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2008Annual ReportDanish Headache Centre

Department of NeurologyGlostrup Hospital, University of Copenhagenwww.danishheadachecenter.com

Table of contents

1. Organization and staff . . . . . . . . . . . . . . .2

2. Clinical activities . . . . . . . . . . . . . . . . . . .4

3. Research . . . . . . . . . . . . . . . . . . . . . . . . .7

3.1 Organization . . . . . . . . . . . . . . . . . . .7

3.2 Research staff . . . . . . . . . . . . . . . . . .8

3.3 Research areas. . . . . . . . . . . . . . . . . .9

3.4 Sponsors . . . . . . . . . . . . . . . . . . . . .16

4. Collaborations . . . . . . . . . . . . . . . . . . . .16

5. Teaching activities . . . . . . . . . . . . . . . . .18

6. Future research areas . . . . . . . . . . . . . .19

7. Publications in 2008 . . . . . . . . . . . . . . .20

8. Perspectives . . . . . . . . . . . . . . . . . . . . .24

Danish Headache Center · Annual Report 2008 1

Preface

This annual report provides an overview of the clinical and research activities that took

place at The Danish Headache Center in 2008.

The clinical activities have been maintained at a very high level both in terms of

productivity and quality thanks to our highly committed staff members. Most important,

the feedback from the patients continues to be very positive.

In order to continuously improve the quality of the clinical work several new treatments

have been introduced in 2008. A new treatment programme for patients with

posttraumatic headache has been introduced as well as a new treatment programme

using functional electrical stimulation for patients with headache due to increased

contraction of jaw muscles. A large project comparing two different treatments for patients

with medication-overuse headache has been started. Furthermore, we are planning to

introduce new treatment strategies for severely affected cluster headache patients.

The research at The Danish Headache Center and the affiliated Glostrup Research Park

continues to be very active with a high number of publications and a large impact factor.

In 2008 no less than 6 Ph.D-theses were successfully defended by our young

researchers. Congratulations.

The European Headache Summer School was held in Baku, Azerbaijan in May. It was

arranged by Messoud Ashina and Rigmor Jensen in collaboration with Professor Rena

Shiraliyeva, Dept. of Neurology, Republican Clinical Hospital, Baku, Azerbaijan and was

a great success.

Additional information can be found at our homepage: www.danishheadachecenter.com

Glostrup, April 2009

Lars Bendtsen

2 Danish Headache Center · Annual Report 2008

1. Organization and Staff

Management

Rigmor Jensen - Professor, MD, DrMedSci. Director of The Danish Headache Center.

Jes Olesen - Professor, MD, DrMedSci. Founder and co-director of The Danish

Headache Center.

Lars Bendtsen - MD, Ph.D., DrMedSci, associate professor. Co-director of The Danish

Headache Center.

Helle Jensby - BSc Economics and business adm., Med. sec. Team leader in The Danish

Headache Center.

Staff Neurologists

Peer Tfelt-Hansen - MD, DrMedSci, associate professor.

Messoud Ashina - MD, Ph.D., DrMedSci, associate professor. Director of Human

Migraine Research Group.

Peter Thede Schmidt-Hansen - MD, Ph.D. Leader of department of inpatient treatment of

headache patients, senior consultant.

Thue Hjortkær Nielsen – MD. Senior consultant.


Secretaries

Helle Jensby (Team leader)

Katrine Kristensen

Karin Aagaard

Pernille Sellelbjerg-Andersen

Jane Sandby

Dorte Helmundt

Birgitte Suhr

Lis Jønsson

Tina Kærgaard

Physio-therapists

Bjarne Madsen

Nina Caspersen

Jeanne Hirsvang

Psychologists

Dorthe Kjeldgaard Nielsen

Bruno Vinter

Trine Zimmer

Nurses

Annette Vangaa Rasmussen

Hjørdis Rasmussen (assistent)

Annette Jonassen

Psychiatrist Marianne Nilsson, Department of

Psychiatry, Glostrup Hospital

Gynecologist

Birgit Hansen, Department of

Gynecology, Glostrup Hospital

Dental expertise Professor, dr. odont Peter Svensson

Department of Oral Physiology, Institute

of Odontology, University of Aarhus

Anaesthesiologist

Jonna Fomsgaard, Department of

Anaesthesiology, Glostrup Hospital


2. Clinical Activities

The clinical activities in DHC consist of a multidisciplinary out-patient service and an in-

patient service. At the end of 2008 the staff consisted of 3 psychologists, 3 physical

therapists, 3 nurses, 1 team leader, 1 laboratory technician, 7 secretaries (several part

time jobs), 7 neurologists specialized in headache (all part time), 1 psychiatrist (one day

per week), 1 dentist (one day per month) and a variable number of younger physicians

(all part time). In addition, nurses at the Department of Neurology N 38 take care of the

in-patients.

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Figure 1. The patient flow in the Danish Headache Center in 2008.

The multidisciplinary out-patient activities in 2008 are shown in figure 1. The intake was

1.087 new patients and 687 patients were discharged. A total of 2.484 patients were

treated in the center during 2008. The total number of visits in the out-patient clinic was

8.304. In addition there was a number of telephone contacts. By the end of the year

2.502 patients were in active treatment. Approximately 120 patients have been treated at

the in-patient department N 38.

