Could Biomarkers Be the Key to Concussion Recovery?

Kari Fraser was out for a trail run on Mount Sanitas, in Boulder, Colorado, in the winter of 2015 when she slipped on some ice and knocked her head. The impact resulted in a black eye, a severe headache, and a concussion. Fraser, who was 53 at the time, went to the ER and was told she’d be OK, but she didn’t know what to expect when she left the hospital. For months after her visit, she had an extreme sensitivity to loud noises that made her “almost violently irritable,” she told me, and she couldn’t run downhill without feeling a painful shaking sensation in her brain. “I wasn’t given any information about what my recovery might look like,” she says. 

Fraser’s experience isn’t unique. Most people who crack their helmet in a bike accident or ding their head while climbing want to know the severity of their injury and what to expect during recovery. Currently, answers to those questions can be frustratingly imprecise. But that could change as researchers turn to biomarkers—substances found in the blood that can alert doctors to what’s happening in the body—to improve diagnosis and learn more about how the body recovers. 

The number of serious head and neck injuries in extreme sports is on the rise, yet doctors are still working on ways to measure and quantify what happens in the brain when someone sustains a concussion. There’s no bloodwork and no imaging tests available—doctors make a diagnosis based on patient history and clinical evaluation, looking for signs of concussion such as dizziness and headaches. But many of these symptoms can be caused by other factors, according to Breton Asken, a neuropsychology fellow at the University of California at San Francisco. And while an MRI or CT scan can reveal life-­threatening swelling or bleeding in the brain, a scan that appears normal doesn’t mean you don’t have a concussion, says Linda Papa, an emergency physician at Orlando Regional Medical Center and a concussion researcher. What’s more, CT scans are expensive and expose patients to a hefty dose of radiation. MRIs, while more detailed, are even costlier, and it can take a while to get results. 

This is why researchers are turning to biomarkers, hoping to find a better way to assess the severity of head injuries. With simple blood analysis, doctors may be able to make a clear diagnosis and identify patients who can be spared a CT scan or an MRI. In 2018, the FDA approved a new blood test that could help with the latter, although it’s not yet widely available. The test looks for two brain proteins that can indicate damage to brain tissues: ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP). In a study published in 2019, Papa and her colleagues measured UCH-L1 and GFAP levels in more than 700 trauma patients. They found that patients with no head trauma had the lowest levels of these biomarkers; those who’d hit their heads but weren’t diagnosed with concussion had higher levels, and those who’d sustained concussions had the highest of all. Of the two proteins, GFAP was the most useful for distinguishing among the three groups. UHC-L1 also rose with orthopedic wounds, suggesting that it isn’t specific enough to isolate head trauma.

While these are promising findings, researchers caution that concussion injuries­— and the damage they can cause to the brain—are so varied and complex that multiple markers are necessary to provide an accurate diagnosis and track patient recovery. In January, Michael McCrea, a neuropsychologist at the Medical College of Wisconsin, and his colleagues published a study in JAMA Network Open looking at GFAP, UCH-L1, and other biomarkers specifically in relation to sports concussions. The team compared blood samples from more than 250 concussed college athletes with samples from non-concussed athletes in contact sports, and with a control group of athletes who didn’t play contact sports or have concussions. Similar to previous studies, they found that athletes with concussions had elevated levels of GFAP one or two days after injury, and in some cases longer than that. Levels of UCH-L1 also went up in athletes who had concussions.

Biomarkers like GFAP may also help doctors identify previously undetected injuries. Some knocks to the brain don’t produce noticeable symptoms but cause damage to neurons and tissue that can diminish brain function, especially if someone experiences multiple head injuries. A test that recognizes subconcussive injuries—those that don’t produce symptoms—would be game-­changing, says Adnan Hirad, an M.D. and a Ph.D. candidate at the University of Rochester who studies brain injuries in football players. In the NFL, for example, trainers could make sure that players who need more recovery time after a hit don’t return to the game until they’ve healed. 

Another challenge for doctors, says Amaal Starling, a neurologist at the Mayo Clinic, is to separate concussion sufferers likely to make a complete recovery after a little rest (the vast majority) from those who will need extra time and treatment. On that front, researchers are looking at two additional biomarkers, IL-6 and IL-1RA, that show promise in identifying injuries that may require a longer recovery period. A blood test for these could prevent athletes from returning to risky sports too soon and receiving another blow to the head. Studies have also shown that after a concussion, risk of musculoskeletal injuries rises twofold, perhaps due to small remaining deficits in the nervous system, according to Thomas Buckley, a concussion researcher at the University of Delaware. If these deficits impair balance or delay reaction times, the result could be a sprained ankle or torn ACL. And while people with head injuries might worry about chronic traumatic encephalopathy—the neurodegenerative disease making headlines in connection with former NFL players—the science seems pretty clear that CTE results from repeated hits, not a single event, Hirad says.

Researchers caution that studies on biomarkers are new and inconclusive. A simple blood test to detect concussion or identify athletes who need extra recovery time is years away, if it ever arrives. In the meantime, if you receive a head injury, your best bet is to use extreme caution and see a doctor. And before jumping back into your sport, listen to your body. Like Kari Fraser, it will likely tell you if you need more rest.

Get Smart

A knock on the noggin doesn’t always lead to a concussion. Here’s a rundown of important facts related to head injuries. 


Sometimes called a mild traumatic brain injury. A diagnosis considers the patient’s medical history and whether they show symptoms like headaches, dizziness, and slowed reaction times. 

Traumatic Brain Injury (Moderate or Severe)

The seriousness of a TBI is determined by one or more diagnostic tests. If a person is unconscious or mentally out of it for 30 minutes to 24 hours, it’s a moderate case. More than 24 hours indicates a severe injury. 

Skull Fracture

A crack in your cranium that may or may not break the skin. Look for clear discharge from the nose or ears, bruises around the eyes or behind the ears, and blood in the eardrums. If the fracture injured the brain, symptoms such as seizures, vomiting, and confusion may develop. 


Neurodegenerative disease associated with memory loss, mood disorders like depression, and cognitive decline. A definitive diagnosis can be made only by examining the brain post-mortem. 

Epidural Hematoma

When blood pools between the brain and the skull. Symptoms may appear soon after the injury and include headaches,vomiting, and seizures.

Outside Magazine: Health

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