Association Between Hemostatic Profile and Migraine: A Mendelian Randomization Analysis.

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.

Serum Homocysteine, Pyridoxine, Folate, and Vitamin B12 Levels in Migraine: Systematic Review and Meta-Analysis.

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.

Plasma Glucose Levels Increase During Spontaneous Attacks of Migraine With and Without Aura.

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.

Serum apolipoprotein E may be a novel biomarker of migraine.

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.

MicroRNA profiling in migraine without aura: pilot study.

BACKGROUND AND PURPOSE: MicroRNAs (miRNAs) are short, non-coding RNAs whose deregulation has been shown in several human diseases, including pain states and diseases associated with increased cardiovascular (CV) risk. This study aimed at identifying differentially expressed circulating miRNAs in patients with 'migraine without aura' (MO), a pain condition whose link with CV risk remains debated. METHODS: Fifteen female MO patients and 13 matching healthy controls underwent a circulating microRNA expression profiling. MiR-22, miR-26a, miR-26b, miR-27b, miR-29b, let-7b, miR-181a, miR-221, miR-30b, and miR-30e were selected for validation by quantitative real-time polymerase chain reaction. RESULTS: In migraineurs versus controls, four miRNAs were differentially expressed: miR-27b was significantly up-regulated (q < 0.004), while miR-181a, let-7b, and miR-22 were significantly down-regulated (q ≤ 0.01). MiR-22 and let-7b down-regulation was also confirmed in circulating blood monocytes. A logistic regression model based on microRNA expression profile showed a high accuracy for identifying migraine (AUC of ROC curve: 0.956; P < 0.001). CONCLUSION: A specific circulating miRNAs profile is associated with migraine without aura. Remarkably, the same miRNAs are known to be modulated in the setting of atherosclerosis and stroke in humans. This study represents a first step towards further characterization of MO diagnosis/pathophysiology, also in relation to its link with cardiovascular risk.

Retinol-binding protein-4 and hs-CRP levels in patients with migraine.

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.

Changes in Serum Amino Acids in Migraine Patients without and with Aura and their Possible Usefulness in the Study of Migraine Pathogenesis.

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.

High sensitivity C-reactive protein and cerebral white matter hyperintensities on magnetic resonance imaging in migraine patients.

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.

Influence of tumor necrosis factor alpha gene promoter polymorphisms and its serum level on migraine susceptibility in Egyptian patients.

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.

Association of endothelial nitric oxide synthase gene polymorphisms (894G/T, -786T/C, G10T) and clinical findings in patients with migraine.

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.

Is serum S100B protein an useful biomarker in migraine?

Experimental data have demonstrated a role for S100B protein through the release of proinflammatory cytokines, following trigeminal nerve activation, implicated in the pathology of migraine. We investigated serum levels of S100B protein, as a peripheral glial biomarker, in patients with migraine. In total, 49 migraineurs and 35 age- and gender-matched controls were enrolled in this prospective clinical study. The migraine diagnosis was made according to the International Classification of Headache Disorders II diagnostic criteria. Serum samples were obtained for the measurement of S100B levels from all participants and were analyzed using commercial enzyme-linked immunosorbent assay kits. Serum S100B levels were significantly lower in migraineurs than controls (p < 0.001). S100B levels did not significantly differ in migraineurs with or without aura (p > 0.05). In addition, there was no correlation between serum S100B levels and headache characteristics, including attack severity, frequency and duration, and disease duration (p > 0.05). These findings suggest that serum S100B levels were significantly decreased in migraine patients, but further research is needed to ascertain the contribution of S100B in the clinical evaluation of migraine.

Low fetuin-A level in migraine: a case-control study.

