13th european headache federation congress (ehf)...individual symptoms. physiotherapy consisted of...

13th European Headache Federation Congress (EHF)

CONGRESS HIGHLIGHTS MAGAZINE

MAY 30th – JUNE 01st, 2019ATHENS, GREECE

EHF 2019 – CONFERENCE HIGHLIGHTSNEUROLOGYBYTES.COM

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!

CONTENTFEATURED ARTICLE

The role of the hypo-thalamus in migraineIn a presentation at the 13th annual congress of 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.

Clinical features of visual aura symptoms

Why include multidisciplinary treatment when organising the headache clinic? Page 5

The role of the hypothalamus in migraine Page 7

Imaging the migraine brainPage 10

New peripheral targets in the treatmentof migrainePage 12

Epidemiology and impact of migrainein EuropePage 14

Can anti-CGRP monoclonal antibodies be beneficial for other painful conditions?Page 17

Societal impact of migrainePage 19

MAY 30TH – JUNE 01ST, 2019ATHENS, GREECE

CONGRESS HIGHLIGHTS MAGAZINE


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 13th annual congress of the European Headache Federation, Dr Michele Viana (Regional Hospital Lugano, Switzerland) provided insights into the clinical features of visual aura symptoms.

Clinical features of visual aura symptoms

Migraine Sessionsat EHF 2019


Visual disturbances are the most frequent symptom in migraine with aura, with 98% of migraineurs with aura experiencing them. Other symptoms are somatosensory (36% of migraineurs) and dyspha-sic symptoms (10%).1 Visual symptoms are multifaceted and spread gradually. Migraineurs report a variety of symptoms, that are often complex and multiple symptoms can occur during a single aura.1,2 Dr Viana highlighted the lack of clinical description of the plethora of visual symptoms, and continued with the current description of visual symptoms: zigzag figures assuming a laterally convex shape with an angular scintillating edge leaving scotoma in its wake.3 Results from a prospective, diary-aided study indicated that the five most frequent ‘elementary’, or individual, visual aura disturbances are flashes of bright light, foggy/blurred vision, zigzag/jagged lines, scotoma and phosphenes (small bright dots). Most aura have two visual symptoms and in 85% of aura, symptoms last for one hour or less.1

Dr Viana proceeded by addressing the visual field in which aura occur. Visual aura typically begin at the periphery of the visual field (40%), followed by initiating in one half (27%) or in the entire (25%) 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.4Dr 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.5

References

1. Viana M, et al. Clinical features of migraine aura: Results from a prospective diary-aided study. Cephalalgia 2017;37:979–989.

2. Viana M, et al. Migraine aura symptoms: Duration, succession and temporal relationship to headache. Cephalalgia 2016;36:413–421.

3. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2018;38:1–211.

4. Queiroz LP, et al. Characteristics of migraine visual aura in Southern Brazil and Northern USA. Cephalalgia 2011;31:1652–1658.

5. Viana M, et al. Clinical features of visual migraine aura: A systematic review. J Headache Pain 2019; in press.


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.

Why include multidisciplinary treatment when organising the headache clinic?



Prof. Georgoudis described how patients attending head-ache clinics may present with a number of symptoms, including intense, bilateral pain that fails to deteriorate with regular physical activity. While patients often receive pharmacological interven-tions, incorporating physical therapy into patient management could provide a second opportunity to improve health outcomes. He further described targets for the management of physical therapy, including cervical spine manipulation or mobilisation,1 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) using a mechanical algometer to measure seven bilateral points, which were measured at baseline, after five treatments and after ten treatments.

Prof. Georgoudis described how a significant improvement on the primary outcome of PPT score was observed for patients in the control group, who received acupuncture treatment along-side stretching, as well as patients in the experimental group, who received treatment incorporating acupuncture, stretching and manual physiotherapy. A significant change from baseline was observed at both week five and week ten. However, at week ten, an augmented benefit on the primary outcome of PPT score was observed in the experimental group compared with the control group. A similar pattern of benefits was observed for all secondary outcomes, including reduction of pain, anxiety and depression, catastrophising, functioning and quality of life.

References

1. Cleland JA, et al. Examination of a clinical prediction rule to identify patients with neck pain likely to benefit from thoracic spine thrust manipulation and a general cervical range of motion exercise: multi-center randomized clinical trial. Phys Ther 2010;90:1239–1250.

2. Hall T, et al. Efficacy of a C1-C2 self-sustained natural apophyseal glide (SNAG) in the management of cervicogenic headache. J Ortho Sport Phys Ther 2007;37:100–107.

