Annual Report 2014

Danish Headache Center

Rigshospitalet, Glostrup

Preface

The year 2014 was busy, not only with clinical activities as always, but also with several important scientific and social events. Rigmor Jensen was main organizer of the 4th European Headache and Migraine Trust International Congress in Copenhagen in September. The congress was a great success with over 1,000 participants and nominated among the top 3 congresses in Copenhagen in 2014. We thank the staff from DHC for excellent help before and during the congress.

In September, Messoud Ashina was appointed professor at the University of Copenhagen as a result of his very producti-ve research and his visions for future high quality research. This will without doubt further strengthen the research profile of the DHC. Congratulations to Messoud Ashina and DHC.

The work on the new building for the centre has been delayed, but it is now back on track. We expect the building to be ready in the spring 2017. We are looking much forward to be able to greet our patients welcome in modern facilities. On the sad side we had to say goodbye to senior consultant Peer Tfelt-Hansen. Peer has decided that it is time cut down on the clinical work load. We thank Peer for his tremendous efforts during many years of excellent clinical service and look forward to continue the scientific collaboration. On the happy side we welcome Vlasta Vukovic Cvetkovic as a senior consultant in DHC. Vlasta is an experienced senior consultant from Croatia with special interest in headaches. Vlasta is doing great progress in learning the difficult Danish language. We look forward to many years of collaboration.

Rigmor Jensen turned 60 years young in November, which was celebrated on several occasions. Rigmor thanks for the many warm greetings.

Research continued to flourish with one doctoral thesis and three defended PhD theses. Congratulations to Christina Kruuse, Hanne Yri, Anders Hougaard and Dorthe Kjeldgaard Nielsen. Jakob Møller Hansen received the prestigious Woolf Award in Boston for his work on human migraine models. Congratulations to Jakob.

We hope that these small pieces of information may interest our readers so much that they feel stimulated to read in more detail about DHC on the following pages.Glostrup, June 2015.

Lars Bendtsen Rigmor Jensen Helle Jensby Jes Olesen

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Table of contents

1. Research 6

1.1 Organization 6

1.2 Research staff 7

1.3 Research areas 8

1.4 Sponsors 17

2. Collaborations 19

3. Publications in 2014 23

4. Clinical activities 28

5. Teaching and public activities 30

6. Organization and staff 32

7. Future 33

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1. Research1.1 Organization

The Danish Headache Centre has 8 vigorous research groups run by 8 senior researchers, 5 post docs and 23 Ph.D. students. The research groups are shown in Figure 1.

Figure 1. Organization of Research.

Trigeminal Neuralgia

Clinical Migraine ModelsMultidisciplinary treatment

Medication Overuse Headache

Cluster Headache

Genetics

Preclinical Migraine Models

CSF Physiology

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1.2 Research Staff

Senior scientists:Jes OlesenRigmor H. JensenPeer Tfelt-HansenInger Jansen OlesenMessoud AshinaLars BendtsenAydin GozalovVlasta Vukovic Cvetkovic

Post docs.Henrik Winther SchytzJakob Møller HansenSigne Bruun MunksgaardDipak Vasantrao AmrutkarDeepak Kumar Bhatt

Technologists:Hanne AndresenLene ElkjærZainab AhtoshWinnie GrønningMari Salan

Administrative assistants:Kirsten HjelmMaria Luisa Jimenez PranovKarin AagaardLine Nørgaard

Medical studentsTrine NielsenMorten Togo SørensenNinett Louise FindBenjamin Janjoa

Amina AharazDana LiSamaira Younis

Ph.D.students:Anders HougaardFaisal AminSong GuoNanna Bjørkhom ArngrimSabrina KhanMarie Deen ChristensenStine Maarbjerg Tone HeinskouMads Christian Johannes Barløse Hanne Marie YriLotte Skytte KrøllBjarne Kjeldgaard MadsenMaria Schmidt UldallMaria Lurenda WestergaardAnn-Louise EsserlindAnne Francke ChristensenMona AmeriSara Hougaard PedersenSarah Louise Tanggaard ChristensenKatrine HansenRikke Elgård ChristensenDorte PhillipJulie Carøe Kristensen

Other researchersSait AshinaSteffen PetersenVibeke Møllegaard Kristensen

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1.3 Research Areas

Human migraine models

Members of the Human Migraine Research Unit (HMRU)Messoud Ashina (director), Jes Olesen, Faisal Amin, Anders Hougaard, Song Guo, Nanna Arngrim, Jakob Møller Hansen, Henrik Schytz, Sabrina Khan, Marie Deen Christensen.

BackgroundThe HMRU is an integral part of the Danish Headache Center and Department of Neurology, Glostrup Hospital. At the HMRU, we seek to understand molecular mecha-nisms of migraine and to identify disease specific biomar-kers (fingerprints of migraine). The core expertise of our members is human provocation models of migraine and ultrasound-based diagnostic imaging techniques used for visualizing vascular responses during experimentally indu-ced migraine attacks. Over recent years, we have added additional expertise in functional and structural magnetic resonance imaging (incl. MR-angiography & functional MRI). These advanced imaging techniques constitute an impor-tant supplement to our provocation models and provide new and exciting insights into migraine pathophysiology. Furthermore, the HMRU has extended its field of interest by utilizing migraine genetic discoveries in human models of migraine to investigate functional consequences of genetic mutations. These achievements would not have been possible without strong collaborative work between the HMRU, the Functional Imaging Unit, Glostrup Hospital and other research groups.

In the future we intend to broaden our research program with novel human models of migraine and new imaging techniques (incl. PET) with the ultimate goal of defining

predictive animal models of migraine, and discovery of tar-gets for more specific and more effective mechanism-ba-sed anti-migraine drugs.

Current projects

Hypotheses:• Hypoxia provokes headache and migraine attacks with

aura• Carbon monoxide provokes headache and migraine

attacks• CGRP provokes more migraine attacks in patients with

high genetic load than in patients with a low genetic load

• PACAP38 provokes more migraine attacks in patients with PACAP-associated gene variant

• Migraine attacks are associated with increased in blood-brain barrier permeability

• Natriuretic peptides dilates cerebral arteries and indu-ces headache

• Patients undergoing endovascular procedures devel-op chronic headache

• Migraine attacks are associated with levels of seroto-nin in the brain

• Prevalence of migraine is higher in persons with the 3243A>G mutation in mitochondrial DNA

• Low frequency neuro-stimulation of SPG provokes mi-graine attacks in migraine patients

• Pre-treatment with antihistamine blocks PACAP38 in-duced migraine attacks

• The migraine brain is characterized by low levels of serotonin

CollaborationHenrik Larsson (Functional and Diagnostic MR Unit, Glo-

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strup); Gitte Moos Knudsen (Center for Experimental Me-dicine Neuropharmacology, NeuroPharm, Neurobiology Research Unit, Rigshospitalet); David Borsook and Lino Becerra (PAIN Group, Mclean Hospital, Harvard University Boston USA); David A Boas (Optical Imaging Core & Lab at Martinos Centre Department of Radiology, Boston USA); Professor van der Geest (Leiden University Medical Centre, Holland); Professor. Michael Hoffmann (Head of Visual Pro-cessing Laboratory, Universitätsaugenklinik, Otto-von-Gu-ericke-Universität, Magdeburg); Prof Till Sprenger (De-partment of Neurology and Division of Neuroradiology, University Hospital Basel, Switzerland); Jens Peter Gøtze & Lars Bo Nielsen (Department of Clinical Biochemistry, Rigs-hospitalet); John Burnett (Departments of Internal Medici-ne and Physiology, Mayo Clinic College of Medicine, USA); John Vissing (Neuromuscular Research Unit, Department of Neurology, Rigshospitalet)

Epidemiology

MembersRigmor Jensen, Lars Bendtsen, Sait Ashina, Maria Wester-gaard.

