S100B Is Not a Reliable Prognostic Index in Paediatric TBI

Department of Anaesthesia and Intensive Care, University of Naples Federico II, Naples, Italy.
Pediatric Neurosurgery (Impact Factor: 0.33). 02/2007; 43(4):258-64. DOI: 10.1159/000103304
Source: PubMed


As far as paediatric traumatic brain injury is concerned, it is difficult to quantify the extent of the primary insult, to monitor secondary changes and to predict neurological outcomes by means of the currently used diagnostic tools: physical examination, Glasgow Coma Scale (GCS) score and computed tomography. For this reason, several papers focused on the use of biochemical markers (S100B, neuron-specific enolase) to detect and define the severity of brain damage and predict outcome after traumatic head injury or cardiac arrest.
The aim of this paper is measuring the range of S100B serum concentrations in children affected by traumatic brain injury and describing the possible roles of this protein in the reaction to trauma.
Fifteen children aged 1-15 years were included in the study. Traumatic brain injury severity was defined by paediatric GCS score as mild (9 patients), moderate (2 patients) or severe (4 patients). Blood samples for S100B serum measurement were taken at emergency department admission and after 48 h.
The serum S100B concentration was higher in the group of severe trauma patients, who scored the lowest on the GCS at admission, and among them, the highest values were reported by the children with concomitant peripheral lesions.
The role of S100B in paediatric traumatic brain injury has not been clarified yet, and the interpretation of its increase when the head trauma is associated with other injuries needs the understanding of the physiopathological mechanisms that rule its release in the systemic circulation. The levels of S100B in serum after a brain injury could be related to the mechanical discharge from a destroyed blood-brain barrier, or they could be due to the active expression by the brain, as a part of its involvement in the systemic inflammatory reaction. Early increase of this protein is not a reliable prognostic index of neurological outcome after pediatric traumatic brain injury, since even very elevated values are compatible with a complete neurological recovery.

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    • "In addition, increased levels of serum s100B have been noted in patients who have made a complete neurological recovery (Piazza et al., 2007). s100B has also been outperformed by GFAP in predicting long-term outcome (6 months), as reflected by the Glasgow Outcome Score Extended (GOSE) and RTW assessment (Metting et al., 2012). "
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    ABSTRACT: Traumatic Brain Injury (TBI) is a global health concern. The majority of TBI's are mild, yet our ability to diagnose and treat mild traumatic brain injury (mTBI) is lacking. This deficiency results from a variety of issues including the difficulty in interpreting ambiguous clinically presented symptoms, and ineffective imaging techniques. Thus, researchers have begun to explore cellular and molecular based approaches to improve both diagnosis and prognosis. This has been met with a variety of challenges, including difficulty in relating biological markers to current clinical symptoms, and overcoming our lack of fundamental understanding of the pathophysiology of mTBI. However, recent adoption of high throughput technologies and a change in focus from the identification of single to multiple markers has given just optimism to mTBI research. The purpose of this review is to highlight a number of current experimental peripheral blood biomarkers of mTBI, as well as comment on the issues surrounding their clinical application and utility.
    Frontiers in Neurology 05/2013; 4:44. DOI:10.3389/fneur.2013.00044
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    • "A very strong correlation of S100B levels and severity of injury has been reported (Savola et al., 2004), as well as a link between high S100B expression and unfavorable outcome (Herrmann et al., 2001; Townend et al., 2002; Vos et al., 2004; Rainey et al., 2009). However, S100B is not ideal as a TBI biomarker because it does not readily cross the BBB, its serum levels increase after peripheral trauma in the absence of brain injury (Anderson et al., 2001; Savola et al., 2004; Torabian and Kashani-Sabet, 2005), and it has not always been found to reliably predict outcome (Berger et al., 2007; Piazza et al., 2007). In the search for a reliable biomarker of TBI, other molecules have been assessed, including glial fibrillary acidic protein (GFAP), NSE, MBP, α-II-spectrin breakdown products (BDPs), ubiquitin C-terminal hydrolase-L1, and various cytokines (Dash et al., 2010; Schiff et al., 2012). "
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    Frontiers in Neurology 03/2013; 4:18. DOI:10.3389/fneur.2013.00018
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    • "OR, odds ratio (significant ORs indicated by asterisks); CI, confidence interval; nc, not calculable; GFAP: glial fibrillary acidic protein; UCH-L1, ubiquitin C-terminal hydrolase-L1; SBDP145, 145-kDa aII-spectrin breakdown product; 1S, first measured level in serum; 1C, first measured level in cerebrospinal fluid; 24S, average of all measured serum levels within 24 h post-injury. breakthrough in this field (Pelinka et al., 2005; Piazza et al., 2007; Svetlov et al., 2009), we believe that our most recent investigations have identified a new set of biomarkers that can be linked to pathobiological processes (calpain-and caspasemediated spectrin breakdown) and/or brain constituents (UCHL-1 and GFAP), that are indicative of traumaticallyevoked brain damage (Brophy et al., 2011; Mondello et al., 2010,2011). The results detailed here of how these biomarkers aided in outcome prediction should spur further research to explore the potential of these substances. "
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    ABSTRACT: Outcome prediction following severe traumatic brain injury (sTBI) is a widely investigated field of research. A major breakthrough is represented by the IMPACT prognostic calculator based on admission data of more than 8500 patients. A growing body of scientific evidence has shown that clinically meaningful biomarkers, including glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), and αII-spectrin breakdown product (SBDP145), could also contribute to outcome prediction. The present study was initiated to assess whether the addition of biomarkers to the IMPACT prognostic calculator could improve its predictive power. Forty-five sTBI patients (GCS score≤8) from four different sites were investigated. We utilized the core model of the IMPACT calculator (age, GCS motor score, and reaction of pupils), and measured the level of GFAP, UCH-L1, and SBDP145 in serum and cerebrospinal fluid (CSF). The forecast and actual 6-month outcomes were compared by logistic regression analysis. The results of the core model itself, as well as serum values of GFAP and CSF levels of SBDP145, showed a significant correlation with the 6-month mortality using a univariate analysis. In the core model, the Nagelkerke R(2) value was 0.214. With multivariate analysis we were able to increase this predictive power with one additional biomarker (GFAP in CSF) to R(2)=0.476, while the application of three biomarker levels (GFAP in CSF, GFAP in serum, and SBDP145 in CSF) increased the Nagelkerke R(2) to 0.700. Our preliminary results underline the importance of biomarkers in outcome prediction, and encourage further investigation to expand the predictive power of contemporary outcome calculators and prognostic models in TBI.
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