Risk Of Migraine Research Articles

Brain structures as potential mediators of the causal effect of COVID 19 on migraine risk.

Migraine is a common neurological disorder observed after coronavirus disease 2019 (COVID 19) infection. However, the intricate relationship between COVID 19 and migraine, particularly the potential mediating role of brain imaging-derived phenotypes (BIPs), remains unclear. This study used linkage disequilibrium score regression (LDSC), a bidirectional two-sample Mendelian randomization (MR) approach, and two-step MR analysis to investigate potential causal links. The robustness of the MR findings was corroborated through generalized summary-data-based Mendelian randomization (GSMR) and MR-Steiger methods. The results of the LDSC analysis revealed that the genetic correlation coefficient between COVID 19 traits and migraine was 0.0277 for infection (P = 0.0051), 0.1690 for hospitalization (P = 0.0016), and 0.1147 for severity (P = 0.0330). The genetic correlation coefficients between COVID 19 infection, hospitalization, severity and migraine and migraine with aura (MA) were 0.2654 (P = 0.0012), 0.2065 (P = 0.0043), and 0.1537 (P = 0.0230), respectively. Two-sample MR analysis revealed a significant causal association of COVID 19 infection (odds ratio [OR] 1.2502, P = 0.0083; OR 1.4956, P = 0.0084), hospitalization (OR 1.0689, P = 0.0138; OR 1.0919, P = 0.0208), and severity (OR 1.0644, P = 0.0072; OR 1.0844, P = 0.0098) with increased risk of migraine and migraine with aura (MA). Cortical thickness (CT), total surface area (TSA), and fractional anisotropy (FA) were identified as BIP intermediaries in the risk trajectory from COVID 19 to migraine. The TSA exhibited a more pronounced mediating effect than did CT. This study revealed that genetically predicted COVID 19 is associated with an increased risk of migraine and MA, and BIPs act as potential mediators of these causal relationships, offering insights into the neurobiological underpinnings of migraine in the context of COVID 19.

The neurotrophic factor artemin and its receptor GFRα3 mediate migraine-like pain via the ion channel TRPM8

Background Migraine has a strong genetic foundation, including both monogenic and polygenic types. The former are rare, with most migraine considered polygenic, supported by genome-wide association studies (GWAS) identifying numerous genetic variants linked with migraine risk. Surprisingly, some of the most common mutations are associated with transient receptor potential melastatin 8 (TRPM8), a non-selective cation channel that is the primary sensor of cold temperatures in cutaneous primary afferents of the somatosensory system. However, it is unlikely that the temperature sensitivity of TRPM8 is relevant in migraine-related tissues, such as the meninges, suggesting other activation mechanisms underly its role in migraine pathogenesis. Thus, to define the basis of the channel's involvement, we reasoned that cellular processes that increase cold sensitivity in the skin, such as the neurotrophic factor artemin, via its receptor glial cell-line derived neurotrophic factor family receptor alpha-3 (GFRα3), also mediate TRPM8-associated migraine-like pain in the meninges. Methods To investigate the role of artemin and GFRα3 in preclinical rodent migraine models, we infused nitroglycerin acutely and chronically, and measured changes in periorbital and hind paw mechanical sensitivity in male and female mice lacking GFRα3, after neutralization of free artemin with specific monoclonal antibodies, or by systemic treatment with a TRPM8-specific antagonist. Further, in mice lacking GFRα3 we tested the effects of supradural infusions of a mix of inflammatory mediators, as well as tested if dura stimulation with artemin or a TRPM8-specific agonist induce migraine-related pain in mice. Results We find that mechanical allodynia induced by systemic nitroglycerin, or supradural infusion of inflammatory mediators, involves GFRα3. In addition, neutralization of circulating artemin reduces the nitroglycerin phenotype, demonstrating the importance of this neurotrophic pathway in headaches. Further, we show TRPM8 expression in the meninges, and that direct supradural infusion of either a TRPM8-specific agonist or artemin itself produces mechanical allodynia, with the latter dependent on TRPM8 and ameliorated by concurrent treatment with sumatriptan. Conclusions These results indicate that neuroinflammatory events in the meninges can produce migraine-like pain in mice via artemin and GFRα3, likely acting upstream of TRPM8, providing a novel pathway that may contribute to headaches or migraine pathogenesis.

