Saliva RNA biomarkers predict concussion duration and detect symptom recovery: a comparison with balance and cognitive testing

Abstract

Objective The goals of this study were to assess the ability of salivary non-coding RNA (ncRNA) levels to predict post-concussion symptoms lasting ≥ 21 days, and to examine the ability of ncRNAs to identify recovery compared to cognition and balance. Methods RNA sequencing was performed on 505 saliva samples obtained longitudinally from 112 individuals (8–24-years-old) with mild traumatic brain injury (mTBI). Initial samples were obtained ≤ 14 days post-injury, and follow-up samples were obtained ≥ 21 days post-injury. Computerized balance and cognitive test performance were assessed at initial and follow-up time-points. Machine learning was used to define: (1) a model employing initial ncRNA levels to predict persistent post-concussion symptoms (PPCS) ≥ 21 days post-injury; and (2) a model employing follow-up ncRNA levels to identify symptom recovery. Performance of the models was compared against a validated clinical prediction rule, and balance/cognitive test performance, respectively. Results An algorithm using age and 16 ncRNAs predicted PPCS with greater accuracy than the validated clinical tool and demonstrated additive combined utility (area under the curve (AUC) 0.86; 95% CI 0.84–0.88). Initial balance and cognitive test performance did not differ between PPCS and non-PPCS groups (p > 0.05). Follow-up balance and cognitive test performance identified symptom recovery with similar accuracy to a model using 11 ncRNAs and age. A combined model (ncRNAs, balance, cognition) most accurately identified recovery (AUC 0.86; 95% CI 0.83–0.89). Conclusions ncRNA biomarkers show promise for tracking recovery from mTBI, and for predicting who will have prolonged symptoms. They could provide accurate expectations for recovery, stratify need for intervention, and guide safe return-to-activities.

Clues for Improving the Pathophysiology Knowledge for Endometriosis Using Plasma Micro-RNA Expression

“…Another crucial issue is to evaluate whether results of NGS require qRT-PCR validation. Previous studies have shown that absolute NGS reads correlated modestly with qRT-PCR but fold changes, as used in the current study, correlated highly supporting that NGS is robust at relative but not absolute quantification of miRNA [ 85 , 86 , 87 , 88 ]. Moreover, as previously demonstrated, the number of microRNAs detected in biofluids by NGS and qRT-PCR was similar after filtering the data and applying thresholds supporting our results.…”

Safeguarding Athletes Against Head Injuries Through Advances in Technology: A Scoping Review of the Uses of Machine Learning in the Management of Sports-Related Concussion

“…The studies in this management phase of SRC are diverse in terms of methodological approach, sample and aim. Three of the 10 studies focus on the role of biomarkers in the prediction of SRC (Helfer et al, 2014 ; Seeger et al, 2020 ; Fedorchak et al, 2021 ). For instance, Seeger et al ( 2020 ) studied youth ice hockey participants (aged 12–17 years) to explore cytokine alterations following pediatric SRC.…”

Salivary miRNA Expression in Children With Persistent Post-concussive Symptoms

“…Prior studies show that miRNAs may control cellular processes essential to neuronal injury and repair in both the primary and secondary pathophysiology involved in TBI ( 21 – 24 ). Furthermore, studies have demonstrated the feasibility of identifying changes in miRNA expression associated with brain injury in biofluids, including blood and saliva ( 19 – 21 , 25 , 26 ).…”

“…Recent investigations, though mostly focused on adult patients, have shown the utility of salivary miRNA expression levels as diagnostic or prognostic biomarkers for TBI ( 17 – 19 , 21 , 27 ). In a study that included patients aged 7–21 years, Johnson et al demonstrated overexpression of five human salivary miRNAs associated with PPCS at four weeks post-injury ( 18 ).…”

“…In a study that included patients aged 7–21 years, Johnson et al demonstrated overexpression of five human salivary miRNAs associated with PPCS at four weeks post-injury ( 18 ). Fedorchak et al found an algorithm of 16 non-coding RNAs, obtained within 14 days of injury among patients aged 8–24 years, predicted concussion symptoms that lasted more than 21 days with greater accuracy than computerized balance and cognitive test performance ( 19 ). Of note, both studies included patients over the age of 18.…”