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Cardiac arrest (CA) is a serious health concern that often results in mortality or severe neurological dysfunction in the case of survival. Our aim was to explore the neurological prognostic factors in patients with CA. This retrospective observational study included adult patients with CA. We investigated serum neuron-specific enolase (NSE), S100 calcium-binding protein β (S100β), and indices and parameters at 1, 3, 5, 7 and intensive care unit (ICU) discharge days after CA. The primary study endpoint was the Cerebral Performance Category (CPC) scale score at ICU discharge, which was dichotomized as good neurological outcome (CPC 1-2: full recovery or moderate disability) and poor neurological outcome (CPC 3-5: severe disability, vegetative state, or death). Of the 191 adult patients with CA, 42 (22%) had good neurological outcomes, and 149 (78%) had poor neurological outcomes. NSE at 1,3,5,7 and ICU discharge days showed excellent predictive accuracy for neurological outcomes (area under the curve [AUC]: 0.666, 0.716, 0.870, 0.739, and 0.901, respectively). However, S100β exhibited general predictive power (AUC: 0.666, 0.573, 0.607, 0.594, 0.727). Finally, the early warning model, which combined day 1 NSE, day 1 S100β, cardiac arrest time, SOFA scores, APACHE II scores, and age, was used to screen CA patients with poor neurological prognosis at early stages and had an AUC of 0.792. Serum concentrations of NSE and S100β were significantly elevated in CA patients and could be prognostic biomarkers to predict neurological outcomes. Day 1 NSE and S100β combined with multiple indicators could be a decent early warning model for poor neurological prognosis in patients with CA., (© 2024. The Author(s).)

Objectives: Neuron-specific enolase (NSE) is frequently used to predict neurological outcomes in patients with hypoxic brain injury. Hanging can cause hypoxic brain damage, and survivors can suffer from neurological deficits that may impair daily activities. Here, we investigated the utility of the initial serum NSE level as a predictor of neurological outcomes in near-hanging patients with decreased consciousness., Methods: This retrospective multicenter study was conducted in patients who visited the emergency department due to near-hanging injury from October 2013 to February 2019 at three university hospitals in Korea. They were divided into two groups according to the presence of out-of-hospital cardiac arrest. The neurological outcome was determined using the Cerebral Performance Category (CPC) measured at the time of discharge. Multivariate analysis was performed to determine whether initial serum NSE is an independent predictor of neurological outcome., Results: Of the 70 patients included in the study, 44 showed a poor neurological outcome (CPC score = 3-5). Among the 52 patients with cardiac arrest, only 10 (19.2%) were discharged with good neurological outcome (CPC score = 1-2). In the whole cohort, a high serum NSE level was a significant predictor of poor neurological outcome (odds ratio [OR], 1.343; 95% confidence interval [CI], 1.003-1.800, p = 0.048). Among the patients with cardiac arrest, a high serum NSE level was a significant predictor of poor neurological outcome (OR, 1.138; 95% CI, 1.009-1.284, p = 0.036)., Conclusions: In near-hanging patients, a high initial serum NSE level is an independent predictor of poor neurological outcome., Competing Interests: The authors have declared that no competing interests exist.

Outcome prognostication after cardiac arrest (CA) is challenging. Current multimodal prediction approaches would benefit from new biomarkers. MicroRNAs constitute a novel class of disease markers and circulating levels of brain-enriched ones have been associated with outcome after CA. To determine whether these levels reflect the extent of brain damage in CA patients, we assessed their correlation with neuron-specific enolase (NSE), a marker of brain damage. Blood samples taken 48 h after return of spontaneous circulation from two groups of patients from the Targeted Temperature Management trial were used. Patients were grouped depending on their neurological outcome at six months. Circulating levels of microRNAs were assessed by sequencing. NSE was measured at the same time-point. Among the 673 microRNAs detected, brain-enriched miR9-3p, miR124-3p and miR129-5p positively correlated with NSE levels (all p < 0.001). Interestingly, these correlations were absent when only the good outcome group was analyzed ( p > 0.5). Moreover, these correlations were unaffected by demographic and clinical characteristics. All three microRNAs predicted neurological outcome at 6 months. Circulating levels of brain-enriched microRNAs are correlated with NSE levels and hence can reflect the extent of brain injury in patients after CA. This observation strengthens the potential of brain-enriched microRNAs to aid in outcome prognostication after CA.