A total of 66% of patients were referred from Region Hovedstaden, i.e., the county of

Copenhagen, the City of Copenhagen and Northern Zealand, while the rest of patients

were referred from other parts of Denmark (and 12 patients from foreign countries).


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Age group

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60-69

50-59

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500

400

300

200

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Sex

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Female

Figure 2. Numbers of patients by gender and age in 2008 (n=2.486). The female/male

ratio was 2.3 and the mean age of our patients was 42 years with a range from 8 to 90

years.


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Migraine

Medication-overuse

headache

Tension-type headache

Cluster headache

Trigeminal neuralgia

Post traumatic headache

Other headache conditions

Figure 3. Migraine, medication-overuse headache and tension-type headache are the

most common types of headache seen in the center.

The in-patient headache service

Six beds at the Department of Neurology N38 are allocated 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, certain specialized diagnostic procedures or treatment that

requires hospitalization. The medication-overuse patients are all primarily seen on an out-

patient basis in the Centre and then admitted for a fixed in-patient period of 14 days and

follow a structured regime. After discharge they are closely followed as out-patients in

DHC for at least one year.


3. Research

3.1 Organization

Danish Headache Center has a vigorous research group including 7 senior researchers,

21 Ph.D. students mostly MD’s and medical students. The organization of research is

shown in Figure 4.

Figure 4. Organization of Research.

Nursing, physiotherapy and

psychology

Rigmor Jensen

Clinical Trials Messoud Ashina P Tfelt-Hansen

Jes Olesen

Molecular

mechanisms

Christina Kruuse Tension-type

Headache

Lars Bendtsen

Genetics and environment

Jes Olesen

Neurobiology of Migraine

Inger Olesen Saraub Gupta

Jes Olesen

Human migraine models

Messoud Ashina P Tfelt-Hansen

Jes Olesen

Epidemiology

IIH

Rigmor Jensen

DHC

Rigmor Jensen Jes Olesen

Lars Bendtsen


3.2 Research Staff

Senior scientists:

Jes Olesen

Rigmor Jensen

Lars Bendtsen

Messoud Ashina

Inger Jansen Olesen

Christina Kruuse

Saraub Gubta

Associate senior researchers:

Lise Lykke Thomsen

Peter Schmidt-Hansen

Technologists:

Hanne Andresen

Lene Elkjær

Kirsten Brunsgaard

Administrative assistants:

Kirsten Hjelm

Susie Andersen

Karin Aagård

Ph.D.students:

Henrik Winther Schytz

Lars Schack Kruuse

Sohail Agshar

Line Buchgreitz

Kim Lindelof

Louise Susanne Juhl Boni

Kenneth Beri Plough

Jakob Møller Hansen

Troels Wienecke

Anne Werner Hauge

Maren Skau

Helle Wulf

Michael Baun

Han Le

Signe Bruun Munksgaard

Dorthe Phillip

Maja Myren

Dipak Vasantrao Amrutkar

Deepak Kumar Bhatt

Roshni Ramachandran

Julie Carøe Kristensen


3.3 Research Areas

Human migraine models

Members

Messoud Ashina, Sohail Asghar, Jakob Møller Hansen, Henrik Schytz, Troels Wienecke,

Dorte Phillip and Jes Olesen.

Background

Fast tracking of new drugs for migraine have faced the major challenge of poorly-

predictive preclinical models. Indeed, novel, migraine-specific preventive drugs have not

been developed in decades. Furthermore, the acute therapy armamentarium remains

suboptimal, with no new chemical entities since the triptans. On the other hand, human

experimental studies are surfacing as a powerful tool in targeted migraine therapy. To this

end, human studies have identified three novel targets: inhibitors of cortical spreading

depression, antagonists of calcitonin gene-related receptors, and chemicals that prevent

the production of nitric oxide. Two of these novel mechanisms are in phase 3 clinical

development and one is in phase 2. These encouraging observations, which are based

on 20 years of research in human models, have led us to develop a research paradigm

for the identification of novel migraine drug targets, which combines human provocation

studies and preclinical models.

Current projects

• GTN and CGRP models of migraine in patients with genetically explained

hemiplegic migraine and migraine with aura

• Carbachol and PACAP models of migraine in patients with migraine without aura

• Role of prostaglandins in migraine pathophysiology: PGI2, PGE2 and PGD2

models of headache

• Activation of trigeminal pain pathways during different sequences of CGRP

induced migraine attack: fMRI study

Collaboration

Henrik Larsson and Adam Espe Hansen (Department of Clinical Physiology); Vibeke

Andre Larsen (Department of Radiology); EUROHEAD (www.eurohead.org); David

Borsook and Lino Becerra, PAIN Group, Mclean Hospital, Harvard University Boston

USA; David A Boas, Optical Imaging Core & Lab at Martinos Center Department of

Radiology, Boston USA; Professor Hayrunnisa Bolay, Department of Neurology, Gazi

University Hospitals, Ankara, Turkey.


