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.

The prevalence of positive right to left shunt in migraine patients with and without aura: A new single-center study in China.

BACKGROUND: Recently, many studies have reported that there may be association between positive right-to-left shunt (RLS) and migraine, especially Migraine with aura (MA) patients. However, these researches are mostly limited in Western country. And the latest study describing the prevalence of RLS in Chinese patients with migraine was conducted five years ago. It indicated the significant higher rate of positive RLS in MA patients than migraine without aura(MWOA) group. However, no consistent results were observed according to our daily work. OBJECTIVE: To investigate the prevalence and grade of RLS in migraine patients with and without aura and to evaluate the potential association between positive RLS and migraine with aura. METHODS: A total of 91 migraine patients were involved, including 57 MWOA patients and 34 MA patients. MWOA and MA were diagnosed according to the International Classification of Headache Disorders, 3rd edition (beta version) (ICHD-3). Contrast transcranial Doppler ultra-sound (cTCD) was used to assess the prevalence of positive RLS, the associations between RLS and presence of aura. RESULTS: The overall prevalence of RLS in migraine patients was 35.2%. In MA group, 44.1% (15/34) were positive for RLS overall, higher than MWOA group (29.8%,17/57). However, the differences were not significant (P = 0.167). And there were no marked differences in the prevalence of large, middle and small shunt between MA and MWOA patients. CONCLUSION: Our study suggested MA patients have the slightly higher prevalence of positive RLS than MWOA patients in China. However, there were no significant differences, which was different from the previous studies. Our findings suggested the negative association between the positive RLS and migraine with aura.

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.

Association between patent foramen ovale and migraine without aura: a community-based cross-sectional study in China.

OBJECTIVES: To assess the influence of patent foramen ovale (PFO) on the prevalence of migraine without aura based on propensity score-matched samples in Southwest China. DESIGN: Propensity-matched cross-sectional study. PARTICIPANTS: Residents over 20 years of age were recruited from 15 communities of Western China from July 2020 to October 2020. A total of 3741 residents having accepted to undergo contrast-transthoracic echocardiography and a standard structured questionnaire was assessed for the relationship between PFO and migraine without aura. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measures were the prevalence of migraine without aura across different degrees of right-left shunts. RESULTS: A total of 3741 participants were included. Among them, 881 participants were diagnosed with PFO. The prevalence of migraine without aura in the PFO group was 12.83%, significantly higher than the other group (7.83%, p<0.0001). Analyses of the matched samples showed that the presence of a PFO increased the morbidity risk of migraine without aura (p < 0.001; OR=1.71, 95% CI 1.19 to 2.47). CONCLUSION: This community-based cross-sectional study pointed to a strong association between PFO and migraine without aura, especially when the shunt is large. TRIAL REGISTRATION NUMBER: ChiCTR1900024623.

Prevalence and impact of visual aura in migraine and probable migraine: a population study.

Visual aura (VA) presents in 98% of cases of migraine with aura. However, data on its prevalence and impact in individuals with migraine and probable migraine (PM) are limited. Data from the nation-wide, population-based Circannual Change in Headache and Sleep Study were collected. Participants with VA rating scale scores ≥ 3 were classified as having VA. Of 3,030 participants, 170 (5.6%) and 337 (11.1%) had migraine and PM, respectively; VA prevalence did not differ between these cohorts (29.4% [50/170] vs. 24.3% [82/337], p = 0.219). Participants with migraine with VA had a higher headache frequency per month (4.0 [2.0-10.0] vs. 2.0 [1.0-4.8], p = 0.014) and more severe cutaneous allodynia (12-item Allodynia Symptom Checklist score; 3.0 [1.0-8.0] vs. 2.0 [0.0-4.8], p = 0.046) than those without VA. Participants with PM with VA had a higher headache frequency per month (2.0 [2.0-8.0] vs. 2.0 [0.6-4.0], p = 0.001), greater disability (Migraine Disability Assessment score; 10.0 [5.0-26.3] vs. 5.0 [2.0-12.0], p < 0.001), and more severe cutaneous allodynia (12-item Allodynia Symptom Checklist score, 2.5 [0.0-6.0] vs. 0.0 [0.0-3.0], p < 0.001) than those without VA. VA prevalence was similar between migraine and PM. Some symptoms were more severe in the presence of VA.