Introduction: Serum neuron-specific enolase (NSE) levels have been shown to correlate with neurologic outcome in comatose survivors of cardiac arrest but use of absolute NSE thresholds is limited. This study describes and evaluates a novel approach to analyzing NSE, the NSE ratio, and evaluates the prognostic utility of NSE absolute value thresholds and trends over time., Methods: 100 consecutive adult comatose cardiac arrest survivors were prospectively enrolled. NSE levels were assessed at 24, 48, and 72 h post-arrest. Primary outcome was the Glasgow Outcome Score (GOS) at 6 months post-arrest; good outcome was defined as GOS 3-5. Absolute and relative NSE values (i.e. the NSE ratio), peak values, and the trend in NSE over 72 h were analyzed., Results: 98 patients were included. 42 (43%) had a good outcome. Five good outcome patients had peak NSE >33 µg/L (34.9-46.4 µg/L). NSE trends between 24 and 48 h differed between outcome groups (decrease by 3.0 µg/L (0.9-7.0 µg/L) vs. increase by 13.4 µg/L (-3.7 to 69.4 µg/L), good vs. poor, p = 0.004). The 48:24 h NSE ratio differed between the good and poor outcome groups (0.8 (0.6-0.9) vs. 1.4 (0.8-2.5), p = 0.001), and a 48:24 h ratio of ≥1.7 was 100% specific for poor outcome., Conclusions: The NSE ratio is a unique method to quantify NSE changes over time. Values greater than 1.0 indicate increasing NSE and may be reflective of ongoing neuronal injury. The NSE ratio obviates the need for an absolute value cut-off., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Targeted temperature management (TTM) represents the standard of care in comatose survivors after cardiac arrest (CA) and may be applied targeting 33° or 36 °C. While multimodal prognostication has been extensively tested for 33 °C, scarce information exists for 36 °C., Methods: In this cohort study, consecutive comatose adults after CA treated with TTM at 36 °C between July 2014 and October 2016 were included. A combination of neurological examination, electrophysiological features, and serum neuron-specific enolase (NSE) was evaluated for outcome prediction at 3 months (mortality; good outcome defined as cerebral performance categories (CPC) score of 1-2, poor outcome defined as CPC 3-5)., Results: We analyzed 61 patients. The presence of two or more predictors out of, unreactive electroencephalogram (EEG) background, epileptiform EEG, absent pupillary and/or corneal reflex, early myoclonus, bilaterally absent cortical somatosensory evoked potentials, and serum NSE >75 μg/l, had a high specificity for predicting mortality (positive predictive value [PPV] = 1.00, 95% CI 0.87-1.00) and poor outcome (PPV = 1.00, 95% CI 0.80-1.00). Reactive EEG background was highly sensitive for predicting good outcome (0.95, 95% CI 0.74-0.99)., Conclusions: Prediction of outcome after CA and TTM targeting 36 °C seems valid in adults using the same features tested at 33 °C. A reactive EEG under TTM appears highly sensitive for good outcome.

