Cephalalgia最新文献

BackgroundMigraine and gynecological conditions, such as endometriosis (EDM) and polycystic ovarian syndrome (PCOS), are highly prevalent among females and appear to influence each other, with a potential shared pathophysiological mechanism. Therefore, this study aims to provide a comprehensive summary of the current evidence regarding the relationship between migraine and EDM/PCOS from a clinical perspective.MethodsA systematic review was conducted using four databases (MEDLINE(Pubmed), EMBASE (Elsevier), Web of Science and Cochrane Library) along with searches in the grey literature. The protocol was registered prospectively on the PROSPERO platform (CRD42024628010). The primary search was performed on 4 December 2024. Eligible studies included observational studies that compared two or more groups of females with migraine, EDM and/or PCOS diagnosis. The modified Newcastle-Ottawa Scale was used to assess the quality of the included studies. Data extraction was performed and results systematically analyzed.ResultsFrom an initial 408 identified studies, a final selection of 15 was analyzed (14 focused on EDM and 1 on PCOS) with a total of 289,519 individuals included. All selected studies achieved a score of 6 or higher on the mNOS. When comparing females with and without EDM, the prevalence of migraine reached up to 44.7%, with females affected with EDM having up to a five-fold increased risk of developing migraine (adjusted odds ratio = 5.35, 95% confidence interval = 2.11-16.4). When comparing females with and without migraine, a higher prevalence and risk of EDM was observed, with rates reaching 53.4% and an adjusted odds ratio up to 10.5 (95% confidence interval = 2.2-51.4). Mixed findings were found regarding the influence of EDM on migraine characteristics, as well as the impact of migraine in EDM-related symptoms and disease severity. Females with migraine and EDM exhibited higher scores in disability assessment tools (Headache Impact Test-6, 30-item Endometriosis Health Profile), suggesting a greater disease burden. Due to the limited data, no conclusions could be drawn regarding a link between PCOS and migraine.ConclusionsAlthough further high-quality research is required to better understand the underlying mechanisms linking migraine, EDM and PCOS, the current evidence supports a significant association between migraine and endometriosis.Trial Registration: PROSPERO Registration ID: CRD42024628010.

BackgroundDifferent parameters are currently used to evaluate migraine frequency and disability. We aimed to formulate a composite scale including the most relevant clinical measures to better evaluate the burden of migraine.MethodsTo create the composite four dimensions 4D migraine scale, we selected the most commonly used outcome measures: monthly migraine days (MMDs), number of monthly acute medications (MAMs), pain intensity (by Numerical Rating Score, NRS) and Migraine Disability Assessment (MIDAS) Score. Each parameter was categorized in different levels: five for MMDs, seven for MAMs, five for NRS and six for MIDAS to cover the entire empirical range of each variable. First, the relative weight of each level per parameter was rated by 197 migraine patients and 118 headache experts using Conjoint Analysis. Secondly, we applied the 4D migraine score to a sample of patients treated with galcanezumab. We assessed its concurrent validity for the scale's single parameters and the Head Impact Test HIT-6, an external patient-reported outcome measure.ResultsThere was a substantial agreement between clinicians and patients about the weight of each parameter in terms of Relative Importance (RI). For both categories, MMDs were the most relevant attribute (RI: 34% for clinicians, 32% for patients) and pain intensity NRS the least important (RI: 14% vs 13%). Though marginally, MIDAS was more important than MAMs for patients (29% vs. 26%), while for clinicians the relevance of these two attributes was almost equal (26% and 27%). In terms of the utility assigned to each level, strong agreement was confirmed between clinicians and patients. According to the utilities implicitly attributed by participants to the chosen representative levels of the four parameters, four different statistical models were derived, allowing to compute utilities from all possible values of MMDs, MAMs, NRS and MIDAS and finally a unique 4D migraine score for every possible patient, ranging from 0 (without migraine) to 100 (with the most severe migraine). The 4D score was valid in terms of sensitivity to changes and showed concurrent validity with respect to HIT-6.ConclusionThe 4D migraine scale, based on the preference weights of both clinicians and patients, could be useful to fully quantify the migraine burden and the efficacy of a treatment.

BackgroundThe Pan-European Real Life (PEARL) Phase 4 study evaluated real-world effectiveness and safety of fremanezumab for episodic migraine (EM) and chronic migraine (CM) prevention. This post-hoc analysis evaluated the effectiveness of fremanezumab in participants with three or more non-migraine-specific preventive treatment failures, including onabotulinumtoxinA.MethodsBaseline daily headache diary data were compared with diary data following fremanezumab initiation. Primary endpoint: proportion of participants with ≥50% reduction in monthly migraine days (MMD) during the six months after fremanezumab initiation. Secondary endpoints included mean change from baseline in MMD at Months 1-12 and health-related quality of life. Safety was assessed through adverse events.ResultsOf 451 participants, 398 with three or more previous preventive treatment failures were included in the effectiveness analyses (EM, 40.2%; CM, 59.8%). Of the 290 participants with data available, the 50% responder rate was 53.8% (EM, 67.0%; CM, 46.5%) during the six months after fremanezumab initiation. The safety profile was consistent with previous findings.ConclusionsThis post-hoc analysis supports the effectiveness and safety of fremanezumab for migraine prevention in patients with three or more prior preventive treatment failures. These findings are consistent with those from a randomized controlled trial (RCT) in a similar population, illustrating the transferability of RCT data to real-world clinical practice.Trial registrationencepp.eu: EUPAS35111.