Modelo teórico explicativo de la discapacidad moderada y grave por migraña / Explanatory theoretical model of moderate and severe disability due to migraine

Introducción: la migraña es una enfermedad frecuente y discapacitante, sin embargo, existen pocas investigaciones sobre los factores predictivos de la discapacidad. Objetivo: crear un modelo teórico explicativo de la interrelación dinámica entre los factores asociados a la discapacidad por migraña y a su vez la relación individual de cada uno de estos factores con la discapacidad. Métodos: para la realización de esta investigación se asumió el enfoque racionalista-deductivo como postura epistemológica, y los métodos hipotético-deductivo y sistémico-estructural para su consecución. Resultados: se expusieron elementos teóricos reveladores de la compleja relación que existe entre la discapacidad por migraña y sus factores determinantes. Conclusiones: se creó un modelo explicativo de la interrelación dinámica entre los diferentes factores con influencia independiente sobre la discapacidad por migraña y a su vez la relación individual de cada uno de estos factores con la discapacidad(AU)

Introduction: migraine is a common and disabling disease, however, there is little research on the predictive factors of disability. Objective: to create an explanatory theoretical model of the dynamic interrelation between the factors associated with migraine disability and, in turn, the individual relationship of each of these factors with disability. Methods: to carry out this research, the rationalist-deductive approach was assumed as an epistemological position, and the hypothetical-deductive and systemic-structural methods were used to achieve it. Results: revealing theoretical elements of the complex relationship that exists between disability due to migraine and its determining factors were exposed. Conclusions: an explanatory model of the dynamic interrelation between the different factors with independent influence on migraine disability and, in turn, the individual relationship of each of these factors with disability was created(EU)

Acceptance and commitment therapy for high frequency episodic migraine without aura: Findings from a randomized pilot investigation.

OBJECTIVE: We compared the incremental effects of adding acceptance and commitment therapy (ACT) to pharmacological treatment as usual (TAU) in a sample of patients with high frequency episodic migraine without aura (HFEM), assessing impact on a spectrum of measures across multiple domains. BACKGROUND: Patients with HFEM are at risk of developing chronic migraine and medication overuse headache. ACT has been shown to be effective for the treatment of various chronic pain conditions, but little attention has been given to its therapeutic value in the management of recurring headaches. METHODS: In this single-blind (masking for outcome assessor), open-label, randomized clinical trial, 35 patients with HFEM, with a monthly headache frequency ranging from 9 to 14 days, were recruited at the headache center of C. Besta Neurological Institute and randomized to either TAU (patient education and pharmacological prophylaxis; n = 17) or TAU + ACT (n = 18). Patients assigned to the combined treatment arm additionally received six 90-min weekly group sessions of ACT therapy and two supplementary "booster" sessions. All patients were on a stable course of prophylactic medication in the 3 months prior to initiating either treatment. Monthly headache frequency served as the primary outcome measure, with all other data collected being considered as secondary measures (medication intake, disability, headache impact, anxiety and depression, catastrophizing, allodynia, cognitive inflexibility, pain acceptance, mindful attention and awareness). RESULTS: A total of 35 patients were enrolled: 17 randomized to TAU, of whom three dropped out, and 18 to TAU + ACT (no dropouts in this group). Headache frequency and medication intake decreased in both groups over 12 months, with patients in the TAU + ACT group showing statistically significant reduction earlier, that is, by month 3. Headache frequency was reduced by 3.3 days (95% CI: 1.4 to 5.2) among those randomized to ACT + TAU, whereas it increased by 0.7 days (95% CI: -2.7 to 1.3) among those randomized to TAU only (p = 0.007, partial η2  = 0.21), the difference being 4 days (95% CI: 1.2 to 6.8). Medication intake was reduced by 4.1 intakes (95% CI: 2.0 to 6.3) among those randomized to ACT + TAU and by 0.4 intakes (95% CI: -1.8 to 2.5) among those randomized to TAU only (p = 0.016; partial η2  = 0.17), the difference being 3.8 intakes (95% CI: 0.7 to 6.8). At 6 and 12 months, the variations were not different between the two groups for headache frequency and medication intake. The opposite was found for measures of headache impact and pain acceptance, where the differences over time favored patients allocated to TAU. Both groups improved with regard to measures of disability, anxiety and depression, catastrophizing, and cognitive inflexibility, whereas measures of allodynia and pain acceptance were stable over time. CONCLUSIONS: Our preliminary findings indicate that supplementing TAU with ACT can enhance the main clinical outcomes, namely headache frequency and medication intake of patients with HFEM.

