ATHENS, GREECE MAY 30th - JUNE 01st, 2019 - CONGRESS HIGHLIGHTS MAGAZINE
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13 European th Headache Federation Congress (EHF) MAY 30th – JUNE 01st, 2019 ATHENS, GREECE CONGRESS HIGHLIGHTS MAGAZINE
NEUROLOGYBYTES.COM EHF 2019 – CONFERENCE HIGHLIGHTS PAGE 1
It is an exciting era
for us headache and
migraine experts.
The 13th annual congress of the European Headache
Foundation (EHF) is over. For congress co-chair and
Professor of Neurology Zaza Katsarava the event
was a complete success, with over 900 engaged
participants from around the world coming together
to discuss migraine pathophysiology, epidemiology
and novel treatments. There was a real sense that
the rigorous scientific exchange that took place will
further our understanding of headache and migraine,
and translate into new treatments to improve the lives
of patients.
Throughout this magazine, you will find key highlights
and expect opinion from the congress. After reading,
we are sure you will agree with Prof. Katsarava that
the next EHF congress, taking place in Berlin on 3–5
July 2020, is not to be missed!
FEATURED ARTICLE CONTENT
CONGRESS HIGHLIGHTS Clinical features of visual aura symptoms
MAGAZINE
Page 3
Why include multidisciplinary treatment
when organising the headache clinic?
Page 5
The role of the hypothalamus in migraine
Page 7
Imaging the migraine brain
Page 10
New peripheral targets in the treatment
of migraine
Page 12
Epidemiology and impact of migraine
in Europe
Page 14
The role of the hypo- Can anti-CGRP monoclonal antibodies be
beneficial for other painful conditions?
thalamus in migraine Page 17
Societal impact of migraine
In a presentation at the 13th annual congress of
Page 19
the European Headache Federation, Prof. Arne May
(University of Hamburg, Germany) provided an
overview of the role of the hypothalamus in cluster
headache and migraine.
MAY 30TH – JUNE 01ST, 2019
ATHENS, GREECE Go to this artice - page 7NEUROLOGYBYTES.COM EHF 2019 – CONFERENCE HIGHLIGHTS PAGE 3
Migraine Sessions
at EHF 2019
Clinical features
of visual aura
symptoms
When diagnosing and treating patients
with migraine, it is important to have a
clear understanding of the symptoms
and characteristics that a patient may be
experiencing. This is especially true for
migraine with aura – the diagnosis is purely
clinical, and it is difficult to distinguish
migraine with aura from other serious
neurological disorders, such as transient
ischaemic attack or epilepsy. During his
presentation at the 13 annual congress of the
th
European Headache Federation, Dr Michele
Viana (Regional Hospital Lugano, Switzerland)
provided insights into the clinical features of
visual aura symptoms.NEUROLOGYBYTES.COM EHF 2019 – CONFERENCE HIGHLIGHTS PAGE 4
Visual disturbances are the most frequent symptom in migraine with References
aura, with 98% of migraineurs with aura experiencing them. Other
symptoms are somatosensory (36% of migraineurs) and dyspha- 1. Viana M, et al. Clinical features of migraine aura: Results from
sic symptoms (10%).1 Visual symptoms are multifaceted and spread a prospective diary-aided study. Cephalalgia 2017;37:979–989.
gradually. Migraineurs report a variety of symptoms, that are often
complex and multiple symptoms can occur during a single aura.1,2 Dr 2. Viana M, et al. Migraine aura symptoms: Duration, succession
Viana highlighted the lack of clinical description of the plethora of and temporal relationship to headache. Cephalalgia
visual symptoms, and continued with the current description of visual 2016;36:413–421.
symptoms: zigzag figures assuming a laterally convex shape with an
angular scintillating edge leaving scotoma in its wake.3 Results from a 3. Headache Classification Committee of the International
prospective, diary-aided study indicated that the five most frequent Headache Society (IHS). The International Classification of
‘elementary’, or individual, visual aura disturbances are flashes of Headache Disorders, 3rd edition. Cephalalgia 2018;38:1–211.
bright light, foggy/blurred vision, zigzag/jagged lines, scotoma and
phosphenes (small bright dots). Most aura have two visual symptoms 4. Queiroz LP, et al. Characteristics of migraine visual aura in
and in 85% of aura, symptoms last for one hour or less.1 Southern Brazil and Northern USA. Cephalalgia 2011;31:1652–
1658.
