Day-of-injury biomarkers reliable predictors of mortality, unfavorable outcomes after TBI

Biomarkers collected on the day of traumatic brain injury had significant prognostic value for death and unfavorable outcome but not for incomplete recovery at 6 months, according to a study published in The Lancet Neurology.

“During the past 10 years, several blood-based biomarkers of glial and neuronal cell injury obtained on the day of injury have been reported to be associated with structural brain injury visualized by neuroimaging,” Frederick K. Korley, MD, PhD, associate professor of emergency medicine at the University of Michigan, and colleagues wrote. “Increased precision in estimates of the prognostic value of these biomarkers could provide early and more accurate information on which to base clinical decisions and a more refined study design than currently exists.”

Korley and fellow researchers sought to quantify the prognostic accuracy of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) and determine whether these biomarkers could add new prognostic value to existing clinical models.

They enrolled 2,552 individuals, aged 17 years and older, who were evaluated for TBI at 18 level 1 trauma centers in the United States.

Participants were part of the Transforming Research and Clinical Knowledge in Traumatic Brain Injury observational cohort study and underwent head CT scan at evaluation, had adequate preinjury vision and hearing, had plasma samples collected within 24 hours of injury for measurement of GFAP and UCH-L1, and completed 6-month follow-up assessments of functional recovery using the Glasgow Outcome Scale–Extended (GOSE-TBI).

The primary outcomes were death (GOSE-TBI = 1) or unfavorable outcome at 6 months following injury (GOSE-TBI 4), and secondary outcome was incomplete recovery at 6 months (GOSE-TBI < 8).

According to study results, of 1,696 participants with TBI and baseline and 6-month data, 120 died, 235 had an unfavorable outcome, 1,135 had incomplete recovery and 561 had a full recovery. Researchers further reported that day-of-injury GFAP and UCH-L1 concentrations were higher in participants who died or who had GOSE-TBI scores of 2 to 4 within the 6-month follow-up period.

Among 353 participants with Glasglow Coma Scale (GCS) scores of 3 to 12, supplementing GFAP and UCH-L1 (alone or combined) concentrations to each of the three International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) in TBI models significantly increased the area under the curve for predicting death (0.9-0.94) and unfavorable outcome (0.83-0.89). However, of 1,297 participants with GCS scores of 13 to 15, incorporating GFAP and UCH-L1 values to the UPFRONT study model only slightly increased the prognostic value for incomplete recovery (0.69-0.69).

“In addition to their known diagnostic value, day-of-injury GFAP and UCH-L1 concentrations, in conjunction with IMPACT models, can provide a more accurate appraisal than IMPACT models alone of the likelihood of unfavorable outcome, including death, following traumatic brain injury of GCS score 3 to 12,” Korley and colleagues wrote.