RESUMO
BACKGROUND: Migraine is associated with several genetic or acquired comorbidities. Studies conducted in recent years emphasize that the frequency of thrombophilia is high in migraine, especially migraine with aura (MA). Similarly, the presence of white matter lesions (WMLs) on brain magnetic resonance imaging (MRI) scans has been associated with migraine for many years. OBJECTIVE: Based on the knowledge that both WMLs and thrombophilia variants are frequently observed in MA, we aimed to investigate whether there is a relationship between genetic thrombophilia and the presence of WMLs in these patients. METHODS: The levels of proteins S and C, antithrombin III activities, activated protein C (APC) resistance, antiphospholipid immunoglobulin G/immunoglobulin M (IgG/IgM) and anticardiolipin IgG/IgM antibodies were investigated in 66 MA patients between the ages of 18 and 49 years who presented no cardiovascular risk factors. The presence of WMLs and the Fazekas grade was determined from the brain magnetic resonance imaging (MRI) scans' T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequence taken from the patients. The rates of WMLs were compared in patients with and without thrombophilia. RESULTS: Thrombophilia was detected in 34.8% of the patients, and 27.3% were determined to have WMLs in brain MRI scans. The WMLs were detected in 23.3% of the patients without thrombophilia, in 34.8% of those with thrombophilia, and in 50% of the subjects with multiple thrombophilia disorders. Among the thrombophilia disorders, only APC resistance was significantly more common in patients with WMLs. CONCLUSION: The results of the present study showed that thrombophilia may be a mechanism that should be investigated in the etiology of increased WMLs in MA.
ANTECEDENTES: La migraña se asocia con una serie de comorbilidades genéticas o adquiridas. Los estudios realizados en los últimos años destacan que la frecuencia de trombofilia es elevada en la migraña, especialmente en la migraña con aura (MA). De manera similar, la presencia de lesiones de la sustancia blanca (LSB) en las imágenes por resonancia magnética (RM) del cerebro se ha asociado con la migraña hace muchos años. OBJETIVO: Con base en la información de que se suelen observar tanto LSB como variantes de la trombofilia en MA, nuestro objetivo fue investigar si existe una relación entre la trombofilia genética y la presencia de LSB en estos pacientes. MéTODOS: Se investigaron los niveles de proteína S y de proteína C, actividades de antitrombina III, resistencia a la proteína C activada (PCA), anticuerpos antifosfolípidos inmunoglobulina G/inmunoglobulina M (IgG/IgM) y anticuerpos anticardiolipina IgG/IgM en 66 pacientes con MA entre 18 y 49 años que no presentaban factores de riesgo cardiovascular. Se determinaron la presencia de LSB y el grado de Fazekas a partir de imágenes por RM del cerebro en la secuencia ponderada en T2 y recuperación de la inversión atenuada de fluido (fluid-attenuated inversion recovery, FLAIR, en inglés) obtenidas de los pacientes. Se compararon las tasas de LSB en pacientes con y sin trombofilia. RESULTADOS: Se detectó trombofilia en el 34,8% de los pacientes y LSB en el 27,3%. Las LSB estuvieron presentes en el 23,3% de los pacientes sin trombofilia, en el 34,8% de los que tenían trombofilia, y en el 50% de los que tenían múltiples trastornos trombofílicos. La resistencia a la PCA fue significativamente más común en aquellos pacientes con LSB. CONCLUSIóN: Los resultados del presente estudio mostraron que la trombofilia puede ser un mecanismo que debe investigarse en la etiología del aumento de LSB en MA.
Assuntos
Imageamento por Ressonância Magnética , Enxaqueca com Aura , Trombofilia , Substância Branca , Humanos , Adulto , Feminino , Masculino , Trombofilia/sangue , Pessoa de Meia-Idade , Enxaqueca com Aura/diagnóstico por imagem , Enxaqueca com Aura/sangue , Adulto Jovem , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adolescente , Antitrombina III/análise , Proteína S/análise , Fatores de Risco , Anticorpos Anticardiolipina/sangue , Proteína C/análise , Imunoglobulina G/sangue , Anticorpos Antifosfolipídeos/sangueRESUMO
BACKGROUND: The association between serum lipids and migraine is controversial. However, randomized controlled trials have suggested that statins may be efficacious for the prevention of migraine. In this study, we aim to investigate the relationship between lipids metabolism and migraine risk. METHODS: Single-nucleotide polymorphisms (SNPs), relating to the serum lipid traits and the effect of lipid-lowering drugs that target APOB, CETP, HMGCR, NPC1L1, and PCSK9, were extracted from genome-wide association studies (GWAS) summary data. The GWAS summary data were obtained from the Global Lipids Genetic Consortium (GLGC), the UK Biobank, and the FinnGen study, respectively. Mendelian randomization (MR) analysis was performed to evaluate the association between serum lipid traits and lipid-lowering drugs with migraine risk. RESULTS: Regarding serum lipids, it was found that SNPs related to high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), or triglycerides (TG) levels were not associated with migraine, migraine with aura (MA) or migraine without aura (MO). In addition, genotypes of HMGCR related to higher LDL-C levels were associated with increased risk of migraine (OR = 1.46, p = 0.035) and MA (OR = 2.03, p = 0.008); However, genotypes of PCSK9 related to higher LDL-C levels were associated with decreased risk of migraine (OR = 0.75, p = 0.001) and MA (OR = 0.69, p = 0.004); And genotypes of APOB related to higher LDL-C levels were associated with decreased risk of MO (OR = 0.62, p = 0.000). CONCLUSIONS: There is a relationship between lipid metabolism characteristics and migraine risk. SIGNIFICANCE: Based on the genome-wide association summary data, single-nucleotide polymorphisms (SNPs) related to high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), or triglycerides (TG) level were not associated with risk of migraine, migraine with aura (MA) or migraine without aura (MO). However, genotypes of HMGCR related to higher LDL-C levels have shown an increased risk on migraine and MA. And genotypes of APOB or PCSK9 related to higher LDL-C levels have shown a decreased risk on MO, or migraine and MA, respectively. These results suggested that there may be a relationship between lipid metabolism characteristics and the risk for migraine development.