Associations between post-traumatic stress disorder and neurological disorders: A genetic correlation and Mendelian randomization study.

Observational studies have reported a close relationship between post-traumatic stress disorder (PTSD) and neurological disorders, but the existence of a causal link remains uncertain. The aim of this study is to investigate these relationships and potential mediators via Mendelian randomization (MR) analysis. We sourced pooled data for genome-wide association study (GWAS) of PTSD (n = 1,222,882) from the psychiatric genomics consortium. Summary-level data for eight neurological traits were derived from large-scale GWASs. Genetic correlations were computed using linkage disequilibrium (LD) score regression. The inverse variance weighted (IVW) method served as the primary analysis method for MR. We employed a range of sensitivity analysis methods to ensure result robustness. A two-step approach was utilized to ascertain the effects and proportions of mediations. We identified significant genetic associations between PTSD and any dementia, cognitive performance, multiple sclerosis, and migraine. MR analysis revealed a significant association between PTSD and an increased risk of migraine (P = 0.02). This was substantiated by the results of several sensitivity analyses. Notably, the robust association between PTSD and migraine persisted even after adjustment for major depressive disorder and anxiety. Mediation analysis revealed that both alcohol intake frequency and insomnia partially mediated the association between PTSD and migraine. Participants in the MR analysis were of European descent, and verification in other ethnicities was not possible due to data limitations. Our findings indicate a close association between PTSD and migraine. Alcohol intake frequency and insomnia serve as intermediate factors, partially explaining the relationship between PTSD and migraine.

The role of digital device use on the risk of migraine: a univariable and multivariable Mendelian randomization study.

The pervasive integration of digital devices into daily life has raised concerns about their potential health impacts. This study aimed to explore the causal relationships between digital device use and the risk of migraine using Mendelian randomization (MR). Genetic data on digital device use and migraines were sourced from large-scale genome-wide association studies conducted by the UK Biobank, the FinnGen study, and the International Headache Genetics Consortium. Univariable MR (UVMR), meta-analysis, and multivariable MR (MVMR) approaches were conducted to explore and verify the causal effects of digital device use (including mobile phone use, computer use, playing computer games, and watching television) on migraine risk. Sensitivity analyses were conducted using Cochran's Q, MR-Egger intercept test, MR pleiotropy residual sum and outlier, MR Radial, MR Steiger, and leave-one-out methods. UVMR analyses revealed that genetically predicted mobile phone use was significantly associated with an increased risk of overall migraine (odds ratio [OR] = 2.39, p = 9.78e-5) and migraine without aura (MO) (OR = 2.25, p = 0.024). Additionally, there were significant positive associations between genetically predicted television watching and the risk of overall migraine (OR = 1.63, p = 2.12e-5) and MO (OR = 2.10, p = 4.98e-5). These results were further supported by the meta-analysis and MVMR analysis. Sensitivity analysis indicated no heterogeneity or pleiotropy. This comprehensive MR study provides preliminary evidence for the causal impact of mobile phone use and television watching on the risk of migraines. Further studies are needed to explore these associations across different populations.

An Integrative Migraine Polygenic Risk Score Is Associated with Age at Onset But Not Chronification.

