Role of Salivary Biomarkers in Predicting Significant Traumatic Brain Injury

Abstract

Objectives: The highest rates of traumatic brain injury (TBI)-related morbidity and mortality occur in young children and adolescents. The objective of this study was to describe the levels of 3 biomarkers (S100B, glial fibrillary acidic protein, neuron-specific enolase) in saliva of children with TBI requiring inpatient admission at a pediatric trauma center and compare these levels in children without TBI.Methods: A convenience sample of 24 children aged 0 to 18 years, presenting with acute isolated TBI, was enrolled prospectively. The non-TBI comparison groups consisted of patients with medical complaints and musculoskeletal injuries only. Salivary specimens were collected, and biomarkers were measured using quantitative enzyme-linked immunosorbent assay method. Demographic, clinical data, and brain imaging findings were obtained.Results: Seventy-four children were enrolled. Twenty-four had TBI (mean age, 5.07 years; SD, 4.8 years); 14 subjects (58.3%) with TBI were found to have significant traumatic brain injury (SBI) on computed tomography scan. S100B levels were significantly higher in TBI group compared with those with musculoskeletal injury only (median, 113.2 pg/mL vs 18 pg/mL; P = 0.021). Area under the receiver operating characteristic curve for S100B in predicting SBI was 0.675; the optimum threshold for S100B to achieve the optimum sensitivity and specificity of SBI was at 86.9 pg/mL for SBI versus no injury group.Conclusions: S100B levels in saliva were higher in children with TBI and may be predictive of SBI identified by presence of computed tomography abnormalities. Larger studies are needed to replicate our findings in using a noninvasive diagnostic measure for children with TBI and SBI.

Is Salivary S100B a Biomarker of Traumatic Brain Injury? A Pilot Study

“…An additional limitation is the use of normal subjects as controls: a population of non-trauma victims (e.g., orthopedic emergency room patients) may have been more appropriate. It is important to underscore that in a small pediatric study (29), salivary S100B was not increased in polytrauma no-TBI patients.…”

Review: Emerging Eye-Based Diagnostic Technologies for Traumatic Brain Injury

“…Identifying chemical responses to TBI and correlation with injury severity would enable a better mechanistic understanding, development of new diagnostic modalities and opportunities for more effective therapies. Recent publications investigate chemical responses to TBI for early and accurate diagnostics [40] , [66] , [167] , [168] , and the capability to detect changes as early as an hour after trauma [169] – [172] , in biofluids such as blood, CSF, urine and saliva [173] – [177] , using molecular sensing techniques [178] . Changes present in biofluids can be termed as biomarkers and concentrations correspond to changes in metabolism, vascular function, inflammation, extracellular matrix status and damage to axons, neurons and glial cells after injury [80] , [179] , [180] .…”

“…Urine is a potential ex-vivo biofluid for detection of brain biomarkers [176] , however, it has low specificity, varying sample volumes and indirect route for sampling, making it often highly diluted once released from the kidney and requiring patient's cooperation [169] . Saliva has also been investigated as a potential biofluid for TBI biomarkers [173] , [177] , and whilst it is easy to collect non-invasively, only S100B and UCHL1 have been so far successfully measured from it [167] , with the analysis typically including an additional step of exosomes isolation thus, introducing additional challenges for real-time measurements and diagnostics [254] . Biomarker sensing techniques which require ex-vivo sampling incorporate additional risk of samples being affected by preparation and preservation methods as was illustrated by Abdelhak et al who has freeze- thawed CSF samples over 5 cycles showing a 50% decrease of the GFAP within those [255] .…”

S100B, GFAP, UCH-L1 and NSE as predictors of abnormalities on CT imaging following mild traumatic brain injury: a systematic review and meta-analysis of diagnostic test accuracy

“…One area of potential innovation is in less-invasive sampling. Salivary S100B has demonstrated potential utility [32,102]. This represents an avenue for further exploration and would contribute substantially to the development of a rapid, non-invasive, point-of-care test for mTBI screening, which may even be extended to the pre-hospital setting [76].…”

“…This represents an avenue for further exploration and would contribute substantially to the development of a rapid, non-invasive, point-of-care test for mTBI screening, which may even be extended to the pre-hospital setting [76]. However, other biomarkers did not demonstrate the same promise [102], and further studies will be required to ascertain thresholds and performance before clinical use can be considered.…”