Citations

Abstract Objective To assess cardiovascular (CV) safety of erenumab in clinical trial patients associated with degree of CV risk. Background Hypertension has been considered a theoretical risk associated with the inhibition of the calcitonin gene‐related peptide pathway in migraine management, particularly in a patient population with pre‐existing CV risk factors. Methods Data pooled from four double‐blind, randomized trials were used to assess blood pressure (BP) changes and CV safety in patients grouped based on 10‐year risk of cardiac, cerebrovascular, and peripheral artery disease as no‐risk‐factors, low‐risk (>0% to ≤10%), moderate‐risk (>10% to ≤20%), and high‐risk (>20%) categories. CV safety was assessed as ischemic cardiovascular and cerebrovascular adverse events (ICCAE). Results There was no apparent difference between placebo‐ ( N = 1032) and erenumab‐treatment groups (70 mg, N = 885; 140 mg, N = 504) in clinical worsening of BP category from baseline to Months 1–3 (14% [143/1032] placebo vs. 13% [114/885] and 14% [71/504] for erenumab 70 and 140 mg, respectively) regardless of baseline BP category. The adverse event (AE) profile of erenumab was similar across CV risk categories throughout the long‐term analysis. Erenumab‐treated patients with high and moderate 10‐year CV risk ( N = 107) did not experience any ICCAEs during the double‐blind treatment period; there was a single ICCAE (a cerebral dural venous sinus thrombosis) observed in the low‐risk erenumab group ( N = 273). There were no increases in AEs during the long‐term extensions of up to 5 years ( N = 2499; 3482 patient‐years of exposure to erenumab) with exposure‐adjusted incidence rates of cardio/cerebrovascular disorder AEs of 0.4, 0.5, 0.0, and 1.1 (per 100 patient‐years) for no risk factor ( N = 1805), low ( N = 492), moderate ( N = 121), and high ( N = 81) 10‐year CV risk groups, respectively. Conclusions Ischemic CV and cerebrovascular AEs were uncommon and the incidence rates were similar across the 10‐year CV risk categories. This analysis helps provide more detail on the CV safety of erenumab.

Abstract Objective To compare the artificial intelligence‐enabled electrocardiogram (AI‐ECG) atrial fibrillation (AF) prediction model output in patients with migraine with aura (MwA) and migraine without aura (MwoA). Background MwA is associated with an approximately twofold risk of ischemic stroke. Longitudinal cohort studies showed that patients with MwA have a higher incidence of developing AF compared to those with MwoA. The Mayo Clinic Cardiology team developed an AI‐ECG algorithm that calculates the probability of concurrent paroxysmal or impending AF in ECGs with normal sinus rhythm (NSR). Methods Adult patients with an MwA or MwoA diagnosis and at least one NSR ECG within the past 20 years at Mayo Clinic were identified. Patients with an ECG‐confirmed diagnosis of AF were excluded. For each patient, the ECG with the highest AF prediction model output was used as the index ECG. Comparisons between MwA and MwoA were conducted in the overall group (including men and women of all ages), women only, and men only in each age range (18 to <35, 35 to <55, 55 to <75, ≥75 years), and adjusted for age, sex, and six common vascular comorbidities that increase risk for AF. Results The final analysis of our cross‐sectional study included 40,002 patients (17,840 with MwA, 22,162 with MwoA). The mean (SD) age at the index ECG was 48.2 (16.0) years for MwA and 45.9 (15.0) years for MwoA ( p < 0.001). The AF prediction model output was significantly higher in the MwA group compared to MwoA (mean [SD] 7.3% [15.0%] vs. 5.6% [12.4%], mean difference [95% CI] 1.7% [1.5%, 2.0%], p < 0.001). After adjusting for vascular comorbidities, the difference between MwA and MwoA remained significant in the overall group (least square means of difference [95% CI] 0.7% [0.4%, 0.9%], p < 0.001), 18 to <35 (0.4% [0.1%, 0.7%], p = 0.022), and 35 to <55 (0.5% [0.2%, 0.8%], p < 0.001), women of all ages (0.6% [0.3%, 0.8%], p < 0.001), men of all ages (1.0% [0.4%, 1.6%], p = 0.002), women 35 to <55 (0.6% [0.3%, 0.9%], p < 0.001), and men 18 to <35 (1.2% [0.3%, 2.1%], p = 0.008). Conclusions Utilizing a novel AI‐ECG algorithm on a large group of patients, we demonstrated that patients with MwA have a significantly higher AF prediction model output, implying a higher probability of concurrent paroxysmal or impending AF, compared to MwoA in both women and men. Our results suggest that MwA is an independent risk factor for AF, especially in patients <55 years old, and that AF‐mediated cardioembolism may play a role in the migraine–stroke association for some patients.

