Headache patterns in patent foramen ovale patients: beyond migraine with aura.

Patent foramen ovale (PFO) is a common cardiac anomaly linked with cryptogenic strokes and migraine, particularly migraine with aura. This study aims to explore the spectrum of headache disorders in PFO patients, focusing on identifying patterns beyond the well-established migraine-PFO connection. A retrospective observational study was conducted on patients diagnosed with PFO. Headache types were classified using the International Classification of Headache Disorders, 3rd edition. The study analyzed headache prevalence and patterns in PFO patients, comparing those with and without a history of stroke. Of 177 participants, 63 (35.59%) reported headaches. Tension-type headache was the most common (15.25%), followed by migraine without aura (11.30%) and migraine with aura (8.47%). Notably, migraine without aura was more prevalent than migraine with aura, contrasting previous assumptions. No significant differences were found in headache types based on stroke history. The study reveals a diverse spectrum of headache types in PFO patients, with migraine without aura being more common than migraine with aura. These findings suggest a need for broader diagnostic perspective and individualized treatment approaches in PFO patients with headaches.

Headache-related disability as a function of migraine aura: A daily diary study.

OBJECTIVE: To examine the unique role of migraine aura in predicting day-to-day levels of headache-related disability. BACKGROUND: Migraine symptoms and psychological variables contribute to headache-related disability. Migraine aura may be associated with more severe symptom profiles and increased risk of psychiatric comorbidities, but the impact of aura on daily functioning is unknown. The present study sought to evaluate the role of migraine aura in predicting same-day and subsequent-day migraine-related disability while accounting for demographic, headache, and psychological variables. METHODS: This was an observational prospective cohort study among 554 adults with migraine. For each participant, data on migraine symptoms and psychological variables were collected daily for 90 days using the N-1 Headache™ digital app (N = 11,156 total migraine days). Analyses assessed whether the presence of aura predicted daily ratings of migraine-related disability independently of other headache and psychological variables. Given the number of predictors examined, statistical significance was set at p < 0.01. RESULTS: The mean (standard deviation, range) patient-level Migraine Disability Assessment questionnaire score across days of the migraine episode was 1.18 (1.03, 0-3). Aura was significantly associated with higher disability ratings on all days of the migraine episode (odds ratio [OR] 1.40, 99% confidence interval [CI] 1.13-1.74; p < 0.001). This relationship remained unchanged after adjusting for patient-level variables (OR 1.40, 99% CI 1.13-1.73; p < 0.001) and day-level psychological variables (OR 1.39, 99% CI 1.12-1.73; p < 0.001) but was fully negated after controlling for day-level headache variables (OR 1.19, 99% CI 0.95-1.49; p = 0.039). Aura on the first day of the episode was associated with increased odds of allodynia (OR 1.87, 99% CI 1.22-2.86; p < 0.001), phonophobia (OR 1.62, 99% CI 1.17-2.25; p < 0.001), photophobia (OR 1.89, 99% CI 1.37-2.59; p < 0.001), and nausea/vomiting (OR 1.54, 99% CI 1.17-2.02; p < 0.001) on all days of the episode, but not episode duration (p = 0.171), peak severity (p = 0.098), or any examined psychological variables (sleep duration [p = 0.733], sleep quality [p = 0.186], stress [p = 0.110], anxiety [p = 0.102], or sadness [p = 0.743]). CONCLUSION: The presence of aura is predictive of increased headache-related disability during migraine episodes, but this effect is attributable to associated non-pain symptoms of migraine.

Investigating the causal association between systemic lupus erythematosus and migraine using Mendelian randomization analysis.

