Blood Biomarkers Enhance Brain Injury Prognosis

A blood test within 24 hours of a traumatic brain injury (TBI) predicted functional outcomes of some patients 6 months later, independent analyses of data from two observational cohort studies found.

The studies looked at ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1) and glial fibrillary acid protein (GFAP) — both previously approved by the FDA to help clinicians decide whether to order a CT scan for people with mild TBI — as well as neuron-specific enolase (NSE), total tau, neurofilament protein-light (NfL), and S100 calcium-binding protein B (S100B).

Same-day blood biomarkers generally enhanced the value of established prognostic models based on variables like age, motor score, pupil reactivity, and CT characteristics in predicting functional Glasgow Outcome Scale Extended (GOSE)-assessed outcomes of mortality, unfavorable outcome, and incomplete recovery at 6 months, TRACK-TBI and CENTER-TBI researchers reported in Lancet Neurology.

“Considered together, these studies provide the most comprehensive evidence to date that day-of-injury blood biomarkers add value to clinical prognostic models of functional outcome after traumatic brain injury,” noted Sandy Shultz, PhD, of Monash University in Melbourne, Australia, and co-authors in an accompanying editorial.

In clinical practice, biomarkers “might be useful for providing early and reliable prognostic information to patients and their families, and for guiding clinical decision making,” they added.

TRACK-TBI

TRACK-TBI found that day-of-injury blood levels of GFAP and UCH-L1 had “good to excellent discriminative ability” for predicting probability of death and poor outcome at 6 months.

The area under the curve (AUC) for mortality prediction was 0.87 (95% CI 0.83-0.91) and 0.89 (95% CI 0.86-0.92) for the two biomarkers, respectively, and 0.86 for both markers for predicting severe disability at 6 months.

However, levels of accuracy were lower for predictions of incomplete recovery versus complete recovery, at AUCs of 0.62 for GFAP and 0.61 for UCH-L1, reported Frederick Korley, MD, PhD, of the University of Michigan in Ann Arbor, and co-authors.

Investigators enrolled 1,696 patients with a median age of 39 between Feb. 26, 2014, and Aug. 8, 2018. Among them, 7.1% died, 13.9% had an unfavorable outcome (GOSE-TBI ≤4), 66.9% had incomplete recovery (GOSE-TBI <8), and 33.1% recovered fully (GOSE-TBI 8).

Among the 353 participants with a Glasgow Coma Scale (GCS) score of 3–12, adding GFAP and UCH-L1 (alone or combined) to each of the three IMPACT models significantly increased their AUCs for predicting death (range 0.90-0.94) and unfavorable outcome (range 0.83-0.89).

Predictive ability was modest in patients with traumatic brain injury and a GCS score of 13-15.

The study used fast-processing assays to help identify which patients with mild TBI should undergo CT scans. The tests are “both diagnostic and prognostic,” as well as easy to administer, swift and inexpensive, co-author Geoffrey Manley, MD, PhD, of the University of California San Francisco, noted in a statement.

“We believe this tool may encourage clinicians to be more aggressive in their decisions to begin or continue life-saving treatment,” Manley said. “Modern trauma care can result in good outcomes in what we had once believed were non-survivable injuries.”

CENTER-TBI

The similarly designed CENTER-TBI study noted the strongest associations between biomarker levels and functional outcomes for UCH-L1, NFL, S100B, t-tau, and GFAP compared with NSE, reported Andrew Maas, MD, of Antwerp University Hospital in Belgium, and colleagues.

For 6-month GOSE, the Spearman rank correlations were –0.43 for S100B, –0.28 for NSE, –0.50 for GFAP, –0.54 for UCH-L1, –0.52 for t-tau, and –0.56 for NfL.

Of the mostly white cohort of 2,283 patients enrolled between Dec 19, 2014, and Dec 17, 2017, 68% were male and median age was 51. The initial injury was mild TBI (GCS 13-15) for 67%, and 37% of participants had major extracranial injury. At 6 months, 12% of patients had died, 26% had an unfavorable outcome, and 63% had an incomplete recovery.

Compared with prediction based on demographic, clinical, and radiological characteristics alone, adding all six biomarkers improved the C-statistic by 0.014 and R² by 4.9% for predicting GOSE. “Adding biomarkers to established prognostic models resulted in a relative increase in R² of 48-65% for IMPACT and 30-34% for CRASH prognostic models,” the researchers reported.

“We found that UCH-L1 had greatest incremental value for predicting unfavorable outcome in patients with moderate to severe traumatic brain injury, and NFL for predicting incomplete recovery in mild traumatic brain injury,” the group noted. “GFAP is more relevant for diagnostic purposes and less so for predicting functional outcome after traumatic brain injury.”

Limitations of both studies included the minimal or lack of added predictive value in patients with mild TBI which limits generalizability, along with potential variability associated with the biomarker assays used in the studies, the editorial authors noted.