Migraine without Aura and Subclinical Atherosclerosis in Young Females: Is Gut Microbiota to Blame?

Background and Objectives: Migraine with aura (MA) could be considered a risk factor for developing atherosclerosis and cardio-vascular events. However, less is known about the relation between migraine without aura (MWA) and atherosclerosis. Our study aimed to assess whether young female migraineurs, with alterations of gut microbiota could associate early atherosclerosis. Materials and Methods: We conducted an exploratory cross-sectional, pilot study concerning 105 consecutive young females having MWA, with recent normal brain scans, that were free of cardio-vascular risk factors, non-smokers, not on oral contraception, not pregnant, and without thyroid or parathyroid diseases, chronic organ failure, cancer, or on probiotic or antibiotic treatment. Consecutive to assessment of gut microbiota, patients were assigned to two groups: dysbiosis positive (n = 45) and dysbiosis negative (n = 60). All study participants underwent clinical examinations with an assessment of migraine severity, body mass index and carotid intima-media thickness (CIMT), as well as laboratory workups. Statistical analysis was performed using a chi-squared test (χ2), a two-tailed t-test and a nonparametric Spearman's correlation test. Results: The dysbiosis positive migraineurs showed a significant increase in CIMT along with several anthropometrical, biological and clinical particularities. Significant positive correlations between dysbiosis and CIMT, glycosylated hemoglobin, migraine severity and duration, tumor necrosis factor-alpha, and body mass index were found. Conclusions: Young female migraineurs with significant alterations of gut microbiota experienced early signs of atherosclerosis and displayed severe migraine disability, as well as multiple biological and clinical particularities.

Migraineurs show a high prevalence of antiphospholipid antibodies.

BACKGROUND: It has been observed that migraineurs show a higher risk of thrombosis and that the most frequent symptom reported by patients with antiphospholipid syndrome is headache, especially migraine. OBJECTIVES: The aim of our research was to evaluate the prevalence of antiphospholipid antibodies (aPL) in a random cohort of migraineurs. PATIENTS/METHODS: This analytic, comparative case study was performed to evaluate the prevalence of antiphospholipid antibodies by comparing a population of migraineurs with and without aura with sex- and age-matched controls. Both the diagnosis of migraine and the laboratory diagnosis of aPL positivity were made on the basis of the most recent international guidelines. RESULTS: Between September 2008 and August 2009, we recruited 284 consecutive patients (225 women and 59 men, 203 without aura and 81 with aura) and 225 controls (174 women and 51 men). Positivity for at least one test for aPL (LAC, ACA IgG or antiß2GLP1 IgG) was detected and confirmed in 12% (n = 33) of patients and in 3% (n = 7) of controls (odds ratio, 4.08; confidence interval, 1.77-9:39; P = 0.0004). Two of the patients had triple positivity for aPL (LAC, ACA and antiß2GLP1) and one had double positivity (LAC and antiß2GLP1); none of the controls showed multiple positivity. CONCLUSIONS: Our data show that migraineurs have a significantly higher prevalence of antiphospholipid antibodies, and point towards the fact that the two conditions may be comorbid or even that migraine may be an early sign for identifying patients with aPL positivity.

A comparative study of celiac disease in children with migraine headache and a normal control group.

BACKGROUND/AIMS: Migraine headache is one of the most frequent types of headache in children in which multiple factors, including environmental and genetic, are involved. Celiac disease is an autoimmune-mediated disease with intolerance to gluten. The clinical spectrum of celiac disease is wide. Patients may present with malabsorption symptoms or extra-intestinal involvement, or can be totally asymptomatic. The association of migraine headache and celiac disease is not well known. The aim of this study was to assess the prevalence of celiac disease in children with migraine headache, in order to detect any relationship between them. METHODS: A total of 100 patients with migraine headache according to the International Headache Society criteria were enrolled in the study. 1500 children without history of headache or other medical diseases participating in another study for detection of the prevalence of celiac disease were selected in this study as a control group. Serum total IgA and anti-tissue transglutaminase IgA (anti-tTGA) antibodies were measured. In cases with positive serologic tests, duodenal biopsy was performed for confirmation of celiac disease. RESULTS: Two of 100 patients (2%) were found to have positive serologic tests for celiac disease, compared with 30 of 1500 children (2%) in the control group who had celiac disease. CONCLUSIONS: The results of this study showed that the prevalence of celiac disease was not higher in patients with migraine compared with the control group. Therefore, diagnostic tests for celiac disease are not necessary as a part of the management of migraine headache.