OBJECTIVE: To assess whether systemic lupus erythematosus (SLE) may be genetically causally associated with migraine, including the two primary subtypes: migraine with aura (MWA) and migraine without aura (MWoA). BACKGROUND: The association between SLE and migraine has been investigated extensively. Previous studies have shown a higher prevalence of migraine in patients with SLE, although the exact relationship remains unclear. This study investigated the potential causal association between SLE and migraine using the powerful analytical tool of Mendelian randomization (MR). METHODS: We performed two-sample MR analysis of publicly available summary statistic datasets using inverse variance-weighted (IVW), weighted median, and MR-Egger methods based on an SLE genome-wide association study (GWAS; 5201 cases; 9066 controls; the exposure frequency is 36.5%) as an exposure and migraine GWAS (15,905 cases; 264,662 controls) in individuals with European ancestry as outcomes, focusing on the two migraine subtypes MWA (6780 cases; 264,662 controls) and MWoA (5787 cases; 264,662 controls). Thepleiotropy and heterogeneity were performed. RESULTS: We selected 42 single-nucleotide polymorphisms from SLE GWAS as instrumental variables (IVs) for SLE on migraine, and 41 SNP IVs for SLE on MWA or MWoA. The IVW (odds ratio [OR] = 1.01, 95% confidence interval [CI] = [0.99, 1.03], p = 0.271), weighted median (OR = 1.00, 95% CI = [0.97, 1.03], p = 0.914), and MR-Egger (OR = 1.04, 95% CI = [0.99, 1.09], p = 0.153) methods showed no causal effect of SLE on migraine. A causal effect of SLE was observed on MWA (IVW: OR = 1.05, 95% CI = [1.02, 1.08], p = 0.001; weighted median: OR = 1.05, 95% CI = [1.01, 1.10], p = 0.018; MR-Egger: OR = 1.07, 95% CI = [1.01, 1.14], p = 0.035 and pIVW < 0.017 [Bonferroni correction]) but not MWoA (IVW: OR = 0.99, 95% CI = [0.96, 1.02], p = 0.331; weighted median: OR = 0.98, 95% CI = [0.94, 1.03], p = 0.496; MR-Egger: OR = 1.02, 95% CI = [0.95, 1.09], p = 0.652). The results showed no significant pleiotropy or heterogeneity. CONCLUSION: Our MR analysis demonstrated the complex relationship between SLE and migraine, suggesting a potential effect of SLE on the risk of MWA but not MWoA. These findings can aid in the development of improved subtype-specific management of migraine in patients with SLE.

Migraine and cardiovascular disease: what cardiologists should know.

Migraine is a chronic neurovascular disease with a complex, not fully understood pathophysiology with multiple causes. People with migraine suffer from recurrent moderate to severe headache attacks varying from 4 to 72 h. The prevalence of migraine is two to three times higher in women compared with men. Importantly, it is the most disabling disease in women <50 years of age due to a high number of years lived with disability, resulting in a very high global socioeconomic burden. Robust evidence exists on the association between migraine with aura and increased incidence of cardiovascular disease (CVD), in particular ischaemic stroke. People with migraine with aura have an increased risk of atrial fibrillation, myocardial infarction, and cardiovascular death compared with those without migraine. Ongoing studies investigate the relation between migraine and angina with non-obstructive coronary arteries and migraine patients with patent foramen ovale. Medication for the treatment of migraine can be preventative medication, such as beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, antiepileptics, antidepressants, some of the long-acting calcitonin gene-related peptide receptor antagonists, or monoclonal antibodies against calcitonin gene-related peptide or its receptor, or acute medication, such as triptans and calcitonin gene-related peptide receptor antagonists. However, these medications might raise concerns when migraine patients also have CVD due to possible (coronary) side effects. Specifically, knowledge gaps remain for the contraindication to newer treatments for migraine. All cardiologists will encounter patients with CVD and migraine. This state-of-the-art review will outline the basic pathophysiology of migraine and the associations between migraine and CVD, discuss current therapies, and propose future directions for research.

Clinical features of migraine with aura: a REFORM study.