BackgroundNeurovascular coupling (NVC) reflects the interaction between cerebral blood flow (CBF) and functional activity. However, the relationship between NVC and migraine chronification remains unclear. This study investigated the state of NVC in migraine patients and evaluated its potential as an imaging feature for migraine chronification using arterial spin labeling (ASL) combined with resting-state functional magnetic resonance imaging (rs-fMRI).MethodsThis was a cross-sectional study. Thirty-nine episodic migraine (EM), 61 chronic migraine (CM) patients (25 with medication overuse headache, MOH) and 42 healthy controls (HCs) were recruited in the same period. Imaging data were acquired using a 3.0 T MRI. Regional homogeneity (ReHo) represented functional activity, whereas CBF was quantified via ASL. Correlation coefficient between CBF and ReHo values of each participant in voxel level represented the whole-brain NVC status, whereas the CBF/ReHo ratio represented regional NVC status. Correlations between NVC metrics and clinical characteristics were analyzed in CM patients. Exploratory mediation analysis was conducted to identify mediators between NVC alterations and the clinical characteristics of CM patients. Finally, receiver operating characteristic (ROC) curve was generated to evaluate the diagnostic performance of NVC metrics for migraine chronification.ResultsCompared to HCs, both EM and CM patients presented significantly reduced whole-brain CBF-ReHo coupling. Compared to EM patients, CM patients presented a decreased CBF/ReHo ratio in the right precuneus. Correlation analysis revealed that z value of the CBF/ReHo ratio in the right precuneus was negatively correlated with both HIT-6 score and PHQ-9 score; HIT-6 score was positively correlated with PHQ-9 score in CM group. Exploratory mediation analysis indicated that depression mediated the relationship between abnormal NVC and clinical characteristics in CM patients. Finally, ROC curve indicated that the CBF/ReHo ratio in the right precuneus (AUC = 0.75) exhibited high sensitivity and specificity in distinguishing CM from EM patients.ConclusionAbnormal NVC in the precuneus was involved in migraine chronification, with depression potentially serving as a mediator in this process. NVC metric may serve as an imaging feature for migraine chronification in the future.

BackgroundMigraine is a highly prevalent neurological disorder with many treatment options, both pharmacological and non-pharmacological. Artificial intelligence (AI) has great potential to optimize treatment selection strategies for individual patients. This review provides an overview of AI models and the techniques used to predict migraine treatment outcomes.MethodsWe conducted a literature search in PubMed and examined studies that reported employing AI models to predict migraine preventive and acute treatment outcomes. We also explored incorporating AI/machine learning to enhance personalized migraine treatment strategies, including forecasting migraine attacks. Additionally, we summarized future research directions, including incorporating multimodality data, using AI frameworks for the discovery of novel treatment targets, and advancing the field with innovative AI techniques such as digital twins, conversational AI and virtual AI agents.ResultsStudies have employed ML and deep learning on a combination of clinical features and imaging data to predict acute or preventive migraine treatment outcomes with reported success. Continued model optimization, validation, and prospective assessment of the clinical utility of deploying ML models in real-world settings are crucial.ConclusionsWhile AI has demonstrated success in predicting migraine treatment responses, future research incorporating novel AI techniques and diverse data sources could pave the way to advance personalized migraine treatment.

Migraine is a common neurological disorder that predominantly affects women during their reproductive years, presenting unique challenges in the context of pregnancy, breastfeeding, and pregnancy planning. In the present review, we intend to summarize those challenges and propose possible solutions. Women with migraine, particularly those with aura, face an increased risk of pregnancy-related complications, including preeclampsia, stroke, and preterm birth, highlighting the need for careful monitoring throughout gestation. When migraine persists during pregnancy, management should prioritize non-pharmacological approaches, with a strong emphasis on lifestyle modifications and behavioral therapies. In some settings, non-invasive neuromodulation may also be a reasonable option. However, disabling migraine should not be left untreated and may require pharmacological management. Pharmacological treatments should be chosen primarily based on safety considerations, as many migraine medications are not suitable for use during pregnancy. Given the limited safety data available for several treatments, shared decision-making between patients and healthcare providers is essential. During breastfeeding, medication selection should focus on minimizing infant exposure while ensuring effective migraine control for the mother. In women of childbearing potential, caution is needed when prescribing certain migraine treatments, as unplanned pregnancies can occur. Special considerations should also be given to those requiring preventive treatment while planning pregnancy. Given the complexities of migraine management in this population, an individualized approach is crucial to balancing maternal well-being with fetal and infant safety.