Tension-type headache

Members

Lars Bendtsen, Line Buchgreitz, Kim Lindelof, Peter Schmidt-Hansen, Rigmor Jensen.

Background

Increased 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. Experimental 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.

Current projects

Investigations of muscular pain sensitivity, processing, and modulation of peripheral

nociceptive input in the central nervous system.

Collaboration

Professor Jens Elrich; Center for Sensory-Motor Interactions, Department of Health

Science and Technology, Aalborg University, Denmark. Professor Lars Arendt Nielsen,

Center for Sensory-Motor Interactions, Department of Health Science and Technology,

Aalborg University, Denmark.

Epidemiology

Members

Line Buchgreitz, Rigmor Jensen.

Background

Epidemiology is the study of the distribution and determinants of health-related states or

events in specified populations. The Glostrup County population study from 1989 was the

first prevalence study of specific headache entities in a representative general population,

based on a structured interview and examination by a physician. This study demonstrated

the huge impact headache has on individuals and society. A follow-up study showed an

increase in frequency and health care utilisation and thereby indicated a higher impact of

headache in 2001 that in 1989. Risk factors for migraine were young age, female gender,

familial disposition, no vocational education, high work load and frequent tension-type

headache. For tension-type headache risk factors were young age, female gender, poor


self-rated health, inability to relax after work, and sleeping fewer hours per night. In

general migraine and tension-type headache had a favourable prognosis with increasing

age and only a minority of subjects had increased headache frequency. Prognostic

factors were identified.

Current projects

Supplementary dataanalysis of the large follow-up study is ongoing with specific focus on

chronification, clinical headache characteristics and socioeconomic impact. A large

clinical study of patients treated at the Danish Headache Center has already been

conducted with main focus on medication overuse headache. It has been demonstrated

that detoxification have a very positive outcome, especially in migraineurs and that these

patients becomes reactive to migraine prophylactics again. Several new projects focusing

on specific treatment results and neurobiological mechanisms underlying medication

overuse headache are ongoing.


Members

Anne Hauge, Han Le, Jes Olesen.

Background

Family studies and twin studies show that the risk of migraine is 50% inheritance and

50% environment. The identification 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.

Current projects

One 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

more than 1400 migraine patients and the molecular genetic analyses have been

initiated. In twin studies we try to identify the most important environmental risk factors for

migraine.

Intracellular transduction mechanisms in migraine

Members

Christina Kruuse, Carina Jørgensen, Lars Schack Kruse, Julie Carøe Kristensen.

Background

Studies in humans help to explore possible migraine and headache provoking factors, in


order to understand migraine pathophysiology. It is known that pain signalling in humans

involve second messenger signalling through both types of second messengers; cyclic

adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP).

However, the function and interaction of these signalling pathways and the cellular

location in either neuronal or vascular cells is not fully understood. The aim is thus to

localize and investigate function of tissue and cells assumed relevant in initiation of the

pain process in order to investigate potential treatment targets. In collaboration with

Department of Clinical Biochemistry Glostrup, Department of Neuroscience and

Pharmacology and Functional Imaging Unit and Dept Clinical Physiology and Nuclear

medicine we describe the presence of some of the intracellular signaling molecules,

involved in the pain process, the effects of modulating the signalling cascade in pain and

regulation of cerebral artery diameter in cell and tissue based systems as well as in

humans.

Current projects

We are currently looking at the distribution and function of phosphodiseterases (PDE),

which are responsible for controlling the cAMP and cGMP levels in the cells. In particular

how they may relate to the pain sensing structures in the brain and play a part in the

induction and possible maintenance of headache and migraine.

Pharmacological and molecular studies of the cranial circulation

Members

Inger Jansen Olesen, Saurabh Gupta, Louise Juhl Boni, Kenneth Beri Ploug, Helle Wulf,

Michael Baun, Maja Myren, Dipak Vasantrao Amrutkar, Deepak Kumar Bhatt, Roshni

Ramachandran, Jes Olesen.

Background

We have during the last 20 years studied the pharmacology of isolated cranial blood

vessels from animals and humans in vitro. This work has led to several publications on

the characterization of cerebrovascular receptors for 5-hydroxytryptamine and the

sensory neuropeptides calcitonin gene-related peptide and substance P. During the last

5-8 years we have introduced new techniques, giving us the ability to study the

expression of mRNA and proteins for specific receptors in migraine relevant tissue. In

addition, we have established the genuine closed cranial window technique. This method

allows us to perform in vivo measurements of the effect of a drug on pial and dural

arteries when administered intravenously. We have further developed the method such it

is possible to give drugs by intracarotid infusion.


Current projects

The episodic nature of migraine attacks suggests that ion channels are involved in its

pathophysiology. This is confirmed by finding the mutation in patients suffering from

familial hemiplegic migraine within three different ion channel genes identified to date.