BACKGROUND: About one-third of persons with migraine experience transient neurologic symptoms, referred to as aura. Despite its widespread prevalence, comprehensive clinical descriptions of migraine with aura remain sparse. Therefore, we aimed to provide an in-depth phenotypic analysis of aura symptoms and characteristics in a cross-sectional study of a large sample of adults diagnosed with migraine with aura. METHODS: Data were extracted from the baseline characteristics of participants in the Registry for Migraine (REFORM) study - a single-center, prospective, longitudinal cohort study. Participants were adults diagnosed with migraine aura, reporting ≥ 4 monthly migraine days in the preceding 3 months. Trained personnel conducted in-person semi-structured interviews, capturing details on the nature, duration, localization, and progression of individual aura symptoms. RESULTS: Of the 227 enrolled participants with migraine with aura, the mean age was 41.1 years, with a predominant female representation (n = 205 [90.3%]). Visual aura was present in 215 (94.7%) participants, somatosensory aura in 81 (35.7%), and speech and/or language aura in 31 (13.7%). A single type of aura was observed in 148 (65.2%) participants, whilst 79 (34.8%) reported multiple aura types. Most participants (n = 220 [96.9%]) described their aura symptoms as positive or gradually spreading. Headache in relation to aura was noted by 218 (96.0%) participants, with 177 (80.8%) stating that the onset of aura symptoms preceded the onset of headache. CONCLUSIONS: This study offers a detailed clinical depiction of persons with migraine with aura, who were predominantly enrolled from a tertiary care unit. The findings highlight potential gaps in the available literature on migraine with aura and should bolster clinicians' acumen in diagnosing migraine with aura in clinical settings.

Migraine with and without aura in relation to the menstrual cycle and other hormonal milestones: A prospective cohort study.

BACKGROUND: Previous studies showed that the perimenstrual window is associated with an increased susceptibility to migraine attacks without aura, but had conflicting results regarding attacks with aura. METHODS: We performed a longitudinal E-diary study among 526 premenopausal women with migraine. Differences in occurrence of perimenstrual migraine attacks between women with migraine with aura and without aura were assessed using a mixed effects logistic regression model. Additionally, participants completed a questionnaire about the influence of hormonal milestones on migraine frequency. RESULTS: Prevalence of menstrual migraine did not differ between women with migraine without aura and migraine with aura (59% versus 53%, p = 0.176). The increased risk of migraine attacks without aura during the perimenstrual window was similar for women with migraine without aura (OR[95%CI]:1.53 [1.44-1.62]) and those with migraine with aura (1.53 [1.44-1.62]). The perimenstrual window was not associated with increased risk of migraine aura attacks (1.08 [0.93-1.26], p = 0.314). Women with migraine with aura more often reported increased migraine frequency during pregnancy and breastfeeding compared to women with migraine without aura, but not during hormonal contraception use. CONCLUSION: Sex hormone levels seem to differently affect the trigeminovascular system (migraine headache) and the susceptibility to cortical spreading depolarization (aura). Exclusively migraine attacks without aura should be interpreted as perimenstrual attacks.

Sex differences in clinical characteristics of migraine and its burden: a population-based study.

BACKGROUND AND PURPOSE: Understanding migraine in a sex-specific manner is crucial for improving clinical care, diagnosis and therapy for both females and males. Here, data on sex differences are provided in the presentation of migraine in a large European-based population cohort, which is representative of the general population. METHODS: A population-based study of 62,672 Danish blood donors (both present and previous donors), of whom 12,658 had migraine, was performed. All participants completed a 105-item diagnostic migraine questionnaire sent via an electronic mailing system (e-Boks) between May 2020 and August 2020. The questionnaire allowed for correct diagnosis of migraine according to the International Classification of Headache Disorders, third edition. RESULTS: The migraine questionnaire was in-cohort validated and had a positive predictive value of 97% for any migraine, a specificity of 93% and a sensitivity of 93%. There were 9184 females (mean age 45.1 years) and 3434 males (mean age 48.0 years). The 3-month prevalence of migraine without aura was 11% in females and 3.59% in males. The 3-month prevalence of migraine with aura was 1.72% in females and 1.58% in males. In females, the age-related 3-month prevalence of migraine without aura increased markedly during childbearing age. In males, migraine both with and without aura showed less age variation. Females had a higher frequency of migraine attacks (odds ratio [OR] 1.22) but a lower frequency of non-migraine headaches (OR = 0.35). Females also had a greater intensity of pain, more unilateral and pulsatile pain, and exacerbation by physical activity (OR = 1.40-1.49) as well as more associated symptoms (OR = 1.26-1.98). Females carried 79% of the total migraine disease burden, which was almost exclusively driven by migraine without aura (77%), whilst there was no sex difference in the disease burden of migraine with aura. CONCLUSION: Females have more severe disease, resulting in a much higher migraine disease burden than indicated by prevalence alone.

