Dataset Information

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.

ABSTRACT:

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.

SUBMITTER: Papa L

PROVIDER: S-EPMC8805143 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-terminal hydrolase (UCH-L1) have been FDA-approved for clinical use in mild and moderate traumatic brain injury (TBI). Understanding sex differences in their diagnostic accuracy over time will help inform clinical practice. We sought to evaluate the sex differences in the temporal profile of GFAP and UCH-L1 in a large cohort of trauma patients presenting to the emergency department. To compare the biomarkers' diagnostic accuracy in male versus female patients for detecting mild TBI (MTBI), and traumatic intracranial lesions on head CT. This prospective cohort study enrolled female and male adult trauma patients presenting to a Level 1 Trauma Center. All patients underwent rigorous screening to determine whether or not they had experienced a MTBI. Of 3025 trauma patients assessed, 1030 met eligibility criteria and 446 declined. Initial blood samples were obtained in 584 patients enrolled within 4 h of injury. 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-h post-injury. The main outcomes included the diagnostic accuracy in detection of MTBI and traumatic intracranial lesions on head CT scan. A total of 1831 samples were drawn in 584 patients over 7 days, 362 (62%) were male and 222 (38%) were female. The pattern of elevation was similar in both sexes. Although the pattern of elevation was similar between male and female for both biomarkers, male patients had significantly higher concentrations of UCH-L1 compared to female patients at several timepoints post-injury, particularly within 24 h of injury. There were no significant differences in diagnostic accuracy for detecting MTBI or for detecting CT lesions between male and female patients at any timepoint for both GFAP and UCH-L1. Although patterns of GFAP and UCH-L1 release in trauma patients over a week post-injury was similar between the sexes, there were significantly higher concentrations of UCH-L1 in males at several timepoints post-injury. Despite this, the overall diagnostic accuracies of both GFAP and UCH-L1 over time for detecting MTBI and CT lesions were not significantly different between male and female trauma patients.

Project description:Objectives:To 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. Design:Large prospective cohort study. Setting:Three level I trauma centres in the USA. Participants:Paediatric 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 outcomes:Detection 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). Results:A 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. Conclusions:In 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.

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