Most of the time, a concussion comes with a headache that might last a few days. But sometimes the resulting headaches, dizziness, and sleep issues can last for months. Called prolonged concussion symptoms, doctors have been unable to predict who will continue to suffer from these and who will have typical symptoms.
Almost two thirds of all concussions happen in children, and of those children, nearly 30 percent end up with prolonged concussion symptoms. “I think most physicians would agree that we don’t necessarily need a fancy test to tell us that a child has had a concussion,” says Steve Hicks, a pediatrician at Penn State University. “What I am particularly interested in is being able to predict for families how long a child’s concussion could last.”
By predicting symptom durations, Hicks hopes children will receive better, more prompt treatment. Since doctors can’t yet predict which children will have prolonged symptoms, doctors have to send families home with the general recovery timeline of a few days to a week, Hicks says. When that recovery doesn’t happen, it causes significant anxiety for families on top of the potentially debilitating symptoms for the affected children.
In a study published in JAMA Pediatrics at the end of November, Hicks and his team looked at the spit from 52 children with concussions to examine microRNA, molecules that regulate protein creation. They found that there were differences in some of the microRNA found in normal concussion and prolonged concussion sufferers. And the amounts of five of the microRNAs were able to predict prolonged symptoms 85 percent of the time.
Quadrant Biosciences, a biotech company where Hicks is a shareholder, helped fund the study and hopes it’ll eventually lead to a saliva test for concussions that could be used on the side of the field. While the current study is too small to draw firm conclusions, Hicks says, the results are promising for future work.
“A larger study that validates these findings will hopefully lead to a medical test where you could collect spit and say that a child has or does not have a concussion — and then make some accurate predictions about the symptoms that that child might go on to have,” Hicks says.
To try and predict concussions, Hicks and his team sampled microRNA. These small molecules are transported throughout the body and regulate the production of proteins. Because they end up in almost all fluids, they can be easily measured in saliva, says Hicks.
Within fourteen days of getting a concussion, the children in the study (who were between 7 to 21 years old) spat into kits for RNA extraction and their symptoms were evaluated using the most current Sports Concussion Assessment Tool. Four weeks later, the patients were given the same survey again, but didn’t do another spit sample. If they were still experiencing severe symptoms, they were determined to be suffering prolonged concussion symptoms.
The concussion symptoms were then compared to around 437 different microRNA found in the spit samples. Five of the microRNA were correlated with symptoms like memory loss, headaches, or tiredness in children with prolonged concussion symptoms. Hicks found that the presence of the RNA was a better predictor of prolonged symptoms than the concussion assessment tools currently used.
“I think [microRNA biomarkers] hold a lot of promise. In terms of this particular paper, the number of children they saw was very small,” says Linda Papa, who researches concussions at Orlando Health. “The exciting part about it is that they were able to do it in saliva. I think that’s the most promising aspect.” In children, saliva is a lot easier to use than blood, says Papa, who uses proteins in blood as biomarkers to indicate traumatic brain injuries in her research.
“The field is still growing, and we know that there are some good acute measures,” says Papa. “I think microRNA certainly has promise for longer term outcome.” Determining which microRNA are significant and finding the ideal time to sample them are the next big steps, she says.
Hicks and his team have expanded to work with more medical centers and are already working on a larger study. Along with trying to get ten times the number of patients, he says their latest efforts include sampling saliva at different time points to see if there is a specific timescale where microRNA biomarkers are the most accurate.
In particular, he is driven to find something that helps children with prolonged symptoms in order to change the standard of care as soon as they’re injured. “If we could pinpoint those individuals right from the get go after their injury, we could do studies on treatment measurements that might help them,” he says. “But right now we can’t even do those studies because we don’t know who’s going to be the patient that has the prolonged symptoms.”
Even being able to tell a patient that their symptoms will last for longer than a typical mild concussion would be an improvement in care, says Papa. Based on the timeline of her research, she thinks that in ten years we could see this test on the market. More optimistically, Hicks is hoping for four years.
“I think the field will continue to grow very rapidly over the next ten years, and by then hopefully [we have] a panel of markers that could be used at different times after injury to determine how severe the patient is,” says Papa. “This has a lot of promise, but there is still a lot of work that we have to do.”