AimThis study aimed to evaluate the efficacy and tolerability of rimegepant for the prevention of episodic migraine in participants with a documented history of inadequate response to 2-4 categories of traditional oral preventive medication (OPM).MethodsThis multinational phase 4 trial consisted of an untreated 28-day observational phase (OP) and a 12-week double-blind treatment (DBT) phase. Participants with 4-14 monthly migraine days (MMDs), <15 monthly headache days (<7 non-migraine) and documented previous inadequate response to 2-4 traditional OPM categories were enrolled. Participants were randomized to rimegepant 75 mg orally disintegrating tablet (ODT) or placebo every other day (EOD). The primary endpoint was mean change from the OP in MMDs through the 12-week DBT phase. Key secondary endpoints were tested hierarchically to control type I errors. Tolerance and safety were assessed throughout the DBT phase.ResultsIn total, 328 participants received rimegepant and 324 received placebo. The most common OPM categories with prior inadequate response were anticonvulsants (61%), beta-blockers (56%) and amitriptyline (51%). The mean ± SD number of MMDs in the OP was 8.4 ± 2.4 and 8.3 ± 2.3, respectively, in the rimegepant (n = 324) and placebo (n = 319) groups. Across the DBT phase, participants who received rimegepant had a significantly larger mean change from the OP in MMDs than those who received placebo (-2.1 vs. -0.5 days; difference = -1.6 days; 95% confidence interval (CI) = -2.1 to -1.2; p < 0.0001). All key secondary endpoints favored rimegepant: (i) percentage of participants with ≥50% reduction from the OP in MMDs with moderate or severe pain intensity across the DBT phase (difference: 20.1%; 95% CI = 13.7 to 26.5; p < 0.0001); (ii) mean change from the OP in MMDs in the first month of the DBT phase (difference: -1.7 days; 95% CI = -2.3 to -1.2; p < 0.0001); (iii) mean change from the OP in MMDs in the last month of the DBT phase (difference: -1.4 days; 95% CI = -2.1 to -0.8; p < 0.0001); (iv) mean change from baseline in Migraine-Specific Quality-of-Life Questionnaire v2.1 Restrictive Role Function domain score at week 12 of the DBT phase (difference: 6.6 points; 95% CI = 3.6 to 9.5; p < 0.0001); and (v) mean change from baseline in Migraine Interictal Burden Scale score at week 12 of the DBT phase (difference: -0.9 points; 95% CI = -1.4 to -0.4; p = 0.0006). Rimegepant was well tolerated with a safety profile not notably different from placebo.ConclusionsRimegepant 75 mg ODT EOD is efficacious and well tolerated for the prevention of episodic migraine in participants with a documented history of inadequate response to 2-4 categories of traditional OPM.Trial RegistrationClinicalTrials.gov, NCT05518123 (https://clinicaltrials.gov/study/NCT05518123).

BackgroundCalcitonin gene-related peptide (CGRP) has a causative role in migraine pathogenesis but its effects on trigeminal afferents are still unclear. Corticosteroids represent a very useful tool in headache therapy with an unknown mechanism of action. Despite the widespread effects of corticosteroids on gene transcription, whether they regulate CGRP expression within the trigeminovascular system remains to be investigated.MethodsThe effects of dexamethasone on expression of CGRP and its receptor subunits receptor activity-modifying protein (RAMP1) and calcitonin receptor-like receptor (CLR) have been evaluated in rat thyroid parafollicular CA77 and human neuroblastoma SHSY-5Y cell cultures, as well as in isolated human peripheral blood mononuclear cells. The effects of dexamethasone on the rat and human CGRP promoter were also evaluated. In vivo, rats and mice were treated with betamethasone (320 µg/kg for 10 days) to investigate whether the drug altered the expression of CGRP, RAMP1 and CLR in the trigeminal ganglion (TG). We also evaluated the effect of betamethasone on CGRP mRNA stability and release from the mouse TG, as well as on mouse spontaneous or nitroglycerin-induced cephalic allodynia.ResultsWe report that dexamethasone triggered transcriptional activation of the rat and human CGRP gene, also increasing transcript levels of RAMP1 but not of CLR in cultured cells. These effects were paralleled in the TG of rats and mice challenged with betamethasone, with mice also showing increased expression levels of CLR. Of note, although a 13-fold increase of the CGRP releasable pool occurred in the TG of betamethasone-treated mice, the animals were not sensitized to cephalic allodynia.ConclusionsIn keeping with the emerging immunosuppressing effects of CGRP, corticosteroids increase its expression in rat and human cell lines, as well as in rodent TG. Evidence that a substantial increase of releasable CGRP in the TG does not reduce orofacial pain thresholds suggests that basal release of endogenous CGRP differs from its exogenous administration in terms of trigeminal afferent sensitization.