Near-death experiences are associated with rapid eye movement (REM) sleep intrusions in migraine patients, independent of migraine aura.

BACKGROUND AND PURPOSE: Migraine aura, near-death experiences (NDEs), and rapid eye movement (REM) sleep intrusions might share common mechanisms. Here, we investigated the prevalence of NDEs and REM sleep intrusions in people with migraine. We hypothesized that NDEs and REM sleep intrusions are more prevalent in migraine patients with aura than in those without. METHODS: We conducted a prospective cross-sectional cohort study at a tertiary headache center, based on a prespecified sample size (n = 808). Migraine patients completed a series of questionnaires, including questions about demographic and headache characteristics, the 16-item Greyson NDE scale, four questions about REM sleep intrusions, and the Depression, Anxiety, and Stress Scale 21 (DASS-21). RESULTS: Of 808 migraine patients (mean age 44.4 ± 13.3 years, 87.0% women), 353 (43.7%) had a current or previous history of migraine aura. Prevalence of NDE was 2.7% and not different in patients with and without aura (2.8% vs. 2.6%; p > 0.999). REM sleep intrusions were reported by 5.4% of participants and in a similar proportion of patients with and without aura (6.3% vs. 4.9%; p = 0.43). However, participants with REM sleep intrusions had had an NDE more often than participants without REM sleep intrusions (n = 5/44, 11.4% vs. n = 17/754, 2.2%; p = 0.005). Higher DASS-21 scores were associated with REM sleep intrusions (p < 0.001). CONCLUSIONS: In this tertiary center cohort study, the prevalence of NDE and REM sleep intrusions was not influenced by migraine aura status. However, we identified an association between NDE and REM sleep intrusions, which corroborates the notion that they might share pathophysiological mechanisms.

Familial hemiplegic migraine in pediatric patients: A genetic, clinical, and follow-up study.

OBJECTIVE: The aim of this study was to describe a cohort of pediatric patients with genetically confirmed familial hemiplegic migraine (FHM). The knowledge of genotype-phenotype correlations may suggest prognostic factors associated with severe phenotypes. BACKGROUND: Hemiplegic migraine is a rare disease and data concerning the pediatric population are even more rare as they are often extrapolated from mixed cohorts. METHODS: We selected patients who met International Classification of Headache Disorders, third edition criteria for FHM, who had a molecular diagnosis, and whose first attack occurred under the age of 18 years. RESULTS: We enrolled nine patients (seven males and two females) first referred to our three centers. Three of the nine (33%) patients had calcium voltage-gated channel subunit alpha1 A (CACNA1A) mutations, five (55%) had ATPase Na+/K+ transporting subunit alpha 2 (ATP1A2) mutations, and one had both genetic mutations. The patients experienced at least one aura feature other than hemiplegia during the first attack. The mean (SD) duration of HM attacks in the sample was 11.3 (17.1) h; 3.8 (6.1) h in the ATP1A2 group, and 24.3 (23.5) h in the CACNA1A group. The mean (SD, range) duration of follow-up was 7.4 (2.2, 3-10) years. During the first year from the disorder's onset, only four patients had additional attacks. Over the course of follow-up, the attack frequency overall was 0.4 attacks/year without a difference between the two groups (CACNA1A and ATP1A2). CONCLUSION: The study data show that most of our patients with early-onset FHM experienced infrequent and non-severe attacks, which improved over time. Furthermore, the clinical course revealed neither the appearance of novel neurological disorders or a deterioration of basic neurological or cognitive functioning.

Use of combined hormonal contraception and stroke: A case-control study of the impact of migraine type and estrogen dose on ischemic stroke risk.