Background/Objective: Genome-wide association studies (GWASs) demonstrate a complex genetic landscape for migraine risk. Migraine polygenic risk scores (PRSs) developed from GWAS data may have utility for predicting disease course. We analyzed the strength of association between an integrative migraine PRS and age at onset and chronification. Methods: In this retrospective clinical/genetic case-control study, PGS004799 was calculated for adults with European ancestry from two real-world community cohorts. In the DodoNA cohort, 1653 treated, deeply phenotyped migraine cases, diagnosed using International Classification of Headache Disorders 3rd edition criteria, were followed for a mean (range) of 2.3 (1-10) years and compared to 3460 controls (without migraine diagnosis). In the GHI cohort, 2443 cases were identified using the first migraine ICD code as a proxy for migraine onset and compared to 8576 controls (without migraine ICD codes). PRS associations with age at onset (DodoNA) or first migraine ICD code (GHI) and chronification (DodoNA) were evaluated. Results: In both cohorts, PRS was higher in cases (DodoNA mean (range) cases: 0.82 (0.07-1.76), controls: 0.78 (0.04-1.56); t (5111) = -6.1, p = 1.4 × 10-9, GHI: cases: 0.79 (0.003-1.68), controls: 0.75 (-0.06-1.53); t (11,017) = -7.69, p = 1.6 × 10-14), and a higher PRS was associated with earlier onset in females (HR [95% CI] DodoNA: 2.1 [1.6-2.6, p < 0.001; GHI: 1.8 [1.4-2.1], p < 0.001) and in males (DodoNA: 2.5 [1.3-4.7], p = 0.005; GHI: 1.6 [1.1-2.6], p = 0.027). PRS was not different in cases with or without chronification (t (1651) = -1.67, p = 0.094) and was not associated with earlier chronification (1.2 [0.8-1.6], p = 0.424). Conclusions: Higher genetic risk was associated with earlier onset and increased risk of migraine well into adulthood, but not with chronification. This suggests that the PRS quantifies genetic susceptibility that is distinct from factors influencing disease course.

Causal relationships between cortical brain structural alterations and migraine subtypes: a bidirectional Mendelian randomization study of 2,347 neuroimaging phenotypes

BackgroundPrevious studies have shown that migraines are associated with brain structural changes. However, the causal relationships between these changes and migraine, as well as its subtypes, migraine with aura (MA) and migraine without aura (MO), remain largely unclear.MethodsWe utilized genome-wide association study (GWAS) summary statistics from European cohorts for 2,347 cortical structural magnetic resonance imaging (MRI) phenotypes, derived from both T1-weighted and diffusion tensor imaging scans (n = 36,663), with migraine and its subtypes (n = 147,970–375,752). Cortical phenotypes included both macrostructural (e.g., cortical thickness, surface area) and microstructural (e.g., fractional anisotropy, mean diffusivity) features. Genetic correlations were first assessed to identify significant associations, followed by bidirectional Mendelian randomization (MR) analyses to determine causal relationships between these brain phenotypes and migraine, as well as its subtypes (MA and MO). Sensitivity analyses were applied to ensure the robustness of the results.ResultsGenetic correlation analysis identified 510 significant associations between cortical structural phenotypes and migraine across 401 distinct traits. Forward MR analysis revealed nine significant causal effects of cortical structural changes on migraine risk. Specifically, increased cortical thickness and local gyrification index in specific cortical regions were associated with a decreased risk of overall migraine, MA, and MO, while intracellular volume fraction and orientation diffusion index in specific regions increased the risk of MA and MO. Reverse MR analysis demonstrated that MA causally increased mean diffusivity in the insular and frontal opercular cortex. Sensitivity analyses confirmed the robustness of these findings, with no evidence of horizontal pleiotropy or heterogeneity.ConclusionThis study identifies causal relationships between cortical neuroimaging phenotypes and migraine, highlighting potential biomarkers for migraine diagnosis, treatment, and prevention.

New insights into the increased risk of migraines from COVID-19 infection and vaccination: a Mendelian randomization study.

Migraine is a prevalent neurological disorder characterized by recurrent attacks, leading to a substantial global disease burden. Recent observational studies have reported the onset and worsening of migraine following COVID-19 infection and vaccination. However, traditional observational study designs have limitations in controlling for confounding factors, potentially resulting in biased and inconsistent conclusions. To address this, we applied Mendelian randomization (MR) to investigate the causal relationship between COVID-19 infection and vaccination with migraine. This study utilized summary-level genome-wide association study (GWAS) data from the GWAS catalog and FinnGen database to evaluate the effects of varying degrees of COVID-19 infection and vaccination on migraine. We employed inverse variance weighted (IVW) fixed-effect and random-effect models as the primary methods for MR analysis, with MR-Egger and other approaches as complementary methods. Sensitivity analyses, including Cochran's Q test, MR-Egger intercept regression, and MR-PRESSO, were conducted to ensure robustness of the results. Our MR analysis revealed no significant causal association between COVID-19 infection and migraine. However, a significant causal association was found between COVID-19 vaccination and migraine (beta = 0.071, P = 0.034). The results were confirmed through a series of sensitivity tests, demonstrating the robustness of the findings. This study provides novel evidence of a significant causal link between COVID-19 vaccination and migraine, while no such association was observed with COVID-19 infection. These findings may have important implications for clinical practice, particularly in planning treatment adjustments and optimizing patient care for individuals with migraines in the context of COVID-19 vaccination.

