GFAP out-performs S100β in detecting traumatic intracranial lesions on computed tomography in trauma patients with mild traumatic brain injury and those with extracranial lesions

Linda Papa, Salvatore Silvestri, Gretchen M Brophy, Philip Giordano, Jay L Falk, Carolina F Braga, Ciara N Tan, Neema J Ameli, Jason A Demery, Neha K Dixit, Matthew E Mendes, Ronald L Hayes, Kevin K W Wang, Claudia S Robertson, Linda Papa, Salvatore Silvestri, Gretchen M Brophy, Philip Giordano, Jay L Falk, Carolina F Braga, Ciara N Tan, Neema J Ameli, Jason A Demery, Neha K Dixit, Matthew E Mendes, Ronald L Hayes, Kevin K W Wang, Claudia S Robertson

Abstract

Both glial fibrillary acidic protein (GFAP) and S100β are found in glial cells and are released into serum following a traumatic brain injury (TBI), however, the clinical utility of S100β as a biomarker has been questioned because of its release from bone. This study examined the ability of GFAP and S100β to detect intracranial lesions on computed tomography (CT) in trauma patients and also assessed biomarker performance in patients with fractures and extracranial injuries on head CT. This prospective cohort study enrolled a convenience sample of adult trauma patients at a Level I trauma center with and without mild or moderate traumatic brain injury (MMTBI). Serum samples were obtained within 4 h of injury. The primary outcome was the presence of traumatic intracranial lesions on CT scan. There were 397 general trauma patients enrolled: 209 (53%) had a MMTBI and 188 (47%) had trauma without MMTBI. Of the 262 patients with a head CT, 20 (8%) had intracranial lesions. There were 137 (35%) trauma patients who sustained extracranial fractures below the head to the torso and extremities. Levels of S100β were significantly higher in patients with fractures, compared with those without fractures (p<0.001) whether MMTBI was present or not. However, GFAP levels were not significantly affected by the presence of fractures (p>0.05). The area under the receiver operating characteristics curve (AUC) for predicting intracranial lesions on CT for GFAP was 0.84 (0.73-0.95) and for S100β was 0.78 (0.67-0.89). However, in the presence of extracranial fractures, the AUC for GFAP increased to 0.93 (0.86-1.00) and for S100β decreased to 0.75 (0.61-0.88). In a general trauma population, GFAP out-performed S100β in detecting intracranial CT lesions, particularly in the setting of extracranial fractures.

Keywords: S100β; computed tomography (CT); fractures; glial fibrillary acidic protein (GFAP); mild traumatic brain injury/concussion.

Figures

FIG. 1.
FIG. 1.
Flow diagram of enrolled patients. Flow diagram showing the number of enrolled trauma patients with and without mild or moderate traumatic brain injury.
FIG. 2.
FIG. 2.
Temporal profile of S100β and glial fibrillary acidic protein (GFAP) in trauma patients within 4 h of injury. Bars represent median serum levels with interquartile ranges of S100β and GFAP (ng/mL) at different times post-injury. (n=1, 6, 38, 60, 89, 95, and 138, respectively).
FIG. 3.
FIG. 3.
Boxplot of levels of serum glial fibrillary acidic protein (GFAP) and S100β in general trauma patients divided into three groups: 1) No mild and moderate traumatic brain injury (MMTBI); 2) MMTBI (without intracranial lesions on CT); and 3) MMTBI (with intracranial lesions on CT). Bars represent median serum levels with interquartile ranges of S100β and GFAP (ng/mL) measured within 4 h of injury in trauma patients without MMTBI (n=188) versus trauma patients with MMTBI (n=189) versus trauma patients with intracranial lesions on CT (n=20). There were significant differences (p<0.001) between each of the three groups for both GFAP and S100β. Those with lesions on CT scan had the highest levels.
FIG. 4.
FIG. 4.
Receiver operating characteristics curves of glial fibrillary acidic protein (GFAP) versus S100β for detecting traumatic intracranial lesions on CT. (A) Performance of GFAP versus S100β measured within 4 h of injury in detecting intracranial lesions on CT in 262 trauma patients. (B) Performance of GFAP versus S100β measured within 4 h of injury in detecting intracranial lesions on CT in 257 trauma patients with GCS 14–15.
FIG. 5.
FIG. 5.
Comparison of levels of glial fibrillary acidic protein (GFAP) and S100β in various extracranial injuries (hematoma, facial fracture, isolated skull fracture) versus intracranial lesions found on head computed tomography (CT). Bars represent median serum levels with interquartile ranges of S100β and GFAP (ng/mL) measured within 4 h of injury in patients with extracranial versus intracranial lesions on head CT (n=194, 32, 14, 2, and 20, respectively). GFAP was able to discriminate between intracranial and extracranial lesions on CT. However, S100β was unable to discriminate between intracranial and extracranial lesions on CT.
FIG. 6.
FIG. 6.
Boxplot of levels of serum glial fibrillary acidic protein (GFAP) and S100β in patients with fractures on the torso and extremities. Bars represent median serum levels with interquartile ranges of S100β and GFAP (ng/mL) measured within 4 h of injury. (A) Comparison of GFAP versus S100β levels in trauma patients without mild or moderate traumatic brain injury (MMTBI) who had fractures to the torso and extremities. Even without traumatic brain injury, S100B was significantly elevated (p<0.001) in those with fractures to the torso and extremities. There was, however, no significant elevation in GFAP (p=0.521). (B) Comparison of GFAP versus S100β levels in all trauma patients (with and without MMTBI) who had fractures to the torso and extremities. Again, S100β was significantly elevated (p<0.001) in those with fractures but GFAP was not (p=0.104).

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