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Background: The relationship between chronic Helicobacter pylori (HP) infection and headache has been discussed for long; nevertheless, the results of the studies are still contrasting., Objective: This cross-sectional study is aimed to investigate a possible association between HP and headache, mainly migraine., Methods: We screened, by a self-administered questionnaire, the subjects undergoing a breath test or an esophagogastroduodenoscopy. Migraine was diagnosed according to the international criteria., Results: A total of 3914 patients underwent a breath test and 2200 an esophagogastroduodenoscopy at two hospitals, in Piedmont (Italy), in a 5-year period; a total of 1362 questionnaires were included in the study. The mean age of the subjects was 53 years; there were 777 women (57%). HP was detected in 364 (27%) subjects. A total of 702 (51%) subjects suffered from headache: migraine with aura was diagnosed in 176 subjects (176/702, i.e., 25% of the headache group; 176/1362, i.e., 13% of the total population); migraine without aura in 98 subjects (98/702, i.e., 14% of the headache group; 98/1362, i.e., 7% of the total). The logistic regression model did not detect any significant association between HP infection and headache, while a significant association between HP and headache frequency (p =0.009) was found, independently of age, gender, comorbidity, and diagnostic category., Conclusion: Our study does not reveal an association between chronic HP infection and migraine. However, since HP is significantly associated with higher headache frequency, a role for HP as a risk factor for headache chronification, possibly underlain by inflammatory mechanisms, may be supposed., (© 2022. Fondazione Società Italiana di Neurologia.)

Background: The association between thrombophilic alterations, migraine, and vascular events has been broadly investigated but not been completely clarified., Methods: In this cross-sectional, case-control study, we included consecutive outpatients diagnosed with migraine referring to a tertiary headache center. Migraine patients were matched to headache-free control subjects. All participants were evaluated for free protein S anticoagulant, functional protein C anticoagulant, homocysteine, and antiphospholipid antibodies (aPLs). History of ischemic stroke (IS) or transient ischemic attack (TIA), coronary heart disease, and peripheral venous thrombosis was also ascertained., Results: We included 329 migraine patients and 329 control subjects (mean age 41 years, 77% women in both groups). Among migraine patients, 239 (72.6%) had migraine without aura and 90 (27.4%) had migraine with aura. Migraine patients had more frequently arterial hypertension, hypercholesterolemia, history of IS or TIA and, peripheral venous thrombosis compared to control subjects, whereas we found no differences in diabetes mellitus, BMI, and coronary heart disease between the two groups. At least one thrombophilic alteration was detected in 107 (32.5%) migraine patients and in 74 (22.5%) control subjects (OR = 1.66, 95% CI 1.17-2.35, p = 0.004). We identified an association of migraine with aPL positivity (OR = 2.6, 95% CI 1.5-4.7, p = 0.001) and with free protein S deficiency (OR = 4.7, 95% CI 1.6-14.0, p = 0.002), whereas we found no differences in protein C deficiency, APCR, and hyperhomocysteinemia between the two groups. Furthermore, aPL positivity and free protein S deficiency were more common in migraine patients with and without aura than in control subjects. We found that in migraine patients, aPL positivity was associated with both IS or TIA (OR = 5.6, 95% CI 1.5-20.4, p = 0.009) and with coronary heart disease (OR = 27.6, 95% CI 1.4-531.1, p = 0.028), whereas free protein S deficiency was associated with IS or TIA only (OR = 14.3, 95% CI 2.8-74.4, p = 0.002)., Conclusions: Our research documented a significative higher prevalence of aPL positivity and protein S deficiency in migraineurs than in controls. Data also showed an association between these alterations and some vascular thrombotic events in migraine patients. We can argue that thrombophilic disorders associated with migraine may contribute to the occurrence of vascular events., (© 2021. Fondazione Società Italiana di Neurologia.)

Background: Migraine is a diffuse and disabling disease. Its pathophysiology is complex and involves both central and peripheral dysfunctions., Objective: This review will discuss the pathogenesis of migraine from the origin of the neuro-inflammatory theory, to the modern pathophysiological model and the latest therapies., Methods: PUBMED and EMBASE (up to May 2019) were searched for: migraine, inflammation, immunomodulation. An additional search was carried out from the bibliography of previous review articles., Results: Migraine was thought to be mainly a vascular disorder, according to the so-called "vascular theory". Based on animal models, a new hypothesis called "the neuro-inflammatory" was conceived at the end of the 20th century. The growing knowledge about the trigeminovascular system and its role in the inflammatory-pain pathway, allowed to identify other specific neurotransmitters, such as the Calcitonin Gene-Related Peptide and Pituitary Adenylate Cyclase-Activating Peptide. Evidence was provided that the inflammatory-pain system could become sensitised and, due to this sensitisation, the pain could also perpetuate, even in the absence of any triggers of the migraine attack. At last, brain immune cells modification during cortical spreading depression in migraine was demonstrated, along with the existence and function of the glymphatic system. The better comprehension of the immune system abnormalities allowed the development of new immunomodulating drugs: the monoclonal antibodies against the CGRP or the CGRP receptor. Moreover, new insights into the molecular mechanism of CGRP, and the function of C-fibres and Aδ-fibres, highlighted the mechanism of action of Botulinum Toxin type A in the treatment of chronic migraine., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Objective: Migraine and systemic autoimmune diseases are 2-3-fold more common in women and various studies have reported an association between the two pathologies., Methods: This review takes into account epidemiological studies involving migraine and systemic lupus erythematosus, antiphospholipid syndrome, Sjogren's syndrome, and other diffuse connective tissue diseases. This scientific literature analysis consists of the main articles found in Medline with a search up to April 2017., Results: Many epidemiological studies were carried out on patients suffering from systemic lupus erythematosus. Results showed that headache and migraine are more prevalent in systemic lupus erythematosus patients compared to controls, especially migraine with aura. Patients with Lupus and migraine show a higher lupus activity and association with Raynaud and/or antiphospholipids in these populations are contradictory. There are not enough data to establish an association between antiphospholipid syndrome and migraine. However, data are more consistent between antiphospholipid carrier condition and migraine. Systemic sclerosis is a rare disease, for this reason the amount of available data on this disorder are scanty. However, some studies reported an association between headache, migraine and systemic sclerosis, especially where gliotic brain lesions and Raynaud are coexisting. Finally, large propensity cohort population based studies suggested that systemic autoimmune diseases are more frequent in patients suffering from migraine., Conclusion: An attempt at explaining the possible link between these disorders and migraine is discussed at the end of the review. Several autoimmune alterations are shared by most autoimmune diseases and headache types. Endothelial dysfunction is the only alteration that is common among all these disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