Associations between the waist-to-height ratio index and migraine: A cross-section study of the NHANES 1999-2004.

The importance of obesity as a factor that increases the probability of migraine episodes is increasingly acknowledged. Thus, this study aimed to explore the potential correlation between central obesity and migraine, emphasizing the waist-to-height ratio (WHtR) as a key measure in assessing this relationship. This cross-sectional analysis included 13,344 individuals who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999-2004. To investigate the association associations between WHtR and migraine, we utilized refined multivariate logistic regression models, smoothing curve fitting methods, subpopulation analysis, and interactive testing. Of the 13,344 participants, 2,764 (20.72%) had migraines. A significant positive correlation was observed between the WHtR and migraine incidence in both the partially adjusted model (3.08 [95% CI: 1.92-4.94]) and the crude model (1.95 [95% CI: 1.23-3.08]). The participants in the highest quartile of the WHtR had a 13% greater incidence of migraine than those in the lowest quartile [1.13(0.99,1.28)]. The interaction analysis revealed a statistically significant difference (p<0.01) in this relationship among the subgroups. Notably, the correlation between WHtR and migraine risk was not significant and negative in patients ≥60 years, indicating that obesity has a mitigating role in preventing migraine in this elderly population. The incidence of migraine increased concomitantly with increased WHtR. However, central obesity has a protective effect against migraine occurrence in individuals ≥60 years. Thus, our findings underscore the importance of WHtR in migraine prevention and management strategies and highlight its potential as a critical biomarker for mitigating migraine incidence.

Cannabis use disorder increases risk of large-artery atherosclerotic stroke and migraine with aura through mendelian randomization study

Observational studies have shown some association between cannabis use disorder (CUD) and neurological disorders, but their causal relationship is unclear. In this study, we tested the potential causal relationship between CUD and three common neurological disorders using two-sample Mendelian randomization (TSMR) and multivariate MR (MVMR) methods. Thirty-two genetic loci were extracted as exposure factors from the largest genome-wide association study (GWAS) summary statistics for CUD to date. TSMR results showed that genetic prediction of CUD with all stroke, ischemic stroke, large-artery atherosclerotic stroke, migraine with aura, and Alzheimer’s disease (AD) had a positive causal relationship (P < 0.05), which was not found in several other diseases. The association between CUD and stroke, ischemic stroke, and AD in the MVMR study may have been influenced by confounding factors (P > 0.05). Subgroup analyses highlighted a causal relationship between genetically predicted CUD and large-artery atherosclerotic stroke (OR = 1.169; 95%CI 1.030–1.328; P = 0.016) and migraine with aura (OR = 1.142; 95% 1.021–1.278; P = 0.020). Our further functional mapping and annotation enrichment analyses using FUMA suggest that the brain-gut axis may serve as another layer of explanation for the existence of an association between CUD and neurological disorders.

Association between brain resting-state functional activities and migraine: a bidirectional mendelian randomization study

Researchers have conducted extensive research on the correlation between brain resting-state functional activities (RSFA) and migraine. However, we still do not fully understand the exact nature of the causal relationship between these RSFA and migraine. We conducted a bidirectional two-sample Mendelian randomization (MR) study to investigate the causal association between migraine and RSFA. We gathered summary statistics from genome-wide association studies for 191 resting-state functional magnetic resonance imaging phenotypes. We employed various analytical methods for bidirectional two-sample MR analyses. This included inverse variance weighted, weighted median, MR Egger, and the constrained maximum likelihood approaches. We also conducted pleiotropy and heterogeneity analyses to evaluate the robustness and reliability. We found the functional connectivity between the default mode and the central executive network (OR = 1.39, p = 4.77 × 10−4, FDR corrected p value = 0.040) and the intensity of spontaneous brain activity in the calcarine or lingual gyrus within the visual network (OR = 0.74, p = 5.94 × 10−4, FDR corrected p value = 0.040) having a causal effect on the risk of migraine. Our MR analysis provided genetic support for these networks, which may play an important role in influencing migraine susceptibility.