BackgroundEpidemiology is the study of the distribution and determi-nants of health-related states or events in specified popu-lations. The Glostrup Research for Health and Prevention is the unique Danish facility for epidemiological studies in all chronic diseases including headache and several PhD theses have been conducted from this institution.

Current projectsThe Danish National Health Survey (DNHS) was a cross-se-ctional survey involving 130.000 individuals and that used

a self-administered questionnaire with 52 core questions on chronic illness, health behaviour, perceived stress, and quality of life. The survey was implemented in 2010 and headache related questions are now under evaluation. Supplementary data analysis with specific focus on chro-nification, medication overuse, use of prescription medi-cation and socioeconomic impact are ongoing and will be supplemented with data from the extensive national registers. The prevalence of medication overuse heada-che in Denmark is 1.8%, equivalent to 80.000 adults and such large figures call for further attention as Medication Overuse Headache is a unique type of disabling pain that in principle both can be prevented and treated. Several new projects focusing on specific treatment results and neurobiological mechanisms underlying medication over-use headache are ongoing. Data from the epidemiological studies are related to newer population studies and pre-dictors for chronification are identified.

Genetics and environment

MembersJes Olesen, Anne Francke Christensen, Ann-Louise Esser-lind, Benjamin Janjoa, Amina Aharaz, Mona Ameri.

BackgroundFamily studies and twin studies show that the risk of mi-graine is 50% inheritance and 50% environment. The iden-tification of genes involved in migraine may give clues to underlying pathophysiological mechanisms. It is equally important to identify the environmental factors, which so far are largely unknown.

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Current projectsOne aim of our studies is to identify the genes involved in migraine with aura, familial hemiplegic migraine, and migraine without aura. To date we have collected blood from 3000 migraine patients. Genome wide association typing (GWAS) and exome chipping have been performed. The results are now being utilized in collaboration with the gene finding company DeCode in Iceland and as members of the International Headache Genetics Consortium. We also participate in the STEMBANCC consortium funded under the Innovative Medicines program of the EU taking skin biopsies for fibroblast culture and reprogramming to pluripotent stem cells and further differentiation.

Medication-overuse headache

MembersRigmor Jensen, Ninett Louise Find, Lars Bendtsen, Signe Bruun Munksgaard, Maria Westergaard, Rossana Terlizzi.

BackgroundMedication-overuse headache (MOH) is a daily or almost-daily type of headache that usually results from the chro-nification of primary forms, such as migraine or tension-type headache, as a consequence of the progressive increase in the intake of symptomatic drugs. Limited amount of data exists on the burden of MOH, even in developed countri-es, but there is general agreement that the disease repre-sents one of the most disabling disorders, which markedly deteriorates the quality of life of patients, exposing them to the risks of side-effects and co-morbid conditions.

Our knowledge on the mechanisms leading to MOH is limi-ted, and there are virtually no data on how these severe-ly patients are treated optimally. Thus, there is an urgent

need for studies investigating the pathophysiology and treatment possibilities of MOH.

Current projectsAn EU-founded multi-centre study (COMO-ESTAS) inve-stigating the benefit of electronic headache diaries during detoxification of MOH has been finalized and results are underway for publication. The first reports demonstrate a highly significant reduction in headache frequency, more than 2 thirds reverse from chronic to episodic headache. The depression and anxiety-scores are markedly reduced by mere detoxification and indicate that these comorbidi-ties are a function of severe headache and not causative to the pain. A new project testing the efficacy of 2 diffe-rent detoxification programmes and the potential biomar-kers for relapse in close collaboration with University of Bologna is drafted.

CollaborationC. Tassorelli, Fondazione Istituto Neurologico Casimi-ro Mondino, Italy. M. Lainez, Fundación de la Comunidad Valenciana para la Investigación Biomédica del Hospital Clínico Universitario De Valencia, Spain. Z. Katsarava, Uni-versitaetsklinikum Essen, Germany. R. Fadic, Pontificia Universidad Catolica de Chile, Santiago, Chile. A. Stop-pini, Fundacion para la Lucha contra las Enfermedades Neurologicas de la Infancia, Buenos Aires, Argentina. Lars Thorbjørn, Klinisk Biokemisk afdeling, Glostrup Hospital. Dr Csaba Ertsey, Department of Neurology, Semmelweis Uni-versity, Budapest, Hungary, Pietro Cortelli, Department of Neurology, University of Bologna.

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Cluster headache

MembersRigmor Jensen, Mads Barløse, Nunu Lund, Anja Petersen, Lars Bendtsen.

BackgroundCluster headache is one of the most severe and disabling type of headaches. The pathophysiology of this disorder is largely unknown and it may be very difficult to treat, in particular the chronic form of cluster headache. There is a peculiar but yet unclarified relation between cluster headache and sleep as most of these severe headache attacks occur during the night, believed to be caused by a hypothalamic disturbance in the chronobiology.

Current projectsExtensive sleep analysis in cluster headache patients as an inpatient study during the active bouts of cluster headache has been finalized and results indicate that clu-ster headache has a clear diurnal and circannual pattern but are not linked to specific sleep stages. We are con-tinuing a large scale survey on the eventual relation bet-ween sleep and cluster headache based on questionnai-res. Neurostimulation has been used in selected cases of chronic neuropathic pain and evidence is now accumu-lating for their use in headache disorders. As chronic clu-ster headache is one of the most disabling pain disorders known by mankind there is a constant search for new and better strategies, especially for those patients that are re-fractive to medical treatment strategies. Since 2011 the Danish Headache Center has participated in an internati-onal multicentre study of the effect of neurostimulation of the sphenopalatine ganglion in patients with cluster headache, and we have now demonstrated a successful

outcome in two-thirds of severely affected patients, and also with a long-lasting effect in 61% after 2 years obser-vation. The significant cost-savings of medication lead to a general approval of this new promising treatment for clu-ster headache. We have continued to offer this treatment strategy to selected patients in an open labelled register study and in total 62 cluster patients are implanted now in Denmark. Further neuromodulation studies on other stra-tegies are also emerging and DHC is now one of the lea-ding centres for neuromodulation in Europe. DHC is also chairing a new European multicentre study of the effect of SPG stimulation in disabling migraine and results are pro-mising.

CollaborationSøren Hillerup, professor, DDS, and Jørgen Rostgaard, CMT surgeon, DDS, Department of Oromaxillofacial Surgery, Na-tional Hospital, Copenhagen, Denmark. Anthony Carparso, Principal Clinical Scientist, Autonomic Technologies, Inc., CA, USA, Poul Jennum, Danish Center for Sleep Medicine, Glostrup Hospital, ElectroCore LLC, 51 Gibraltar Drive, Sui-te 3C, Morris Plains, NJ, USA.

Clinical trials

MembersMessoud Ashina (director), Rigmor Jensen and Jes Olesen.

Background The Centre participates in number of clinical trials desig-ned to test new therapies, or new ways of using known treatments to improve the treatment of headache disor-ders.

