Abstract
Mild traumatic brain injury (mTBI) patients may have trauma-induced brain lesions detectable using CT scans. However, most patients will be CT-negative. There is thus a need for an additional tool to detect patients at risk. Single blood biomarkers, such as S100B and GFAP, have been widely studied in mTBI patients, but to date, none seems to perform well enough. In many different diseases, combining several biomarkers into panels has become increasingly interesting for diagnoses and to enhance classification performance. The present study evaluated 13 proteins individually—H-FABP, MMP-1, MMP-3, MMP-9, VCAM, ICAM, SAA, CRP, GSTP, NKDA, PRDX1, DJ-1 and IL-10—for their capacity to differentiate between patients with and without a brain lesion according to CT results. The best performing proteins were then compared and combined with the S100B and GFAP proteins into a CT-scan triage panel. Patients diagnosed with mTBI, with a Glasgow Coma Scale score of 15 and one additional clinical symptom were enrolled at three different European sites. A blood sample was collected at hospital admission, and a CT scan was performed. Patients were divided into two two-centre cohorts and further dichotomised into CT-positive and CT-negative groups for statistical analysis. Single markers and panels were evaluated using Cohort 1. Four proteins—H-FABP, IL-10, S100B and GFAP—showed significantly higher levels in CT-positive patients. The best-performing biomarker was H-FABP, with a specificity of 32% (95% CI 23–40) and sensitivity reaching 100%. The best-performing two-marker panel for Cohort 1, subsequently validated in Cohort 2, was a combination of H-FABP and GFAP, enhancing specificity to 46% (95% CI 36–55). When adding IL-10 to this panel, specificity reached 52% (95% CI 43–61) with 100% sensitivity. These results showed that proteins combined into panels could be used to efficiently classify CT-positive and CT-negative mTBI patients.
Highlights
Biomarkers have been intensively studied for their potential as diagnostic tools in cases of mild traumatic brain injury: to allow accurate diagnosis, improve patient management speeds and reduce medical costs.[1, 2] mTBI is diagnosed from its clinical symptoms and a Glasgow Coma Scale (GCS) score between 13 and 15.[3]. Determining whether patients have a trauma-induced brain lesion requires a head CT scan.[4, 5]
These include S100 calcium binding protein B (S100B) and glial fibrillary acidic protein (GFAP) both astrocyte damage markers, heart fatty acid binding protein (H-FABP) an intracellular vascular and brain fatty-acid transporter and interleukin 10 (IL-10) an anti-inflammatory protein. [8,9,10,11,12,13,14,15,16,17,18,19,20,21] The wide range of biomarker types investigated so far can be explained by the complex pathophysiological nature of TBI.[1]
The four proteins—S100B, GFAP, H-FABP and IL-10—have all previously been identified for their potential to differentiate CT-positive and CT-negative mTBI patients, confirming the results found here.[10, 16, 19, 41]
Summary
Biomarkers have been intensively studied for their potential as diagnostic tools in cases of mild traumatic brain injury (mTBI): to allow accurate diagnosis, improve patient management speeds and reduce medical costs.[1, 2] mTBI is diagnosed from its clinical symptoms and a Glasgow Coma Scale (GCS) score between 13 and 15.[3] Determining whether patients have a trauma-induced brain lesion requires a head CT scan.[4, 5] CT scans are widely overused, as only 10% of mTBI patients who undergo one will be diagnosed with a brain lesion.[6, 7] In an attempt to reduce the high numbers of CT scans performed, several proteins have been investigated as potential triage markers. Despite the similarities between these conditions, the performances of several of these biomarkers have never been studied in relation to mTBI
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