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Altered Hypothalamic Region Covariance in Migraine and Cluster Headache: A Structural MRI Study.

The hypothalamus plays a key role in both migraine and cluster headache (CH). As brain region-to-region structural correlations are believed to reflect structural and functional brain connectivity patterns, we assessed the structural covariance patterns between the volume of the hypothalamic region and vertex-by-vertex measurements of cortical thickness in patients with migraine and in those with CH relative to healthy controls (HC).

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Mindfulness in migraine.

: Migraine is the second leading cause of disability worldwide, yet many patients are unable to tolerate, benefit from, or afford pharmacological treatment options. Non-pharmacological migraine therapies exist, especially to reduce opioid use, which represents a significant unmet need. Mindfulness-based interventions (MBI) have potential as a non-pharmacological treatment for migraine, primarily through the development of flexible attentional capacity across sensory, cognitive, and emotional experiences.: The authors review efficacy and potential mechanisms of MBIs for migraine, including mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT).: While most mindfulness research studies for migraine to date have been pilot trials, which are small and/or lacked rigor, initial evidence suggests there may be improvements in overall headache-related disability and psychological well-being. Many research questions remain to help target the treatment to patients most likely to benefit, including the ideal dosage, duration, delivery method, responder characteristics, and potential mechanisms and biomarkers. A realistic understanding of these factors is important for patients, providers, and the media. Mindfulness will not "cure" migraine; however, mindfulness may be an important tool as part of a comprehensive treatment approach to help patients "mindfully" engage in valued life activities.

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Multisensorial perception in chronic migraine and the role of medication overuse.

Multisensory processing can be assessed by measuring susceptibility to crossmodal illusions such as the Sound-Induced Flash Illusion (SIFI). When a single flash is accompanied by two or more beeps, it is perceived as multiple flashes (fission illusion); conversely, a fusion illusion is experienced when more flashes are matched with a single beep, leading to the perception of a single flash. Such illusory perceptions are associated to crossmodal changes in visual cortical excitability. Indeed, increasing occipital cortical excitability, by means of transcranial electrical currents, disrupts the SIFI (i.e. fission illusion). Similarly, a reduced fission illusion was shown in patients with episodic migraine, especially during the attack, in agreement with the pathophysiological model of cortical hyperexcitability of this disease. If episodic migraine patients present with reduced SIFI especially during the attack, we hypothesize that chronic migraine patients should consistently report less illusory effects than healthy controls; drugs intake could also affect SIFI. On such a basis, we studied the proneness to SIFI in chronic migraine (CM) patients (n=63), including 52 patients with Medication Overuse Headache (MOH), compared to 24 healthy controls. All migraine patients showed reduced fission phenomena than controls (p<0.0001). Triptan MOH patients (n=23) presented significantly less fission effects than other chronic migraine groups (p=0.008). This exploratory study suggests that CM – both with and without medication overuse – is associated to a higher visual cortical responsiveness which causes deficit of multisensorial processing, as assessed by the SIFI. Perspective: This observational study shows reduced susceptibility to the sound-induced flash illusion in chronic migraine, confirming and extending previous results in episodic migraine. Medication overuse headache contributes to this phenomenon, especially in case of triptans.

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Short- and Long-Term Effects of Cannabis on Headache and Migraine.

Use of cannabis to alleviate headache and migraine is relatively common, yet research on its effectiveness remains sparse. We sought to determine whether inhalation of cannabis decreases headache and migraine ratings as well as whether gender, type of cannabis (concentrate vs. flower), THC, CBD, or dose contribute to changes in these ratings. Finally, we explored evidence for tolerance to these effects. Archival data were obtained from Strainprint, a medical cannabis app that allows patients to track symptoms before and after using different strains and doses of cannabis. Latent change score models and multilevel models were used to analyze data from 12,293 sessions where cannabis was used to treat headache and 7,441 sessions where cannabis was used to treat migraine. There were significant reductions in headache and migraine ratings after cannabis use. Men reported larger reductions in headache than women and use of concentrates was associated with larger reductions in headache than flower. Further, there was evidence of tolerance to these effects. Perspective: Inhaled cannabis reduces self-reported headache and migraine severity by approximately 50%. However, its effectiveness appears to diminish across time and patients appear to use larger doses across time, suggesting tolerance to these effects may develop with continued use.

