Browse by Audience
Migraine is heritable and formally diagnosed by structured criteria that require presence of some but not all possible migraine symptoms which include aura, several distinct manifestations of pain, nausea/vomiting, and sensitivity to light or sound. The most recent genome-wide genetic association study (GWAS) for migraine identified 38 loci. We investigated whether 46 single-nucleotide polymorphisms (SNPs), i.e., genetic variants, at these loci may have especially pronounced, i.e., selective, association with migraine presenting with individual symptoms compared to absence of migraine. Selective genetic associations of SNPs were evaluated through a likelihood framework in the Women's Genome Health Study (WGHS), a population-based cohort of middle-aged women including 3,003 experiencing migraine and 18,108 not experiencing migraine, all with genetic information. SNPs at 12 loci displayed significant selective association for migraine subclassified by specific symptoms, among which six selective associations are novel. Symptoms showing selective association include aura, nausea/vomiting, photophobia, and phonophobia. The selective associations were consistent whether the women met all formal criteria for diagnostic for migraine or lacked one of the diagnostic criteria, formally termed probable migraine. Subsequently, we performed latent class analysis of migraine diagnostic symptoms among 69,861 women experiencing migraine from the WGHS recruitment sample to assess whether there were clusters of specific symptoms that might also have a genetic basis. However, no globally robust latent migraine substructures of diagnostic symptoms were observed nor were there selective genetic associations with specific combinations of symptoms revealed among weakly supported latent classes. The findings extend previously reported selective genetic associations with migraine diagnostic symptoms while supporting models for shared genetic susceptibility across all qualifying migraine at many loci.
Learn More >The aims of the present systematic review were to explore the prevalence of migraine with anxiety exclusively and determine if and why there are likely to be differences across genders. Migraine is a very common neurological disorder and cause of productive disability worldwide that is more frequent in women of childbearing age than males. Previous studies have frequently demonstrated comorbidity of migraine and other psychiatric disorders. Although the prevalence of migraine across gender is well-established there are few if any systematic reviews on the prevalence of migraine comorbidity with anxiety cross-genders. The present systematic review included prevalence studies, clinic-based and cohort studies that reported the frequency of migraine with anxiety within the study sample. Eleven studies were included in the review after screening by two independent reviewers. Studies included participants who were 16 years and older diagnosed with migraine. The main findings of this review indicated that anxiety is a major comorbidity of migraine worldwide, with a wide range (16-83%) of prevalence and a mean of ~43% of patients experiencing comorbid symptoms. Subjective anxiety symptoms appear to be greater among males with migraine than females which could be attributable to both environmental and/or hormonal and genetic predispositions. The results reemphasize the high prevalence of migraine and comorbid anxiety symptoms worldwide while showing that although migraine is far more prevalent among women in general co-morbidity of migraine with anxiety unfolds a different gender difference. The results highlight the significance of exploring the impact of existing and pre-existing comorbid conditions of patients with migraines and further consideration into their diagnostic and treatment strategies.
Learn More >To study chronic headache and medication-overuse headache (MOH) prevalence; to identify groups with high prevalence of these conditions; and to identify the most frequently used pain medications among respondents with chronic headache.
