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Multicenter Study
. 2012 Jun;59(6):471-83.
doi: 10.1016/j.annemergmed.2011.08.021. Epub 2011 Nov 8.

Elevated levels of serum glial fibrillary acidic protein breakdown products in mild and moderate traumatic brain injury are associated with intracranial lesions and neurosurgical intervention

Linda Papa  1 , Lawrence M Lewis, Jay L Falk, Zhiqun Zhang, Salvatore Silvestri, Philip Giordano, Gretchen M Brophy, Jason A Demery, Neha K Dixit, Ian Ferguson, Ming Cheng Liu, Jixiang Mo, Linnet Akinyi, Kara Schmid, Stefania Mondello, Claudia S Robertson, Frank C Tortella, Ronald L Hayes, Kevin K W Wang
Affiliations
Multicenter Study

Elevated levels of serum glial fibrillary acidic protein breakdown products in mild and moderate traumatic brain injury are associated with intracranial lesions and neurosurgical intervention

Linda Papa et al. Ann Emerg Med. 2012 Jun.

Abstract

Study objective: This study examines whether serum levels of glial fibrillary acidic protein breakdown products (GFAP-BDP) are elevated in patients with mild and moderate traumatic brain injury compared with controls and whether they are associated with traumatic intracranial lesions on computed tomography (CT) scan (positive CT result) and with having a neurosurgical intervention.

Methods: This prospective cohort study enrolled adult patients presenting to 3 Level I trauma centers after blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale (GCS) score of 9 to 15. Control groups included normal uninjured controls and trauma controls presenting to the emergency department with orthopedic injuries or a motor vehicle crash without traumatic brain injury. Blood samples were obtained in all patients within 4 hours of injury and measured by enzyme-linked immunosorbent assay for GFAP-BDP (nanograms/milliliter).

Results: Of the 307 patients enrolled, 108 were patients with traumatic brain injury (97 with GCS score 13 to 15 and 11 with GCS score 9 to 12) and 199 were controls (176 normal controls and 16 motor vehicle crash controls and 7 orthopedic controls). Receiver operating characteristic curves demonstrated that early GFAP-BDP levels were able to distinguish patients with traumatic brain injury from uninjured controls with an area under the curve of 0.90 (95% confidence interval [CI] 0.86 to 0.94) and differentiated traumatic brain injury with a GCS score of 15 with an area under the curve of 0.88 (95% CI 0.82 to 0.93). Thirty-two patients with traumatic brain injury (30%) had lesions on CT. The area under these curves for discriminating patients with CT lesions versus those without CT lesions was 0.79 (95% CI 0.69 to 0.89). Moreover, the receiver operating characteristic curve for distinguishing neurosurgical intervention from no neurosurgical intervention yielded an area under the curve of 0.87 (95% CI 0.77 to 0.96).

Conclusion: GFAP-BDP is detectable in serum within an hour of injury and is associated with measures of injury severity, including the GCS score, CT lesions, and neurosurgical intervention. Further study is required to validate these findings before clinical application.

