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Migraine Disorders: HELP
Articles from Denmark
Based on 284 articles published since 2008
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These are the 284 published articles about Migraine Disorders that originated from Denmark during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · 11 · 12
1 Guideline European headache federation guideline on the use of monoclonal antibodies acting on the calcitonin gene related peptide or its receptor for migraine prevention. 2019

Sacco, Simona / Bendtsen, Lars / Ashina, Messoud / Reuter, Uwe / Terwindt, Gisela / Mitsikostas, Dimos-Dimitrios / Martelletti, Paolo. ·Neuroscience Section, Department of Applied Clinical Sciences and Biotechnology, University of L'Aquila, via Vetoio, 67100, L'Aquila, Italy. simona.sacco@univaq.it. · Department of Neurology, Danish Headache Center, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany. · Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. · 1st Department of Neurology, National and Kapodistrian University of Athens, Athens, Greece. · Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy. ·J Headache Pain · Pubmed #30651064.

ABSTRACT: BACKGROUND AND AIM: Monoclonal antibodies acting on the calcitonin gene-related peptide or on its receptor are new drugs to prevent migraine. Four monoclonal antibodies have been developed: one targeting the calcitonin gene-related peptide receptor (erenumab) and three targeting the calcitonin gene-related peptide (eptinezumab, fremanezumab, and galcanezumab). The aim of this document by the European Headache Federation (EHF) is to provide an evidence-based and expert-based guideline on the use of the monoclonal antibodies acting on the calcitonin gene-related peptide for migraine prevention. METHODS: The guideline was developed following the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. The working group identified relevant questions, performed systematic review and analysis of the literature, assessed the quality of available evidence, and wrote recommendations. Where the GRADE approach was not applicable, expert opinion was provided. RESULTS: We found low to high quality of evidence to recommend eptinezumab, erenumab, fremanezumab, and galcanezumab in patients with episodic migraine and medium to high quality of evidence to recommend erenumab, fremanezumab, and galcanezumab in patients with chronic migraine. For several clinical questions, there was not enough evidence to provide recommendations using the GRADE approach and recommendations relied on experts' opinion. CONCLUSION: Monoclonal antibodies acting on the calcitonin gene-related peptide are new drugs which can be recommended for migraine prevention. Real life data will be useful to improve the use of those drugs in clinical practice.

2 Guideline Guidelines for controlled trials of drugs in migraine: third edition. A guide for investigators. 2012

Tfelt-Hansen, Peer / Pascual, Julio / Ramadan, Nabih / Dahlöf, Carl / D'Amico, Domenico / Diener, Hans-Christopher / Hansen, Jakob Møller / Lanteri-Minet, Michel / Loder, Elisabeth / McCrory, Douglas / Plancade, Sandra / Schwedt, Todd / Anonymous5150719. ·Danish Headache Center, Department of Neurology, University of Copenhagen, Glostrup, Denmark. ptha@glo.regionh.dk ·Cephalalgia · Pubmed #22384463.

ABSTRACT: -- No abstract --

3 Editorial Triptans and ergot alkaloids in the acute treatment of migraine: similarities and differences. 2013

Tfelt-Hansen, Peer C. ·Department of Neurology, Danish Headache Center, University of Copenhagen, Glostrup Hospital, Glostrup, Denmark +45 3863 3050 +45 3863 2639 ptha@regionh.dk. ·Expert Rev Neurother · Pubmed #23980649.

ABSTRACT: -- No abstract --

4 Editorial Early responses in randomized clinical trials of triptans in acute migraine treatment. Are they clinically relevant? A comment. 2010

Tfelt-Hansen, Peer. ·Danish Headache Centre, Department of Neurology, University of Copenhagen, Glostrup Hospital, DK-2600 Glostrup, Denmark. ·Headache · Pubmed #19178578.

ABSTRACT: One can question the clinical relevance of early headache responses after oral and intranasal triptans. Thus, for pain-free the early responses were significant but in absolute values they were only a few percentages: the therapeutic gains (TGs) were 1.8% (95% CI = 0.3-3%) for oral almotriptan 12.5 after 30 minutes and 1.0% (95% CI = 0-2%) after intranasal zolmitriptan 5 mg after 15 minutes. These results are compared with subcutaneous sumatriptan 6 mg which has TGs of 11% (95% CI = 7-15%) to 14% (95% CI = 11-17%) for pain-free after 30 minutes. Subcutaneous sumatriptan has a 2 times higher response rate than intranasal zolmitriptan and is 5 times more effective than oral almotriptan at these early time points. It is concluded that if a very early and clinically relevant effect is desired then the migraine patient should use the subcutaneous administration form of sumatriptan.

5 Editorial Is there an inherent limit to the efficacy of calcitonin gene-related peptide receptor antagonists in the acute treatment of migraine? A comment. 2009

Tfelt-Hansen, Peer C. ·Danish Headache Centre, Glostrup Hospital, Glostrup, Denmark. ptha@glo.regionh.dk ·J Headache Pain · Pubmed #19779958.

ABSTRACT: Calcitonin gene-related peptide (CGRP) receptor antagonists are a new treatment principle in acute migraine attacks. Intravenous olcegepant 2.5 mg resulted in 66% headache relief after 2 h, whereas subcutaneous sumatriptan resulted in 81-92% headache relief after 2 h. The intrinsic activity of a parenteral triptan, a 5HT(1B/1D) receptor agonist, is thus higher than the maximum effect of the parenteral CGRP receptor antagonist olcegepant. For the orally bioavailable CGRP antagonist telcagepant 300 mg, the headache relief was only 55% in one phase III study. These results indicate that CGRP receptor antagonism results in success in the acute treatment of migraine in only a certain fraction of the patients.

