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      The Prognostic Value of Serum Neuron-Specific Enolase in Traumatic Brain Injury: Systematic Review and Meta-Analysis

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          Abstract

          Background

          Several studies have suggested that neuron-specific enolase (NSE) in serum may be a biomarker of traumatic brain injury. However, whether serum NSE levels correlate with outcomes remains unclear. The purpose of this review was to evaluate the prognostic value of serum NSE protein after traumatic brain injury.

          Methods

          PubMed and Embase were searched for relevant studies published up to October 2013. Full-text publications on the relationship of NSE to TBI were included if the studies concerned patients with closed head injury, NSE levels in serum after injury, and Glasgow Outcome Scale (GOS) or Extended GOS (GOSE) scores or mortality. Study design, inclusion criteria, assay, blood sample collection time, NSE cutoff, sensitivity and specificity of NSE for mortality prediction (if sufficient information was provided to calculate these values), and main outcomes were recorded.

          Results

          Sixteen studies were eligible for the current meta-analysis. In the six studies comparing NSE concentrations between TBI patients who died and those who survived, NSE concentrations correlated with mortality (M.D. 0.28, 95% confidence interval (CI), 0.21 to 0.34; I 2 55%). In the eight studies evaluating GOS or GOSE, patients with unfavorable outcomes had significantly higher NSE concentrations than those with favorable outcomes (M.D. 0.24, 95% CI, 0.17 to 0.31; I 2 64%). From the studies providing sufficient data, the pooled sensitivity and specificity for mortality were 0.79 and 0.50, and 0.72 and 0.66 for unfavorable neurological prognosis, respectively. The areas under the SROC curve (AUC) of NSE concentrations were 0.73 (95% CI, 0.66–0.80) for unfavorable outcome and 0.76 (95% CI, 0.62–0.90) for mortality.

          Conclusions

          Mortality and unfavorable outcome were significantly associated with greater NSE concentrations. In addition, NSE has moderate discriminatory ability to predict mortality and neurological outcome in TBI patients. The optimal discrimination cutoff values and optimal sampling time remain uncertain because of significant variations between studies.

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          Most cited references27

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          Predicting outcome after traumatic brain injury: practical prognostic models based on large cohort of international patients.

          To develop and validate practical prognostic models for death at 14 days and for death or severe disability six months after traumatic brain injury. Multivariable logistic regression to select variables that were independently associated with two patient outcomes. Two models designed: "basic" model (demographic and clinical variables only) and "CT" model (basic model plus results of computed tomography). The models were subsequently developed for high and low-middle income countries separately. Medical Research Council (MRC) CRASH Trial. 10,008 patients with traumatic brain injury. Models externally validated in a cohort of 8509. The basic model included four predictors: age, Glasgow coma scale, pupil reactivity, and the presence of major extracranial injury. The CT model also included the presence of petechial haemorrhages, obliteration of the third ventricle or basal cisterns, subarachnoid bleeding, midline shift, and non-evacuated haematoma. In the derivation sample the models showed excellent discrimination (C statistic above 0.80). The models showed good calibration graphically. The Hosmer-Lemeshow test also indicated good calibration, except for the CT model in low-middle income countries. External validation for unfavourable outcome at six months in high income countries showed that basic and CT models had good discrimination (C statistic 0.77 for both models) but poorer calibration. Simple prognostic models can be used to obtain valid predictions of relevant outcomes in patients with traumatic brain injury.
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            Biomarkers for the clinical differential diagnosis in traumatic brain injury--a systematic review.

            Rapid triage and decision-making in the treatment of traumatic brain injury (TBI) present challenging dilemma in "resource poor" environments such as the battlefield and developing areas of the world. There is an urgent need for additional tools to guide treatment of TBI. The aim of this review is to establish the possible use of diagnostic TBI biomarkers in (1) identifying diffuse and focal brain injury and (2) assess their potential for determining outcome, intracranial pressure (ICP), and responses to therapy. At present, there is insufficient literature to support a role for diagnostic biomarkers in distinguishing focal and diffuse injury or for accurate determination of raised ICP. Presently, neurofilament (NF), S100β, glial fibrillary acidic protein (GFAP), and ubiquitin carboxyl terminal hydrolase-L1 (UCH-L1) seemed to have the best potential as diagnostic biomarkers for distinguishing focal and diffuse injury, whereas C-tau, neuron-specific enolase (NSE), S100β, GFAP, and spectrin breakdown products (SBDPs) appear to be candidates for ICP reflective biomarkers. With the combinations of different pathophysiology related to each biomarker, a multibiomarker analysis seems to be effective and would likely increase diagnostic accuracy. There is limited research focusing on the differential diagnostic properties of biomarkers in TBI. This fact warrants the need for greater efforts to innovate sensitive and reliable biomarkers. We advocate awareness and inclusion of the differentiation of injury type and ICP elevation in further studies with brain injury biomarkers. © 2013 John Wiley & Sons Ltd.
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              Neuron-specific enolase, S100B, and glial fibrillary acidic protein levels as outcome predictors in patients with severe traumatic brain injury.

              The availability of markers able to provide an early insight related to prognostic and functional outcome of patients with traumatic brain injury (TBI) are limited. The relationship of clinical outcome with CSF neuron-specific enolase (NSE), S100B and glial fibrillary acidic protein (GFAP) levels in patients with severe TBI was investigated. Twenty patients with severe TBI (7 days at unit care) and controls were studied. Patients were grouped according to the outcome: (1) nonsurvival (n=5): patients who died; (2) survival A (n=15): CSF sampled between 1st and 3rd day from patients who survived after hospital admission; and (3) survival B (n=7): CSF sampled between 4th and 7th day from patients who survived after hospital admission and were maintained with intraventricular catheter up to 7 days. Up to 3 days, S100B and NSE levels (ng/mL) were significantly elevated in the nonsurvival compared with survival A group (S100: 12.45 ± 5.46 vs 5.64 ± 3.36; NSE: 313.20 ± 45.51 vs 107.80 ± 112.10). GFAP levels did not differ between groups. In the survival B group S100B, GFAP, and NSE levels were still elevated compared with control (4.59 ± 2.19, 2.48 ± 2.55, and 89.80 ± 131.10, respectively). To compare S100B and NSE for the prediction of nonsurvival and survival patients we performed receiver operating characteristic curves. At admission, CSF NSE level predicts brain death more accurately than S100B. Early elevations (up to 3 days) of S100B and NSE secondary to severe TBI predict deterioration to brain death. However, this feature was more prominently associated with NSE than S100B. Copyright © 2011 by the Congress of Neurological Surgeons
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                4 September 2014
                : 9
                : 9
                : e106680
                Affiliations
                [1 ]Department of Neurosurgery, The First People's Hospital of Kunshan, affiliated with Jiangsu University, Suzhou, PR China
                [2 ]Department of Neurosurgery, Huashan Hospital, affiliated to Fudan University, Shanghai, PR China
                St Michael's Hospital, University of Toronto, Canada
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: HL. Performed the experiments: FC QY. Analyzed the data: FC QY. Contributed reagents/materials/analysis tools: FC QY HL JY WMW. Contributed to the writing of the manuscript: FC QY.

                Article
                PONE-D-14-22693
                10.1371/journal.pone.0106680
                4154726
                25188406
                02aacddb-40ae-41a8-9956-5a035af6f75f
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 23 May 2014
                : 30 July 2014
                Page count
                Pages: 15
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Medicine and Health Sciences
                Critical Care and Emergency Medicine
                Trauma Medicine
                Brain Damage
                Head Injury
                Trauma Surgery
                Neurology
                Custom metadata
                The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files.

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