OBJECTIVE: To clarify how factors such as estrogen dose and migraine history (including migraine subtype) impact ischemic stroke risks associated with combined hormonal contraceptive (CHC) use. BACKGROUND: CHC use in those with migraine with aura has been restricted due to concerns about stroke risk. METHODS: We conducted a case-control analysis of stroke risk associated with estrogen dose and migraine history among CHC users in a large tertiary care center. All women aged 18-55 who used a CHC between January 1, 2010, and December 31, 2019, were identified. Those with a stroke diagnosis were identified using ICD codes and confirmed via chart and imaging review. Details of personal and family medical history, stroke evaluation, ethinyl estradiol dosing (EE; ≥30 vs. <30 µg), and demographics were collected. From a random sample of 20,000 CHC users without stroke, a control cohort (n = 635) was identified and matched based on patient characteristics, medical and family histories, as well as stroke risk factors, to assess association between migraine diagnosis, migraine subtype, estrogen dose, and stroke. RESULTS: Of the 203,853 CHC users in our cohort, 127 had confirmed stroke (0.06%; CI 0.05%, 0.07%). In unadjusted analyses, a higher number of patients in the case cohort had a diagnosis of migraine (34/127, 26.8%) compared to controls (109/635, 17.2%; p = 0.011). Stroke risk was higher with ≥30-µg EE doses compared to those using a <30-µg dose (OR, 1.52; CI 1.02, 2.26; p = 0.040). Compared to no migraine, personal history of migraine increased the odds of stroke (OR, 2.00; CI 1.27, 3.17; p = 0.003). Compared to no migraine, stroke risk was not significantly increased in those with migraine with aura, but migraine without aura increased the risk (OR, 2.35; CI 1.32, 4.2; p = 0.004). CONCLUSIONS: Overall stroke risk in our cohort of CHC users was low. When CHCs are used in those with migraine, formulations containing ≤30 µg EE are preferred. Shared decision-making should include discussions about ischemic stroke risks in patients with migraine, even those without aura.

Hemiplegic Migraine.

PURPOSE OF REVIEW: In this article, we review recent updates to the epidemiology, diagnostic testing, genetics, pathophysiology, and management of hemiplegic migraine. RECENT FINDINGS: While three genes have been historically associated with hemiplegic migraine, recent studies suggest two additional genes may also be implicated including PPRT2 and SLC1A3. Hemiplegic migraine is a severe subset of migraine with aura with symptoms including reversible hemiparesis in addition to other aura symptoms such as visual, sensory, or speech. The exact pathophysiology of hemiplegic migraine is not clear, but it is thought that this phenomenon is due to neuronal and glial depolarization causing cortical spreading depression. Due to the severity of presentation as well as the numerous mimickers, it is important to know a comprehensive differential and work-up. Given the low prevalence of the disease, most studies regarding treatment are limited to case studies. There is still an important need for further and larger studies regarding management of these cases.

Factors associated with migraine aura mimicking stroke in code stroke.

INTRODUCTION: Migraine with aura (MA) is a frequent stroke simulator that can lead to erroneous diagnosis and subsequent unnecessary acute or secondary prevention treatments. We analyzed clinical and laboratory data of migraine with aura and ischemic stroke patients to detect differences that could help in the diagnosis. METHODS: Retrospective analysis of a consecutive register of code strokes between January 2005 and June 2020. Diagnosis of ischemic stroke or MA was collected. Multivariable logistic regression analyses were performed to test associations between clinical and blood data with ischemic stroke. RESULTS: Of 3140 code strokes, 2424 (77.2%) were ischemic strokes and 34 (1.1%) were MA. Migraine cases were younger, more frequently females and with lower prevalence of vascular risk factors. Initial NIHSS was lower in MA cases, but no differences were seen in fibrinolysis rate (30%). Blood test showed lower levels of glucose, D-dimer, and fibrinogen in MA cases. Multivariable model showed and independent association for ischemic stroke with age [OR, (95%CI): 1.09, (1.07-1.12, p < 0.001], male sex [OR, (95%CI): 4.47, (3.80-5.13), p < 0.001], initial NIHSS [OR, (95%CI): 1.21, (1.07-1.34), p < 0.01], and fibrinogen levels [OR, (95%CI): 1.01, (1.00-1.01), p < 0.05]. A model including sex male OR: 3.55 [2.882; 4.598], p < 0.001, and cutoff points (age > 65, OR: 7.953 [7.256; 8.649], p < 0.001, NIHSS > 6, OR: 3.740 [2.882; 4.598], p < 0.01, and fibrinogen > 400 mg/dL, OR: 2.988 [2.290; 3.686], p < 0.01) showed a good global discrimination capability AUC = 0.89 (95%CI: 0.88-0.94). CONCLUSIONS: In code stroke, a model including age, sex, NIHSS, and fibrinogen showed a good discrimination capability to differentiate between MA and Ischemic stroke. Whether these variables can be implemented in a diagnostic rule should be tested in future studies.

