Measurement of the glial fibrillary acidic protein and its breakdown products GFAP-BDP biomarker for the detection of traumatic brain injury compared to computed tomography and magnetic resonance imaging

Abstract

Glial fibrillary acidic protein and its breakdown products (GFAP-BDP) are brain-specific proteins released into serum as part of the pathophysiological response after traumatic brain injury (TBI). We performed a multi-center trial to validate and characterize the use of GFAP-BDP levels in the diagnosis of intracranial injury in a broad population of patients with a positive clinical screen for head injury. This multi-center, prospective, cohort study included patients 16-93 years of age presenting to three level 1 trauma centers with suspected TBI (loss of consciousness, post-trauma amnesia, and so on). Serum GFAP-BDP levels were drawn within 24 h and analyzed, in a blinded fashion, using sandwich enzyme-linked immunosorbent assay. The ability of GFAP-BDP to predict intracranial injury on admission computed tomography (CT) as well as delayed magnetic resonance imaging was analyzed by multiple regression and assessed by the area under the receiver operating characteristic curve (AUC). Utility of GFAP-BDP to predict injury and reduce unnecessary CT scans was assessed utilizing decision curve analysis. A total of 215 patients were included, of which 83% suffered mild TBI, 4% moderate, and 12% severe; mean age was 42.1±18 years. Evidence of intracranial injury was present in 51% of the sample (median Rotterdam Score, 2; interquartile range, 2). GFAP-BDP demonstrated very good predictive ability (AUC=0.87) and demonstrated significant discrimination of injury severity (odds ratio, 1.45; 95% confidence interval, 1.29-1.64). Use of GFAP-BDP yielded a net benefit above clinical screening alone and a net reduction in unnecessary scans by 12-30%. Used in conjunction with other clinical information, rapid measurement of GFAP-BDP is useful in establishing or excluding the diagnosis of radiographically apparent intracranial injury throughout the spectrum of TBI. As an adjunct to current screening practices, GFAP-BDP may help avoid unnecessary CT scans without sacrificing sensitivity (Registry: ClinicalTrials.gov Identifier: NCT01565551).

Keywords: biomarkers; imaging; traumatic brain injury.

FIG. 1.

Box plots showing median levels of GFAP-BDP measured on admission in two groups of patients. Boxes show interquartile ranges, and I bars represent highest and lowest values. CT, computed tomography;GFAP-BDP, glial fibrillary acidic protein and its breakdown products.

FIG. 2.

Box plots showing median levels of GFAP-BDP measured on admission among patients in each of the Rotterdam classifications of injury on CT. Boxes show interquartile ranges, and I bars represent highest and lowest values. Overall, GFAP-BDP was significantly different across each level of Rotterdam score (p≤0.001). CT, computed tomography; GFAP-BDP, glial fibrillary acidic protein and its breakdown products.

FIG. 3.

Receiver-operating-characteristic curves for various cut-off levels of GFAP-BDP in differentiating presence or absence of intracranial injury on CT. Curves for GFAP-BDP alone and after adjustment for known predictors of injury and severity (age, GCS, pupillary reactivity, and ISS). AUC, area under the receiver operating characteristic curve; CI, confidence intreval; CT, computed tomography; GCS, Glasgow Coma Scale; GFAP-BDP, glial fibrillary acidic protein and its breakdown products; ISS, Injury Severity Scale.

FIG. 4.

(A) Decision curve analysis of the net benefit of GFAP-BDP to predict injury compared to current clinical screening method or scanning all patients regardless of screening across various probabilities of injury. (B) Decision curve analysis of the reduction of unnecessary CT scans per 100 patients using GFAP-BDP as an adjunct to predict injury compared to current clinical screening methods across various probabilities of injury. CT, computed tomography; GFAP-BDP, glial fibrillary acidic protein and its breakdown products.