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Original Investigation
January 2018

Association of Salivary MicroRNA Changes With Prolonged Concussion Symptoms

Author Affiliations
  • 1Department of Pediatrics, Penn State College of Medicine, Pennsylvania State University, Hershey
  • 2Department of Emergency Medicine, Penn State College of Medicine, Pennsylvania State University, Hershey
JAMA Pediatr. 2018;172(1):65-73. doi:10.1001/jamapediatrics.2017.3884
Key Points

Question  Can salivary microRNA levels be used to identify prolonged concussion symptoms in children?

Findings  In this prospective cohort study of 52 children with mild traumatic brain injury, concentrations of 5 salivary microRNAs identified prolonged concussion symptoms with 85% accuracy and outperformed standard survey measures of symptom burden.

Meaning  Salivary microRNA levels may represent an accurate, objective, and easily collected measure of prolonged concussion symptom risk.


Importance  Approximately one-third of children who experience a concussion develop prolonged concussion symptoms. To our knowledge, there are currently no objective or easily administered tests for predicting prolonged concussion symptoms. Several studies have identified alterations in epigenetic molecules known as microRNAs (miRNAs) following traumatic brain injury. No studies have examined whether miRNA expression can detect prolonged concussion symptoms.

Objective  To evaluate the efficacy of salivary miRNAs for identifying children with concussion who are at risk for prolonged symptoms.

Design, Setting, and Participants  This prospective cohort study at the Penn State Medical Center observed 52 patients aged 7 to 21 years presenting for evaluation of concussion within 14 days of initial head injury, with follow-up at 4 and 8 weeks.

Exposures  All patients had a clinical diagnosis of concussion.

Main Outcomes and Measures  Salivary miRNA expression was measured at the time of initial clinical presentation in all patients. Patients with a Sport Concussion Assessment Tool (SCAT3) symptom score of 5 or greater on self-report or parent report 4 weeks after injury were designated as having prolonged symptoms.

Results  Of the 52 included participants, 22 (42%) were female, and the mean (SD) age was 14 (3) years. Participants were split into the prolonged symptom group (n = 30) and acute symptom group (n = 22). Concentrations of 15 salivary miRNAs spatially differentiated prolonged and acute symptom groups on partial least squares discriminant analysis and demonstrated functional relationships with neuronal regulatory pathways. Levels of 5 miRNAs (miR-320c-1, miR-133a-5p, miR-769-5p, let-7a-3p, and miR-1307-3p) accurately identified patients with prolonged symptoms on logistic regression (area under the curve, 0.856; 95% CI, 0.822-0.890). This accuracy exceeded accuracy of symptom burden on child (area under the curve, 0.649; 95% CI, 0.388-0.887) or parent (area under the curve, 0.562; 95% CI, 0.219-0.734) SCAT3 score. Levels of 3 miRNAs were associated with specific symptoms 4 weeks after injury; miR-320c-1 was associated with memory difficulty (R, 0.55; false detection rate, 0.02), miR-629 was associated with headaches (R, 0.47; false detection rate, 0.04), and let-7b-5p was associated with fatigue (R, 0.45; false detection rate, 0.04).

Conclusions and Relevance  Salivary miRNA levels may identify the duration and character of concussion symptoms. This could reduce parental anxiety and improve care by providing a tool for concussion management. Further validation of this approach is needed.