Polymorphisms of Estrogen receptor alpha (ESR1) rs9340799, rs2234693, rs1801132, and rs2228480 and their association with migraine risk: a meta-analysis with meta-regression and trial sequential analysis

Polymorphisms of Estrogen receptor alpha (ESR1) rs9340799, rs2234693, rs1801132, and rs2228480 and their association with migraine risk: a meta-analysis with meta-regression and trial sequential analysis

The neurotrophic factor artemin and its receptor GFRα3 mediate migraine-like pain via the ion channel TRPM8.

Migraine has a strong genetic foundation, including both monogenic and polygenic types. The former are rare, with most migraine considered polygenic, supported by genome-wide association studies (GWAS) identifying numerous genetic variants associated with migraine risk. Surprisingly, some of the most common mutations are associated with TRPM8, a non-selective cation channel that is the primary sensor of cold temperatures in primary afferent neurons of the somatosensory system. However, it is unlikely that the temperature sensitivity of TRPM8 underlies its role in migraine pathogenesis. To define the basis of the channel's involvement, we reasoned that cellular processes that increase cold sensitivity in the skin, such as the neurotrophic factor artemin, via its receptor GFRα3, also mediate TRPM8-associated migraine-like pain in the meninges. To investigate the role of artemin and GFRα3 in preclinical rodent migraine models, we infused nitroglycerin acutely and chronically, and measured changes in periorbital and hind paw mechanical sensitivity in male and female mice lacking GFRα3, after neutralization of free artemin with specific monoclonal antibodies, or by systemic treatment with a TRPM8-specific antagonist. Further, in wildtypes and mice lacking either GFRα3 or TRPM8, we tested the effects of supradural infusions of a mix of inflammatory mediators, artemin, and a TRPM8-specific agonist on migraine-related pain in mice. We find that mechanical allodynia induced by systemic nitroglycerin, or supradural infusion of inflammatory mediators, involves GFRα3. In addition, neutralization of circulating artemin reduces the nitroglycerin phenotype, demonstrating the importance of this neurotrophic pathway. Further, we show TRPM8 expression in the meninges and that direct supradural infusion of either a TRPM8-specific agonist or artemin itself produces mechanical allodynia, the latter dependent on TRPM8 and ameliorated by concurrent treatment with sumatriptan. These results indicate that neuroinflammatory events in the meninges can produce migraine-like pain in mice via artemin and GFRα3, likely acting upstream of TRPM8, providing a novel pathway that may contribute to migraine pathogenesis.

Clinical Efficacy of Transcatheter Closure of Patent Foramen Ovale with Positive Foaming Test

Background and Aims: To explore and evaluate the clinical therapeutic effect of interventional occlusion in the treatment of patent foramen ovale (PFO) with positive foaming test in the prevention and treatment of cryptogenic stroke (CS) and to provide clinical basis for individualized treatment of CS patients with PFO. Methods: A total of 151 patients who was admitted to Beijing Anzhen Nanchong Hospital Hospital from January 2019 to June 2021 were divided into two groups: drug therapy group (n = 63) and interventional occlusion + drug therapy group (n = 88). The general clinical data of the patients were collected by retrospective study, including sex, age, body weight, right to left shunt (RLS) magnitude, the degree of migraine before treatment, and telephone follow-up of all patients after treatment. Results: There was no significant difference in general clinical data (p &gt; 0.05). In the interventional occlusion + drug therapy group, the stroke recurrence rate within 6th month after operation was significantly lower than that in the drug therapy group, and the difference was statistically significant (p &lt; 0.05); The degree of migraine was lower than that in the drugs treatment group at the 3rd month after operation and the difference was statistically significant (p &lt; 0.01); The degree of migraine at the 6th month was lower than that in the drug therapy group but the difference was not statistically significant (p &gt; 0.05). The results of comprehensive generalized analysis showed that the risk of moderate or severe headache in the interventional occlusion + drug therapy group decreased by 40% (odds ratio [OR] = 0.60, p &lt; 0.05). The degree of migraine in female patients was statistically lower after three and six months postoperatively (p &lt; 0.05 and p = 0.01, respectively). Combined with generalized analysis, the risk of moderate or severe migraine in female patients was reduced by 55%. There were significant differences in the migraine before operation, migraine at the 3rd month and migraine at the 6th month in patients with three different kinds RLS grades (p &lt; 0.01, p &lt; 0.01, p &lt; 0.05). Compared with the preoperative migraine and the migraine at the 3rd month, patients with RLS grade 3 had the most obvious migraine relief at the 6th month after operation than those with RLS grade 2. Conclusion: Compared with the drug therapy, interventional occlusion + drug therapy can reduce the risk of CS recurrence, improve the prognosis and significantly reduce the degree of migraine. Patients of different genders had different degrees of migraine, women had a lighter degree of migraine and a reduced risk of moderate or severe migraine, women benefited more after treatment. Patients with different RLS grades have different postoperative migraine relief. Patients with preoperative RLS grade 3 have the most obvious postoperative migraine relief and patients with preoperative RLS grade 3 benefit more after treatment.

