Background Many guidelines list migraine with aura (MwA) as a contraindication to estrogen-containing combined hormonal contraceptives (CHCs) due to vascular risks. However, current evidence is based on small sample studies with potential influence by confounding factors. Additionally, few studies have examined the vascular risk associated with modern CHCs with lower dose estrogen, particularly in relation to aura status. The present study aims to investigate the vascular risk of modern CHCs in women with migraine with and without aura. Methods We used a de-identified electronic medical record database with 120 million patients across multiple health systems in the United States of America. We included female patients aged 18–45 years who received a migraine diagnosis code, had at least three office visits within three years, and were prescribed at least one migraine-specific medication within 6 months following the first outpatient visit. All data after 2010 were included. Patients with prior cardiovascular events were excluded. Our composite endpoint consisted of acute ischemic stroke, acute myocardial infarction, deep vein thrombosis/pulmonary embolism and intravenous thrombolytic administration. We stratified our analysis according to CHC exposure and aura status and compared the incidence of the endpoint with high-dimensional propensity score-matching between CHC users and non-users in (i) the overall cohort, (ii) MwA and (iii) migraine without aura (MwoA); between MwA and MwoA in (iv) patients prescribed CHCs; and in (v) those without CHC prescriptions. Results We included 5535 patients who received CHC prescriptions and 21,520 who did not. 114 (2.06%) of CHC users and 547 (2.54%) of CHC non-users had at least one vascular event. With propensity score-matched comparison, the composite endpoint did not significantly differ between CHC and non-CHC in the overall migraine group, those with MwA and the MwoA group. In those prescribed CHC, MwA and MwoA did not differ in all the outcomes. For CHC non-users, MwA was associated with a higher incidence of acute ischemic stroke (hazard ratio = 2.45; 95% confidence interval = 1.58–3.78; p < 0.001; n = 6201 in each group) and the composite endpoint (hazard ratio = 1.34; 95% confidence interval = 1.08–1.67; p = 0.008). Conclusions Our real-world study showed that exposure to modern CHC was not associated with a significant increase in vascular risk in women aged 18–45 years with migraine, MwA or MwoA who have no prior cardiovascular events. However, in those who never received CHC, MwA was associated with higher vascular risks compared to MwoA. While limitations exist using large scale electronic medical record databases for analysis, our results suggest that carefully designed prospective studies should be conducted to reassess the vascular risk associated with CHC use in women with migraine, especially MwA.
The promise of artificial intelligence and machine learning for migraine treatment outcome prediction: A narrative review
Background Migraine 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. Methods We 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. Results Studies 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. Conclusions While 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.
Evaluation of Brain Stiffness in Patients Undergoing Carotid Angioplasty and Stenting Using Magnetic Resonance Elastography
ABSTRACTBackgroundPercutaneous transluminal angioplasty and stenting (PTAS) in patients with carotid stenosis may have potential effects on brain parenchyma. However, current studies on parenchymal changes are scarce due to the need for advanced imaging modalities. Consequently, the alterations in brain parenchyma following PTAS remain an unsolved issue.PurposeTo investigate changes to the brain parenchyma using magnetic resonance elastography (MRE).Study TypeProspective.Population13 patients (6 women and 7 men; 39 MRI imaging sessions) with severe unilateral carotid stenosis patients indicated for PTAS were recruited between 2021 and 2024.Field Strength/SequenceNoncontrast MRI sequences including MRE (spin echo) were acquired using 3 T scanners.AssessmentAll patients underwent MRE before (preprocedural), within 24 h (early postprocedural) and 3 months after (delayed postprocedural) PTAS. Preprocedural and delayed postprocedural ultrasonographic peak systolic velocity (PSV) was recorded. MRE stiffness and damping ratio were evaluated via neural network inversion of the whole brain, in 14 gray matter (GM) and 12 white matter (WM) regions.Statistical TestsStiffness and damping ratio differences between each pair of MR sessions for each subject were identified by paired sample t tests. The correlations of stiffness and damping ratio with stenosis grade and ultrasonographic PSV dynamics were evaluated by Pearson correlation coefficients. The statistical significance was defined as p < 0.05.ResultsThe stiffness of lesion side insula, deep GM, and deep WM increased significantly from preprocedural to delayed postprocedural MRE. Increasing deep GM stiffness on the lesion side was positively correlated with the DSA stenosis grade significantly (r = 0.609). The lesion side insula stiffness increments were positively correlated with PSV decrements significantly (r = 0.664).Data ConclusionRegional brain stiffness increased 3 months after PTAS. Lesion side stiffness was positively correlated with stenosis grades in deep GM and PSV decrements in the insula.Evidence Level2.Technical EfficacyStage 2.
Evidence-based guidelines for the pharmacological treatment of migraine, summary version
We here present evidence-based guidelines for the pharmacological treatment of migraine. These guidelines, created by the Italian Society for the Study of Headache and the International Headache Society, aim to offer clear, actionable recommendations to healthcare professionals. They incorporate evidence-based recommendations from randomized controlled trials and expert-based opinions. The guidelines follow the GRADE approach for assessing the quality of evidence. The guideline development involved a systematic review of literature across multiple databases, adherence to Cochrane review methods, and a structured framework for data extraction and interpretation. Although the guidelines provide a robust foundation for migraine treatment, they also highlight gaps in current research, such as the paucity of head-to-head drug comparisons and the need for long-term outcome studies. These guidelines serve as a resource to standardize migraine treatment and promote high-quality care across different healthcare settings.