Dr Viana proceeded by addressing the visual field in which aura
occur. Visual aura typically begin at the periphery of the visual field 5. Viana M, et al. Clinical features of visual migraine aura:
(40%), followed by initiating in one half (27%) or in the entire (25%) A systematic review. J Headache Pain 2019; in press.
visual field. Only 36% of visual aura are reported to occur on both
sides of the visual field, indicating that the majority are unilateral.1
Dr Viana alerted the audience that while in most patients visual aura
occur in both eyes, there is currently no clinical evidence supporting
this observation. As for colours, half of migraineurs report always hav-
ing black and white (30%) or black and silver (21%) visual aura. The
remaining migraineurs described having both black and white and
colourful (22%), colourful (18%) or no colour (9%) visual aura.4
Dr Viana concluded by emphasising that migraine with aura is a mul-
tifaceted phenomenon and understanding its ‘hundred faces’ is of
paramount importance for accurate diagnosis and treatment. Addi-
tionally, Dr Viana alerted the audience that an updated list of all
evaluated visual symptoms of migraine with aura and their descrip-
tion will be promptly published in the Journal of Headache and Pain.5NEUROLOGYBYTES.COM EHF 2019 – CONFERENCE HIGHLIGHTS PAGE 5 Migraine Sessions at EHF 2019 Why include multidisciplinary treatment when organising the headache clinic? At a teaching course at the 13th annual congress of the European Headache Federation, Prof. George Georgoudis (University of West Attica, Greece) described a biopsychosocial approach to treating headache, as well as clinical research to evaluate the benefits of this approach. In Prof. Georgoudis’ opinion, there is an opportunity for patients to benefit from a supplementary approach to headaches that incorporates physiotherapy.
NEUROLOGYBYTES.COM EHF 2019 – CONFERENCE HIGHLIGHTS PAGE 6
Prof. Georgoudis described how patients attending head- In the opinion of Prof. Georgoudis, the observed results demon-
ache clinics may present with a number of symptoms, including strate that hands-on physiotherapy techniques, alongside
intense, bilateral pain that fails to deteriorate with regular physical acupuncture and stretching, can produce desireable physio-
activity. While patients often receive pharmacological interven- logical improvements in patients with TTH, alongside providing
tions, incorporating physical therapy into patient management cognitive and psychological benefits. Considering this, a bio-
could provide a second opportunity to improve health outcomes. psychosocial approach to treating patients in the headache
He further described targets for the management of physical clinic could, therefore, complement existing pharmacological
therapy, including cervical spine manipulation or mobilisation,1 interventions.
exercise to strengthen deep neck flexors and upper quarter
muscles, thoracic spine thrust manipulation and exercise, and
C1–C2 self-sustained natural apophyseal glide (SNAG).2 These
treatments combine physiological benefits with cognitive and
psychological benefits in patients.
During the presentation, Prof. Georgoudis described a pragmatic,
randomised, controlled trial designed to investigate whether a
biopsychosocial approach provides benefits for patients with
TTH (tension-type headache) cephalagia.3 In the study, patients
received ten treatment sessions within a four-week period, along-
side a daily stretching regimen. Treatment sessions consisted
of either acupuncture alone (control group) or acupuncture and
physiotherapy (experimental group). Acupuncture was conducted
at 17–20 acupuncture sites, of which 15–17 remained constant
across patients, with the remainder being decided based on
individual symptoms. Physiotherapy consisted of microwave
diathermy and myofascial release with manual techniques. The
primary outcome was mechanical pressure pain threshold (PPT) References
using a mechanical algometer to measure seven bilateral points,
which were measured at baseline, after five treatments and after 1. Cleland JA, et al. Examination of a clinical prediction rule to
ten treatments. identify patients with neck pain likely to benefit from thoracic
spine thrust manipulation and a general cervical range of
Prof. Georgoudis described how a significant improvement on motion exercise: multi-center randomized clinical trial. Phys
the primary outcome of PPT score was observed for patients in Ther 2010;90:1239–1250.
the control group, who received acupuncture treatment along-
side stretching, as well as patients in the experimental group, 2. Hall T, et al. Efficacy of a C1-C2 self-sustained natural
who received treatment incorporating acupuncture, stretching apophyseal glide (SNAG) in the management of cervicogenic
and manual physiotherapy. A significant change from baseline headache. J Ortho Sport Phys Ther 2007;37:100–107.