3. Georgoudis G, et al. The effect of myofascial release and microwave diathermy combined with acupuncture versus acupuncture therapy in tension-type headache patients: A pragmatic randomized controlled trial. Physiother Res Int 2018;23:e1700.t

In the opinion of Prof. Georgoudis, the observed results demon-strate that hands-on physiotherapy techniques, alongside acupuncture and stretching, can produce desireable physio-logical improvements in patients with TTH, alongside providing cognitive and psychological benefits. Considering this, a bio-psychosocial approach to treating patients in the headache clinic could, therefore, complement existing pharmacological interventions.


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.

The role of the hypothalamus in migraine



Migraine is defined by the attack phase, however, the brain of migraineurs is also different from that of healthy controls outside of the attack.Arne May (University of Hamburg, Germany)

Chronic headache and the hypothalamus

Prof. May started his presentation with an overview of the role 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 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 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 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 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

Transitioning into hypothalamic involvement in migraine, Prof. May stressed that previously, only the brainstem was linked to 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 brain


of a migraine patient in the 24 hours immediately preceding a migraine attack.7 Combined, these results suggest that while the brainstem may be the ‘migraine generator’, the hypothalamus may play the role of mediator in the pathophysiology of migraine. Prof. May concluded that the different subregions of the hypothalamus play different roles in migraine – the anterior hypothalamus might be the driver of attacks, while the posterior hypothalamus is involved in acute migraine headache. Addition-ally, he indicated that beta-blockers, but not topiramate, may have an effect on hypothalamic control, which could, in turn, inform treatment decisions.

References

1. May A, et al. Hypothalamic activation in cluster headache attacks. Lancet 1998;352:275–278.

2. Giffin NJ, et al. Premonitory symptoms in migraine – An electronic diary study. Neurology 2003;60:935–940.

3. Quintela E, et al. Premonitory and resolution symptoms in migraine: A prospective study in 100 unselected patients. 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.


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 Headache Federation, Prof. Todd J Schwedt (Mayo Clinic, USA) and Dr Anders Hougaard (University of Copenhagen, Denmark) discussed the past, present and future of migraine brain imaging.

Diagnosing Chronic Migraine

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-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.

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-paring the brains of migraineurs with healthy controls, including magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and magnetic resonance (MR) tractography. A study using MRI has demonstrated cortical thinning in migraineurs compared with healthy controls, with differences observed bilaterally in the cen-tral sulcus, the left middle-frontal gyrus, the left visual cortices and the right occipito-temporal gyrus.1 Similarly, structural abnor-malities of the brainstem have been observed in migraineurs, including smaller midbrain volume, inward deformation of the ventral midbrain and pons, and outward deformations in the lat-eral medulla and dorsolateral pons.2

In Prof. Schwedt’s opinion, understanding aberrant brain struc-ture in migraine patients could lead to the development of objective, replicable biomarkers for migraine. These biomark-ers could be beneficial for diagnostic and prognostic purposes, and may eventually be used to predict how a specific patient will respond to treatment.



References

1. Magon S, et al. Cortical abnormalities in episodic migraine: A multi-center 3T MRI study. Cephalalgia 2019;39:665–673.

2. Chong CD, et al. Structural alterations of the brainstem in migraine. Neuroimage Clin 2017;12:223–227.

3. Weiller C, et al. Brain stem activation in spontaneous human migraine attacks. Nat Med 1995;1:658–660.

4. Hougaard A, et al. Increased intrinsic brain connectivity between pons and somatosensory cortex during attacks of migraine with aura. Human Brain Map 2017;38:2635–2642.

5. Schwedt TJ, et al. Migraine subclassification via a data-driven automated approach using multimodality factor mixture modeling of brain structure measurements. Headache 2017;57:1051–1064.

6. Chen W-T, et al. Comparison of gray matter volume between migraine and “strict-criteria” tension-type headache. J Headache Pain, 2018;19:4.

Functional changes in migraine

Dr Hougaard used his presentation to highlight successes in using functional imaging to understand migraine. He began by discussing research in which brainstem activation was observed during a spontaneous migraine attack, with increased activity persisting after an injection was administered to induce com-plete relief from headache, phonophobia and photophobia.3 While researchers have used different techniques to explore the reproducibility of these findings,4 there is still a need to uncover precisely which brainstem subregions are involved in migraine, whether this evidence can be used to diagnose migraine, and the effect of different migraine therapies on brainstem activity. In Dr Hougaard’s opinion, functional imaging is a powerful approach for studying migraine pathophysiology. The example of research into brainstem activity during migraine attacks high-lights the need for clinical evidence to be reproducible, and for researchers to build on existing research to gain greater insights into the underlying cause of migraine.

The future of brain imaging in patients with migraine

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.


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.

New peripheral targets in the treatment of migraine



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.

The periphery deserves a central role in migraine research.Antoinette Maassen Van Den Brink(Erasmus University Rotterdam, Netherlands)

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-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, 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 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/PAC1, 5-hydroxytryptamine (HT)1F, purinergic and gamma-ami-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.