Increased C-reactive protein in young adult patients with migraine.

Interictal serum C-reactive protein (CRP) was measured in 50 young adult patients with migraine and compared with 50 controls. The median CRP level was 1.42 mg/l in patients with migraine and 0.90 mg/l in controls (P = 0.03). This finding supports the role of inflammation in migraine, but needs confirmation in larger controlled studies. Prospective studies may establish whether measurements of CRP can identify patients with migraine at risk for cardiovascular events.

[Antiphospholipid antibodies in children with migraine]. / Przeciwciala antyfosfolipidowe w migrenie u dzieci.

BACKGROUND AND PURPOSE: There are only a few investigations in the literature, that address the occurrence and the role of anticardiolipin antibodies (aCL) in children with migraine. The results of those studies are often contradictory. The aim of the study was to determine if the values of aCL in children with migraine differ from the control group. We tried to assess whether the type of migraine (with aura or without aura) had the influence on those values. MATERIAL AND METHODS: Sixty patients (mean age: 10.9+/-3.3 years), including 30 children with migraine hospitalized from January 2000 to December 2003 in the Department of Developmental Neurology Medical University of Gdansk and 30 healthy children, were studied. The values of aCL in class IgA, IgM and IgG were assessed by the immunoenzymatic method (ELISA test). RESULTS: The values aCL in IgA and IgG class were significantly different between the migraineurs and control group. The mean value of aCL in patients with migraine was 8.7+/-1.27 U/ml, while in the control group--3.81+/-1.74 U/ml. The positive values of aCL in class IgG were found in 11 (37%) children with migraine, and positive values of aCL in class IgM were noted in 6 (20%) cases in the same group. The type of migraine had no influence on the values of aCL. CONCLUSIONS: Children with migraine present with the higher values of aCL than the control group. The mean values of aCL were within the normal range, therefore their role in pathogenesis of migraine remains unclear. The further observation is needed to assess the reliable role of higher values of aCL in pathophysiology of vascular disorders.

Cytotoxic T lymphocyte antigen 4 polymorphism 49 (A>G) and migraine.

Migraine without aura (MO) and migraine with aura (MA) are disorders involving multiple environmental and genetic factors. The A/G polymorphism located within exon 1 of the gene encoding the cytotoxic T lymphocyte antigen 4 (CTLA-4) is associated with several HLA-associated multifactorial diseases. The CTLA-4 family shows a negative control on T-cell proliferation and cytokine production (TNF-alpha and IL-10). In the present study we investigated the contribution of the candidate gene CTLA-4 in migraine pathophysiology. Included in the study were 96 MO and 39 MA migraine patients and 106 healthy individuals as control group. The results showed no statistical difference of allele frequencies between patient group and control group. These results would indicate no association between MA and MO migraine and CTLA-4 polymorphism, excluding any possible role of the CTLA-4 gene as a genetic factor determining susceptibility to migraine.

Platelet activation and platelet-leucocyte interaction in patients with migraine. Subtype differences and influence of triptans.

As migraine is the result of an inflammatory mechanism with serotonergic signalling, leucocyte function, platelet function and intercellular communication between those cells is likely to be connected to the final pathway of the disease. We examined P-selectin expression on platelets (platelet activation) and leucocyte-platelet aggregate formation in 72 migraine patients during their attack-free interval and controls using a flow cytometric assay. Patients suffering from migraine without aura had a significantly increased platelet activation and leucocyte-platelet aggregation compared with the control group, unlike the migraine patients with aura. Patients who had taken a triptan within 3 days prior to the investigation showed platelet activation values similar to the control group. The variations in platelet activation patterns of migraine subgroups could indicate different pathomechanisms. Even outside an attack, migraine patients, particularly those without aura, show an increased level of platelet activation which seems to be down-regulated by triptans. This mechanism may account for the triptan-induced increases in headache frequency. The involvement of proinflammatory platelet-leucocyte cross-talk suggests a possible therapeutic strategy using anti-inflammatory drugs.