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Researchers say biomarker found in saliva can identify concussion, predict length of recovery

Upstate Medical University News May 13, 2017

Researchers at SUNY Upstate Medical University and Penn State University have identified a novel and accurate biomarker that both identifies concussion in children, and predicts the length of recovery. The results of this groundbreaking research, sponsored by Quadrant Biosciences Inc. (formerly Motion Intelligence Inc.), were presented at the Pediatric Academic Societies 2017 Meeting. The study also showed compelling data that this unique biomarker may be a better predictor of symptom duration than current standard concussion assessments.

Steven Hicks, MD, PhD, FAAP, assistant professor in pediatrics at Penn State Hershey Medical Center, lead author of the study, and collaborator Frank Middleton, PhD, associate professor of neuroscience and physiology/biochemistry and molecular biology at SUNY Upstate Medical University, focused their attention on small non–coding nucleic acid molecules in the body called microRNA.

Over the past 10 years, researchers have learned that these microRNA’s can have an effect on gene expression. Moreover, microRNA’s have been found in relative abundance in the saliva which, when coupled with their unique epigenetic properties, make them attractive biomarker candidates.

“Given the robust, stable expression of microRNA in saliva and its ease of collection in pediatric patients,” Hicks said, “we sought to explore the utility of salivary microRNA as a diagnostic tool in children and adolescents with traumatic brain injury.” The research, supported by Quadrant Biosciences, examined whether circulating levels of these microRNAs could be used to detect the presence of traumatic brain injury. Their inquiry proved very fruitful.

Middleton explained the findings. “We identified microRNA changes that occur in cerebrospinal fluid following severe head injury and then investigated whether those same microRNAs were changed in saliva of 60 children with mild head injury.

Six microRNAs had parallel changes in CSF and saliva and could accurately separate concussion and control cases. One of these microRNAs targeted genes involved in neuron formation and was correlated with parental and child reports of attention difficulty following concussion.

“This study shows that the microRNAs found in saliva may be used to accurately identify mild concussion in children,” Hicks added. “Because these microRNAs may drive some of the symptoms associated with concussion, such as difficulties with concentration and memory, they have exciting diagnosis and therapeutic potential.”

And that was just half of the story. Follow up research presented at the Pediatric Academic Societies meeting this week showed that not only are these microRNA highly predictive of concussion and correlated with symptoms, but appear to be an accurate predictor of the length of recovery. Researchers studied 52 children between the ages of 7 and 21 years with mild traumatic brain injury, collecting microRNA as well as evaluating them with the Sports Concussion Assessment Tool (SCAT–3) parent and child surveys, one of the well–accepted concussion assessment tools. SCAT–3 results showed that the 30 children with prolonged concussion symptoms had higher scores for headaches, fatigue and difficulties concentrating.

“One of the other exciting things to come out of this research is that the microRNAs in saliva correctly predicted whether concussion symptoms would remain present for at least a month nearly 90 percent of the time,” said Hicks. “Moreover, we found that salivary microRNA levels were significantly more effective than evaluations using the SCAT–3 survey in predicting which children would continue to experience headaches, fatigue, concentration difficulties and other concussion symptoms that lasted longer than 4 weeks.”
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