was observed at both week five and week ten. However, at week
ten, an augmented benefit on the primary outcome of PPT score 3. Georgoudis G, et al. The effect of myofascial release and
was observed in the experimental group compared with the microwave diathermy combined with acupuncture versus
control group. A similar pattern of benefits was observed for all acupuncture therapy in tension-type headache patients: A
secondary outcomes, including reduction of pain, anxiety and pragmatic randomized controlled trial. Physiother Res Int
depression, catastrophising, functioning and quality of life. 2018;23:e1700.tNEUROLOGYBYTES.COM EHF 2019 – CONFERENCE HIGHLIGHTS PAGE 7 Migraine Sessions at EHF 2019 The role of the hypothalamus in migraine The role of hypothalamus in cluster headache is well established. In his presentation at the 13th annual congress of the European Headache Federation, Prof. Arne May (University of Hamburg, Germany) gave an overview of the role of the hypothalamus in cluster headache and recent clinical research into the nature of hypothalamic involvement in migraine.
NEUROLOGYBYTES.COM EHF 2019 – CONFERENCE HIGHLIGHTS PAGE 8
Migraine is defined
Chronic headache and the hypothalamus
Prof. May started his presentation with an overview of the role
by the attack phase,
of the hypothalamus in cluster headache. Trigeminal autonomic
cephalgias (TAC), which include cluster headache and paroxys-
mal hemicrania, show a circadian and circannual rhythm of attack
however, the brain of
implicating the hypothalamus as a disease modulator. He con-
tinued by illustrating how hypothalamic activity is increased in
chronic headache.1 Indeed, all TAC show hypothalamic activation
migraineurs is also
in the acute headache phase. While alcohol and histamine pro-
voke attacks, Prof. May indicated that this is only the case during
active phases of the disease. He added that this observation
different from that
could translate into optimised treatment. Medication schedul-
ing could be tailored to coincide with active disease phases as
a means to decrease treatment burden on patients. Prof. May
of healthy controls
concluded the first part of his presentation by indicating that the
hypothalamus plays a crucial role in attack generation in cluster
headache.
Migraine and the hypothalamus outside of the attack.
Transitioning into hypothalamic involvement in migraine, Prof.
May stressed that previously, only the brainstem was linked to Arne May (University of Hamburg, Germany)
migraine neurobiology. However, hypothalamic involvement
in migraine was suspected since migraineurs experience pre-
monitory symptoms.2,3 Initially demonstrated by Denuelle et
al. in 2007,4 hypothalamic activity during migraine attacks was
observed.5 Prof. May highlighted research from his laboratory
in which episodic migraineurs, chronic migraineurs and healthy
controls received painful ammonia stimulation alongside simul-
taneous recording of brain activity using magnetic resonance
imaging (MRI).6 Increased activity of the posterior hypothalamus
was observed during the acute pain stage of migraineurs, while
increased activity in the anterior hypothalamus was observed
during attack generation and chronification. This research into
the distinct roles of subregions of the hypothalamus builds on
earlier research in which altered connectivity between the hypo-
thalamus and specific subregions of the brainstem (dorsal rostral
pons and spinal trigeminal nuclei) was observed in the brainNEUROLOGYBYTES.COM EHF 2019 – CONFERENCE HIGHLIGHTS PAGE 9
of a migraine patient in the 24 hours immediately preceding a References
migraine attack.7 Combined, these results suggest that while the
brainstem may be the ‘migraine generator’, the hypothalamus 1. May A, et al. Hypothalamic activation in cluster headache
may play the role of mediator in the pathophysiology of migraine. attacks. Lancet 1998;352:275–278.
Prof. May concluded that the different subregions of the
hypothalamus play different roles in migraine – the anterior 2. Giffin NJ, et al. Premonitory symptoms in migraine –
hypothalamus might be the driver of attacks, while the posterior An electronic diary study. Neurology 2003;60:935–940.
hypothalamus is involved in acute migraine headache. Addition-
ally, he indicated that beta-blockers, but not topiramate, may 3. Quintela E, et al. Premonitory and resolution symptoms in
have an effect on hypothalamic control, which could, in turn, migraine: A prospective study in 100 unselected patients.
inform treatment decisions. Cephalalgia 2006;26:1051–1060.