6 Review Neurostimulation for the treatment of chronic migraine and cluster headache. 2019

Vukovic Cvetkovic, Vlasta / Jensen, Rigmor H. ·Danish Headache Center, Rigshospital-Glostrup, Glostrup, Denmark. ·Acta Neurol Scand · Pubmed #30291633.

ABSTRACT: Small subsets of patients who fail to respond to pharmacological treatment may benefit from alternative treatment methods. In the last decade, neurostimulation is being explored as a potential treatment option for the patients with chronic, severely disabling refractory primary headaches. To alleviate pain, specific nerves and brain areas have been stimulated, and various methods have been explored: deep brain stimulation, occipital nerve stimulation, and sphenopalatine ganglion stimulation are among the more invasive ones, whereas transcranial magnetic stimulation and supraorbital nerve stimulation are noninvasive. Vagal nerve stimulation can be invasive or noninvasive, though this review included only data for noninvasive VNS. Most of these methods have been tested in small open-label patient series; recently, more data from randomized, controlled, and blinded studies are available. Although neurostimulation treatments have demonstrated good efficacy in many studies, it still has not been established as a standard treatment in refractory patients. This review analyzes the available evidence regarding efficacy and safety of different neurostimulation modalities for the treatment of chronic migraine and cluster headache.

7 Review Male and female sex hormones in primary headaches. 2018

Delaruelle, Zoë / Ivanova, Tatiana A / Khan, Sabrina / Negro, Andrea / Ornello, Raffaele / Raffaelli, Bianca / Terrin, Alberto / Mitsikostas, Dimos D / Reuter, Uwe / Anonymous5121010. ·Department of Neurology, University Hospital Ghent, Corneel Heymanslaan 10, 9000, Ghent, Belgium. zoe.delaruelle@uzgent.be. · First Moscow State Medical University, Moscow, Russia. · Danish Headache Center, Glostrup Hospital, Copenhagen, Denmark. · Dipartimento di Medicina Clinica e Molecolare, Universita degli Studi di Roma La Sapienza, Rome, Italy. · Department of Neurology, University of La'Aquila, L'Aquila, Italy. · Departmentt of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany. · Department of Neurosciences, Headache Center, University of Padua, Padua, Italy. · Neurology Department, Aeginition Hospital, National and Kapodistrian University of Athens, Athens, Greece. · Charite Universitatsmedizin Berlin, Berlin, Germany. ·J Headache Pain · Pubmed #30497379.

ABSTRACT: BACKGROUND: The three primary headaches, tension-type headache, migraine and cluster headache, occur in both genders, but all seem to have a sex-specific prevalence. These gender differences suggest that both male and female sex hormones could have an influence on the course of primary headaches. This review aims to summarise the most relevant and recent literature on this topic. METHODS: Two independent reviewers searched PUBMED in a systematic manner. Search strings were composed using the terms LH, FSH, progesteron*, estrogen*, DHEA*, prolactin, testosterone, androgen*, headach*, migrain*, "tension type" or cluster. A timeframe was set limiting the search to articles published in the last 20 years, after January 1st 1997. RESULTS: Migraine tends to follow a classic temporal pattern throughout a woman's life corresponding to the fluctuation of estrogen in the different reproductive stages. The estrogen withdrawal hypothesis forms the basis for most of the assumptions made on this behalf. The role of other hormones as well as the importance of sex hormones in other primary headaches is far less studied. CONCLUSION: The available literature mainly covers the role of sex hormones in migraine in women. Detailed studies especially in the elderly of both sexes and in cluster headache and tension-type headache are warranted to fully elucidate the role of these hormones in all primary headaches.

8 Review Migraine and cluster headache - the common link. 2018

Vollesen, Anne Luise / Benemei, Silvia / Cortese, Francesca / Labastida-Ramírez, Alejandro / Marchese, Francesca / Pellesi, Lanfranco / Romoli, Michele / Ashina, Messoud / Lampl, Christian / Anonymous5040974. ·Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · Health Sciences Department, University of Florence and Headache Centre, Careggi University Hospital, Florence, Italy. · Department of Medico-Surgical Sciences and Biotechnologies, Sapienza, University of Rome, Polo Pontino, Latina, Italy. · Dep Internal Medicine, Division of Vascular Pharmacology, Erasmus Medical Center, Rotterdam, The Netherlands. · Child Neuropsichiatry Unit, University of Palermo, Palermo, Italy. · Medical Toxicology, Headache and Drug Abuse Center, University of Modena and Reggio Emilia, Modena, Italy. · Neurology Clinic, University of Perugia - S.M. Misericordiae Hospital, Perugia, Italy. · Department of Neurogeriatric Medicine, Headache Medical Center Linz, Ordensklinikum Linz Barmherzige Schwestern, Seilerstaette 4, 4010, Linz, Austria. christian.lampl@ordensklinikum.at. ·J Headache Pain · Pubmed #30242519.

ABSTRACT: Although clinically distinguishable, migraine and cluster headache share prominent features such as unilateral pain, common pharmacological triggers such glyceryl trinitrate, histamine, calcitonin gene-related peptide (CGRP) and response to triptans and neuromodulation. Recent data also suggest efficacy of anti CGRP monoclonal antibodies in both migraine and cluster headache. While exact mechanisms behind both disorders remain to be fully understood, the trigeminovascular system represents one possible common pathophysiological pathway and network of both disorders. Here, we review past and current literature shedding light on similarities and differences in phenotype, heritability, pathophysiology, imaging findings and treatment options of migraine and cluster headache. A continued focus on their shared pathophysiological pathways may be important in paving future treatment avenues that could benefit both migraine and cluster headache patients.

