Risk Of Migraine Research Articles

A Comprehensive Review on the Role of Genetic Factors in the Pathogenesis of Migraine.

Migraine is a common neurovascular condition. This disorder has a complex genetic background. Several single-nucleotide polymorphisms (SNPs) or mutations within genes regulating glutamatergic neurotransmission, cortical excitability, ion channels, and solute carriers have been associated with polygenic and monogenic forms of migraine. SNPs within ACE, DBH, TRPM8, COMT, GABRQ, CALCA, TRPV1, and other genes have been reported to affect the risk of migraine or the associated clinical parameters. The distribution of some HLA alleles within the HLA-DRB1, HLA-DR2, HLA-B, and HLA-C regions have also been found to differ between migraineurs and healthy subjects. In addition, certain mitochondrial DNA changes and polymorphisms in this region have been shown to increase the risk of migraine. A few functional studies have investigated the molecular mechanisms contributing to these genetic factors in the development of migraine. Here we review studies evaluating the role of genetic polymorphisms and mRNA/miRNA dysregulation in migraine.

Association between tumor necrosis factor alpha and lymphotoxin alpha gene polymorphisms and migraine occurrence among Jordanians.

Inflammatory reactions in the body have been shown to contribute to migraine development. Therefore, genes involved in the inflammatory pathways might play a role in the susceptibility and development of migraine. In this study, polymorphisms in tumor necrosis factor alpha (TNFα) and lymphotoxin alpha (LTA) genes were tested for association with migraine. A total of 398 participants (198 migraine patients and 200 controls) were recruited in the study. Serum TNF level was measured using a sandwich ELISA kit. Lymphocytes' and monocytes' counts were obtained from a differential complete blood count profile. Participants' DNA was extracted and genotyped for rs1800629 and rs1799724 in TNFα, and rs909253 in LTA. Controls had a significantly higher mean lymphocyte count (P = 0.018), while the mean monocyte count and serum TNFα levels did not differ between the two groups (P > 0.05). With respect to gene polymorphisms, the rs1800629 and rs1799724 variants showed significant association with migraine in all subjects, and in males and females when analyzed separately (P < 0.001). The rs909253 did not show any statistical difference in frequencies among the two groups (P > 0.05). Having the A allele in rs1800629 was associated with a higher risk of migraine in both male (OR, 95%; CI, G/A = 3.79 [1.87-7.69]; A/A = 14.22 [1.67-121.14]; P < 0.01) and female (OR, 95%; G/A = 2.54 [1.47-4.38]; A/A = 2.52 [1.12-5.69]; P < 0.001) subjects. In conclusion, rs1800629 and rs1799724 in TNFα showed significant association with migraine among the Jordanian population.

Migraine and Vascular Risk: An Update.

Migraine is a common neurological disorder with significant morbidity and disability. There is growing evidence that migraine is associated with cardiovascular diseases and stroke. The aim of this study was to provide an update on the association of migraine with some common vascular diseases in persons suffering from the disease and discuss the clinical implications. We searched PUBMED database using the MeSH terms "Stroke", "Coronary Artery Disease", "Myocardial Ischemia", "Atrial Fibrillation", "White Matter" and "Dementia, Vascular", in combination with "Migraine Disorders", "Migraine with Aura" and "Migraine without Aura" and reviewed the relevant studies. We studied articles mostly in English for the past 10 years, without excluding older articles that were relevant to this review. We also searched the reference lists of articles obtained and included some insightful reviews on 'Migraine and Vascular Risk'. The association between migraine and vascular diseases is strong and consistent for ischemic stroke and migraine with aura especially in young women, with oral contraceptive use and smoking. Although literature reports a higher prevalence of obesity, dyslipidemia, and family history of cardiovascular diseases in migraineurs, the 'migraine-vascular' connection persists in models where the traditional vascular risk factors are adjusted, implicating a migraine-specific pathophysiology at work. There is some evidence linking an adverse vascular risk factor profile to incident myocardial infarction in people with migraine. The association with hemorrhagic stroke is more variable. Although the absolute effect of migraine on 'vascular risks' is small, good practice parameters dwell on treating and reducing existing cardiovascular risk factors through lifestyle modification, encouraging smoking cessation, and advocating the wise use of agents like ergot alkaloids and oral contraceptives, after a risk-benefit analysis.

