Migraine is among the most debilitating conditions in medicine

WSJ, June, 6, 2011

A migraine is among the most debilitating conditions in medicine—a blinding, throbbing pain that typically lasts between four and 72 hours. There is no cure.

Yet, a few hours or days before the dreaded headache sets in, subtle symptoms emerge: Some people feel unusually fatigued, cranky or anxious. Some have yawning jags. Others have food cravings or excessive thirst.

If migraine sufferers can learn to identify their particular warning signs, they may be able to head off the headache pain with medication or lifestyle changes before it begins, experts say.

"The holy grail of migraine treatment would be to have something you could take tonight to ward off an attack tomorrow," says neurologist Peter Goadsby, director of the headache program at the University of California-San Francisco. At a conference of the American Headache Society last week, he and other experts said these early symptoms may hold clues to what causes migraines in the first place.

Scientists have long known about this so-called premonitory phase, which occurs well before the better-known aura, the flashing lights and wavy lines that about 30% of migraine sufferers see shortly before the headache begins. Yet there have been only a handful of clinical trials treating patients in the premonitory stage—in part because the symptoms are so vague. Still, once patients know what to look for, many can identify some early warning signs.

"If you ask the average migraine sufferer, 'Do you have any symptoms a few hours before the headache starts?' about 30% will say yes," says Werner Becker, professor of neuroscience at the University of Calgary in Alberta. But given a list of 20 common signs, from changes in mood, appetite or energy to urinating frequently or yawning excessively, about 80% of patients will say, "Oh yes, I've noticed that," he says.

Dr. Becker says one of his patients frequently feels dizzy and loses her appetite about 6 p.m. and knows that an attack is imminent. She finds that taking the migraine drug rizatriptan—usually taken only after the headache starts—can ward it off. "If she doesn't take it, then the next morning, she wakes up with a full-blown migraine," Dr. Becker says.

Sheena Selvey, a 28-year old special-education teacher in Northbrook, Ill., says she knows a migraine is coming when co-workers say her neck muscles have tightened up. She rubs her neck with an essential peppermint oil until she can inject herself with Imitrex, another medication usually used to stop rather than prevent headache pain. She says such steps have helped reduce attacks to two or three times a month from three or four times a week.

Ben McKeeb, a 35-year-old nursing student in Bellingham, Wash., says his wife noticed that his forehead muscles tense up in the shape of a "V" a few hours before his headaches begin. "I can almost always catch that feeling, and if I do all the right things—stay hydrated, stay out of the sun, get plenty of sleep, don't work too hard—I probably won't get one," he says.

Nationwide, about 36 million Americans suffer from migraines. Although some people use the word very loosely, migraines are far more severe than a typical headache, last longer and tend to involve nausea, vomiting and sensitivity to light. Women are three times as likely as men to get migraines, and they've been diagnosed in children as young as 6 months. Migraines cost the country more than $20 billion a year in lost wages, disability payments and health-care bills, according to the American Headache Society, an organization of health-care professionals who specialize in headaches.

As many as half of all sufferers don't seek treatment, in part because they think there is little doctors can do for them. In fact, treatments are proliferating, including over-the-counter pain relievers for mild cases and a class of drugs called triptans typically used to stop migraine pain. For chronic migraines, doctors also prescribe beta blockers, antiseizure medications and antidepressants, but they have significant side effects and help only about 50% of patients about 50% of the time. More drugs are in clinical trials, and non-drug treatments such as acupuncture, massage, biofeedback and transcranial-magnetic stimulation are also showing some promise at alleviating migraine pain.

Doctors used to tell patients to wait until their headache pain was severe to moderate before taking medication. But that's changing. "Now we know the closer we can get to the beginning of the attack, the better the outcome will be," says David Dodick, president of the American Headache Society and neurologist at the Mayo Clinic in Phoenix.

Experts also think that they can learn a lot about the origin of migraines by studying how the body changes in the premonitory phase.

For example, "Many people tell us that they vomit yesterday's food," says Joel Saper, director of the Michigan Head-Pain and Neurological Institute in Ann Arbor. That's a sign, he notes, that their digestion slowed long before they knew a migraine was coming.

Some experts are also re-examining the role of common migraine triggers such as alcohol, chocolate, red wine, aged cheese and caffeine. It could be that physiological changes in the premonitory phase trigger a sensitivity to such foods, rather than the other way around.

"For years, patients would say they got a migraine because they ate chocolate or pizza or a hot dog," says Dr. Saper. "But when you ask why they ate those things, they say, 'I had this insatiable craving....' We need to understand where that craving came from."

Functional-imaging studies of the brain have revealed another tantalizing clue: During the aura phase, a wave of electrical activity sweeps over the outer, furrowed layer of the brain known as the cortex, at a pace of 2 to 3 millimeters per minute. This wave—known as "cortical spreading depression"—activates nerve cells as it goes, and the symptoms sufferers report typically correspond to the area of the brain the wave is passing over. For example, the patient sees flashing lights and wavy lines when the wave is over the visual cortex, and tingling in the hands and feet when the wave is in the motor cortex. Once the wave passes by, the nerve cells become quiet and spent.

Dr. Goadsby and colleagues at UCSF are conducting more imaging studies to determine what brain activity occurs during the premonitory phase.

Experts say migraine sufferers can help themselves and their physicians by keeping a careful log of when their headaches occur, what they ate, drank and did several days in advance, as well as any early symptoms they experienced. They may notice patterns and find their own warning signs.

And even though there is no scientific evidence that taking medication at that early stage will stave off migraine headaches, some experts say it makes sense for patients to avoid their known triggers if a migraine seems imminent.

"If stress seems to be a trigger, cut back on your schedule, try a relaxation technique, don't plan a 12-hour day," says Dr. Becker. "You could potentially stop an attack."