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Medical News & Perspectives
May 2, 2018

Taking a Closer Look at the Biomarker Test for Mild Traumatic Brain Injury

JAMA. Published online May 2, 2018. doi:10.1001/jama.2018.4644

Not long after a first-of-its-kind blood test received approval to evaluate patients with mild traumatic brain injury, headlines dubbed it a “concussion test.” But experts in biomarkers are clarifying certain misconceptions about what the test can and can’t reveal.

“It’s used to rule out the need for a [computed tomography] scan within 12 hours” after a suspected mild traumatic brain injury (TBI), said Steven Richieri, MBA, president and chief operating officer of San Diego-based Banyan Biomarkers Inc, which developed the test.

The test measures 2 proteins—glial fibrillary acidic protein and ubiquitin C-terminal hydrolase L1—that can be detected in peripheral blood within an hour after a mild TBI. A positive result would indicate a higher risk of more severe injury that could be detected on a computed tomography (CT) scan. A negative result would denote a far lower risk of serious injury. The test doesn’t specifically diagnose concussion.

“A positive test [result] in this case would actually be indicative of something we might call a complicated mild traumatic brain injury,” said Christopher Giza, MD, professor of pediatrics and neurosurgery at the University of California, Los Angeles (UCLA) and director of the UCLA Steve Tisch BrainSPORT Program. “It looks a little bit like a concussion but then there’s some bleeding or bruising in the brain or something else that would be detected on a CT scan,” added Giza, lead author of the American Academy of Neurology’s sports concussion guideline.

Even though a clinical definition of concussion isn’t exactly written in stone, Giza offered a description of the condition that he conceded is still subject to some debate. “Concussion is a type of mild traumatic brain injury,” he explained. “Within mild TBI you could have a small bleed in your head and it could still be mild or you could have a concussion where there shouldn’t be any bleeding or bruising on the brain.

“Think of concussion almost as kind of a subset of mild traumatic brain injury.”

Military Origins

Early on, funding for the test’s development came in part from the US Department of Defense. The military was interested in a point-of-care test that could be used immediately to evaluate battlefield injuries. “We’re not there yet; we’re still in generation one. It’s just a standard lab test,” Richieri said. “But the next generation we think will be a point-of-care test.”

For now, the primary clinical uses are in hospitals, notably emergency departments. “This particular test is a very good test. The FDA process that [approved] it quickly is good,” said Rade Vukmir, MD, an adjunct professor of emergency medicine at Temple University and spokesperson for the American College of Emergency Physicians.

In clinical studies, the test had a 97.5% accuracy rate in detecting intracranial lesions that showed up on CT scans and it was 99.6% accurate in predicting which patients did not have lesions. “Over 90% of the time, when someone gets a CT scan, [the results] are negative,” Richieri said. “That means the physician learned nothing from that test. It’s really a big waste of resources plus there’s the risk of radiation exposure.”

“If it’s truly used as a screening test and you can avoid downstream radiation risk in a patient, [the test] is absolutely valuable,” Vukmir said.

Blood Test vs Prediction Rule

Despite its utility, the test comes with caveats. It takes about 3 to 4 hours to analyze in a hospital laboratory; in contrast, a CT scan takes about 30 minutes from start to finish. “In an active, busy clinical emergency department, taking your time from half an hour to 4 hours could present a problem just in the efficiency part of it for other patients that may have illness or injury,” Vukmir said.

Currently, Giza said, neurologists and emergency department physicians evaluate mild head injuries by using clinical prediction rules that have been validated in tens of thousands of emergency patients. Certain symptoms including vomiting, loss of consciousness, headache, or persistent anterograde amnesia can distinguish high-risk patients who should have a CT scan from low-risk patients who would undergo observation without a scan. “A lot of decision making comes from the [patient] history,” Vukmir said.

“You can apply a clinical prediction rule in about a minute or less,” Giza noted, adding that although the blood test is adequate in predicting complicated mild TBI, it isn’t necessarily superior to a different test or clinical prediction rule.

With a negative blood test, Richieri said, the chances of having a positive CT scan are “slim to none.” However, Giza said using clinical prediction rules already takes scanning out of the clinical equation for many patients. “They don’t meet the criteria,” he said. But even among patients who do, positive CT scan findings don’t necessarily change patient care.

“You can find a lot of small bleeds on CT scans in mild TBI patients that you wouldn’t do anything other than observe it,” Giza said.

For the estimated one-third of patients with mild TBI whose risk of serious injury is considered intermediate, the blood test could provide clarity. “Where the doctor’s trying to spare the patient unnecessary radiation exposure but may not feel quite comfortable to just send them home and say everything’s okay, then the blood test like this might assist in those situations,” Giza said.

Vukmir suggested the test could also be used to confirm findings from a CT scan. “Some people will use it on the front end to do some triage testing if that’s what the patient wants and some people may do it on the back end because the patient wants that kind of certainty as well.”

Next Steps

For now, the test is indicated for use only in adults. But Vukmir said it probably won’t be long until a version is approved for children.

“Most people would suggest that if we had to worry about a group most at risk, it would be our kids,” he said. “Very quickly someone will get approval now to do a pediatric study and within a year, perhaps 2, we’ll be at this point again for kids.”

Work is ongoing to develop a faster point-of-care version of the test for potential use on the battlefield or in ambulances during transport to an emergency department. Richieri said Banyan Biomarkers has a licensing agreement to develop its test for use with Abbott’s i-STAT handheld device that can deliver blood test results within minutes. Banyan also is working to develop a point-of-care test with French diagnostics giant bioMérieux.

Richieri said there’s a lot of interest in a return-to-play test that could be used on the sidelines of sports events to determine whether athletes who’ve sustained a blow to the head can get back in the game. “That’s not what the indication for our test is,” he said. “Is it possible? We do have studies going on with the NCAA [National Collegiate Athletic Association] and sports trainers. We hope over the next months or years [that] data will be coming out on those populations.”

In the meantime, Vukmir said clinicians will begin to determine how the test best meets their patients’ needs—as a diagnostic, a confirmatory test, or both. He suggested that additional research could determine the test’s efficacy in monitoring recovery or predicting outcomes following mild TBI. “It’s an exciting new technology,” he said.

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