Migraine in children and adults born preterm: A nationwide register linkage study.

Being born preterm is related to adverse health effects later in life. We studied whether preterm birth predicts the risk of migraine. In this nationwide register study, we linked data from six administrative registers for all 235,624 children live-born in Finland (January 1987 to September 1990) and recorded in the Finnish Medical Birth Register. n = 228,610 (97.0%) had adequate data and were included. Migraine served as primary outcome variable and was stringently defined as a diagnosis from specialised health care and/or ≥2 reimbursed purchases of triptans. We applied sex- and birth year-stratified Cox proportional hazard regression models to compute hazard ratios and confidence intervals (95% confidence intervals) for the association between preterm categories and migraine. The cohort was followed up until an average age of 25.1 years (range: 23.3-27.0). Among individuals born extremely preterm (23-27 completed weeks of gestation), the adjusted hazard ratios for migraine was 0.55 (0.25-1.24) when compared with the full-term reference group (39-41 weeks). The corresponding adjusted hazard ratios and 95% confidence intervals for the other preterm categories were: Very preterm (28-31 weeks); 0.95 (0.68-1.31), moderately preterm (32-33 weeks); 0.96 (0.73-1.27), late preterm (34-36 weeks); 1.01 (0.91-1.11), early term (37-38 weeks); 0.98 (0.93-1.03), and post term (42 weeks); 0.98 (0.89-1.08). Migraine was predicted by parental migraine, lower socioeconomic position, maternal hypertensive disorder and maternal smoking during pregnancy. We found no evidence for a higher risk of migraine among individuals born preterm.

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

The prevalence of migraine and non-migraine headache declines with age. 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. 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. 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.

The association between migraine genetic risk and dementia: A Mendelian randomization study

AbstractBackgroundAlthough some studies have suggested a possible link between migraine and dementia, there have been concerns that these associations may be due to diagnostic bias or unmeasured confounding. We tested whether migraine causes an increased risk of dementia using Mendelian randomization, which leverages genetic variability in migraine risk to estimate effects independent of confounding.MethodIn a sample of 259,839 individuals of European Ancestry aged 55 years or older from the UK Biobank, we calculated a migraine genetic risk score (MGRS) for each individual based on 38 known genome‐wide significant risk single nucleotide polymorphisms. Using algorithmically defined dementia diagnosis and migraine diagnosis from hospital and primary care sources, 2,069 and 11,357 individuals were diagnosed with dementia and migraine, respectively. Fluid intelligence score (score on a 13‐item test to assess logic and reasoning ability) and total brain volume normalized for skull size (TBV) were used as outcomes in addition to dementia diagnosis and were available for 174,609 and 10,229 individuals, respectively. Linear, logistic, and linear mixed‐effects models were used to assess the associations between the MGRS and TBV, dementia diagnosis, and fluid intelligence, respectively. Using instrumental variable regression with the MGRS as the instrument, we estimated the causal effect of migraine on dementia diagnosis, fluid intelligence, and TBV. All analyses were adjusted for the first 10 genetic ancestry principal components, orthogonal polynomials of degrees 1‐4 for age at time of outcome assessment, and genetic sex.ResultThe MGRS was strongly associated with migraine (p &lt; 0.0001), but not dementia diagnosis (p = 0.22), fluid intelligence (p = 0.15), or TBV (p = 0.12). The estimated causal effect of migraine was a 3% (95% CI: [‐2%, 8%]) increase in absolute risk of dementia, a 1.1 (95% CI: [‐1.0, 3.1]) point increase in total fluid intelligence score, and a 123 (95% CI: [‐50, 296]) cubic centimeter decrease in TBV.ConclusionThe MGRS was not significantly associated with dementia diagnosis, fluid intelligence, or TBV. Using a Mendelian randomization approach, we did not find evidence that migraine causes dementia.