Association Between Hemostatic Profile and Migraine: A Mendelian Randomization Analysis.

OBJECTIVE: To assess support for a causal relationship between hemostatic measures and migraine susceptibility using genetic instrumental analysis. METHODS: Two-sample Mendelian randomization instrumental analyses leveraging available genome-wide association study (GWAS) summary statistics were applied to hemostatic measures as potentially causal for migraine and its subtypes, migraine with aura (MA) and migraine without aura (MO). Twelve blood-based measures of hemostasis were examined, including plasma level or activity of 8 hemostatic factors and 2 fibrinopeptides together with 2 hemostasis clinical tests. RESULTS: There were significant instrumental effects between increased coagulation factor VIII activity (FVIII; odds ratio [95% confidence interval] 1.05 [1.03, 1.08]/SD, p = 6.08 × 10-05), von Willebrand factor level (vWF; 1.05 [1.03, 1.08]/SD, p = 2.25 × 10-06), and phosphorylated fibrinopeptide A level (1.13 [1.07, 1.19]/SD, p = 5.44 × 10-06) with migraine susceptibility. When extended to migraine subtypes, FVIII, vWF, and phosphorylated fibrinopeptide A showed slightly stronger effects with MA than overall migraine. Fibrinogen level was inversely linked with MA (0.76 [0.64, 0.91]/SD, p = 2.32 × 10-03) but not overall migraine. None of the hemostatic factors was linked with MO. In sensitivity analysis, effects for fibrinogen and phosphorylated fibrinopeptide A were robust, whereas independent effects of FVIII and vWF could not be distinguished, and FVIII associations were potentially affected by pleiotropy at the ABO locus. Causal effects from migraine to the hemostatic measures were not supported in reverse Mendelian randomization. However, MA was not included due to lack of instruments. CONCLUSIONS: The findings support potential causality of increased FVIII, vWF, and phosphorylated fibrinopeptide A and decreased fibrinogen in migraine susceptibility, especially for MA, potentially revealing etiologic relationships between hemostasis and migraine.

Association of Migraine With Incident Hypertension After Menopause: A Longitudinal Cohort Study.

OBJECTIVE: Migraine has been identified as a potential risk factor for hypertension in prospective studies. In women, migraine prevalence decreases after menopause, but no studies have determined whether migraine is associated with hypertension after menopause. This study sought to determine whether history of migraine was associated with an increased risk of hypertension among menopausal women. METHODS: We assessed associations between migraine and hypertension in a longitudinal cohort study of 56,202 menopausal women participating in the French E3N cohort, with follow-up beginning in 1993. We included women who did not have hypertension or cardiovascular disease at the time of menopause. Migraine was classified as ever or never at each questionnaire cycle. Cox proportional hazards models were used to investigate relations between migraine and hypertension, controlling for potential confounding. A secondary analysis with baseline in 2011 considered aura status, grouping participants reporting migraine as migraine with aura, migraine without aura, or unknown migraine type. RESULTS: During 826,419 person-years, 12,501 cases of incident hypertension were identified, including 3,100 among women with migraine and 9,401 among women without migraine. Migraine was associated with an increased risk of hypertension in menopausal women (hazard ratio [HR]migraine 1.29 [95% confidence interval 1.24, 1.35]) and was consistent in post hoc sensitivity analyses, such as when controlling for common migraine medications. Associations between migraine and hypertension were similar whether or not women reported aura (HRmigraine aura 1.54 [1.04, 2.30], HRmigraine no aura 1.32 [0.87, 2.02], p heterogeneity 0.60). Associations were slightly stronger among ever users of menopausal hormone therapy (HRmigraine 1.34 [1.27, 1.41]) than among never users (HRmigraine 1.19 [1.11, 1.28]). CONCLUSIONS: Migraine was associated with an increased risk of hypertension among menopausal women. In secondary analysis, we did not observe a significant difference between migraine with aura and migraine without aura.

