Migraines — The Dana Guide

by Michael A. Moskowitz

March, 2007

sections include: who gets migraines?, diagnosis and treatment 

Migraine attacks account for the bulk of headache-related visits to physicians. In contrast to other headaches, migraine is characterized by episodes of head pain that is moderate to severe, pulsing, and often on only one side. The pain typically lasts 4 to 72 hours and worsens with physical activity. Nausea and vomiting so frequently accompany a migraine headache that these symptoms help define the problem.

About 15 percent of migraine headaches are also preceded by an aura—a neurological symptom that begins gradually over minutes and typically persists less than an hour. Most often an aura appears as a slowly expanding visual disturbance, usually starting at the center of a person’s vision and spreading to the edge, with shimmering and wavy images. Severe headache follows the aura. Typically within 15 to 20 minutes, a person suffers nausea, vomiting, and sensitivity to light, sound, and smell, particularly after the aura has disappeared.

Some migraine sufferers, or “migraineurs,” sense tingling or numbness on one side, particularly in the arm, hand, and face, that then spreads like the visual aura. Other people may experience difficulties with language, balance, or weakness. In some cases, euphoria, increased energy, or depression can precede a headache, with abnormal cravings for certain types of food that may last up to 24 hours.

Migraine headaches may be incapacitating, requiring a person to take time off from work or other important activities. Another factor that brings migraineurs to the doctor are the related neurological symptoms. The aura can be disturbing. Sufferers sometimes worry that the symptoms are the first sign of a brain tumor, stroke (ischemic, hemorrhagic) or epilepsy. Fortunately, a physician can readily distinguish between epilepsy and migraine and rule out the more sinister diagnoses through brain imaging. Furthermore, it’s rare for the neurological symptoms and signs to persist in migraine, but a brain tumor or stroke creates an ongoing dysfunction of the nervous system affecting vision, sensory, or motor activity.

Who Gets Migraines?

Before the age 11, migraine is equally common in boys and girls—which is to say, not very common at all. Migraines commonly begin in the second or third decade of life and become less frequent after middle age. In adulthood, migraine headaches both with and without auras occur more commonly in women than in men, in a 3-to-1 ratio. Surveys in industrialized countries show that 10 percent to 12 percent of people suffer migraines in a given year, 15 percent to 18 percent of women and 6 percent of men. Most migraine sufferers experience attacks less than once a month. Typically, about 60 percent of migraineurs suffer fewer than eight attacks per year, 25 percent have eight to fourteen per year, and 15 percent have more than fourteen per year.

There is a widely held impression that migraine occurs more commonly in individuals with greater intelligence, more education, or higher social class. Comforting as this belief may be for a migraineur, it’s not supported by data from the general population. In fact, people with lower socioeconomic status appear to be at greater risk, perhaps because the condition is associated with stress.

Perfectionism was also thought to predispose a person to migraines, but a rigorous measurement of obsessionality among people suffering from the problem hasn’t shown that to be a risk factor. There is, however, good evidence that migraineurs are at a higher than usual risk for depression and anxiety and panic disorders. Depression in this instance is not just a response to the headaches; it often appears before the onset of migraine. Of course, the recurrent pain and debility can make depression and anxiety worse.

A wide variety of factors in the environment are thought to trigger migraine attacks, though these are rarely reliable or predictable. Several triggers may have to combine to precipitate a person’s headache, possibly during a vulnerable period. Some of the most frequently reported causes include certain foods or food additives, too much or too little sleep, fasting or missing a meal, strong odors, changes in weather (especially barometric pressure), flickering or glaring light, emotional upset, physical exertion, and fluctuation in hormonal levels.

The biological basis for migraine is not well understood but is being carefully studied. Because so many people suffer migraines, the condition may have a lot to tell us about the brain’s normal organization and function. New techniques developed over the past two decades are beginning to provide more focused investigations, especially in genetics, the mechanisms of pain generation, and the changes in the brain that occur during the aura.

At present, two theories shape thinking about the biological basis for an attack. The first assumes that the aura is caused by a temporary lack of blood to the brain due to a contraction and narrowing of the blood vessels, and that the headache develops from the subsequent expansion of those vessels, which activates the pain fibers around them. As evidence to support this theory, the drugs most commonly used to stop a migraine attack act to constrict blood vessels. The main competing theory suggests that migraine arises primarily from a disturbance in the brain, and the abnormal brain cell functioning is what disturbs the blood vessels. Proponents of this hypothesis say the narrowing and widening of the vessels are neither necessary nor sufficient to generate the migraine symptoms. There are indeed multiple neurological symptoms during the aura that would be difficult to blame entirely on the blood vessels in a specific region of the head. If applied rigidly, neither theory explains all the features of an attack.