Assessment of the impact of PTGS1, PTGS2 and CYP2C9 polymorphisms on pain, effectiveness and safety of NSAID therapies

Cyclooxygenase 1 and 2 (COX-1, COX-2) are enzymes that catalyze the first reaction in the arachidonic acid pathway. COXs are the therapeutic target for non-steroidal anti-inflammatory drugs. Inhibition of COX enzymatic activity has an analgesic, anti-inflammatory and sometimes antiplatelet effect. Single-nucleotide polymorphisms (SNPs) within genes encoding COX-1 and COX-2 (PTGS1, PTGS2) influence the risk of pain and their intensity in some diseases. They also affect the effectiveness of NSAID therapy in rheumatoid diseases. Moreover, the relationship between certain polymorphisms of PTGS2 and a higher risk of migraine and the development of aspirin resistance in the prophylaxis of cardiovascular diseases was demonstrated. The isoform of cytochrome P450, CYP2C9 has a significant influence on the efficacy and safety of NSAID use. It is responsible for the metabolism and speed of removal of these drugs. The occurrence of some of its polymorphic forms is associated with a decrease in CYP2C9 enzymatic activity, leading to changes in the pharmacokinetics and pharmacodynamics of NSAIDs. The prolonged half-life and decrease in clearance of these drugs lead to serious side effects such as hepatotoxicity, nephrotoxicity, anaphylactic reactions, cardiovascular or gastrointestinal incidents. Studies on polymorphisms of cyclooxygenases and CYP2C9 may improve the safety and efficacy of NSAIDs therapy by adjusting the dose to individual polymorphic variants, as well as expanding knowledge about the pathomechanism of inflammatory diseases.

Migraine and cardiovascular risk factors: A clinic-based study

ObjectiveThe 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. MethodsA 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. ResultsThis 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. ConclusionChronic 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.

Migraine and Sport in a Physically Active Population of Students: Results of a Cross-Sectional Study.

In this study, we explored the relationship between migraine and sport in a physically active population of students, analyzing the risk of migraine among sporty students. The relationship between sport and migraine is controversial; moreover, several studies report on sport as a migraine trigger, but there is evidence that physical activity could have a relevant role in migraine prevention. A cross-sectional survey was conducted using the validated ID-migraine questionnaire including specific demo-anthropometric (gender, age, weight, height) and sports variables on a potentially active student population of the University of Palermo. Evaluation in putative migraine subjects of clinical features and disability was explored through the administration of the Italian version of the Migraine Disability Assessment Scale. Statistical analyses were performed using univariate and logistic regression analyses. Three hundred and ninety-three out of 520 students (210 F, mean age: 23.5±0.7years; 183M; mean age: 20.5±0.7years) participated in this study. Migraine screened positive in 102 subjects (26.0%) and its prevalence was significantly higher among females (P<.001). An increased risk of migraine was found in females, and a protective effect of sport on the risk of migraine among females, but not among males. The role of exercise in migraine is still unclear. This study supports a protective role of sport in migraine reporting a protective effect in females. Further studies are needed to deepen the association between sport and migraine.

Noninvasive vagus nerve stimulation and morphine transiently inhibit trigeminal pain signaling in a chronic headache model.

Chronic headache conditions are characterized by persistent sensitization of the trigeminal system, which involves dysfunction of descending pain modulation. We previously reported that noninvasive vagus nerve stimulation (nVNS) inhibits trigeminal nociception in models of episodic migraine through a mechanism involving enhanced serotonergic and GABAergic descending pain signaling. The analgesic effectiveness of nVNS and morphine were investigated in an animal model of chronic headache mediated by the combination of the 3 migraine risk factors of neck muscle tension, paradoxical sleep deprivation, and pungent odors. Sprague-Dawley rats were injected with complete Freund's adjuvant in the trapezius and sleep deprived for 1 night to promote trigeminal sensitization. After 7 days, animals were exposed to a pungent odor, and mechanical nocifensive head withdrawal responses were determined using von Frey filaments. Beginning on day 3 after odor exposure, animals were treated daily with either nVNS or morphine for 7 days. Exposure of animals sensitized by neck inflammation and sleep deprivation to a pungent odor resulted in a prolonged state of trigeminal nociception. Daily administration of nVNS or morphine significantly repressed the nocifensive response; however, cessation resulted in a return to heightened pretreatment nocifensive levels. The combination of reported migraine risk factors promotes a state of sustained trigeminal hypersensitivity characteristic of chronic headache. Daily nVNS was similarly effective as morphine in inhibiting nociception and may represent a safer, opioid-sparing therapeutic option for other chronic pain disorders involving sensitization of the trigeminal system by promoting descending pain modulation.