Visual Aura in Non-Migraine Headaches: A Population Study.

BACKGROUND: Visual aura (VA) occurs mostly in migraine with aura (MA), but some case studies have reported aura in non-migraine headaches. Thus, information of VA in non-migraine headaches is scarce. Aim of this study was to investigate the prevalence and impact of VA in non-migraine headache and compare it with that of migraine headache. METHODS: This study was a nationwide population-based study. We used an internet-based headache diagnosis questionnaire to diagnose headache, and various modules to evaluate clinical features and comorbidities of participants with headache. We defined migraine headache as migraine and probable migraine (PM), whereas non-migraine headache was defined as a headache but not migraine or PM. VA was defined as a self-reporting VA rating scale score ≥ 3. RESULTS: Of the 3,030 participants, 1,431 (47.2%) and 507 (16.7%) had non-migraine headache and migraine headache, respectively. VA prevalence was much lower in the non-migraine headache group than in the migraine headache group (14.5% [207/1,431] vs. 26.0% [132/507], P < 0.001). In subjects with non-migraine headache, those with VA had a markedly higher number of headache days per 30 days (median [25th-75th percentiles]: 2.0 [1.0-5.0] vs. 2.0 [1.0-3.0], P < 0.001), and headache-related disability (6.0 [3.0-16.0] vs. 2.0 [0.0-7.0], P < 0.001) than those without VA. VA prevalence did not differ significantly according to age and sex. CONCLUSION: Non-migraine headache with VA patients had more severe symptoms than those without VA. These findings may improve the understanding of VA and the management of individuals with non-migraine headache.

Changes of migraine aura with advancing age of patients.

AIM: Given the similar presentation of migraine aura and acute ischemic stroke, advancing patient age might change the characteristics of migraine with aura (MA) and be clinically important. Clinical data, however, are limited. Experimental studies indicate a decrease in the magnitude of cortical spreading depression (CSD), the pathophysiological correlate of migraine aura, with advancing age. Our study aimed to assess the influence of age on the clinical features of MA. METHODS: Three hundred and forty-three patients were interviewed using a structured questionnaire. The questions covered the headache characteristics and symptom types including the characteristics of the C-criterion, as defined by the International Classification of Headache Disorders 3rd Edition. The association of age with MA characteristics was assessed. RESULTS: The median age was 29 (IQR 28-52) and 235 of the 343 patients were women (69%). Individual symptoms of the C-criterion such as gradual aura spreading over longer than 5 min (P < 0.001), two or more aura symptoms occurring in succession (P = 0.005), duration of at least one MA symptom for longer than 60 min (P = 0.004), and associated headache (P = 0.01) were more frequent in younger patients. The number of symptoms including the C-characteristics decreased with increasing age (P < 0.001). Patients with sensory (P < 0.001), motor (P = 0.004) and speech disturbance (P = 0.02) were younger, and older patients with headache had less photophobia (P = 0.04) and phonophobia (P = 0.03). Sensitivity analyses yielded similar results. CONCLUSION: The frequency of typical characteristics of migraine aura and migraine headache including photophobia and phonophobia decreases with advancing patient age. This might have potentially difficult implications for the diagnosis of MA in the elderly.

Association between Migraine and Cryptogenic Ischemic Stroke in Young Adults.