Aim: To investigate if the serum biomarkers of cerebral injury, neuron-specific enolase and S100b protein, may classify unfavourable neurological outcome after paediatric cardiac arrest., Methods: We performed a retrospective study of neuron-specific enolase and S100b measurements from 95 children treated in our paediatric cardiac intensive care unit after cardiac arrest. Neurological outcome at discharge was evaluated using the paediatric cerebral performance category scale, with unfavourable outcome defined as a change of >1 compared to pre-arrest status or death., Results: Fifty-eight patients (61.1%) survived to discharge with 48 (50.5%) having a favourable neurological outcome. We observed significantly higher levels of both biomarkers in the unfavourable outcome group at designated time points (neuron-specific enolase at 24, 48, and 72h and S100b at 12, 24, and 48h after cardiac arrest, p<0.05). Receiver operating characteristic areas under the curve for neuron-specific enolase were 0.83, 0.80, and 0.73 at time points 24, 48, and 72h and 0.87, 0.81, and 0.82 for S100b at 12, 24, and 48h after cardiac arrest, respectively. Neuron-specific enolase measurement at 24h after cardiac arrest was an independent predictor of unfavourable outcome in a multivariable analysis., Conclusions: Neuron-specific enolase and S100b classify unfavourable neurological outcome in this large paediatric cardiac arrest cohort. Further multi-institutional prospective studies to comprehensively evaluate the diagnostic accuracy of these biomarkers under various clinical conditions and to determine reliable cut-off values in children are warranted., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To test serum tau as a predictor of neurological outcome after cardiac arrest., Methods: We measured the neuronal protein tau in serum at 24, 48, and 72 hours after cardiac arrest in 689 patients in the prospective international Target Temperature Management trial. The main outcome was poor neurological outcome, defined as Cerebral Performance Categories 3-5 at 6 months., Results: Increased tau was associated with poor outcome at 6 months after cardiac arrest (median = 38.5, interquartile range [IQR] = 5.7-245ng/l in poor vs median = 1.5, IQR = 0.7-2.4ng/l in good outcome, for tau at 72 hours, p < 0.0001). Tau improved prediction of poor outcome compared to using clinical information (p < 0.0001). Tau cutoffs had low false-positive rates (FPRs) for good outcome while retaining high sensitivity for poor outcome. For example, tau at 72 hours had FPR = 2% (95% CI = 1-4%) with sensitivity = 66% (95% CI = 61-70%). Tau had higher accuracy than serum neuron-specific enolase (NSE; the area under the receiver operating characteristic curve was 0.91 for tau vs 0.86 for NSE at 72 hours, p = 0.00024). During follow-up (up to 956 days), tau was significantly associated with overall survival. The accuracy in predicting outcome by serum tau was equally high for patients randomized to 33 °C and 36 °C targeted temperature after cardiac arrest., Interpretation: Serum tau is a promising novel biomarker for prediction of neurological outcome in patients with cardiac arrest. It may be significantly better than serum NSE, which is recommended in guidelines and currently used in clinical practice in several countries to predict outcome after cardiac arrest. Ann Neurol 2017;82:665-675., (© 2017 Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

Objective: Outcome prediction after cardiac arrest is important to decide on continuation or withdrawal of intensive care. Neuron-specific enolase is an easily available, observer-independent prognostic biomarker. Recent studies have yielded conflicting results on its prognostic value after targeted temperature management., Design, Setting, and Patients: We analyzed neuron-specific enolase serum concentrations 3 days after nontraumatic in-hospital cardiac arrest and out-of-hospital cardiac arrest and outcome of patients from five hospitals in Germany, Austria, and Italy. Patients were treated at 33°C for 24 hours. Cerebral Performance Category was evaluated upon ICU discharge. We performed case reviews of good outcome patients with neuron-specific enolase greater than 90 μg/L and poor outcome patients with neuron-specific enolase less than or equal to 17 μg/L (upper limit of normal)., Measurements and Main Results: A neuron-specific enolase serum concentration greater than 90 μg/L predicted Cerebral Performance Category 4-5 with a positive predictive value of 99%, false positive rate of 0.5%, and a sensitivity of 48%. All three patients with neuron-specific enolase greater than 90 μg/L and Cerebral Performance Category 1-2 had confounders for neuron-specific enolase elevation. An neuron-specific enolase serum concentration less than or equal to 17 μg/L excluded Cerebral Performance Category 4-5 with a negative predictive value of 92%. The majority of 14 patients with neuron-specific enolase less than or equal to 17 μg/L who died had a cause of death other than hypoxic-ischemic encephalopathy. Specificity and sensitivity for prediction of poor outcome were independent of age, sex, and initial rhythm but higher for out-of-hospital cardiac arrest than for in-hospital cardiac arrest patients., Conclusion: High neuron-specific enolase serum concentrations reliably predicted poor outcome at ICU discharge. Prediction accuracy differed and was better for out-of-hospital cardiac arrest than for in-hospital cardiac arrest patients. Our "in-the-field" data indicate 90 μg/L as a threshold associated with almost no false positives at acceptable sensitivity. Confounders of neuron-specific enolase elevation should be actively considered: neuron-specific enolase-producing tumors, acute brain diseases, and hemolysis. We strongly recommend routine hemolysis quantification. Neuron-specific enolase serum concentrations less than or equal to 17 μg/L argue against hypoxic-ischemic encephalopathy incompatible with reawakening.