Habitual sleep disturbances and migraine: a Mendelian randomization study.

ObjectiveSleep disturbances are associated with increased risk of migraine, however the extent of shared underlying biology and the direction of causal relationships between these traits is unclear. Delineating causality between sleep patterns and migraine may offer new pathophysiologic insights and inform subsequent intervention studies. Here, we used genetic approaches to test for shared genetic influences between sleep patterns and migraine, and to test whether habitual sleep patterns may be causal risk factors for migraine and vice versa.MethodsTo quantify genetic overlap, we performed genome‐wide genetic correlation analyses using genome‐wide association studies of nine sleep traits in the UK Biobank (n ≥ 237,627), and migraine from the International Headache Genetics Consortium (59,674 cases and 316,078 controls). We then tested for potential causal effects between sleep traits and migraine using bidirectional, two‐sample Mendelian randomization.ResultsSeven sleep traits demonstrated genetic overlap with migraine, including insomnia symptoms (rg = 0.29, P < 10−31) and difficulty awakening (rg = 0.11, P < 10−4). Mendelian randomization analyses provided evidence for potential causal effects of difficulty awakening on risk of migraine (OR [95% CI] = 1.37 [1.12–1.68], P = 0.002), and nominal evidence that liability to insomnia symptoms increased the risk of migraine (1.09 [1.02–1.16], P = 0.02). In contrast, there was minimal evidence for an effect of migraine liability on sleep patterns or disturbances.InterpretationThese data support a shared genetic basis between several sleep traits and migraine, and support potential causal effects of difficulty awakening and insomnia symptoms on migraine risk. Treatment of sleep disturbances may therefore be a promising clinical intervention in the management of migraine.

Risk of Subsequent Migraines in Facial Fracture Patients: A Population-Based Cohort Study.

Background: Limited studies have discussed the association between facial fractures and subsequent migraines. In this study, we examined this association and the effect of facial fracture and surgery on the development of migraines. Methods: We selected 5034 patients with facial fractures and a matched cohort of 20,136 patients without facial fractures or facial-associated surgery with a history of migraine from the National Health Insurance database. Risk factors included age, gender, occupation (white-collar, blue-collar, and others), and comorbidities. Patients were frequency matched by age, gender, and index year. The incidence of migraine and the association between migraine development and facial surgery were identified by facial fracture location stratification. Results: The incidence of migraines in the facial fracture cohort was 1.37-fold higher when compared with the comparison cohort (6.47 vs. 4.73 per 1000 person-years). There was a 1.31-fold risk of migraines in the adjusted hazard model and a 1.30-fold risk of migraines in the subdistribution hazard model (95% confidence interval [CI], 1.12-1.52 and 1.12-1.51, respectively). Malar/maxillary and nasal fractures showed 1.48- and 1.29-fold risks of migraines in the adjusted hazard model and subdistribution hazard model (95% CI, 1.16-1.89 and 1.05-1.59, respectively). There were no significant differences in migraine occurrence among patients who underwent surgery. Conclusions: Our findings indicated that malar/maxillary and nasal fractures were associated with a subsequent risk of migraines. There were no significant differences in migraine occurrence among patients who underwent surgery. Because of the retrospective nature of this study, further studies are warranted.

Development and Internal Validation of a Multivariable Prediction Model for Individual Episodic Migraine Attacks Based on Daily Trigger Exposures.

