I trained in Clinical Neurology and Neuropathology at Liège University (Belgium) and at the Massachusetts General Hospital (Harvard Medical School). Since my second year of medical studies I've been involved in basic neuroscience research and later in clinical research. Before becoming a full professor I had thus combined a career as a researcher employed by the National Funds for Scientific Research of Belgium and clinical work as an academic neurologist.

My first research interest was the spinal cord; its morphological organization in humans was the topic of my Ph.D. thesis, and at present I'm still coordinating a research group that studies regeneration and plasticity in experimental models of spinal cord injury.

“I was struck by the prevalence of migraine, the relative paucity of scientific studies and the need for progress both in the understanding of mechanisms and the management of patients.”

My interest in migraine research started 25 years ago when the Faculty members of my university, among several topics, chose "headaches" for the public lesson I had to deliver to obtain the degree of "Agrégé de l'Enseignement Supérieur." While preparing this lesson, I was struck by the prevalence of migraine, the relative paucity of scientific studies and the need for progress both in the understanding of mechanisms and the management of patients.

After some discussion with my supervisors I decided therefore to engage my clinical and research activities in migraine, which at that time, and to some extent still nowadays, was considered by many as a "minor" topic for a neuroscientist. I thus created a headache clinic and research unit locally, struggled to obtain support and facilities, and got involved rather quickly in the foundation and/or establishment of headache societies at the national (Belgian Headache Society), European (European Headache Federation), and international level (International Headache Society).

This study was initiated by studies from an American and an Italian group showing that the mitochondrial energy reserve in brain cells was reduced between attacks in migraine patients. High-dose riboflavin (vitamin B2) had been used with some success in so-called mitochondriopathies, i.e., genetic disorders causing muscle weakness and brain dysfunctions in children. As riboflavin does not induce any adverse effects (except very rare gastric intolerance and cutaneous allergy), we thought a trial in migraine prevention would be worthwhile.

After a pilot study with good results, we subsequently embarked on a multicenter, randomized, placebo-controlled trial, which had to be sponsored by the Belgian Headache Society because riboflavin is cheap and of no interest to the pharmaceutical industry. The trial was clearly positive, showing that, after three months, 400 mg of riboflavin once daily produced a ≥ 50% reduction in monthly headache days in 59% of patients compared to placebo effective in 15% of patients. These results have been replicated in only a couple of small studies because of the lack of industry support.

As a consequence, and for other reasons such as the rather long delay to maximal efficacy (2-3 months) as well as the lack of availability in many countries of capsules dosed at 400 mg, riboflavin remains underused in many migraine patients in whom it could be the first-choice treatment, such as children, patients with moderate attack frequency or with contraindications for other anti-migraine prophylactics, most of which have a high incidence of side effects. Meanwhile our riboflavin study—of which the 10th anniversary will be celebrated in 2008—has paved the way for the use of other metabolic enhancers in the preventive treatment of migraine, such as co-enzyme Q10.

I have used clinical neurophysiology as a tool for exploring migraine pathophysiology since the very beginning of my research activities in migraine. The first study we did was on an event-related cerebral potential called "contingent negative variation." It showed for the first time that between attacks the brain of migraineurs responded differently in a reaction time-expectation paradigm compared with a normal brain: the response was exaggerated at the end of the trial but this was mainly due to the fact that the cerebral response did not habituate, i.e., decrease in amplitude, during the repetition of the stimulations.

This initiated a number of studies in our group in which various stimulation modalities (tactile, auditory, visual, etc.) were used to show that the most reproducible abnormality of the migrainous brain between attacks is the lack of habituation when stimuli are repeated. This hyperresponsivity may have two deleterious consequences: it increases the metabolic strain on the migrainous brain, and it may interfere with focused attention, and thus learning.

We have shown recently that the lack of habituation is probably due to a deficit of cortical tuning by thalamic afferents and serotoninergic input from the brain stem. This functional abnormality fluctuates in temporal relation to the attacks and the ovarian cycle, and it can be reversed by certain treatments.

I think personally that in the next ten years migraine research will progress by establishing more precise correlations between the genotype (polygenic profile) and the phenotype (clinical features, electrophysiological and biochemical profiles, etc.). Migraine research will also become more "translational" by deciphering in animal models basic migraine mechanisms identified in patients, and by testing in clinical trials novel therapeutic approaches developed in animal models.

My message for the general public is that the future looks bright for the management of migraine. However, to realize these expectations greater support is needed from public-health policymakers for care facilities and programs, and for clinical and basic research. Progress in care indeed depends quasi-exclusively on progress in knowledge.