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Characteristics of N400 component elicited in patients who have migraine with aura.

This study aimed to examine the N400 effect and event-related potentials (ERPs) elicited from congruent and incongruent stimuli in patients who have migraines with aura (MwA).

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Pattern-Induced Visual Discomfort and Anxiety in Migraineurs: Their Relationship and the Effect of Colour.

In migraineurs, coloured lenses were found to reduce the visual stress caused by an aversive pattern known to trigger migraines by 70%, but do such patterns also produce a low-level anxiety/fear response? Is this response lessened by colour? We sought to investigate this in a study comprising a broad screening component followed by a dot-probe experiment to elicit attentional biases (AB) to aversive patterns. Undergraduate psychology students completed headache and visual discomfort (VD) questionnaires ( = 358), thereby forming a subject pool from which 13 migraineurs with high visual discomfort and 13 no-headache controls with low visual discomfort, matched on age and sex, completed a dot-probe experiment. Paired stimuli were presented for 500 ms: aversive achromatic 3 cpd square wave gratings vs control, scrambled patterns. These conditions were repeated using the colour that was most comfortable for each participant. VD was greater in the more severe headache groups. On all measures, the migraineurs were more anxious than the controls, and a positive relationship was found between VD and trait anxiety. The 3 cpd gratings elicited an aversive AB in the migraine group which was somewhat reduced by the use of colour, and this was not seen in the controls. The results suggest a new role for colour in reducing visual stress via anxiety/fear reduction.

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OnabotulinumtoxinA alters inflammatory gene expression and immune cells in chronic headache patients.

Occipital headache, the perception of pain in the back of the head, is commonly described by patients diagnosed with migraine, tension-type headache, and occipital neuralgia. The greater and lesser occipital nerves play central role in the pathophysiology of occipital headache. In the clinical setup, such headaches are often treated with onabotulinumtoxinA, a neurotoxin capable of disrupting ability of nociceptors to get activated and/or release proinflammatory neuropeptides. Attempting to understand better onabotulinumtoxinA mechanism of action in reducing headache frequency, we sought to determine its effects on expression of inflammatory genes in injected occipital tissues. To achieve this goal, we injected 40 units of onabotulinumtoxinA into 4 muscle groups (occipitalis, splenius capitis, semispinalis capitis, and trapezius muscles – all located on one side of the occiput) of patients with chronic bilateral occipital headache scheduled for occipital nerve decompression surgery 1-month latter. At the time of surgery, we collected discarded muscle, fascia and periosteum tissues from respective locations on both sides of the neck and occiput and performed targeted transcriptome analyses to determine expression level of inflammatory genes in onabotulinumtoxinA-injected and onabotulinumA-uninjected tissues. We found that (a) onabotulinumtoxinA alters expression of inflammatory genes largely in periosteum, minimally in muscle and not at all in fascia; (b) expression of inflammatory genes in uninjected periosteum and muscle is significantly higher in historical onabotulinumA responders than historical non-responders; (c) in historical responders' periosteum, onabotulinumA decreases expression of nearly all significantly altered genes, gene sets that define well-recognized inflammatory pathways (e.g., pathways involved in adaptive/innate immune response, lymphocyte activation, and cytokine, chemokine, NF-kB, TNF and interferon signaling), and abundance of 12 different immune cell classes (e.g., neutrophils, macrophages, cytotoxic T-, NK-, Th1-, B- and dendritic-cells), whereas in historical non-responders it increases gene expression but to a level that is nearly identical to the level observed in the uninjected periosteum and muscle of historical responders, and surprisingly, (d) that the anti-inflammatory effects of onabotulinumA are far less apparent in muscles and absent in fascia. These findings suggest that in historical responders' periosteum – but not muscle or fascia – inflammation contributes to the pathophysiology of occipital headache, and that further consideration should be given to the possibility that onabotulinumA mechanism of action in migraine prevention could also be achieved through its ability to reduce pre-existing inflammation, likely through localized interaction that lead to reduction in abundance of immune cells in the calvarial periosteum.

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Real-world impact of fremanezumab on migraine symptoms and resource utilization in the United States.

Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for migraine prevention in adults. Real-world data on the effectiveness of fremanezumab are limited. This retrospective, observational cohort study assessed patient-reported migraine symptoms, health care resource utilization (HCRU), and direct medical costs before and after fremanezumab treatment initiation.

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Assessment of Erenumab Safety and Efficacy in Patients With Migraine With and Without Aura: A Secondary Analysis of Randomized Clinical Trials.

Migraine with aura may respond differently to therapies than migraine without aura. Individuals with migraine with aura have an elevated vascular risk, necessitating a safety assessment of migraine preventive treatments in this patient subgroup.

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Evaluation of sex differences in the pharmacokinetics of oral sumatriptan in healthy Korean subjects using population pharmacokinetic modeling.