Learn More >Migraine is a common neurovascular disorder affecting ~15% of the general population. Ranking second in the list of years lived with disability (YLD), people living with migraine are greatly impacted by this especially burdensome primary headache disorder. In ~30% of individuals with migraine, transient neurological symptoms occur (migraine aura) that further increase migraine burden. However, migraine burden is differential with respect to sex. Though one-year prevalences in childhood are similar, starting with puberty, migraine incidence increases at a much higher rate in females than males. Thus, migraine over the life course occurs in women three to four times more often than in men. Attacks are also more severe in women, leading to greater disability and a longer recovery period. The sex disparity in migraine is believed to be partly mediated through fluctuations in ovarian steroid hormones, especially estrogen and progesterone, although the exact mechanisms are not yet completely understood. The release of the neuropeptide calcitonin gene-related peptide (CGRP), followed by activation of the trigeminovascular system, is thought to play a key role in the migraine pathophysiology. Given the burden of migraine and its disproportionate distribution, the underlying cause(s) for the observed differences between sexes in the incidence, frequency, and intensity of migraine attacks must be better understood. Relevant biological as well as behavioral differences must be taken into account. To evaluate the scope of the existing knowledge on the issue of biological sex as well as gender differences in migraine, we conducted a systematized review of the currently available research. The review seeks to harmonize existing knowledge on the topic across the domains of biological/preclinical, clinical, and population-level research, which are traditionally synthesized and interpreted in isolation. Ultimately, we identify knowledge gaps and set priorities for further interdisciplinary and informed research on sex and gender differences as well as gender-specific therapies in migraine.
Learn More >Migraine is a common and highly disabling headache disorder associated with a substantial socioeconomic burden. Migraine treatments can be categorized as preventive treatment, aimed at reducing the frequency and severity of migraine attacks, and acute therapy, intended to abort attacks. Traditionally, acute treatment can be classified as specific (ergot derivatives and triptans) or nonspecific (analgesics and nonsteroidal anti-inflammatory drugs). Triptans, a class of 5-HT receptor agonists with some affinity for the 5-HT receptor subtype, have been proven to be efficacious for acute treatment of moderate to severe migraine and have been deemed the gold standard. The availability of triptans in non-oral formulations, such as subcutaneous (SC) and intranasal forms, can be beneficial for patients who suffer from prominent nausea or vomiting, have a suboptimal response to oral agents, and/or seek a more rapid onset of treatment effects. However, triptans are contraindicated in patients with preexisting cardiovascular and/or cerebrovascular diseases due to their 5-HT-mediated vasoconstrictive action. For this reason, studies have focused on the development of ditans, a group of antimigraine drugs targeting 5-HT and 5-HT receptors. Unfortunately, 5-HT receptor agonists have been shown to be ineffective in the acute treatment of migraine. Several ditans targeting the 5-HT receptor have been developed and have shown no vasoconstrictive effect in preclinical studies, but only two of them, lasmiditan and LY334370, have been tested in clinical trials for migraine, and only lasmiditan has reached to Phase III clinical trials. These Phase III trials have demonstrated the efficacy and safety of lasmiditan, a selective 5-HT receptor agonist, in acute migraine treatment. Lasmiditan might offer an alternative migraine therapy without cardiovascular risks. This review will summarize the development of agents targeting the 5-HT and 5-HT receptors and the clinical evidence supporting the use of these agents for acute migraine treatment.
Learn More >Allodynia in Menstrually Related Migraine: Score Assessment by Allodynia Symptom Checklist (ASC-12).
The aim of this study was to compare the allodynia score in headache attacks related and not related to menstruation in women diagnosed with menstrually related migraine without aura.
Learn More >Migraine is a chronic dysfunction characterized by recurrent pain, but its pathogenesis is still unclear. As a result, more and more methods have been focused on the study of migraine in recent years, including functional magnetic resonance imaging (fMRI), which is a mainstream technique for exploring the neural mechanisms of migraine. In this paper, we systematically investigated the fMRI functional connectivities (FCs) between large-scale brain networks in migraine patients from the perspective of multi-channel hierarchy, including static and dynamic FCs of group and individual levels, where the brain networks were obtained using group independent component analysis. Meanwhile, the corresponding topology properties of static and dynamic FCs networks in migraine patients were statistically compared with those in healthy controls. Furthermore, a graph metrics based method was used to detect the potential brain functional connectivity states in dynamic FCs at individual and group levels, and the corresponding topology properties and specificity of these brain functional connectivity states in migraine patients were explored compared with these in healthy controls. The results showed that the dynamic FCs and corresponding global topology properties among nine large-scale brain networks involved in this study have significant differences between migraine patients and healthy controls, while local topological properties and dynamic fluctuations were easily affected by window-widths. Moreover, the implicit dynamic functional connectivity patterns in migraine patients presented specificity and consistency under different window-widths, which suggested that the dynamic changes in FCs and topology structure between them played a key role in the brain functional activity of migraine. Therefore, it may be provided a new perspective for the clinical diagnosis of migraine.
