MicroRNA biomarkers for diagnosis of mild traumatic brain injury and prediction of persistent symptoms: A prospective cohort study

The diagnosis of mild traumatic brain injury (mTBI) and early identification of patients who have persistent symptoms remains challenging. Symptoms are variably reported, and tests for cognitive impairment require specific expertise. The aim of this study was to assess the ability of plasma micro-ribonucleic acid (miRNA) biomarkers to distinguish between patients with mTBI and healthy controls. A secondary aim was to assess whether miRNA biomarker levels on the day of injury could predict persistent symptoms on day 7. Injured patients presented to an adult, tertiary referral hospital emergency department and were diagnosed with isolated mTBI (n = 75). Venous blood samples were collected within 6 h of injury. Symptom severity was assessed using the Rivermead Post-Concussion Symptom Questionnaire (RPQ) on the day of injury and at 7 days post-injury. The comparator group (n = 44) were healthy controls without any injury, who had bloods sampled and symptom severity assessed at the same time-point. Patients after mTBI reported higher symptom severity and had worse cognitive performance than the control group. Plasma miR423-3p levels were significantly higher among mTBI patients acutely post-injury compared to healthy controls and provided moderate discriminative ability (AUROC 0.67; 95 %CI: 0.57-0.77). None of the assessed miRNA biomarkers predicted persistent symptoms at 7 days. Plasma miR423-3p levels measured within 6 h of injury can discriminate for mTBI compared to healthy controls, with potential utility for screening after head injury or as an adjunct to the diagnosis of mTBI. Acute plasma miRNA levels did not predict patients who reported persistent symptoms at 7 days.