Potassium channels have an important role in the regulation of vascular tone and an

opener of ATP sensitive potassium (K(ATP)) channels has in clinical trials been found to

induce headache. An other channel we find might be important in migraine

pathophysiology are the large conductance calcium activated potassium (BK(Ca))

channel. Furthermore, the receptors for vasoactive peptides and prostanoids such as

vasoactive intestinal peptide (VIP) and pituitaty adenylyl cyclase activating peptide

(PACAP), calcitonin gene-related peptide (CGRP), prostaglandin E2 and prostacyclin are

of interest. The aim of the current projects is to explore the subunit composition and role

of these ion channels and receptors in pial and meningeal arteries and trigeminal

ganglion. We have during the last three months of the year initiated three new projects. In

these projects we investigate C-Fos expression after infusion of migraine triggering

substances, the occurrence and mechanisms behind CGRP uptake in migraine relevant

tissue and to investigate the presence and role of the proteinase activated receptor-2 in

migraine relevant tissue. The studies will give us an understanding of which subtype

compositions of ion channels and receptors that are present in theses tissues. In addition,

they will give us information to further understand the pathophysiology of migraine and to

define new targets for the pharmacological treatment of migraine.

Collaboration

Lars Edvinsson (Department of Experimental Clinical Research, Glostrup Hospital)

Anders Hay-Schmidt (Panum Institute, Copenhagen University), Dan Klærke (Faculty of

Life Sciences, Copenhagen University), Majid Sheykhzade (Faculty of Pharmaceutical

Sciences, Copenhagen University), Karl Messlinger (Institute of Physiology and

Experimental Pathophysiology, University of Erlangen-Nürnberg, D-91054 Erlangen,

Germany).

Idiopathic intracranial hypertension

Members

Rigmor Jensen, Maren Skau.

Background

Idiopathic intracranial hypertension (IIH) is an intriguing, clinical condition of increased

intracranial pressure without pathological, laboratory or radiological evidence of

intracranial pathology in young, obese individuals. The clinical symptoms are severe

headache, pulsatile tinnitus, transitory visual obscurations and diplopia. Demographic


studies 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 related to a number of

neuroendocrinological changes which has still not been evaluated in IIH.

Untreated IIH may lead to severe visual loss and blindness resulting from damage to the

optic nerve. The mechanism whereby IIH leads to optic nerve dysfunction is poorly

understood but it seems to be closely linked to edema of the optic nerve head and the

associated elevation of hydrostatic pressure inside the optic nerve.

The multidisciplinary study of IIH comprising neurobiological and ophthalmological

aspects is a unique study of still unsolved aspects in IIH. Read more about IIH on

www.danishheadachecenter.com.

Current projects

One cross-sectional study of ophthalmological and neurobiological aspects in Idiopathic

intracranial hypertension.

One longitidunal study of ophthalmological and neurobiological aspects in Idiopathic

intracranial hypertension, with specific focus on treatment and functional outcome.

Collaboration

Dan Milea, Department of Ophthalmology, Glostrup Hospital, Denmark

Jens Peter Gøtze and Jens Rehfeld, Department of Clinical Biochemistry, Danish

National Hospital, Copenhagen, Denmark.

Medication-overuse headache

Members

Signe Bruun Munksgaard, Rigmor Jensen, Lars Bendtsen.

Background

Medication-overuse headache (MOH) is a daily or almost-daily type of headache that

usually results from the chronification of primary forms, such as migraine or tension-type

headache, as a consequence of the progressive increase in the intake of symptomatic

drugs. MOH affects a percentage of 1.4-3% of the general population. Limited amount of

data exists on the burden of MOH, even in developed Countries, but there is general

agreement that the disease represents 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 are limited, and there are virtually no

data on how these severely patients are treated optimally. Thus, there is an urgent need

for studies investigating the pathophysiology and treatment possibilities of MOH.

Current projects

A prospective study comparing two different treatment options for MOH (abrupt drug

withdrawal and a 2 month drug free period compared with restricted intake of analgesics

combined with prophylactic headache treatment).

A prospective study investigating pain modulation (peripheral and central pain sensitivity)

before and after drug withdrawal.

An EU-founded multi-centre study (COMO-ESTAS) investigating the benefit of electronic

headache diaries during detoxification of MOH.

Collaboration

C. Tasorelli, Fondazione Istituto Neurologico Casimiro Mondino, Italy. M. Lainez,

Fundación de la Comunidad Valenciana para la Investigación Biomédica del Hospital

Clínico Universitario De Valencia, Spain. Z. Katsarava, Universitaetsklinikum Essen,

Germany. R. Fadic, Pontificia Universidad Catolica de Chile, Santiago, Chile. A. Stoppini,

Fundacion para la Lucha contra las Enfermedades Neurologicas de la Infancia, Buenos

Aires, Argentina. Lars Thorbjørn, Klinisk Biokemisk afdeling, Glostrup Hospital.

Clinical trials Members

Messoud Ashina, Jes Olesen and Peer Tfelt-Hansen

Background

The Center participates in number of clinical trials designed to test new therapies, or new

ways of using known treatments to improve the treatment of headache disorders.