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Current trials• Register study of Sphenopalatine Ganglion Stimulation

for the Acute Treatment of Cluster Headache• Sphenopalatine Ganglion Stimulation for the Acute tre-

atment of severe/chronic disabling migraine• GC-003: Treatment of acute episodic and chronic

attacks of cluster headache with GammaCore®, a non-invasive transcutaneous vagal neurostimulation

• Picotamide for the prophylaxis of migraine with aura• A Phase 2 Study to Evaluate the Efficacy and Safety of

AMG 334 in Migraine Prevention• A Study to Evaluate the Efficacy and Safety of AMG

334 in Chronic Migraine Prevention A Study to Assess the Long-term Safety and Efficacy of AMG 334 in Chro-nic Migraine Prevention

Trigeminal neuralgia

MembersLars Bendtsen, Stine Maarbjerg, Tone Heinskou, Samaira Younis, Aydin Gozalov, Morten Togo Sørensen, Jes Olesen.

BackgroundTrigeminal neuralgia is an extremely painful disease, which may be difficult to treat. Management consists of pr-ophylactic pharmacotherapy and surgery in selected ca-ses. There is a huge lack of high quality research in this field and essential aspects such as epidemiology, pathophysi-ology, diagnosis and optimal treatment are far from under-stood.

Current projectsEvaluation of efficacy and side-effects of surgery. Evalu-ation of a structured management programme. Genetic

factors. Investigations on how findings from imaging, e.g. the presence or absence of neurovascular contact on high resolution MR-scans, are correlated to clinical findings and to efficacy of pharmacological treatment and neurosur-gery. Quantitative sensory testing in trigeminal neuralgia.

Collaboration Professor Ralf Baron (Division of Neurological Pain Re-search and Therapy, Universitätsklinikum Schleswig-Hol-stein, Kiel). Frauke Wolfram, Department of Diagnostics, Glostrup University Hospital, Denmark. Dr. Per Rochat, De-partment of Neurosurgery, The National Hospital, Copen-hagen, Denmark. Dr. Jannick Brennum, Department of Neurosurgery, The National Hospital, Copenhagen, Den-mark. Professor, Dr Med Sci, C.G. Faber, neurologist, De-partment of Neurology, Maastricht University Medical Cen-ter (MUMC), Maastricht; the Netherlands.

Receptor characterization and mechanisms activated after infusion of migraine provoking substances

MembersInger Jansen Olesen, Maja Myren, Dipak Vasantrao Am-rutkar, Deepak Kumar Bhatt, Roshni Ramachandran, Sara Hougaard Pedersen, Jes Olesen.

BackgroundUsing the human migraine models mentioned above, we receive knowledge about the headache provoking proper-ties of endogenous signalling substances in man. We beli-eve that a drug or substance that can block the effect of a headache/migraine provoking substance will be effective in the treatment of migraine and thus be a novel target for future development of medicine for migraine. Moving the

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studies of migraine triggering substances from man to ani-mal we have the possibility to characterize the receptors or ion-channels for these substances in the migraine re-levant tissues; cerebral arteries, dural arteries, dura mater, trigeminal ganglion and trigeminal nucleus caudalis. The characterization is performed by combining several diffe-rent molecular and in vitro and in vivo functional studies.

• RT-PCR and in situ hybridization for investigating the presence of mRNA for different subtypes of receptors

• Western blotting and immunohistochemistry to inve-stigate the presence and localization of protein for the different subtypes of the receptors and/or ion channels

• In vitro studies of the calcitonin gene-related peptide (CGRP) (a sensory peptide with a role in migraine pat-hophysiology) releasing properties of the migraine trig-gering substances in dura mater, trigeminal ganglion and trigeminal nucleus caudalis

• In vivo pharmacological characterization of the recep-tors activated in dural and pial arteries after intra caro-tid infusion of the migraine provoking substances

During infusion of a headache/migraine triggering sub-stance the migraine sufferers experience more pain than non-migraineurs. This immediate headache is 4-5 hrs af-ter the infusion followed by a delayed headache some-times fulfilling the criteria for migraine. We have recently developed an animal model, where the migraine triggering substances are infused to un-anaesthetized rats and the molecular changes in the migraine relevant tissues menti-oned above are investigated. By these studies we expect to unravel the cascade of molecular changes taking place in the time period between infusion of a migraine triggering substance and the development of a migraine attack.

Current projectsAt present we characterize the receptors for prostanoids and the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PA-CAP) in migraine relevant tissues.

We are in addition studying the effect of these substances on CGRP release and nitric oxide synthase (NOS) activity.In the conscious rat migraine model, we further exami-ne what markers are up-regulated after infusion and the possible pathway for this up-regulation after infusion of migraine triggering substances. These studies will give us an understanding of which subtype of receptors that are present in these tissues. In addition, they will give us infor-mation to further understand the pathophysiology of mi-graine and to define new targets for the pharmacological treatment of migraine.

Collaboration Professor Dan Klærke (Faculty of Life Sciences, Copen-hagen University), Associate Professor Majid Sheykhzade (Faculty of Pharmaceutical Sciences, Copenhagen Uni-versity), Professor Karl Messlinger (Institute of Physiology and Experimental Pathophysiology, University of Erlan-gen-Nürnberg, D-91054 Erlangen, Germany), Professor Frank Porreca (Department of Pharmacology, College of Medicine, University of Arizona, Tucson, Arizona, USA), Pro-fessor Sue Duckles and Professor Diana Krause, Depart-ment of Pharmacology, University of California Irvine, Irvine, California, USA).

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Behavioral animal migraine models

MembersInger Jansen Olesen, Sarah Louise T Christensen, Steffen Pedersen, Jes Olesen.

BackgroundDespite advances in migraine treatment, there are still huge unmet needs in terms of both prophylactic and acute therapy. At present the lack of suitable, predictive and valid animal models holds up the development of new drugs for migraine. Using the rat model described above, we study a wide range of different behavioural models before and after administration of migraine provoking sub-stances.

Current projectsWe study the effect of i.v. glyceryltrinitrate (GTN) infusion on behaviour in running wheel, burrowing and preferen-ce for darkness or light. Also the behavioural effect after administration of the orally available long acting NO do-nor 5-isosorbidemononitrate is studied. We will establish more behavioural models in 2013.

CollaborationAssociate Professor Dorthe Bratbo Sørensen, the Labora-tory Animal Science group at Department of Veterinary Di-sease Biology, Copenhagen University and Staff Scientist, PhD Johnny Roughan, Laboratory Animal Welfare Group, University of Newcastle upon Tyne, United Kingdom.

Tension-type headache

MembersLars Bendtsen, Rigmor Jensen, Sait Ashina, Bjarne Kjeld-gaard Madsen, Lotte Skytte Krøll.

BackgroundIncreased understanding of the relative importance of peripheral factors (mainly muscular) and central factors (mainly central pain processing) in the pathophysiology of tension-type headache are crucial for the development of more effective treatment options for this disorder. Expe-rimental models studying muscular factors, e.g. muscle pain sensitivity, and central factors, e.g. degree of wind-up, and the interaction between these factors are needed to explore the cause/effect relationship between the various peripheral and central abnormalities reported in tension-type headache. Previous studies from our group have, e.g., demonstrated abnormal tenderness and pain perception indicating central sensitization. Headache pa-tients are often physically inactive because of their heada-che and a linear relationship between low level of physi-cal activity and increased headache frequency has been demonstrated. The clinical experience and some studies have suggested that physical activity may prevent migra-ine attacks. However the effect of physical activity in pa-tients suffering from migraine and co-existing tension-type headache and neck-pain has not yet been investigated.

Current projectsEpidemiology of neck pain and headache. The effect of specific strength training and the role of muscle strength in neck pain in tension-type headache and migraine. The effect of an exercise program in patients with migraine and co-existing tension-type headache and neck pain.