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., (© 2011 International Society on Thrombosis and Haemostasis.)

Background: Some reports demonstrated vascular alterations in brain magnetic resonance imaging (MRI) in migraineurs and a relationship between circle of Willis (Circle) variants and lacunar brain infarcts. We examined anomalies of the whole circle of Willis and their relationship with vascular brain lesions in migraineurs, to identify any possible vascular mechanism in migraine., Methods: We studied, with a cohort controlled study, the circle of Willis in migraineurs seen consecutively in our Headache Center, and in non-headache controls, using angio-MRI of the brain. Statistical analysis used ANOVA, Scheffè's criterion, t-student test., Results: We recruited 270 migraineurs (204 without aura (MWOA), 66 with aura (MWA) and 159 controls. Migraineurs presented an anatomical variant in 108 (40%) cases with 34 controls (21.4%) presenting a variant. We found a significant association between MWOA and variants (OR=2.4 CI95% [1.5 to 3.9]) and between MWA and variants (OR=3.2 CI95% [1.6 to 4.1]). Unilateral posterior variants with basilar hypoplasia are statistically associated only with MWA compared to controls (OR=9.2, CI95% [2.3 to 37.2]). Thirty-three percent of MWOA and 24% of MWA sufferers present some kind of brain lesion, included 2% of infra-tentorial lesions. We did not find any statistical association between the presence of Circle variants and ischemic lesions on MRI (OR=1.5 CI95% [0.68; 1.94]), or with infratentorial lacunar lesions (OR=1.58 CI95% [0.48 to 5.24])., Conclusions: Anatomical variants of the Circle of Willis are significantly more frequent in migraineurs; posterior anomalies are more frequent in MWA, suggesting a vascular mechanism provoking changes in cerebral blood flow, thereby stimulating cortical spreading depression.

Background: Migraine is a complex biochemical dysfunction attributed to a disorder of the trigeminal and hypothalamic pathways. Impairment of glucose metabolism has been reported in migraine, but data are scanty and inconsistent., Objective: The main aim was to verify whether migraineurs have abnormalities of the glucose and insulin metabolism. We also studied correlations between blood glucose and insulin and between insulin levels and migraine severity., Patients and Methods: Patients with migraine or headache other than migraine, and healthy volunteers were included. All had general blood tests and a standard oral glucose tolerance test after a 12-hour fast, and glucose and insulin were measured., Results: Over a 6-month period, we recruited 84 migraineurs (73 women, 11 men), 25 patients with nonmigraine headache (20 women, 5 men), and 26 healthy controls (24 women, 2 men). Multivariate analysis confirmed a significant difference between groups for glucose levels (P < .0001), but no significant time interaction. The differences were mostly between migraine and healthy controls (P < .0001) and to a lesser extent between other headaches and healthy controls (P < .05). A significant difference between groups was also found for insulin (P < .0001), with a significant time interaction. The difference was confirmed for migraine compared to other headaches (P < .0001) and healthy controls (P < .0001)., Conclusions: Blood glucose levels may be high in headache patients, but do not seem to be specific to migraineurs. Insulin levels were higher in migraineurs, and seemed specific to this group. These findings are in keeping with recent reports on the effects of insulin on brain functions and lend support to the possibility that insulin is involved in the pathogenesis of migraine.

Many factors should be considered when an episodic migraine worsens and becomes chronic. Prolactin (PRL) was linked to the origin of pain in patients with microprolactinomas who developed different types of headaches. Our team carried out studies on 27 patients with a background of episodic headaches that became chronic. The patients were evaluated by means of a general examination, a neurological examination and a hormonal profile. Of the 27 patients, 7 of them had an increased level of prolactinaemia. All the patients were women, ranging from 17 to 57 years of age. Four of them had a pure form of migraine without aura, whereas 3 patients had both migraines without aura and tension-type headaches. They suffered from headache for a period ranging from 3 to 32 years and their headache became chronic 4-12 months prior to the visit. Their headache did not change in type, but only in severity and frequency. Two patients had no symptoms referable to high PRL levels; 4 patients had irregular menses or amenorrhoea. One of these patients also suffered galactorrhoea and two of these patients had a microprolactinoma at MRI; one patient was using estroprogestinic drugs, so her menstrual alteration could not be considered. The patients were followed-up for a period of 6-16 months. Six patients responded favourably after being treated with cabergoline, although some had already tried other drugs, which, however, had no effect on their headache. One patient improved after ceasing to take estroprogestinic, in spite of increased levels of PRL. Therefore, on this basis, PRL levels should always be considered when headache worsens. It is an adjunctive worsening factor, which can be easily eliminated.