Sumatriptan was introduced in 1983, as the first of the triptans, selective 5-hydroxytryptamine (5-HT ) receptor agonists, to treat moderate to severe migraine. Migraine predominates in females. Although there have been reports of sex differences in migraine-associated features and pharmacokinetics (PKs) of some triptans, sex differences in the PKs of oral sumatriptan have never been evaluated in Korean. We conducted this study of oral sumatriptan to assess the sex differences in Korean population. Thirty-eight healthy Korean subjects who participated in two separate clinical studies receiving a single oral dose of 50 mg sumatriptan with the same protocols were included in this analysis. A total of 532 sumatriptan concentration observations were used for a population PK modeling. Validation of final population PK model of sumatriptan was performed using bootstrap and visual predictive check. The PK profile of oral sumatriptan was adequately described by a one-compartmental model with combined transit compartment model and a first-order absorption. The covariate analysis showed that the clearance of oral sumatriptan was significantly higher in males than in females (male: 444 L/h, female: 281 L/h). Our results showed that there were sex differences in the clearance of oral sumatriptan. These results encourage further studies to establish the sumatriptan pharmacokinetic-pharmacodynamic (PK-PD) model considering sex-related PK differences, which may help to determine optimal dosing regimens for effective treatment of migraine in males and females. This article is protected by copyright. All rights reserved.

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The relationship between headache-attributed disability and lost productivity: 2. Empirical evidence from population-based studies in nine disparate countries.

Headache disorders are disabling, with major consequences for productivity, yet the literature is silent on the relationship between headache-attributed disability and lost productivity, often erroneously regarding the two as synonymous. We evaluated the relationship empirically, having earlier found that investment in structured headache services would be cost saving, not merely cost-effective, if reductions in headache-attributed disability led to > 20% pro rata recovery of lost productivity.

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Impact of age and sex on the efficacy of fremanezumab in patients with difficult-to-treat migraine: results of the randomized, placebo-controlled, phase 3b FOCUS study.

Migraine prevalence is age and sex dependent, predominating in women in early and middle adulthood; however, migraine also represents a substantial burden for men and adults of all ages. Thus, understanding this burden and the efficacy of migraine preventive medications in both sexes and across age groups is critical. The randomized, placebo-controlled, double-blind, phase 3b FOCUS study demonstrated the safety and efficacy of fremanezumab, a fully humanized monoclonal antibody (IgG2∆a) that selectively targets calcitonin gene-related peptide as a migraine preventive treatment for individuals with migraine and prior inadequate response to 2 to 4 migraine preventive medication classes. Here, we assessed the efficacy of fremanezumab in participants from FOCUS subgrouped by age (18-45 years and > 45 years) and sex.

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Effects of Different Therapeutic Exercise Modalities on Migraine or Tension-Type Headache: A Systematic Review and Meta-Analysis with a Replicability Analysis.

The primary aim of this study was to review the effect of exercise in comparison with a non-active treatment on pain intensity, frequency of headache episodes, headache duration, quality of life, medication use, and psychological symptoms, in patients with migraine or tension-type headache (TTH). A systematic search was conducted in various electronic databases to identify all relevant studies: Medline (PubMed), PEDro, EBSCO and Google Scholar. Clinical trials assessing the effects of exercise interventions in patients with primary headaches were selected. Methodological quality was evaluated using the Cochrane Risk of Bias Tool and PEDro scale and qualitative analysis was based on classifying the results into levels of evidence according to the GRADE. 19 studies (2776 participants; 85% female) were included. The meta-analysis showed statistically significant differences in pain intensity for aerobic training in patients with migraine (SMD=-0.65; 95% CI=-1.07 to -0.22, very low certainty evidence) and for strength training in patients with TTH (SMD=-0.84; 95% CI=-1.68 to -0.01, very low certainty evidence). Statistically significant differences were also found in the medication use (SMD=-0.51; 95% CI=-0.85 to -0.17, low certainty evidence). Low transparency, replicability and high risk of bias were found. Aerobic training has a small to moderate clinical effect on pain intensity and medication use on migraine patients, with very low to low certainty of evidence. Strength training showed a moderate clinical effect with very low quality of evidence in patients with TTH. Exercise could be considered as clinically relevant for the management of patients with primary headaches, but the presence of low certainty of evidence and low transparency and replicability limited its clinical application. Perspective: This article presents current evidence about exercise interventions in patients with primary headaches, including migraine and tension-type headache. Existing findings are reviewed, and relevant data are provided on the effectiveness of each exercise modality, as well as its certainty of evidence and clinical applicability.

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Relation of hypertension with episodic primary headaches and chronic primary headaches in population of Rafsanjan cohort study.

Headache has a variety of types, such as episodic primary headaches (EPH) and chronic primary headache (CPH) in its primary form. There is a positive correlation between these two types of headaches and hypertension (HTN), but in some works this correlation has been reported negatively. Therefore, we planned to study HTN-CPH as well as HTN-EPH correlation in our population. A sample of Rafsanjan population (10,000 individuals) entered the cohort study, as one of the Prospective Epidemiological Research Studies in Iran (PERSIAN). We compared the frequency of HTN categories in CPH and EPH cases with a normal population. Out of 9933 participants (46.6% males and 53.4% females) about 29% had EPH and 7.5% had CPH. HTN was found in 24.27% of EPH cases and 31.98% of CPH cases. HTN was also found to be associated with EPH and CPH in the crude model. Two Categories of HTN (Long controlled and uncontrolled) were not associated with EPH. On the other hand, CPH showed associations with all of the HTN categories. After included all variables and confounders, EPH and CPH had association with HTN without any considerable changes. There is strong HTN-EPH as well as HTN-CPH correlations in the studied population.

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