4. Denuelle M, et al. Hypothalamic activation in spontaneous
migraine attacks. Headache 2007;47:1418-1426.
5. Maniyar FH, et al. The premonitory phase of migraine –
What can we learn from it? Headache 2015;55:609–620.
6. Schulte LH, et al. Hypothalamus as a mediator of chronic
pain. Evidence from high resolution fMRI. Neurology
2017;88:2011–2016.
7. Schulte LH, & May A. The migraine generator revisited:
continuous scanning of the migraine cycle over 30 days and
three spontaneous attacks. Brain 2016;139:1987–1993.NEUROLOGYBYTES.COM EHF 2019 – CONFERENCE HIGHLIGHTS PAGE 10
Migraine Sessions
at EHF 2019
Advances in brain imaging have increased our understanding of
migraine pathophysiology. But could brain imaging be used to
predict migraine progression and how a patient will respond to
treatment? At the 13th annual congress of the European Head-
Diagnosing
ache Federation, Prof. Todd J Schwedt (Mayo Clinic, USA) and
Dr Anders Hougaard (University of Copenhagen, Denmark) dis-
cussed the past, present and future of migraine brain imaging.
Chronic Migraine
Structural changes in migraine
Prof. Schwedt used his presentation to outline how structural
brain imaging has contributed to understanding migraine patho-
physiology and how imaging could be used for developing
migraine biomarkers. He began by outlining techniques for com-
Advances in brain imaging have paring the brains of migraineurs with healthy controls, including
increased our understanding of migraine magnetic resonance imaging (MRI), diffusion tensor imaging (DTI)
and magnetic resonance (MR) tractography. A study using MRI
pathophysiology. But could brain imaging has demonstrated cortical thinning in migraineurs compared with
healthy controls, with differences observed bilaterally in the cen-
be used to predict migraine progression and tral sulcus, the left middle-frontal gyrus, the left visual cortices
and the right occipito-temporal gyrus.1 Similarly, structural abnor-
how a patient will respond to treatment? At malities of the brainstem have been observed in migraineurs,
the 13th annual congress of the European including smaller midbrain volume, inward deformation of the
ventral midbrain and pons, and outward deformations in the lat-
Headache Federation, Prof. Todd J Schwedt eral medulla and dorsolateral pons.2
(Mayo Clinic, USA) and Dr Anders Hougaard In Prof. Schwedt’s opinion, understanding aberrant brain struc-
(University of Copenhagen, Denmark) ture in migraine patients could lead to the development of
objective, replicable biomarkers for migraine. These biomark-
discussed the past, present and future of ers could be beneficial for diagnostic and prognostic purposes,
and may eventually be used to predict how a specific patient will
migraine brain imaging. respond to treatment.NEUROLOGYBYTES.COM EHF 2019 – CONFERENCE HIGHLIGHTS PAGE 11
Functional changes in migraine References
Dr Hougaard used his presentation to highlight successes in 1. Magon S, et al. Cortical abnormalities in episodic migraine: A
using functional imaging to understand migraine. He began by multi-center 3T MRI study. Cephalalgia 2019;39:665–673.
discussing research in which brainstem activation was observed
during a spontaneous migraine attack, with increased activity 2. Chong CD, et al. Structural alterations of the brainstem in
persisting after an injection was administered to induce com- migraine. Neuroimage Clin 2017;12:223–227.
plete relief from headache, phonophobia and photophobia.3
While researchers have used different techniques to explore the 3. Weiller C, et al. Brain stem activation in spontaneous human
reproducibility of these findings,4 there is still a need to uncover migraine attacks. Nat Med 1995;1:658–660.
precisely which brainstem subregions are involved in migraine,
whether this evidence can be used to diagnose migraine, and the 4. Hougaard A, et al. Increased intrinsic brain connectivity
effect of different migraine therapies on brainstem activity. between pons and somatosensory cortex during attacks of
In Dr Hougaard’s opinion, functional imaging is a powerful migraine with aura. Human Brain Map 2017;38:2635–2642.
approach for studying migraine pathophysiology. The example
of research into brainstem activity during migraine attacks high- 5. Schwedt TJ, et al. Migraine subclassification via a data-driven
lights the need for clinical evidence to be reproducible, and for automated approach using multimodality factor mixture
researchers to build on existing research to gain greater insights modeling of brain structure measurements. Headache
into the underlying cause of migraine. 2017;57:1051–1064.