Assuntos
Estudo de Associação Genômica Ampla , Hidroximetilglutaril-CoA Redutases , Metabolismo dos Lipídeos , Análise da Randomização Mendeliana , Transtornos de Enxaqueca , Polimorfismo de Nucleotídeo Único , Humanos , Metabolismo dos Lipídeos/genética , Transtornos de Enxaqueca/genética , Transtornos de Enxaqueca/sangue , Hidroximetilglutaril-CoA Redutases/genética , Pró-Proteína Convertase 9/genética , Proteínas de Transferência de Ésteres de Colesterol/genética , Enxaqueca com Aura/genética , Enxaqueca com Aura/sangue , LDL-Colesterol/sangue , Fatores de Risco , Lipídeos/sangue , Triglicerídeos/sangue , HDL-Colesterol/sangue , Enxaqueca sem Aura/genética , Enxaqueca sem Aura/sangue , Proteínas de Membrana Transportadoras , Apolipoproteína B-100RESUMO
OBJECTIVE: To assess support for a causal relationship between hemostatic measures and migraine susceptibility using genetic instrumental analysis. METHODS: Two-sample Mendelian randomization instrumental analyses leveraging available genome-wide association study (GWAS) summary statistics were applied to hemostatic measures as potentially causal for migraine and its subtypes, migraine with aura (MA) and migraine without aura (MO). Twelve blood-based measures of hemostasis were examined, including plasma level or activity of 8 hemostatic factors and 2 fibrinopeptides together with 2 hemostasis clinical tests. RESULTS: There were significant instrumental effects between increased coagulation factor VIII activity (FVIII; odds ratio [95% confidence interval] 1.05 [1.03, 1.08]/SD, p = 6.08 × 10-05), von Willebrand factor level (vWF; 1.05 [1.03, 1.08]/SD, p = 2.25 × 10-06), and phosphorylated fibrinopeptide A level (1.13 [1.07, 1.19]/SD, p = 5.44 × 10-06) with migraine susceptibility. When extended to migraine subtypes, FVIII, vWF, and phosphorylated fibrinopeptide A showed slightly stronger effects with MA than overall migraine. Fibrinogen level was inversely linked with MA (0.76 [0.64, 0.91]/SD, p = 2.32 × 10-03) but not overall migraine. None of the hemostatic factors was linked with MO. In sensitivity analysis, effects for fibrinogen and phosphorylated fibrinopeptide A were robust, whereas independent effects of FVIII and vWF could not be distinguished, and FVIII associations were potentially affected by pleiotropy at the ABO locus. Causal effects from migraine to the hemostatic measures were not supported in reverse Mendelian randomization. However, MA was not included due to lack of instruments. CONCLUSIONS: The findings support potential causality of increased FVIII, vWF, and phosphorylated fibrinopeptide A and decreased fibrinogen in migraine susceptibility, especially for MA, potentially revealing etiologic relationships between hemostasis and migraine.