To develop and internally validate a multivariable predictive model for days with new-onset migraine headaches based on patient self-prediction and exposure to common trigger factors. Accurate real-time forecasting of one's daily risk of migraine attack could help episodic migraine patients to target preventive medications for susceptible time periods and help decrease the burden of disease. Little is known about the predictive utility of common migraine trigger factors. We recruited adults with episodic migraine through online forums to participate in a 90-day prospective daily-diary cohort study conducted through a custom research application for iPhone. Every evening, participants answered questions about migraine occurrence and potential predictors including stress, sleep, caffeine and alcohol consumption, menstruation, and self-prediction. We developed and estimated multivariable multilevel logistic regression models for the risk of a new-onset migraine day vs a healthy day and internally validated the models using repeated cross-validation. We had 178 participants complete the study and qualify for the primary analysis which included 1870 migraine events. We found that a decrease in caffeine consumption, higher self-predicted probability of headache, a higher level of stress, and times within 2days of the onset of menstruation were positively associated with next-day migraine risk. The multivariable model predicted migraine risk only slightly better than chance (within-person C-statistic: 0.56, 95% CI: 0.54, 0.58). In this study, episodic migraine attacks were not predictable based on self-prediction or on self-reported exposure to common trigger factors. Improvements in accuracy and breadth of data collection are needed to build clinically useful migraine prediction models.

Headache in Children: Selected Factors of Vascular Changes Involved in Underlying Processes of Idiopathic Headaches.

Headaches are common complaints in children. The International Classification of Headache Disorders, 3rd edition (beta version), defines more than 280 types of headaches. Primary headaches refer to independent conditions that cause pain and include migraine, tension-type headaches (TTH), and trigeminal autonomic cephalalgias (TACs). Several agents are involved in the pathogenesis of headaches. The factors associated with predisposition to atherosclerosis seem to be particularly important from the clinical point of view. The influence of obesity on the incidence of headaches has been well established. Moreover, idiopathic headaches, especially migraine, are thought to be one of the first signs of disorders in lipid metabolism and atherosclerosis. The risk of migraine increases with increasing obesity in children. Another factor that seems to be involved in both obesity and headaches is the adiponectin level. Recent data also suggest new potential risk factors for atherosclerosis and platelet aggregation such as brain-derived neurotrophic factor (BDNF), sCD40L (soluble CD40 ligand), serpin E1/PAI I (endothelial plasminogen activator inhibitor), and vascular endothelial growth factor (VEGF). However, their role is controversial because the results of clinical studies are often inconsistent. This review presents the current knowledge on the potential markers of atherosclerosis and platelet aggregation, which may be associated with primary headaches.

Association of the cyclooxygenase-2 1759A allele with migraine in Chinese Han individuals.

Cyclooxygenase-2 (COX-2) is known to be involved in the pathogenesis of migraine, and some polymorphisms are known to affect the expression of COX-2. This retrospective case-control study aimed to explore the associations between the -765 G>C (rs20417), -1759 G>A (rs3218625), and -8473 C>T (rs5275) COX-2 polymorphisms and migraine in Chinese Han individuals. One hundred and ten unrelated Han Chinese patients with migraine and 108 healthy controls were recruited between 03/2014 and 08/2016 at the First Affiliated Hospital of Nanjing Medical University and the First People's Hospital of Lianyungang City. The genotypes of all polymorphisms in controls followed the Hardy-Weinberg equilibrium (P = 0.215, P = 0.884, and P = 0.689). There were differences in the genotype and allele distributions of the COX-2-1759G>A (Gly587Arg) polymorphism between the migraine and control groups (P = 0.038 and P = 0.040, respectively). Compared with the COX-2-1759AG genotype, GG genotype carriers had an increased risk of migraine (odds ratio (OR) = 8.720, 95% confidence interval (CI): 1.072–70.960, P = 0.038). The frequency of the COX-2-1759A allele in patients with migraine was significantly lower than the controls (OR = 0.119, 95%CI: 0.015–0.957, P = 0.040). Adjusted age and sex, a statistical difference was found in the dominant model of COX-2-1759 G>A (OR = 0.118, 95% CI 0.014 to 0.962, P = 0.046). No significant difference was detected regarding the -765G>C and -8473T>C polymorphisms between the two groups. The COX-2 1759A allele might be involved in the development of migraine in Chinese Han individuals, but this will have to be confirmed in large-scale studies.

Going Deep into Synaptic Vesicle Machinery Genes and Migraine Susceptibility - A Case-Control Association Study.

