March 29, 2005
Out of Nowhere, a Devastating Tangle in the Brain
TANFORD, Calif. - Kathleen Young had no reason to believe she was anything but healthy. She led a hectic life, running a tree-trimming business with her husband, studying to become a nurse and bringing up three daughters, ages 10, 12 and 13, in Raymore, Mo.
But in an instant last September, everything changed. While working out at the gym, Mrs. Young, 41, suddenly went blind in her left eye. Minutes later, her head began to pound. The diagnosis, after an M.R.I. and other tests, was almost beyond comprehension: a rare disease had created blockages in arteries deep inside her skull, cutting off blood flow to part of her brain and causing a stroke, which had partly blinded her.
The disorder, called moyamoya disease, is so uncommon that her family doctor admitted he had never heard of it. The name is Japanese for puff of smoke, which is what the disease looks like on X-rays: a wispy cloud of fragile blood vessels that develop in the brain where normal vessels are blocked. It was first identified in Japan in 1959.
When Mrs. Young looked it up, what she learned was devastating. The disease causes a progressive narrowing of the internal carotid arteries, which carry blood to the brain. Patients suffer multiple strokes, mental decline and, usually, death from brain hemorrhage. The cause is unknown, and there is no cure. Reading a textbook chapter on it, she was stunned to realize that much of the information came from autopsies.
She swung between disbelief and dread. What would happen to her family if she died or became disabled from a stroke? How could she explain her illness to her 12-year-old, who has Down syndrome?
"I feel like I'm a walking time bomb," she said.
She found one bit of encouragement: a Web site, www.moyamoya.com, created by a patient, described an operation for the disease, a type of bypass in the skull that could improve circulation to the brain and prevent further strokes. The site included a link to Dr. Gary Steinberg, the head of neurosurgery at Stanford University Medical Center. Dr. Steinberg, who has operated on more than 130 people with the disease, is one of the few surgeons in the United States who have treated more than a handful of patients with moyamoya.
Mrs. Young e-mailed him. After studying her records and ordering more tests to map the blood vessels in her head, he recommended two operations, one on each side of her skull, a week apart. Her health insurer balked at first, insisting that she be treated in Missouri, but ultimately agreed that no brain surgeon there had Dr. Steinberg's expertise in moyamoya. By late February, Mrs. Young was on her way to Stanford.
On March 1, the day before her first operation, Dr. Steinberg peered at a light box holding X-rays of the blood vessels inside Mrs. Young's head. He turned to her and gently touched her right temple.
"You've got some nice scalp arteries," he said. "I'm going to take this one here and sew it to one of the arteries on the surface of your brain" -he tapped his pen against the X-ray- "one of these that you can't even see."
By 7:10 the next morning, Mrs. Young was under general anesthesia. The word "yes" was scrawled in black marker on her right temple to mark the incision site. A cooling element was inserted into a vein in her groin to lower her temperature by about 7 degrees Fahrenheit and cool her brain, to help protect it during surgery. Electrodes were attached to her skull to monitor brain activity.
Dr. Steinberg would not arrive until he was needed for the critical parts of the operation, but could watch its progress on a video monitor in his office.
Two assisting surgeons, Dr. Bernard Coert and Dr. Stephen Ryu, shaved a small rectangle just above Mrs. Young's ear. Using ultrasound to find the scalp artery, they marked its path on her scalp. Next, they turned her head to the left and fitted her into a viselike skull immobilizer with pins that pierced her forehead and the back of her skull.
The vessels they would be working on were so small - only one to two millimeters wide - that they would need magnification. A microscope with two eyepieces was wheeled in, and the lights were dimmed. A four-foot-wide flat screen showed the surgical field, magnified 100 times, but the surgeons looked only into the eyepieces as they wielded forceps and scissors to expose the superficial temporal artery in her scalp.
Dr. Steinberg arrived at 8:55, and the other doctors stepped aside as he sat on a stool, rested his wrists on Mrs. Young's skull and, looking through the microscope, quickly finished freeing the artery. Then he pushed it aside, cut through the muscle and separated it from the skull, and removed a disk of skull bone about the size of a half dollar. The other surgeons opened the membranes that cover the brain to expose an artery on its surface.
When Dr. Steinberg began operating on moyamoya patients in the 1990's, he saw only a few cases a year. But in 2004 he operated on 35, and now he sees about one a week. One-third are children. He has so many patients not because there is an epidemic of moyamoya but because he is one of the few surgeons with much experience in it. The rate of new cases each year in the United States is estimated at one in two million people. It is twice as common in Southeast Asia, and some cases may be hereditary.
But Dr. Steinberg said that the number of patients he has been seeing makes him wonder if the disease is really so rare.
"It's probably more common than we thought and a more common cause of stroke than we had thought, stroke in young people, and an unusual type that we can prevent," he said.
An M.R.I. can detect the disease, he added, and increased use of the scans may be finding patients whose symptoms would have been misinterpreted in the past.
Moyamoya is still unlikely to account for more than a fraction of a percent of the 700,000 strokes that occur in the United States every year. But the National Institutes of Health sponsors research on the disease.