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CollaborationProfessor Tim Steiner, Division of Neuroscience and Men-tal Health, Imperial College London, London W6 8RP, UK. Professor Karen Søgaard, Institute of sports science and clinical biomechanics, University of southern Denmark. Catharina Sjödahl Hammarlund. University Lecturer, Gun-vor Gard, professor, Department of Health Sciences, Lund University, Lund, Sweden.

Idiopathic intracranial hypertension

MembersRigmor Jensen, Hanne Yri, Maria Schmidt Uldall, Inger Jan-sen Olesen.

BackgroundIdiopathic intracranial hypertension (IIH) is an intriguing, cli-nical condition of increased intracranial pressure without pathological, laboratory or radiological evidence of intra-cranial pathology in young, obese individuals. The clinical symptoms are severe headache, pulsatile tinnitus, transi-tory visual obscurations and diplopia. Demographic stu-dies report a rapidly increasing incidence of IIH in obese young females and with the global epidemic increase of obesity a significant increase in the number of IIH patients in Denmark can be predicted. Severe obesity is closely re-lated to a number of neuroendocrinological changes which have still not been evaluated in IIH.

Untreated IIH may lead to severe visual loss and blindness resulting from damage to the optic nerve and chronic disa-bling headache. The mechanism whereby IIH leads to op-tic nerve dysfunction is poorly understood but it seems to be closely linked to oedema of the optic nerve head and the associated elevation of hydrostatic pressure inside the optic nerve.

A PhD study from this group has analysed the clinical pre-sentation in more than 40 patients detail and their heada-che characteristics, provided new suggestions for diag-nostic criteria and tested their cognitive function before and after treatment. Our new study of IIH thus comprise neurobiological and ophthalmological aspects is a unique study of still unsolved aspects in IIH.

A new experimental PhD study of the mechanisms of IIH has also been initiated in the research park. A reliable animal model for measuring the intracranial pressure over time has been developed and we continue the search for a better understanding of the CSF dynamics and regulati-on as well as for the understanding of the molecular basis for IIH.

Current projectsLong term follow-up of patients with idiopathic intracranial hypertension, ophthalmological and neurobiological aspe-cts. Biomarkers in idiopathic intracranial hypertension. Experimental models of idiopathic intracranial hypertensi-on and mechanisms of water transport in the brain.

CollaborationSteffen Hamann and Marianne Wegener, Department of Opthalmology, Glostrup Hospital.Marianne Juhler and Anders Skjolding, Department of Neu-rosurgery, National Hospital, Denmark and the Copenha-gen CSF study Group.Alexandra Sinclair and her CSF-research group, University of Birmingham, UK.

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Chronic post-traumatic headache

MembersRigmor Jensen, Dorte Kjeldgaard and Hysse Forchhammer.

BackgroundChronic post-traumatic headache (CPTH) attributed to mild head injury is still a significant mystery for patients as well as for headache experts and very costly for the so-ciety. Clear correlation between severity of injury and the persistence of symptoms over time is lacking and has led to a hypothesis of psychological aetiology to CPTH. Both pharmacological treatments as well as a psychological in-tervention have not yet shown promising results.

Current projectsDescribe a large CPTH population in detail in terms of demographics, headache characteristics and personali-ty profile and compare them to a group of patients with chronic primary headache.

A group intervention based on cognitive behavioural the-rapy, in order to provide the patients with knowledge and strategies to manage their CPTH has been conducted. The results were rather disappointing as very little pro-gress were achieved compared to the waiting list group. Further analysis is ongoing and the treatment strategy will be adjusted accordingly.

Headache in cerebrovascular disorders

MembersElena Lebedeva, Jes Olesen, Nathalia Gourary, Nathalia Kobzeva, Tatiana Tsypushkina, Anton Ushenin and Anast-asia Busygina.

JO has directed a major collaborative project with associ-ate professor Elena lebedeva, Ural State University, Jeka-terinburg, Russia. He is co-supervisor of 5 PhD students, all neurologists. The first project is completed and in the publishing phase. It is an interview study of more than 3000 Russians from 3 different social Groups. It focuses on prevalence, risk factors and previous diagnosis and tre-atment. The NeXT is a large study where more than 600 stroke patients have been interviewed in the acute phase of stroke and at least 3 months later. It contains a wealth of data and will result in 3 PhD theses. Lastly more than 300 patients with saccular intracranial aneurysm have been interviewed and have donated blood for genetic ana-lysis. Collection is still ongoing. It will result in one, maybe two PhD theses.

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1.4 Sponsors

Major sponsors:- Faculty of health and medical science, University of Copenhagen (Ph.D. grants)- Lundbeck Foundation (independent grant for genetics)- Lundbeck Foundation (independent grant for trigeminal neuralgia)- Lundbeckfoundation (independent grant for studying

mechanisms of migraine provoking substances)- Candys Foundation- The Capital Region of Denmark, Foundation for Health Research- The Danish Agency for Science, Technology and Innovation, and the Danish Council for Independent Research-Medical Sciences - European Commission, STEMBANCC project- European Commission, EUROHEAD project- IMK Foundation

Sponsors:- Danish Headache Society- The Danish Headache Foundation- Augustinus Foundation- Foundation of Lægevidenskabens Fremme- Kong Christian IX og Dronning Louises Jubilæumslegat- The Foundation for Neurological Research- Trigeminus Foreningen- Novo Nordisk Foundation - Spar Nord Foundation- Gangsted Foundation- Lykfeldts legat- The Migraine- and Headache Association (Patient Organization)- The Cluster Headache Association (Patient Organization)

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Figure 2. The research group of Messoud Ashina, who was appointed as a professor in 2014.

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2. CollaborationsDepartments within Glostrup Hospital• Department of Ophthalmology• Danish Center for Sleep Medicine• Department of Clinical Neurophysiology• Department of Clinical Experimental Research• Department of Clinical Physiology• Department of Clinical Biochemistry• Department of Diagnostics• Department of Anaesthesiology• Functional Imaging Unit, Department of Clinical Physiology and Nuclear Medicine• Stroke Unit, Department of Neurology

External collaborators

Clinical research• Department of Oral and Maxillo-Facial Surgery, National Hospital, Copenhagen • Centre for Health and Preventive Medicine, Copenhagen County, Denmark• Department of Neurosurgery, National Hospital, Copenhagen, Denmark• Danish twin registry, University of Odense, Denmark• Department of Neurology, Hillerød Hospital, Denmark• Associate Professor Elena Lebedeva, Department of emergency neurology, University of Ural Region, Yekaterinburg, Russia• Professor John-Anker Zwart, Department of Neurology, Ullevaal University

Hospital, University of Oslo, Oslo, Norway• Professor Knut Hagen, Department of Neuroscience,

Faculty of medicine, Norwegian University of Science and Technology, Trondheim, Norway

• Professor Timothy Steiner, Department of Neuro-science, Faculty of medicine, Norwegian University

of Science and Technology, Trondheim, Norway• Professor Hartmut Goebel, The Headache Clinic, Kiel University, Germany• Mondino Institute of Neurology Foundation, Pavia, Italy• Department of Physical Therapy, Department of

Health Sciences, University of Lund, Sweden• Department of Neurology, Semmelweis University,

Budapest, Hungary• PAIN Group, Mclean Hospital, Harvard University Boston USA• Optical Imaging Core & Lab at Martinos Centre Department of Radiology, Boston USA• Leiden University Medical Centre, Holland• Division of Neurological Pain Research and Therapy,

Universitätsklinikum Schleswig-Holstein, Kiel• Visual Processing Laboratory, Universitätsaugenklinik,

Otto-von-Guericke- Universität, Magdeburg • Department of Neurology and Division of Neuroradio-

logy, University Hospital Basel, Switzerland• Centre for Sensory-Motor Interaction, University of Ålborg

Basic Pain Mechanisms• Department of Pharmacology, University of Washington, Seattle, USA • Department of Medical Physiology, Faculty of Life

Sciences, Copenhagen University, Denmark• Institute of Pharmacology, Faculty of Pharmaceutical

Sciences, Copenhagen University, Denmark• Department of Biology, Bioinformatics Copenhagen

University, Denmark• Institute of Experimental Research, University of Lund, Sweden

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• Professor Karl Messlinger, Institute of Physiology and Experimental Pathophysiology, University of Erlan-gen-Nürnberg, D-91054 Erlangen, Germany

• Institute of Anatomy, Panum Institute, University of Copenhagen, Denmark• The Laboratory Animal Science group at Department

of Veterinary Disease Biology, Copenhagen University • Laboratory Animal Welfare Group, University of

Newcastle upon Tyne, United Kingdom.