6. Chen W-T, et al. Comparison of gray matter volume between
The future of brain imaging in patients migraine and “strict-criteria” tension-type headache.
with migraine J Headache Pain, 2018;19:4.
Brain imaging has been used to identify aberrant structures and
alterations in brain activity in patients with migraine. Both Prof.
Schwedt and Dr Hougaard highlighted the potential of brain
imaging to identify biomarkers of migraine that can be applied
at a patient level. While imaging can be used to identify migraine
subtypes5 and to differentiate between headache types,6 there is
more work to be done in this area. This may include using brain
imaging to predict patient outcomes and responses to individual
therapies, and combining structural and functional evidence to
gain more powerful insights into migraine.NEUROLOGYBYTES.COM EHF 2019 – CONFERENCE HIGHLIGHTS PAGE 12 Migraine Sessions at EHF 2019 New peripheral targets in the treatment of migraine Migraine treatments generally target the central nervous system (CNS) and potential peripheral targets are not investigated in depth. As part of the session entitled “New targets in migraine treatment” at the 13th annual congress of the European Headache Federation, Prof. Antoinette Maassen Van Den Brink (Erasmus University Rotterdam, Netherlands) emphasised the importance of investigating peripheral targets for migraine treatment and described the latest developments in this area.
NEUROLOGYBYTES.COM EHF 2019 – CONFERENCE HIGHLIGHTS PAGE 13
The periphery
Her presentation started with the blood-brain barrier (BBB), the
semipermeable lining that ensures a tightly regulated exchange
between the blood and the brain. She highlighted a study demon-
deserves a central
strating that the trigeminal ganglion (TG) is more permeable than
the brain,1 a result suggesting that some migraine treatments
might have peripheral, in addition to CNS, targets. Moreover,
role in migraine
some triptans have the potential ability of crossing the BBB and,
conversely, antibodies targeting the calcitonin gene-related pep-
tide (CGRP) are not expected to permeate this tightly regulated
research.
barrier. Combined, these observations indicate that periph-
eral effects of existing treatments, and the investigation of new
peripheral targets for migraine treatment, is of high importance.
Prof. Maassen Van Den Brink introduced new pharmacologi-
cal peripheral targets – including the receptors: amylin, PACAP/ Antoinette Maassen Van Den Brink
PAC1, 5-hydroxytryptamine (HT)1F, purinergic and gamma-ami- (Erasmus University Rotterdam, Netherlands)
nobutyric acid (GABA), as well as the transient receptor potential
(TRP) channels – and proceeded with an overview of the latest
developments. Recent research from her laboratory has shown
that lasmiditan (a 5-HT1F agonist) inhibited CGRP release in the
dura mater, the TG and the trigeminal nucleus caudalis (TNC).
The efficacy of 5-HT1F agonists might, therefore, have both CNS
and peripheral components. As for purinergic receptors, the P2X
receptor mediates vasocontraction and induces CGRP release.2
This receptor is expressed in the meningeal artery and the TG,
and antagonists of the P2X3 receptor in particular, might be a via-
ble new class of migraine treatment. Prof. Maassen Van Den Brink
highlighted that while TRPV1, a member of the TRP channels,
failed to show promising results in the clinic, these ion channels
remain interesting targets.3 While only a few of the new periph-
eral targets were discussed during this presentation, there is
much promise in this emerging field of migraine research. References
1. Eftekhari S, et al. Localization of CGRP, CGRP receptor,
PACAP and glutamate in trigeminal ganglion. Relation to the
blood-brain barrier. Brain Res 2015;1600:93–109.
2. Haanes KA, et al. Exploration of purinergic receptors as
potential anti-migraine targets using established pre-clinical
migraine models. Cephalalgia 2019; in press.
3. Benemei S & Dussor G. TRP Channels and Migraine: Recent
Developments and New Therapeutic Opportunities.