9 Review Myofascial trigger points in migraine and tension-type headache. 2018

Do, Thien Phu / Heldarskard, Gerda Ferja / Kolding, Lærke Tørring / Hvedstrup, Jeppe / Schytz, Henrik Winther. ·Headache Diagnostic Laboratory, Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark. · Headache Diagnostic Laboratory, Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark. henrik.winther.schytz.01@regionh.dk. ·J Headache Pain · Pubmed #30203398.

ABSTRACT: BACKGROUND: A myofascial trigger point is defined as a hyperirritable spot in skeletal muscle that is associated with a hypersensitive palpable nodule in a taut band. It has been suggested that myofascial trigger points take part in chronic pain conditions including primary headache disorders. The aim of this narrative review is to present an overview of the current imaging modalities used for the detection of myofascial trigger points and to review studies of myofascial trigger points in migraine and tension-type headache. FINDINGS: Different modalities have been used to assess myofascial trigger points including ultrasound, microdialysis, electromyography, infrared thermography, and magnetic resonance imaging. Ultrasound is the most promising of these modalities and may be used to identify MTrPs if specific methods are used, but there is no precise description of a gold standard using these techniques, and they have yet to be evaluated in headache patients. Active myofascial trigger points are prevalent in migraine patients. Manual palpation can trigger migraine attacks. All intervention studies aiming at trigger points are positive, but this needs to be further verified in placebo-controlled environments. These findings may imply a causal bottom-up association, but studies of migraine patients with comorbid fibromyalgia syndrome suggest otherwise. Whether myofascial trigger points contribute to an increased migraine burden in terms of frequency and intensity is unclear. Active myofascial trigger points are prevalent in tension-type headache coherent with the hypothesis that peripheral mechanisms are involved in the pathophysiology of this headache disorder. Active myofascial trigger points in pericranial muscles in tension-type headache patients are correlated with generalized lower pain pressure thresholds indicating they may contribute to a central sensitization. However, the number of active myofascial trigger points is higher in adults compared with adolescents regardless of no significant association with headache parameters. This suggests myofascial trigger points are accumulated over time as a consequence of TTH rather than contributing to the pathophysiology. CONCLUSIONS: Myofascial trigger points are prevalent in both migraine and tension-type headache, but the role they play in the pathophysiology of each disorder and to which degree is unclarified. In the future, ultrasound elastography may be an acceptable diagnostic test.

10 Review The association between migraine and physical exercise. 2018

Amin, Faisal Mohammad / Aristeidou, Stavroula / Baraldi, Carlo / Czapinska-Ciepiela, Ewa K / Ariadni, Daponte D / Di Lenola, Davide / Fenech, Cherilyn / Kampouris, Konstantinos / Karagiorgis, Giorgos / Braschinsky, Mark / Linde, Mattias / Anonymous1051094. ·Department of Neurology, Danish Headache Center, Rigshospitalet Glostrup, University of Copenhagen, Valdemar Hansens Vej 5, 2600, Glostrup, Denmark. faisal@dadlnet.dk. · 1st Neurology of Department, Eginition Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. · Department of Diagnostic, Medical Toxicology, Headache and Drug Abuse Research Center, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy. · Epilepsy and Migraine Treatment Centre, Kraków, Poland. · Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino, Latina, Italy. · Headache Centre, Guys and St Thomas NHS Trust, London, UK. · Neurology Clinic's Headache Clinic, Tartu University Clinics, Tartu, Estonia. · Department of Neuromedicine and Movement Science, NTNU Norwegian University of Science and Technology, Trondheim, Norway. · Norwegian Advisory Unit on Headache, St Olavs University Hospital, Trondheim, Norway. ·J Headache Pain · Pubmed #30203180.

ABSTRACT: BACKGROUND: There is an unmet need of pharmacological and non-pharmacological treatment options for migraine patients. Exercise can be used in the treatment of several pain conditions, including. However, what exact role exercise plays in migraine prevention is unclear. Here, we review the associations between physical exercise and migraine from an epidemiological, therapeutical and pathophysiological perspective. METHODS: The review was based on a primary literature search on the PubMed using the search terms "migraine and exercise". RESULTS: Low levels of physical exercise and high frequency of migraine has been reported in several large population-based studies. In experimental studies exercise has been reported as a trigger factor for migraine as well as migraine prophylaxis. Possible mechanisms for how exercise may trigger migraine attacks, include acute release of neuropeptides such as calcitonin gene-related peptide or alternation of hypocretin or lactate metabolism. Mechanisms for migraine prevention by exercise may include increased beta-endorphin, endocannabinoid and brain-derived neurotrophic factor levers in plasma after exercise. CONCLUSION: In conclusion, it seems that although exercise can trigger migraine attacks, regular exercise may have prophylactic effect on migraine frequency. This is most likely due to an altered migraine triggering threshold in persons who exercise regularly. However, the frequency and intensity of exercise that is required is still an open question, which should be addressed in future studies to delineate an evidence-based exercise program to prevent migraine in sufferers.

