ObjectivesTo evaluate the ability of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1) to detect concussion in children and adult trauma patients with a normal mental status and assess biomarker concentrations over time as gradients of injury in concussive and non-concussive head and body trauma.DesignLarge prospective cohort study.SettingThree level I trauma centres in the USA.ParticipantsPaediatric and adult trauma patients of all ages, with and without head trauma, presenting with a normal mental status (Glasgow Coma Scale score of 15) within 4 hours of injury. Rigorous screening for concussive symptoms was conducted. Of 3462 trauma patients screened, 751 were enrolled and 712 had biomarker data. Repeated blood sampling was conducted at 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 and 180 hours postinjury in adults.Main outcomesDetection of concussion and gradients of injury in children versus adults by comparing three groups of patients: (1) those with concussion; (2) those with head trauma without overt signs of concussion (non-concussive head trauma controls) and (3) those with peripheral (body) trauma without head trauma or concussion (non-concussive body trauma controls).ResultsA total of 1904 samples from 712 trauma patients were analysed. Within 4 hours of injury, there were incremental increases in levels of both GFAP and UCH-L1 from non-concussive body trauma (lowest), to mild elevations in non-concussive head trauma, to highest levels in patients with concussion. In concussion patients, GFAP concentrations were significantly higher compared with body trauma controls (p<0.001) and with head trauma controls (p<0.001) in both children and adults, after controlling for multiple comparisons. However, for UCH-L1, there were no significant differences between concussion patients and head trauma controls (p=0.894) and between body trauma and head trauma controls in children. The AUC for initial GFAP levels to detect concussion was 0.80 (0.73–0.87) in children and 0.76 (0.71–0.80) in adults. This differed significantly from UCH-L1 with AUCs of 0.62 (0.53–0.72) in children and 0.69 (0.64–0.74) in adults.ConclusionsIn a cohort of trauma patients with normal mental status, GFAP outperformed UCH-L1 in detecting concussion in both children and adults. Blood levels of GFAP and UCH-L1 showed incremental elevations across three injury groups: from non-concussive body trauma, to non-concussive head trauma, to concussion. However, UCH-L1 was expressed at much higher levels than GFAP in those with non-concussive trauma, particularly in children. Elevations in both biomarkers in patients with non-concussive head trauma may be reflective of a subconcussive brain injury. This will require further study.

In adults, glial fibrillary acidic protein (GFAP) has been shown to out-perform S100b in detecting intracranial lesions on computed tomography (CT) in mild traumatic brain injury (TBI). This study examined the ability of GFAP and S100b to detect intracranial lesions on CT in children and youth involved in trauma. This prospective cohort study enrolled a convenience sample of children and youth at two pediatric and one adult Level 1 trauma centers following trauma, including both those with and without head trauma. Serum samples were obtained within 6 h of injury. The primary outcome was the presence of traumatic intracranial lesions on CT scan. There were 155 pediatric trauma patients enrolled, 114 (74%) had head trauma and 41 (26%) had no head trauma. Out of the 92 patients who had a head CT, eight (9%) had intracranial lesions. The area under the receiver operating characteristic curve (AUC) for distinguishing head trauma from no head trauma for GFAP was 0.84 (0.77-0.91) and for S100b was 0.64 (0.55-0.74; p < 0.001). Similarly, the AUC for predicting intracranial lesions on CT for GFAP was 0.85 (0.72-0.98) versus 0.67 (0.50-0.85) for S100b ( p = 0.013). Additionally, we assessed the performance of GFAP and S100b in predicting intracranial lesions in children ages 10 years or younger and found the AUC for GFAP was 0.96 (95% confidence interval [CI] 0.86-1.00) and for S100b was 0.72 (0.36-1.00). In children younger than 5 years old, the AUC for GFAP was 1.00 (95% CI 0.99-1.00) and for S100b 0.62 (0.15-1.00). In this population with mild TBI, GFAP out-performed S100b in detecting head trauma and predicting intracranial lesions on head CT. This study is among the first published to date to prospectively compare these two biomarkers in children and youth with mild TBI.

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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