Heightened migraine risk in patients with rheumatoid arthritis: A national retrospective cohort study.

This study aimed to evaluate the association between rheumatoid arthritis (RA) and subsequent migraine risk using the Korean National Health Insurance Service database. Migraine may be related to immune dysfunction and previous studies have suggested an association with chronic inflammatory rheumatic diseases; however, the relationship between RA and migraine remains unclear. This was a population-based, nationwide, retrospective, longitudinal cohort study. Participants were enrolled from 2010 to 2017 and followed up until 2019. A total of 42,674 patients who had undergone a health checkup within 2 years prior to the initial diagnosis of RA were included in the study, after applying the exclusion criteria (previous migraine, other rheumatic disease, missing variables of interest). A non-RA control was obtained by age and sex-matching (1:5). Finally, 42,644 patients with RA were enrolled, with 213,370 individuals without RA included as controls. Among the patients with RA, 29,744 had seropositive RA (SPRA), and 12,900 had seronegative RA (SNRA). SPRA was defined by the International Classification of Diseases 10th revision (ICD-10) code M05, prescription of disease-modifying anti-rheumatic drugs (DMARDs), and enrollment in a special copayment reduction program. SNRA was defined by the ICD-10 code M06 and prescription of any DMARD. The primary endpoint was the occurrence of migraine incidents, defined using the ICD-10 code of migraine (G43). A total of 22,294 migraine cases (17,912/213,370 [8.3%] in controls and 4382/42,674 [10.2%] in RA) were reported during a mean follow-up of 4.4 years after a 1-year lag period. Patients with RA had a 1.2-fold higher risk of migraine compared with controls (adjusted hazard ratio [aHR] 1.21, 95% confidence interval [CI] 1.17-1.26). Increased risk of migraine was found in both patients with SNRA and SPRA compared with controls (aHR 1.20, CI 1.15-1.24 in SPRA; aHR 1.26, CI 1.19-1.34 in SNRA). Compared to patients with SNRA, those with SPRA did not demonstrate a heightened risk (aHR 0.94, CI 0.88-1.01). A significant interaction was confirmed between covariates (male, current smoker, those with diabetes mellitus, and dyslipidemia) and the risk of migraine (p for interaction of <0.05). RA was linked to a higher migraine risk, regardless of seropositivity.

Serum Vitamin D, Calcium, and Magnesium Levels in Patients with Migraine Presenting to PEMH, Pakistan: A Case-Control Study