11 Review Effect of exogenous estrogens and progestogens on the course of migraine during reproductive age: a consensus statement by the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESCRH). 2018

Sacco, Simona / Merki-Feld, Gabriele S / Ægidius, Karen Lehrmann / Bitzer, Johannes / Canonico, Marianne / Gantenbein, Andreas R / Kurth, Tobias / Lampl, Christian / Lidegaard, Øjvind / Anne MacGregor, E / MaassenVanDenBrink, Antoinette / Mitsikostas, Dimos-Dimitrios / Nappi, Rossella Elena / Ntaios, George / Paemeleire, Koen / Sandset, Per Morten / Terwindt, Gisela Marie / Vetvik, Kjersti Grøtta / Martelletti, Paolo / Anonymous32610960. ·Department of Applied Clinical Sciences and Biotechnology, University of L'Aquila, L'Aquila, Italy. simona.sacco@univaq.it. · Clinic for Reproductive Endocrinology, Department of Gynecology, University Hospital, Zürich, Switzerland. · Department of Neurology, Bispebjerg Hospital and University of Copenhagen, Copenhagen, Denmark. · Department of Obstetrics and Gynecology, University Hospital of Basel, Basel, Switzerland. · Université Paris-Saclay, University Paris-Sud, UVSQ, CESP, Inserm UMRS1018, Paris, France. · Neurology & Neurorehabilitation, RehaClinic, Bad Zurzach, University of Zurich, Zürich, Switzerland. · Institute of Public Health, Charité - Universitätsmedizin Berlin, Berlin, Germany. · Headache Medical Center Seilerstaette Linz, Linz, Austria. · Department of Geriatric Medicine Ordensklinikum Linz, Linz, Austria. · Department of Obstetrics & Gynaecology, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. · Centre for Neuroscience & Trauma, BICMS, Barts and the London School of Medicine and Dentistry, London, UK. · Barts Health NHS Trust, London, UK. · Erasmus Medical Center Rotterdam, Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Rotterdam, The Netherlands. · Department of Neurology, University of Athens, Athens, Greece. · Research Centre for Reproductive Medicine, Gynecological Endocrinology and Menopause, IRCCS S. Matteo Foundation, Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy. · University Consortium for Adaptive Disorders and Head Pain (UCADH), University of Pavia, Pavia, Italy. · Department of Medicine, University of Thessaly, Larissa, Greece. · Department of Neurology, Ghent University Hospital, Ghent, Belgium. · University Hospital Rikshospitalet, University of Oslo, Oslo, Norway. · Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands. · Department of Neurology, Akershus University Hospital, Lørenskog, Norway. · Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy. ·J Headache Pain · Pubmed #30171365.

ABSTRACT: We systematically reviewed data about the effect of exogenous estrogens and progestogens on the course of migraine during reproductive age. Thereafter a consensus procedure among international experts was undertaken to develop statements to support clinical decision making, in terms of possible effects on migraine course of exogenous estrogens and progestogens and on possible treatment of headache associated with the use or with the withdrawal of hormones. Overall, quality of current evidence is low. Recommendations are provided for all the compounds with available evidence including the conventional 21/7 combined hormonal contraception, the desogestrel only oral pill, combined oral contraceptives with shortened pill-free interval, combined oral contraceptives with estradiol supplementation during the pill-free interval, extended regimen of combined hormonal contraceptive with pill or patch, combined hormonal contraceptive vaginal ring, transdermal estradiol supplementation with gel, transdermal estradiol supplementation with patch, subcutaneous estrogen implant with cyclical oral progestogen. As the quality of available data is poor, further research is needed on this topic to improve the knowledge about the use of estrogens and progestogens in women with migraine. There is a need for better management of headaches related to the use of hormones or their withdrawal.

12 Review PACAP38 and PAC 2018

Rubio-Beltrán, Eloisa / Correnti, Edvige / Deen, Marie / Kamm, Katharina / Kelderman, Tim / Papetti, Laura / Vigneri, Simone / MaassenVanDenBrink, Antoinette / Edvinsson, Lars / Anonymous6340957. ·Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. a.rubiobeltran@erasmusmc.nl. · Department of Child Neuropsychiatry, University of Palermo, Palermo, Italy. · Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Glostrup, Denmark. · Department of Neurology, University Hospital, LMU Munich, Munich, Germany. · Department of Neurology, Ghent University Hospital, Ghent, Belgium. · Headache Center, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. · Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo; Pain Medicine Unit, Santa Maria Maddalena Hospital, Occhiobello, Italy. · Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. · Department of Internal Medicine, Institute of Clinical Sciences, Lund University, Lund, Sweden. ·J Headache Pain · Pubmed #30088106.

ABSTRACT: Pituitary adenylate cyclase activating polypeptide-38 (PACAP38) is a widely distributed neuropeptide involved in neuroprotection, neurodevelopment, nociception and inflammation. Moreover, PACAP38 is a potent inducer of migraine-like attacks, but the mechanism behind this has not been fully elucidated.Migraine is a neurovascular disorder, recognized as the second most disabling disease. Nevertheless, the antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor are the only prophylactic treatment developed specifically for migraine. These antibodies have displayed positive results in clinical trials, but are not effective for all patients; therefore, new pharmacological targets need to be identified.Due to the ability of PACAP38 to induce migraine-like attacks, its location in structures previously associated with migraine pathophysiology and the 100-fold selectivity for the PAC

13 Review Transport of the pituitary adenylate cyclase-activating polypeptide across the blood-brain barrier: implications for migraine. 2018

Amin, Faisal Mohammad / Schytz, Henrik Winther. ·Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, University of Copenhagen, Valdemar Hansens Vej 1A, 2600, Glostrup, Denmark. faisal@dadlnet.dk. · Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, University of Copenhagen, Valdemar Hansens Vej 1A, 2600, Glostrup, Denmark. ·J Headache Pain · Pubmed #29785578.

