INSERM Collective Expertise On Migraine

December 16, 1998

Distinguish between headache and migraine, insist on the fact that paramedical examinations (cerebral CT, MRI, etc.) are unnecessary for the diagnosis of migraine, inform patients that effective treatments exist, avoid confusing triggering factors and causes, give more importance to migraine at medical school, develop research on the origin of migraine and the mechanisms that lead to attacks, and develop a socioeconomic approach to the problem, these are the main conclusions of the Collective Expertise report on migraine done by the French National Institute of Health and Medical Research, INSERM, at the request of MGEN, the first French mutual. Distinguish between headache and migraine, insist on the fact that paramedical examinations (cerebral CT, MRI, etc.) are unnecessary for the diagnosis of migraine, inform patients that effective treatments exist, avoid confusing triggering factors and causes, give more importance to migraine at medical school, develop research on the origin of migraine and the mechanisms that lead to attacks, and develop a socioeconomic approach to the problem, these are the main conclusions of the Collective Expertise report on migraine done by the French National Institute of Health and Medical Research, INSERM, at the request of MGEN, the first French mutual.

Migraine is underdiagnosed, not taken seriously, poorly treated and little taught in France.

Yet this condition, which is a major source of incapacity and affects 12% of the French population, has been the focus over the last decade of a strict scientific approach that has led to remarkable advances, especially in the pathophysiology, genetics and therapy of migraine. The aim of the collective expertise report on migraine written by the french national institute of health and medical research, INSERM, is to provide an update on these advances and to summarize current knowledge on migraine.

The hope is to stimulate interest among physicians, researchers and decision-makers and to improve patient management.

Paraclinical examinations are unnecessary for the diagnosis of migraine

In the vast majority of cases the diagnosis of migraine is straightforward, being based on precise clinical criteria. The expert group stressed the fact that a meticulous and lengthy interview with the patient and friends/family (especially the parents when the sufferer is a child), together with a simple medical examination, is now sufficient to diagnose migraine. In the view of the expert group, too many needless examinations are prescribed (cerebral CT, MRI, Doppler US, EEG, etc.). In contrast, such investigations are warranted for atypical forms of migraine, or if the physical examination identifies the slightest abnormality.

The first diagnostic interview for migraine is necessarily long, lasting from 30 minutes to an hour. The experts underline that this is incompatible with the current price charged for a consultation with a general practitioner, and recommend that the fees be increased with a view to improving the management of migraine patients.

Avoid confusion between triggering factors and the underlying cause of the disease

Between a third and one-half of migraine patients identify factors that trigger their attacks. Anxiety, stress, fatigue, menstruation, fasting, heat, light, alcohol, some foods (chocolate, cheese, fatty food), etc. are all incriminated, but triggering factors can be multiple and can differ from one patient to another, and even from one attack to another in a given patient. Migraine patients mention an average of at least 4 triggering factors.

The experts underline the confusion that still persists between triggering factors and the cause of the condition, which remains unknown. This confusion maintains the idea that good management of triggering factors can make migraine disappear, and leads to a great deal of disillusionment among patients. When there is only one triggering factor, its elimination or modification can prove effective, but many patients have multiple factors that are difficult to modify, while other patients' attacks seem to occur with no forewarning.

Inform patients that effective treatments exist

About half of all patients never see a doctor for their migraine, convinced that there is no effective treatment; they decide to live with their migraine and often resort to disorderly self-treatment.

The experts criticize the defeatist attitude still encountered among some physicians and patients. If there is still no curative treatment for migraine, an impressive panoply of treatments can nevertheless relieve most patients and improve their quality of life. There is no one standard treatment applicable to all migraine sufferers, and the optimal treatment is often found only by a process of trial and error. But the experts underline that it is currently possible, thanks to judicious use of these treatments (both pharmacological and non pharmacological), to relieve migraine headache in 60 to 80% of cases. Rapid and total disappearance of the headache is obtained in no more than about 40% of cases. The management of migraine sufferers necessitates close collaboration between the patient and physician, a good deal of patience and rigor on the part of both, an open mind on the choice of treatment, and active involvement of the patient in therapeutic decisions.

