Helping Identify Biomarker for Concussions in Saliva

The study was led by Steven Hicks, MD, PhD, of Penn State College of Medicine with researchers from the Jacobs School of Medicine and Biomedical Sciences and peers from other institutions.

John J. Leddy, MD, clinical professor of orthopaedics and director of the UB Concussion Management Clinic at UBMD Orthopaedics & Sports Medicine, and Mohammad Nadir Haider, MD, assistant director at the clinic, were co-authors.

The traditional method of diagnosing mild traumatic brain injury (mTBI) involves measuring physical and cognitive changes, along with symptom reports from patients. The latter is problematic because patients can purposely misrepresent their symptoms in order to speed up or slow down their return to activities.   

A saliva swab, on the other hand, is a non-invasive, specific, objective and easy-to-use biological assessment tool.

“Concussions can be difficult to diagnose due to lack of objective, diagnostic testing. The diagnosis often relies on a patient’s self-reported symptoms, which are not specific to concussion,” Haider says. “This saliva test is a significant development because it can improve diagnostic accuracy, which could potentially improve clinical management.”

Mild traumatic brain injuries are characterized by a brief alteration in mental status, post-traumatic amnesia, and often vestibular and vision abnormalities. 

Nearly 3 million of these injuries occur in the United States each year, mostly in teens and young adults. The occurrence of mTBI in adolescents is on the rise, resulting in an increased burden on the nation’s economic and health care systems.

The study took place between April 2017 and February 2020. It included 538 participants between 5 and 66 years of age. Of this sample, 251 had a clinical diagnosis of mTBI as defined by the 2016 Concussion in Sport Group criteria. 

The mTBI group was compared to a control group of 287 individuals with absence of mTBI in the previous 12 weeks and clinical resolution of any previous mTBI.

Following enrollment, saliva and survey data were collected from mTBI participants across five time points: at 72 hours, four to seven days, eight to 14 days, 15 to 30 days and 31 to 60 days after the initial injury. 

The saliva samples were collected at various institutions and sent for analysis to Quadrant Biosciences in Syracuse.

The researchers found that the combination of saliva biomarkers and patient-reported symptoms proved to be 92.5 percent accurate in differentiating patients with and without a concussion.

According to Haider, the group of researchers found a combination of micro RNA biomarkers in saliva that could be used to distinguish between people with mTBI/concussion and non-mTBI controls who presented with concussion-like symptoms.

“This test was compared with disorders that present with symptoms that are similar to concussion, like mood disorders, non-head-related trauma and learning disorders, and was still able to differentiate between them,” he says. “This means the test is specific as well as sensitive, making it superior to subjective symptom reports alone.”

Haider notes the results will be validated in a larger population.

Quadrant Biosciences has received a $2.3 million grant from the National Institutes of Health to develop a saliva-based microRNA diagnostic test. Quadrant will work with researchers from UB, SUNY Upstate, Arkansas Children’s Hospital in Little Rock, Children’s Hospital of Michigan in Detroit and Penn State College of Medicine.

The research will be conducted in a study of 2,500 adolescents and young adults with either a formal diagnosis of an mTBI or an overlapping medical condition.

“We are confident that an objective, rapid screen for concussion will be an important addition to concussion management protocols in the future, and we think that salivary micro RNAs have potential because they are non-invasive and relatively easy to use,” Haider says.

The prospective multicenter, case‐control study is titled “Diagnosing Mild Traumatic Brain Injury Using Saliva RNA Compared to Cognitive and Balance Testing.” It was published online in Clinical and Translational Medicine on October 4.

The other participating institutions include:

• Adena Health System
• Bridgewater College
• Colgate University
• United States Army Fort Benning
• Marist College
• Penn State College of Medicine
• New York Institute of Technology
• SUNY Upstate Medical University
• Temple University
• Vanderbilt University Medical Center