Clinician-scientists hope to expand the use of blood-based biomarker tests for traumatic brain injury (TBI) to improve identification and escalation of care for patients whose diagnosis otherwise might be missed.
In a study published today in the Journal of Neurosurgery , a multi-institutional research team led by University of Pittsburgh School of Medicine neurosurgery clinician-scientists report clinical cutoffs for two brain-associated proteins detected in the blood after brain injury that may help better identify and triage patients with TBI.
Approximately 2.8 million people experience a TBI each year in the U.S. , with significant mortality, morbidity and long-term disability. "There are amazingly poor long-term outcome rates for people with a TBI who get seen in the emergency department," said Shawn Eagle, Ph.D., assistant professor in Pitt's Department of Neurological Surgery and lead author of the study.
Pitt's Neurotrauma Clinical Trials Center (NCTC) team collects data and biospecimens from patients with TBI presenting at the emergency department (ED) for TRACK-TBI, a federally funded, multi-center, longitudinal study. The NCTC, led by David Okonkwo, M.D., Ph.D. , professor of neurological surgery at Pitt and director of neurotrauma at UPMC, and Ava Puccio, R.N., Ph.D., associate professor of neurological surgery at Pitt, serves as the primary biorepository for the study, which aims to provide physicians with tools to diagnose brain injuries and better support their patients.
Previous findings from TRACK-TBI show that over 50% of participants with a mild brain injury have functional limitations at one year. Eagle suspects a major driver of poor long-term outcomes is that patients are not being properly identified. "Prior to this research, in the absence of a positive CT scan, there was no objective way to identify if you had a brain injury," he added.
For a patient presenting with TBI, a head CT scan is generally the first-line evaluation tool. CT scans are inexpensive and widely available and can quickly identify injuries. While CTs can identify acute injury, approximately 25% of patients have intracranial pathologies that CT scans miss.
"We're sending people home with a negative CT scan, but 1 in 4 have an abnormality visible on MRI indicating that they should have specialized follow-up care," said Eagle.
Many patients with normal CT scans continue to have symptoms. MRI scans give a more sensitive, detailed look at the brain tissue, and can capture what a head CT may miss. However, MRIs are slow, costly and inappropriate for patient triage in an emergency setting.
A test measuring two proteins released from the brain after injury can help clinicians determine if a CT scan is needed in patients with mild TBI. In 15 minutes, clinicians can rule out unnecessary imaging.
"We were curious about how the test would perform if you flipped it on its head," he said. "What level could you be pretty certain that someone does have a bleed in their head versus certainty that they don't?"
The two proteins, glial fibrillary acidic protein (GFAP) and ubiquitin c-terminal hydrolase-L1 (UCH-L1), rise in the bloodstream immediately post-injury and fall over time. Researchers asked if these two proteins could distinguish between patients with mild TBI who had positive CT scans versus negative CT scans and, importantly, distinguish patients who had negative CT scans and positive MRI results from patients with negative CT and MRI scans.
They found that within 24 hours of TBI, the level of GFAP in the blood could be used to differentiate patients with acute brain injury from those with no evidence of pathology on neuroimaging. Released from glial cells in the brain, GFAP has a rapid acute spike between 4 and 20 hours, with a slow decline over days after injury. In contrast, UCH-L1, a protein released from neurons, showed less ability to distinguish between the different groups tested in this study.
A point-of-care, whole-blood version of this test is now available, increasing feasibility. This test can be done bedside, rather than requiring that samples are sent to a lab.
"We're working to incorporate this test into the daily clinical practice in the ED," said Eagle. He expects that increased adoption will lead to broader uses for the test and is actively exploring if blood biomarkers could help predict long-term outcomes for patients following TBI.
Additional authors can be found in the Journal of Neurosurgery article.
Funding for this study was provided by the Department of Defense (W81XWH-13-1-0441, W81XWH-14-2-0176, W81XWH-18-2-0042, and W81XWH-15-9-0001), and the National Institute of Neurological Disorders and Stroke (U01NS086090 and U01NS1365885; RC2NS069409).
