Abstract
Diagnosing traumatic brain injury (TBI) from body fluids in cases where there are no obvious external signs of impact would be useful for emergency physicians and forensic pathologists alike. None of the previous attempts has so far succeeded in establishing a single biomarker to reliably detect TBI with regards to the sensitivity: specificity ratio in a post mortem setting. This study investigated a combination of body fluid biomarkers (obtained post mortem), which may be a step towards increasing the accuracy of biochemical TBI detection. In this study, serum and cerebrospinal fluid (CSF) samples from 30 acute lethal TBI cases and 70 controls without a TBI-related cause of death were evaluated for the following eight TBI-related biomarkers: brain-derived neurotrophic factor (BDNF), ferritin, glial fibrillary acidic protein (GFAP), interleukin 6 (IL-6), lactate dehydrogenase, neutrophil gelatinase-associated lipocalin (NGAL), neuron-specific enolase and S100 calcium-binding protein B. Correlations among the individual TBI biomarkers were assessed, and a specificity-accentuated threshold value analysis was conducted for all biomarkers. Based on these values, a decision tree modelling approach was performed to assess the most accurate biomarker combination to detect acute lethal TBIs. The results showed that 92.45% of acute lethal TBIs were able to be diagnosed using a combination of IL-6 and GFAP in CSF. The probability of detecting an acute lethal TBI was moderately increased by GFAP alone and considerably increased by the remaining biomarkers. BDNF and NGAL were almost perfectly correlated (p = 0.002; R2 = 0.944). This study provides evidence that acute lethal TBIs can be detected to a high degree of statistical accuracy using forensic biochemistry. The high inter-individual correlations of biomarkers may help to estimate the CSF concentration of an unknown biomarker, using extrapolation techniques.
Highlights
Traumatic brain injury (TBI) substantially contributes to the global injury burden with a continuously increasing prevalence over the last quarter of a century [1]
Fluid biomarkers are promising, as (i) they may help detect traumatic brain injury (TBI) in geriatric and pediatric patients, who account for a significant proportion of TBI-related emergency visits and may have limited ability to describe the underlying traumatic event [2]; (ii) they may prevent misdiagnosis of concussion, in which obvious external injury is often lacking and patient symptoms might not be characteristic [3]; and (iii) they may serve as a predictor for the outcome and mortality of a patient following TBI [10,11]
The assessment of eight TBI-related biomarkers performed here enables forensic pathologists to diagnose an acute lethal TBI with an accuracy of 92.45%, using cerebrospinal fluid (CSF) levels of interleukin 6 (IL-6) and glial fibrillary acidic protein (GFAP) with the cut off values stated in this study
Summary
Traumatic brain injury (TBI) substantially contributes to the global injury burden with a continuously increasing prevalence over the last quarter of a century [1]. With a lethal outcome in about a fifth of these cases [1,2] Fluid biomarkers such as acute-phase proteins and specific proteins of the central nervous system (CNS) are an emerging objective tool to detect TBIs ante [3] and post mortem [4,5,6,7,8,9]. Fluid biomarkers are promising, as (i) they may help detect TBIs in geriatric and pediatric patients, who account for a significant proportion of TBI-related emergency visits and may have limited ability to describe the underlying traumatic event [2]; (ii) they may prevent misdiagnosis of concussion, in which obvious external injury is often lacking and patient symptoms might not be characteristic [3]; and (iii) they may serve as a predictor for the outcome and mortality of a patient following TBI [10,11]. Complementary to the post mortem confirmation of a TBI as a potential cause of death, fluid TBI-related biomarkers can be used for estimating time since death [8] and survival time [6,7,9] following the traumatic event
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