Blood Biomarkers Predict TBI Disability, Mortality

Megan Brooks

August 22, 2022

Two biomarkers present in blood measured on the day of traumatic brain injury (TBI) can accurately predict a patient's risk for death or severe disability 6 months later, new research suggests.

In new data from the TRACK-TBI study group, high levels of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) proteins found in glial cells and neurons, respectively, correlated with death and severe injury.

Investigators note that measuring these biomarkers may give a more accurate assessment of a patient's prognosis following TBI.

This study is the "first report of the accuracy of a blood test that can be obtained rapidly on the day of injury to predict neurological recovery at 6 months after injury," lead author Frederick Korley, MD, PhD, associate professor of emergency medicine at the University of Michigan, Ann Arbor, said in a news release.

The findings were published online August 10 in The Lancet Neurology.

Added Value

The researchers measured GFAP and UCH-L1 in blood samples taken from 1696 patients with TBI on the day of their injury, and they assessed patient recovery 6 months later.

The markers were measured using the i-STAT TBI Plasma test (Abbott Labs). As reported by Medscape Medical News, the test was approved last year by the US Food and Drug Administration (FDA) to determine which patients with mild TBI should undergo computed tomography (CT) scans.

About two thirds of the study population were men, and the average age was 39 years. All patients were evaluated at Level I trauma centers for injuries caused primarily by traffic accidents or falls.

Six months following injury, 7% of the patients had died and 14% had an unfavorable outcome, ranging from vegetative state to severe disability requiring daily support. In addition, 67% had incomplete recovery, ranging from moderate disabilities requiring assistance outside of the home to minor disabling neurological or psychological deficits.

Day-of-injury GFAP and UCH-L1 levels had a high probability of predicting death (87% for GFAP and 89% for UCH-L1) and severe disability (86% for both GFAP and UCH-L1) at 6 months, the investigators report.

The biomarkers were less accurate in predicting incomplete recovery (62% for GFAP and 61% for UCH-L1).

The researchers also assessed the added value of combining the blood biomarkers to current TBI prognostic models that take into account variables such as age, motor score, pupil reactivity, and CT characteristics.

In patients with a Glasgow Coma Scale (GCS) score of 3 to 12, adding GFAP and UCH-L1 alone or combined to each of the three International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) models significantly increased their accuracy for predicting death (range, 90%-94%) and unfavorable outcome (range, 83%-89%).

In patients with milder TBI (GCS score, 13-15), adding GFAP and UCH-L1 to the UPFRONT prognostic model modestly increased accuracy for predicting incomplete recovery (69%).

Important Findings

Commenting for Medscape Medical News, Cyrus A. Raji, MD, PhD, assistant professor of radiology and neurology, Washington University in St. Louis, Missouri, said this "critical" study shows that these biomarkers can "predict key outcomes," including mortality and severe disability.

"Thus, in conjunction with clinical evaluations and related data such as neuroimaging, these tests may warrant translation to broader clinical practice, particularly in acute settings," said Raji, who was not involved in the research.

Also weighing in, Heidi Fusco, MD, assistant director of the traumatic brain injury program at NYU Langone Rusk Rehabilitation, New York City, said the findings are "important."

"Prognosis after brain injury often is based on the initial presentation, ongoing clinical exams, and neuroimaging; and the addition of biomarkers would contribute to creating a more objective prognostic model," Fusco told Medscape Medical News.

She noted "it's unclear" whether clinical hospital laboratories would be able to accommodate this type of laboratory drawing.

"It is imperative that clinicians still use the patient history, clinical and radiological exam when making clinical decisions for a patient and not just lab values. It would be best to incorporate the GFAP and UCH-L1 into a preexisting prognostic model," Fusco said.

The study was funded by the US National Institutes of Health, National Institute of Neurologic Disorders and Stroke, US Department of Defense, One Mind, and US Army Medical Research and Development Command. Korley reported having previously consulted for Abbott Laboratories and has received research funding from Abbott Laboratories, which makes the assays used in the study. Raji is a consultant for Brainreader ApS and Neurevolution LLC. Fusco has reported no relevant financial relationships.

Lancet Neurology. Published online August 10, 2022. Abstract.

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