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.

Epidemiology and impact of migraine in Europe



We need to make sure societies and governments understand that migraine is a disease that needs to be treated.Patricia Pozo-Rosich(Vall d’Hebron University Hospital of Barcelona, Spain)

Epidemiology of migraine in Europe

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 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 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 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 translated into clear and concise messaging that can be under-stood and acted upon.

Impact of migraine in Europe

Prof. Pozo-Rosich further emphasised that migraine has a sub-stantial negative impact at both an individual and societal level. The impact of migraine on individuals is considerable, with a cross-sectional analysis of survey data in France, Germany, Italy, 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 for


changing the perception of migraine among healthcare systems and employers. This includes educating clinicians, governments and workplaces about the devastating impact of migraine.

Moving forward: reducing the impact of migraine

Prof. Pozo-Rosich concluded with the positive message that treatment options are rapidly improving for migraineurs. New therapies are reducing the effect of migraine on functional abil-ity, increasing health-related quality of life and decreasing the financial burden of migraine. However, to realise the benefits of an improved treatment landscape, it is vital that the need for new treatments is fully communicated to all relevant stakeholders.

References

1. Stovner LJ, et al. Epidemiology of headache in Europe. Eur J Neurol 2006;13:333–345.

2. Stovner LJ, et al. Global, regional, and national burden of migraine and tension-type headache, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2018;17:954–976.

3. Stovner LJ, et al. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia 2007;27:193–210.

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.

http://www.dolordecabeza.net/wp-content/uploads/2018/11/3302.-Libro-Atlas-Migaran%CC%83a_baja.pdf




Can anti-CGRP monoclonal antibodies be beneficial for other painful conditions?


The neuropeptide calcitonin gene-related peptide (CGRP) plays a significant role in chronic neuropathic pain, and the therapeutic benefits of anti-CGRP monoclonal antibodies (mAbs) in migraine treatment are well established. However, CGRP is not only expressed in the central nervous system, but also in nearly all human organs.1 In a presentation at the 13th annual congress of the European Head-ache Federation, Prof. David W. Dodick (Mayo Clinic, USA) provided a brief overview of recent studies on the use of anti-CGRP mAbs in non-migraine pain conditions.

Primary headache

Thus far, clinical trial results have not demonstrated a therapeutic 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 emphasised that additional studies of anti-CGRP mAbs in cluster headache should be conducted.

Secondary headache

Animal studies have shown that concussions lead to headache and pain-related behaviours, and that the administration of anti-CGRP 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.

Non-headache pain

A recent systematic literature review showed an association between measured CGRP levels and somatic, visceral, neuropathic and inflam-matory pain.4 In particular, CGRP levels had a positive correlation with pain in somatic pain conditions. However, an initial investigation of anti-CGRP mAbs in patients with osteoarthritis knee pain failed to demonstrate a therapeutic benefit compared with placebo.5 In Prof. Dodick’s opinion, this was an unexpected result and he questioned whether the correct joint was targeted in this study. Prof. Dodick fur-ther commented that other pain syndromes that could be potentially addressed with anti-CGRP are those of visceral, inflammatory and neuropathic etiology.4, 6


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.

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.


Patients with migraine report diminished functioning and well-being on health-related quality of life measures.1 Underdiagnosis and undertreatment means that the magnitude of the clinical economic burden to individuals, relatives and society may be underestimated.2 During a session at 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.

Societal impact of migraine



If we want women to be leaders, we need to treat their migraines.Prof. Gisela Terwindt(Leiden University Medical Centre, the Netherlands)

Migraine burden and barriers

Prof. Gisela Terwindt (Leiden University Medical Centre, the Neth-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 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 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, migraine represents a significant barrier to the progression of 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 use


and lost employment over a 4-month period were acquired and used to estimate the economic costs of migraine.9 Prof. McCrone explained that alongside expenditure on healthcare services including inpatient, emergency department and other specialist care, individuals incurred large costs related to informal care. The latter accounted for 74% of the total migraine-related cost per person of £6588 over 4 months.

A need for greater evidence explaining the full cost of migraineDuring the question and answer session, all speakers agreed that there is a need for more evidence on the economic cost of migraine. However, the optimal way of presenting this evidence to regulatory and reimbursement bodies is still being debated.

References

1. Terwindt GM, et al. The impact of migraine on quality of life in the general population. Neurology 2000;55:624–629.

2. Agosti R. Migraine burden of disease: from the patient’s experience to a socio-economic view. Headache 2018;58:17–32.

3. Vos T, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic 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 PREPARATIONJUNE 2019

13th european headache federation congress (ehf)...individual symptoms. physiotherapy consisted of...

Documents