Pharmaceuticals 2019;12:e54.NEUROLOGYBYTES.COM EHF 2019 – CONFERENCE HIGHLIGHTS PAGE 14 Migraine Sessions at EHF 2019 Epidemiology and impact of migraine in Europe Despite consensus among the scientific community that migraine is a prevalent and disabling condition, migraine remains both underdiagnosed and undertreated. 1 In her presentation at a Teva-sponsored satellite symposium that took place during the 13th annual congress of the European Headache Federation, Prof. Patricia Pozo- Rosich (Vall d’Hebron University Hospital of Barcelona, Spain) highlighted attempts that have been made to describe the epidemiology of migraine in Europe, alongside the negative impact of migraine on individuals and society.
NEUROLOGYBYTES.COM EHF 2019 – CONFERENCE HIGHLIGHTS PAGE 15
Epidemiology of migraine in Europe
We need to make
sure societies
Prof. Pozo-Rosich started by outlining key studies that described
the epidemiology of migraine in Europe. Migraine is not fatal and
causes no outward disability, which explains why the prevalence
and governments
and severity of migraine is often underestimated.2 However,
every year over 136 million individuals throughout Europe expe-
rience one or more episodes of migraine that fulfils International
understand that
Classification of Headache Disorders (ICHD) criteria.2 The prev-
alence of migraine is greater in Europe and North America than
in Asia and Africa.3 In individuals aged 15–49 years, migraine is
the leading cause of years lived with disability (YLD), accounting
migraine is a disease
for 8.2% of all YLDs.4 Prof. Pozo-Rosich discussed the challenge
of communicating important epidemiological migraine data to
societies and governments, arguing that evidence needs to be
that needs to be
translated into clear and concise messaging that can be under-
stood and acted upon.
Impact of migraine in Europe
treated.
Prof. Pozo-Rosich further emphasised that migraine has a sub-
stantial negative impact at both an individual and societal level.
Patricia Pozo-Rosich
The impact of migraine on individuals is considerable, with a
cross-sectional analysis of survey data in France, Germany, Italy, (Vall d’Hebron University Hospital of Barcelona, Spain)
Spain and the United Kingdom demonstrating a number of poor
outcomes for patients experiencing more than three monthly
headache days.5 This includes reduced functional ability, poorer
health-related quality of life and decreased work productivity and
attendance when compared with healthy individuals.
Migraine also presents a large and widespread financial burden.
Healthcare systems are faced with the cost of primary and sec-
ondary care appointments, emergency department visits and
hospitalisations.5 Evidence from Spain shows that the annual direct
cost of episodic migraine per patient is €964.19, while the annual
direct cost of chronic migraine per patient is €3847.29.6 When
combined with the financial implications of reduced workplace
attendance and productivity, the annual cost to European econo-
mies of migraine is estimated to be €18.5 billion (2012 data).7 Prof.
Pozo-Rosich stated that while these figures are widely available,
the scientific community needs to consider practical solutions forNEUROLOGYBYTES.COM EHF 2019 – CONFERENCE HIGHLIGHTS PAGE 16
changing the perception of migraine among healthcare systems References
and employers. This includes educating clinicians, governments
and workplaces about the devastating impact of migraine. 1. Stovner LJ, et al. Epidemiology of headache in Europe.
Eur J Neurol 2006;13:333–345.
Moving forward: reducing the impact of migraine 2. Stovner LJ, et al. Global, regional, and national burden
of migraine and tension-type headache, 1990–2016: a
Prof. Pozo-Rosich concluded with the positive message that systematic analysis for the Global Burden of Disease Study
treatment options are rapidly improving for migraineurs. New 2016. Lancet Neurol 2018;17:954–976.
therapies are reducing the effect of migraine on functional abil-
ity, increasing health-related quality of life and decreasing the 3. Stovner LJ, et al. The global burden of headache: a
financial burden of migraine. However, to realise the benefits of documentation of headache prevalence and disability
an improved treatment landscape, it is vital that the need for new worldwide. Cephalalgia 2007;27:193–210.
treatments is fully communicated to all relevant stakeholders.
4. Steiner TJ, et al. Migraine is first cause of disability in under
50s: will health politicians now take notice? J Headache Pain
2018;19:17.
5. Vo P, et al. Patients’ perspective on the burden of migraine
in Europe: a cross-sectional analysis of survey data in France,
Germany, Italy, Spain, and the United Kingdom. J Headache
Pain 2018;19:82.
6. Editorial Universidad de Sevilla. Impacto y situación de la
Migraña en España: Atlas 2018. http://www.dolordecabeza.
net/wp-content/uploads/2018/11/3302.-Libro-Atlas-
Migaran%CC%83a_baja.pdf. Accessed 1 June 2019.
