July 1, 2008
By GINA KOLATA
On Dec. 18, 2005, Ariel Sharon, then Israel’s prime minister, was taken to a Jerusalem hospital with symptoms of a stroke, unable to speak or understand what others were saying.
Over the next 36 hours, his doctors found themselves in a quandary. Mr. Sharon had two conditions that might lead to a new and devastating stroke. And treating one condition could make the other one worse.
First, he was susceptible to blood clots that could be swept from his heart to his brain, causing a major stroke. Anticlotting drugs might protect him.
But his brain scans showed microbleeds, pinpoint drops of blood that leaked from blood vessels in the brain. The fear was that an anticlotting drug might turn a new microbleed into a life-threatening, incapacitating hemorrhagic stroke.
Until recently, microbleeds were all but unknown. Now, with improved scans, they are turning up constantly; one recent study found them in the brains of 1 out of 5 people age 60 and older. And they are leading to a classic conundrum of modern medicine: Just because something turns up on an M.R.I. scan, is it significant? And if it may or may not be significant, what to do about it?
With strokes, the stakes can be life or death. Or, as happened with Mr. Sharon, somewhere in between.
His doctors decided that blood clots were his biggest risk, so they gave him heparin, an anticlotting drug. Two weeks later, he had a major bleeding stroke. Mr. Sharon remains in a persistent vegetative state to this day, awake but not aware, unable to respond, unable to communicate, able to breathe but unable to think.
It can never be proved that an anticlotting drug caused a stroke in an individual case. But it is known that when patients taking such drugs have hemorrhagic strokes, the strokes are much worse, with double the normal fatality rate.
The microbleed story began when neurologists, using newer magnetic resonance imaging techniques, began seeing them in patients who had symptoms of a stroke or, in some cases, signs of an electrical disturbance in the brain. A patient might have numbness or tingling in part of the face that then migrated to a hand and went away.
On scans, neurologists would see a few drops of blood in the patient’s brain, smaller than the tip of a pen. Or they would see tiny drops in routine scans in patients with dementia, or in patients who had had a serious stroke.
Now, neurologists are seeing microbleeds even in some patients who seemed free of neurological problems — people who were given a scan because of a blow to the head, or memory problems, or headaches.
“They clearly are being picked up more often,” said Dr. Steven M. Greenberg, a neurologist at Massachusetts General Hospital who studies microbleeds. “That’s one reason why we all get nervous about getting scans on people who don’t necessarily need them. You have to be able to deal with the consequences.”
With microbleeds, that can be difficult. At a loss as to what to do, doctors call specialists like Dr. Greenberg, asking for advice.
“I get a lot of calls I didn’t used to get,” Dr. Greenberg says. “And they mostly involve questions I can’t answer.”
When the bleeds are on the outer surface of the brain, they often seem associated with a condition in which blood vessels are damaged by the protein amyloid. This is the same protein that piles up in the brains of patients with Alzheimer’s disease; microbleeds from amyloid can be associated with dementia.
Other times, the microbleeds are deep in the brain and may be linked to high blood pressure, a leading cause of strokes. But it is not clear whether microbleeds, especially those deep in the brain, are of any real consequence. Until recently, no one asked how often they turn up in healthy people, nor whether they predict strokes or other serious brain damage.
That changed when Dr. Monique M. B. Breteler, a neuroepidemiologist at Erasmus University in Rotterdam, the Netherlands, decided to look for microbleeds among residents of her city.
“If there were more than we knew of in the general population, that might — and I want to stress might — have important consequences,” Dr. Breteler said. “That is why we started to look for them.”
For more than a decade, Dr. Breteler and her colleagues have followed a group of Rotterdam residents age 45 and older. The goal is to do repeated brain scans on 8,000 people; so far they have scanned nearly 4,000 and are analyzing those data.
“What we found came as a big surprise,” Dr. Breteler said. Previous estimates were that 5 to 7 percent of healthy older people had microbleeds. The Rotterdam study found them in more than 20 percent. And the older the person, the more likely the microbleeds. They were present in 18 percent of 60-year-olds and nearly 40 percent of those over 80.
“We now know that these changes are there and that they are frequent,” Dr. Breteler said. “But we don’t know yet what their clinical impact is, what their prognosis is.”
Still, she and other experts say, there is reason for concern.
Dr. Greenberg has found that if the microbleed is near the brain’s surface, where it might be associated with amyloid, then anticlotting drugs are more likely to precipitate a brain hemorrhage. But sometimes a patient is at such grave risk of a stroke that the balance tips in favor of an anticlotting drug anyway, he says.
If the microbleed is deep in the brain, it is not clear whether anticlotting drugs are dangerous.
Even patients who come in with symptoms that might be caused by microbleeds can pose a problem.
Edward Reynolds, 74, of Beverly, Mass., was referred to Dr. Greenberg after an episode in which part of his face went numb, then his hand, and then the numbness faded and he felt fine. He had an abnormal heart rhythm, which meant that anticlotting drugs might help him avoid a stroke caused by blood clots in his heart.
But an M.R.I. scan found microbleeds on the surface of his brain, which meant they were probably associated with amyloid. And that meant powerful anticlotting drugs like warfarin could be dangerous for him.
“Here’s a guy on a knife edge of being anticoagulated or not,” Dr. Greenberg said. “There really are major risks on both sides. You can see bad things happening either way.”
Dr. Greenberg decided in the end that the risk from drug like warfarin was not justified. He advised Mr. Reynolds to take baby aspirin, with its mild anticlotting properties.
“It’s only one decision, but it’s a big one,” Dr. Greenberg said.
So far, Mr. Reynolds has done well, with no recurrence of the numbness and no signs of a stroke.
“I’m feeling pretty good,” he said.