Research published in JAMA Pediatrics reports that non-invasive salivary microRNA testing identifies prolonged concussion symptoms with 85% accuracy
Sports-related concussions are always tragic, but doubly so when they involve child athletes. Quick diagnoses and treatments are critical to prevent permanent brain injury. But doctors are often hampered by the pace at which traditional medical imaging modalities and clinical laboratory diagnostic technologies provide crucial feedback.
Now, researchers at Penn State Health Children’s Hospital have determined that microRNA in saliva could be used as biomarkers in point-of-care concussion testing during sports events, according to a Penn State Health news release. Such sideline saliva analyses could provide quick feedback to field doctors on whether a head injury is serious enough to put injured athletes out of play, and how long the effects of such injuries might last. But is it accurate?
Jeremiah J. Johnson, MA, BS, Department of Pediatrics, at Penn State College of Medicine in Hershey, Pa., et al, recently published a study in the Journal of the American Medical Association (JAMA) Pediatrics that evaluated the ability of salivary microRNA to identify concussion in children. The salivary test of microRNA levels, Johnson and colleagues argued, does accurately identify the “duration and character of concussion symptoms.” According to the researchers, the test demonstrated high prognostic potential as a “toolset for facilitating concussion management” and may provide an additional biomarker source for use in clinical laboratory testing.
MicroRNA Offers New Biomarkers for Concussion Diagnosis
The study tested the saliva of 52 adolescents with a clinical diagnosis of mild traumatic brain injury in the form of concussion for specific microRNA expressions. Researchers identified five microRNA molecules which “accurately identify” patients with concussion symptoms. Three of those molecules served to diagnose specific symptoms of headache, fatigue, and memory difficulties up to one month after injury with low false detection rates. Because these microRNA molecules are not specific to children, could the test maintain diagnostic accuracy for patients of all ages?
William P. Meehan III, MD, with the Micheli Center for Sports Injury Prevention at Boston General Hospital, and Rebekah Mannix, MD, MPH, with the Brain Injury Center at Boston Children’s Hospital wrote an editorial responding to the original research article stating that “the use of salivary microRNA in this study is both novel and clinically relevant.” Adding that “using this salivary microRNA panel to diagnose and manage concussions could be a major advancement to the field.”
Meehan and Mannix also remarked on the speed and relative ease of obtaining saliva samples, stating that “salivary microRNAs could also offer insights into the underlying biological mechanisms of injuries, potentially identifying specific targets to modify disease.”
More Accurate than Current Concussion Diagnosis Tools
There has been a marked interest in microRNA analysis and testing in recent years. MicroRNA analysis and testing has found use in cancer prognosis and personalized medicine that help predict responses to specific treatments for individual patients with a variety of chronic diseases. The news that microRNA can be used to predict concussion and duration of symptoms further solidifies the role microRNA may play in medical laboratory testing in the near future.
In an interview with CNN, Steve Hicks, MD, PhD, senior author of the JAMA Pediatrics research article and Assistant Professor of Pediatrics at Penn State College of Medicine, reported that the salivary microRNA test predicted concussion with 85% accuracy in comparison to current clinical survey measures, which are “approximately 65% accurate.” Hicks added that “the technology required to measure saliva RNA is already employed in medicine” as a common means of testing for upper respiratory viruses and that “modifying this approach for patients with concussions could potentially provide a rapid, objective tool for managing brain injury.”
Currently the Standard Concussion Assessment Tool, Third Edition (SCAT 3), which includes a series of cognitive and physical tests, is used on sports sidelines to detect concussion symptoms. Hicks notes that one problem with SCAT 3 is that “an athlete may have a concussion even if [his or her] score is ‘normal.’” Therefore, the microRNA saliva test could provide objective evidence of concussion in patients SCAT 3 fails to accurately diagnose.
Too Early to Know How Helpful the Test May Be?
In the same CNN interview, Neurologist Jeffery Kutcher, MD, head of the Sports Neurology Clinic at The Core Institute in Brighton, Mich., stated that the Penn State study’s findings were “promising” and that “work like this is important because it does provide potential for tests that can be helpful in the clinical setting.” Kutcher cautioned however, that it was “too early to know what this type of tool can do for us.”
In an NPR article, Manish Bhomia, M.Eng., PhD, a brain injury researcher with the Uniformed Services University of the Health Sciences commented that “a saliva test could greatly improve care for young people who don’t have obvious symptoms of a concussion.” Bhomia stated that “micro-RNAs offer a promising way to assess concussions in adults as well as children,” but he is wary to laud saliva tests as the best method of measuring relevant microRNA molecules. Bhomia states that blood samples “which tend to contain greater numbers of the genetic fragments” are perhaps a better option.
Hicks disagrees. In an article from Penn State News, Hicks stated that the novel aspect of this study was that it focused on microRNA levels “in saliva rather than blood.” Thus, a test based on saliva, rather than a phlebotomy stick or more invasive blood testing, requires no need for venous blood.
“The ultimate goal is to be able to objectively identify that a concussion has happened and then predict how long the symptoms will go on for,” Hicks noted in the Penn State News article. “Then, we can use that knowledge to improve the care that we provide for children who have concussions, either by starting medicine earlier or holding them out of activities for longer.”
Quadrant Biosciences, a biotech company in Syracuse, N.Y., that helped fund the study, is hoping to “bring a saliva test for concussion to market in the next 12 to 24 months,” according to Hicks in his CNN interview. If development proceeds as planned, the saliva test could prove a “game changer” for sports medicine diagnostics and possibly open new avenues for related microRNA in clinical laboratory testing.