Assuntos
Hemostasia/genética , Enxaqueca com Aura/genética , Enxaqueca sem Aura/genética , Estudos de Casos e Controles , Fator VII/metabolismo , Fator VIII/metabolismo , Fator XI/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Fibrinopeptídeo A/metabolismo , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Coeficiente Internacional Normatizado , Análise da Randomização Mendeliana , Transtornos de Enxaqueca/sangue , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/genética , Enxaqueca com Aura/sangue , Enxaqueca com Aura/epidemiologia , Enxaqueca sem Aura/sangue , Enxaqueca sem Aura/epidemiologia , Tempo de Tromboplastina Parcial , Inibidor 1 de Ativador de Plasminogênio/sangue , Tempo de Protrombina , Ativador de Plasminogênio Tecidual/sangue , Fator de von Willebrand/metabolismoRESUMO
BACKGROUND: Migraine, especially migraine with aura (MA), has been linked to increased risk for ischemic cerebrovascular disease. The possible role of elevated serum homocysteine (Hcy, a cause of thrombophilia) in migraine has been demonstrated by several studies. OBJECTIVE: The present study aims to review and meta-analyze data from studies investigating the difference of serum Hcy and Hcy lowering vitamins between migraine patients and healthy controls (HC), as well as between patients with MA and migraine without aura (MO). METHODS: Literature search involved MEDLINE, Embase, CENTRAL, Google Scholar, and trial registries. The Newcastle-Ottawa Scale was used to evaluate the quality of the retrieved studies. Standardized mean differences (SMDs) and 95% confidence intervals (95%CIs) were calculated. Funnel-plots were utilized for the evaluation of publication bias. RESULTS: Overall, 29 (28 case-control and 1 cross-sectional) studies were retrieved. Meta-analysis was indicative of higher Hcy concentration in migraine patients vs HC overall [adults and children: 16 studies, I2 = 81%, SMD = 0.41, 95%CI = (0.20, 0.61)]. Hcy was consistently elevated in adults with migraine [adults: 12 studies, I2 = 76%, SMD = 0.35, 95%CI = (0.15, 0.54); children: 1 study, SMD = 0.37, 95%CI = (-0.05, 0.79)]. Subgroup analyses reproduced the results for both adults with MA [7 studies, I2 = 83%, SMD = 0.37, 95%CI = (0.03, 0.71)] and MO [5 studies, I2 = 84%, SMD = 0.46, 95%CI = (0.03, 0.89)]. Figures for serum folate were lower in the overall comparison of migraine patients with HC [adults and children: 11 studies, I2 = 87%, SMD = -0.36, 95%CI = (-0.68, -0.05); adults: 8 studies, I2 = 6%, SMD = -0.11, 95%CI = (-0.22, 0.01); children: 1 study, SMD = -0.71, 95%CI = (-1.14, -0.29); MA adults: 4 studies, I2 = 44%, SMD = -0.16, 95%CI = (-0.35, 0.04); MO adults: 4 studies, I2 = 47%, SMD = -0.17, 95%CI = (-0.44, 0.10)]. Serum vitamin B12 levels were not different between migraine patients and HC [adults and children: 11 studies, I2 = 88%, SMD = -0.24, 95%CI = (-0.57, 0.09); adults: 8 studies, I2 = 57%, SMD = -0.10, 95%CI = (-0.28, 0.08); children: 1 study, SMD = 0.29, 95%CI = (-0.13, 0.71); MA adults: 4 studies, I2 = 63%, SMD = -0.14, 95%CI = (-0.48, 0.20); MO adults: 4 studies, I2 = 59%, SMD = -0.15, 95%CI = (-0.45, 0.15)]. Serum Hcy was lower in MO than MA [adults and children: 10 studies, I2 = 39%, SMD = 0.30, 95%CI = (0.14, 0.46), adults: 6 studies, I2 = 29%, SMD = 0.21, 95%CI = (0.09, 0.36), children: 1 study, SMD = 0.51, 95%CI = (0.22, 0.80)]. Serum folate and vitamin B12 did not differ between MA and MO. CONCLUSIONS: Our results suggest that there is a possible link between migraine, mainly MA, and elevated serum Hcy.
Assuntos
Ácido Fólico/sangue , Homocisteína/sangue , Enxaqueca com Aura/sangue , Enxaqueca sem Aura/sangue , Piridoxina/sangue , Vitamina B 12/sangue , HumanosRESUMO
OBJECTIVE: To investigate plasma glucose changes during the ictal state of migraine compared to the interictal state. BACKGROUND: Previous studies suggest abnormal glucose metabolism in migraine patients during and outside of attacks. It is not known if plasma glucose levels change during spontaneous migraine attacks. METHODS: Plasma glucose levels were measured during and outside of spontaneous migraine attacks with and without aura. Plasma glucose values were corrected for diurnal variation of plasma glucose by subtracting the difference between the moving average (intervals of 2 hours) and overall mean from the plasma glucose values. RESULTS: This was a sub-study of a larger study conducted at Rigshospitalet Glostrup in the Capital Region of Denmark. Thirty-one patients (24 F, 7 M, 13 with aura, 18 without aura) were included in the study. Mean time from attack onset to blood sampling was 7.6 hours. Mean pain at the time of investigation was 6 on a 0-10 verbal rating scale. Plasma glucose was higher ictally compared to the interictal phase (interictal mean: 88.63 mg/dL, SD 11.70 mg/dL; ictal mean: 98.83 mg/dL, SD 13.16 mg/dL, difference 10.20 mg/dL, 95% CI = [4.30; 16.10]), P = .0014). The ictal increase was highest in patients investigated early during attacks and decreased linearly with time from onset of migraine (-1.57 mg/dL/hour from onset of attack, P = .020). The attack-related increase in blood glucose was not affected by pain intensity or presence of aura symptoms. CONCLUSIONS: We demonstrated higher plasma glucose values during spontaneous migraine attacks, independent of the presence of aura symptoms and not related to pain intensity, peaking in the early phase of attacks. Additional studies are necessary to confirm our findings and explore the possible underlying mechanisms.
