Performance of Glial Fibrillary Acidic Protein in Detecting Traumatic Intracranial Lesions on Computed Tomography in Children and Youth With Mild Head Trauma

Abstract

Objectives This study examined the performance of serum glial fibrillary acidic protein (GFAP) in detecting traumatic intracranial lesions on computed tomography (CT) scan in children and youth with mild and moderate traumatic brain injury (TBI), and assessed its performance in trauma control patients without head trauma. Methods This prospective cohort study enrolled children and youth presenting to three Level I trauma centers following blunt head trauma with Glasgow Coma Scale (GCS) scores of 9 to 15, as well as trauma control patients with GCS scores of 15 who did not have blunt head trauma. The primary outcome measure was the presence of intracranial lesions on initial CT scan. Blood samples were obtained in all patients within six hours of injury and measured by ELISA for GFAP (ng/ml). Results A total of 257 children and youth were enrolled in the study and had serum samples drawn within 6 hours of injury for analysis: 197 had blunt head trauma and 60 were trauma controls. CT scan of the head was performed in 152 patients and traumatic intracranial lesions on CT scan were evident in 18 (11%), all of whom had GCS scores of 13 to 15. When serum levels of GFAP were compared in children and youth with traumatic intracranial lesions on CT scan to those without CT lesions, median GFAP levels were significantly higher in those with intracranial lesions (1.01, IQR 0.59 to 1.48) than those without lesions (0.18, IQR 0.06 to 0.47). The area under the receiver operating characteristic (ROC) curve (AUC) for GFAP in detecting children and youth with traumatic intracranial lesions on CT was 0.82 (95% CI = 0.71 to 0.93). In those presenting with GCS scores of 15, the AUC for detecting lesions was 0.80 (95% CI = 0.68 to 0.92). Similarly, in children under five years old the AUC was 0.83 (95% CI = 0.56 to 1.00). Performance for detecting intracranial lesions at a GFAP cutoff level of 0.15 ng/ml yielded a sensitivity of 94%, a specificity of 47%, and a negative predictive value of 98%. Conclusions In children and youth of all ages, GFAP measured within 6 hours of injury was associated with traumatic intracranial lesions on CT and with severity of TBI. Further study is required to validate these findings before clinical application.

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“…4 In adults and children, serum GFAP levels distinguish MTBI patients from trauma patients without TBI and detect intracranial lesions on CT with a sensitivity of 94%–100%. 32, 33, 52, 54 Moreover, GFAP out-performs S100β in detecting CT lesions in the setting of multiple trauma when extracranial fractures are present. 33, 54 GFAP also predicts the need for neurosurgical intervention in patients with MTBI.…”

“…32, 33, 52, 54 Moreover, GFAP out-performs S100β in detecting CT lesions in the setting of multiple trauma when extracranial fractures are present. 33, 54 GFAP also predicts the need for neurosurgical intervention in patients with MTBI. 52, 55 …”

“…Although GFAP has been studied in brain injury since the 1990’s, it is not until recently that it has been assessed in serum following trauma 4, 33, 52, 53, 55 and more specifically in children 32, 54 and in sports. 49, 56–58 The performance of GFAP has been much better (more accurate in detecting injury) in trauma patients presenting with MTBI to the emergency department compared to the studies performed in athletes to-date.…”

“…This discrepancy may stem from the timing of the blood draws relative to time of injury or from the type of assay used. 55 In studies with trauma patients, samples have been drawn within 4–6 hours 32, 33, 52, 54, 55 and up to 24 hours after injury. 4, 53 However, in athletes, the samples tend to be drawn later from days to months.…”

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“…Due to these consequences, much focus has been placed on technologies that can aid in the detection of concussion 12,13 ; however, less attention has been placed on facilitating and managing recovery after concussion. Given the significance of sport concussion as a leading public health concern, 14 it is prudent to explore a wide array of approaches to facilitate the recovery of individuals after a sport concussion and to assist athletic trainers in this process.…”