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Brain Sciences
Special Issues
Recent Advances and New Insights in Cluster Headache
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Recent Advances and New Insights in Cluster Headache

A special issue of Brain Sciences (ISSN 2076-3425).

Deadline for manuscript submissions: closed (15 December 2019) | Viewed by 22849

Special Issue Editor

Dr. Andrea Carmine Belin

E-Mail Website
Guest Editor
Department of Neuroscience, Karolinska Institutet, Biomedicum D7, Stockholm, Sweden
Interests: genetics; headache; neuroscience; pain; circadian rhythm; neurology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cluster headache is a primary headache which strikes as a unilateral pain of extreme intensity. In the majority of cases, the headache attacks appear in a circadian pattern. This potentially life-threatening disorder (referred to as suicide headache due to reported suicide attempts by untreated sufferers) affects 0.1% of the population worldwide. Cluster headache is reported to be more common in men than women (68% vs 32%), but there is insufficient knowledge of the disease differences between the sexes. The cause of cluster headache is currently unknown, and there is no cure. It is known that 7–20% of cluster headache patients report a familial aggregation of the disorder, and genetic factors have been proposed as having a causative role. In addition, cluster headache and migraine share certain phenotype properties and are, to some extent, successfully treated with the same drugs. Critical steps in cluster headache pathophysiology have been suggested to be the activation of the trigeminovascular system, involving a dilation of blood vessels, and inflammation behind the eye. This has been reported to occur as a result of the release of vasodilatory molecules, including calcitonin gene-related peptide (CGRP), around the blood vessels. CGRP and its receptor complex have recently become a therapeutic target mainly for migraine, but also for cluster headache. Multiple treatments based on CGRP and CGRP receptor antibodies, as well as antagonists, are on their way, constituting a new frontier of cluster headache and migraine medication

This Special Issue of Brain Sciences will focus on the progress that has been made towards understanding the disease mechanisms of cluster headache. Submissions addressing the role of genetics, circadian rhythm, gender, life style, and pain in relation to cluster headache are encouraged.

Dr. Andrea Carmine Belin
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

  • Genetics
  • Pain
  • Treatment
  • CGRP
  • Circadian rhythm
  • Biomarker
  • Gender

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Published Papers (3 papers)

