Purpose Up to one-third of children with concussion develop persistent post-concussion symptoms (PPCS), which can give rise to subsequent problems for years post-injury. This pilot study aimed to (1) monitor gene expression of a panel of salivary miRNAs over time post-concussion and (2) identify biomarkers that differentiate concussed children who develop PPCS from those who do not.

Methods Saliva samples were collected from concussed children ages 11–17 at ≤1 week, 2-weeks, and 4-weeks post-injury. Post-concussion symptoms were also monitored daily throughout enrollment. PPCS was defined as a symptom score of 5 or higher than pre-injury level beyond 28 days post-injury. Changes in salivary miRNA expression over time post-injury were analyzed using the NanoString nCounter® human v3 miRNA panel to compare children with and without PPCS.

Results Of the 23 children studied (64 saliva samples provided), the average age was 14.4 years, 52.2% were male, and 34.7% (n=8) experienced PPCS. Of the 798 different human miRNAs analyzed, 46 (5.8%) had gene expression levels above threshold in at least 75% of the saliva samples analyzed. Six miRNAs that were differentially expressed in the PPCS group were significantly under expressed within one week of injury (p<0.05). Compared to children without PPCS, children with PPCS showed significant changes in 18 miRNA expression levels from within one week to 2-weeks post-injury (17 increased, p<0.05; 1 decreased, p<0.01). Significant changes were also observed in 21 miRNA expression levels from 2-weeks to 4-weeks post-injury (19 miRNAs decreased, p<0.05; 2 miRNAs increased, p<0.05).

Conclusion Additional studies are needed to verify our findings and to examine the biological regulatory or inflammatory mechanisms of the differently expressed miRNAs.

Significance The identification of clinically-relevant biomarker miRNAs could inform the development of individually-tailored treatment plans for children at risk for PPCS.