Assuntos
Glicemia/metabolismo , Enxaqueca com Aura/sangue , Enxaqueca com Aura/fisiopatologia , Enxaqueca sem Aura/sangue , Enxaqueca sem Aura/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: We aimed to examine arterial stiffness and vitamin K2 status in migraine subjects by comparison to controls. BACKGROUND: Migraine is a primary headache disorder that has been associated with an increased risk of cardiovascular events. Mechanisms underlying this increased risk, however, remain unclear. Vitamin K2 deficiency emerged as a cardiovascular risk factor, but vitamin K2 status has never been explored in migraine subjects. DESIGN AND METHODS: This is a case-control, single-center, observational study that includes a cohort of subjects with migraine and their age- and sex-matched controls. Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV). Dephosphorylated-uncarboxylated matrix-Gla-protein (dp-ucMGP) was used as a marker for vitamin K2 status. A propensity-matched scoring method was used. RESULTS: A total of 146 patients (73 matched pairs) were included in this study, of whom 89% were women with a mean age of 31.9 ± 8.4 years. Compared with controls, migraine patients had statistically significantly higher mean cfPWV (7.2 ± 1.1 vs 6.4 ± 0.8 m/s, 95% confidence interval (CI) of mean difference [0.45, 1.08], P < .001), as well as higher dp-ucMGP (454.3 ± 116.7 pmol/L vs 379.8 ± 126.6 pmol/L, 95% CI of mean difference [34.63, 114.31], P < .001). Higher cfPWV was associated with higher dp-ucMGP concentrations only in the migraine with aura (MWA) group. Moreover, migraine subjects had a higher frequency of vitamin K2 deficiency (dp-ucMGP ≥ 500 pmol/L) compared to controls, but this association was not statistically significant (23/73 [31.5%] vs 16/73 [21.9%], P = .193). CONCLUSIONS: Individuals with migraine have worse indices of arterial stiffness as compared with their age- and sex-matched control subjects. This increase in arterial stiffness is associated with an increase in markers of vitamin K2 deficiency in the MWA group.
Assuntos
Proteínas de Ligação ao Cálcio/sangue , Proteínas da Matriz Extracelular/sangue , Transtornos de Enxaqueca/sangue , Transtornos de Enxaqueca/fisiopatologia , Rigidez Vascular/fisiologia , Vitamina K 2/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Enxaqueca com Aura/sangue , Enxaqueca com Aura/fisiopatologia , Análise de Onda de Pulso , Adulto Jovem , Proteína de Matriz GlaRESUMO
OBJECTIVES: We investigated the state of inflammation, PTX3 level and other routine inflammatory markers (high sensitivity C-reactive protein [hsCRP], and white blood cells [WBC]), in patients who presented to the emergency department (ED) with migraine. We also investigated the relationship between the clinical presentation, PTX3 level, and other routine inflammatory markers in the emergency management of these patients. METHODS: The study included 44 patients (group 1) who presented to the ED due to a migraine attack with aura and 44 controls (group 2) with similar demographic characteristics. RESULTS: The WBC count was 8.82⯱â¯2.10â¯×â¯109/L in group 1 and 7.85⯱â¯2.04â¯×â¯109/L in group 2. The mean PTX3 level was 11.57⯱â¯3.99â¯ng/mL in patients who presented at the ED with a migraine attack, and 4.59⯱â¯1.28â¯ng/mL in controls. The differences values of WBC and PTX3 between the two groups were significant (respectively; Pâ¯=â¯0.031, Pâ¯<â¯0.001). ROC analyses indicated significant results for PTX3 as a marker for acute migraine attack. It had a sensitivity of 93% and specificity of 84% at a cut-off value of 5.80â¯ng/mL. CONCLUSION: This is the first study to investigate plasma levels of PTX3 in patients with acute migraine. PTX3 as a biomarker may be used as an additional examination to the current subjective criteria to support the diagnosis of patients presenting to the ED with an acute migraine attack.