7. Oleson J, et al. The economic cost of brain disorders in
Europe. Eur J Neurol 2012;19:155–162.NEUROLOGYBYTES.COM EHF 2019 – CONFERENCE HIGHLIGHTS PAGE 17
Migraine Sessions
at EHF 2019
Can anti-CGRP Primary headache
Thus far, clinical trial results have not demonstrated a therapeutic
monoclonal
benefit of anti-CGRP mAbs in cluster headache. Prof. Dodick ques-
tioned whether patient population and outcome measure selection
could be improved to properly answer the research question, and
antibodies be
emphasised that additional studies of anti-CGRP mAbs in cluster
headache should be conducted.
Secondary headache
beneficial for Animal studies have shown that concussions lead to headache and
pain-related behaviours, and that the administration of anti-CGRP
other painful
mAbs prevents allodynia in murine models of post-traumatic head-
ache (PTH).2,3 Prof. Dodick highlighted an ongoing clinical trial
(NCT03347188) that investigates anti-CGRP mAbs in patients with
PTH. The results of this study are expected in October 2020.
conditions? Non-headache pain
A recent systematic literature review showed an association between
measured CGRP levels and somatic, visceral, neuropathic and inflam-
The neuropeptide calcitonin gene-related peptide (CGRP) plays matory pain.4 In particular, CGRP levels had a positive correlation
a significant role in chronic neuropathic pain, and the therapeutic with pain in somatic pain conditions. However, an initial investigation
benefits of anti-CGRP monoclonal antibodies (mAbs) in migraine of anti-CGRP mAbs in patients with osteoarthritis knee pain failed to
treatment are well established. However, CGRP is not only expressed demonstrate a therapeutic benefit compared with placebo.5 In Prof.
in the central nervous system, but also in nearly all human organs.1 Dodick’s opinion, this was an unexpected result and he questioned
In a presentation at the 13th annual congress of the European Head- whether the correct joint was targeted in this study. Prof. Dodick fur-
ache Federation, Prof. David W. Dodick (Mayo Clinic, USA) provided ther commented that other pain syndromes that could be potentially
a brief overview of recent studies on the use of anti-CGRP mAbs in addressed with anti-CGRP are those of visceral, inflammatory and
non-migraine pain conditions. neuropathic etiology.4, 6NEUROLOGYBYTES.COM EHF 2019 – CONFERENCE HIGHLIGHTS PAGE 18
Non-pain syndromes
The prophylactic administration of anti-CGRP antibodies was found
to block CGRP-induced diarrhoea in mice.7 These preclinical results
illustrate the potential of anti-CGRP mAbs as a novel therapeutic
strategy for infectious diarrhoea and other gastro-intestinal patholo-
gies, such as colitis and inflammatory bowel disease.
Prof. Dodick concluded his presentation with a call to action to track
patients in clinical trials not only from a migraine standpoint, but
to integrate measures that record other pain syndromes as well.
Patient-reported outcome questionnaires were highlighted as appro-
priate tools for this purpose.
References
1. Russell FA, et al. Calcitonin gene-related peptide: physiology
and pathophysiology. Physiol Rev 2014;94:1099–1142.
2. Bree D & Levy D. Development of CGRP-dependent pain and
headache related behaviours in a rat model of concussion:
Implications for mechanisms of post-traumatic headache.
Cephalalgia 2018;38:246–258.
3. Porreca F and coworkers. manuscript in preparation
4. Sophie Schou W, et al. Calcitonin gene-related peptide and
pain: a systematic review. J Headache Pain 2017;18:34.
5. Jin Y, et al. CGRP blockade by galcanezumab was not
associated with reductions in signs and symptoms of knee
osteoarthritis in a randomized clinical trial. Osterarthritis
Cartilage 2018;26:1609–1618.
6. Bowler KE, et al. Evidence for anti-inflammatory and putative
analgesic effects of a monoclonal antibody to calcitonin
gene-related peptide. Neuroscience 2013;228:271–282.