Current trials

• A multicenter, double-blind, placebo-controlled, parallel group multiple attacks

study to compare the efficacy and safety of oral MK-0974 with placebo for the

acute treatment of migraine with and without aura. Included 72 patients

• Tonabersat in the prophylaxis of migraine with aura. Included 39 patients


3.4 Sponsors

Major sponsors:

Lundbeck Foundation as part of the Lundbeck Foundation Center for

Neuro-vascular Signalling

Mauritzen LaFontaine Foundation

Toyota Foundation

Copenhagen County Foundation

Augustinus Foundation

Faculty of health, University of Copenhagen

Danish Research Council

European Commission

Sponsors:

Danish Headache Society

Cool Sorption Foundation

Danielsens Foundation

The Danish Horton Patient Assocation

Danish Headache Foundation

4. Collaborations

Departments within Glostrup Hospital

• Department of Neurosurgery

• Department of Ophthalmology

• Department of Clinical Experimental Research

• Department of Clinical Physiology

• Department of Clinical Biochemistry

• Department of Pediatrics

• Department of Radiology

• Department of Gynecology

• Department of Anesthesiology

• Department of Oral and Maxillo-Facial Surgery

• Department of Clinical Neurophysiology

• Functional Imaging Unit, Dept Clinical Physiology and Nuclear medicine


External collaborators

Clinical research

• Center for Health and Preventive Medicine, Copenhagen County, Denmark

• Danish twin registry, University of Odense, Denmark

• The Pain Clinic, The National University Hospital, Rigshospitalet, Copenhagen,

Denmark

• Department of Neurology, Hillerød Hospital, Denmark

• 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

• 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

• Dept. of Pharmacology, University of Washington, Seattle, USA

• Center for Neurosurgery, Harvard University, Boston, USA

Basic Pain Mechanisms

• Professor Lars Arendt-Nielsen, Center for Sensory-Motor Interaction, University

of Ålborg, DK

• Professor Jens Elrich, Center for Sensory-Motor Interactions, Department of

Health Science and Technology, Aalborg University, Denmark

• 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 Experimental Research, University of Lund, Sweden

• Professor Karl Messlinger, Institute of Physiology and Experimental

Pathophysiology, University of Erlangen-Nürnberg, D-91054 Erlangen, Germany

• Institute of Anatomy, Panum Institute, University of Copenhagen, Denmark


• DeCode, Reykjavik, Iceland

• Danish twin registry


Headache Epidemiology

• Professor Michael Bjørn Russell, University of Oslo, Akershus Hospital, Norway

• Professor Lars-Jacob Stovner, Kompetencecenter for epidemiology, University of

Trondheim, Norway

Headache diagnosis

• Professor Guiseppe Nappi, Institute Mondino, University of Pavia, Italy (EU-

project)

Idiopathic Intracranial Hypertension

• Professor Dan Milea, Department of Opthalmology, Glostrup Hospital

• Copenhagen CSF-study group, Department of neurosurgery, Glostrup and

Rigshospitalet

• Jens Peter Gøtze and Jens Rehfeld, Department of Clinical Biochemistry,

Rigshospitalet

Medication-overuse headache

• Dr. C. Tasorelli, 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

Guest lectures and visitors

Professor Jens Ellrich, Aalborg, Denmark

Professor Ann MacGregor, London, England.

Dr. Rosella Nappi, Roma, Italy.

As well as numerous Danish colleagues.

5. Teaching activities

The European Headache Summer School was held in Baku, Azerbaijan in May. It was

arranged by Messoud Ashina and Rigmor Jensen in collaboration with Professor Rena

Shiraliyeva, Dept. of Neurology, Republican Clinical Hospital, Baku, Azerbaijan.


Gala Dinner at the highly successful European Headache School held in Baku, Azerbaijan, May 28-30, 2008.

6. Future Research Areas

In 2009 the scientific focus is directed towards • Neurovascular signalling in the LUCENS center • Experimental human models of migraine with implementation of new

imaging techniques

• Basic mechanisms of migraine in animal models

• Pain processing in tension-type headache • Medication-overuse headache • Idiopathic intracranial hypertension • Clinical research in The Headache Center • Diagnostic procedures in Headache (EU-project) • Monitoring of Medication Overuse Headache and development of a

decision support system in Europe and Latin America (EU-project)


7. Publications in 2008

PhD Theses 1. Buchgreitz L. Pain processing in tension-type headache. Københavns Universitet.

Det Sundhedsvidenskabelige Fakultet, 2008.

2. Gozalov A. Role of K+ channels in cephalic vasodilatation - implications for migraine pathophysiology. Københavns Universitet. Det sundhedsvidenskabelige Fakultet. 2008.

3. Kruse LS. Molecular mechanisms involving cyclic nucleotides in migraine. Københavns

Universitet. Det sundhedsvidenskabelige fakultet. 2008.

4. Ploug KB. Katp channels in intracranial arteries – implications for migraine pathophysiology. Københavns Universitet. Det sundhedsvidenskabelige fakultet. 2008.

5. Schmidt-Hansen PT. A controlled study on muscle pain sensitivity in Tension-Type

Headache patients. Aarhus Universitet og Københavns Universitet. Det sundhedsvidenskabeilge fakultet. 2008.