Background: Migraine is a common neurological disorder characterized by recurrent headaches of varying intensity and duration. Micronutrient deficiencies, particularly in vitamin D, calcium, and magnesium, have been implicated in migraine pathogenesis.Objective: This study aimed to assess serum levels of vitamin D, calcium, and magnesium in migraine patients compared to healthy controls.Methods: A case-control study was conducted at Pak Emirates Military Hospital, Rawalpindi, involving 180 participants, divided equally into migraine cases and healthy controls. Serum vitamin D levels were measured using electrochemiluminescence, while calcium and magnesium levels were determined using photometry. Data were analyzed using SPSS version 25.0, with p-values &lt;0.05 considered significant.Results: Migraine patients had significantly lower serum levels of vitamin D (18.2 ± 5.6 ng/mL vs. 28.4 ± 6.2 ng/mL, p&lt;0.001), calcium (8.7 ± 0.6 mg/dL vs. 9.2 ± 0.5 mg/dL, p=0.013), and magnesium (1.8 ± 0.2 mg/dL vs. 1.9 ± 0.3 mg/dL, p=0.025). Multivariate analysis showed significant associations between higher levels of these nutrients and reduced migraine risk.Conclusion: Lower serum levels of vitamin D, calcium, and magnesium are associated with an increased risk and severity of migraines, suggesting potential targets for preventive and therapeutic strategies.

Effect of Smoking on the Development of Migraine in Women: Nationwide Cohort Study in South Korea.

Smoking is known to be a significant risk factor for various diseases. Migraine, a condition requiring careful lifestyle management, currently lacks specific guidelines advocating for smoking cessation as a preventive measure. Although cross-sectional studies have suggested a potential link between smoking and an increased risk of migraine, the findings have been inconsistent and conflicting. To date, there has been no longitudinal study which investigated the effect of smoking on the risk of migraine in a prospective setting. This longitudinal study aimed to investigate the impact of smoking on the incidence of migraine in women and examine the modifying effect of menopausal status. Using nationally representative National Health Insurance Service (NHIS) data, women aged ≥40 years who participated in national breast cancer screening in 2009 were followed-up until the end of 2019. Baseline data on smoking status (non-, ex-, and current smoker) as well as the duration and amount of cigarette smoking were collected. A Cox proportional hazards regression model was used to examine the independent effect of smoking on the risk of incident migraine after adjusting for demographics, comorbidities, and female reproductive factors. The results were stratified by menopausal status, and an interaction analysis (smoking × menopause) was performed. In total, 1,827,129 women were included in the analysis. Women with a history of smoking exhibited a higher risk of developing migraine, compared with nonsmokers. Specifically, a higher risk of migraine was observed in women with past (adjusted hazard ratio [HR] 1.044, 95% CI 1.000-1.089) and current cigarette use (adjusted HR 1.050, 95% CI, 1.023-1.079) than in nonsmokers. The effect was greater in premenopausal women (adjusted HR 1.140, 95% CI, 1.108-1.172) than in postmenopausal women (adjusted HR 1.045, 95% CI 1.018-1.073; P<.001). The risk increased with an increased amount of smoking, with a greater association in premenopausal women (P<.001). Smoking increases the risk of migraine in women, with a dose-dependent relationship. Menopause modifies this effect. Our findings suggest that smoking is an important modifiable risk factor of migraine, with a higher impact in premenopausal women. The interaction between smoking and estrogen may increase the vulnerability of the migraine brain.

COVID-19, vaccination and migraine: Causal association or epiphenomenon?

Diverse studies have revealed discrepant evidence concerning the causal association between Corona Virus Disease 2019 (COVID-19) and COVID-19 vaccination in relation to migraines. Investigating the correlation between the former two factors and migraines can facilitate policymakers in the precise formulation of comprehensive post-pandemic interventions while urging the populace to adopt a judicious perspective on COVID-19 vaccination. We undertook a Mendelian randomization (MR) study. The primary assessment of the causal relationship between the three different COVID-19 exposures and migraine was conducted using the standard inverse variance weighted (IVW) approach. In the supplementary analysis, we also employed two methodologies: the weighted median estimator (WME) and the MR-Egger regression. Ultimately, the reliability and stability of the outcomes were assessed via Cochran's Q test, the leave-one-out method, the MR-Egger intercept test, and the MR pleiotropy residual sum and outlier (MR-PRESSO) test. The results indicate an absence of correlation between genetically predicted COVID-19 (①Very severe respiratory confirmed COVID-19: odds ratio [OR], 1.0000881; 95%CI, 0.999748-1.000428; p = 0.6118; ②Hospitalized COVID-19: OR, 1.000024; 95%CI, 0.9994893-1.000559; p = 0.931;③SARS-CoV-2 infection: OR, 1.000358; 95%CI, 0.999023-1.001695; p = 0.5993) and the risk of migraine. Furthermore, the MR-Egger regression and WME also yielded no evidence of COVID-19 elevating the risk of migraine occurrence. Sensitivity analysis affirmed the robustness and consistency of all outcomes. The results of this study do not offer genetic evidence to substantiate a causal relationship between COVID-19 and migraines. Thus, the deduction drawn from COVID-19 genetic data is that COVID-19 vaccination is unlikely to exert an impact on the occurrence of migraines, though this conclusion warrants further investigation.