A number of observations, including among our study population, have implicated variants in the syntaxin-1A, a component of the synaptic vesicles, in migraine susceptibility. Therefore, we hypothesize that variants in other components of the vesicle machinery are involved in migraine. Migraine is a common and complex neurologic disorder that affects approximately 15-18% of the general population. The exact cause of migraine is unknown; however, genetic studies have made possible substantial progress toward the identification of underlying molecular pathways. Neurotransmitters have been for long considered to have a key role in migraine pathophysiology; so we investigated common variants in genes involved in the synaptic vesicle machinery and their impact in migraine susceptibility. We performed a case-control study comprising 188 unrelated patients with headache and 286 healthy controls in a population from the north of Portugal. Benefiting from the presence of linkage disequilibrium, we selected and genotyped 119 tagging single-nucleotide polymorphisms in 18 genes. We found significant associations between single-nucleotide variants and migraine in 7 genes, SYN1, SYN2, SNAP25, VAMP2, STXBP1, STXBP5, and UNC13A, either conferring an increased risk or protection of migraine. Due to SYN1 X-chromosomal location, we performed the statistical analysis separated by gender and, in the female group, the C allele of rs5906435 increased the risk for migraine susceptibility (P=.021; OR=1.69; 95% CI: 1.21-2.34). In contrast, the TT genotype of the same variant emerged as a potential protective factor (P=.003; OR=0.45; 95% CI: 0.27-0.74). The SYN2 analysis supported the rs3773364's G allele (P=.014) as a risk factor for migraine, and although not statistically significant after correction, the AG genotype (P=.006; OR=1.86; 95% CI: 1.20-2.90) reinforced the allelic findings. Additionally, we found the SNAP25-rs363039's CT genotype (P=.001; OR=2.14; 95% CI: 1.36-3.34), the STXBP5-rs1765028's T allele (P=.041; OR=1.46; 95% CI: 1.13-1.90), and the UNC13B-rs7851161's TT genotype (P=.001; OR=2.14; 95% CI: 1.36-3.34) as statistically significant risk factors for migraine liability. VAMP2-rs1150's G allele revealed a risk association to migraine, not statistically significant after correction (P=.068). Additionally, we found haplotypes in SYN1, SYN2, STXBP1, and UNC13B to be associated with migraine. Overall, this study provides a new insight into migraine liability, identifying possible starting points for functional studies.

Increased Risk of Migraine in Patients with Temporomandibular Disorder: A Longitudinal Follow-Up Study Using a National Health Screening Cohort.

Background: The aim of this study was to investigate the association between temporomandibular disorder (TMD) and migraine through a longitudinal follow-up study using population data from a national health screening cohort. Methods: This cohort study used data from the Korean National Health Insurance Service-Health Screening Cohort from 2002 to 2015. Of the 514,866 participants, 3884 TMD patients were matched at a 1:4 ratio with 15,536 control participants. Crude models and models adjusted for obesity, smoking, alcohol consumption, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, and Charlson Comorbidity Index (CCI) scores were calculated. Chi-squared test, Kaplan–Meier analysis, and two-tailed log-rank test were used for statistical analysis. Stratified Cox proportional hazard models were used to assess hazard ratios (HR) and 95% confidence intervals (CIs) for migraine in both control groups. Results: The adjusted HR for migraine was 2.10 (95% CI: 1.81–2.44) in the TMD group compared to the control group, which was consistent in subgroup analyses according to age, sex, and Kaplan–Meier analysis. Conclusions: This study demonstrated that TMD patients have a higher risk of migraine. These results suggest that dentists can decrease the risk of migraine in TMD patients by managing TMD properly.

