Linda Papa, MD Emergency Physicians of Central Florida Orlando Health Orlando, Florida

Blood Biomarker Appears to be Good Biomarker to Detect Mild Brain Injuries Interview with:

Linda Papa, MD Emergency Physicians of Central Florida Orlando Health Orlando, Florida

Dr. Papa

Linda Papa, MD
Emergency Physicians of Central Florida
Orlando Health
Orlando, Florida What is the background for this study?

Response: In 2018 serum biomarkers Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-terminal hydrolase (UCH-L1) were FDA-approved in adults to detect abnormalities on CT scan in mild to moderate traumatic brain injury. However, they have not been approved to detect concussion and they have not been approved for use in children.

Previous studies have focused on detecting lesions on CT in more severely injured patients. However, not having brain lesions on a CT scan does not mean there is no brain injury or concussion. Therefore, this study focused on patients with concussion who looked well and likely had normal-appearing CT scans of the brain.

This study includes THREE groups of trauma patients:

  • 1) those with concussion,
  • 2) those who hit their head but had no symptoms (subconcussive), and
  • 3) those who injured their bones but did not hit their head (no concussion).

There is a group of individuals with head trauma who have been significantly understudied, and in whom biomarkers are rarely, if at all, examined. These are people who experience head trauma without symptoms of concussion. They may be classified as having “no injury” or they may represent milder forms of concussion that do not elicit the typical signs or symptoms associated with concussion and are referred to as “subconcussive” injuries. What are the main findings? 

Response: In this study GFAP was much better than UCH-L1 in detecting concussion in both children and adults. Although blood levels of both GFAP and UCH-L1 showed incremental increases from body trauma (lowest levels), to head trauma without concussion (higher levels than body trauma), to concussion (highest levels), GFAP was much better in distinguishing between the groups. GFAP did not elevated after body trauma only after head trauma making it more specific to brain injury. GFAP was also able to detect concussion up to a week after injury. What should readers take away from your report?

Response:   It is difficult for clinicians is to detect concussion after a trauma when patients have a normal mental status. Having an objective measure of concussion would be very helpful to determine if there is an injury and how severe it is.

This study examined a blood test in patients of all ages with concussion (also known as mild traumatic brain injury). There were a total of 1904 samples drawn in 712 patients making it a very large study compared to most of the studies that have been previously published.

The study examined this blood test over 7 days in patients with and without concussion and showed how milder forms of brain injury can still lead to release of these “brain injury proteins” into the blood after injury. It also shows the potential of using a blood test to gauge the severity of a brain injury even when a CT scan is negative.

GFAP appears to be a very good biomarker to detect mild brain injuries. What recommendations do you have for future research as a result of this work? 

Response: Next steps will include examining these patients over time to see how they recover from their injuries and validating these results in a larger group of patients, particularly children and youth. Is there anything else you would like to add?

Response:  Since this blood test is FDA approved in adults, it is a matter of time before it will be applied to children, so this study compares how the blood test works in children and adults.

Currently, the test requires specialized equipment and takes several hours to get a result, so it is not practical for clinical use. However, companies are working on a benchtop device for the hospital lab and a point-of-care handheld device that can be used on site. Once it becomes practical to use, it could potentially be used in ambulances, on the playing field, in clinics and emergency departments to evaluate concussion.

The study of subconcussive head trauma in the civilian population is rare. The issue of subconcussive trauma has been a particular concern in military personnel and in athletes, as repetitive subconcussive impacts have the potential for long-term deleterious effects. Therefore, studying these biomarkers in patients with head trauma without symptoms provides unique insights into how these biomarkers behave in subconcussive trauma patients of all ages and different injury types.


Linda Papa, Mark R Zonfrillo, Robert D Welch, Lawrence M Lewis, Carolina F Braga, Ciara N Tan, Neema J Ameli, Marco A Lopez, Crystal A Haeussler, Diego Mendez Giordano, Philip A Giordano, Jose Ramirez, Manoj K Mittal. Evaluating glial and neuronal blood biomarkers GFAP and UCH-L1 as gradients of brain injury in concussive, subconcussive and non-concussive trauma: a prospective cohort study. BMJ Paediatrics Open, 2019; 3 (1): e000473 DOI: 10.1136/bmjpo-2019-000473


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Last Updated on August 31, 2019 by Marie Benz MD FAAD