Migraine is a type of primary headache which is caused by the alterations in trigeminovascular system. Migraine attacks are associated with neurovascular inflammation of the cerebral and extracerebral vessels, but its pathophysiological mechanisms have not still been fully delineated. Also, migraine has been found to be associated with higher risks for various metabolic disorders. Thus, we aimed to investigate the matrix metalloproteinases (MMP), fetuin-A, ghrelin, and omentin levels which have important roles in metabolic disorders and inflammation, and to examine their relationship with migraine subtypes and attack frequency. Forty-nine migraine patients and 30 age- and sex-matched healthy control subjects were enrolled. Migraine diagnosis was confirmed according to the International Classification of Headache Disorders-II diagnostic criteria. Analyses of MMP9,MMP3, ghrelin, omentin, and fetuin-A were performed by the ELISA method. Fetuin-A, MMP-9, and MMP-3 levels were significantly lower in migraine than controls (p < 0.05). There were no significant differences between groups with respect to omentin and ghrelin (p > 0.05). In migraine patients, serum fetuin-A levels were positively correlated with MMP-9 and negatively correlated with MMP-3. MMP-3, MMP-9, fetuin-A, omentin and ghrelin levels did not correlate with age, disease duration, or frequency of migraine headache (p > 0.05). Migraine patients have lower fetuin-A, MMP-3 and MMP-9 levels than healthy individuals. Migraine patients have low fetuin-A levels, which may be related to the pathogenesis of migraine. The importance and impact of our findings on the pathogenesis, characteristics, and treatment of migraine needs to be investigated in further detailed studies.

Interictal increase of CGRP levels in peripheral blood as a biomarker for chronic migraine.

OBJECTIVE: To determine calcitonin gene-related peptide (CGRP) levels outside migraine attacks in peripheral blood as a potential biomarker for chronic migraine (CM). METHODS: Women older than 17 years and diagnosed with CM were recruited. Matched healthy women with no headache history and women with episodic migraine (EM) served as control groups, together with a series of patients with episodic cluster headache in a pain-free period. CGRP levels were determined in blood samples obtained from the right antecubital vein by ELISA outside a migraine attack and having taken no symptomatic medication the day before. For ethical reasons, preventatives were not stopped. RESULTS: We assessed plasma samples from 103 women with CM, 31 matched healthy women, 43 matched women with EM, and 14 patients with episodic cluster headache matched for age. CGRP levels were significantly increased in CM (74.90 pg/mL) as compared with control healthy women (33.74 pg/mL), women with EM (46.37 pg/mL), and patients with episodic cluster headache (45.87 pg/mL). Thresholds of 43.45 and 58.22 pg/mL optimize the sensitivity and specificity to differentiate CM from healthy controls and EM, respectively. In the CM group, CGRP levels were significantly increased in women with a history of migraine with aura vs those only experiencing migraine without aura. Variables such as age, analgesic overuse, depression, fibromyalgia, vascular risk factors, history of triptan consumption, or kind of preventative treatment did not significantly influence CGRP levels. CONCLUSION: Increased CGRP level measured in peripheral blood outside migraine attacks and in the absence of symptomatic medication could be a biomarker helping in the diagnosis of CM.

Plasma homocysteine in patients of migraine without aura.

BACKGROUND: Few studies have studied the role of homocysteine in migraineurs and have produced conflicting results. The MTHFR C677T genotype has been associated with increased risk of migraine in selected clinical samples. We assessed the association of the MTHFR C677T variant with migraine, the corresponding homocysteine levels and their correlation. METHOD: We studied 27 random adult migraineurs with aura (MWA), migraine without aura (MWOA), and 32 non-migraineurs (controls) from Lahore, Pakistan in this pilot study which is still under progress. RESULTS: We found significant differences in homocysteine levels between various diagnostic groups (K-W test: p=0.005). One-way ANOVA, post-hoc tests revealed significant differences in homocysteine levels between Non-migraineurs, MWA (p=0.002, CI: 1.93 - 9.19) and MWoA (p=0.002, CI: -9.19 - -1.9). We found a significant association between the migraine group and C677T-MTHFR variant mutant allele (C/T) (p=0.039). We did not find a significant association between C677T-MTHFR variant and homocysteine levels. CONCLUSION: In this pilot study, we found plasma homocysteine levels to be significantly associated with MWOA. Additionally, plasma homocysteine levels were lower in MWA than in MWOA. Furthermore, we did not find a relationship between homocysteine levels and the MTHFR variant (SNP rs1801133). Lastly, there may be a relationship between the MTHFR variant (SNP rs1801133) and migraine in this population.

