Identifying patients who will likely develop prolonged concussion symptoms could lead to new clinical laboratory tests and personalized medicine treatments

Researchers are homing in on a new diagnostic assay for concussion that could potentially generate significant numbers of test referrals to the nation’s clinical laboratories. This innovative work is targeting how concussions are diagnosed and treated.

Each year, thousands of children receive sports-related injuries, including concussions. There are ways for anatomic pathologists and hospital medical laboratories to diagnose concussions; however, testing can be invasive and doesn’t always reveal a complete picture of the injury state.

Additionally, about one third of children with concussions develop prolonged symptoms. However, when prescribing treatment plans, physicians have been unable to predict which patients are likely to recover quickly versus those who will have a longer recovery.

Now, researchers at Penn State College of Medicine (Penn State) believe they have discovered five microRNAs in saliva that could be used to identify patients who will likely experience prolonged concussion symptoms even one month after the initial injury.

The study also found that certain materials in saliva can help diagnose the severity of concussions and could hold the key to more effective clinical laboratory tests and personalized medicine treatments.

The Penn State researchers published their study results in JAMA Pediatrics, a publication of the Journal of the American Medical Association (JAMA).

Concussion Leading Sports-related Brain Injury

There are approximately 3.8 million sports and recreation-related traumatic brain injuries in the United States each year and the majority of those cases are concussions, according to The Concussion Place. Most concussions treated in emergency rooms are due to falls, motor-vehicle related injuries, being struck by an object, assaults, or playing sports.

Also known as mild traumatic brain injuries (mTBI), concussions are caused by blows or jolts to the head or body that cause the brain to move with excessive force inside the skull. The sudden impact damages brain cells and causes chemical changes within the brain that alter normal functioning. Though usually not life threatening, the damage can be serious and linger for months.

Symptoms of concussion include: headaches, fatigue, nausea, vomiting, dizziness, balance problems, confusion, memory problems, sleep disturbances, and double or blurry vision. Symptoms usually occur immediately, but could take days or even weeks to appear.

Identifying Severity/Predicting Prolonged Symptoms of Traumatic Brain Injuries

After a concussion occurs, brain cells release small fragments of genetic material known as microRNAs while they attempt to repair themselves. A portion of these microRNAs appear in the injured person’s blood and saliva.

In order to determine whether these microRNAs could be used to determine the severity of a traumatic brain injury and predict whether prolonged symptoms would occur, the prospective cohort study researchers gathered saliva samples from 52 concussion patients between the ages of seven and 21:

  • The average age of the subjects was 14;
  • Twenty-two of the participants were female;
  • They were all athletes; and,
  • The majority of the samples were collected one to two weeks after the initial injury.

The researchers examined distinct microRNAs in the samples and identified some that enabled them to predict how long a patient’s concussion symptoms might last. In addition, they found one microRNA in children and young adults that accurately predicted which subjects would experience memory and problem-solving difficulties as part of their symptomatology.

The researchers also evaluated the concussion patients using the Sport Concussion Assessment Tool (SCAT-3), Third Edition. Physicians use this questionnaire to assess the symptoms and severity of concussions. The researchers also asked the parents of the concussed patients for observations about their children’s symptoms.

During follow up visits, which occurred at four- and eight-week increments following the original assessment, the Penn State researchers collected additional saliva samples and re-evaluated the patients using SCAT-3.

New Biomarkers Based on MicroRNAs Instead of Protein

“There’s been a big push recently to find more objective markers that a concussion has occurred, instead of relying simply on patient surveys,” Steven Hicks, MD, PhD, Assistant Professor of Pediatrics, Penn State College of Medicine, Hershey, Pa., one of the study researchers, told Penn State News.

“Previous research has focused on proteins, but this approach is limited because proteins have a hard time crossing the blood-brain barrier. What’s novel about this study is we looked at microRNAs instead of proteins, and we decided to look in saliva rather than blood,” he noted.

According to Steven Hicks, MD, PhD (above), who worked on the Penn State College of Medicine study, microRNAs could be more accurate than the traditional questionnaire when diagnosing and forecasting the effects of concussions. “The microRNAs were able to predict whether symptoms would last beyond four weeks with about 85% accuracy,” he told Penn State News. “In comparison, using the SCAT-3 report of symptoms alone is about 64% accurate. If you just go off the parent’s report of symptoms, it goes down to the mid-50s. In this pilot study, these molecular signatures are outperforming survey tools.” (Photo copyright: MD Magazine.)

The goal of this research was to develop a way to definitively ascertain that a concussion had occurred, predict the length and type of symptoms, and then use that data to improve and personalize care for children and young adults who have had a concussion.

“With that knowledge physicians could make more informed decisions about how long to hold a child out of sports, whether starting more aggressive medication regimens might be warranted, or whether involving a concussion specialist might be appropriate,” Hicks told MD Magazine. “Anytime we can use accurate, objective measures to guide medical care, I think that represents an opportunity to improve concussion treatment.”

Further research and clinical trials will be needed to solidify the effectiveness and accuracy of these new biomarkers. However, a rapid, non-invasive saliva test that can determine the severity of a concussion, and predicted whether prolonged symptoms will likely occur, would be widely used and could be an important assay for clinical laboratories. Particularly those associated with hospital medical laboratories and emergency rooms.

—JP Schlingman

Related Information:

Association of Salivary MicroRNA Changes with Prolonged Concussion Symptoms

Saliva Test May Detect Biomarker for Prolonged Concussion

Molecules in Spit May be Able to Diagnose and Predict Length of Concussions

Prolonged Concussion Symptoms Identifiable by Salivary MicroRNA

Spit Test May Help Reveal Concussion Severity

Saliva Test May Lead to Improved Concussion Care for Youths