7. Kaiser EA, et al. Anti-CGRP antibodies block CGRP-induced
diarrhea in mice. Neuropeptides 2017;64:95–99.NEUROLOGYBYTES.COM EHF 2019 – CONFERENCE HIGHLIGHTS PAGE 19
Migraine Sessions
at EHF 2019
Societal impact
of migraine
Patients with migraine report diminished
functioning and well-being on health-related
quality of life measures. Underdiagnosis
1
and undertreatment means that the
magnitude of the clinical economic burden
to individuals, relatives and society may
be underestimated. During a session at
2
the 13th annual congress of the European
Headache Foundation – chaired by Prof.
Paolo Martelletti (University of Rome, Italy)
and Dr Mark Braschinsky (University of Tartu,
Estonia) – the invited faculty discussed the
societal burden of migraine.NEUROLOGYBYTES.COM EHF 2019 – CONFERENCE HIGHLIGHTS PAGE 20
If we want women
Migraine burden and barriers
Prof. Gisela Terwindt (Leiden University Medical Centre, the Neth-
to be leaders, we
erlands) began her talk by highlighting that while migraine is the
second most disabling disorder worldwide,3 it affects men and
women very differently. She observed that not only is lifetime
need to treat their
prevalence of migraine much higher in women than in men (33%
vs. 13%, respectively),4 the risks associated with migraine are far
greater for women. Migraine is a risk factor for stroke in women,5
migraines.
with the presence of aura, smoking and regular use of oral con-
traceptives cumulatively increasing this risk. Similarly, women with
migraine are at increased risk of white matter lesions compared
with healthy controls, while men with migraine are not.6 Prof. Ter-
windt concluded by highlighting the disabling debilitating effect
of migraine on women, especially those of working age. As such, Prof. Gisela Terwindt
migraine represents a significant barrier to the progression of
(Leiden University Medical Centre, the Netherlands)
women in the workforce.
Impact on working activity
Continuing the discussion of the societal impact of migraine, Prof.
Paolo Martelletti emphasised the impact of migraine on working
activity. Chronic migraine is associated with increased absentee-
ism, including missed work days and productivity loss.7 In Prof.
Martelletti’s opinion, the fact that absenteeism is greater in young
workers aged 18–34 years is of utmost concern.8 He concluded
that the general population does not consider migraine to be a
disability, despite the effects of migraine on workplace produc-
tivity and absenteeism being comparable with other major public
health problems.
Economic cost of migraine
Prof. Paul McCrone (King’s College London, United Kingdom) fin-
ished the session by discussing the cost of migraine from a health
economics perspective, and reviewing attempts to quantify and
predict the economic cost of migraine for patients referred to
specialists. In the UK, self-report data on healthcare resource useNEUROLOGYBYTES.COM EHF 2019 – CONFERENCE HIGHLIGHTS PAGE 21
and lost employment over a 4-month period were acquired and References
used to estimate the economic costs of migraine.9 Prof. McCrone
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care, individuals incurred large costs related to informal care. The
latter accounted for 74% of the total migraine-related cost per
2. Agosti R. Migraine burden of disease: from the patient’s
person of £6588 over 4 months.
experience to a socio-economic view. Headache 2018;58:17–32.
A need for greater evidence explaining the full cost of migraine
3. Vos T, et al. Global, regional, and national incidence,
During the question and answer session, all speakers agreed
that there is a need for more evidence on the economic cost of prevalence, and years lived with disability for 328 diseases
migraine. However, the optimal way of presenting this evidence to and injuries for 195 countries, 1990–2016: a systematic
regulatory and reimbursement bodies is still being debated. analysis for the Global Burden of Disease Study 2016. Lancet
2017;390:1211–1259.
4. Launer LJ, et al. The prevalence and characteristics of migraine
in a population-based cohort: the GEM study. Neurology
1999;53:537–542.
5. MacClellan LR, et al. Probable migraine with visual aura and
risk of ischemic stroke: the stroke prevention in young women
study. Stroke 2007;38:2438–2445.
6. Palm-Meinders IH, et al. Structural brain changes in migraine.
JAMA 2012;308:1889–1897.
7. Zhang W, et al. The relationship between chronic conditions
and absenteeism and associated costs in Canada. Scand J
Work Environ Health 2016;42:413–422.
8. Mesas AE, et al. The association of chronic neck pain, low back
pain, and migraine with absenteeism due to health problem in
Spanish workers. Spine 2014;39:1243–1253.JOB CODE: HQ/CNS/19/0019 DATE OF PREPARATION JUNE 2019
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