Serum Concentrations of Ubiquitin C-Terminal Hydrolase-L1 and Glial Fibrillary Acidic Protein after Pediatric Traumatic Brain Injury

Abstract

Objective reliable markers to assess traumatic brain injury (TBI) and predict outcome soon after injury are a highly needed tool for optimizing management of pediatric TBI. We assessed serum concentrations of Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-Terminal Hydrolase-L1 (UCH-L1) in a cohort of 45 children with clinical diagnosis of TBI (Glasgow Coma Scale [GCS] 3-15) and 40 healthy subjects, evaluated their associations with clinical characteristics and outcomes, and compared their performance to previously published data on two well-studied blood biomarkers, S100B and MBP. We observed higher serum levels of GFAP and UCH-L1 in brain-injured children compared with controls and also demonstrated a step-wise increase of biomarker concentrations over the continuum of severity from mild to severe TBI. Furthermore, while we found that only the neuronal biomarker UCH-L1 holds potential to detect acute intracranial lesions as assessed by computed tomography (CT), both markers were substantially increased in TBI patients even with a normal CT suggesting the presence of undetected microstructural injuries. Serum UCH-L1 and GFAP concentrations also strongly predicted poor outcome and performed better than S100B and MBP. Our results point to a role of GFAP and UCH-L1 as candidate biomarkers for pediatric TBI. Further studies are warranted.

Figure 1. Box-and-whisker plots demonstrating serum GFAP and UCH-L1 concentrations cases with mild (GCS 13 to 15), moderate (GCS 9 to 12) or severe TBI (GCS 3 to 8) compared with controls.

The black horizontal line in each box represents the median, with the boxes representing the interquartile range. Significant differences are indicated (Jonckheere-Terpstra test).

Figure 2. Receiver operating characteristic curves demonstrating the diagnostic accuracy of serum UCH-L1 concentrations for discriminating between patients who have relevant intracranial lesions on CT scans and those with a normal CT.