Dr. Tom Jacobs, director of the stroke program at the National Institute of Neurological Disorders and Stroke, said, "This is an important disease that could have implications for further understanding other vascular diseases in the brain."
He said that if research could explain more about the disease process and possible genetic links, the information might have relevance for other disorders that cause strokes.
Most patients with moyamoya are children from 5 to 15, or adults from 30 to 40, and nearly two-thirds are female. Some have strokes; others, in earlier stages, have temporary speech problems, headaches, seizures or attacks of numbness or weakness in their limbs.
The symptoms, though transient, can occur so often that people cannot function. Some adult patients also notice problems with thinking or memory.
But often the symptoms are mild, ignored by patients or misdiagnosed as coming from pinched nerves or migraines. Mrs. Young, for instance, had episodes of eye trouble and tingling in her arm for a year or two before her stroke, but paid little attention to them.
The artery blockages in moyamoya are nothing like the fatty deposits in atherosclerosis. In moyamoya, the inner surface of the arteries and the muscle in the artery walls grow thicker.
"The whole vessel actually closes off," Dr. Steinberg said. "We don't know why it happens. If we knew, we might be able to prevent it."
The shutdowns occur in a limited but vital area near the base of the brain, a loop of vessels about the size of a quarter, called the circle of Willis. It looks a bit like a traffic rotary - with branches that provide nearly all the brain's circulation.
Over the years doctors tried giving moyamoya patients aspirin, blood thinners, clot busters and other drugs in hopes of preventing strokes. None worked. They also tried opening blocked vessels with balloons, or severing nerves believed to be causing artery spasm, but those techniques failed, too.
Surgery to restore blood flow is the only thing that works, Dr. Steinberg said. The most common operation is a bypass of the pinched off-vessels. Because the disease seems to affect arteries at just a few specific points, surgeons can usually find healthy vessels to splice together, rerouting blood around the blockages. In children or other patients whose arteries are too small to sew together, surgeons use other techniques like placing a scalp artery or other tissue containing blood vessels on the brain so that branches will grow into the oxygen-starved areas.
"We're not curing the disease, but the bypass is effectively treating it," Dr. Steinberg said. "You want to treat them before they have the big stroke, the devastating stroke that's going to change their life forever."
Over all, he said, a majority of patients, 95 percent or more, have no further strokes or related problems after the surgery. Three of his patients died from brain hemorrhages after surgery, though not recently, Dr. Steinberg said, and he abandoned an early surgical technique he had used on one of them.
At 11 a.m., Dr. Steinberg clamped Mrs. Young's scalp artery in two places and cut it between the clips. Its flow would be diverted into the brain artery instead of the scalp.
Tension began to build as the neurologist monitoring Mr. Young's brain activity at a computer in the operating room warned that he was seeing worrisome dips, a possible sign of lack of oxygen. Hoping to improve the circulation to her brain, the anesthesiologist administered a drug to raise her blood pressure.
The next step was to prepare the brain vessel to accept the graft. Because he would be opening the vessel, it would have to be clamped to prevent blood loss. But clamping a brain artery is risky business, especially in a patient like Mrs. Young, whose brain circulation is already poor.
At Dr. Steinberg's signal, the anesthesiologist gave her a drug to quiet the brain's activity and diminish its need for oxygen. When the drug took effect, Dr. Steinberg applied the clamps and announced that the artery was shut down, or occluded. The occlusion time would be clocked; ideally, it should be as short as possible and is usually about 30 minutes.
Looking through the microscope, Dr. Steinberg snipped a tiny window into the side of the brain artery and began stitching the open end of the scalp artery to it. The suture line was finer than a hair and the curved needle, passed between pairs of forceps, no bigger than an eyelash. To the naked eye, he seemed to be sewing with an imaginary needle and thread.
By noon, the vessels were sewn together, and Dr. Steinberg tested the connection by loosening the clamps. Blood welled up into the field. He closed the clamps, cauterized, added two stitches, released the clamps. More blood. He reapplied the clamps and added another stitch. He did this again and again. Finally, after the 10th extra stitch, the bleeding stopped, and he removed the clamps. The occlusion time had been long, 55 minutes. Still, Mrs. Young's brain activity had returned to a safe level.
Ultrasound measurements showed that blood flow through the graft was excellent. At 12:43 Dr. Steinberg said, "O.K., let's get out of here."
An hour later, Dr. Ryu and Dr. Coert stapled Mrs. Young's skin closed and released the skull immobilizer. By 2 p.m. the anesthesiologist was tapping her on the forehead, pulling open her eyelids and calling her name. Soon, her eyes opened, and she wiggled her toes on request. Patting her shoulder, the anesthesiologist said: "Everything is O.K. You're done with your surgery."
Three days later, Mrs. Young was well enough to leave the hospital, despite a headache and some bruises. Her peripheral vision began to improve. After four more days, she went back to the hospital and had the same operation all over again, on the other side of her brain. On March 17, she flew home to her family in Missouri, ready to resume the hectic life she had left behind.