Biomarkers that support concussion diagnosis found

Researchers have identified variations in levels of certain proteins in the blood after sustained head trauma, which could be measured to confirm concussions.

This could improve the diagnosis of mild traumatic brain injuries (mTBI or concussion) in emergency departments, according to researchers from Monash University and Alfred Health in Melbourne.

In a study of 74 participants aged 18-50 with observed or reported head strikes and a hospital-standard diagnosis of mTBI, and a control group without injury, the research team observed levels of interleukin-6 – a cytokine protein that regulates inflammatory and immune processes in the body – had “profound” elevation in subjects within 6 hours of sustaining mTBI.

But IL-6 is not specific to the brain or central nervous system, so other region-specific proteins – GFAP, UCH-L1 and NfL – were also analysed.

These had varying elevations in the injury group compared to the control group. GFAP had “good accuracy” in distinguishing mTBI blood samples, while UCH-L1 was deemed “moderate/acceptable”.  While NfL was unsuitable for distinguishing mTBI within six hours of injury, it improved as a marker after a week.

“The performance of GFAP was pretty close to that of IL-6,” says the study’s lead researcher Dr Stuart McDonald, who is principal investigator of Monash’s Trauma Group.

“What we’re thinking is that by combining the two, you might be picking up some who don’t have GFAP changes, but might have an inflammatory response, potentially likely coming from the brain.

“So you’re essentially having a bit more accuracy by covering different aspects of the pathophysiology.”

In essence, these biomarkers should be considered in concert with one another. Doing so could provide a good mechanism to determine whether a person has sustained mTBI.

It doesn’t preclude the use of NfL though. Short for ‘neurofilament light’, this protein is released by neurons and present in brain fluid. McDonald says the slow release of NfL post-injury could provide a target biomarker for review in the event of delayed presentation to a clinic.

“We did follow up these participants at one week with the rationale being that we knew from our previous work that neurofilament light levels take a while to go up and they tend to peak in the weeks following injury,” McDonald says.

“By following these same people we could then compare how neurofilament light performed as a diagnostic at 7 days, to those same people when they had that acute blood sample [one taken shortly after injury].

“The point of that was if people present in a delayed manner – and it might not be to an ED, it might be to a GP – can you still get an ‘as good’ diagnostic information from neurofilament light levels?

“We think that’s where neurofilament light as a biomarker might really come in – outside that acute window.”

Applications proposed in hospitals, sport

Victims of falls, sports injuries and motor vehicle accidents were among those evaluated. The research group suggests their blood biomarker test could enable hospitals to provide a timely concussion evaluation upon presentation to emergency.

It’s unlikely a blood biomarker test like this would have much relevance to demands for more immediate evaluations, such as in sporting events, but McDonald believes there might be an opportunity for bloodwork to form part of ongoing monitoring and management of mTBI in athletes.

He’s hoping to trial the findings within an elite sport setting. Study contributors Dr Jonathan Reyes and Associate Professor Catherine Willmott both hold positions at the Australian Football League.

“We’re having discussions,” McDonald says. “They’re very aware of potential conflict of interest and so there’s a scientific committee they [the AFL] use and hopefully this evidence and other work we’re doing can mean we can further those conversations, and we’ll wait and see how it evolves.”

Elite and community-level sport settings have driven much public discussion around head impacts and trauma throughout 2023, but McDonald is quick to emphasise the merits of biomarker testing for mTBI in other scenarios.

As well as trauma sustained by falls and motor vehicle accidents, he raises the value of testing for domestic violence as another important application for blood samples.

“More and more numbers are coming out showing how common brain injury is in intimate partner violence and how common intimate partner violence is,” McDonald says. “We think these markers might be potentially even more useful as a diagnostic in that setting when you don’t necessarily have a patient that is willing to communicate the symptoms.”

In Australia, if you or someone you know requires confidential information, counselling or support related to domestic, family or sexual violence, call 1800RESPECT (1800 737 732). If you are in danger, call 000.

Please login to favourite this article.