Prevalence and grade of RLS in migraine: A prospective study of 251 migraineurs by synchronous test of c-TTE and c-TCD.

BACKGROUND: Right-to left shunt (RLS) is regarded as a risk factor resulting in migraine, but the relevance between the RLS and migraine remains controversial. This paper aims at investigating the prevalence and RLS grade of patent foramen ovale (PFO) in cases of migraine (including migraine with and without aura) and evaluate the relationship between PFO and migraine. METHODS: Synchronous test of contrast transthoracic echocardiography and contrast transcranial Doppler ultrasonography was performed in 251 cases of migraine, which contains 62 cases of migraine with aura (MA) and 189 cases without aura (MO) and 275 healthy adults. Among these cases, 25 cases with migraine and 14 healthy adults were evaluated through transesophageal echocardiography. RESULTS: (1). The prevalence of permanent RLS, total RLS, and large RLS in migraine was 11.16%, 39.04%, and 17.13%, respectively, which was significantly higher than that of the controls (P = .042, <.001, and.001, respectively). (2). Permanent RLS was detected as 7.93% of the cases in MO, 20.96% in MA, and 6.18% in controls. Total RLS was detected as 35.98% of the cases in MO, 48.38% in MA, and 23.64% in controls. Large RLS was detected as 13.76% of the cases in MO, 27.41% in MA, and 7.27% in controls. Compared with controls, the positive rate of total RLS and large RLS in MO increased (P = .004 and.022, respectively), the that of permanent RLS, total RLS, and large RLS in MA also increased (P < .001 for each of the comparisons). The positive rate of permanent RLS and large RLS in MA was remarkably higher than that in MO (P = .005 and.013, respectively). (3) The presence of large-size PFO (≥2.0 mm) of migraine showed higher than that of the controls (P = .048). CONCLUSIONS: PFO is associated with the migraine (especially with aura), when it is permanent RLS, large RLS, and large-size PFO (≥2.0 mm).

Early treatment with sumatriptan prevents PACAP38-induced migraine: A randomised clinical trial.

OBJECTIVE: To determine whether early treatment with sumatriptan can prevent PACAP38-induced migraine attacks. METHODS: A total of 37 patients with migraine without aura were enrolled between July 2018 to December 2019. All patients received an intravenous infusion of 10 picomole/kg/min of PACAP38 over 20 min followed by an intravenous infusion of 4 mg sumatriptan or placebo over 10 min on two study days in a randomised, double-blind, placebo-controlled, crossover study. RESULTS: Of 37 patients enrolled, 26 (70.3%) completed the study and were included in analyses. Of the 26 patients, four (15%) developed a PACAP38-induced migraine attack on sumatriptan and 11 patients (42%) on placebo (p = 0.016). There were no differences in area under the curve for headache intensity between sumatriptan (mean AUC 532) and placebo (mean AUC 779) (p = 0.35). Sumatriptan significantly constricted the PACAP38-dilated superficial temporal artery immediately after infusion (T30) compared with infusion of placebo (p < 0.001).Conclusions and relevance: Early treatment with intravenously administered sumatriptan prevented PACAP38-induced migraine. Prevention of migraine attacks was associated with vasoconstriction by sumatriptan in the earliest phases of PACAP provocation. These results suggest that sumatriptan prevents PACAP38-induced migraine by modulation of nociceptive transmission within the trigeminovascular system.Trial Registration: ClinicalTrials.gov (NCT03881644).

Premonitory symptoms in migraine from China: A multi-clinic study of 4821 patients.

