Time Course and Diagnostic Accuracy of Glial and Neuronal Blood Biomarkers GFAP and UCH-L1 in a Large Cohort of Trauma Patients With and Without Mild Traumatic Brain Injury

Abstract

acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) have been widely studied and show promise for clinical usefulness in suspected traumatic brain injury (TBI) and concussion. Understanding their diagnostic accuracy over time will help translate them into clinical practice.OBJECTIVES To evaluate the temporal profiles of GFAP and UCH-L1 in a large cohort of trauma patients seen at the emergency department and to assess their diagnostic accuracy over time, both individually and in combination, for detecting mild to moderate TBI (MMTBI), traumatic intracranial lesions on head computed tomography (CT), and neurosurgical intervention. DESIGN, SETTING, AND PARTICIPANTSThis prospective cohort study enrolled adult trauma patients seen at a level I trauma center from March 1, 2010, to March 5, 2014. All patients underwent rigorous screening to determine whether they had experienced an MMTBI (blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale score of 9-15). Of 3025 trauma patients assessed, 1030 met eligibility criteria for enrollment, and 446 declined participation. Initial blood samples were obtained in 584 patients enrolled within 4 hours of injury. Repeated blood sampling was conducted at 4,

An investigation of neuroinjury biomarkers after sport-related concussion: from the subacute phase to clinical recovery

“…Indeed, alterations in various circulating indices of brain tissue damage such as glial fibrillary acidic protein (GFAP), s100 calcium-binding protein B (s100B), neuron specific enolase (NSE), αII-spectrin N-terminal fragment (SNTF) (22)(23)(24), and inflammatory genes (25,26) have been observed in the acute and subacute phases after SRC.…”

Current State and Prospects of Development of Blood-based Biomarkers for Mild Traumatic Brain Injury

“…Recent studies have shown that UCH-L1 levels rapidly increase in the plasma after brain injury and rapidly decrease subsequently within 36 hours [38]. In a recent study involving mild and moderate TBI, UCH-L1 levels were highly correlated with the GCS scores and the presence of lesions on brain CT [64].…”

“…In another prospective study, the UCH-L1 concentration in blood was found to be superior to that of GFAP or s100B in predicting the presence of CT lesions within 6 hours after mild and moderate brain injury [65]. However, a recently published prospective cohort study confirmed that the accuracy of UCH-L1 was lower than that of GFAP in determining the presence of brain damage, presence of lesions on CT, and necessity of neurosurgical intervention [38].…”

“…Recently, blood-based biomarkers that can be measured easily and quantitatively have been recognized as useful in the diagnosis of mTBI. Recent studies have shown glial fibrillary acidic protein (GFAP) and ubiquitin carboxyterminal hydrolase-L1 (UCH-L1) as emerging biomarker candidates for diagnosing TBI [38].…”

“…Moreover, to date, the time to detection in blood after the injury is different for each biomarker. For example, GFAP levels in the plasma were reported to increase significantly 8 hours after the injury, whereas markers such as UCH-L1 increase significantly at baseline and then return to normal levels after 12 hours [38]. When the biomarkers are not specific to the brain, blood concentration is vulnerable to "noise" from other organs.…”