Genetics and environment• DeCode, Reykjavik, Iceland• Danish twin registry• Innovative Medicing Initiative EU• International Headache Genetics Consortium• Oluf Petersen and Torben Hansen, Marie Krog Centrer

for Metabolic research, The Novo Nordisk Foundation Center for Basic Metabolic Research

Headache Epidemiology• Professor Lars-Jacob Stovner, Kompetencecenter for

epidemiology, University of Trondheim, Norway• Professor Tim Steiner, Lifting The Burden, WHO

Headache diagnosis• Professor Guiseppe Nappi, Institute Mondino, University of Pavia, Italy (EU-project)

Idiopathic Intracranial Hypertension• PhD Steffen Hamann, Dr Sci Birgit Sander and Consul-

tant Marianne Wegener, Department of Opthalmology, Glostrup Hospital

• Copenhagen CSF-study group, Professor Marianne Juhler, Department of neurosurgery, National Hospital

• University of Birmingham, UK

Cluster headache• Søren Hillerup, professor and Jørgen Rostgaard, DDS,

Department of Oromaxillofacial Surgery, National Hospital, Copenhagen, Denmark

• Anthony Carparso, Principal Clinical Scientist, Autonomic Technologies, Inc., CA, USA• Poul Jennum, Danish Center for Sleep Medicine, Glostrup Hospital

Medication-overuse headache• Dr. C. Tassorelli, Fondazione Istituto Neurologico Casimiro Mondino, Italy• Dr. M. Lainez, Fundación de la Comunidad Valenciana

para la Investigación Biomédica del Hospital Clínico Universitario De Valencia, Spain

• Dr. Z. Katsarava, Universitaetsklinikum Essen, Germany• Dr. R. Fadic, Pontificia Universidad Catolica de Chile,

Santiago, Chile• Dr. A. Stoppini, Fundacion para la Lucha contra las

Enfermedades Neurologicas de la Infancia, Buenos Aires, Argentina• Dr. Csaba Ertsey, Department of Neurology, Semmelweis University, Budapest, Hungary

Trigeminal neuralgia• Professor Ralf Baron, Division of Neurological Pain Research and Therapy, Universitätsklinikum Schleswig-Holstein, Kiel• Frauke Wolfram, Department of Diagnostics, Glostrup University Hospital, Denmark• Dr. Per Rochat, Department of Neurosurgery, The National Hospital, Copenhagen, Denmark• Dr. Jannick Brennum, Department of Neurosurgery,

The National Hospital, Copenhagen, Denmark

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• Professor, Dr Med Sci, C.G. Faber, neurologist, Department of Neurology, Maastricht University Medical Center (MUMC), Maastricht; the Netherlands

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Figure 3. The trigeminal neuralgia group (Stine Maarbjerg, Hanne Andresen, Samaira Younis and Lars Bendtsen) du-ring their visit at Professor Ralf Baron, Division of Neurological Pain Research and Therapy, Universitätsklinikum Sch-leswig-Holstein, Kiel.

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3. Publications in 2014Papers in peer-reviewed scientific journals

1. Amin,F.M., Hougaard,A., Schytz,H.W., Asghar,M.S., Lund-holm,E., Parvaiz,A.I., de Koning,P.J., Andersen,M.R., Lars-son,H.B., Fahrenkrug,J., Olesen,J. & Ashina,M. (2014a) Investigation of the pathophysiological mechanisms of migraine attacks induced by pituitary adenylate cy-clase-activating polypeptide-38. Brain., 137, 779-794.

2. Amin,F.M., Lundholm,E., Hougaard,A., Arngrim,N., Wiinberg,L., de Koning,P.J., Larsson,H.B. & Ashina,M. (2014b) Measurement precision and biological varia-tion of cranial arteries using automated analysis of 3 T magnetic resonance angiography. J.Headache Pain., 15:25. doi: 10.1186/1129-2377-15-25., 25-15.

3. Arngrim,N., Schytz,H.W., Asghar,M.S., Amin,F.M., Hou-gaard,A., Larsen,V.A., de Koning,P.J., Larsson,H.B., Ole-sen,J. & Ashina,M. (2014a) Association of acetazola-mide infusion with headache and cranial artery dilation in healthy volunteers. Pain., 155, 1649-1658.

4. Arngrim,N., Schytz,H.W., Hauge,M.K., Ashina,M. & Ole-sen,J. (2014b) Carbon monoxide may be an important molecule in migraine and other headaches. Cephalal-gia., 34, 1169-1180.

5. Barloese,M., Jennum,P., Lund,N., Knudsen,S., Gammel-toft,S. & Jensen,R. (2014a) Reduced CSF hypocretin-1 levels are associated with cluster headache. Cephalal-gia., 0333102414562971.

6. Barloese,M., Lund,N. & Jensen,R. (2014b) Sleep in trigeminal autonomic cephalagias: a review. Cephalal-gia., 34, 813-822.

7. Bendtsen,L., Munksgaard,S., Tassorelli,C., Nappi,G., Katsarava,Z., Lainez,M., Leston,J., Fadic,R., Spadafor-a,S., Stoppini,A. & Jensen,R. (2014) Disability, anxiety and depression associated with medication-overuse

headache can be considerably reduced by detoxifica-tion and prophylactic treatment. Results from a mul-ticentre, multinational study (COMOESTAS project). Cephalalgia., 34, 426-433.

8. Bhatt,D.K., Gupta,S., Olesen,J. & Jansen-Olesen,I. (2014a) PACAP-38 infusion causes sustained vasodi-lation of the middle meningeal artery in the rat: possible involvement of mast cells. Cephalalgia., 34, 877-886.

9. Bhatt,D.K., Gupta,S., Ploug,K.B., Jansen-Olesen,I. & Ole-sen,J. (2014b) mRNA distribution of CGRP and its re-ceptor components in the trigeminovascular system and other pain related structures in rat brain, and effe-ct of intracerebroventricular administration of CGRP on Fos expression in the TNC. Neurosci.Lett., 559:99-104. doi: 10.1016/j.neulet.2013.11.057. Epub;%2013 Dec 7., 99-104.

10. Dodick,D.W., Goadsby,P.J., Silberstein,S.D., Lipton,R.B., Olesen,J., Ashina,M., Wilks,K., Kudrow,D., Kroll,R., Ko-hrman,B., Bargar,R., Hirman,J. & Smith,J. (2014) Safe-ty and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: a randomised, double-blind, place-bo-controlled, exploratory phase 2 trial. Lancet Neurol., 13, 1100-1107.