ABSTRACT: BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) is widely distributed in the nervous system and is involved in migraine pathophysiology. Understanding the function of the blood-brain barrier (BBB) in relation to PACAP is important to the understand the mechanisms behind PACAP-induced migraine attacks, but also to develop antimigraine drugs targeting the PACAP receptors Here, we aim to review the transport ability of PACAP across the BBB. METHODS: We performed a systematic literature search on PubMed to identify studies reporting original data on PACAP and BBB. The search was finalized in July 2017. RESULTS: The literature search identified 96 papers of which 11 contained relevant data. In addition, two papers were known to be relevant and were included. A total of 13 papers studies were included in the final analysis. Preclinical studies (n = 10) suggest the existence of specific PACAP transport systems across the BBB, while human PACAP studies failed to show vasodilator effect of PACAP on the cerebral arteries from the lumen (n = 3). CONCLUSION: PACAP38 is transported over the BBB actively, while PACAP27 cross the BBB by diffusion over the membrane, but after crossing the endothelial membrane both isoforms are either rapidly degraded or efflux back from brain to blood. Thus, a direct central action of the PACAPs is unlikely. This is supported by studies showing selective PACAP effect on extra-cerebral arteries.

14 Review Polygenic risk score: use in migraine research. 2018

Chalmer, Mona Ameri / Esserlind, Ann-Louise / Olesen, Jes / Hansen, Thomas Folkmann. ·Department of Neurology, Danish Headache Center, Copenhagen University Hospital, DK-2600, Glostrup, Denmark. mona.ameri.chalmer@regionh.dk. · Department of Neurology, Danish Headache Center, Copenhagen University Hospital, DK-2600, Glostrup, Denmark. ·J Headache Pain · Pubmed #29623444.

ABSTRACT: BACKGROUND: The latest Genome-Wide Association Study identified 38 genetic variants associated with migraine. In this type of studies the significance level is very difficult to achieve (5 × 10 RESULTS: Polygenic Risk Score has been used in studies of neuropsychiatric disorders to assess prediction of disease status in case-control studies, shared genetic correlation between co-morbid diseases, and shared genetic correlation between a disease and specific endophenotypes. CONCLUSION: Polygenic Risk Score provides an opportunity to investigate the shared genetic risk between known and previously unestablished co-morbidities in migraine research, and may lead to better and personalized treatment of migraine if used as a clinical assistant when identifying responders to specific drugs. Polygenic Risk Score can be used to analyze the genetic relationship between different headache types and migraine endophenotypes. Finally, Polygenic Risk Score can be used to assess pharmacogenetic effects, and perhaps help to predict efficacy of the Calcitonin Gene-Related Peptide monoclonal antibodies that soon become available as migraine treatment.

15 Review The Role of Endothelin in the Pathophysiology of Migraine-a Systematic Review. 2018

Iljazi, Afrim / Ayata, Cenk / Ashina, Messoud / Hougaard, Anders. ·Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Nordre Ringvej 57, DK-2600, Glostrup, Denmark. · Stroke Service and Neuroscience Intensive Care Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. · Institute of Clinical Medicine, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark. · Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Nordre Ringvej 57, DK-2600, Glostrup, Denmark. ahougaard@dadlnet.dk. ·Curr Pain Headache Rep · Pubmed #29557064.

ABSTRACT: PURPOSE OF REVIEW: Vasoactive peptides play a key role in the attack-initiating cascade of migraine. Recent studies have highlighted a potentially important role for endothelin-1, a potent vasoconstrictor peptide, in migraine pathophysiology. Here, we review the current data on endothelin's involvement in migraine. RECENT FINDINGS: We identified 23 articles. Nine studies reported on endothelin-1 plasma concentrations in patients with migraine, eight studies investigated relevant genetic associations, five studies investigated endothelin-1 and spreading depression in animals, and one randomized controlled clinical trial tested the efficacy of an endothelin antagonist in the acute treatment of migraine in patients both with and without aura. Elevated endothelin-1 plasma levels have been reported in the early phase of migraine attacks. Genetic abnormalities related to the endothelin type A receptor have been reported in migraineurs. Endothelin-1 potently induces spreading depression in animals, which may explain the connection between endothelial irritation and migraine aura. Endothelin-1 could be a primary factor in the attack-triggering cascade of migraine attacks with and without aura. Additional studies in humans and animal models are needed to further elucidate the role of endothelin-1 in migraine.

16 Review Targeted Pituitary Adenylate Cyclase-Activating Peptide Therapies for Migraine. 2018

Vollesen, Anne Luise Haulund / Amin, Faisal Mohammad / Ashina, Messoud. ·Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2600, Glostrup, Copenhagen, Denmark. · Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2600, Glostrup, Copenhagen, Denmark. ashina@dadlnet.dk. ·Neurotherapeutics · Pubmed #29464574.

ABSTRACT: Here, we review the role of pituitary adenylate cyclase-activating peptide-38 (PACAP38) in migraine pathophysiology and data implicating PAC

17 Review PACAP and its receptors in cranial arteries and mast cells. 2018

Jansen-Olesen, Inger / Hougaard Pedersen, Sara. ·Danish Headache Center, Department of Neurology, Glostrup Research Institute, Rigshospitalet and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. inger.jansen-olesen@regionh.dk. · Department of Neurology, Danish Headache Center, Glostrup Research Institute, Nordre Ringvej 69, 2600, Glostrup, Denmark. inger.jansen-olesen@regionh.dk. · Danish Headache Center, Department of Neurology, Glostrup Research Institute, Rigshospitalet and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. ·J Headache Pain · Pubmed #29460121.

