Blood-Based CNS-Injury and Inflammation Biomarkers Sampled at Acute, Subacute, and Chronic phases After Mild TBI Demonstrate Diagnostic Utility For Patients With and Without Intracranial Injuries on Acute CT and MRI

Abstract

Background Identifying individuals with intracranial injuries following mild traumatic brain injury (mTBI), i.e. complicated mTBI cases, is important for follow-up and prognostication. The aim of the current study was to identify the ability of single and multi-panel blood biomarkers of CNS injury and inflammation, from the acute to chronic phase after injury, to classify people with complicated mTBI on computer tomography (CT) and/or magnetic resonance imaging (MRI) acquired within 72 hours. Methods Patients with mTBI (n = 207, 16–60 years), i.e., Glasgow Coma Scale (GCS) score between 13 and 15, loss of consciousness (LOC) < 30 min and post-traumatic amnesia (PTA) < 24 hours, were included. Complicated mTBI was present in 8% (n = 16) based on CT (CT+) and 12% (n = 25) based on MRI (MRI+). Blood biomarkers were sampled at four timepoints following injury: admission (within 72 hours), 2 weeks (± 3 days), 3 months (± 2 weeks) and 12 months (± 1 month). CNS biomarkers included were GFAP, NFL and tau, along with a panel of 12 inflammation markers. Predictive models were generated with both single and multi-panel biomarkers and assessed using area under the curve analyses (AUCs). Results The most discriminative single biomarkers were GFAP at admission (CT+: AUC = 0.78; MRI+: AUC = 0.82) and NFL at 2 weeks (CT+: AUC = 0.81; MRI+: AUC = 0.89) and 3 months (MRI+: AUC = 0.86). MIP-1β and IP-10 concentrations were significantly lower at almost all timepoints in patients who were CT + and MRI+. Eotaxin and IL-9 were significantly lower in patients who were MRI + only. FGF-basic concentrations increased over time in patients who were MRI- and were significantly higher than patients MRI + at 3- and 12 months. Multi-biomarker panels improved discriminability at all timepoints (AUCs ≈ 0.90 of admission and 2-week models for CT + and AUC > 0.90 of admission, 2-week and 3-month models for MRI+). Conclusions The CNS biomarkers GFAP and NFL were useful diagnostic biomarkers of complicated mTBI in acute, subacute and chronic phases after mTBI. Several inflammation markers were significantly lower in patients with complicated mTBI, at all timepoints, and could discriminate between CT + and MRI + even after 12 months. Multi-biomarker panels improved diagnostic accuracy at all timepoints.