Evidence-based guidelines for the pharmacological treatment of migraine
We here present evidence-based guidelines for the pharmacological treatment of migraine. These guidelines, created by the Italian Society for the Study of Headache and the International Headache Society, aim to offer clear, actionable recommendations to healthcare professionals. They incorporate evidence-based recommendations from randomized controlled trials and expert-based opinions. The guidelines follow the Grading of Recommendations, Assessment, Development and Evaluation approach for assessing the quality of evidence. The guideline development involved a systematic review of literature across multiple databases, adherence to Cochrane review methods, and a structured framework for data extraction and interpretation. Although the guidelines provide a robust foundation for migraine treatment, they also highlight gaps in current research, such as the paucity of head-to-head drug comparisons and the need for long-term outcome studies. These guidelines serve as a resource to standardize migraine treatment and promote high-quality care across different healthcare settings.
Estrogen Exposure from Modern Hormonal Contraceptives and Vascular Risk in Women with Migraine: A Nationwide Electronic Health Record Database Study (S35.002)
Higher Atrial Fibrillation Probability and Delta Age Computed by Artificial Intelligence-ECG Models Predict More Cardiovascular Events in Patients with Migraine (P4-12.001)
Abstract Objective The objective was to determine if migraine is independently associated with a greater odds of spontaneous coronary artery dissection (SCAD) in a case–control study. Background There is growing evidence that migraine is associated with SCAD, a non‐atherosclerotic, non‐traumatic cause of myocardial infarction. However, few studies have examined the independent association between migraine and SCAD. Methods A total of 1295 SCAD cases and 1291 (1:1) age, sex, and race/ethnicity matched controls presenting to the Boston, Massachusetts area, using the International Classification of Diseases ninth revision and 10th revision codes from our Research Patient Data Registry, were identified between the years 1990 and 2022. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. For mediation, total effects, natural direct, and indirect effects were estimated using causal inference. Receiver operating characteristic (ROC) curves and area under the curve (AUC) was used to determine predictive power. Statistical significance was defined as p < 0.05. Results Adjusting for age, sex, and race/ethnicity, the data demonstrated an almost two‐fold increased odds of SCAD in patients with migraine (aOR 1.96, 95% CI 1.48–2.6; p < 0.001). There was no effect of aura phenotype on this association. Fibromuscular dysplasia (FMD) was found only in patients with SCAD ( n = 133). After accounting for vascular risk factors, there was no longer an independent association between migraine and SCAD (aOR 0.90, 95% CI 0.63–1.29; p = 0.568). Using a model that adjusted for only demographic variables produced a ROC curve with the lowest predictive power (AUC 0.55) for SCAD, while the vascular risk factor‐adjusted model had a higher predictive power (AUC 0.83). Hypertension appeared to mediate some of the effect of migraine on SCAD (proportion of effect mediated 0.70). FMD was highly associated with an increased risk of SCAD. There remained no independent association between SCAD and migraine when FMD was included in the model. Conclusions The migraine–SCAD association can be partially attributed to the connection between migraine and vascular comorbidities including hypertension and FMD.
Abstract WP328: Higher Artificial Intelligence (AI)-ECG Atrial Fibrillation Prediction Model Output and Delta Age Computed from AI-ECG are Associated with Adverse Vascular Outcomes in Patients with Migraine
Migraine with aura(MwA) is associated with an increased risk of stroke and adverse vascular outcomes compared to those with migraine without aura (MwoA). AI-ECG prediction models developed at our institution can evaluate the probability of atrial fibrillation (AF) and estimate a patient’s age based on a normal sinus rhythm (NSR) ECG. Delta age, AI-ECG estimated age minus chronological age, indicates endothelial dysfunction and is associated with cardiovascular mortality. We aim to assess how AI-ECG prediction model outputs, specifically the AF probability and delta age, are associated with adverse vascular outcomes in patients with migraine. Adult patients diagnosed with MwA and MwoA from 2000-2020 with at least one digital, standard 12-lead ECG were identified. The first ECG that showed NSR is used as the index ECG. Patients with any adverse vascular outcomes before the index ECG were excluded. Adverse vascular outcomes used as endpoints include acute ischemic stroke, acute myocardial infarction, deep vein thrombosis/pulmonary embolism, AF, and carotid artery dissection. A total of 31301 patients (13783 MwA, 17518 MwoA) were included in our analysis. The mean age at the time of the index ECG was 44.3 (14.5), and the average follow-up time was 71.6 (69.8) months. Based on the index ECG, the mean AF probability was significantly higher in MwA compared to MwoA (2.39 vs 2.06, p< 0.001), while the delta age was lower in MwA compared to MwoA (3.7 vs 4.2, p <.001). The prevalences of all vascular outcomes are summarized in Table 1. Multivariate Cox regression models showed that a higher AF prediction model output (every 10% increase), as well as a higher delta age (every 10-year increase), are associated with an increased risk of composite vascular outcomes (HR1.20, 95%CI 1.17-1.23, p<.001, and HR1.19, 95%CI 1.14-1.23, p < .001) [Table 2]. The Kaplan-Meier curve of adverse vascular outcome-free survival by AF prediction model output, using 1% as the cutoff (HR 1.49, 95% CI 1.41, 1.57, p<.001), and by delta age, using 2-year as the cutoff (HR 1.14, 95% CI 1.08, 1.21, p <. 001) are presented in Figure 1. Having aura, older age, male, coronary artery disease, congestive heart failure, diabetes, hypertension, and tobacco use were also associated with a higher risk of adverse vascular outcomes. Our results demonstrated the potential of using AI-ECG AF prediction model output and delta age to identify migraine patients at risk for adverse vascular outcomes.