By William J. Cromie

Gazette Staff

Doctors can now watch what happens to a brain that is being treated for stroke.

A new scanning technique produces detailed images of where the stroke is taking place, how severe it is, and whether a drug is preventing further damage or not.

In the first test of its kind, a new type of magnetic resonance imaging, known as diffusion weighted MRI, revealed that a drug called citicoline reduced brain damage in 7 of 8 patients.

"When we used diffusion weighted MRI, to check patients' brains before and after giving the drug, we clearly saw positive results," said Steven Warach, associate professor of neurology and of radiology at the Medical School. "Damage was more limited in those who received citicoline than in those who did not."

Warach and his colleagues at Beth Israel Deaconess Medical Center described the use of the technique in four reports given yesterday at a meeting of the American Academy of Neurology in Boston.

The scanning method, developed by Warach and Robert Edelman, professor of radiology, makes it possible to detect a stroke in minutes -- while it is actually happening. Only five years ago, some stroke victims who came to an emergency room went untreated for hours because doctors thought there was nothing they could do to prevent further brain damage.

"Now we have the ability to locate a stroke within minutes and determine how severe it is," Warach noted. "The next goal involves helping to develop and test drugs that will prevent or limit brain damage."

Warach and his collaborators are leading a large study that will involve hundreds of patients at 15 centers across the nation. Citicoline, the drug being tested, is one of several new antistroke medications undergoing trials in Harvard-affiliated hospitals and other medical centers in the U.S. and Europe.

Strong Results

Large numbers of patients must be tested to determine how much of any improvement is due to a drug and how much to nature. "Over time, stroke patients often get better naturally," Warach says.

To distinguish between the two effects, patients are separated into a group that receives the drug and one that does not. In the first and only test to date monitored by diffusion weighted MRI, 8 people got citicoline and 4 did not. Seven of the 8, or 87.5 percent, showed improvement, while only one of 4, or 25 percent, in the control group improved.

Warach calls that "a surprisingly strong result."

One would think that people with the most brain damage would be the most impaired. That's not necessarily so. A tiny wound in one part of the brain might leave a person with one side completely paralyzed. Another patient with a wound twice that size in another part of the brain might survive without a noticeable problem.

But the size of the affected area can continue to grow, reducing the chance of survival, or survival without permanent damage. "Therefore, a decrease in size of damaged brain, as shown by the scan, is highly correlated with an improvement in patient recovery," Warach and his colleagues told those at yesterday's meeting.

Most strokes, or brain attacks, occur when a blood vessel bringing oxygen to the brain becomes blocked. Deprived of oxygen, brain cells begin to die. Citicoline and other antistroke drugs work either by preventing damage to endangered cells or by breaking up the clots.

To date, the only drug approved by the Food and Drug Administration for this purpose is called tPA (tissue plasminogen activator). "This drug has to be started within three hours after onset of stroke symptoms," Warach points out. "It also involves other restrictions, so only about 1-2 percent of stroke victims receive tPA."

About 500,000 people suffer a new or recurrent brain attack each year, and more than 150,000 people die from them. Some 4 million people living in the U.S. today have survived a stroke.

Shrinking the Halo

On an MRI scan, the damaged area shows up as an unusually bright spot in the brain. Around it appears a halo of still healthy but jeopardized cells. Preventing or reducing the expansion of this ring of dying cells is the key to saving brain tissue.

"Since we made our first images in 1990, we're getting better at determining which part of the [halo] will evolve into permanent damage, and at predicting which patients have the most tissue at risk," Warach comments.

This type of MRI scanning follows the movement, or diffusion, of water through the brain. A patient lies inside what looks like a giant white doughnut while water in-between and inside his or her brain cells is labeled magnetically. The scanner then follows the path of the magnetic tags.

"In acute stroke, the water diffuses through the brain at about half the normal rate," Warach explains. "The slower the diffusion, the brighter the affected area. This is why the technique is called 'diffusion weighted.' A series of scans before and after a patient takes a drug reveals whether the damage is increasing or decreasing."

Four years ago, Beth Israel Hospital had the only such scanner. Warach predicted then that the imaging procedure would become almost routine in three or four years (see May 21, 1993 Gazette).

"Today, most commercially available MRI machines can be fitted with software to do diffusion scanning," he says.

Citicoline, made by Interneuron Pharmaceuticals of Lexington, Mass., has also been tested without scanning. Results of these multicenter trials appear to show that patients experience significant improvement compared to those who didn't take the drug.