Accuracy of a rapid glial fibrillary acidic protein/ubiquitin carboxyl-terminal hydrolase L1 test for the prediction of intracranial injuries on head computed tomography after mild traumatic brain injury.

OBJECTIVE: The objective was to determine the accuracy of a new, rapid blood test combining measurements of both glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) for predicting acute traumatic intracranial injury (TII) on head CT scan after mild traumatic brain injury (mTBI). METHODS: Analysis of banked venous plasma samples from subjects completing the Prospective Clinical Evaluation of Biomarkers of Traumatic Brain Injury (ALERT-TBI) trial, enrolled 2012-2014 at 22 investigational sites in the United States and Europe. All subjects were ≥18 years old, presented to an emergency department (ED) with a nonpenetrating head injury and Glasgow Coma Scale score (GCS) 9-15 (mild to moderate TBI), underwent head CT scanning as part of their clinical care, and had blood sampling within 12 h of injury. Plasma concentrations of GFAP and UCH-L1 were measured using i-STAT Alinity and TBI plasma cartridge and compared to acute TII on head CT scan. RESULTS: Of the 2011 subjects enrolled in ALERT-TBI, 1918 had valid CT scans and plasma specimens for testing and 1901 (99.1%) had GCS 13-15 (mTBI), for which the rapid test was intended. Among these subjects, the rapid test had a sensitivity of 0.958 (95% confidence interval [CI] = 0.906 to 0.982), specificity of 0.404 (95% CI = 0.382 to 0.427), negative predictive value of 0.993 (95% CI = 0.985 to 0.997), and positive predictive value of 0.098 (95% CI = 0.082 to 0.116) for acute TII. CONCLUSIONS: A rapid i-STAT-based test had high sensitivity for prediction of acute TII, comparable to lab-based platforms. The speed, portability, and high accuracy of this test may facilitate clinical adoption of brain biomarker testing as an aid to head CT decision making in EDs.

Comparison of GFAP and UCH-L1 Measurements from Two Prototype Assays: The Abbott i-STAT and ARCHITECT Assays.

Glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) may aid in the evaluation of traumatic brain injury (TBI). The objective of this analysis was to compare GFAP and UCH-L1 values measured using a handheld device compared with a core laboratory platform. We analyzed plasma samples from patients with TBI and healthy controls enrolled in the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) cohort study. GFAP and UCH-L1 were measured twice in each subject using prototype assays, first with the Abbott i-STAT™ handheld device, and second with the Abbott ARCHITECT® platform. We then quantified the agreement in biomarker values obtained using these two methods. GFAP and UCH-L1 were measured twice in 570 and 572 samples, respectively. GFAP values measured by the ARCHITECT platform (median 143.3 [interquartile range (IQR): 19.8-925.8] pg/mL) were higher than values measured by the i-STAT (median 116.0 [IQR: 9.2-856.5] pg/mL). GFAP values from the two platforms were strongly correlated (p = 0.985). Similarly, UCH-L1 values measured by the ARCHITECT platform (median 163.9 [IQR: 82.5-412.4] pg/mL) were higher than values measured by the i-STAT (median 122.5 [IQR: 63.0-297.3] pg/mL). UCH-L1 values from the two platforms were strongly correlated (p = 0.933). Passing-Bablok regression equations were developed to estimate the relationship between the two platforms, specifically to predict i-STAT values from the ARCHITECT platform. GFAP and UCH-L1 values measured using the prototype assays on the Abbott i-STAT and ARCHITECT platforms are strongly correlated and values from either platform may be converted to the other.

Evaluation of Acute Glial Fibrillary Acidic Protein and Ubiquitin C-Terminal Hydrolase-L1 Plasma Levels in Traumatic Brain Injury Patients with and without Intracranial Lesions.

This pilot study aimed to evaluate the association of plasma ubiquitin C-terminal hydrolase-L1 (UCH-L1), glial fibrillary acidic protein (GFAP), and S100 calcium-binding protein B (S100B) with intracranial abnormalities visible on a computed tomography (CT) scan (CT positive) and injury severity in acute traumatic brain injury (TBI). For these purposes, a cohort of 109 adult TBI patients was recruited within 6 h from the injury event. A hyperacute subcohort of 20 patients who had their blood collected within 2 h from injury was analyzed separately for early acute biomarker levels. Levels of GFAP and UCH-L1 were analyzed using the prototype Abbott i-STAT™ TBI Plasma Test (Abbott Laboratories, Abbot Park, IL), alongside S100B measurement (Elecsys; Roche Diagnostics, Penzberg, Germany). In the hyperacute subcohort, GFAP and UCH-L1, but not S100B, levels were significantly higher in the CT-positive group compared to CT-negative patients. AUC values for differentiation between CT-positive and CT-negative patients were 0.97 for GFAP, 0.87 for UCH-L1, and 0.60 for S100B. Severity discrimination, defined by Glasgow Coma Scale (GCS) score, was then analyzed in the total patient cohort. Levels of all three biomarkers were significantly different between mild (GCS, 13-15) and moderate/severe (GCS, 3-12) injury groups. UCH-L1 showed the highest area under the curve value for severity discrimination (0.94), followed by GFAP (0.91) and S100B (0.83). These results support the clinical utility of GFAP and UCH-L1 as TBI biomarkers able to rule out CT-positive injury in acute TBI. Moreover, excellent differentiation of GFAP and UCH-L1 between mild and moderate/severe TBI groups affirms their close association with the underlying pathology.