Understanding the origin of the condition and the mechanisms that lead to attacks

Despite much progress in our understanding of migraine, the experts call for further research to identify the origin of the condition, and to answer outstanding questions such as What is the cascade of events that triggers attacks; What are the mechanisms underlying the pain; What are the links between triggering factors and the attack itself? What is the mechanism of the aura? and Why do attacks end spontaneously? We are still unable to offer a simple explanation for migraine, but one thing is sure: attacks are associated with vascular, neuronal and biochemical modifications, and many active substances in the brain are involved (serotonine, dopamine, histamine, substance P and NO). Major advances in our understanding of the pathophysiology of attacks have been made through studies of blood flow, brain metabolism and an animal model of meningeal inflammation. This model has led a new, although imperfect, hypothesis on the onset of an attack: migraine headache may be due to inflammation provoked by activation of nerve endings present around blood vessels of the meninges and dura mater, resulting in stimulation of the trigeminal nerve, vasodilation, and transmission of nerve impulses to higher brain structures.

The familial nature of migraine has long been known, but only very recently has this condition entered field of genetic research. In spite of major advances, the respective roles of genetic and environmental factors, and the modes of transmission, remain poorly defined. It is now essential to conduct research to identify the genes (possibly several) responsible for migraine and to elucidate the mechanisms by which mutations can generate the different patterns of migraine. Such studies could lead to a better understanding of the pathophysiology of the condition and to more effective treatments. Research has already begun on a rare form, called Familial Hemiplegic Migraine (FHM), in which at least 3 genes are involved. It remains to be determined if the same genes are also involved in the other, far more frequent forms of migraine.

Who to consult ?

One of the major questions posed by migraine sufferers is who to consult. Given the frequency of migraine, the experts consider that the condition should be managed principally by general practitioners. In contrast, a specialist (preferably a neurologist) should intervene whenever a therapeutic or diagnostic problem arises.

This implies that all physicians must have a good knowledge of migraine. The experts recommend that more importance be given to migraine in medical schools, which currently hardly touch on the subject.

Develop the socioeconomic approach to migraine

The socioeconomic approach to migraine is still in its infancy. This approach started with the emergence of the triptan drug class, the first truly costly treatment. Work on direct costs (diagnosis, treatments, etc.) confirm the high degree of self-treatment and the difficulty in identifying the care process used by those who consult. According to a French study done in 1993, the mean yearly cost of medical treatment is 469 francs per patient (around 100 US Dollars), but this figure is probably underestimated. Indirect costs (absenteeism, reduced productivity, etc.) are even more difficult to determine, but it appears that 1 to 4 working days are lost per year and per patient.

A great deal of research remains to be done. Optimization of migraine management could limit the current waste of resources due to unnecessary examinations and inappropriate treatments. It will also be necessary to determine the global cost for society, as well as intangible costs (career changes, desertion of certain activities, loss of self-confidence, etc.).

The experts' main recommendations Questions and answers

Do a woman's hormones affect migraine?
Yes Migraine often appears around puberty, improves during pregnancy in about two-thirds of cases, often worsens during the menstrual period, and disappears after the menopause in two-thirds of cases. The fall in estrogen levels at the end of the monthly cycle appears to be the main triggering factor in menstrual migraine.

Can children have migraine?
Yes. The frequency is often underestimated because the diagnosis is more difficult. Migraine in children is a source of suffering, behavioral changes and problems at school. A significant improvement can be achieved in most pediatric cases of migraine.

Do migraine sufferers have a particular psychological profile?
No. Migraine sufferers do not have the pathological personality that was often attributed to them (rigid, hesitant, perfectionist, frustrated, etc.). In contrast, a link has been established with anxiety and depressive disorders, although the reasons are unclear.

Are the higher socioprofessional categories more susceptible to migraine?
No. This notion is based on an ancient belief. There appears to be no simple relationship between socioprofessional category and the risk of migraine. For example, white-collar workers are not, in principal, more susceptible to migraine than manual workers.

Do migraine sufferers have a higher risk of stroke?
The answer is unclear The risk of cerebral infarction is slightly higher in young women with migraine, especially those with migraine announced by an aura and those who take the contraceptive pill and smoke. The absolute risk remains extremely low in this population, but migraine sufferers are strongly advised not to smoke and, if they choose to use oral contraception, to take a "mini pil"".

Universal, frequent, most often affecting young females

Migraine is very frequent, affecting nearly 7 million people in France. Women are the main victims:
18% of women have migraine, compared to 6% of men. In children the prevalence is 5 to 10%. At the time of puberty the prevalence increases rapidly in girls, leading to the clear female predominance observed in adulthood. Although people of all ages are affected, young adults account for the bulk of sufferers. Indeed, the disease almost always begins before the age of 40, and both the frequency and severity of attacks fall in the second half of life. The disease is truly universal, affecting people of all countries.