6. Boni LJ. In vivo studies on the effect on neuropeptides on rat intracranial arteries.

Københavns Universitet. Det sundhedsvidenskabelige Fakultet. 2008. In reviewed scientific journals (1) Ashina M, Jensen R. Et nyt behandlingsprincip. Ugeskr Laeger 2008; 170:1029.

(2) Ballegaard V, Thede-Schmidt-Hansen P, Svensson P, Jensen R. Are headache and temporomandibular disorders related? A blinded study. Cephalalgia 2008; 28:832-841.

(3) Bendtsen L., Jensen R. Pharmacological and non-pharmacological management of tension-type headache. Eur Neurological review 2008; 3:119-122.

(4) Boiusse V, Calvetti O, Drebz-Botsch CD, Sathornsumetee B, Newman NJ, Frederiksen JL. Management of optic neuritis and impact of trials. An international survey. J Neurol sci 2008;

(5) Buchgreitz L, Lyngberg AC, Bendtsen L, Jensen R. Increased pain sensitivity is not a risk factor but a consequence of frequent headache: a population-based follow-up study. Pain 2008; 137:623-630.

(6) Christiansen I, Iversen HK, Olesen J, Tfelt-Hansen P. Nitric oxide-induced headache may arise from extracerebral arteries as judged from tolerance to isosorbide-5-mononitrate. J Headache Pain 2008; 9:215-220.

(7) Dodick DW, Lipton RB, Goadsby PJ, Tfelt-Hansen P, Ferrari MD, Diener HC, Almas M, Albert KS, Parsons B. Predictors of migraine headache recurrence: A pooled analysis from the eletriptan database. Headache 2008; 48:184-193.

(8) Edvinsson L, Tfelt-Hansen P. The blood-brain barrier in migraine treatment. Cephalalgia 2008; 28:1245-1258.

(9) Ethic Subcommittee of the International Headache Society, Tfelt-Hansen P. Ethical issues arising from commercial sponsorship and from relationship with the pharmaceutical industry-report and recommendations of the Ethics Committee of the International Headache Society. Cephalalgia 2008; 28:1-25.

(10) Fabricius M, Fuhr S, Willumsen L, Dreier JP, Bhatia R, Boutelle MG, Hartings JA, Bullock R, Strong AJ, Lauritzen M. Association of seizures with cortical spreading depression and peri-infarct depolarisations in the acutely injured human brain. Clinical Neurophysiology 2008; 119:1973-1984.


(11) Gozalov A, Jansen-Olesen I, Klaerke D, Olesen J. Role of K ATP channels in cephalic vasodilatation induced by calcitonin gene-related peptide, nitric oxide, and transcranial electrical stimulation in the rat. Headache 2008; 48:1202-1213.

(12) Hansen JM, Thomsen LL, Olesen J, Ashina M. Calcitonin gene-related peptide does not cause the familial hemiplegic migraine phenotype. Neurology 2008; 71:841-847.

(13) Hansen JM, Thomsen LL, Olesen J, Ashina M. Familial hemiplegic migraine type 1 shows no hypersensitivity to nitric oxide. Cephalalgia 2008; 28:496-505.

(14) Hansen JM, Thomsen LL, Marconi R, Casari G, Olesen J, Ashina M. Familial hemiplegic migraine type 2 does not share hypersensitivity to nitric oxide with common types of migraine. Cephalalgia 2008; 28:367-375.

(15) Jensen R, Bendtsen L. Medication overuse in Scandinavia. Headache Currents. Cephalalgia 2008; 28:1237-1239.

(16) Jensen R, Stovner LJ. Epidemiology and comorbidity of headache. Lancet Neurol 2008; 7:354-361.

(17) Kallenbach K, Frederiksen JL. Unilateral optic neuritis as the presenting symptom of human immunodeficiency virus toxoplasmosis infection. Acta Ophthalmol 2008; 86:459-460.

(18) Knudsen S, Jennum PJ, Korsholm K, Sheikh SP, Gammeltoft S, Frederiksen JL. Normal levels of cerebrospinal fluid hypocretin-1 and daytime sleepiness during attacks of relapsing-remitting multiple sclerosis and monosymptomatic optic neuritis. Mult Scler 2008; 14:734-738.

(19) Korsholm K, Madsen KH, Frederiksen JL, Rowe JB, Lund TE. Cortical neuroplasticity in patients recovering from acute optic neuritis. Neuroimage 2008; 42:836-844.

(20) Lassen LH, Jacobsen VB, Haderslev PA, Sperling B, Iversen HK, Olesen J, Tfelt-Hansen P. Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients. J Headache Pain 2008; 9:151-157.

(21) Linnet K, Steentoft A, Simonsen KW, Sabers A, Hansen SH. An oxcarbazepine-related fatality with an overview of 26 oxcarbazepine postmortem cases. Forensic Sci Int 2008; 177:248-251.

(22) Mett A, Tfelt-Hansen P. Acute migraine therapy: recent evidence from randomized comparative trials. Current Opinion in Neurology 2008; 21:331-337.

(23) Olesen J. The role of nitric oxide (NO) in migraine, tension-type headache and cluster headache. Pharmacol Ther 2008; 120:157-171.

