Can a Blood Test Warn of Brain injury?

Go to the emergency room with chest pains, and physicians can determine fairly routinely–with blood tests and an electrocardiogram–whether or not you’ve had a heart attack. A bump to the head is another matter. Currently, no blood tests are approved as a way to diagnose brain injury in the United States. In the case of mild head injuries or more serious ones that take time to develop, it’s difficult to tell early on how severely a patient has been hurt and whether she will suffer long-term consequences.

The high-profile case of actress Natasha Richardson, who died last month after a seemingly minor fall on the ski slopes, demonstrates this uncertainty in a dramatic fashion. According to news reports, she was walking and talking after the fall and refused medical attention, but later developed a headache and was rushed to the hospital. Richardson died two days later of an epidural hematoma, an injury in which blood builds up between the brain’s outer membrane and the skull.

One of the most challenging situations for physicians is deciding how to deal with patients who come into the emergency room with mild traumatic brain injury or concussion. Those with telltale symptoms such as dizziness and nausea will be given a computed axial tomography (CT) scan to look for signs of bleeding in the brain; patients who do show bleeding will need further monitoring and sometimes surgery. But because it’s difficult to determine who needs the scan, many patients get it unnecessarily, and others who do need it may be sent home.

Scientists hope that a blood test to detect proteins and other molecules released into the blood after brain injury could help. But developing such tests has been a challenge. “It’s very hard, because not every head injury is the same,” says David Hovda, director of the Brain Injury Research Center at the University of California, Los Angeles. “Getting hit in the forehead or rotating the neck damage different parts of the brain. And men and women, young and old, people who come in drunk, can all show brain injury differently.”

One blood test already used in Europe to screen head-trauma patients before CT scans detects a protein called S100B, which is released by astrocyte cells in the brain after injury. “The thinking is, if you don’t have [this marker] in the blood, then you don’t have the kind of brain injury you could see on CAT scan,” says Jeffrey Bazarian, an emergency-room physician and scientist at the University of Rochester Medical Center, in New York. The test is not approved for use in the United States, however. In a set of clinical guidelines for evaluating head trauma published recently, Bazarian and others estimated that the S100B test could significantly reduce unnecessary CT scanning. “We predict it could eliminate unnecessary radiation in a lot of people–about 30 percent [of those who come into the ER with brain injury],” he says.

The utility of the S100B test is limited, however. It cannot predict how well a patient will do in the long term. For example, those who have low levels of the protein after trauma may have cellular damage not visible on a CT scan. And some patients who do have brain bleeds will recover with no long-term consequences. “We and others are looking for markers that are more sophisticated, markers that correlate with cellular damage and with problems down the road,” says Bazarian.

The S100B test might actually aid in this quest. New research by Bazarian and his collaborators shows that it can accurately predict whether the blood-brain barrier–a molecular gate between the bloodstream and the nervous system that prevents the exchange of proteins and other compounds–is open or closed. (Previously, the only way to measure the status of the blood-brain barrier was an invasive test that involves threading a catheter through the skull into the brain.)

While the status of the blood-brain barrier itself is not a specific marker of traumatic brain injury–the barrier can open for other reasons, including heavy exercise, seizures, and meningitis–it could aid in the interpretation of other biomarkers in the blood. If the blood-brain barrier is closed, proteins that accompany brain injury might not reach the blood, making it difficult to evaluate the results of other tests. “If you don’t find any markers of brain injury in the blood, it could be because there is no brain injury, or because there is brain injury but the gate is closed,” says Bazarian.

The test may also aid in clinical trials of new drugs for treating brain injury. A number of trials for drugs designed to stop inflammation and other harmful biological processes that flair up soon after brain injury have failed, possibly because the drugs did not make it into the brain. If physicians knew whether a patient’s blood-brain barrier was open, they could reassess these drugs and test new ones only in these patients.

In the long term, scientists would like to develop a blood test that can predict the severity of a patient’s injury, as well as his or her prognosis. Banyan Biomarkers, a startup based inAlachua, FL, may be the farthest along in this endeavor. Researchers there are testing ways to detect a panel of biomarkers linked to mild, moderate, and severe traumatic brain injury in humans. Scientists at the company are now looking for these biomarkers in several hundred patients shortly after they suffer brain trauma, to determine when the biomarkers appear in the blood, how long they last, and how reliably they can predict the magnitude of an injury. Ronald Hayes, one of the company’s founders, says that the scientists expect to complete those studies late this year and early next year, and to start the larger-scale trials required for FDA approval in early 2010.