A handheld device that uses a newly developed test can rapidly identify even mild concussion by measuring two key biomarkers of neuronal injury.
The new test for traumatic brain injury – the i-STAT concussion biomarker test – may be deployed within 2 years by the Department of Defense, according to Col. Dallas Hack, M.D., Brain Health Coordinator at the U.S. Army Medical Research and Materiel Command, Ft. Detrick, Md.
The test will be integrated into a device that the military already uses – the i-STAT System, manufactured by Abbott. The unit already performs a wide variety of tests, including measurements of glucose, blood gases, coagulation factors, and cardiac markers. Each test is loaded on a single-use cartridge. The new test for concussion biomarkers will be on a similar cartridge, eliminating the need to buy or train on a new device, Col. Hack said in an interview.
Whether used in a battle setting or on a military base, the rapid test will speed up diagnosis and treatment. "This test is going to provide definitive proof of a brain injury very quickly, and that will kick in our set of treatment algorithms, which are already in place," he said.
Although it’s being designed for use in a military setting, the i-STAT concussion biomarker test will eventually be available in the civilian world, where the need is just as great, Col. Hack added.
The search for biomarkers of brain injury has been a long one – and its birthday is ironic, he noted. "It was literally the morning of 9-11 (in 2001) at the Advanced Technology Applications for Combat Casualty Care Conference [a precursor to the Military Health Systems Research Symposium] when researchers from the military and the University of Florida decided to embark together on this project."
Thirteen years later, at the same conference where the concept was first proposed, researchers presented data on one of the candidate biomarkers – ubiquitin C-terminal hydrolase-L1 (UCH-L1) – which is released when neurons are damaged. "This is a very early marker, present as soon as 15 minutes after an injury," Col. Hack said.
Maj. Walter Carr, of the Walter Reed Army Institute of Research, Washington, presented the new data, drawn from an observational cohort study of 220 soldiers serving in Afghanistan. Of these, 70 had sustained a concussion and 74 had a nonconcussion injury; there were 76 uninjured control subjects. Each patient had two blood draws, one within 8 hours after injury and the second about 24 hours after the injury.
At both time points, UCH-L1 levels were significantly higher in the concussed patients than in either of the other groups.
The protein is one of two biomarkers that will be included in the new test, which is being developed in collaboration with Abbott. The other biomarker, glial fibrillary acidic protein (GFAP), indicates astrocyte activation after neuronal injury.
When the search for biomarkers of brain injury was proposed in 2001, some researchers considered the blood-brain barrier to be inviolate – an impenetrable block that would prevent any chemical signals of brain injury from escaping into the circulatory system.
But Army researchers partnered with a spin-out company from the University of Florida, and the search was on. "By 2010, we had phase I and II data showing that we could not only identify those with a severe brain injury but [also identify those with mild traumatic brain injury] in limited numbers of patients," Col. Hack said. The findings indicated even mild injuries can cause biochemical disruptions that release proteins into the blood. With continued improvements in the sensitivity also came recognition of proteins specific for a brain injury.
The approval process for the test in combination with the i-STAT device is underway, but the path probably won’t be completely straight, he added. Concussion biomarkers are a new concept with no place in any existing diagnostic guidelines – all of which rely exclusively on imaging findings.
"Because of the immature state of this field, the FDA [Food and Drug Administration] doesn’t recognize any comparison measure for brain injury except a CT scan showing a subdural hematoma. So when we did our pivotal trials, we were limited by this. A fundamental problem in brain injury research is this use of CT as the standard for validation," Col. Hack said.
"There have been several Institute of Medicine reports decrying the lack of research in this huge public health problem. In fact, there’s no national research program for trauma of any kind, except in the military. This is a huge problem because it’s our young people who are most at risk for these injuries," which often exert a lifelong effect, he added.