Assuntos
Proteína C-Reativa/metabolismo , Serviço Hospitalar de Emergência , Enxaqueca com Aura/sangue , Enxaqueca com Aura/diagnóstico , Componente Amiloide P Sérico/metabolismo , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Ferritinas/sangue , Humanos , Contagem de Leucócitos , Masculino , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
Migraine attacks alter various molecules that might be related to the pathophysiology of migraine, such as serotonin, calcitonin gene-related peptide, and nitric oxide. The underlying pathophysiology of migraine is as yet unclear. We explored key proteins related to the pathogenesis of migraine here. Serum was collected from two patients with migraine with aura (MA) and seven patients with migraine without aura (MO) during attack-free periods and migraine attacks. Samples were analyzed using 2-dimensional gel electrophoresis. Nineteen protein spots were altered between the attack-free versus migraine attack periods. Mass spectrometric analysis was performed to identify the proteins within each of the 19 altered spots. Thirty-six proteins were significantly altered in samples collected during attack-free periods versus migraine attacks. The protein with the statistically most significant MASCOT/Mowse score (268±112) among lipoproteins was apolipoprotein (ApoE). In the MA and MO groups, ApoE protein levels were significantly higher during migraine attack than during the attack-free period (p<0.05). ApoE protein levels were also significantly increased in the MA group during the attack-free period compared to healthy controls and patients with tension type headaches (p<0.01). Migraine alters ApoE levels, especially in MA. ApoE might play an important role in the pathophysiology of migraine, and may act as a diagnostic biomarker of migraine.
Assuntos
Apolipoproteínas E/sangue , Biomarcadores/sangue , Enxaqueca com Aura/sangue , Enxaqueca sem Aura/sangue , Adulto , Eletroforese em Gel Bidimensional , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Pessoa de Meia-Idade , Espectrometria de Massas em TandemRESUMO
Migraine is one of the most common types of pain associated with sterile inflammatory conditions. Soluble urokinase plasminogen activator receptor (suPAR) is a potential novel inflammatory marker. We aim to determine the association between serum values of suPAR, procalcitonin, fibrinogen, and high-sensitivity C-reactive protein (hs-CRP) and migraine disease characteristics. The study involved a total of 60 migraine patients (33 patients in the interictal period, 27 patients in the attack period) and 30 healthy individuals. The serum values of suPAR were found to be significantly higher in migraine patients in the attack period than in migraine patients in the interictal period, and in healthy individuals (p < .01 for both). In addition, levels of suPAR were determined to be higher in migraine with aura patients than in migraine without aura patients. When we subdivided migraine patients according to frequency of attack (attacks/month), significant differences were found between the suPAR and procalcitonin levels (measured during the attack period) of those in the frequent-attack group (4-5 or more) versus those in the less frequent attack group (less than 4). Serum levels of procalcitonin were shown to be significantly higher in migraine patients during the attack period compared with migraine patients in the interictal period and in control subjects (p = .001 for both). Significant differences were found between plasma levels of fibrinogen in migraine patients versus control subjects (p < .01). No statistically significant difference was found between levels of hs-CRP in migraine patients versus the control group. These findings may show that presenting a high level of suPAR in migraine patients with attack and aura results to predisposition to occurring on the symptoms and that high levels of suPAR, procalcitonin and fibrinogen in patients with migraine result in neurogenic inflammation during migraine headaches.
Assuntos
Transtornos de Enxaqueca/sangue , Enxaqueca com Aura/sangue , Inflamação Neurogênica/sangue , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Proteína C-Reativa/metabolismo , Calcitonina/sangue , Feminino , Fibrinogênio/metabolismo , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Transtornos de Enxaqueca/genética , Transtornos de Enxaqueca/fisiopatologia , Enxaqueca com Aura/genética , Enxaqueca com Aura/fisiopatologia , Inflamação Neurogênica/genética , Inflamação Neurogênica/fisiopatologia , Receptores de Ativador de Plasminogênio Tipo Uroquinase/genéticaRESUMO
BACKGROUND The aim of this study was to determine the plasma levels of cyclooxygenase-2 (COX-2) and visfatin in different stages and different subtypes of migraine headaches compared to a control group to elucidate the pathological mechanisms involved. MATERIAL AND METHODS We recruited a case-control cohort of 182 adult migraine patients and 80 age-matched and gender-matched healthy controls. The migraine patients were divided into two groups: the headache-attack-period group (Group A, n=77) and the headache-free-period group (Group B, n=105). The two groups were further divided into subgroups according to whether they had aura symptoms. Solid phase double antibody sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma levels of COX-2 and visfatin. Statistical analysis was performed using SPSS 17.0. RESULTS The plasma levels of COX-2 and visfatin in the headache-attack-period group were significantly higher than in the headache-free-period group and the control group; there were no significant differences between the headache-free group and the control group. There were no significant differences in plasma levels of COX-2 and visfatin between the subgroups: headache-attack-period with aura subgroup and the headache-attack-period without aura sub group. CONCLUSIONS COX-2 and visfatin participated in the pathogenesis of migraine headaches. The presence of aura had no effect on the serum levels of COX-2 and visfatin.