OBJECTIVE: To observe the prevalence and characteristics of premonitory symptoms in Chinese migraineurs and explore their associations with migraine-related factors. METHOD: Migraineurs who visited a tertiary headache clinic and one of nine neurology clinics between May 2014 and November 2019 were studied. RESULT: Among the 4821 patients meeting the migraine criteria (International Classification of Headache Disorders, 3rd edition), 1038 (21.5%) patients experienced at least one premonitory symptom. The most common premonitory symptoms were neck stiffness, dizziness, yawning and drowsiness. The logistic regression analysis demonstrated that aura, photophobia, aggravation by routine physical activity, triggers, family history, depression, coffee consumption and physical exercise were associated with an increased probability of experiencing premonitory symptoms (p ≤ 0.001). The premonitory symptoms of migraine with and without aura differ in prevalence and most common symptoms. The cluster analysis revealed pairwise clustering of the following premonitory symptoms: Photophobia/phonophobia, concentration change/dysesthesia, loquacity/overactivity, yawning/drowsiness, fatigue/dizziness, and mood change/irritability. The correlation analysis of triggers and premonitory symptoms revealed that temperature change, environment change, sleep disorder, activity and stress were related to multiple premonitory symptoms, and that food, light, menstruation, alcohol and odor were related to special premonitory symptoms (p ≤ 0.001). CONCLUSION: The prevalence of premonitory symptoms among migraineurs in China is 21.5%. Some factors influence the probability of experiencing premonitory symptoms. Paired premonitory symptoms in the clustering analysis may share similar origins. Certain triggers associated with multiple premonitory symptoms may induce brain dysfunction; however, other triggers that overlap with corresponding special premonitory symptoms may be premonitory symptoms or a form of premonitory symptom.

Aberrant activity within auditory network is associated with psychiatric comorbidities in interictal migraineurs without aura.

The present study aimed to explore associations between brain activity in the auditory cortex and clinical and psychiatric characteristics in patients with migraine without aura (MwoA) during interictal periods. Resting-state data were acquired from patients with episodic MwoA (n = 34) and healthy controls (n = 30). Independent component analysis was used to extract and calculate the resting-state auditory network. Subsequently, we analyzed the correlations between spontaneous activity in the auditory cortex and clinical and psychiatric features in interictal MwoA. Compared with healthy controls, patients with MwoA showed increased activity in the left superior temporal gyrus (STG), postcentral gyrus (PoCG) and insula. Brain activity in the left STG was positively correlated with anxiety scores, and activity in the left PoCG was negatively correlated with anxiety and depression scores. No significant differences were found in intracranial volume between the two groups. This study indicated that functional impairment and altered integration linked to the auditory cortex existed in patients with MwoA in the interictal period, suggesting that auditory-associated cortex disruption as a biomarker may be implemented for the early diagnosis and prediction of neuropsychiatric impairment in interictal MwoA patients.

Migraine and cardiovascular risk factors: A clinic-based study.

OBJECTIVE: The relation between migraine and vascular risk factors is an unclear issue. Furthermore, the reasons for chronification are still unknown. Probably, the age-related risk and other factors leading to migraine progression will also change in the future. Under these questions, we aimed to investigate whether or not there is a specific association with vascular risk factors between several age groups and subtypes of migraine and also in their families. METHODS: A dataset (the Turkish Headache Database) from four tertiary headache centres in Turkey was used. This database included headache-defining features according to ICHD criteria based on face-to-face interviews and examinations by a Neurologist. Vascular risk factors of migraine without aura (MwoA), migraine with aura (MwA) and chronic migraine (CM) were compared between three age groups (under 30 years, 30-50 years and over 50 years) and in first-degree relatives of the patients. Our study included 2712 patients comprising 1868 (68.9 %), 246 (9.1 %) and 598 (22.1 %) subjects with MwoA, MwA and CH, respectively. RESULTS: This study showed that both the patients and the first-degree relatives were more frequently associated with vascular risk factors in CM than episodic MwA and MwoA. MwoA showed a weaker association with vascular risk factors than MwA and CM. CONCLUSION: Chronic migraine was associated with vascular risk factors at all ages and first-degree relatives as well. Vascular risk factors should be investigated with greater focus on chronic migraine.

Prevalence and risk factors of migraine and non-migraine headache in older people - results of the Heinz Nixdorf Recall study.