Learn More >It is known that perivascular application of CGRP induces cerebral vasodilatation. However, it is unclear whether intravenous alfa CGRP (αCGRP) induces changes in cerebral and systemic hemodynamics. Therefore, we studied the influence of an αCGRP intravenous infusion at a rate of 1.5 mcg/min in 20 min on mean arterial velocity in the middle cerebral artery (vm MCA) and in the posterior cerebral artery (vm PCA) in twenty healthy subjects using transcranial Doppler (TCD). We found out that αCGRP decreased vm MCA ( < 0.001), vm PCA ( < 0.001), mean arterial pressure (MAP) ( < 0.001) and end-tidal CO (Et-CO) ( = 0.030). The heart rate (HR) increased during αCGRP infusion ( < 0.001). In addition, we found a positive relationship between Et-CO and vm MCA ( = 0.001) as well as vm PCA ( = 0.043). In our view, αCGRP induces changes in cerebral and systemic circulation in healthy volunteers. It might cause vasodilatation of MCA and PCA and a compensatory decrease of Et-CO to αCGRP related hemodynamic changes.
Learn More >: Hypothesis-driven functional connectivity (FC) analyses have revealed abnormal functional interaction of regions or networks involved in pain processing in episodic migraine patients. We aimed to investigate the resting-state FC patterns in episodic migraine by combining data-driven voxel-wise degree centrality (DC) calculation and seed-based FC analysis. : Thirty-nine patients suffering from episodic migraine without aura and 35 healthy controls underwent clinical assessment and functional MRI. DC was analyzed voxel-wise and compared between groups, and FC of regions with DC differences were further examined using a seed-based approach. : Compared with the control group, the migraine group showed increased and decreased DC in the right posterior insula and left crus I, respectively. Seed-based FC analyses revealed that migraine patients demonstrated increased right posterior insula connections with the postcentral gyrus, supplementary motor area/paracentral lobule, fusiform gyrus and temporal pole. The left crus I showed decreased FC with regions of the default mode network (DMN), including the medial prefrontal cortex (mPFC), angular gyrus, medial and lateral temporal cortex in patients with migraine. Furthermore, pain intensity positively correlated with DC in the right amygdala/parahippocampal gyrus, and migraine frequency negatively correlated with FC between the left crus I and mPFC. : Patients with episodic migraine without aura have increased FC with the right posterior insula and decreased FC within the DMN, which may underlie disturbed sensory integration and cognitive processing of pain. The left crus I-mPFC connectivity may be a useful biomarker for assessing migraine frequency.
Learn More >Migraine is a highly heritable complex brain disorder, imposing a huge burden of disability on sufferers. The genetic architecture of migraine ranges from the rare Mendelian forms whereby a single gene mutation is sufficient to cause disease to gene variants that individually impart only a small increase in migraine risk. Despite the considerable advances in the last decade, there are significant challenges to translate genetic findings into drug targets and eventually successful treatments. The need for such treatments remains, even with the new wave of biological therapies targeting CGRP or the CGRP receptor. This will require integration of genetic data with new technologies such as human stem cell models of migraine that allow the interpretation of genetic risk into disease relevant cellular phenotypes. This was recently undertaken for the first time in migraine, whereby stem cells from patients with the rare TRESK frameshift mutation converted into pain sensory neurons demonstrated hyper-excitability. The continued study of the molecular basis of migraine thus offers new paths to drug targets and precision medicine approaches.
Learn More >