Assuntos
Ciclo-Oxigenase 2/sangue , Citocinas/sangue , Transtornos de Enxaqueca/sangue , Transtornos de Enxaqueca/enzimologia , Nicotinamida Fosforribosiltransferase/sangue , Adulto , Estudos de Casos e Controles , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/terapia , Enxaqueca com Aura/sangue , Enxaqueca com Aura/enzimologia , Enxaqueca com Aura/terapiaRESUMO
Background Migraine is a prevalent disorder characterised by recurrent headache attacks preceded or accompanied by aura in a subgroup of patients. Migraine often occurs together with major depressive disorder (MDD). Alterations of adipokine levels have been reported both in migraine and in MDD. In this cross-sectional study, we aimed to assess the associations between serum leptin and adiponectin levels and migraine or migraine subtypes. Analyses were adjusted for a lifetime history of MDD in order to investigate the association between adipokines and migraine under consideration of depression status. Methods We included 3025 participants from the CoLaus/PsyCoLaus study. The impact of leptin and adiponectin levels on a diagnosis of migraine was analysed by binary regression analyses, adjusting for variables known to influence adipokine levels. Subgroup analyses were conducted based on the presence of aura. Results Crude leptin levels were significantly higher in subjects with migraine than controls (Mann-Whitney U = 515,102, p = 6 × 10-7). When performing adjusted analyses, leptin levels were found to be significantly higher in subjects with migraine (odds ratio = 1.22, p = 0.024) and migraine with aura (odds ratio = 1.34, p = 0.004). Conclusion High leptin levels might play a role in the pathogenesis of migraine and migraine with aura.
Assuntos
Leptina/sangue , Enxaqueca com Aura/sangue , Enxaqueca com Aura/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Enxaqueca com Aura/epidemiologia , Distribuição Aleatória , Suíça/epidemiologiaRESUMO
OBJECTIVES: Migraine is a debilitating condition that affects approximately 15% of the general population. It represents a huge proportion of presentations to the emergency department and a significant number of neurology admissions. Patients are often investigated with imaging. This is particularly the case with migraine with aura (MA). The yield of imaging is however low. There is limited information on Australian hospital presentations and utility of imaging. We aimed to analyse the demographics of migraine presentations to our hospital and the yield of imaging in our centre to help guide future approaches to these patients. PATIENTS AND METHODS: We retrospectively looked at medical records of patients presenting to the western health from January 2012 to June 2013. Patients were classified as either having migraine with aura or without. Baseline demographics, cardiovascular risk factors and imaging studies (CT brain, MRI brain and carotid Doppler studies) in each group were evaluated. Patients found to have white matter hyperintensities on MRI were further evaluated. RESULTS: We found patients with aura were more likely to have hypercholesterolemia (12% vs 7%, p=0.05). Patients with aura were more likely to be evaluated with imaging (CT brain (70% vs 41% p<0.0001) and MRI brain (44% vs 17% p<0.0001)). The patients investigated with imaging had no clinically significant findings. 21% of patients with aura were investigated with carotid Doppler studies. Only 1 patient had an abnormal result. Patients with white matter hyperintensities were older (51 vs 39 years; p<0.0001) and were more likely to have Hypertension (29% vs 14% p=0.019), Hypercholesterolemia (29% vs 11% p=0.003) and T2DM (16% vs 4% p=0.011). CONCLUSION: We found patients with MA and without aura to be largely similar. We also found imaging in either group to be of almost no clinical value.
Assuntos
Hipercolesterolemia/sangue , Enxaqueca com Aura , Substância Branca/diagnóstico por imagem , Adulto , Comorbidade , Feminino , Humanos , Hipercolesterolemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Enxaqueca com Aura/sangue , Enxaqueca com Aura/diagnóstico por imagem , Enxaqueca com Aura/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Retinol-binding protein-4 (RBP4) and high-sensitivity C-reactive protein (hs-CRP) levels are associated with inflammation in patients with migraine. The release of proinflammatory cytokines during migraine results in recurrent sterile neurogenic inflammation. This study aimed to determine the correlation between RBP4 and hs-CRP levels, and migraine, which is considered an inflammatory disease. The study included 48 migraine patients and 40 age- and gender-matched controls. Migraine was diagnosed according to International Classification of Headache Disorders-II. The serum RBP4 level was measured using a commercial ELISA kit and hs-CRP was measured using an enzyme immunoassay test kit. The serum RBP4 level was significantly lower in the migraine patients than in the controls (P < 0.001), whereas the hs-CRP level was significantly higher in the migraine patients (P < 0.001). RBP4 and hs-CRP levels did not differ between the migraine patients with and without aura (P > 0.05). Migraine headache severity, frequency and duration were not correlated with serum RBP or hs-CRP levels (P > 0.05). The observed high hs-CRP level and low RBP4 level in migraine patients suggest that vitamin A might play a major role in the pathogenesis of migraine. It is known that inflammation is a key factor in many diseases. Additional research might result in a better understanding of the anti-inflammatory effects of vitamin A.
