Lucky Timing Helps Scientists Unlock Secrets of Migraine : Research: A woman’s headache began while hooked up to monitors, enabling doctors to watch a theory play itself out. As a result, new treatments may be possible.
The fortuitous onset of a migraine in a research subject who was already in the brain imaging laboratory has provided UCLA researchers with a sharp new insight into the initiation of migraine headaches and may lead to the development of new ways to treat and prevent the disabling disorder.
Scientists discovered that the headache began when blood flow to a small region at the rear of the brain was reduced about 30% by constriction of blood vessels. The decrease in blood flow then spread across the surface of the brain like a wave washing over a small pond, they reported in last week’s New England Journal of Medicine.
The results confirm the so-called “spreading depression” theory about migraine onset, a relatively new theory that so far has been validated only in mice. Until recently, researchers had believed that migraines were the result of reduced blood flow in a localized area of the brain, but the new theory, not yet widely accepted, suggests that migraines are a result of low blood flow throughout the entire brain.
Researchers termed the phenomenon spreading depression because it was originally detected as a depression in electrical output of the brain.
The UCLA study “documents beyond any reasonable doubt that spreading (depression) is a real phenomenon,” said Dr. Jes Olesen of the University of Copenhagen. And that knowledge could lead to new treatments, he said.
“There is a class of drugs known as NMDA receptor antagonists that show great promise in mice in stopping spreading depression,” said Dr. Roger Woods of UCLA. “Now we have more confidence that these drugs will work in humans as well.”
Some of those receptor antagonists are being tested in humans as a treatment to limit brain damage in strokes, he said, and their safety has been demonstrated.
Woods noted, however, that the spreading depression theory may apply only to the so-called classical migraine headaches in which the victim perceives an “aura”--a combination of visual, sensory and movement sensations--at the onset of the headache. Some evidence suggests that migraine headaches not accompanied by an aura, about 40% of the total, may have a different mechanism, he said.
Although migraines are not life-threatening, they are severely disabling for about 23 million Americans who suffer them regularly. In addition to extreme pain, the symptoms typically include nausea and an aversion to light and sound. The symptoms can last from two hours to two days, and most victims are unable to work or carry out other activities while suffering from them.
Woods and his colleagues have been studying the normal functions of the brain using a technique called positron emission tomography. In PET, a harmless radioactive gas is injected into the bloodstream and tracked with a sensitive detector as it flows through blood vessels. Relatively high levels of radioactivity in a particular blood vessel in the brain represent a high blood flow and thus, presumably, increased activity by brain cells in that area.
One of Woods’ subjects, who had previously reported headaches triggered by exposure to a flickering television screen, was placed in the PET scanner with a TV screen in front of her.
More than an hour into the test, she felt a sharp pain in the center of the back of her head that she said was “as if someone had hit me there.” The headache worsened into a full-blown migraine with an aura, but she continued to stare at the screen while doctors took more brain scans. They were able to monitor the progression of the headache from start to finish--a first because previous studies involved subjects who came to a clinic only after a migraine had begun.
Their observation is important, Woods said, because it validates the animal model of migraines that many researchers have begun using. In the model, the rat’s brain is pricked with a pin or a small amount of potassium or an amino acid is applied to a specific spot, triggering the wave of reduced blood flow known as spreading depression.
But researchers could not know if the animals were suffering headaches, Woods said. The new study, he said, “shows that the animal model really is mimicking the human condition.”
That knowledge will make researchers more confident in extrapolating results from the animal model to humans, he added. It also suggests that experimental drugs that prevent or halt the process in animals can do so in humans.
Olesen added that the results should finally persuade many physicians who have remained doubters that migraines are a biological problem and not a psychological one.
More on Medicine
* Articles on the latest medical research covering everything from cholesterol to cancer are available on the TimesLink on-line service. Sign on and “jump” to keyword “medicine.”
Details on Times electronic services, A14