ABSTRACT: BACKGROUND: In migraineurs pituitary adenylate cyclase activating peptide1-38 (PACAP1-38) is a potent migraine provoking substance and the accompanying long lasting flushing suggests degranulation of mast cells. Infusion of the closely related vasoactive intestinal peptide (VIP) either induces headache or flushing. This implicates the pituitary adenylate cyclase activating peptide type I receptor (PAC1) to be involved in the pathophysiology of PACAP1-38 provoked headaches. Here we review studies characterizing the effects of mainly PACAP but also of VIP on cerebral and meningeal arteries and mast cells. DISCUSSION: PACAP1-38, PACAP1-27 and VIP dilate cerebral and meningeal arteries from several species including man. In rat cerebral and meningeal arteries the dilation seems to be mediated preferably via vasoactive intestinal peptide receptor type 1 (VPAC1) receptors while, in human, middle meningeal artery dilation induced via vasoactive intestinal peptide receptor type 2 (VPAC2) receptors cannot be ruled out. PACAP1-38 is a strong degranulator of peritoneal and dural mast cells while PACAP1-27 and VIP only have weak effects. More detailed characterization studies suggest that mast cell degranulation is not mediated via the known receptors for PACAP1-38 but rather via a still unknown receptor coupled to phospholipase C. CONCLUSION: It is suggested that PACAP1-38 might induce migraine via degranulation of dural mast cells via a yet unknown receptor.

18 Review Botulinum toxin: A review of the mode of action in migraine. 2018

Do, T P / Hvedstrup, J / Schytz, H W. ·Headache Diagnostic Laboratory, Danish Headache Center and Department of Neurology, Rigshospitalet-Glostrup, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark. ·Acta Neurol Scand · Pubmed #29405250.

ABSTRACT: Botulinum toxin serotype A (BoNT/A) was originally used in neurology for the treatment of dystonia and blepharospasms, but is now clinically used worldwide for the treatment of chronic migraine. Still, the possible mode of action of BoNT/A in migraine is not fully known. However, the mode of action of BoNT/A has been investigated in experimental pain as well as migraine models, which may elucidate the underlying mechanisms in migraine. The aim of this study was to review studies on the possible mode of action of BoNT/A in relation to chronic migraine treatment. Observations suggest that the mode of action of BoNT/A may not be limited to the injection site, but also includes anatomically connected sites due to axonal transport. The mechanisms behind the effect of BoNT/A in chronic migraine may also include modulation of neurotransmitter release, changes in surface expression of receptors and cytokines as well as enhancement of opioidergic transmission. Clinical and experimental studies with botulinum toxin in the last decade have advanced our understanding of headache and other pain states. More research into botulinum toxin as treatment for headache is warranted as it can be an attractive alternative for patients who do not respond positively to other drugs.

19 Review Dysautonomia in the pathogenesis of migraine. 2018

Gazerani, Parisa / Cairns, Brian Edwin. ·a Department of Health Science and Technology, Faculty of Medicine , Aalborg University , Aalborg , Denmark. · b Faculty of Pharmaceutical Sciences , The University of British Columbia , Vancouver , BC , Canada. ·Expert Rev Neurother · Pubmed #29212396.

ABSTRACT: INTRODUCTION: Migraine is a common complex neurological disorder involving multiple brain areas that regulate autonomic, affective, cognitive, and sensory functions. This review explores autonomic nervous system (ANS) dysfunction in migraine headache sufferers. Areas covered: Reference material for this review was obtained through PubMed searches. Migraine attacks can present with up to 4 phases (premonitory, aura, headache, postdrome) each with distinguishable signs and symptoms. Altered ANS tone can be found from the premonitory through the postdrome phases. Features of the migraine attack that are indicative of altered autonomic function, which include nausea, vomiting, diarrhea, polyuria, eyelid edema, conjunctival injection, lacrimation, nasal congestion, and ptosis, are discussed and putative mechanisms explored. In addition, alteration of ANS function by endogenous and exogenous stressors, such as bright lights, hunger, poor sleep quality, menses, and special dietary components is discussed. The influence of currently employed pharmacological treatments on altered autonomic function during the migraine attack is explored. Expert commentary: Migraine-related alterations in ANS function have a complex pattern, but, in general, an imbalance occurs between sympathetic and parasympathetic tone. Through an improved understanding the role of autonomic changes in pathogenesis of migraine, it may be possible to develop even more effective treatments for migraine sufferers.

20 Review CGRP in human models of primary headaches. 2018

Ashina, Håkan / Schytz, Henrik Winther / Ashina, Messoud. ·Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. ·Cephalalgia · Pubmed #27940880.

ABSTRACT: Objective To review the role of CGRP in human models of primary headaches and to discuss methodological aspects and future directions. Discussion Provocation experiments demonstrated a heterogeneous CGRP migraine response in migraine patients. Conflicting CGRP plasma results in the provocation experiments are likely due to assay variation; therefore, proper validation and standardization of an assay is needed. To what extent CGRP is involved in tension-type headache and cluster headache is unknown. Conclusion Human models of primary headaches have elucidated the role of CGRP in headache pathophysiology and sparked great interest in developing new treatment strategies using CGRP antagonists and antibodies. Future studies applying more refined human experimental models should identify biomarkers of CGRP-induced primary headache and reveal whether CGRP provocation experiments could be used to predict efficacy of CGRP antagonists in migraine patients.