Background: We investigated the brain-derived proteins neuron-specific enolase (NSE) and protein S-100b (S-100b) in survivors of cardiac arrest who had either received therapeutic hypothermia (TH) or had not., Methods: In a retrospective cohort study, we analysed serum levels of these two proteins over 5 days in 201 adult cardiac arrest survivors admitted to our intensive care unit between 2003 and 2010. These were all survivors that remained comatose and survived at least 48 h. Of these, 140 received therapeutic hypothermia (hypothermia group). The remainder received only standard therapy without hypothermia (normothermia group)., Results: There was no difference in survival between the hypothermia and normothermia groups. At 4 weeks after arrest, 61 (43.6%) patients of the hypothermia group and 26 (42.6%) patients of the normothermia group were still alive with favourable to moderate neurological outcome (Cerebral Performance Category Scale 1-3). We observed no change in the mean serum levels of either protein between the two groups. Within each group, we found significantly higher serum levels of NSE and S-100b in patients with unfavourable neurological outcome (Cerebral Performance Category Scale 4 and 5) than in those with moderate to favourable outcome. Cut-off levels 3 days after cardiac arrest predicting an unfavourable outcome were >40 ng/ml for NSE [specificity 95.2%, Sensitivity 74.1%, areas under the curve (AUC):0.889], false positive rate 4 [confidence interval (CI): 0.0131-0.1175] and >1.03 μg/1 for S-100b (specificity 95.6%, Sensitivity 57.8%, AUC: 0.875) false positive rate 3 (CI: 0.0091-01218)., Conclusions: Additional application of TH was not associated with significant changes in serum levels of NSE and S-100b in comatose survivors of cardiac arrest, compared to those treated without TH., (© 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: The neuropeptide secretoneurin (SN) shows widespread distribution in the brain. We evaluated whether SN is elevated after cardiopulmonary resuscitation (CPR) and could serve as a potential new biomarker for hypoxic brain injury after CPR., Methods: This was a prospective observational clinical study. All patients admitted to a tertiary medical intensive care unit after successful CPR with expected survival of at least 24 h were consecutively enrolled from September 2008 to April 2013. Serum SN and neuron-specific enolase were determined in 24 h intervals starting with the day of CPR for 7 days. Neurological outcome was assessed with the Cerebral Performance Categories Scale (CPC) at hospital discharge., Results: A total of 134 patients were included with 49 % surviving to good neurological outcome (CPC 1-2). SN serum levels peaked within the first 24 h showing on average a sixfold increase above normal. SN levels were significantly higher in patients with poor (CPC 3-5) than in patients with good neurological outcome [0-24 h: 75 (43-111) vs. 38 (23-68) fmol/ml, p < 0.001; 24-48 h: 45 (24-77) vs. 23 (16-39) fmol/ml, p < 0.001]. SN determined within the first 48 h showed a receiver operating characteristic (ROC) area under the curve (AUC) of 0.753 (0.665-0.841). NSE in the first 72 h had a ROC-AUC of 0.881 (0.815-0.946). When combining the two biomarkers an AUC of 0.925 (0.878-0.972) for outcome prediction could be reached., Conclusions: SN is a promising early biomarker for hypoxic brain injury. Further studies will be required for confirmation of these results.