Assuntos
Proteína C-Reativa/metabolismo , Enxaqueca com Aura/sangue , Enxaqueca sem Aura/sangue , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Adolescente , Adulto , Análise Química do Sangue , Estudos Transversais , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Adulto JovemRESUMO
Migraine is the most common form of headache disorder globally. The etiology of migraine is multifactorial, with genetic components and environmental interactions considered to be the main causal factors. Some researchers postulate that deficits in mitochondrial energy reserves can cause migraine or an increase in homocysteine levels can lead to migraine attacks; therefore, vitamins could play a vital role in migraine prevention. For instance, riboflavin influences mitochondrial dysfunction and prevents migraine. Genes such as flavoenzyme 5,10-methylenetetrahydrofolate reductase (MTHFR), especially the C677T variant, have been associated with elevated plasma levels of homocysteine and migraine with aura. Homocysteine catalyzation requires the presence of vitamins B6, B12, and folic acid, which can decrease the severity of migraine with aura, making these vitamins potentially useful prophylactic agents for treating migraine with aura. Menstrual migraine, on the other hand, is associated with increased prostaglandin (PG) levels in the endometrium, indicating a role for vitamin E, which is an anti-PG. Vitamin C can also be used as a scavenger of reactive oxygen species for treating neurogenic inflammation in migraine patients. This paper reviews possible therapies based on vitamin supplementation for migraine prophylaxis, focusing on migraine with aura and menstrual migraine.
Assuntos
Epilepsia/dietoterapia , Menstruação , Transtornos de Enxaqueca/dietoterapia , Enxaqueca com Aura/dietoterapia , Adulto , Ácido Ascórbico/administração & dosagem , Epilepsia/sangue , Epilepsia/patologia , Feminino , Ácido Fólico/administração & dosagem , Genótipo , Homocisteína/sangue , Humanos , Transtornos de Enxaqueca/sangue , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/patologia , Enxaqueca com Aura/sangue , Enxaqueca com Aura/patologia , Vitamina B 12/administração & dosagem , Vitamina B 6/administração & dosagem , Vitamina E/administração & dosagemRESUMO
BACKGROUND: Results of several studies suggest that serum amino acids monitoring in migraine might be useful as an objective measurement of the disease status. OBJECTIVE: The aim of the present work was to analyze the profile of aliphatic and aromatic amino acids in blood serum of migraine patients without and with aura between attacks. METHODS: A total number of 37 migraine patients (26 with migraine without aura and 11 with migraine with aura), mean age 39±12 years, and 40 age-matched healthy subjects as the control group, mean age 38±14 years, were included into the study. The levels of glutamic acid, glutamine, histidine (His), valine (Val), isoleucine, leucine (Leu), phenyloalanine, lysine were evaluated. RESULTS: The level of His was significantly higher in both groups of migraine patients (without and with aura) compared to the control group (F(2,74)=10.17, p=0.00). The levels of Val and Leu were significantly different in migraine without but not with aura, when compared with the control group (F(2,74)=4.70, p=0.01 and F(2,74)=4.39, p=0.02, respectively). CONCLUSION: We found higher level of His in migraine patients without and with aura and lower level of Val and Leu in patients with migraine without aura.
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Aminoácidos/sangue , Enxaqueca com Aura/sangue , Enxaqueca sem Aura/sangue , Adulto , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Migraine is a common headache disorder that may be associated with vascular disease and cerebral white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) scan. High sensitivity C-reactive protein (hs-CRP) is a marker of inflammation that may predict subclinical atherosclerosis. However, the relation between migraine, vascular risks, and WMHs is unknown. We evaluated hs-CRP levels and the relation between hs-CRP level and WMHs in adult migraine patients. METHODS: This case-control study included 432 subjects (216 migraine patients [without aura, 143 patients; with aura, 73 patients]; 216 healthy control subjects without migraine; age range 18-50 y). Migraine diagnosis was determined according to the International Classification of Headache Disorders II diagnostic criteria. The migraine patients and control subjects had no known vascular risk factors, inflammatory disease, or comorbid disease. The presence and number of WMHs on MRI scans were determined, and serum hs-CRP levels were measured by latex-enhanced immunoturbidimetry. RESULTS: Mean hs-CRP level was significantly greater in migraine patients (1.94 ± 2.03 mg/L) than control subjects (0.82 ± 0.58 mg/L; P ≤ .0001). The mean number of WMHs per subject and the presence of WMHs was significantly greater in migraine patients (69 patients [31.9%]; 1.68 ± 3.12 mg/dL) than control subjects (21 subjects [9.7%]; 0.3 ± 1.3; P ≤ .001). However, there was no correlation between hs-CRP level and WMHs in migraine patients (r = 0.024; not significant). The presence of WMHs was increased 4.35-fold in migraine patients (odds ratio 4.35, P ≤ .001). CONCLUSIONS: High hs-CRP level may be a marker of the proinflammatory state in migraine patients. However, the absence of correlation between hs-CRP level and WMHs suggests that hs-CRP is not causally involved in the pathogenesis of WMHs in migraine patients. The WMHs were located mostly in the frontal lobe and subcortical area.
