Serum CGRP, VIP, and PACAP usefulness in migraine: a case-control study in chronic migraine patients in real clinical practice.

Calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypetide-38 (PACAP-38) have relevant roles in migraine pathophysiology. Their serum levels have been proposed as biomarkers for migraine. Our aim was to assess their diagnostic value in real clinical practice in a cohort of chronic migraine (CM), episodic migraine (EM) and healthy controls (HC). We recruited subjects with CM, EM and HC at two medical centers. Blood samples were drawn under fasting conditions in the interictal period, immediately centrifuged and stored at - 80 ºC. Serum levels were determined by ELISA. Neuropeptide levels, the effect of preventatives, correlations with clinical and demographic variables, and their diagnostic value were studied among clinical categories. 296 age- and sex-matched subjects (101 CM, 98 EM and 97 HC) were included. All three neuropeptide serum levels were higher in CM [median and IQ for CGRP = 18.023 pg/ml (14.4-24.7); VIP = 121.732 pg/ml (48.72-186.72) and PACAP = 204.931 pg/ml (101.08-597.64)] vs EM [CGRP = 14.659 pg/ml (10.29-17.45); VIP = 75.603 pg/ml (28.722-107.10); and PACAP = 94.992 pg/ml (65.77-128.48)] and vs HC [CGRP = 13.988 pg/ml (10.095-17.87); VIP = 84.685 pg/ml (35.32-99.79), and PACAP = 103.142 pg/ml (59.42-123.97)]. Using multinomial modeling, only VIP (OR 1.011, 95% CI 1.003-1.018, p = 0.005) and PACAP (OR 1.003, 95% CI 1.001-1.005, p = 0.002) increased the risk for CM, but not for EM. CGRP did not predict CM or EM. This model could correctly classify only 62/101 (61.38%) of CM, 75/98 (76.53%) of EM, and 5/97 (4.12%) of HC [globally 147/296 (49.8%)]. Individually, PACAP performed the best for classifying clinical categories [global accuracy 150/296 (50.67%)]. In CM, neuropeptide levels were higher in those OnaBT-treated than in no-treated patients. Although interictal serum CGRP and VIP were higher in CM than both EM or HC, their utility to discriminate migraine categories was low. Contrary to other studies, PACAP serum levels were also higher in CM than in EM or HC and had more discriminative capability to distinguish CM from EM and HC. Further investigation is needed for determination technique standardization.

Systemic and cerebral endothelial dysfunction in chronic migraine. A case-control study with an active comparator.

BACKGROUND AND OBJECTIVE: Unlike migraine and migraine with aura, little information exists regarding chronic migraine (CM) as a risk factor for cardiovascular disease. In this study we aim to determine whether an association between CM and endothelial dysfunction exists. METHODS: Individuals 18 years and older diagnosed with episodic migraine (EM) and CM according to ICHD criteria were studied. After an overnight fast and abstinence from vasoactive drugs, ultrasound studies were performed and blood samples taken from patients and matched controls according to internationally agreed on protocols. RESULTS: A total of 113 individuals were enrolled (35 CM, 37 EM, 41 controls). CM patients had a lower percentage of flow-mediated vasodilation (FMD; difference of means = 5.03%; p = 1.0E-6) and breath-holding index (BHI; difference of means 0.754; p = 2.0E-6), as well as increased carotid intima media thickness (cIMT; difference of means = 0.128 mm; p = 7.0E-5) than controls. The EM patients and controls comparison found similar, but less pronounced, differences: decreased BHI (p = 0.031), and increased cIMT (p = 0.028). Fibrinogen (r = 0.277; p = 0.006), C-reactive protein (r = 0.288; p = 0.003), and erythrocyte rate sedimentation (r = 0.298; p = 0.002) also correlated with cIMT, and inversely with BHImV and FMD. CONCLUSIONS: Migraine is associated with systemic and cerebral endothelial dysfunction demonstrated by ultrasound studies and biological markers. The degree of these changes was strongly associated with the severity of migraine. Our data indicate that migraine may be a cerebral disorder with systemic endothelial damage.

Analysis of endothelial precursor cells in chronic migraine: a case-control study.

BACKGROUND: Migraine has been considered a vascular risk factor especially in young women. Factors predisposing to endothelial damage in migraine are still being debated. The insufficiency of circulating endothelial precursor circulating cells (EPCs) suggested a link between migraine and cardiovascular risk. This research aimed to study a subtype of EPCs, those expressing e-selectin, to assess endothelial activation and, therefore, endothelial dysfunction in migraine. METHODS: Consecutive headache patients (n = 99) and 35 adjusted controls were recruited. Total EPCs, defined as CD34+/KDR+ cells, and EPC colony-forming units (CFUs) were assayed. We identified as "early" EPCs those CD62E- EPCs, and "late" EPCs, CD62E+, a surrogate marker for endothelial damage. Plasmatic calcitonin-gene related protein (CGRP) and vascular-endothelial growth factor (VEGF) were analyzed. RESULTS: We did not find differences in the total number of CFUs among clinical groups. Means of total CD34+/KDR+ and "early" EPCs were not significant among clinical groups. Nevertheless, the mean of "late" EPCs was lower (log(10)-transformed mean = 1.715; SD = 0.393) in the control group than in the migraine patients (log(10)-transformed mean = 2.167; SD = 0.685), even after adjustment by VEGF plasma level and other confounding factors. Linear regression analyses disclosed significant predictors for "late" EPCs for controls vs migraine (ß = 0.452 SE ± 0.13; p = 0.001). We did not observe differences between migraine with or without aura. CONCLUSION: We observed higher number of activated EPCs in migraine patients than in controls. CD62E+ EPCs might be considered a marker for vascular damage in migraine patients.