OBJECTIVE: To assess the association between migraine and cryptogenic ischemic stroke (CIS) in young adults, with subgroup analyses stratified by sex and presence of patent foramen ovale (PFO). METHODS: We prospectively enrolled 347 consecutive patients aged 18 to 49 years with a recent CIS and 347 age- and sex-matched (±5 years) stroke-free controls. Any migraine and migraine with (MA) and migraine without aura (MO) were identified by a screener, which we validated against a headache neurologist. We used conditional logistic regression adjusting for age, education, hypertension, diabetes, waist-to-hip ratio, physical inactivity, current smoking, heavy drinking, and oral estrogen use to assess independent association between migraine and CIS. The effect of PFO on the association between migraine and CIS was analyzed with logistic regression in a subgroup investigated with transcranial Doppler bubble screen. RESULTS: The screener performance was excellent (Cohen kappa > 0.75) in patients and controls. Compared with nonmigraineurs, any migraine (odds ratio [OR] = 2.48, 95% confidence interval [CI] = 1.63-3.76) and MA (OR = 3.50, 95% CI = 2.19-5.61) were associated with CIS, whereas MO was not. The association emerged in both women (OR = 2.97 for any migraine, 95% CI = 1.61-5.47; OR = 4.32 for MA, 95% CI = 2.16-8.65) and men (OR = 2.47 for any migraine, 95% CI = 1.32-4.61; OR = 3.61 for MA, 95% CI = 1.75-7.45). Specifically for MA, the association with CIS remained significant irrespective of PFO. MA prevalence increased with increasing magnitude of the right-to-left shunt in patients with PFO. INTERPRETATION: MA has a strong association with CIS in young patients, independent of vascular risk factors and presence of PFO. ANN NEUROL 2021;89:242-253.

Associations between migraine and major cardiovascular events in type 2 diabetes mellitus.

BACKGROUND: Migraine is one of the most common primary headache disorders and a well-known risk factor for cardiovascular disorders. We aimed to investigate the association between migraine and major cardiovascular outcomes, including myocardial infarction (MI), ischemic stroke (IS), and cardiovascular death (CVD) in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 2,229,598 people from the nationwide Korean National Health Insurance Service database with type 2 diabetes but without a previous history of MI and IS were included in this study. We identified patients over 20 years of age with migraine using the claim data of International Statistical Classification of Diseases Related Health Problems, Tenth Revision (ICD-10) code G43. The patients with migraine were divided according to their migraine aura status. RESULTS: Migraine was present in 6.3% of the study population. Cases observed for MI, IS, CVD, and all-cause death were 2.6%, 3.6%, 5.9%, and 7.9%, respectively. The diagnosis of migraine was significantly associated with an increased risk of MI, IS, and CVD. The results remained significant after adjusting for covariates, including age, sex, body mass index, alcohol intake, smoking habits, physical activity, economic status, hypertension history, dyslipidemia, and duration of type 2 diabetes (MI, adjusted hazard ratio [aHR]: 1.182, 95% confidence interval [CI]: 1.146-1.219; IS, aHR: 1.111, 95% CI 1.082-1.14; CVD, aHR: 1.143, 95% CI 1.12-1.167). In particular, the presence of aura was associated with a higher risk of MI development compared to the non-aura group. The difference became more prominent with progressing age. CONCLUSIONS: In this nationwide population-based study, people with type 2 diabetes and migraines were found to be at a significantly higher risk for major cardiovascular events, including MI, IS, and CVD. The risk of MI and CVD significantly increased with the presence of aura symptoms among patients with migraine.

Aura in trigeminal autonomic cephalalgia is probably mediated by comorbid migraine with aura.

OBJECTIVE: The presence of aura is rare in cluster headache, and even rarer in other trigeminal autonomic cephalalgias. We hypothesized that the presence of aura in patients with trigeminal autonomic cephalalgias is frequently an epiphenomenon and mediated by comorbid migraine with aura. METHODS: The study retrospectively reviewed 480 patients with trigeminal autonomic cephalalgia in a tertiary medical center for 10 years. Phenotypes and temporal correlation of aura with headache were analyzed. Trigeminal autonomic cephalalgia patients with aura were further followed up in a structured telephone interview. RESULTS: Seventeen patients with aura (3.5%) were identified from 480 patients with trigeminal autonomic cephalalgia, including nine with cluster headache, one with paroxysmal hemicrania, three with hemicrania continua, and four with probable trigeminal autonomic cephalalgia. Compared to trigeminal autonomic cephalalgia patients without aura, trigeminal autonomic cephalalgia patients with aura were more likely to have a concomitant diagnosis of migraine with aura (odds ratio [OR] = 109.0, 95% CI 30.9-383.0, p < 0.001); whereas the risk of migraine without aura remains similar between both groups (OR = 1.10, 95% CI = 0.14-8.59, p = 0.931). Aura was more frequently accompanied with migraine-like attacks, but not trigeminal autonomic cephalalgia attacks. INTERPRETATION: In most patients with trigeminal autonomic cephalalgia, the presence of aura is mediated by the comorbidity of migraine with aura. Aura directly related to trigeminal autonomic cephalalgia attack may exist but remains rare. Our results suggest that aura may not be involved in the pathophysiology of trigeminal autonomic cephalalgia.