(24) Olesen J, Sobscki P, Truelsen T, Sestoft D, Jonsson B. Cost of disorders of the brain in Denmark. Nord J Psychiatry 2008; 62:114-120.

(25) Olesen J. The International Classification of Headache Disorders. Headache 2008; 48:691-693.

(26) Ploug KB, Sorensen MA, Strobech L, Klaerke DA, Hay-Schmidt A, Sheykhzade M, Olesen J, Jansen-Olesen I. K(ATP) channels in pig and human intracranial arteries. Eur J Pharmacol 2008.

(27) Ploug KB, Boni LJ, Baun M, Hay-Schmidt A, Olesen J, Jansen-Olesen I. K(ATP) channel expression and pharmacological in vivo and in vitro studies of the K(ATP) channel blocker PNU-37883A in rat middle meningeal arteries. Br J Pharmacol 2008; 154:72-81.

(28) Rahmann A, Wienecke T, Hansen JM, Fahrenkrug J, Olesen J, Ashina M. Vasoactive intestinal peptide causes marked cephalic vasodilation, but does not induce migraine. Cephalalgia 2008; 28:226-236.


(29) Rogojan C, Tfelt-Hansen P. [Numbness of the chin as a paraneoplastic syndrome]. Ugeskr Laeger 2008; 170:3135-3136.

(30) Sabers A. Pharmacokinetic interactions between contraceptives and antiepileptic drugs. Seizure 2008; 17:141-144.

(31) Sabroe TP, Sabers A. Progressive anticonvulsant hypersensitivity syndrome associated with change of drug product. Acta Neurol Scand 2008; 117:428-431.

(32) Schytz H, Birk S, Wienecke T, Kruuse C, Olesen J, Ashina M. PACAP38 induces migraine-like attacks in patients with migraine without aura. Brain 2008; dec.:1093.

(33) Silberstein S, Tfelt-Hansen P, Dodick DW, Limmroth V, Lipton RB, Pascual J, Wang SJ. Guidelines for controlled trials of prophylactic treatment of chronic migraine in adults. Cephalalgia 2008; 28:484-495.

(34) Stefansson H, Rujescu D, Cichon S, Pietilainen OPH, Ingason A, Steinberg S, Fossdal R, Sigurdsson E, Sigmundsson T, Buizer-Voskamp JE, Hansen T, Jakobsen KD, Muglia P, Francks C, Matthews PM, Gylfason A, Halldorsson BV, Gudbjartsson D, Thorgeirsson TE, Sigurdsson A, Jonasdottir A, Jonasdottir A, Bjornsson A, Mattiasdottir S, Blondal T, Haraldsson M, Magnusdottir BB, Giegling I, Moller HJ, Hartmann A, Shianna KV, Ge DL, Need AC, Crombie C, Fraser G, Walker N, Lonnqvist J, Suvisaari J, Tuulio-Henriksson A, Paunio T, Toulopoulou T, Bramon E, Di Forti M, Murray R, Ruggeri M, Vassos E, Tosato S, Walshe M, Li T, Vasilescu C, Muhleisen TW, Wang AG, Ullum H, Djurovic S, Melle I, Olesen J, Kiemeney LA, Franke B, Sabatti C, Freimer NB, Gulcher JR, Thorsteinsdottir U, Kong A, Andreassen OA, Ophoff RA, Georgi A, Rietschel M, Werge T, Petursson H, Goldstein DB, Nothen MM, Peltonen L, Collier DA, St Clair D, Stefansson K. Large recurrent microdeletions associated with schizophrenia. Nature 2008; 455:232-U61.

(35) Tassorelli C, Sances G, Allena M, Ghiotto N, Bendtsen L, Olesen J, Nappi G, Jensen R. The usefulness and applicability of a basic headache diary before first consultation: results of a pilot study conducted in two centres. Cephalalgia 2008; 28:1023-1030.

(36) Tfelt-Hansen P. Parenteral versus oral sumatriptan and naratriptan: plasma levels and efficacy in migraine. A comment. J Headache Pain 2008; 8:273-276.

(37) Tfelt-Hansen P, Koehler PJ. History of the use of ergotamine and dihydroergotamine in migraine from 1906 and onward. Cephalalgia 2008; 28:877-886.

(38) Tfelt-Hansen P, Ashina M, Olesen J. [Clinical symptoms and pathophysiology of migraine]. Ugeskr Laeger 2008; 170:3231-3234.

(39) Tfelt-Hansen P, Thorbjorn JL, Olesen J. Delayed hyperperfusion following migraine with a prolonged aphasic aura in a patient with CADASIL. Cephalalgia 2008; 28:899-902.

(40) Tfelt-Hansen P, Bjarnason NH, Dahlof C, Derry S, Loder E, Massiou H. Evaluation and registration of adverse events in clinical drug trials in migraine. Cephalalgia 2008; 28:683-688.

(41) Tfelt-Hansen P, Brosen K. Pharmacogenomics and migraine: possible implications. J Headache Pain 2008; 9:13-18.

