevated qT2 values in the left lateral occipital cortex ( = 0.0002). Compared with migraine, those with PPTH exhibited lower ADC values in the left superior frontal cortex ( = 0.0020). Relative to migraine with aura, additional reductions in qT1 and ADC values were found in the right middle and inferior temporal gyri (all < 0.01), and, relative to migraine without aura, lower ADC values were detected in the right middle temporal gyrus ( = 0.0002).ConclusionsCortical microstructural alterations in PPTH suggest underlying neurobiological processes distinct from both migraine and healthy adults. The findings support a pathophysiological model involving chronic low-grade neuroinflammation.
Severity of physical, emotional, and cognitive symptoms is associated with future persistence of acute post-traumatic headache attributed to mild traumatic brain injury.
Mao L, Li J, Dumkrieger G … +8 more , Smith DC, Leonard M, Chirravuri R, Wu T, Ross K, Starling A, Schwedt TJ, Chong CD
Cephalalgia · 2026 Feb · PMID 41622920 · Publisher ↗
AimPost-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) frequently co-occurs with other physical, cognitive, and emotional symptoms. This study assessed associations between PTH improvement and...
AimPost-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) frequently co-occurs with other physical, cognitive, and emotional symptoms. This study assessed associations between PTH improvement and these symptoms in individuals with acute headaches (APTH) and compared symptoms between those who had recently developed persistent PTH (PPTH) to those who had long-standing PPTH.MethodsThis study included 105 individuals with APTH (mean age = 43.4, SD = 15.8; 70 females, 35 males) and 46 individuals with PPTH (mean age = 38.2, SD = 10.9; 16 females, 30 males) with an average duration of 11.3 years from two prospective longitudinal studies. For those who had APTH, PTH improvement was assessed at three months post-enrollment using an electronic headache diary. Participants completed questionnaires evaluating physical (including headache symptoms, photosensitivity, hyperacusis, insomnia, autonomic symptoms, and disability), emotional (including depression, anxiety, pain catastrophizing, and post-traumatic stress disorder screening), and cognitive symptoms (including memory and attention). The APTH cohort completed questionnaires at baseline, follow-up #1 (three to four months from baseline), and follow-up #2 (six to seven months from baseline). Mixed Effects Models were used to analyze the temporal trend of symptoms among the APTH improved and non-improved groups.ResultsAmong the 105 individuals with APTH, 60 experienced PTH improvement and 45 did not. At baseline, compared to those who had PTH improvement, those who did not have PTH improvement had higher SCAT total scores and physical subscores, greater levels of hyperacusis, pain catastrophizing, anxiety and depression. At follow-up #1 (three to four months), these individuals continued to show more pronounced physical and emotional symptoms and worse cognitive function and insomnia. Most of these group differences persisted at follow-up #2 (six to seven months). Most symptoms showed progressive improvement over three months for individuals who had PTH improvement but not for those without PTH improvement. Furthermore, individuals with long-standing PPTH showed more severe insomnia, pain catastrophizing, and PTSD compared to those who had recently developed PPTH.ConclusionIndividuals with APTH who did not experience PTH improvement at three months had more severe physical, cognitive, and emotional symptoms at baseline compared to those who had PTH improvement. While most symptoms normalized in individuals with PTH improvement, symptoms overall persisted at three and at six months for those with PTH persistence. Individuals who had long-standing PPTH had more severe insomnia and more negative cognitive/emotional responses to pain compared to those who had recently developed PPTH.
Corneal confocal microscopy reveals nerve fiber alterations in migraine irrespective of subtype or visual hypersensitivity.
van Welie RF, van Welie FC, Dahan A … +3 more , Tavakoli M, van Velzen M, Terwindt GM
Cephalalgia · 2026 Jan · PMID 41603452 · Publisher ↗
AimCorneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging technique for evaluating the corneal microstructure, particularly the subepithelial nerve plexus. This dense, dynamic plexus contains small nerve...
AimCorneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging technique for evaluating the corneal microstructure, particularly the subepithelial nerve plexus. This dense, dynamic plexus contains small nerve fibers from the ophthalmic branch of the trigeminal nerve. This study aimed to evaluate corneal nerve alterations in individuals with migraine, including its subtypes and visual hypersensitivity (measured with the Leiden visual sensitivity scale (L-VISS), a validated nine-item questionnaire).MethodsIn total, 55 migraine participants were included, including 26 with episodic migraine and 29 with chronic migraine, as well as 55 age- and sex-matched controls. All subjects underwent CCM, and automated corneal nerve fiber density (ACNFD), length (ACNFL) and branch density (ACNBD) were assessed using the Rostock Cornea Module (Heidelberg Retina Tomograph III). Data were compared with age- and sex-matched healthy volunteers.ResultsReduced ACNFD, ACNFL and ACNBD were found in migraine participants compared to controls (all < 0.001). No difference was found between episodic migraine and chronic migraine, and regression analysis showed no significant effect for (inter)ictal visual hypersensitivity.ConclusionsThese findings support the utility of CCM as a sensitive tool for detecting nerve fiber pathology in migraine and highlight its potential in further understanding migraine pathophysiology. The observed nerve changes, present irrespective of migraine frequency status or visual hypersensitivity, suggest a broader role for peripheral nerve dysfunction in migraine beyond sensory hypersensitivity symptoms.
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