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Original Investigation |

Time Course and Diagnostic Accuracy of Glial and Neuronal Blood Biomarkers GFAP and UCH-L1 in a Large Cohort of Trauma Patients With and Without Mild Traumatic Brain Injury

Linda Papa, MDCM, MSc1; Gretchen M. Brophy, PharmD2,3; Robert D. Welch, MD, MS4; Lawrence M. Lewis, MD5; Carolina F. Braga, BA1; Ciara N. Tan, BS, MHSH1; Neema J. Ameli, BS1; Marco A. Lopez, AS1; Crystal A. Haeussler, BS1; Diego I. Mendez Giordano, BS1; Salvatore Silvestri, MD1; Philip Giordano, MD1; Kurt D. Weber, MD1; Crystal Hill-Pryor, PhD6; Dallas C. Hack, MD, MPH7
[+] Author Affiliations
1Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, Florida
2Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond
3Department of Neurosurgery, Virginia Commonwealth University, Richmond
4Division of Emergency Medicine, Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan
5Division of Emergency Medicine, Washington University School of Medicine in St Louis, Missouri
6US Department of Defense, Silver Springs, Maryland
7Brain Health, Harpers Ferry, West Virginia
JAMA Neurol. 2016;73(5):551-560. doi:10.1001/jamaneurol.2016.0039.
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Importance  Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) have been widely studied and show promise for clinical usefulness in suspected traumatic brain injury (TBI) and concussion. Understanding their diagnostic accuracy over time will help translate them into clinical practice.

Objectives  To evaluate the temporal profiles of GFAP and UCH-L1 in a large cohort of trauma patients seen at the emergency department and to assess their diagnostic accuracy over time, both individually and in combination, for detecting mild to moderate TBI (MMTBI), traumatic intracranial lesions on head computed tomography (CT), and neurosurgical intervention.

Design, Setting, and Participants  This prospective cohort study enrolled adult trauma patients seen at a level I trauma center from March 1, 2010, to March 5, 2014. All patients underwent rigorous screening to determine whether they had experienced an MMTBI (blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale score of 9-15). Of 3025 trauma patients assessed, 1030 met eligibility criteria for enrollment, and 446 declined participation. Initial blood samples were obtained in 584 patients enrolled within 4 hours of injury. Repeated blood sampling was conducted at 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 hours after injury.

Main Outcomes and Measures  Diagnosis of MMTBI, presence of traumatic intracranial lesions on head CT scan, and neurosurgical intervention.

Results  A total of 1831 blood samples were drawn from 584 patients (mean [SD] age, 40 [16] years; 62.0% [362 of 584] male) over 7 days. Both GFAP and UCH-L1 were detectible within 1 hour of injury. GFAP peaked at 20 hours after injury and slowly declined over 72 hours. UCH-L1 rose rapidly and peaked at 8 hours after injury and declined rapidly over 48 hours. Over the course of 1 week, GFAP demonstrated a diagnostic range of areas under the curve for detecting MMTBI of 0.73 (95% CI, 0.69-0.77) to 0.94 (95% CI, 0.78-1.00), and UCH-L1 demonstrated a diagnostic range of 0.30 (95% CI, 0.02-0.50) to 0.67 (95% CI, 0.53-0.81). For detecting intracranial lesions on CT, the diagnostic ranges of areas under the curve were 0.80 (95% CI, 0.67-0.92) to 0.97 (95% CI, 0.93-1.00)for GFAP and 0.31 (95% CI, 0-0.63) to 0.77 (95% CI, 0.68-0.85) for UCH-L1. For distinguishing patients with and without a neurosurgical intervention, the range for GFAP was 0.91 (95% CI, 0.79-1.00) to 1.00 (95% CI, 1.00-1.00), and the range for UCH-L1 was 0.50 (95% CI, 0-1.00) to 0.92 (95% CI, 0.83-1.00).

Conclusions and Relevance  GFAP performed consistently in detecting MMTBI, CT lesions, and neurosurgical intervention across 7 days. UCH-L1 performed best in the early postinjury period.

Figures in this Article

Figures

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Figure 1.
Flow Diagram of Screened and Enrolled Patients

CT indicates computed tomography; GCS, Glasgow Coma Scale; and MMTBI, mild to moderate traumatic brain injury.

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Figure 2.
Temporal Profiles of Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-Terminal Hydrolase L1 (UCH-L1)

A-B, Shown are the means, with error bars representing the SEMs. B, In trauma patients who had clinical evidence of mild to moderate traumatic brain injury (MMTBI) compared with those who experienced trauma but had no evidence of MMTBI.

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Figure 3.
Temporal Profiles of Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-Terminal Hydrolase L1 (UCH-L1)

A, In trauma patients who had computed tomography(CT) performed. Those with traumatic intracranial lesions on CT are compared with those without intracranial lesions on CT. B, In trauma patients who had a neurosurgical intervention. Those having a neurosurgical intervention are compared with those not having a neurosurgical intervention.

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