Elevated Levels of Serum Glial Fibrillary Acidic Protein Breakdown Products in Mild and Moderate Traumatic Brain Injury Are Associated With Intracranial Lesions and Neurosurgical Intervention

Abstract

Objective This study examined whether serum levels of GFAP breakdown products (GFAP-BDP) were elevated in mild and moderate TBI compared to controls and if they were associated with traumatic intracranial lesions on CT scan (+CT) and having a neurosurgical intervention (NSI). Methods This prospective cohort study enrolled adult patients presenting to three Level 1 Trauma Centers following blunt head trauma with loss of consciousness, amnesia, or disorientation and a GCS 9–15. Control groups included normal uninjured controls and trauma controls presenting to the ED with orthopedic injuries or an MVC without TBI. Blood samples were obtained in all patients within 4 hours of injury and measured by ELISA for GFAP-BDP (ng/ml). Results Of the 307 patients enrolled, 108 were TBI patients (97 with GCS 13–15, and 11 with GCS 9–12) and 199 were controls (176 normal controls and 16 MVC controls and 7 orthopedic controls). ROC curves demonstrated that early GFAP-BDP levels were able to distinguish TBI from uninjured controls with an AUC of 0.90 (95%CI 0.86–0.94) and differentiated TBI with a GCS 15 with an AUC 0.88 (95%CI 0.82–0.93). Thirty two TBI patients (30%) had lesions on CT. The AUC for discriminating those patients with CT lesions versus those without CT lesions was 0.79 (95%CI 0.69–0.89). Moreover, the ROC curve for distinguishing NSI from no NSI yielded an AUC of 0.87 (95%CI 0.77–0.96). Conclusions GFAP-BDP is detectable in serum within an hour of injury and is associated with measures of injury severity including the GCS score, CT lesions and neurosurgical intervention. Further study is required to validate these findings before clinical application.

GFAP-BDP as an Acute Diagnostic Marker in Traumatic Brain Injury: Results from the Prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study

“…[25][26][27] Our findings are also consistent with previous reports in terms of predictive power and measured levels of serum GFAP in TBI. 4 We found that serum GFAP-BDP Odds ratio (GOS-E £ 7)…”

“…GFAP-BDP levels were greater in patients with CT scans positive for traumatic lesions (0.26 -0.41 ng/mL vs. 2.88 -3.74 ng/mL; p < 0.01), which is consistent with the previous findings of . 4 The ability of GFAP-BDP to discriminate between the likelihood of an unfavorable 6 month outcome, measured by the AUC, was adequate at 0.74, and the ability of GFAP-BDP to discriminate between the likelihood of a full recovery was 0.65. The optimal GFAP-BDP cutoff value was 0.68 ng/mL for identifying patients who failed to return to pre-injury baseline, and resulted in a 21.61 OR for a positive head CT and a 2.07 OR for failure to return to pre-injury baseline.…”

“…From high concentration to low, the previously reported intra-assay coefficient of variance for the ELISA was 4.3-7.8%, and the inter-assay coefficient of variance was 7.8-14.3%. 4 The estimated limit of detection (LOD) for GFAP was *0.1 ng/mL.…”

“…The GFAP ELISA utilized a proprietary mouse monoclonal antibody for solid phase immobilization, and a proprietary polyclonal rabbit antibody for detection. 4,8 The test sample was allowed to react sequentially with the capture and detection antibodies, resulting in GFAP molecules being sandwiched between the two antibodies. The antibodies detected both whole GFAP molecules and GFAPBDPs, potentially resulting in a more complete measure of GFAP levels in circulation.…”

“…3 In moderate to mild TBI, GFAP-BDP has been investigated by Papa et al with associations to injury severity as well as positive CT findings and the need for neurosurgical intervention. 4 GFAP is an intermediate filament protein that is expressed by several cell types, including astrocytes, in the central nervous system, and is thought to maintain mechanical strength of cells. The exact mechanisms leading to elevation of GFAP and GFAP-BDPs are not completely understood, and may be caused by such phenomena as astrocyte reactivity or damage, such as that seen in brain damage.…”