Genetic overlap and Mendelian randomization analysis highlighted the causal relationship between psoriatic disease and migraine.

Despite observational studies suggesting a link between psoriatic disease (including psoriasis and psoriatic arthritis) and migraine, it is unclear whether there is a shared genetic etiology or a causal relationship between the two conditions. We aimed to reveal the genetic overlap and causality using the Mendelian randomization (MR) framework. The genetic analysis utilized summary data from the most extensive European genome-wide association study (GWAS) of migraine. Well-powered psoriatic disease GWAS data were obtained from two independent cohort studies, which served as discovery and validation datasets. Global and regional genetic correlations between psoriatic disease and migraine were assessed, and pleiotropic regions identified by pairwise GWAS analysis were further annotated. We further applied a two-sample MR multivariate MR to investigate the potential causal relationship between them. The global genetic correlation test indicated weak correlations between psoriatic disease and migraine, while regional correlation analyses delineated one significant shared locus between psoriasis and migraine. Pathway enrichment analysis revealed that shared genes were involved biological processes to the major histocompatibility and antigen processing and presentation. In terms of causality estimates, genetically predicted psoriasis (Pmeta = 0.003) and psoriatic arthritis (Pmeta = 0.028) were associated with an increased risk of migraine. Multivariate MR analysis indicated that psoriasis was an independent risk factor for migraine (P < 0.05). No significant associations were found in the reverse direction. Our study supported the causal role of psoriasis on migraine, and the central role for immunomodulatory etiology. These findings have significant implications for the management of migraine and clinical practice in patients with psoriasis.

The Glymphatic System and its Relationship to Migraine.

We aim to critically review animal and human studies of the glymphatic system in migraine and propose a model for how the glymphatic system may function in migraine, based on the available evidence. Early studies in animal models report migraine attacks temporarily disrupt glymphatic flow. Human imaging studies suggest chronic migraine may be associated with alterations in glymphatic system function, albeit with conflicting results. Presently, it remains unknown whether repetitive migraine attacks or frequent nights of insomnia impair glymphatic system function over time in those with migraine, and whether alterations in glymphatic function could contribute to worsening migraine disability or risk for cognitive disease. Longitudinal studies of glymphatic function in patients with migraine and insomnia, with inclusion of cognitive assessments, may be informative.

Inflammo-immune perspective on the association of eight migraine risk factors with migraine: a multi-omics Mendelian randomization study.

Migraine risk factors are associated with migraine susceptibility, yet their mechanisms are unclear. Evidence suggests a role for inflammatory proteins and immune cells in migraine pathogenesis. This study aimed to examine the inflammo-immune association between eight migraine risk factors and the disorder. This study utilized inverse variance weighted (IVW) method and colocalization analysis to explore potential causal relationships between eight migraine risk factors, migraine, 731 immune cells, and 91 circulating inflammatory proteins. Mediation Mendelian randomization (MR) was further used to confirm the mediating role of circulating inflammatory proteins and immune cells between the eight migraine risk factors and migraine. Migraine risk factors are linked to 276 immune cells and inflammatory proteins, with cigarettes smoked per day strongly co-localized with CD33-HLA DR+ cells. Despite no co-localization, 23 immune cells/inflammatory proteins relate to migraine. Depression, all anxiety disorders, and sleep apnea are correlated with migraine, and all anxiety disorders are supported by strong co-localization evidence. However, the mediating effect of inflammatory proteins and immune cells between eight migraine risk factors and migraine has not been confirmed. We elucidate the potential causal relationships between eight migraine risk factors, migraine, immune cells, and inflammatory proteins, enhancing our understanding of the molecular etiology of migraine pathogenesis from an inflammatory-immune perspective.