Visual evoked potential and spatial frequency in migraine: a longitudinal study.

OBJECTIVES: Reduced habituation of visual evoked potentials (VEP) has been reported in migraine. We aimed to study if preattack excitability changes were related to check size using a paired longitudinal design. MATERIALS AND METHODS: Magnocellular and parvocellular functions were studied with monocular 31 and 62 checks in 33 adult migraine patients without aura (MwoA), 8 with aura (MA) and 31 controls. VEP was recorded in four blocks of 50 stimuli. N1P1 and P1N2 amplitudes were measured. Sessions were classified as preattack or interictal. RESULTS: MA patients had significantly higher P1N2 and N1P1 amplitude than the controls and MwoA. VEP amplitude habituation was not found in controls. Migraine patients had significantly higher P1N2 amplitude before the attack compared with a paired interictal recording for large checks. CONCLUSIONS: Cortical excitability is high in MA. Headache severity affects visual excitability. Increased P1N2 VEP amplitude before the attack suggests a cyclic decreased intracortical inhibition in extrastriate magnocellular pathways in migraine.

Migraine and biomarkers of endothelial activation in young women.

BACKGROUND AND PURPOSE: There is mounting evidence of endothelial activation and dysfunction in migraine. Our objectives were to determine in a population of premenopausal women whether endothelial activation markers are associated with migraine. METHODS: Women (18 to 50 years) with and without migraine and free from cardiovascular disease were evaluated with tests of coagulation (von Willebrand factor activity, prothrombin fragment), fibrinolysis (tissue-type plasminogen activator antigen), inflammation (high-sensitivity C-reactive protein), and oxidative stress (homocysteine, total nitrate/nitrite concentrations, thiobarbituric acid-reactive substances). RESULTS: Sixty-one participants had migraine with aura (MA), 64 had migraine without aura (MO), and 50 were controls. Compared with controls, women with migraine had higher adjusted odds ratios for elevated von Willebrand factor activity of 6.51 (95% CI, 1.94 to 21.83) in those with MA and of 4.59 (95% CI, 1.37 to 15.38) in those with MO, elevated high-sensitivity C-reactive protein of 7.99 (95% CI, 2.32 to 27.61) in those with MA and of 2.63 (95% CI, 0.73 to 9.45) in those with MO, and for lower nitrate/nitrite levels of 6.60 (95% CI, 2.06 to 21.16) in those with MA and of 3.03 (95% CI, 0.90 to 10.15) in those with MO. Within the migraine group, von Willebrand factor activity was correlated with tissue-type plasminogen activator antigen (P=0.035) and nitrate/nitrite (P=0.024). There was a trend with high-sensitivity C-reactive protein (P=0.09). CONCLUSIONS: In premenopausal women with migraine, particularly in those with MA, there is evidence of increased endothelial activation, a component of endothelial dysfunction.

Proinflammatory plasma cytokines in children with migraine.

Toward understanding the role of cytokines in migraine, this study focused on selected proinflammatory cytokines. The study group consisted of 21 children who had migraine with and without aura; the control group was 24 children with episodic tension-type headache. Plasma interleukin-1 alpha was undetectable in 19 control subjects with tension-type headache, but was detectable in 16 patients with migraine, which suggests that interleukin-1 alpha level might be higher in migraine. Soluble tumor necrosis factor receptor 1 in the migraine group was significantly higher than in the control group (P < 0.0005). Migraine patients tended to have increased tumor necrosis factor alpha level, compared with the control group. The interleukin-1 alpha level was significantly higher in migraine with aura than in migraine without aura (P < 0.05). Tumor necrosis factor alpha and soluble tumor necrosis factor receptor 1 levels tended to be increased in the migraine with aura subgroup. The results suggest that proinflammatory cytokines may be involved in the pathogenesis of migraine attacks, although fluctuations in cytokine levels could be different in children than in adults. Such difference could be due to long medical history of migraine in adult patients and frequent intake of analgesic drugs or prophylactic treatment.