11. Dullaart,R.P., Al-Daghri,N.M., Ashina,M., Bouzas-Mo-squera,A., Brunetti,N.D., Buechler,C., Chen,H.S., Corrales,J.J., D’Archivio,M., Dei,C.A., Pino,G.G., Go-mez-Abril,S.A., Gyori,D., Haslacher,H., Herder,C., Ker-stens,M.N., Koutsilieris,M., Lombardi,C., Lupattelli,G., Mocsai,A., Msaouel,P., Orfao,A., Ormazabal,P., Pacher,R., Perkmann,T., Peteiro,J., Plischke,M., Reynaert,N.L., Ric-ci,M.A., Robles,N.R., Rocha,M., Rutten,E.P., Sabico,S., Santamaria,F., Santoro,F., Schmid,A., Schmidt,M., Schytz,H.W., Shyu,K.G., Tada,H., Thorand,B., Valerio,G., Vesely,D.L., Wu,T.E., Yamagishi,M. & Yeh,Y.T. (2014) Re-search update for articles published in EJCI in 2012.

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Eur.J.Clin.Invest., 44, 1010-1023.12. Ezzatian-Ahar,S., Amin,F.M., Obaid,H.G., Arngrim,N.,

Hougaard,A., Larsson,H.B. & Ashina,M. (2014) Migraine without aura is not associated with incomplete circle of Willis: a case-control study using high-resolution magnetic resonance angiography. J.Headache Pain., 15:27. doi: 10.1186/1129-2377-15-27., 27-15.

13. Gaist,D., Gonzalez-Perez,A., Ashina,M. & Rodriguez,L.A. (2014) Migraine and risk of hemorrhagic stroke: a stu-dy based on data from general practice. J.Headache Pain., 15:74. doi: 10.1186/1129-2377-15-74., 74-15.

14. Gram,B., Andersen,C., Zebis,M.K., Bredahl,T., Peder-sen,M.T., Mortensen,O.S., Jensen,R.H., Andersen,L.L. & Sjogaard,G. (2014) Effect of training supervision on effectiveness of strength training for reducing neck/shoulder pain and headache in office workers: cluster randomized controlled trial. Biomed.Res.Int., 2014:693013. doi: 10.1155/2014/693013. Epub;%2014 Feb;%19., 693013.

15. Guo,S., Barringer,F., Zois,N.E., Goetze,J.P. & Ashina,M. (2014a) Natriuretic peptides and cerebral hemody-namics. Regul.Pept., 192-193:15-23. doi: 10.1016/j.regpep.2014.07.003. Epub;%2014 Aug 6., 15-23.

16. Guo,S., Olesen,J. & Ashina,M. (2014b) Phosphodieste-rase 3 inhibitor cilostazol induces migraine-like attacks via cyclic AMP increase. Brain., 137, 2951-2959.

17. Guo,S., Shalchian,S., Gerard,P., Kuper,M., Katsarava,Z., Ashina,M. & Schoenen,J. (2014c) Prevalence of right-to-left shunts on transcranial Doppler in chronic migra-ine and medication-overuse headache. Cephalalgia., 34, 37-41.

18. Hansen,J.M. & Ashina,M. (2014) Calcitonin gene-rela-ted peptide and migraine with aura: A systematic re-view. Cephalalgia., 34, 695-707.

19. Hougaard,A., Amin,F.M. & Ashina,M. (2014a) Migraine and structural abnormalities in the brain. Curr.Opin.

Neurol., 27, 309-314.20. Hougaard,A., Amin,F.M., Hoffmann,M.B., Rostrup,E.,

Larsson,H.B., Asghar,M.S., Larsen,V.A., Olesen,J. & As-hina,M. (2014b) Interhemispheric differences of fMRI responses to visual stimuli in patients with side-fixed migraine aura. Hum.Brain Mapp., 35, 2714-2723.

21. Jansen-Olesen,I., Baun,M., Amrutkar,D.V., Ramachan-dran,R., Christophersen,D.V. & Olesen,J. (2014) PA-CAP-38 but not VIP induces release of CGRP from trigeminal nucleus caudalis via a receptor distinct from the PAC1 receptor. Neuropeptides., 48, 53-64.

22. Jensen,R.H. & Bendtsen,L. (2014) Tension-Type Headache. Case-Based Diagnosis and Management of Headache Disorders, Headache. Springer International, Switzerland.

23. Jurgens,T.P., Schoenen,J., Rostgaard,J., Hillerup,S., Lai-nez,M.J., Assaf,A.T., May,A. & Jensen,R.H. (2014) Stimu-lation of the sphenopalatine ganglion in intractable clu-ster headache: Expert consensus on patient selection and standards of care. Cephalalgia., 34, 1100-1110.

24. Khan,S., Schoenen,J. & Ashina,M. (2014) Sphenopala-tine ganglion neuromodulation in migraine: what is the rationale? Cephalalgia., 34, 382-391.

25. Kjeldgaard,D., Forchhammer,H., Teasdale,T. & Jen-sen,R.H. (2014a) Chronic post-traumatic headache after mild head injury: a descriptive study. Cephalalgia., 34, 191-200.

26. Kjeldgaard,D., Forchhammer,H., Teasdale,T. & Jensen,R. (2014b) Cognitive behavioural treatment for the chronic post-traumatic headache patient: a randomized con-trolled trial. The Journal of Headache and Pain, 15, 81.

27. Lampl,C., Jensen,R., Martelletti,P. & Mitsikostas,D.D. (2014) Refractory headache: one term does not cover all--a statement of the European Headache Federati-on. J.Headache Pain., 15:50..

28. Lempert,T. & Olesen,J. (2014) Migraine vestibulaire :

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critères diagnostiques. Document consensuel de la Société Bárány et de la Société internationale des cép-halées. Revue Neurologique, 170, 401-406.

29. Li,D., Christensen,A.F. & Olesen,J. (2014) Field-te-sting of the ICHD-3 beta/proposed ICD-11 diag-nostic criteria for migraine with aura. Cephalalgia., 0333102414559731.

30. Lund,N., Westergaard,M.L., Barloese,M., Glumer,C. & Jensen,R.H. (2014) Epidemiology of concurrent heada-che and sleep problems in Denmark. Cephalalgia., 34, 833-845.

31. Maarbjerg,S., Gozalov,A., Olesen,J. & Bendtsen,L. (2014a) Concomitant persistent pain in classical trigeminal neuralgia--evidence for different subtypes. Headache., 54, 1173-1183.

32. Maarbjerg,S., Gozalov,A., Olesen,J. & Bendtsen,L. (2014b) Trigeminal neuralgia--a prospective syste-matic study of clinical characteristics in 158 patients. Headache., 54, 1574-1582.

33. Martelletti,P., Katsarava,Z., Lampl,C., Magis,D., Bendt-sen,L., Negro,A., Russell,M.B., Mitsikostas,D.D. & Jen-sen,R.H. (2014) Refractory chronic migraine: a consen-sus statement on clinical definition from the European Headache Federation. J.Headache Pain., 15:47. doi: 10.1186/1129-2377-15-47., 47-15.

34. Mitsikostas,D., Edvinsson,L., Jensen,R., Katsarava,Z., Lampl,C., Negro,A., Osipova,V., Paemeleire,K., Siva,A., Valade,D. & Martelletti,P. (2014) Refractory chronic clu-ster headache: a consensus statement on clinical de-finition from the European Headache Federation. The Journal of Headache and Pain, 15, 79.

35. Moore,R.A., Derry,S., Wiffen,P.J., Straube,S. & Bendt-sen,L. (2014) Evidence for efficacy of acute treatment of episodic tension-type headache: methodological critique of randomised trials for oral treatments. Pain., 155, 2220-2228.