21 Review PACAP38 in human models of primary headaches. 2017

Ashina, Håkan / Guo, Song / Vollesen, Anne L H / Ashina, Messoud. ·Department of Neurology, Danish Headache Center, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · Department of Neurology, Danish Headache Center, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. ashina@dadlnet.dk. ·J Headache Pain · Pubmed #29453754.

ABSTRACT: BACKGROUND: To review the role of PACAP38 in human models of primary headaches, discuss possible mechanisms of PACAP38-induced migraine, and outline future directions. DISCUSSION: Experimental studies have established PACAP38 as a potent pharmacological "trigger" molecule of migraine-like attacks. These studies have also revealed a heterogeneous PACAP38 migraine response in migraine without aura patients. In addition, findings from brain imaging studies have demonstrated neuronal and vascular changes in migraine patients both ictally and interictally after PACAP38 infusion. CONCLUSION: Human migraine models have shed light on the importance of PACAP38 in the pathophysiology of primary headaches. These studies have also pointed to the PAC

22 Review Experts' opinion about the primary headache diagnostic criteria of the ICHD-3rd edition beta in children and adolescents. 2017

Özge, Aynur / Faedda, Noemi / Abu-Arafeh, Ishaq / Gelfand, Amy A / Goadsby, Peter James / Cuvellier, Jean Christophe / Valeriani, Massimiliano / Sergeev, Alexey / Barlow, Karen / Uludüz, Derya / Yalın, Osman Özgür / Lipton, Richard B / Rapoport, Alan / Guidetti, Vincenzo. ·Department of Neurology, Mersin University Medical Faculty, Mersin, Turkey. · Phd program in Behavioural Neuroscience, Department of Paediatrics and Child and Adolescent Neuropsychiatry, Sapienza University of Rome, Rome, Italy. · Royal Hospital for Sick Children, Glasgow, G3 8SJ, UK. · UCSF Headache Center and UCSF Benioff Children's Hospital, Pediatric Brain Center 2330 Post St 6th Floor San Francisco, Campus Box 1675, San Francisco, CA, 94115, USA. · NIHR-Wellcome Trust King's Clinical Research Facility, King's College London, London, England. · Division of Paediatric Neurology, Department of Paediatrics, Lille Faculty of Medicine and Children's Hospital, Lille, France. · Division of Neurology, Ospedale Pediatrico Bambino Gesù, Piazza Sant'Onofrio 4, 00165, Rome, Italy. · Center for Sensory-Motor Interaction Aalborg University, Aalborg, Denmark. · Department of Neurology and Clinical Neurophysiology, University Headache Clinic, Moscow State Medical University, Moscow, Russia. · Faculty of Medicine, University of Calgary, Alberta Children's Hospital, C4-335, 2888 Shaganappi Trail NW, Calgary, AB, T3B 6A8, Canada. · Cerrahpaşa Medical Faculty, Department of Neurology, İstanbul University, Kocamustafapaşa, İstanbul, Turkey. · İstanbul Research and Education Hospital, Kocamustafapaşa, İstanbul, Turkey. · Department of Neurology Montefiore Headache Center, Albert Einstein College of Medicine, Louis and Dora Rousso Building, 1165 Morris Park Avenue, Room 332, Bronx, NY, 10461, USA. · The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. · Department of Pediatrics and Child and Adolescent Neuropsychiatry, Sapienza University, Rome, Italy. vincenzo.guidetti@uniroma1.it. ·J Headache Pain · Pubmed #29285570.

ABSTRACT: BACKGROUND: The 2013 International Classification of Headache Disorders-3 (ICHD-3) was published in a beta version to allow the clinicians to confirm the validity of the criteria or to suggest improvements based on field studies. The aim of this work was to review the Primary Headache Disorders Section of ICHD-3 beta data on children and adolescents (age 0-18 years), and to suggest changes, additions, and amendments. METHODS: Several experts in childhood headache across the world applied different aspects of ICHD-3 beta in their normal clinical practice. Based on their personal experience and the literature available on pediatric headache, they made observations and proposed suggestions for the primary headache disorders section of ICHD-3 beta data on children and adolescents. RESULTS: Some headache disorders in children have specific features which are different from those seen in adults and which should be acknowledged and considered. Some features in children were found to be age-dependent: clinical characteristics, risks factors and etiologies have a strong bio psycho-social basis in children and adolescents making primary headache disorders in children distinct from those in adults. CONCLUSIONS: Several recommendations are presented in order to make ICHD-3 more appropriate for use with children.

23 Review Triptans and CGRP blockade - impact on the cranial vasculature. 2017

Benemei, Silvia / Cortese, Francesca / Labastida-Ramírez, Alejandro / Marchese, Francesca / Pellesi, Lanfranco / Romoli, Michele / Vollesen, Anne Luise / Lampl, Christian / Ashina, Messoud / Anonymous10660923. ·Health Sciences Department, University of Florence, and Headache Centre, Careggi University Hospital, Viale Pieraccini 6, 50134, Florence, Italy. silvia.benemei@unifi.it. · Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Polo Pontino, Latina, Italy. · Dept Internal Medicine, Division of Vascular Pharmacology, Erasmus Medical Center, Rotterdam, The Netherlands. · Child Neuropsichiatry Unit, University of Palermo, Palermo, Italy. · Medical Toxicology Headache and Drug Abuse Center, University of Modena and Reggio Emilia, Modena, Italy. · Neurology Clinic, University Hospital of Perugia, Perugia, Italy. · Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medicl Sciences, University of Copenhagen, Copenhagen, Denmark. · Department of Neurogeriatric Medicine, Headache Medical Center Linz, Linz, Austria. · Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. ·J Headache Pain · Pubmed #29019093.