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Proteína C-Reativa/análise , Enxaqueca com Aura/sangue , Enxaqueca com Aura/patologia , Enxaqueca sem Aura/sangue , Enxaqueca sem Aura/patologia , Substância Branca/patologia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Migraine is a common chronic neurological disorder with still largely unknown pathogenesis. We aimed to explore the possible role of tumor necrosis factor alpha (TNF-α) gene polymorphisms as risk factors of migraine, and whether they influence the TNF-α level. MATERIALS AND METHODS: Two hundred patients with migraine and 200 controls were enrolled in this study. Polymorphisms of TNF-α gene were detected using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum TNF-α level was measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: TNF-α-308 GA, AA genotypes and A allele, TNF-α-857 CT genotype and T allele were associated with increased risk of migraine, while the TNF-α-238 polymorphism was not. TNF-α-308 GA, AA genotypes and A allele or AA genotype were associated with increased risk of migraine with aura (MA) and migraine without aura (MO) respectively; this was more significant in female patients with MA than in males. TNF-α-857 CT genotype was associated with increased risk of MO, or MA in females or males. While -857T allele was significantly associated with MO or MA in males and with MA only in females. On the other hand, we didn't find any significant associations of TNF-α-238 polymorphism with MO, or MA in males or females. TNF-α levels were higher in patients with migraine, MA, or MO than in controls (P<0.001). CONCLUSION: TNF-α polymorphisms were associated with migraine, MA, or MO in Egyptians.
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Enxaqueca com Aura , Enxaqueca sem Aura , Fator de Necrose Tumoral alfa , Adulto , Egito/epidemiologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Enxaqueca com Aura/sangue , Enxaqueca com Aura/epidemiologia , Enxaqueca com Aura/genética , Enxaqueca sem Aura/sangue , Enxaqueca sem Aura/epidemiologia , Enxaqueca sem Aura/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genéticaRESUMO
BACKGROUND AND PURPOSE: Endothelial microparticles (EMPs) are vesicles that are released from activated endothelial cells and serve as a surrogate for endothelial dysfunction (ED). ED may be involved in migraine pathophysiology and contribute to the increased risk of ischemic stroke, particularly in female migraineurs with aura (MA). We sought to determine whether EMPs are elevated in women with MA. METHODS: In this case-control study, EMPs were detected by analysing surface markers using fluorescence-activated cell sorting (FACS). Surface markers were measured covering the main cell lines relevant in cardiovascular disease like endothelial cells, platelets, monocytes and leucocytes. Microparticles (MPs) were identified in correlation to calibration by 1 -µm calibrator beads (Beckman Coulter). Arterial stiffness was assessed using fingertip tonometry and the heart rate-adjusted augmentation index (AI). RESULTS: We included 29 patients with MA and 29 matched controls. MA patients had significantly higher EMPs (CD62E(+)AnnexinV(+): 5142/µl vs 1535/µl; p < 0.001; CD144(+)AnnexinV(+): 6683/µl vs 3107/µl; p < 0.001), monocytic (CD14(+)AnnexinV(+) 6378 vs 3161; p < 0.001), and platelet MPs (CD62P(+)CD42b(+)AnnexinV(+) 5450 vs 3204; p < 0.001). Activated EMPs (CD62E(+)AnnexinV(+)) correlated with heart-rate adjusted AI (r = 0.46; p < 001). CONCLUSION: EMP levels are significantly elevated in women with MA and correlated with increased AI. Our findings suggest that endothelial activation is present in women with MA. This might contribute to higher stroke risk in MA.
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Micropartículas Derivadas de Células/patologia , Enxaqueca com Aura/sangue , Adulto , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , HumanosRESUMO
Migraine is a common neurological disorder characterized by recurrent attacks, unilateral head pain, and related symptoms. The aim of this study was to investigate three endothelial nitric oxide synthase (eNOS) polymorphisms in 176 patients with migraine and 123 healthy individuals. Clinical and biochemical parameters were investigated. Genetic analysis was performed using the polymerase chain reaction-restriction fragment length polymorphism method. The differences between migraine cases and the control group were significant for two polymorphisms (-786T/C and 894G/T) (p = 0.000). Homocysteine and body mass index (BMI) were significantly higher in the migraine group than in the control group (p = 0.001 and p = 0.000). The relation between -786T/C genotype and BMI and allodynia was significant. TC heterozygotes and CC homozygotes were significantly higher in the migraine group than in the control group (OR 2.843 and 95 % CI 1.681-4.808 and OR 3.729 and 95 % CI 1.784-7.792, respectively). The 894G/T genotype was correlated with BMI, pain intensity, age at the onset of migraine, nausea, tension, compression, and allodynia. For this polymorphism, GT heterozygotes and TT homozygotes were significantly higher in the migraine group than in the control group (OR 3.027 and 95 % CI 1.830-5.008 and OR 3.221 and 95 % CI 1.223-8.484, respectively). The G10T genotype was correlated with attack duration and age at the onset of migraine (p = 0.008 and p = 0.040). eNOS polymorphisms may be useful markers for assessing migraine risk and clinical diagnosis.