In the study, researchers from Penn State University College of Medicine in Hershey, Pennsylvania, compared saliva samples from 251 people with a mild traumatic brain injury (aka a concussion) with those from 287 control subjects without head injuries. They found that differences in specific microRNA levels distinguished those with concussions from those without. In some cases, participants were assessed with computerized neurocognitive testing, balance measures, and standardized symptom scales, and the saliva tests displayed similar accuracy in identifying concussions as a combination of the traditional approaches. “Even though saliva RNA accuracy is comparable to traditional approaches, it might have added utility when there is suspicion an athlete is minimizing symptoms after their head injury to expedite return to play, when an athlete may have purposely underperformed a baseline balance/neurocognitive test to avoid being held out after a suspected concussion, or in busy emergency department or outpatient settings where doctors don’t have 30 minutes to administer balance/neurocognitive tests,” explains Steven Hicks, MD, PhD, an associate professor of pediatrics at Penn State College of Medicine. “Patients can’t alter their saliva RNA content, and it takes only seconds for a physician to collect a saliva sample.”
What Saliva Reveals
Why can testing saliva detect concussions? Throughout the body, “cells use microRNAs to communicate with each other — this includes [cells in the] nerves in the mouth that connect directly with your brain stem and control things like chewing, speaking, and sensation,” explains Dr. Hicks. “We believe that the microRNA signals from these nerves are disrupted after a concussion — some go up and some go down — and measuring the levels of various microRNAs gives us insight into the severity of the injury.” Though he was not involved in the study, Andrew Gregory, MD, an associate professor of orthopedics, pediatrics, and neurosurgery at Vanderbilt University Medical Center in Nashville, Tennessee, sees the value in this approach. “It is an objective measure,” he explains. “MicroRNA can be measured in various body fluids, but saliva is easiest to access.”
A New Addition to the Diagnostic Arsenal
This is a potential game changer since the usual methods for diagnosing a concussion are so subjective. They typically depend on the symptoms reported by the patient and a neurocognitive examination of the patient’s reflexes, strength, vision, balance, memory, and cognitive functioning. Hicks hopes that the saliva test, rather than being a stand-alone tool for concussion diagnosis, will become “an additional tool available to clinicians that allows them to detect concussion with greater accuracy.” This is especially important because symptoms of concussions can vary widely, ranging from headache, blurry vision, confusion, and difficulty concentrating to nausea, dizziness, and sensitivity to noise or light. Some people are forthcoming about their symptoms while others may be less so. Indeed, sometimes people “minimize their symptoms to expedite returning to activities,” Hicks says. “Even semi-objective tools like balance or reaction time testing can be tricked by patients who purposely sandbag their baseline test.” Following a head trauma, “analyzing microRNA profiles in saliva is a noninvasive way to test for concussion that can’t be influenced by a patient’s feelings or motives,” he adds.
Pluses and Minuses of the Spit Test
Even though saliva RNA can be rapidly collected and objectively measured, the saliva test isn’t 100 percent accurate in detecting concussions. “When used by itself, the RNA test was 85.7 percent accurate; when used together with a validated symptom survey, the RNA test was 93.2 percent accurate,” Hicks notes. (By contrast, diagnosing concussions by surveying symptoms and performing neurocognitive testing is 88.8 accurate, Hicks notes.) “I think it could be potentially useful for diagnosis in cases with minimal or unclear symptoms or with an athlete suspected to be lying,” Dr. Gregory says. It could also be useful in making decisions about whether it’s safe for someone to return to playing a sport after suffering a concussion. Before the saliva RNA test can be brought into widespread use, however, larger studies need to be conducted to confirm its efficacy. That said, a handheld tool is already being developed to measure microRNA samples from saliva in less than 30 minutes, Hicks says. “We are hopeful this technology could be clinically available within three years.”
