Research Widens Range of Therapies To Treat Migraines
by Marilyn Chase
from The Wall Street Journal

Migraines aren't for sisies. Yankee catcher Joe Girardi was hammered by a headache so bad that he ended up in the hospital after a recent winter workout in Tampa, Fla.

They're the 1812 Overture of headaches, with pulsating percussion and cerebral cymbals that make you fell like your head will all but explode. But after centuries of myth and mystery, the science of migraine only now is expanding our knowledge of its causes and treatment options.

For an estimated 11 million to 23 million Americans, the debilitating condition features pulsing pain (often one-sided) with nausea and sensitivity to light and sound. A visual "aura" sometimes precedes the headache with a shower of colored stars, or images fractured into herringbone or cubist patterns.

Women outnumber men among sufferers, but migraine isn't an exclusively female condition. Thomas Jefferson and Sigmund Freud were among male sufferers.

History records heroic and desperate efforts at cure. in the sixth century A.D., the emperor Justinian pressed his pounding head to a watery stone called the "column of tears" in the cisterns of Istanbul. Other failed remedies included purging, bleeding, encircling the head with a hangman's noose and drilling a hole in the skull.

Long observed to run in families, migraines now claim a gene of their own. An international team recently identified a gene on chromosome 19 that causes familial hemiplegic migraine, a severe form coupled with paralysis. Genes for more common migraines are expected to follow.

What Causes migraine? A region in the brain's core - the brain stem - becomes abnormally activated. Chemical messengers provoke inflammation and pain in fibers surrounding vessels. Reduced blood levels of key brain chemical serotonin may also play a role. Such insights have helped spawn specific designer drugs, beginning with Glaxo Wellcome's sumatriptan (Imitrex), an injection which mimics serotonin. Now five or more similar compounds are in the pipeline. But sumatriptan's cardiac side effects, which rule out anyone with heart disease, remain a factor.

By trial and error, migraine sufferers learn what aggravates their headaches. Red whine, chocolate, aged cheese and cured meats containing nitrates are among triggers.

Drugs such as nitroglycerin can also be culprits. Estrogen in birth-control pills and replacement therapy aggravate migraines, especially in women whose headaches occur according to their monthly cycle. Food additives such as MSG and the sweetener aspartame also have been implicated. But triggers are individual and variable.

"Don't go crazy with diets unless you're sure," says Stephen Silberstein, co-director of the Comprehensive Headache Center at Germantown Hospital in Philadelphia.

Scores of drugs now can prevent and treat migraine. Treatment can include simple analgesics such as aspirin and acetaminophen (Tylenol), nonsteroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen and naproxen, combination products blending painkillers with caffeine and narcotics, such as Demerol. Antinausea drugs also help, but nothing is 100% effective.

New tools include oral sumatriptan, plus nasal forms of the drugs lidocaine and dihydroergotamine (DHE). The mineral magnesium can abort a migraine when given intravenously, and pill forms are being studied. The downside is that most drugs - even aspirin - can cause a "rebound" or withdrawal headache, if taken for more than two or three days in a row.

The Internet is abuzz with alternative treatments like the herb Ferverfew, which showed some benefit in a study, says Richard Lipton, co-director of the headache unit at Montefiore Medical Center in the Bronx, N.Y. but he cautions "capsules full of leaves" deliver imprecise doses.

When migraines attack relentlessly (more than twice a month), doctors turn to daily prevention using calcium channel blockers, beta blockers, tricyclic drugs of the antiseizure drug Depakote. Some take Prozac. But all were developed for other conditions, and all have side effects.

After years of experimenting with treatments, Ann Kurzweil of San Francisco now uses the combination pill Fiorinal with codeine as her first line of treatment, reserving sumatriptan injections as a last resort. She gave up chocolate, adding, "It's just not worth it."

Many people never visit a doctor, managing with over-the-counter analgesics. But when migraines disrupt daily life, professional care is in order. Doctors elicit detailed histories, and may order brain-imaging to rule out a stroke. People worry about having brain tumors or aneurysms, says Michael Moskowitz, a professor at Harvard Medical School. "It's the role of the doctor to reassure through various tests that this is not a life-threatening even," he says.

Doctors, however, urge emergency care if you experience a "thunderclap" headache, "the worst headache of your life" or any headache with paralysis, confusion, loss of vision, fever and stiff neck, or an inability to communicate.

Resources to help sufferers include the American Council for Headache Education in Woodbury, N.J.; books such as "Migraine: The Complete Guide" (Dell Publishing) and "Taking Control of Your Headaches" (Guilford Press); and the National Headache Foundation's Web site at