Simple blood tests taken on the day of a traumatic brain injury (TBI) can predict with fairly high reliability which patients are likely to die and which are likely to survive with severe disability, according to a study published Wednesday in Lancet Neurology.
The rapid assay looks for two protein biomarkers — GFAP, found in glial cells, and UCH-L1, found in neurons. Tests of both biomarkers have been approved by the Food and Drug Administration for their ability to show structural damage to the brain and are used as tools to determine if patients with mild TBI should have costly CT scans.
Now, this paper, by a group of scientists associated with a brain injury research initiative called TRACK-TBI, shows that the assays are not only diagnostic, but also prognostic. Having a strong indication of outcome can shape conversations with families in cases of devastating injury, the researchers said, or contribute to triage decisions and resource allocation in a military setting.
While typical prognostic tests “require an assemblage of some clinical data, some CT imaging data, and some laboratory data,” this test is easy to use and the results are immediate, said Geoffrey Manley, a trauma neurosurgeon at the University of California, San Francisco and senior author on the study.
Firas Kobeissy, an assistant professor in emergency medicine at the University of Florida who is unaffiliated with this research, said that the ability to predict unfavorable outcomes for patients with TBI is a novel and strong finding, though the biomarkers fall short of predicting partial recovery.
Researchers used a rapid portable blood analyzer to look for the biomarkers in samples from 1,500 patients on the day of their traumatic brain injury. Most were injured in traffic accidents or falls. Patients with trauma in addition to a brain injury were excluded.
That could be a limitation. “Without including the polytrauma, you’re excluding a large group of patients that we typically see in the ICU,” said Gretchen Brophy, professor of pharmacotherapy and outcomes science and neurosurgery at Virginia Commonwealth University, who was not involved with this research but serves on the steering committee of TRACK-TBI.
Brophy noted that 30% of the patients in the study reported previous TBI, which might mean there were elevated baseline levels of the protein biomarkers. She also pointed out that secondary injuries can occur while patients are hospitalized and influence biomarker levels. Brophy said it is important for future studies to see if the predictive powers of the biomarkers holds true when patients with more diverse brain injury profiles are included.
The researchers followed the participants for two weeks, three months, and six months to see how they fared. They used the Glasgow Outcome Scale Extended, which is a widely used tool for assessing disability and recovery after a TBI. Patients are assigned a score from 1 — dead — to 8 — fully recovered.
Six months after the initial admission, 7% of the patients had died, 14% had level 2 to 4 injuries, and the rest had incomplete recovery. Researchers found that high initial levels of the biomarkers were associated with death and severe injury — a score of 1-4 — and that the biomarker blood test improved on the most widely validated current prediction tool, the IMPACT prediction model.
The day-of-injury blood tests had a probability of predicting death at six months of 87% for GFAP and 89% for UCH-L1; and a probability of predicting severe disability at the same time point of 86% for both GFAP and UCH-L1. They were significantly less accurate in predicting incomplete recovery compared to complete recovery.
“If these proteins are significantly elevated, we need to share this with families to say that there’s a higher likelihood of incomplete recovery or even death,” Manley said.
But Eric Thelin, an associate professor in experimental neurology at the Karolinska Institute in Stockholm, Sweden, cautions that the tool cannot be applied clinically yet since there might be false positives.
“Right now it’s sort of a guess with brain injuries,” Brophy said. “The biomarkers will help us be a little bit more definitive in speaking with the families of the patients, and also the patients to give them some idea of the recovery from the injury, which we haven’t really been as confident in before.”
While both biomarkers were independently prognostic, they worked best in tandem. The UCH-L1 protein is very rapidly released and cleared from the bloodstream while the GFAP protein peaks a bit later and then sticks around for a while.
“Both of these proteins are highly complementary, in that you’re not going to miss things because you did the test too early, or you’re not going to miss things because you did the test too late,” Manley explains.
Because so-called mild traumatic brain injury has long been considered a one-and-done event as opposed to a potentially chronic illness, a lot of patients with high Glasgow scores at initial evaluation are not given robust follow-up. But Manley says that paradigm is changing and that these blood-based biomarkers could eventually be an effective tool to predict unfavorable outcomes and identify patients who will benefit from follow-up care.