Abstract Objective To improve the understanding of the role and utility of various neuroimaging modalities (clinical and research) for the evaluation of migraine aura (MA) and hemiplegic migraine during the ictal and interictal phases. Background MA is defined by reversible neurologic symptoms and is considered a manifestation of a primary condition. As such, most patients with MA do not require imaging. However, if there are atypical features, change in symptom pattern, or it is a first‐time presentation, neuroimaging may be used to evaluate for secondary conditions. Neuroimaging includes many modalities, and it is important to consider what information is being captured by these modalities (i.e., structural vs. functional). Imaging abnormalities may be noted both during (ictal) and between (interictal) MA attacks, and it is important for clinicians to be familiar with neuroimaging findings reported in migraine with aura (MWA) compared with other conditions. Methods With the assistance of a medical librarian, we performed a review of the literature pertaining to MWA and neuroimaging in PubMed. Search terms included were magnetic resonance imaging, positron‐emission tomography, single photon‐emission computed tomography, functional magnetic resonance imaging, and migraine with aura. We hand‐searched these references to inform our subsequent literature review. Results Acute MA can be associated with several unique neuroimaging findings—reversible cortical diffusion restriction, cortical venous engorgement, and a “biphasic” transition from hypoperfusion to hyperperfusion. Imaging findings during MA tend to span more than one vascular territory. Between acute attacks, neuroimaging in people with MWA can resemble migraine without aura in terms of white matter abnormalities and “infarct‐like lesions.” Research imaging modalities such as volumetric analysis and functional imaging have demonstrated unique findings in migraine with aura. Conclusion Although migraine is a clinical diagnosis, understanding of neuroimaging findings in MWA can help clinicians interpret imaging findings and improve patient care.

Background and Objectives Migraine with aura (MwA) is associated with increased brain hyper‐responsiveness to visual stimuli and increased visual network connectivity relative to migraine without aura (MwoA). Despite this, prior studies have provided conflicting results regarding whether MwA is associated with higher photophobia symptom scores compared to MwoA. The relationships between MwA and other types of sensory hypersensitivity, such as phonophobia and cutaneous allodynia (CA), have not been previously investigated. The purpose of this cross‐sectional observational study was to investigate whether MwA is associated with greater symptoms of photophobia, phonophobia, and CA compared to MwoA. Methods This analysis included 321 migraine patients (146 MwA; 175 MwoA) who had been enrolled into the American Registry for Migraine Research. The diagnosis of either MwoA or MwA was determined by headache specialists using ICHD diagnostic criteria. Patients completed the Photosensitivity Assessment Questionnaire, the Hyperacusis Questionnaire, and the Allodynia Symptom Checklist. Mean or median values were compared between groups. Regression models were created to analyze the relationship between MwA with photophobia scores, hyperacusis scores, and the presence of interictal CA. Results Those with MwA had higher mean photophobia scores than those with MwoA (4.1 vs 3.0, P = .0003). MwA was positively associated with photophobia symptom severity ( B = 0.50 [SE = 0.14], P = .0003), after controlling for age, patient sex, and headache frequency. Aura was not associated with hyperacusis symptom severity ( B = 0.07 [SE = 0.08], P = .346) or the presence of interictal CA (OR 1.33 [95% CI 0.70‐2.53], P = .381). Conclusion MwA is associated with higher photophobia symptom scores compared to MwoA. Aura is not associated with greater hyperacusis or interictal allodynia scores. These findings complement prior imaging and neurophysiologic studies that demonstrated MwA to be associated with hyper‐responsiveness of brain visual processing regions. The findings suggest that MwA is associated specifically with visual hypersensitivity, as opposed to being associated with a general hypersensitivity to multiple types of sensory stimuli.

Background and Objective Some individuals with migraine report the presence of speech changes during their migraine attacks. The goal of this study was to compare objective features of speech during the migraine pre-attack, the migraine attack, and during the interictal period. Methods This was a prospective, longitudinal, observational study of adults with episodic migraine and healthy non-migraine controls. Participants provided speech samples three times per day using a speech elicitation tool included within a mobile app. Six complementary speech features that capture articulation and prosody were extracted from speech samples. Participants with migraine maintained a daily headache diary using the same app. A mixed effects model and t-tests were used to investigate differences in speech features between controls, the migraine pre-attack phase, the migraine attack, and the interictal period. Results In total, 56,767 speech samples were collected, including 43,102 from 15 individuals with migraine and 13,665 from matched healthy controls. Significant group-level differences in speech features were identified between those with migraine and healthy controls and within the migraine group during the pre-attack vs. attack vs. interictal periods (all p < .05). Most consistently, speech changes occurred in the speaking rate, articulation rate and precision, and phonatory duration. Within-subject analysis revealed that seven of 15 individuals with migraine showed significant change in at least one speech feature when comparing the migraine attack vs. interictal phase and four showed similar changes when comparing the pre-attack vs. interictal phases. Conclusions Changes in speech occurred in almost half of the individuals during migraine attacks. Once confirmed in subsequent studies, speech changes could be considered a feature of the migraine attack.