(42) Thomsen LL, Oestergaard E, Bjornsson A, Stefansson H, Fasquel AC, Gulcher J, Stefansson K, Olesen J. Screen for CACNA1A and ATP1A2 mutations in sporadic hemiplegic migraine patients. Cephalalgia 2008; 28:914-921.

(43) Wienecke T, Hansen JM, Petersen J, Olsen KS, Ashina M, Tfelt-Hansen P. Sumatriptan does not affect arteriovenous oxygen differences in jugular and cubital veins in normal human subjects. Cephalalgia 2008; 28:1081-1085.

(44) Wienecke T, Olesen J, Oturai PS, Ashina M. Prostacyclin (epoprostenol) induces headache in healthy subjects. Pain 2008; 139:106-116.


(45) Wulf H, Hay-Schmidt A, Poulsen AN, Klaerke DA, Olesen J, Jansen-Olesen I. Molecular studies of BK(Ca) channels in intracranial arteries: presence and localization. Cell Tissue Res 2008.

(46) Yusuf S, Diener HC, Sacco RL, Cotton D, Ounpuu S, Lawton WA, Palesch Y, Martin RH, Albers GW, Bath P, Bornstein N, Chan BPL, Chen ST, Cunha L, Dahlof B, De Keyser J, Donnan GA, Estol C, Gorelick P, Gu V, Hermansson K, Hilbrich L, Kaste M, Lu C, Machnig T, Pais P, Roberts R, Skvortsova V, Teal P, Toni D, VanderMaelen C, Voigt T, Weber M, Yoon BW, the PRoFESS Study Group. Telmisartan to Prevent Recurrent Stroke and Cardiovascular Events. N Engl J Med 2008; 359:1225-1237.

(47) Zeeberg P, Olesen J, Jensen R. Medication overuse headache and chronic migraine in a specialized headache centre: field-testing proposed new appendix criteria. Cephalalgia 2008.

(48) Buchgreitz L, Egsgaard LL, Jensen R, Arendt-Nielsen L, Bendtsen L. Abnormal pain processing in chronic tension-type headache: a high-density EEG brain mapping study. Brain 2008; 131(Pt 12):3232-3238.

Textbooks 1. MacGregor A, Jensen R. Migraine and other Primary Headaches. London: Oxford

University Press; 2008.

2. Olesen J, Ramadan N. Innovative Drug Development for Headache Disorders. Oxford: Oxford University Press; 2008.

Bookchapters in International Textbooks

(1) Bendsen L. Tension-type headache. In: MacGregor A, Jensen J, editors. Migraine and other

primary headaches.London: Oxford University Press; 2008. p. 103-12.

(2) Bendtsen L, Jensen R. Epidemiology of headache. In: Fernández de las Peñas C, Arendt-Nielsen L, Gerwin RD, editors. Physicaltherapy for tension-type and cervicogenic headache: physical examination, muscle and joint management. Jones and Barnett; 2008. p. 7-13.

(3) Jensen R. Tension-type Headache. In: MacGregor A, Jensen R, editors. Migraine and other Primery Headaches.London: Oxford University Press; 2008. p. 23-30.

(4) Jensen R. Calcitonin gene-related peptide and 5-hydroxytryptamine modulators. In: Olesen J, Remadan N, editors. Innovative drug development for headache disorders. Frontiers in Headache research. 2008. p. 129-30.

(5) Jensen R, Torelli P. Treatment of Tension-type Headache. Handbook of clinical Neurology. Press; 2008.

(6) Tfelt-Hansen P, Jensen R. Headache. In: Jensen TS, Wilson PR, Rice ASC, editors. Clinical pain management. Chronic pain. 2 ed. London: Hodder Arnold Publisherss; 2008. p. 450-66.

(7) Tfelt-Hansen P, Jensen R. Headache. Clinical pain Management. Press; 2008.

(8) Tfelt-Hansen P, Jensen R. Headache. Handbook of Clinical Neurology. IN press; 2008.

(9) Torelli P, Jensen R. Diagnosis of headache. Handbook of clinical Neurology. Press; 2008.


8. Perspectives

We aim to continue the high research productivity, and facilitate scientific documentation

and development of the treatment strategies in the Danish Headache Center. It is of

utmost importance to improve the quality of the services offered to our patients, and

increasingly try to combine basic experimenttal research with clinical experience on a

daily basis in order to develop new therapeutic avenues. We aim to continue to develop

the Danish Headache Center in order to achieve our goal to be in among the leading

international centres for headache and neurological pain.

Editors:Lars Bendtsen Rigmor JensenJes Olesen

Frontpage:CTTH baseline P200 5th trainControls baseline P200 5th trainFrom Buchgreitz et al. 2008

Issues:150 ex.

Copyright:Danish Headache Center

Contact:Danish Headache Center DHC Glostrup Hospital Nord Building 14 Ndr. Ringvej 69 DK-2600 Glostrup Denmark Phone: +45 43 23 20 62

Layout and production:www.bureauLIST.dk / 14344

Danish Headache Center DHC Glostrup Hospital Nord Building 14, Ndr. Ringvej 69 DK-2600 Glostrup, Denmark

Phone: +45 43 23 20 62

www.danishheadachecenter.com

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