Fall 2005

UCSF Targets Cerebrovascular Malformations

Hemorrhagic strokes make up 15 percent of all strokes, tend to be particularly lethal and are an important form of stroke in young adults. Despite these facts, vascular malformations that can lead to stroke have not been intensively studied, says neuroanesthesiologist William Young, M.D. "Vascular malformations are under appreciated as a source of neurological injury," he says. Young is a professor of neurological surgery and neurology and a professor and vice chair of the Department of Anesthesia and Perioperative Care.

Questions about the most common cerebrovascular malformations — intracranial aneurysms and arteriovenous malformations (AVMs) — are particularly important because these conditions can consume heath care resources even when they do not cause injury. Now that cerebral CT scans are routinely taken after accidents or as part of normal care, physicians are spotting an increasing number of asymptomatic cerebrovascular malformations.

The difficult question then becomes what to do about them. "Doing nothing carries the risk a vascular malformation might suddenly burst, but surgery carries its own risks," Young says. "We are trying to make high-stakes decisions with very little data to base them upon."

UCSF has launched a drive to understand the natural history, molecular biology, genetics and physiology of vascular malformations such as aneurysms and AVMs. "We have constructed a registry and are trying to obtain tissue, blood and saliva samples from every patient with cerebrovascular malformation that comes through UCSF," Young says.

The study of cerebrovascular malformations is multidisciplinary by necessity, he adds, bringing together the big three of neurosurgery, neurology and vascular medicine, along with experts in other clinical departments such as radiology, anesthesiology, medicine and neuropathology. A complete understanding of these vascular malformations requires additional input from molecular biologists, bioengineers, geneticists and developmental biologists.

"This really is a model for studying complex disorders that cut across specialty lines," Young says. "The bedrock of the effort is that we have an unbelievably strong and collaborative group of experts at UCSF."

Such interdisciplinary studies have already brought to light some interesting facts, Young says. For instance, by studying the genetics of people with a cerebrovascular malformation, researchers have discovered an unexpected association between the disease and the proteins that control the inflammatory process. The molecules, interleukin-6 and a tumor necrosis factor (TNF-alpha), appear to be associated with increased risk of bleeding from AVMs.

Much of the interdisciplinary UCSF research group is focused on using resources to expand the small arsenal of existing tools to treat AVMs. One of their first efforts will be to construct a clinical trial with tetracycline, which they discovered may be useful to inhibit enzymes that destabilize the vascular wall.

A number of other studies point away from the textbook portrayal that AVMs are congenital lesions and toward the idea that they are a disordered form of angiogenesis. The thought is that although blood vessels normally grow only in the womb and as a response to injury, AVMs may represent a loss of control of what is usually a very tightly controlled process, Young says.

Another idea is that AVMs are, in a sense, a very slowly growing vascular tumor. "This bucks the conventional wisdom because they would be 'neoplasia' that grow so slowly that they behave like static lesions," Young says. Or there may be multiple kinds of AVM that have completely different etiologies, but look similar. "There may be at least two diseases — one being the old congenital model that you find more often in younger patients and one being the new model that affects older people," Young says.

To contact Dr. Young, call (415) 206-8906.

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