MTIS takes place every two years to enhance international researchers’ scientific knowledge and promote a better understanding of migraine through debate and exchange of ideas. Here is a summary of presented data that we found particularly interesting at the September 2018 meeting in London.
Migraine and women1
- The MacDonald Critchley Lecture opening the MTIS 2018 meeting was delivered by Gisela Terwindt (Leiden University Medical Centre, The Netherlands). She explained that across all age groups, more women than men suffer from migraine, with around 1 in 3 women affected by this condition over their lifetime.
- In migraine patients, intrinsic factors increasing the risk of an attack include genetic factors and sex hormones. Multiple genetic risk variants have been identified in genome-wide analyses. Unlike psychiatric disorders, where several disorders may have the same genetic variants as risk factors, gene variants associated with migraine do not appear to be linked to other neurological disorders.
- Changes in hormone levels during the menstrual cycle influence onset of attacks and this relationship is recognised in the International Headache Society (IHS) Classification ICHD-3.
- Migraine is a risk factor for stroke in women and, among patients with migraine, the risk of stroke increases further for women aged <50 years, those who have migraine with aura, and those taking combined oral contraceptives.
Migraine co-morbidities; what have we learned recently?2
- Richard Lipton (Albert Einstein College of Medicine, NY, USA) stressed that comorbidities can complicate the diagnosis of migraine. They can also increase the disease burden (e.g. by negatively affecting quality of life), increase the risk of progression, and limit therapeutic options.
- The recently reported Chronic Migraine Epidemiology and Outcomes (CaMEO) Study applied a latent class analysis (LCA) modelling approach and identified eight natural subgroups of persons with migraine based on comorbidity profiles. These classes showed differences in demographic and headache features not used to form the classes. These findings may help inform the classification of headache, predict prognosis, identify people who respond to specific treatment classes. They may also allow future clinical trials to selectively target subgroups of migraine patients more effectively. Professor Lipton noted that although the CaMEO findings will need to be replicated, they provide direction for research to understand the pathophysiology underlying the comorbidity patterns identified.
Human models of migraine – Short-term pain for long-term gain3
- In the Migraine Trust lecture, Professor Messoud Ashina (University of Copenhagen, Denmark) discussed progress in studying induced migraine in humans. In the early premonitory phase of a migraine attack, brain activation occurs in the posterior hypothalamic region, the periaqueductal region, and the dorsal pons. Neuroimaging studies show that the vasodilator nitroglycerin (GTN) induces hypothalamic reactivity similar to that occurring in spontaneous migraine attacks. Pituitary adenylate cyclase activating polypeptide-38 (PACAP38) has also been explored as a pharmacological ‘trigger’ molecule of migraine-like attacks in humans.
- More recently, attention has focused on targets downstream from signalling pathway molecules involved in vascular muscle cell tone, including the vasodilator levcromakalim. In a preliminary study, 100% of patients with migraine receiving levcromakalim developed migraine attacks, suggesting that blocking of KATP channels may provide a new therapeutic target.
- Professor Ashina concluded that although there is an extensive supply of arteries and blood vessels expressing CGRP in the brain, more research is needed on the relationships between vascular and neuronal signaling to understand why some patients do not respond to CGRP pathway-directed therapies.
Signatures of the migraine brain4,5
- In the first talk in this session,4 Laura Schulte (University Medical Center Hamburg - Eppendorf, Gemany) showed how neuroimaging is providing insights into the mechanisms of neuronal activity for migraine phases, identifying specific brain regions involved. For example, during spontaneous and GTN-triggered migraine attacks, increased activation of the rostral pons is observed. The hypothalamus and visual cortex show increased activity during the early premonitory phase of GTN-induced attacks. Increased activity in the hypothalamus is also seen in chronic migraine.
- Shuu-Jiun Wang5 (Taipei Veterans General Hospital, Taiwan) looked at neuroimaging research on medication overuse headache (MOH). Patients with MOH comprise a heterogeneous population, including those with psychiatric disorders, substance dependence, and subjects taking a variety of medicines. Headaches may be a cause or consequence of their medication overuse. Combining imaging studies that used a variety of modalities has enabled the creation of a ‘pain matrix’ of features. A pain matrix shows areas where there is increased volume in patients with MOH. Neuroimaging has also shown involvement of reward/habit-forming circuits, increased volume in the putamen/dorsal striatum, and disruptions in the orbitofrontal cortex (OFC). Future studies are needed to understand the role of neurotransmitters and receptors in MOH to identify potential treatment targets.