BACKGROUND: The prevalence of migraine and non-migraine headache declines with age. METHODS: Data from the third visit (2011-2015) of the population-based Heinz Nixdorf Recall study were analysed (n = 2038, 51% women, 65-86 years). Possible risk factors for headache activity (obesity, education, smoking, sports, alcohol, partnership status, living alone, having children, sleep quality, depression, hypertension, diabetes mellitus, stroke, coronary heart disease, medication), and headache symptoms were assessed. We estimated the lifetime prevalence and the prevalence of current active headache of migraine with and without aura, and non-migraine headache. The associations between possible risk factors and headache activity (active vs. inactive) were estimated by age and sex-adjusted odds ratios and 95% confidence intervals (OR [95% CI]) using multiple logistic regression. RESULTS: The lifetime prevalence of migraine was 28.6% (n = 584). One hundred and ninety-two (9.4%) had still-active migraine, 168 (3.5%) had migraine with aura, and 416 (5.9%) had migraine without aura. One hundred and sixty-eight (8.2%) had "episodic infrequent migraine, 0-8 headache days/month", 10 (0.5%) had "episodic frequent migraine, 9-14 headache days/month", and five (0.2%) had "chronic migraine, ≥15 headache days/month". Overall, 10 (0.5%) had "chronic headache, any headache on ≥15 days/month". Female gender and younger age were the most important associated migraine risk factors. Depression (1.62 [1.06; 2.47]) and poor sleep (1.06 [1.00; 1.12]) were associated with migraine and headache activity in general. Antihypertensives were associated with headache remission (0.80 [0.64; 1.00]). Additionally, undertaking less sports (0.72 [0.51; 1.03]) was associated with higher migraine activity. CONCLUSIONS: Headaches and migraines are not rare in the older population. They are related to mood and sleep disturbance, and migraine even to less physical activity. Antihypertensives are related to headache remission.

Atrial fibrillation and migraine with aura in young adults with ischemic stroke.

BACKGROUND: Migraine is associated with an increased risk of ischemic stroke. The associations are stronger in migraine with aura than in migraine without aura, in women than in men, and in younger subjects. However, the mechanisms by which migraine might increase the risk of ischemic stroke are debated. METHODS: We analysed the associations between migraine without aura and migraine with aura and the causes of ischemic stroke in patients aged 18-54 years treated consecutively in a university hospital stroke center. RESULTS: A total of 339 patients (mean/SD age 43.8/8.8 years, 62.83% male) were included. Migraine with aura was diagnosed in 58 patients, and migraine without aura in 54 patients. Patients with migraine with aura were younger and had fewer traditional cardiovascular risk factors than patients with no migraine. Migraine with aura was strongly associated with atrial fibrillation (odds ratio, 5.08; 95% confidence interval, 1.24-21.92; p = 0.011) and negatively associated with atherosclerosis (odds ratio, 0.29; 95% confidence interval, 0.05-0.97; p = 0.033) and small vessel disease (odds ratio, 0.13; 95% confidence interval, 0.00-0.87; p = 0.022). No other cause of stroke was significantly associated with migraine. The most common cause of stroke was atherosclerosis in no-migraine patients, dissection in migraine without aura patients and patent foramen ovale in migraine with aura patients. Atrial fibrillation was, together with dissection, the second leading cause of stroke in migraine with aura patients, accounting for 10.34% of cases in this subgroup. CONCLUSION: We showed that atrial fibrillation was a common cause of ischemic stroke in young adults with migraine with aura.

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.

Lasmiditan in patients with common migraine comorbidities: a post hoc efficacy and safety analysis of two phase 3 randomized clinical trials.

