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Safety and efficacy of galcanezumab in patients for whom previous migraine preventive medication from two to four categories had failed (CONQUER): a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial.

Many patients who require migraine preventive treatment have not been able to tolerate or have not responded to multiple previous preventive medications. We aimed to assess the safety and efficacy of galcanezumab, an antibody to calcitonin gene-related peptide, in patients with migraine who had not benefited from preventive medications from two to four categories.

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Galcanezumab CONQUERs migraine prevention.

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Moving the Needle: Desiloing the Stakeholders in the Headache Space.

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Impaired functional connectivity of limbic system in migraine without aura.

Aberrant functional connectivity of brain networks has been demonstrated in migraine sufferers. Functional magnetic resonance imaging (fMRI) may illustrate altered connectivity in patients suffering from migraine without aura (MwoA). Here, we applied a seed-based approach based on limbic regions to investigate disrupted functional connectivity between spontaneous migraine attacks. Resting-state fMRI data were obtained from 28 migraine patients without aura and 23 well-matched healthy controls (HC). The functional connectivity of the limbic system was characterized using a seed-based whole-brain correlation method. The resulting functional connectivity measurements were assessed for correlations with other clinical features. Neuropsychological data revealed significantly increased connectivity between the limbic system (bilateral amygdala and right hippocampus) and left middle occipital gyrus (MOG), and a positive correlation was revealed between disease duration and connective intensity of the left amygdala and the ipsilateral MOG. There was decreased functional connectivity between the right amygdala and contralateral orbitofrontal cortex (OFC). In addition, resting-state fMRI showed that, compared to HC, patients without aura had significant functional connectivity consolidation between the bilateral hippocampus and cerebellum, and a negative correlation was detected between scores on the headache impact test (HIT) and connectivity intensity of the right hippocampus and bilateral cerebellum. There was decreased functional connectivity between the left hippocampus and three brain areas, encompassing the bilateral inferior parietal gyri (IPG) and contralateral supplementary motor area (SMA). There were no structural differences between the two groups. Our data suggest that migraine patients have disrupted limbic functional connectivity to pain-related regions of the modulatory and encoding cortices, which are associated with specific clinical characteristics. Disturbances of resting-state functional connectivity may play a key role in neuropathological features, perception and affection of migraine. The current study provides further insights into the complex scenario of migraine mechanisms. .

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Three new drugs for the prevention of migraine.

DTB drug reviews provide an overview of medicines that have been recently launched in the UK. The articles include a summary of the evidence of benefits and harms as well as details of the regulatory authority's assessment report.

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Abnormal neurovascular coupling as a cause of excess cerebral vasodilation in familial migraine.

Acute migraine attack in familial hemiplegic migraine type 2 (FHM2) patients is characterized by sequential hypo- and hyperperfusion. FHM2 is associated with mutations in the Na,K-ATPase α2 isoform. Heterozygous mice bearing one of these mutations (α2+/G301R) were shown to have elevated cerebrovascular tone and, thus, hypoperfusion that might lead to elevated concentrations of local metabolites. We hypothesize that these α2+/G301R mice also have increased cerebrovascular hyperemic responses to these local metabolites leading to hyperperfusion in the affected part of the brain.

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Closing the gender gap in migraine research.

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Pain, Motivation, Migraine, and the Microbiome: New Frontiers for Opioid Systems and Disease.

For decades the broad role of opioids in addiction, neuropsychiatric disorders, and pain states has been somewhat well established. However, in recent years, with the rise of technological advances, not only is the existing dogma being challenged, but we are identifying new disease areas in which opioids play a critical role. This review highlights four new areas of exploration in the opioid field. The most recent addition to the opioid family, the nociceptin receptor system, shows promise as the missing link in understanding the neurocircuitry of motivation. It is well known that activation of the kappa opioid receptor system modulates negative affect and dysphoria, but recent studies now implicate the kappa opioid system in the modulation of negative affect associated with pain. Opioids are critical in pain management; however, the often-forgotten delta opioid receptor system has been identified as a novel therapeutic target for headache disorders and migraine. Lastly, changes to the gut microbiome have been shown to directly contribute to many of the symptoms of chronic opioid use and opioid related behaviors. This review summarizes the findings from each of these areas with an emphasis on identifying new therapeutic targets. SIGNIFICANCE STATEMENT: The focus of this minireview is to highlight new disease areas or new aspects of disease in which opioids have been implicated; this includes pain, motivation, migraine, and the microbiome. In some cases, this has resulted in the pursuit of a novel therapeutic target and resultant clinical trial. We believe this is very timely and will be a refreshing take on reading about opioids and disease.

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Migraine headache: Is it only a neurological disorder? Links between migraine and cardiovascular disorders.

Migraine headache (MH) is a common disorder affecting millions of people in the United States. MH is substantially more prevalent in women compared to men. An association between migraine with or without aura and risk of cardiovascular disease (CVD) has been extensively reported. There are several proposed theories that may explain the pathophysiologic relationship between MH and CVD. This review will summarize the recent literature on this topic and provide an evidence-based perspective regarding the current knowledge and controversies regarding association of MH and CVD.

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Decreased grey matter volume in mTBI patients with post-traumatic headache compared to headache-free mTBI patients and healthy controls: a longitudinal MRI study.

Traumatic brain injury (TBI) occurs in 1.7 million people annually and many patients go on to develop persistent disorders including post-traumatic headache (PTH). PTH is considered chronic if it continues past 3 months. In this study we aimed to identify changes in cerebral grey matter volume (GMV) associated with PTH in mild TBI patients. 50 mTBI patients (31 Non-PTH; 19 PTH) underwent MRI scans: within 10 days post-injury, 1 month, 6 months and 18 months. PTH was assessed at visit 4 by a post-TBI headache questionnaire. Healthy controls (n = 21) were scanned twice 6 months apart. Compared to non-PTH, PTH patients had decreased GMV across two large clusters described as the right anterior-parietal (p = 0.012) and left temporal-opercular (p = 0.027). Compared to healthy controls non-PTH patients had decreased GMV in the left thalamus (p = 0.047); PTH patients had decreased GMV in several extensive clusters: left temporal-opercular (p = 0.003), temporal-parietal (p = 0.041), superior frontal gyrus (p = 0.008) and right middle frontal/superior frontal gyrus (0.004) and anterior-parietal (p = 0.003). Differences between PTH and non-PTH patients were most striking at early time points. These early changes may be associated with an increased risk of PTH. Patients with these changes should be monitored for chronic PTH.

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