ABSTRACT: The trigeminovascular system plays a key role in the pathophysiology of migraine. The activation of the trigeminovascular system causes release of various neurotransmitters and neuropeptides, including serotonin and calcitonin gene-related peptide (CGRP), which modulate pain transmission and vascular tone. Thirty years after discovery of agonists for serotonin 5-HT

24 Review Blocking CGRP in migraine patients - a review of pros and cons. 2017

Deen, Marie / Correnti, Edvige / Kamm, Katharina / Kelderman, Tim / Papetti, Laura / Rubio-Beltrán, Eloisa / Vigneri, Simone / Edvinsson, Lars / Maassen Van Den Brink, Antoinette / Anonymous7800920. ·Danish Headache Center, Department of Neurology, Rigshospitalet, Copenhagen, Denmark. mariedeen85@gmail.com. · Department of Child Neuropsychiatry, University of Palermo, Palermo, Italy. · Department of Neurology, University Hospital, LMU, Munich, Germany. · Department of Neurology, Ghent University Hospital, Ghent, Belgium. · Headache Center, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. · Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. · Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo; Advanced Algology Research and Pain Medicine Unit, Santa Maria Maddalena Hospital, Occhiobello, Italy. · Department of Internal Medicine, Institute of Clinical Sciences, Lund University, Lund, Sweden. ·J Headache Pain · Pubmed #28948500.

ABSTRACT: Migraine is the most prevalent neurological disorder worldwide and it has immense socioeconomic impact. Currently, preventative treatment options for migraine include drugs developed for diseases other than migraine such as hypertension, depression and epilepsy. During the last decade, however, blocking calcitonin gene-related peptide (CGRP) has emerged as a possible mechanism for prevention of migraine attacks. CGRP has been shown to be released during migraine attacks and it may play a causative role in induction of migraine attacks. Here, we review the pros and cons of blocking CGRP in migraine patients. To date, two different classes of drugs blocking CGRP have been developed: small molecule CGRP receptor antagonists (gepants), and monoclonal antibodies, targeting either CGRP or the CGRP receptor. Several trials have been conducted to test the efficacy and safety of these drugs. In general, a superior efficacy compared to placebo has been shown, especially with regards to the antibodies. In addition, the efficacy is in line with other currently used prophylactic treatments. The drugs have also been well tolerated, except for some of the gepants, which induced a transient increase in transaminases. Thus, blocking CGRP in migraine patients is seemingly both efficient and well tolerated. However, CGRP and its receptor are abundantly present in both the vasculature, and in the peripheral and central nervous system, and are involved in several physiological processes. Therefore, blocking CGRP may pose a risk in subjects with comorbidities such as cardiovascular diseases. In addition, long-term effects are still unknown. Evidence from animal studies suggests that blocking CGRP may induce constipation, affect the homeostatic functions of the pituitary hormones or attenuate wound healing. However, these effects have so far not been reported in human studies. In conclusion, this review suggests that, based on current knowledge, the pros of blocking CGRP in migraine patients exceeds the cons.

25 Review Migraine, Neurogenic Inflammation, Drug Development - Pharmacochemical Aspects. 2017

Lukacs, Melinda / Tajti, Janos / Fulop, Ferenc / Toldi, Jozsef / Edvinsson, Lars / Vecsei, Laszlo. ·Department of Neurology, University of Szeged, Szeged. Hungary. · Institute of Pharmaceutical Chemistry and MTA-SZTE Research Group for Stereochemistry, University of Szeged. Hungary. · Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged. Hungary. · Department of Clinical Experimental Research, Copenhagen University, Glostrup Hospital, Copenhagen. Denmark. · Department of Neurology, University of Szeged, Hungary and MTA-SZTE Neuroscience Research Group, Szeged. Hungary. ·Curr Med Chem · Pubmed #28707585.

ABSTRACT: BACKGROUND: Migraine is a primary headache disorder. Despite numerous studies conducted with the aim to understand the pathophysiology of migraine, several aspects are still unclear. The trigeminovascular system plays a key role. Neurogenic inflammation is presumed to be an important factor in migraine pathophysiology, mediated by the activation of primary neurons, leading to the release of various pro-inflammatory neuropeptides and neurotransmitters such as Calcitonin Gene-Related Peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP). Nitric oxide (NO), Pituitary adenylate cyclase-activating polypeptide (PACAP) and Glutamate (Glu) also play an important role in the modulation of inflammatory mechanisms. OBJECTIVE: To review the literature focusing on novel therapeutic targets in migraine, related to neurogenic inflammation. METHOD: A systematic literature search in the database of PUBMED was conducted regarding therapeutic strategies in migraine, focusing on substances and cytokines released during neurogenic inflammation, published until January 2017. RESULTS: Ongoing phase III clinical studies with monoclonal antibodies against CGRP and CGRP receptors offer promising novel aspects for migraine treatment. Preclinical and clinical studies targeting SP and nitric oxide synthase (NOS) were all terminated with no significant results compared to placebo. New promising therapeutic goal could be PACAP and its receptor (PAC1), and kynurenic acid (KYNA) analogues. CONCLUSION: Current migraine treatment offers pain relief only for a small proportion of migraine patients and might not be adequate for patients with cardiovascular comorbidity due to side effects. Better understanding of migraine pathophysiology might, therefore, lead to novel therapeutic lines both in migraine attack treatment and prophylaxis.

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