I am very pleased to be asked for an interview on the occasion on my receipt of The Brain Prize. EAN is very close to my heart and I regard it as partly being my brainchild. I started out my work for European Neurology in the late 1980s, drafted the future constitution of the European Federation of Neurological Society (EFNS) and became its first vice president. The EFNS went through an enormous development in parallel with the development of the European Neurological Society (ENS). I made several unsuccessful attempts to fuse the two organizations, but this was accomplished by my successors in particular professor Jacques Dereuck. Nothing has made me happier because the united organization, the EAN, is a very strong organization that can match- and work in parallel with the American Academy of Neurology.
To receive a prize like The Brain Prize is obviously an enormous honor. Some people call it the Nobel Prize of brain research. The main importance is, however, that it draws attention and respect to a field of research somewhat neglected and disregarded, research into migraine and other headaches. What is perhaps even more important is that sufferers of severe migraine and other headaches are subject to prejudice and have received little understanding, even from their physicians and even from neurologist. I am sure my colleagues in future will hold these diseases in higher regard and will work harder to improve their service to these patients. Maybe the prize will also make it a little easier to fund research into migraine and other headaches. Years ago, we showed that this field is the least funded of all neurological research fields in comparison to the huge prevalence and disability of these disorders. There is a lot of research showing that patients are poorly diagnosed and very poorly treated throughout the world. Therefore, more teaching about migraine and other headaches at the pre graduate level is necessary and the prestige of this prize may perhaps help a little bit to amend the situation.
The prize was given for broad efforts in migraine research but in particular for the discovery of the importance of calcitonin gene-related peptide (CGRP). It was first shown in sensory nerves around cranial blood vessels by my colleague Lars Edvinsson. He also showed that CGRP is the strongest vasodilator in the cranial vasculature that is known. He and Goadsby showed that CGRP may perhaps be increased in blood from the head during a migraine attack. We then showed that infusion of CGRP to normal people caused headache and to migraine patients it caused a migraine attack. We also showed that blocking CGRP was safe and finally, I headed the proof of concept study showing that a blocker of the CGRP receptor is effective in treating acute migraine attacks. Next followed a long development and the marketing of monoclonal human antibodies against CGRP or its receptor a few years ago, drugs that are now revolutionizing the prophylactic treatment of migraine. Although these drugs are effective, they are far from solving the whole problem of migraine and therefore it is extremely important to continue investigating the causes of migraine. One aspect is the genetics because it has been clear for many years that migraine is a heritable disorder, approximately 50% of the risk is genetic and 50% environmental. In the rare sub-form familial hemiplegic migraine 3 genes are now known in which mutations cause the disease and this type of migraine and probably also migraine with typical aura are related to the ion homeostasis across neuronal cell membranes. Migraine without aura is complex. We are in the process of publishing 123 genetic variants all associated with migraine but all with a small increase in the relative risk. This has also been the fate of other neurological disorders such as multiple sclerosis. A lot of variants with small effect but nothing that really changes our diagnosis, prophylaxis or treatment. We have shown that polygenic risk score is correlated to effect of triptans but in my opinion big efforts in migraine genetics have so far not led to the break though that we are all hoping for.
During my 40 years of migraine research I have worked on numerous other problems than the ones that have given me The Brain Prize. One has been The Classification of Headache Disorders. 40 years ago, it was completely uncertain how to diagnose migraine and other headaches and it was done very differently in different countries. In 1988 we published The International Classification of Headache Disorders which gave explicit diagnostic criteria for all headache disorders i.e. more than 100 different disorders. During two successive editions of the classification I continued with progress but still a lot of uncertain issues remain in relation to classification and diagnosis. One of them is the question of migraine with brainstem aura, originally called basilar migraine 50 years ago. During this period, it was first shown that there is no spasm of the basilar artery as originally proposed. The name was then changed to basilar migraine and finally to migraine with brain stem aura. The typical aura of migraine is caused by a cortical spreading depression, but does that occur in the brain stem? We know that it can occur in the hippocampus and therefore probably also in other deep gray structures, but it cannot spread throughout the brainstem. It was proposed by professor Ducros that it is in fact not brain stem mechanisms but bilateral cortical mechanisms that cause the symptomatology called migraine with brain stem aura. We went through the entire literature, plus a huge patient material at the Danish Headache Center and concluded in a paper published in Brain that brain stem aura does occur, but it is extremely rare. I am going to report about this at the forthcoming congress of the EAN and professor Ducros is going to oppose my views. A wonderful thing about science in general and neuroscience in particular is that for every step forward there are always new avenues of research opening up.