A severe migraine attack can be agonizingly painful and accompanied by extreme light sensitivity and powerful nausea. For some people prone to migraines, medications keep their headaches under control, but for others no drug completely prevents debilitating attacks.

For such people, hope may come from a new clinical trial at the School of Medicine that offers an unexpected solution — doctors are closing a hole in the heart to try to fix the ache in the head.

The trial's first patient, Brenda Hoock, has undergone the heart procedure and found relief.

"Migraines ran my life so completely that when I heard about this new study, I thought, 'Maybe it sounds a little crazy, but I'm not going to turn down any opportunity that might help relieve this burden,'" she says. "I'm thoroughly amazed with the results. I haven't had a migraine in the six months since I came home. It's given me back my life."

Doppler imaging signals the presence of a patent foramen ovale.

About 600 million people around the world, including some 28 million Americans, get migraine headaches. Physicians and researchers suspect a link between migraines and a particular heart defect in some people.

The defect is called a patent foramen ovale or PFO. A remnant of fetal development, a PFO is a hole between the two upper chambers of the heart and is generally smaller than a pencil eraser. In the fetus, the foramen ovale passes blood from the heart's right atrium directly to the left atrium, bypassing the unused lungs. After birth, the foramen ovale grows shut — most of the time. In about 25 percent of people, it stays partially open, leaving a tiny, flap-covered passage between the atria — a patent foramen ovale.

"A PFO serves as a strain valve," explains John M. Lasala, MD, PhD, who oversees the Washington University portion of the migraine/PFO study. "If the pressure gets too high on the right side of the heart, the PFO can open, and blood can travel from the right to the left side. We think something usually cleared out by the lungs is in that blood and can trigger migraines."

One source of the idea that PFOs could be a cause of migraines was a study of divers with decompression illness. Researchers looked for a correlation between PFOs and "the bends," but they also asked the patients if they had migraines. It turned out that those with PFOs were more likely to get migraines than those without.

Other studies showed closing PFOs to prevent strokes had the side effect of significantly decreasing migraines. All in all, such studies have shown that about three-fourths of migraine patients who underwent PFO closure to prevent stroke or treat other problems got some migraine relief.

Estimates now hold that PFOs are present in about half of migraine sufferers who experience aura — an arc of zigzag lines in the visual field, numbness of one side of the face, weakness or altered consciousness — and in about a quarter of those who don't have aura with their migraines.

Early results from a set of ongoing British clinical trials of PFO closure in migraine patients found a 37 percent reduction in migraine frequency and duration. Now the School of Medicine is one of 13 centers conducting a new trial called the ESCAPE trial in which Hoock is a participant. (ESCAPE stands for Effect of Septal Closure of Atrial PFO on Events of Migraine with Premere™.) Led by St. Jude Medical in Minnetonka MN, the study aims to close PFOs in 500 migraine patients who haven't responded well to current medications.

"We don't believe this will be a cure for all migraines," says Lasala, medical director of the cardiac catheterization laboratory and professor of medicine. "But even if it's effective in just 50 percent of migraine patients with PFOs, it could benefit a lot of people."

The apparatus used to close PFOs in the ESCAPE trial delivers a small device to the heart through a vein in the leg. Once in place at the PFO, the tip of the device can be opened like a miniature umbrella with two opposing canopies that sit on either side of the wall separating the atria. Smaller and trimmer than previously available mechanisms for repairing heart defects, the device, called Premere™, is about a half an inch across and contains just a few fabric-covered wires.

"I designed Premere specifically for sealing PFOs — it has a very minimal, open architecture," says Dennis W. Wahr, MD, of St. Jude Medical. "With a PFO, you just have to hold the door shut for a while until it heals, so you don't need a lot of metal and fabric."

John M. Lasala, MD, PhD, right, with the inventor of the Premere™ patent foramen ovale closure system, Dennis W. Wahr, MD, of St. Jude Medical.

Lasala closed the PFO in Hoock's heart in late June of this year. Hoock had suffered from migraines since she was 7 years old, and in recent years, the 44-year-old had experienced more frequent and more debilitating attacks.

"I would have at least one really severe one every month," she says. "They would totally knock me down. I would basically say, 'Throw an ice pack on me, turn out the lights and leave me alone.'"

Hoock's migraines did not prevent her from working — she is a plant technician at a phone company — but she frequently had to disappoint her husband and three children by bowing out of family activities during migraine attacks.

Over the years, she tried many migraine treatments. Medications prescribed for migraines include beta-blockers, calcium-channel blockers and anti-hypertensive medications, as well as anti-seizure and antidepressant drugs. A new category of drugs developed especially for migraines, called triptans, came on the market in 1993.

"At various times, my doctors have had me on epilepsy and blood pressure medications, but they didn't work well," Hoock says. "With one of the epilepsy drugs, there was never a day in the three months I took it that I didn't have a headache."

Hoock got some benefit from triptans, which often took the edge off her migraines and allowed her to function, but still she lived in constant fear of an attack and was continually wary of anything that might trigger one.

Common migraine triggers include fluctuations in estrogen and progesterone levels, certain foods such as cheese or chocolate, alcohol, caffeine, stress or changes in the weather. For Hoock, triggers included artificial sweeteners, raw onions, sunlight flashing through trees, getting overheated, having a sip of alcohol or oversleeping.

Hoock no longer needs migraine medications. And, while she hasn't yet had the nerve to chug down a glass of Diet Dr. Pepper™, her favorite brand of soda, she gradually has been incorporating a few other former migraine triggers into her life since her procedure. She recently savored the taste of raw onions on a salad and sipped a margarita at a social gathering without getting a migraine.

Hoock's two daughters and son also experience migraines, and she has hopes that research such as the ESCAPE trial also may someday help them.

"I think it's wonderful that doctors give their time to research like this," she says. "It means so much to people like my family and me."