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Familial “Diplegic” Migraine – Description of a Family With a Novel CACNA1A Mutation.

To characterize phenotypes of a novel CACNA1A mutation causing familial hemiplegic migraine type 1.

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Potential for treatment benefit of small molecule CGRP receptor antagonist plus monoclonal antibody in migraine therapy.

To provide the first clinical report that 2 calcitonin gene-related peptide (CGRP) therapies, a small molecule CGRP receptor antagonist and an anti-CGRP receptor antibody, can be used concomitantly to treat refractory migraine.

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Intranasal Ketamine for Abortive Migraine Therapy in Pediatric Patients: A Single-Center Review.

Ketamine has recently emerged as a promising therapeutic alternative for abortive migraine therapy, likely secondary to N-methyl-d-aspartate antagonism. Most reports examine adults and the intravenous route. Fewer utilize intranasal administration or pediatric populations. Given the limited evidence for intranasal ketamine in pediatric migraine populations, we retrospectively reviewed our experience to further characterize safety and efficacy of intranasal ketamine in this population.

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Sex hormone-related polymorphisms in endometriosis and migraine: A narrative review.

Some evidence indicates endometriosis and migraine have a common genetic predisposition in sex-hormone genes, which could have important implications for the treatment of these two heterogenous conditions. To date, the genes responsibility remains unknown. Based on the biological hypothesis that polymorphisms of genes involved in sex-hormone pathways may influence estrogen levels and phenotypes of both disorders, we did a literature search for candidate sex-hormone genes and genes involved in the metabolism of estradiol. The aim was to review the evidence for shared sex-hormone-related polymorphisms between endometriosis and migraine and provide an exhaustive overview of the current literature. We included case-control studies investigating associations between candidate sex-hormone-related genes and the disorders endometriosis and migraine, respectively. Results showed three overlapping sex-hormone-associated polymorphisms in estrogen receptor genes that are associated with both conditions. To confirm possible associations with other sex-hormone genes, larger studies are needed.

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Association Between Temporomandibular Disorders Pain and Migraine: Results of the Health 2000 Survey.

To study the possible associations of various clinically assessed painful signs of temporomandibular disorders (TMD) with the presence of migraine using a large population-based dataset.

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Low-dose interleukin-2 reverses behavioral sensitization in multiple mouse models of headache disorders.

Headache disorders are highly prevalent and debilitating, with limited treatment options. Previous studies indicate that many pro-inflammatory immune cells contribute to headache pathophysiology. Given the well-recognized role of regulatory T (Treg) cells in maintaining immune homeostasis, we hypothesized that enhancing Treg function may be effective to treat multiple headache disorders. In a mouse model of chronic migraine, we observed that repeated nitroglycerin (NTG, a reliable trigger of migraine in patients) administration doubled the number of CD3 T cells in the trigeminal ganglia without altering the number of Treg cells, suggesting a deficiency in Treg-mediated immune homeostasis. We treated mice with low-dose interleukin-2 (ld-IL2) to preferentially expand and activate endogenous Treg cells. This not only prevented the development of NTG-induced persistent sensitization, but also completely reversed the established facial skin hyper-sensitivity resulting from repeated NTG administration. The effect of ld-IL2 was independent of mouse sex and/or strain. Importantly, ld-IL2 treatment did not alter basal nociceptive responses, and repeated usage did not induce tolerance. The therapeutic effect of ld-IL2 was abolished by Treg depletion and was recapitulated by Treg adoptive transfer. Furthermore, treating mice with ld-IL2 1-7 days after mild traumatic brain injury effectively prevented as well as reversed the development of behaviors related to acute and chronic post-traumatic headache. In a model of medication overuse headache, Ld-IL2 completely reversed the cutaneous hyper-sensitivity induced by repeated administration of sumatriptan. Collectively, the present study identifies ld-IL2 as a promising prophylactic for multiple headache disorders with a mechanism distinct from the existing treatment options.

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