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).

Imaging and serum biomarkers reflecting the functional efficacy of extended erythropoietin treatment in rats following infantile traumatic brain injury

“…21,26,56,107 Using immunoblotting, we found elevations in total GFAP and GFAP-DPs in serum at 3 days after CCI, which corresponded to CNS levels. Huang and colleagues did not find elevated GFAP in serum at 24 hours after TBI; however, they used a different age (adults), injury mechanism (fluid percussion), and method of detection (enzyme-linked immunosorbent assay [ELISA]), 30 differences that emphasize the need for age and assay specificity.…”

“…8,13,26 Clinically, elevated peripheral levels of GFAP following TBI are associated with unfavorable neurological outcomes. 20,56 Notably, in children with TBI, GFAP outperforms other biomarkers such as S100β in detecting head trauma and predicting intracranial lesions on head CT. 66 Moreover, GFAP levels are typically higher in serum following severe injury than after diffuse injury, and serum GFAP levels may be especially relevant in the pediatric patient population to detect contusion or intracerebral hemorrhage. 105 Additionally, rapid measurement of GFAP-DPs may be useful in establishing or excluding the diagnosis of intracranial injury apparent on imaging across the spectrum of TBI.…”

A Panel of Serum MiRNA Biomarkers for the Diagnosis of Severe to Mild Traumatic Brain Injury in Humans

“…Much of the efforts have been directed towards identifying blood based protein biomarkers of TBI25. Many of the protein markers which have shown promise in cases of moderate to STBI are still not approved for clinical use.…”

Are UCH-L1 and GFAP promising biomarkers for children with mild traumatic brain injury?

“…TBI with a Glasgow Coma Scale (GCS) score of 15) from uninjured control patients. 7-9 Finally, these two markers were significantly associated with head injury severity and predictive of six-month mortality following severe TBI. 10 …”