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Figures

Figure 1
Figure 1. Flow diagram of enrolled patients
Flow diagram showing the number of all TBI and control patients enrolled.
Figure 2
Figure 2. Temporal profile of GFAP-BDP in TBI patients within 4 hours of injury
The dots represent levels of GFAP-BDP (ng/ml) at different times post-injury. GFAP-BDP demonstrated a rapid appearance in serum post-injury with levels detectible within an hour of injury.
Figures 3a, 3b, 3c, & 3d
Figures 3a, 3b, 3c, & 3d
Figure 3a. A comparison of serum levels of GFAP-BDP drawn within 4 hours of injury in TBI patients with different GCS scores versus normal and trauma controls. GCS scores were divided as GCS 15, GCS 13–14, and GCS 9–12. There are 3 control groups: i- non-injured, ii- non-head injured orthopedic controls, and iii- non-head injured controls from motor vehicle collisions. There are statistically significant differences between the uninjured controls and each of the groups (indicated by the asterisk “*”) and serum levels of GFAP-BDP increased incrementally with worsening GCS scores. Boxplots represent medians in ng/ml and interquartile ranges. Figure 3b. A comparison of serum levels of GFAP-BDP drawn within 4 hours of injury in TBI patients with GCS 15 versus trauma controls. When TBI patients with an ED GCS score of 15 are isolated from the TBI group early GFAP-BDP levels demonstrate significant differences between patients with a GCS 15 versus trauma controls. Boxplots represent medians in ng/ml and interquartile ranges. Figure 3c. A comparison of serum levels of GFAP-BDP in TBI patients with GCS dichotomized into GCS 13–15 versus GCS 9–12. When TBI patients are dichotomized into the traditional GCS 13–15 versus GCS 9–12, early GFAP-BDP levels are significantly different between the 2 groups. Boxplots represent medians in ng/ml and interquartile ranges. Figure 3d. A comparison of serum levels of GFAP-BDP in TBI patients with GCS dichotomized into GCS 14–15 versus GCS 9–13. When TBI patients are dichotomized into the more recently suggested dichotomy of GCS 14–15 versus GCS 9–13, early GFAP-BDP levels are significantly different between the 2 groups. Boxplots represent medians in ng/ml and interquartile ranges. * Statistically significant difference
Figures 4a & 4b
Figures 4a & 4b
Figure 4a. ROC Curve for distinguishing TBI versus uninjured controls. The area under the ROC curve (AUC) demonstrates that early GFAP-BDP levels are able discriminate between patients without injuries from patients with TBI with an AUC 0.90 (95%CI 0.86–0.94). Figure 4b. ROC Curve for distinguishing TBI patients with a GCS 15 versus uninjured controls. TBI Patients with a GCS 15 are isolated from the group and compared to uninjured controls. Early GFAP-BDP levels are able discriminate between patients without injuries from TBI patients with a GCS 15 with an AUC 0.88 (95%CI 0.82–0.93).
Figures 5a, 5b & 5c
Figures 5a, 5b & 5c
Figure 5a. Boxlplot comparing serum GFAP-BDP levels drawn within 4 hours of injury in patients with and without traumatic intracranial lesions on CT. Levels of serum GFAP-BDP are significantly higher in patients with traumatic intracranial lesions on CT (CT positive) than those without CT lesions (CT negative). Bars represent medians in ng/ml and interquartile ranges. Figure 5b. Boxplot comparing serum GFAP-BDP levels drawn within 4 hours of injury in patients with and without traumatic intracranial lesions on CT in TBI patients with GCS 15. In a subset of TBI patients with a GCS 15 levels of serum GFAP-BDP are significantly higher in those with traumatic intracranial lesions on CT (CT positive) than those without CT lesions (CT negative). Bars represent medians in ng/ml and interquartile ranges. Figure 5c. ROC Curve for distinguishing CT positive versus CT negative patients. The area under the ROC curve (AUC) demonstrates that early GFAP-BDP levels are able discriminate between patients with and without traumatic intracranial lesions on CT (AUC 0.79; 95%CI 0.69–0.89). Figure 5d. Boxplot comparing serum GFAP-BDP levels drawn within 4 hours of injury in patients with and without traumatic intracranial lesions on CT in both TBI and trauma controls. GFAP-BDP levels are significantly higher in patients with traumatic intracranial lesions on CT (CT positive) than those without CT lesions (CT negative) regardless of whether they are trauma controls or TBI. Bars represent medians in ng/ml and interquartile ranges. * Statistically significant difference
Figures 6a, 6b
Figures 6a, 6b
Figure 6a. Boxplot comparing serum GFAP-BDP levels drawn within 4 hours of injury in patients with neurosurgical intervention versus those without intervention. Levels of serum GFAP-BDP are significantly higher in patients with who had neurosurgical intervention versus those who did not. Bars represent medians in ng/ml and interquartile ranges. Figure 6b. ROC Curve for distinguishing those who had a neurosurgical intervention versus those who did not. The area under the ROC curve (AUC) demonstrates that early GFAP-BDP levels are able discriminate between patients with who required neurosurgical intervention versus those who did not (AUC 0.87; 95%CI 0.77–0.96). * Statistically significant difference
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