Association of rs1801133 polymorphism with migraine susceptibility: A case-control study followed by updated meta-analysis and trial sequential analysis

Migraine is a multi-factorial neurovascular disorder causes nausea and headache. This study was aimed to determine the association between MTHFR gene rs1801133 polymorphism with migraine risk in South-Indian population using ARMS-PCR and DNA sequencing. Further, we have performed an updated meta-analysis of case-control studies relating rs1801133 polymorphism with migraine. Additionally, to identify the risk of type-I error trial sequential analysis was executed. The genotyping results of MTHFR gene polymorphism from our study revealed a positive association with migraine in a homozygous recessive (TT) genotype (OR = 2.52 (95% CI [0.96–6.64]), P = 0.046). For meta analysis, twenty case-control studies were assessed which revealed positive relationship between rs1801133 polymorphism with migraine in mixed ethnic populations (TT vs CT + CC, OR = 1.33 (95% CI [1.04–1.68]), P = 0.02; CT vs CC, OR = 0.85 (95% CI [0.74–0.97]), P = 0.02; TT vs CC, OR = 1.37 (95% CI [1.03–1.82]), P = 0.03; T vs C, OR = 1.20 (95% CI [1.02–1.41]), P = 0.03) of all analyzed genetic models. Further, ethnicity-based stratification analyses showed consistent results in Asian ethnic population. To conclude, our findings from meta-analysis confirm that rs1801133 MTHFR gene polymorphism might play a significant role in migraine susceptibility.

A Paradoxical Vasodilatory Nutraceutical Intervention for Prevention and Attenuation of Migraine—A Hypothetical Review

Studies suggest that migraine pain has a vascular component. The prevailing dogma is that peripheral vasoconstriction activates baroreceptors in central, large arteries. Dilatation of central vessels stimulates nociceptors and induces cortical spreading depression. Studies investigating nitric oxide (NO) donors support the indicated hypothesis that pain is amplified when acutely administered. In this review, we provide an alternate hypothesis which, if substantiated, may provide therapeutic opportunities for attenuating migraine frequency and severity. We suggest that in migraines, heightened sympathetic tone results in progressive central microvascular constriction. Suboptimal parenchymal blood flow, we suggest, activates nociceptors and triggers headache pain onset. Administration of NO donors could paradoxically promote constriction of the microvasculature as a consequence of larger upstream central artery vasodilatation. Inhibitors of NO production are reported to alleviate migraine pain. We describe how constriction of larger upstream arteries, induced by NO synthesis inhibitors, may result in a compensatory dilatory response of the microvasculature. The restoration of central capillary blood flow may be the primary mechanism for pain relief. Attenuating the propensity for central capillary constriction and promoting a more dilatory phenotype may reduce frequency and severity of migraines. Here, we propose consideration of two dietary nutraceuticals for reducing migraine risk: L-arginine and aged garlic extracts.

Mid- to late-life migraine diagnoses and risk of dementia: a national register-based follow-up study

BackgroundPrevious studies found an association between migraine and dementia, which are two leading causes of disability. However, these studies did not differentiate between migraine types and did not investigate all prevalent dementia subtypes. The main objective of this national register-based study was to investigate whether migraine was a risk factor for dementia. Additionally, we explored potential differences in dementia risk for migraine with and without aura.MethodsWe obtained data on birth cohorts born between 1935 and 1956 (n = 1,657,890) from Danish national registers. Individuals registered with migraine before age 59 (n = 18,135) were matched (1:5) on sex and birthdate with individuals without migraine (n = 1,378,346). Migraine was defined by International Classification of Diseases (ICD) diagnoses and dementia was defined by ICD diagnoses and anti-dementia medication. After matching, 62,578 individuals were eligible for analysis. For the statistical analyses, we used Cox regression models and adjusted for socio-demographic factors and several psychiatric and somatic morbidities.ResultsDuring a median follow-up time of 6.9 (IQR: 3.6–11.2) years, 207 individuals with migraine developed dementia. Compared with individuals without migraine, we found a 50% higher rate of dementia among individuals with migraine (HR = 1.50; 95% CI: 1.28–1.76). Individuals without aura had a 19% higher rate of dementia (HR = 1.19; 95% CI: 0.84–1.70), and individuals with aura had a two times higher rate of dementia (HR = 2.11; 95% CI: 1.48–3.00).ConclusionsOur findings support the hypothesis that migraine is a midlife risk factor for dementia in later life. The higher rate of dementia in individuals with a hospital-based diagnosis of migraine with aura emphasizes the need for studies on pathological mechanisms and potential preventative measures. Furthermore, given that only hospital-based migraine diagnoses were included in this study, future research should also investigate migraine cases derived from the primary healthcare system to include less severe migraine cases.