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Comparative Study
. 2011 Jun 24;15(3):R156.
doi: 10.1186/cc10286.

Neuronal and glial markers are differently associated with computed tomography findings and outcome in patients with severe traumatic brain injury: a case control study

Stefania Mondello  1 , Linda Papa, Andras Buki, M Ross Bullock, Endre Czeiter, Frank C Tortella, Kevin K Wang, Ronald L Hayes
Affiliations
Comparative Study

Neuronal and glial markers are differently associated with computed tomography findings and outcome in patients with severe traumatic brain injury: a case control study

Stefania Mondello et al. Crit Care. .

Abstract

Introduction: Authors of several studies have studied biomarkers and computed tomography (CT) findings in the acute phase after severe traumatic brain injury (TBI). However, the correlation between structural damage as assessed by neuroimaging and biomarkers has not been elucidated. The aim of this study was to investigate the relationships among neuronal (Ubiquitin carboxy-terminal hydrolase L1 [UCH-L1]) and glial (glial fibrillary acidic protein [GFAP]) biomarker levels in serum, neuroradiological findings and outcomes after severe TBI.

Methods: The study recruited patients from four neurotrauma centers. Serum samples for UCH-L1 and GFAP were obtained at the time of hospital admission and every 6 hours thereafter. CT scans of the brain were obtained within 24hrs of injury. Outcome was assessed by Glasgow Outcome Scale (GOS) at discharge and at 6 months.

Results: 81 severe TBI patients and 167 controls were enrolled. The mean serum levels of UCH-L1 and GFAP were higher (p < 0.001) in TBI patients compared to controls. UCH-L1 and GFAP serum levels correlated significantly with Glasgow Coma Scale (GCS) and CT findings. GFAP levels were higher in patients with mass lesions than in those with diffuse injury (2.95 ± 0.48 ng/ml versus 0.74 ± 0.11 ng/ml) while UCH-L1 levels were higher in patients with diffuse injury (1.55 ± 0.18 ng/ml versus 1.21 ± 0.15 ng/ml, p = 0.0031 and 0.0103, respectively). A multivariate logistic regression showed that UCH-L1 was the only independent predictor of death at discharge [adjusted odds ratios 2.95; 95% confidence interval, 1.46-5.97], but both UCH-L1 and GFAP levels strongly predicted death 6 months post-injury.

Conclusions: Relationships between structural changes detected by neuroimaging and biomarkers indicate each biomarker may reflect a different injury pathway. These results suggest that protein biomarkers could provide better characterization of subjects at risk for specific types of cellular damage than that obtained with neuroimaging alone, as well as provide valuable information about injury severity and outcome after severe TBI.

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Figures

Figure 1
Figure 1
Serum levels of ubiquitin C-terminal hydrolase-L1 protein (UCH-L1) and glial fibrillary acidic protein (GFAP) in patients with diffuse injury or focal mass lesion. (a and b) Box plots of biomarker boxes enclose 25th to 75th percentiles; vertical whiskers extend to 10th and 90th percentiles. Median (50th percentile) is marked by the line inside the box; mean is marked by the diamond; outliers are plotted with circles. (a) Serum levels of UCH-L1 versus Marshall Score (Diffuse Injury vs Focal Mass Lesion) (Kruskal-Wallis Test, P = 0.0006). (b) Serum levels GFAP versus Marshall Score (Diffuse Injury vs Focal Mass Lesion) (Kruskal-Wallis Test, P = 0.0163). (c and d) Scatterplot with average smoothing superimposed on a graph of (c) UCH-L1 and in (d) GFAP levels versus time. The figure was generated using the LOWESS (LOcally WEighted Scatterplot Smoother) technique to draw a smooth line representing the average value of the variable on the y-axis as a function of the variable on the x-axis.
Figure 2
Figure 2
Ubiquitin C-terminal hydrolase-L1 protein (UCH-L1) and glial fibrillary acidic protein (GFAP) dynamics in human serum after acute injury. (a and b) Computed tomography scans demonstrating focal and diffuse brain injury in individual patients. (c and d) UCH-L1 (green circles) and GFAP (blue triangles) serum concentrations measured every six hours in corresponding individual patients. Time (x axis) reflects interval after injury.
Figure 3
Figure 3
Serum levels of ubiquitin C-terminal hydrolase-L1 protein (UCH-L1) and glial fibrillary acidic protein (GFAP) in relation to 6 months mortality after severe traumatic brain injury. Mortality increased with increasing (UCH-L1) and (GFAP) levels (average serum levels in the first 24 hours).
Figure 4
Figure 4
Spline function analysis showing the association between the serum ubiquitin C-terminal hydrolase-L1 protein (UCH-L1) levels and in hospital mortality, probability of mortality. The risk of mortality increases slowly up to a "threshold" range of UCH-L1, followed by a more rapid increase and a subsequent levelling off.
Figure 5
Figure 5
Associations between Marshall Score and mortality at discharge and six months. The percentage mortality was low in patients with Marshall Score I and II. The highest mortality rate was observed in patients with Marshall Score III-IV for both in hospital mortality and at six months.
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