OBJECTIVE: Determine whether common migraine comorbidities affect the efficacy and safety of lasmiditan, a 5-HT1F receptor agonist approved in the United States for the acute treatment of migraine. METHODS: In SPARTAN and SAMURAI (double-blind Phase 3 clinical trials), patients with migraine were randomized to oral lasmiditan 50 mg (SPARTAN only), 100mg, 200 mg, or placebo. Lasmiditan increased the proportion of pain-free and most bothersome symptom (MBS)-free patients at 2 h after dose compared with placebo. Most common treatment-emergent adverse events (TEAEs) were dizziness, paraesthesia, somnolence, fatigue, nausea, muscular weakness, and hypoesthesia. Based upon literature review of common migraine comorbidities, Anxiety, Allergy, Bronchial, Cardiac, Depression, Fatigue, Gastrointestinal, Hormonal, Musculoskeletal/Pain, Neurological, Obesity, Sleep, and Vascular Comorbidity Groups were created. Using pooled results, efficacy and TEAEs were assessed to compare patients with or without a given common migraine comorbidity. To compare treatment groups, p-values were calculated for treatment-by-subgroup interaction, based on logistic regression with treatment-by-comorbidity condition status (Yes/No) as the interaction term; study, treatment group, and comorbidity condition status (Yes/No) were covariates. Differential treatment effect based upon comorbidity status was also examined. Trial registration at clinicaltrials.gov: SAMURAI (NCT02439320) and SPARTAN (NCT02605174). RESULTS: Across all the Comorbidity Groups, with the potential exception of fatigue, treatment-by-subgroup interaction analyses did not provide evidence of a lasmiditan-driven lasmiditan versus placebo differential treatment effect dependent on Yes versus No comorbidity subgroup for either efficacy or TEAE assessments. CONCLUSIONS: The efficacy and safety of lasmiditan for treatment of individual migraine attacks appear to be independent of comorbid conditions.

Prevalence of ischemic stroke and atrial fibrillation in young patients with migraine national inpatient sample analysis.

OBJECTIVE: To estimate the prevalence of ischemic stroke (IS) and atrial fibrillation (AF) in young patients with migraine and to identify the independent predictors of IS in a large cohort of hospitalized patients. METHODS: A cohort of patients with migraine with aura (MA) and migraine without aura (MO) was identified from the National Inpatient Sample database for the years 2012 to 2015. Ischemic stroke was identified by the International Classification of Diseases-9-CM codes. Binary logistic regression and Chi-square tests were utilized. RESULTS: A total number of 834,875 young patients (18-44 years) were included in this study with a mean age of 33 years. The prevalence of IS was 1.3% and was significantly higher in patients with MA (3.7% versus 1.2%, P <0.001). The prevalence of AF was 0.9% and it was significantly higher in patients with MA (1.2% versus 0.8%, P <0.001). Migraine with aura was an independent predictor of IS (OR 3.23, 95% CI 3.05-3.42, P <0.001) and AF (OR 1.63, 95% CI 1.42-1.88, P <0.001). Other predictors of IS were hypertension (OR 2.2, 95% CI 2.12-2.3, P <0.001), diabetes mellitus (DM) (OR 1.37, 95% CI 1.31-1.42, P <0.001), peripheral vascular disease (PVD) (OR 12.08, 95% CI 11.23-12.98, P <0.001) and smoking (OR 1.37, 95% CI 1.31-1.42, P <0.001). CONCLUSION: In this relatively large study, the overall prevalence of IS in young migraine patients was low at 1.3%. The prevalence of IS and AF was significantly higher in patients with MA. Presence of PVD confers a high risk of IS in young patients with migraine. Migraine aura was observed to be an independent predictor of IS and AF in patients with history of migraine. Optimal control of vascular risk factors in migraine patients appears to be indicated despite the overall low risk.

On the utility of the trail making test in migraine with and without aura: a meta-analysis.

This meta-analytical review assesses the utility of the Trail Making Test (TMT), versions A and B, in detecting migraine-related cognitive deficits. A comprehensive literature search was performed in two electronic databases and other sources to obtain relevant studies administering TMT to migraine patients. Search terms included "migraine" and "Trail Making". Only studies in which the TMT-A, TMT-B or both were administered to adult patients suffering from migraine with and without aura were included. All pooled meta-analyses were based on random effects models. A total of 14 studies for TMT-A and 15 for TMT-B met inclusion criteria and were subjected to meta-analyses. Results showed that performance is worse in migraine patients than in controls for both the TMT-A (Hedges' g = -.28) and TMT-B (g = -.37), with no difference between migraine with and without aura. This study demonstrates the sensitivity of the TMT in detecting cognitive alterations in migraine. This test should be considered for inclusion in cognitive batteries assessing patients with migraine.