A biomarker combination that includes interleukin-6 (IL-6) together with the established markers glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) has shown excellent discriminatory ability in CT-negative patients with mild traumatic brain injury (mTBI).
The new study led by Monash University and The Alfred Emergency Department in Melbourne, Australia, and published in the journal Neurology, found that this combination of protein biomarkers showed sensitivity and specificity in distinguishing patients with mTBI who were under the age of 50 and presented to an emergency department within six hours of injury.
Study lead and Monash Trauma Group principal investigator Dr Stuart McDonald said: ‘Concussion diagnosis is notoriously challenging in many cases because clinicians rely on subjective observations of physical signs and self-reported symptoms, neither of which are specific to concussion and often exhibit subtlety and rapid evolution.
‘Consequently, even in the ED, individuals can be discharged without a definitive diagnosis. Our findings showed that the panel of biomarkers we assessed performed really well even in patients that lacked the more overt signs of concussion, such as loss of consciousness or post-traumatic amnesia.‘
In 2018, the US FDA approved a blood test using the Banyan Brain Trauma Indicator, which measures GFAP and UCH-L1 to help determine the need for a CT scan in suspected mTBI.
Researchers in the current study sought to determine if there was a better combination of biomarkers that could more accurately be linked to mTBI and thus help diagnose the condition in CT negative patients.
If approved, a blood test identifying these three biomarkers could improve the accuracy diagnostic process of mTBI when used alongside existing measures such as physical signs and symptom self-reporting.
Biomarker combination and mTBI
The researchers measured a number of biomarkers, including IL-6, GFAP and UCH-L1 within six hours of of injury. The values of each biomarker were then compared to those seen in uninjured controls.
The results showed that adding plasma IL-6 to the standard panel which includes only GFAP and UCH-L1 showed incredible sensitivity and specificity in distinguishing individuals with mTBI (n=74) compared to control (n=44) within six hours of injury.
The biomarker performance was similar between sexes and for participants with and without loss of consciousness and/or post traumatic amnesia.
Co-study lead and Monash University Professor Biswadev Mitra, who is director of emergency medicine research at The Alfred, said that ‘if further research validated these results‘ and the biomarkers were granted regulatory approval, ‘they could increase diagnosis certainty not just for clinicians but for patients too, enabling earlier management‘.
He added: ‘Within the ED, we believe the test might prove useful in providing certainty in difficult-to-assess cases, especially when a patient may be unwilling or unable to communicate their symptoms. One example could be in cases of domestic violence, where the test might reveal a mild brain injury that could otherwise go unnoticed.‘
In the same patients studied a week after their concussion, the researchers found the biomarker neurofilament light (NfL) was elevated and had comparable diagnostic properties as the acute markers (AUC=0.81, 95%CI=0.72-0.90).
Dr McDonald said this suggested NfL could be particularly suited for assisting concussion diagnosis in cases of delayed assessments.
‘Beyond the ED, measures of blood NfL may be most beneficial when individuals consult a GP multiple days after an impact, especially in situations where diagnostic certainty is crucial for making safe return-to-work or return-to-play decisions, such as in military or sports settings,‘ Dr McDonald added.