36. Munksgaard,S.B. & Jensen,R.H. (2014) Medication overuse headache. Headache., 54, 1251-1257.

37. Olesen,J. (2014a) Highlights in headache research in 2013. Lancet Neurol., 13, 5-7.

38. Olesen,J. (2014b) Problem areas in the Internatio-nal Classification of Headache Disorders, 3rd edition (beta). Cephalalgia., 34, 1193-1199.

39. Peck,C.C., Goulet,J.P., Lobbezoo,F., Schiffman,E.L., Alstergren,P., Anderson,G.C., de,L.R., Jensen,R., Mi-chelotti,A., Ohrbach,R., Petersson,A. & List,T. (2014) Expanding the taxonomy of the diagnostic criteria for temporomandibular disorders. J.Oral Rehabil., 41, 2-23.

40. Petersen,A.S., Barloese,M.C. & Jensen,R.H. (2014) Oxy-gen treatment of cluster headache: A review. Cephalal-gia., 34, 1079-1087.

41. Ramachandran,R., Bhatt,D.K., Ploug,K.B., Hay-Sch-midt,A., Jansen-Olesen,I., Gupta,S. & Olesen,J. (2014) Nitric oxide synthase, calcitonin gene-related peptide and NK-1 receptor mechanisms are involved in GTN-in-duced neuronal activation. Cephalalgia., 34, 136-147.

42. Schiffman,E., Ohrbach,R., Truelove,E., Look,J., An-derson,G., Goulet,J.P., List,T., Svensson,P., Gonza-lez,Y., Lobbezoo,F., Michelotti,A., Brooks,S.L., Ceu-sters,W., Drangsholt,M., Ettlin,D., Gaul,C., Goldberg,L.J., Haythornthwaite,J.A., Hollender,L., Jensen,R., John,M.T., De,L.A., de,L.R., Maixner,W., van der Meulen,M., Mur-ray,G.M., Nixdorf,D.R., Palla,S., Petersson,A., Pionchon,P., Smith,B., Visscher,C.M., Zakrzewska,J. & Dworkin,S.F. (2014) Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for Clinical and Research Appli-cations: recommendations of the International RDC/TMD Consortium Network* and Orofacial Pain Special Interest Groupdagger. J.Oral Facial.Pain Headache., 28, 6-27.

43. Schytz,H.W., Ashina,M., Magyari,M., Larsen,V.A., Ole-

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sen,J. & Iversen,H.K. (2014) Acute headache and persistent headache attributed to cervical artery dis-section: Field testing of ICHD-III beta. Cephalalgia., 34, 712-716.

44. Schytz,H.W. & Bendtsen,L. (2014) Sumatriptan plus naproxen for acute migraine attacks in adults. Ugeskr.Laeger., 176, V03140155.

45. Steiner,T.J., Gururaj,G., Andree,C., Katsarava,Z., Ayzen-berg,I., Yu,S.Y., Al,J.M., Tekle-Haimanot,R., Birbeck,G.L., Herekar,A., Linde,M., Mbewe,E., Manandhar,K., Risal,A., Jensen,R., Queiroz,L.P., Scher,A.I., Wang,S.J. & Stov-ner,L.J. (2014) Diagnosis, prevalence estimation and burden measurement in population surveys of heada-che: presenting the HARDSHIP questionnaire. J.Heada-che Pain., 15, 3-15.

46. Stovner,L.J., Al,J.M., Birbeck,G.L., Gururaj,G., Jensen,R., Katsarava,Z., Queiroz,L.P., Scher,A.I., Tekle-Haimanot,R., Wang,S.J. & Steiner,T.J. (2014) The methodology of po-pulation surveys of headache prevalence, burden and cost: Principles and recommendations from the Global Campaign against Headache. J.Headache Pain., 15, 5-15.

47. Tassorelli,C., Jensen,R., Allena,M., De,I.R., Sances,G., Katsarava,Z., Lainez,M., Leston,J., Fadic,R., Spadafor-a,S., Pagani,M. & Nappi,G. (2014) A consensus protocol for the management of medication-overuse heada-che: Evaluation in a multicentric, multinational study. Cephalalgia., 34, 645-655.

48. Tfelt-Hansen,P. (2014a) Is orally inhaled dihydroergo-tamine (DHE) equivalent in efficacy in migraine to intra-venous DHE? Headache., 54, 383.

49. Tfelt-Hansen,P. (2014b) Why is guanfacine recom-mended by AHS and ANN for migraine prevention? Headache., 54, 754-755.

50. Tfelt-Hansen,P.C. & Diener,H.C. (2014) Use of dihydro-ergotamine (DHE) should be restricted to no more than twice a week. Headache., 54, 1523-1525.

51. Tfelt-Hansen,P.C. & Hougaard,A. (2014) Migraine: Diffe-rential effects of placebos in migraine clinical trials. Nat.Rev.Neurol., 10, 10-11.

52. Tfelt-Hansen,P.C., Pihl,T., Hougaard,A. & Mitsikostas,D.D. (2014) Drugs targeting 5-hydroxytryptamine recep-tors in acute treatments of migraine attacks. A review of new drugs and new administration forms of esta-blished drugs. Expert.Opin.Investig.Drugs., 23, 375-385.

53. Tronvik,E., Sorensen,T., Linde,M., Bendtsen,L., Artto,V., Laurell,K., Kallela,M., Zwart,J.A. & Hagen,K. (2014) The relationship between headache and religious at-tendance (the Nord-Trondelag health study-HUNT). J.Headache Pain., 15:1. doi: 10.1186/1129-2377-15-1., 1-15.

54. Uldall,M., Juhler,M., Skjolding,A.D., Kruuse,C., Jan-sen-Olesen,I. & Jensen,R. (2014) A novel method for long-term monitoring of intracranial pressure in rats. J.Neurosci.Methods., 227, 1-9.

55. Westergaard,M.L., Glumer,C., Hansen,E.H. & Jensen,R.H. (2014a) Prevalence of chronic headache with and without medication overuse: Associations with soci-oeconomic position and physical and mental health status. Pain., 155, 2005-2013.

56. Westergaard,M.L., Hansen,E.H., Glumer,C., Olesen,J. & Jensen,R.H. (2014b) Definitions of medication-over-use headache in population-based studies and their implications on prevalence estimates: a systematic review. Cephalalgia., 34, 409-425.

57. Yri,H.M., Fagerlund,B., Forchhammer,H.B. & Jensen,R.H. (2014a) Cognitive function in idiopathic intracranial hypertension: a prospective case-control study. BMJ Open., 4, e004376.

58. Yri,H.M. & Jensen,R.H. (2014) Idiopathic intracranial hypertension: Clinical nosography and field-testing of the ICHD diagnostic criteria. A case-control study. Cephalalgia., 0333102414550109.

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59. Yri,H.M., Ronnback,C., Wegener,M., Hamann,S. & Jen-sen,R.H. (2014b) The course of headache in idiopathic intracranial hypertension: a 12-month prospective fol-low-up study. Eur.J.Neurol., 21, 1458-1464.

Doctoral Thesis1. Kruuse, C. Role of phosphodiesterase 5 and cGMP

signalling in cerebral arteries, cerebral blood flow, and headache - contributions to understanding migraine pathophysiology. Faculty of Health Sciences, Universi-ty of Copenhagen, 2014.

PhD Theses1. Yri, HM. Idiopathic intracranial hypertension - Exploring

headache and cognitive function. Faculty of Health Sciences, University of Copenhagen, 2014.

2. Hougaard, A. Investigations of functional and structural changes in migraine with aura by magnetic resonan-ce imaging. Faculty of Health Sciences, University of Copenhagen, 2014.