Non-aura visual disturbance with high visual aura rating scale scores has stronger association with migraine chronification than typical aura.

OBJECTIVES: To investigate the clinical correlates of visual symptoms in patients with migraine. METHOD: Patients with migraine that attended our headache clinics were enrolled. Headache profiles, disability, and comorbidities were acquired with structured questionnaires. A semi-structured visual phenomenon questionnaire was also used to assess the characteristics of visual symptoms, including visual aura in patients with migraine with aura and transient visual disturbance in patients with migraine without aura. Headache specialists interviewed with the participants for the ascertainment of diagnosis and verification of the questionnaires. RESULT: Migraine with aura patients with visual aura (n = 743, female/male = 2.3, mean age: 34.7 ± 12.2 years) and migraine without aura patients with non-aura transient visual disturbance (n = 1,808, female/male = 4.4, mean age: 39.4 ± 12.6 years) were enrolled. Patients with transient visual disturbance had higher headache-related disability and more psychiatric comorbidities. Chronic migraine was more common in migraine without aura than migraine with aura patients (41.9% vs. 11.8%, OR = 5.48 [95% CI: 4.33-7.02], p < 0.001). The associations remained after adjusting confounding factors. CONCLUSION: Presence of non-aura transient visual disturbance may suggest a higher migraine-related disability and is linked to higher risk of chronic migraine than typical migraine aura in migraine patients. Further studies are needed to elucidate the potential mechanism.

Physical activity pattern and migraine according to aura symptoms in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohort: A cross-sectional study.

OBJECTIVE: To estimate the associations of physical activity (PA) levels with migraine subtypes. BACKGROUND: Physical activity has been associated with reduced migraine prevalence, but less is known about its relationship with migraine subtypes and PA levels as recommended by World Health Organization (WHO). METHODS: In this cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we estimated the odds ratios (ORs) of migraine with aura (MA) and migraine without aura (MO), compared to participants without headaches, according to PA levels in the leisure time (LTPA), commuting time (CPA), and combined PA domains. RESULTS: In total, 2773 participants provided complete data, 1556/2773 (56.1%) were women, mean (SD) age of 52.3 (9.1) years. In this study's sample, 1370/2773 (49.4%) participants had overall migraine, 480/2773 (17.3%) had MA, and 890/2773 (32.0%) had MO. In the LTPA domain, there were reduced odds of MA (OR 0.72, 95% confidence interval [CI] 0.53-0.96; p = 0.030) and MO (OR 0.71, 95% CI 0.56-0.90; p = 0.005) in participants who met the WHO PA guidelines after adjustment for confounder variables. In the analyses stratified by intensity, moderate LTPA was associated with reduced odds of MA (OR 0.56, 95% CI 0.320-0.99; p = 0.049), while vigorous LTPA was associated with reduced odds of MO (OR 0.55, 95% CI 0.395-0.77; p = 0.001). There were no significant associations between migraine subtypes and CPA or combined PA domains. In the whole migraine sample, meeting the WHO PA guidelines in the LTPA (OR 0.275, 95% CI 0.083-0.90; p = 0.034), CPA (OR 0.194, 95% CI 0.064-0.58; p = 0.004), and combined domains (OR 0.115, 95% CI 0.032-0.41; p = 0.001) was associated with reduced odds of daily migraine attack frequency. CONCLUSIONS: Meeting the WHO PA guidelines for LTPA, but not CPA or combined PA domains, is associated with lower migraine occurrence. Moderate LTPA favors MA reduction, while vigorous LTPA favors MO reduction.

Migraine with aura associates with a higher artificial intelligence: ECG atrial fibrillation prediction model output compared to migraine without aura in both women and men.

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.