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Research

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15 pages, 2399 KiB  
Article
Development and Evaluation of a Screening Tool to Aid the Diagnosis of Cluster Headache
by Alina Buture, Jason W Boland, Lisa Dikomitis, Chao Huang and Fayyaz Ahmed
Brain Sci. 2020, 10(2), 77; https://doi.org/10.3390/brainsci10020077 - 1 Feb 2020
Cited by 2 | Viewed by 3381
Abstract
Cluster headache (CH), a severe primary headache, is often misdiagnosed and mismanaged. The aim of this study was to develop and evaluate a screening tool to aid the diagnosis of CH. We developed a novel 12-item screening tool. This was comprised of four [...] Read more.
Cluster headache (CH), a severe primary headache, is often misdiagnosed and mismanaged. The aim of this study was to develop and evaluate a screening tool to aid the diagnosis of CH. We developed a novel 12-item screening tool. This was comprised of four components: (1) images depicting headache pain; (2) pain descriptors; (3) key questions that could differentiate between CH and migraine; and (4) a visual analogue pain scale. The total possible questionnaire score ranged from 3-32. Patients with CH and migraines (control group) were recruited prospectively from a headache centre in the North of England, UK. Two-hundred and ninety-six patients were included in the study: 81 CH patients, 36 of which suffer with episodic CH and 45 with chronic CH; 215 migraine patients, 92 of which suffer with episodic migraine and 123 with chronic migraine. The mean questionnaire score was higher in CH patients versus migraine patients (28.4 versus 19.5). At a cut-off score of >25 out of 32, the screening tool had a sensitivity of 86.4% and a specificity of 92.0% in differentiating between CH and migraine. The screening tool could be a useful instrument to aid the diagnosis of a CH. The images depicting headache pain do not clearly discriminate between CH and migraine. Full article
(This article belongs to the Special Issue Recent Advances and New Insights in Cluster Headache)
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13 pages, 788 KiB  
Article
Anoctamin 3: A Possible Link between Cluster Headache and Ca2+ Signaling
by Caroline Ran, Carmen Fourier, Donia Arafa, Franziska Liesecke, Christina Sjöstrand, Elisabet Waldenlind, Anna Steinberg and Andrea Carmine Belin
Brain Sci. 2019, 9(8), 184; https://doi.org/10.3390/brainsci9080184 - 30 Jul 2019
Cited by 9 | Viewed by 6214
Abstract
Cluster headache is a severe primary headache characterized by extremely painful attacks of unilateral headache. Verapamil is commonly used as a prophylactic treatment with good effect. In order to search for new pathways involved in the pathophysiology of cluster headache, we analyzed genetic [...] Read more.
Cluster headache is a severe primary headache characterized by extremely painful attacks of unilateral headache. Verapamil is commonly used as a prophylactic treatment with good effect. In order to search for new pathways involved in the pathophysiology of cluster headache, we analyzed genetic variants that were previously linked to verapamil response in migraine in a Swedish cluster headache case-control sample. We used TaqMan qPCR for genetic screening and performed a gene expression analysis on associated genes in patient-derived fibroblasts, and further investigated which reference genes were suitable for analysis in fibroblasts from cluster headache patients. We discovered a significant association between anoctamin 3, a gene encoding a calcium-activated ion channel, and cluster headache. The association was not dependent on verapamil treatment since the associated variant, rs1531394, was also overrepresented in patients not using verapamil. No difference was found in the anoctamin 3 gene expression between controls and patients. Also, we determined that TBP, IPO8 and PDHB were suitable reference genes in cluster headache fibroblasts. This finding is the first report of an association between a variant in a gene encoding an ion-channel and cluster headache, and the first significant genetic evidence of calcium involvement in cluster headache pathophysiology. Full article
(This article belongs to the Special Issue Recent Advances and New Insights in Cluster Headache)
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Review

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16 pages, 1918 KiB  
Review
Calcitonin Gene-Related Peptide (CGRP) and Cluster Headache
by Andrea Carmine Belin, Caroline Ran and Lars Edvinsson
Brain Sci. 2020, 10(1), 30; https://doi.org/10.3390/brainsci10010030 - 6 Jan 2020
Cited by 42 | Viewed by 12248
Abstract
Cluster headache (CH) is a severe primary headache with a prevalence of 1/1000 individuals, and a predominance in men. Calcitonin gene-related peptide (CGRP) is a potent vasodilator, originating in trigeminal neurons and has a central role in CH pathophysiology. CGRP and the CGRP [...] Read more.
Cluster headache (CH) is a severe primary headache with a prevalence of 1/1000 individuals, and a predominance in men. Calcitonin gene-related peptide (CGRP) is a potent vasodilator, originating in trigeminal neurons and has a central role in CH pathophysiology. CGRP and the CGRP receptor complex have recently taken center stage as therapeutic targets for primary headaches, such as migraine. Multiple CGRP and CGRP receptor monoclonal antibodies, as well as small molecule antagonists (gepants) are on their way constituting a new frontier of migraine and possibly CH medication. During a CH attack, there is an activation of the trigeminal-autonomic reflex with the release of CGRP, and inversely if CGRP is administered to a CH patient in an active disease phase, it triggers an attack. Increased levels of CGRP have been found in ipsilateral jugular vein blood during the active phase of CH. This process is hypothesized to have a key role in the intense pain perception and in the associated distinctive vasodilation. So far, clinical tests of CGRP antibodies have been inconclusive in CH patients. This review summarizes the current state of knowledge on the role of CGRP in CH pathology, and as a target for future treatments. Full article
(This article belongs to the Special Issue Recent Advances and New Insights in Cluster Headache)
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