C-reactive protein in migraine sufferers similar to that of non-migraineurs: the Reykjavik Study.

C-reactive protein (CRP), a marker of inflammation, has been associated with cardiovascular disease. Risk of cardiovascular disease is increased in migraineurs with aura. Results from a clinical report, case-control and a cohort study suggest that CRP is elevated in migraineurs compared with non-migraineurs. We examined the proposed association in a case-control study nested within two large population-based studies. The relationship between migraine and CRP (high-sensitivity CRP) was studied in 5906 men and women aged 55.0 +/- 8.5 years in the Reykjavik Study and 1345 men and women aged 27.7 +/- 5.5 years from the Reykjavik Study for the Young. A modified version of the International Headache Society's criteria was used to categorize people into migraineurs (two or more symptoms) or non-migraineurs. Migraineurs with visual or sensory symptoms were further defined as having migraine with aura (MA) or without aura (MO). Multivariable-adjusted CRP levels were similar in migraineurs and non-migraineurs for men (0.83 vs. 0.79 mg/l, P = 0.44) and for women (0.87 vs. 0.87 mg/l, P = 0.90). When further stratified by migraine aura and age, no differences were found between non-migraineurs, MO and MA among men. In women, CRP levels were borderline higher in those with MO compared with non-migraineurs and those with MA (1.01 mg/l vs. 0.81 and 0.75 mg/l, P = 0.08 and P = 0.08) in age group 19-34 years, but significantly lower in age group 60-81 years (0.52 mg/l vs. 1.07 and 1.01 mg/l, P = 0.007 and P = 0.03). CRP levels were not increased among migraine sufferers compared with non-migraineurs. Older women migraineurs without aura had lower CRP values than non-migraineurs and migraineurs with aura.

[Effect of ear point combined therapy on plasma substance P in patients of no-aura migraine at different stages].

OBJECTIVE: To evaluate the therapeutic effect of ear point combined therapy on no-aura migraine at different stages and the mechanism. METHODS: Thirty cases of no-aura migraine at different stages were treated with ear point combined therapy, including blood-letting at the ear back, injection of auto-blood into Fengchi (GB 20), Yanglingquan (GB 34), and pricking at ear points Nie (AT2), Yidan (CO11), Shenmen (TF4), etc. Their clinical therapeutic effects were evaluated at the end of one therapeutic course, and substance P (SP) contents were detected before and after treatment. RESULTS: The clinical effective rate was 86.7%, and the effective rate was 87.5% at the attack stage and 86.4% at the remission stage with no significant difference between the attack stage and the remission stage (P>0.05); after treatment, SP content had significant change as compared with that before treatment (P<0.05, P<0.01), and there was very significant difference in SP content between the attack stage before treatment and the remission stage (P<0.01). CONCLUSION: The ear point combined therapy can relieve pain possibly through decreasing plasma SP content, and the SP con tent possibly is one of main factors inducing migraine attack.

Oxidative stress in migraine with and without aura.

Migraine is the most common neurological disorder, but the molecular basis is still not completely understood. An impairment of mitochondrial oxidative metabolism might play a role in the pathophysiology. The goal of this study was to investigate the differences in oxidative stress status with the measurement of erythrocyte superoxide dismutase (SOD), catalase activity, and malondialdehyde (MDA) levels in the migraine patients with or without aura and attack. There were 56 patients (46 female, 10 male) in the migraine group and 25 matched healthy subjects in the control group. The patients comprised 37 with migraine without aura (MWoA], 19 with migraine with aura (MWA), and 22 with headache attack. The MDA levels of patients in the migraine group were significantly higher than that in the control group. The SOD activity was significantly higher in the MWA as compared to MWoA. There was no significant correlation between these levels and headache attack period. Conclusively, in this preliminary study, we had found increased oxidative stress in the migraine patients especially the patients with MWA. Further knowledge about this issue may contribute the cause and complications of migraine and may be essential for development of treatment approaches.