Gerald Grant, PHD; Duke University; PH/TBI Clinical Consortium Site Award:

This is a study that we did to look at a cohort of civilian patients that came in after a mild traumatic brain injury, which we would define as a concussive injury. We define that by a Glasgow Coma score where they have to be very high on that score meaning 14 or 15. And these are patients we have to triage in the emergency room everyday and decide if they should get a CAT scan or not based on their history. And there are certain red flags to look for after a concussive injury that try to help us triage these folks in the waiting room and decide who should get a scan, who should not, and who should go home. And that's the disposition of these patients we struggle with everyday, just like we do on the battlefield with soldiers. With this study we took blood from these patients on a consented IRB study to enroll them and prospectively look at their injury. These are all patients who would have gotten a CAT scan anyway by the criteria of the emergency room physicians that are treating these patients. And then we took blood at different time points, on average about 8 hours after the initial injury for this study. The goal was to try to determine if there was a panel of biomarkers that we can help predict if they had a scan that was going to be positive. A scan positive means that some kind of hemorrhage or contusion or bruising on the brain, and try to pick that up using a biomarker in the blood. Cause we really want to have this Holy Grail to have a blood test, point of care test, with a little drop of blood - kind of like we do for heart disease or for diabetes. A point of care simple test to basically determine are they at risk. Has the football player on the field suffered a concussive injury? Can they go right back to play? You know, we would love to have a specific kind of test that we could do right then at the field to say "nope, maybe you shouldn't go back" cause it a little more of a risk. The same with the soldier. Faced these decisions when I was in Iraq, deployed with the Air Force - 2006. Had to make these decisions 10 or 15 times a day. Do I send this soldier back to combat? And we have very little to go by because these injuries are so subclinical, scans are all normal - their CAT scans. And we need something better, something more specific. And we really feel this panel is going to be much more useful. So this study is really a triage tool for whether to get a CAT scan or not. When you have a traumatic brain injury, there is a release of many different markers that gets dumped out from the brain when the blood/brain barrier opens up. And you have also an injury to the brain. And you pick up these markers at different times based on the injury cascade as well as the timing of the barrier opening up. And we looked at three markers, biomarkers, in particular. Brain natriuretic protein - BNP, the D-dimer as well as S100 beta. We can do an ROC curve, called a receiver operating characteristic, and this was quite high using all three together. Much better than anyone marker model. And it gives us an ROC value of .73, which is pretty good. We wish it was 80s or 90s. But it's pretty good for this type of first analysis, where we want to get a very, very high negative predictive value. Which in this study was 92 percent, that we can feel pretty confident that they won't have a positive scan based on normal biomarker panel for these three. It was exploratory, but it demonstrates the feasibility of using a panel of biomarkers to try and predict the absence of a positive scan. Luckily, most concussions, they get better but unfortunately some don't. And they have ongoing symptoms, which are really under-recognized. And that's what we are really trying to do is to raise the awareness of that, and also look at these biomarker profiles over time--not just the first 6 hours, but over the next several months actually. So this is a first step. We were doing this for a while. I think it has really helped us think beyond just the CAT scan and think about the neuropsychological profile up front. And think more about resilience and vulnerability, which are new terms for us to think about. It's not just a CAT scan and triage in the emergency room, it's way beyond that because of their risk from a secondary injury and what the cognitive aspects are following a traumatic event. These studies are critical and that's why the CDMRP is so powerful in their approach to these disorders in that it brings these people together as a consortium to help move along the science much faster. Because we have that opportunity with more patients available, more centers, and folks with many different disciplines that we can think about the same problem from different angles.