Migraine and headache : the confusion persists

Not all headaches are migraine headaches. Migraine is characterized by headaches attacks lasting hours or days, and is very often associated with signs such as nausea, vomiting, intolerance of light and noise, visual disorders, irritability, memory disorders... The attacks are separated by symptom-free periods. They can be preceded by transient neurological manifestations known as the aura. Although usually visual (scintillation, flashing lights, visual disorders, etc.), the signs can also consist of sensory disorders, speech problems and, far more rarely, paralysis.

A broad range of treatments

The main advance in drug therapy of migraine over the last decade is the emergence of a new pharmacological class, the triptans, which are used for treating attacks. These substances are effective on the headache and act on a special type of serotonine receptor (5HT1B/1D). Three triptans (sumatriptan, zolmitriptan and naratriptan) are already on the market, and the latter two are reimbursed by the social security in France. Others are awaiting a marketing license. This new class adds to the other three main drug classes used in this setting, i.e. analgesics (aspirin and paracetamol), nonsteroidal antiinflammatory drugs, and ergotic derivatives. Long-term prophylaxis can also prove necessary to reduce the frequency of attacks. About 15 drugs belonging to various pharmacological classes (betablockers, calcium antagonists, serotonine antagonists, etc.) are used but prophylaxis is painstaking and can have adverse effects. The experts recommend that research in this neglected area be reinforced. Non drug treatment s, such as acupuncture, relaxation and biofeedback have obtained noteworthy success rates. The experts state that the placebo effect is extremely important and variable in migraine (about 20% on average, up to 60% in some clinical trials). This implies that the efficacy of new treatments can only be assessed in double-blind clinical trials. The experts underline that while double-blind methodology is easily applicable to drugs, it is not suited to acupuncture and clearly unsuitable for relaxation and biofeedback.

Often misunderstood

Migraine is a an incapacitating condition: most patients have more than one attack a month, many attacks necessitate bedrest, and the malaise can persist between attacks. When the migraine is very severe the patient's quality of life can suffer markedly between attacks, with a negative self-image, avoidance of potential triggers, and a constant fear of unpredictable attacks. Migraine can hinder a person's career and upset his or her family life. The handicap is underestimated by the family of migraine sufferers, and is generally misunderstood by colleagues at work. Specialists in quality of life are starting to examine the impact of migraine in this respect. The experts recommend that quality of life now be considered one of the main end points in trials of new antimigraine therapies, be they treatments for attacks or long-term prophylactic therapies. The notion of quality of life must be taken into account in the management of migraine patients.
-end-
Who wrote the expert report ?

- 18 experts, presided by Professor Marie-Germaine Bousser (Hôpital Lariboisière, Paris) :
Daniel Annequin (hôpital Armand Trousseau, Paris), Jean-Claude Baron (INSERM, Caen), Isabelle Baszanger (INSERM, Paris), François Boureau (hôpital Saint Antoine, Paris), François Couraud (INSERM, Marseille), Bruno de Lignières (hôpital Necker, Paris), Nelly Fabre (hôpital Rangueil, Toulouse), Michel Hamon (INSERM, Paris), Patrick Henry (hôpital Pellegrin, Bordeaux), Isabelle Hirtzlin (INSERM, le Kremlin-Bicêtre), Jean-Marie Launay (hôpital Lariboisière, Paris), Hélène Massiou (hôpital Lariboisière, Paris), André Pradalier (hôpital Louis Mourier, Colombes), Françoise Radat (CHS Charles Perrens, Bordeaux), Jean-Michel Sénard (faculté de médecine de Purpan, Toulouse), Elizabeth Tournier-Lasserve (INSERM, Paris), and Christophe Tzourio (INSERM, Paris).

Scientific and editorial coordination was ensured by Roberto Flores-Guevara (INSERM "Molecular Medicine and Health Impact", Paris).

INSERM press office Phone: 33-01-44-23-60-84 Fax: 33-01-45-70-76-81 e.mail: presse@tolbiac.INSERM.fr

What is collective expertise?

INSERM's collective expertise reports provide updates on current medical and scientific knowledge in precise areas. To answer a question posed by the public or private sector, INSERM brings together a multidisciplinary group of scientists and physicians. The experts analyze the world scientific literature and summarize the main points. Recommendations are then made to help the organization that commissioned the report with their decision-making processes.



French National Institute for Health and Medical Research (INSERM)

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