Cephalalgia最新文献

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.

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.

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 (P = 0.003). Headache intensity scores, as quantified by the AUC, were significantly higher after sildenafil than after placebo (P < 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.Trial registration: ClinicalTrials.gov (Identifier: NCT05669885).

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.

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.

BackgroundResidential deprivation is a long-established risk factor for poor health outcomes including migraine, depression and anxiety that are significant public health problems in Sweden and globally. Yet the relationship between residential deprivation and patterns of comorbidity among these three conditions is less understood. We aimed to estimate the magnitude and determinants of comorbid depression or anxiety among migraine patients in Sweden including the relationship between residential deprivation and comorbidity prevalence.MethodsA nationwide register-based cross-sectional study was conducted of persons aged ten years or older in Sweden in 2015-2023. Comorbid depression or anxiety was defined as any depression or anxiety diagnosis or treatment during the migraine-exposed period (from three months before until three months after the first and last recorded migraine exposure in the study period). Small-area deprivation was based on an Index for Multiple Deprivation in Sweden (IMDIS) applied to 5984 small geographic areas. Prevalence ratios (PR) estimated the association between comorbidity and small-area deprivation adjusted for other covariates (age, sex, area of residence, birthplace) using Poisson regression models with robust error variance. We compared sick leave utilization (over fourteen days) for any reason in the migraine-affected years among migraine patients with or without comorbidity.ResultsThere were 372,926 migraine patients in the study, and 35.7% (n = 133,219) had comorbid depression or anxiety. There was higher comorbidity prevalence among migraine patients in the most versus the least deprived areas (PR: 1.18, 95% CI: 1.17-1.20). Although the data have limitations, we found that one-third (31.9%) of migraine patients took sick leave (over fourteen days) for any reason during the migraine-exposed years, which rose to 50.9% among migraine patients with comorbid depression or anxiety.ConclusionsMore than one-third of migraine patients had comorbid depression or anxiety with higher prevalence of comorbidity in the most deprived areas. Common comorbid depression or anxiety among migraine patients underscores the need to consider all three conditions in clinical encounters especially for residents of more deprived residential areas.

AimHeadaches are a common complaint among children and adolescents, with prevalence rising over the past decades. This study aimed to retrospectively analyze all emergency consultations presenting with headache as the primary symptom at a Level 1 Pediatric Emergency Department (PED) over 7 years, encompassing the COVID-19 pandemic.MethodsAll electronic health records (EHR) of patients aged 2 to 18 years who presented to the PED with non-traumatic headache between January 2018 and December 2024 were retrospectively reviewed. In addition to primary headache diagnoses, conditions commonly associated with headaches were included to identify relevant emergency department cases. Statistical analyses included the chi-square test or Fishers exact test, calculation of Odds Ratios and ANOVA, significant at p < 0.05.ResultsA total of 1278 children and adolescents (564 males, 44.1%; 714 females, 55.9%) with acute headaches visited our PED 1447 times. Of those patients, 668 (46.2%) were diagnosed with primary headaches, 677 (46.8%) with secondary headaches, five (0.3%) with cranial neuropathies and facial pain, and 97 (6.7%) had headaches that could not be clearly classified. Acute headache cases accounted for 3.6% of all PED visits. The largest relative increase compared to the baseline year (2018) was observed in 2023 (+36.2%). Immediate neuroimaging was performed in 19.1% of cases. Red flag symptoms, including systemic symptoms with fever, neoplasm in history, progressive headache, headache associated with severe vomiting and papilledema, were significantly associated with abnormal brain MRI findings. Pharmacological analgesic therapy was administered in 31.9% of cases, and pain assessment was recorded in 46.1% of cases.ConclusionVisits to the PED for headaches are increasing, particularly following the COVID-19 pandemic. The high prevalence of primary headache diagnoses, combined with still insufficient pain management, highlights the need for enhanced education for both pediatricians and parents. For secondary headaches, a thorough headache history focusing on all red flag symptoms, along with a detailed neurological examination assessing clinical features, should form the basis for deciding whether immediate neuroimaging is necessary.Trial registrationThe study has also been officially registered on the public webpage of the German Clinical Trials Registry (GermanCTR) at https://drks.de/search/en/trial/DRKS00036917 (Clinical Trial Number/ DRKS-ID: DRKS00036917, Date of Registration: 2025-05-16, last update: 2025-07-28, registration type: retrospective, status: recruiting complete, study complete).

AimSeveral studies have reported a higher prevalence of migraine in patients with multiple sclerosis (MS) than in healthy controls (HCs). The aim of this study was to elucidate the headache prevalence in patients with MS or other neuroimmunological disorders, as well as to investigate the associations between headache characteristics and disease activity.MethodsIn this multicenter study in Japan, a headache questionnaire was distributed to patients with MS (n = 338), aquaporin-4 IgG-positive neuromyelitis optica spectrum disorder (NMOSD; n = 106), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD; n = 51) or acetylcholine receptor antibody-positive myasthenia gravis (MG; n = 104), and healthy controls (HCs; n = 407). We included only participants aged 18-65 years in this study. The questionnaire responses were classified according to the International Classification of Headache Disorders, 3rd edition. The questionnaire was designed to systematically capture headache characteristics based on established diagnostic criteria.ResultsIn total, any type of headache was found for 54.1% in MS, 63.2% in NMOSD, 43.1% in MOGAD, 43.3% in MG and 43.5% in HCs. After Holm-Bonferroni correction for comparisons among the five groups, the MS (p = 0.015) and NMOSD (p < 0.001) groups had significantly higher odds of any headache compared to the HC group. No difference was observed for migraine (MS 16.0%, NMOSD 16.0%, MOGAD 9.8%, MG 12.5%, HCs 17.0%). In contrast, patients with MS (24.0%) and NMOSD (37.7%) showed a significantly higher frequency of tension-type headache (TTH) than HCs (16.7%) even after adjusting for age and sex. Neither disease activity nor disease-modifying therapy displayed any association with headache severity in patients with MS, NMOSD, or MOGAD.ConclusionsOur study showed no increased prevalence of migraine in MS and other neuroimmunological disorders, whereas TTH comorbidity was higher in MS and NMOSD than in controls.

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.