Migraine attacks can be divided into stages, and the initiation stage is the least understood. Some researchers have suggested that there is a migraine generator in the brain stem; this would act as a control switch, rendering people more or less susceptible and conceivably activating an attack itself. Other studies suggest that the attacks start in the cerebral cortex with an event closely resembling a spreading excitation of cells within the brain, not unlike what migraineurs experience during the flashing light of a visual aura. This spreading excitation is then followed by a “quieting” or depression of neuronal activity. Researchers have found evidence for this latter theory by using a variety of imaging techniques on the brains of people suffering attacks. These recent studies confirm that a migraineur’s brain is unusually susceptible to slow spreading waves across the cerebral cortex.

A number of twin studies show that identical twins have a higher rate of migraine than nonidentical twins. This hints that there are genetic factors in a person’s susceptibility, but no one has identified a clear pattern of inheritance.

A recent study convincingly linked a mutation in a particular gene to a rare variant of migraine in which motor weakness is very common. This disorder, called familial hemiplegic migraine, seems to be due to a mutation on chromosome 19 and relates to problems with a protein that controls the flow of calcium into and out of cells. We know from other studies that calcium flux is very important in determining nerves’ excitability and their release of neurotransmitters, and thus affects how cells communicate with one another. Approximately 50 percent of families with this rare form of migraine have an abnormality of this gene, so it seems likely that similar genes and proteins are related to other inherited forms of migraine.

This indication that calcium flux is involved in some migraines has led researchers to focus on the channels that move calcium, potassium, sodium, and other ions into and out of cells. These channels cause occasional transient disturbances, called channelopathies, in muscles and nerves. Neurons are for the most part unaffected, but every so often a disturbance in channel function appears as a neurological problem lasting minutes or hours, after which the nerves resume working normally. Stress seems to be important in inducing these attacks, just as it is in migraines. If we can better understand these ion-flux channels and how they produce transient disturbances, we may be able to develop drug therapies for those problems and possibly migraine as well.

Diagnosis and Treatment

There are no blood tests, urine tests, or X rays to diagnose migraine, though doctors may use such studies to exclude other conditions that masquerade as an attack. Rather, migraine is identified by collecting the symptoms that a person reports and matching them to a list of diagnostic criteria.

Fortunately, migraine can be well treated and controlled by medications. Aspirin-like drugs (nonsteroidal anti-inflammatory drugs) are often effective. Ergotamine is frequently prescribed specifically for debilitating migraines and can be taken orally or with an inhaler. For faster effect, the related drug dihydroergotamine mesylate can be taken by injection. Both of these chemicals cause blood vessels to constrict. A new group of drugs, the triptans, that bind to receptors for the molecule serotonin have also proved useful in treating acute migraine attacks. As many as 80 percent of people find significant relief during attacks by taking these medications.

For people who want to or have to minimize their use of these medications, untreated migraine attacks generally persist for a few hours and rarely more than 72 hours. Sleep is an excellent way to terminate an attack. Relaxation techniques work in some individuals but are less effective than medication. Removing sources of stress or emotional turbulence often reduces the severity and frequency of symptoms, though this may not always be feasible for an individual.

Usually migraines don’t require a person to see a headache specialist. When they do, there are physicians and centers specializing in the treatment of migraine. The headache specialist is particularly useful when the disorder no longer responds to medications, and when the migraine changes its character by becoming more frequent and incapacitating. Often when migraine attacks are severe, doctors prescribe medication on a daily basis, not waiting for the headaches to begin; this is meant to lessen the frequency and intensity of attacks when they occur.

Sometimes migraineurs become anxious or depressed, or overuse pain relievers, and start suffering daily headaches without the other symptoms of migraine. This condition, called transformed migraine, is a form of tension headache and should be treated as such. The medicines and other treatments for migraine won’t be as effective.

At present, there are no cures for migraine, but the natural history for most people is a waxing and waning course. Periods with increasing attacks will be followed by periods in which the attacks become much less common and medication unnecessary. There is no surgical treatment for migraine, and that approach is unlikely in the future.

As we start to understand the neurological events early in a migraine attack, we’ll be able to identify additional targets for therapy, most likely including the waves of excitation and depression in nerve cells, and the genes associated with the flux of specific ions into and out of cells. Until the past decade, most drugs for migraine were discovered through serendipity: they decreased attacks when migraineurs happened to be taking them for unrelated disorders. That situation has changed with the introduction of better imaging technology and tools that let us work at a molecular level. Our challenge for the future lies in identifying the genetic and environmental factors that render an individual susceptible to an attack, and in better understanding how those factors alter brain function for a transient but painful time. 

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