3. Kjeldgaard, DN. Personality profile and psychological treatment of patients with chronic post-traumatic headache. Faculty of Health Sciences, University of Copenhagen, 2014.

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4. Clinical Activities in DHCThe clinical activities in DHC consist of a multidisciplinary out-patient service and an in-patient service. At the end of 2014 the staff consisted of 3 psychologists (one on maternity leave), 4 physical therapists (hereof 2 PhD stu-dents), 4 nurses, 1 team leader, 1 laboratory technician, 9 secretaries, 7 neurologists specialized in headache (all part time), 1 dentist (one day per month) and a variable number of younger physicians on rotation (all part time). In addition, the nursing staff at the Department of Neuro-logy N 38 take care of the in-patients in close collaboration with DHC.

The out-patient activities continued on a high level in 2014. A total of 3,185 patients were treated in the centre during 2014. Approximately 120 patients have been trea-ted at the in-patient department N 38.

A total of 65% of patients were referred from The Capital Region, while the rest of patients were referred from other parts of Denmark and Scandinavia.

Migraine is the most common disorder seen in out cen-tre followed by cluster headache, tension-type headache and medication-overuse headache (Figure 4). Almost all these patients have previously been seen by several physicians including neurologists and have been referred to DHC, because they are highly disabled and considered treatment resistant. Because of the tertiary nature of our centre, we manage a relatively high number of patients suffering from the excruciating painful disorders cluster headache and trigeminal neuralgia.

Distribution of main diagnosis in patients with headache disorders and facial pain treated in 2014

Figure 4. Migraine, medication-overuse headache, tensi-on-type headache, cluster headache and combinations hereof are the most common types of headache seen in the centre. Figures add up to more than 100%, because several of our patients suffer from more than disorder.

40% Migraine16% Medication-overuse headache24% Tension-type headache14% Cluster headache08% Trigeminal neuralgia04% Atypical facial pain05% Idiopathic intracranial hypertension06% Post traumatic headache06% Other headache conditions

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The in-patient headache serviceSix beds at the Department of Neurology N 38 are alloca-ted to the in-patient programme. The majority of patients are suffering from medication-overuse and are admitted for detoxification. In addition, patients suffering from other types of headache can be admitted for observation, cer-tain specialized diagnostic procedures or treatment that requires hospitalization. The medication-overuse patients are all primarily seen on an out-patient basis in the Cen-tre and then admitted for a fixed in-patient period of 14 days where they follow a structured regime. After dischar-ge they are closely followed as out-patients in DHC for at least one year.

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5. Teaching and public activitiesTeaching activitiesHeadache disorders. Clinical course for neurologists, gene-ral practitioners and younger doctors. Glostrup Hospital, May, 2014.Medical students, Faculty of Health Sciences, University of Copenhagen.Neurology trainees, Faculty of Health Sciences, University of Copenhagen.Trainees from General Practise, an essential part of their educational programme.PhD students, Faculty of Health Sciences, University of Copenhagen.General practitioners at Læge Dage, the annual national congress for general practitioners.In addition, numerous teaching activities at international and national congresses.

Public activitiesOver the years the Danish Headache Center has organi-zed the annual public meeting at Glostrup Hospital for patients, relatives and other with an interest in headache and facial pain. In 2014 the event was held in Bellacentret during the EHMTIC 2014 and organized in close collabora-tion with the Patient organization Hovedpinesagen. More than 120 participants attended and the event was very successful with lively discussion. The event was chaired by Peter Quortrup Geisling, the TV-doctor from DR who entertained the audience successfully along with a lively discussion and multiple questions to the scientific panel with updates from the scientific congress. The patient day was introduced by Audrey Craven the president for The European Headache Alliance and Director Wendy Thomas from the Migraine Trust in UK exchanged valuable experi-ence about their patient organisation and activities in UK.Staff from the Danish Headache Center has been intervie-wed on national television and radio more than 10 times in

2014 and contributed to several public meetings arranged by the Danish patient organizations. The staff has contri-buted to numerous articles in Danish newspapers and other media during the year.

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Figure 5. Rigmor Jensen together with Helle Jensby, Jane Sandby-Møller, Karin Aagaard, Ane Lundgaard Dahl and Di-anna Bartolin from DHC during the 4th European Headache and Migraine Trust International Congress in Copenhagen in September.

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6. Organization and Staff in DHCManagementRigmor Jensen - Professor, MD, DMSci. Director of The Danish Headache Centre.Jes Olesen - Professor, MD, DMSci. Founder and co-director of The Danish Headache Centre.Lars Bendtsen - MD, Ph.D., DMSci, associate professor. Co-director of The Danish Headache Centre.Helle Jensby - BSc Economics and business adm., Med. sec. Team leader in The Danish Headache Centre.

Staff NeurologistsPeer Tfelt-Hansen - MD, DMSc.Messoud Ashina - MD, Ph.D., DMSc, associate professor. Director of Human Migraine Research Unit.Thue Hjortkær Nielsen – MD, senior consultant. Leader of the department of inpatient treatment of headache patients.Aydin Gozalov - MD, PhD, senior consultant. Co-leader of trigeminal neuralgia research.Vlasta Vukovic Cvetkovic - MD, PhD, senior consultant.

Medical secretariesKarin AagaardKatrine KristensenTina Würgler KærgaardJane Sandby-MøllerDorte HelmundtLis JønssonDianna BartolinAne Lundgaard DahlGitte Ellesgaard SørensenMalou Sandvær Harrild

PhysiotherapistsBjarne Kjeldgaard MadsenNina CaspersenJeanne René HirsvangLotte Skytte Krøll

Laboratory technicianHanne Andresen

PsychologistsDorthe Kjeldgaard NielsenTrine ZimmerCamilla Bjørbæk Møller (maternity leave)Kirsten Larsen

NursesAnnette Vangaa RasmussenAnnette Fjeldborg Jonasson Hjørdis Rasmussen (nurse assistent)Malene Kjærgaard Danø

PsychiatristAndreas Tang Varnild-Jørgensen, Centre of Psychiatry, Glostrup

Dental expertiseDr. odont. Merete Bakke, University of Copenhagen

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7. FutureTraditionally there is quite limited collaboration between pain specialists and headache specialists. This should not be so. From January 1st, 2015 our centre is part of Rigsho-spitalet due to the fusion of Rigshospitalet Blegdamsvej and Glostrup Hospital. This will provide new possibilities for collaboration between pain specialists from Rigshospi-talet Blegdamsvej, Rigshospitalet Glostrup and DHC. We have much to learn from each other regarding both clinical and research activities. We are planning a closer collabora-tion between the two specialities along with other excel-lent opportunities for collaboration between highly specia-lized departments. We expect that this will further improve the treatment possibilities we can offer to our patients.

The demand for qualified management of headache and facial pain continues to increase. At the same time we lack senior doctors with special knowledge on headache and we are facing increased demands for documentation and implementation of computer programs which are often not functioning optimally. Together this results in unaccep-tably long waiting lists for our patients. We will work hard to solve this by increasing our efforts for recruiting talen-ted doctors from Denmark or abroad into our field and to handle the registration and computer issues in the most efficient way. At the same time we will consider how the development in registration requirements and digitalizati-on of our clinical work can improve our possibilities for cli-nical research.

We will continue to focus on our most important task – the management that we can offer to every single patient. Our wonderful staff is the key here – only by offering the highest standards from every member of our multidiscipli-nary team can we achieve our ultimate goal – to provide the best care for patients with headache and facial pain in the world.

Danish Headache CenterDepartment of Neurology,Rigshospitalet, Glostrup, University of Copenhagen

www.danishheadachecenter.dk