Background: Neuron specific enolase (NSE) and astroglial protein S100B are associated with outcome following resuscitation from cardiac arrest. We tested whether NSE and S100B levels are associated with illness severity on hospital arrival, and whether levels are independently associated with survival to hospital discharge after adjusting for initial illness severity., Methods: Levels of NSE and S100B were obtained at arrival, 6, 12, 24, 48, and 72h after successful resuscitation from cardiac arrest. Clinical data included demographics, Pittsburgh Cardiac Arrest Category (PCAC I-IV) and survival to hospital discharge. Univariable and multivariable predictive models including NSE and S-100B were created to predict survival. ROC analyses were performed to determine sensitivity and specificity of NSE and S-100B at each time interval., Results: Of 77 comatose subjects, 5 did not receive therapeutic hypothermia and were excluded. Mean age was 59 (SD 16) years, with 58% male (N=42), 72% out-of-hospital arrest (N=52), and 43% VF/VT. Survival was 36% (N=26). PCAC IV was associated with higher levels of NSE at 24h (p=0.001) and S100B at 24h (p=0.005). In the multivariate analysis, survival was associated with initial S100B level (OR 0.24; 95% CI 0.07-0.86). NSE values>49.5ng/mL at 48h and NSE values>10.59ng/mL at 72h predicted mortality. S100B levels>0.414ng/mL at 72h predicted mortality., Conclusions: More severe neurologic injury on initial examination is associated with higher levels of NSE and S100B. Elevated levels of S100B immediately following resuscitation were associated with death. Persistently elevated levels of NSE and S100B at 48 and 72h were associated with death., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Reactive electroencephalography (EEG) background during therapeutic hypothermia (TH) is related to favorable prognosis after cardiac arrest (CA), but its predictive value is not 100 %. The aim of this study was to investigate outcome predictors after a first reactive EEG recorded during TH after CA., Methods: We studied a cohort of consecutive comatose adults admitted between February 2008 and November 2012, after successful resuscitation from CA, selecting patients with reactive EEG during TH. Outcome was assessed at three months, and categorized as survivors and non-survivors (no patient was in vegetative state). Demographics, clinical variables, EEG features, serum neuron-specific enolase (NSE) and procalcitonin, were compared using uni- and multivariable analyses., Results: A total of 290 patients were treated with TH after cardiac arrest; 146 had an EEG during TH, which proved reactive in 90 of them; 77 (86 %) survived and 13 (14 %) died (without recovery from coma). The group of non-survivors had a higher occurrence of discontinuous EEG (p = 0.006; multivariate analysis p = 0.026), and a higher serum NSE peak (p = 0.021; multivariate analysis p = 0.014); conversely, demographics, and other clinical variables including serum procalcitonin did not differ., Conclusions: A discontinuous EEG and high serum NSE are associated with mortality after CA in patients with poor outcome despite a reactive hypothermic EEG. This suggests more severe cerebral damage, but not to higher extent of systemic disease.

Introduction: Prognostication of cardiac arrest survivors is challenging since therapeutic hypothermia (TH) has been introduced. We evaluated serum biomarkers and motor response., Methods: This was a retrospective data analysis including patients in the years 2007-2012. Blood was drawn and a neurological examination was performed on admission and every morning. Outcomes were evaluated 6 months after discharge and dichotomized into good (cerebral performance category (CPC)=1 or 2) and poor (CPC=3, 4 or 5)., Results: 123 patients (79.7% male, 63±14 years) received TH; 50% had a good outcome. On admission, S-100B (P=0.004) was significantly associated with the outcome, as well as neuron-specific enolase (NSE; P=0.020) and S-100B (P=0.004) on day 1 after admission. NSE on day 2, NSE progression from day 1 to 2 and motor response on day 3 also predicted the outcome (all P<0.001). NSE>33μgl(-1) only predicted a poor outcome with a specificity of 76%. An absent motor response on day 3 was the most sensitive marker (94%). NSE>41.1μgl(-1) combined with S-100B>0.461μgl(-1) on day 1 was the most specific marker (96%)., Conclusion: Although NSE and S-100B levels are associated with the outcome, the use of previously described cut-off values was insufficiently predictive of neurologic outcome. Caution should be exercised in the use of these tests to provide neuroprognostication., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: This study was designed to evaluate multimodal prognostication in patients after cardiac arrest (CA)., Background: Accurate methods to predict outcome after CA are lacking., Methods: Seventy-five patients with CA treated with therapeutic hypothermia after cardiac resuscitation were enrolled in this prospective observational study. Serum levels of neuron-specific enolase (NSE) and neuron-enriched S100 beta (S100β) were measured 48 h after CA. Bispectral index (BIS) was continuously monitored during the first 48 h after CA. The primary endpoint was neurological outcome, as defined by the cerebral performance category (CPC) at 6-month follow-up: scores 1 or 2 indicated good outcome, and scores 3 to 5, poor outcome. The secondary endpoint was survival., Results: A total of 46 (61%) patients survived at 6 months and 41 (55%) patients had CPC 1 or 2. Levels of NSE and S100β were higher in patients with poor outcomes compared with patients with good outcomes (4-fold and 10-fold, respectively; p < 0.001). BIS was lower in patients with poor outcomes (10-fold; p < 0.001). NSE, S100β, or BIS alone predicted neurological outcome, with areas under the receiver-operating characteristic curve (AUC) above 0.80. Combined determination of S100β and BIS had an incremental predictive value (AUC: 0.95). S100β improved discriminations based on BIS (p = 0.0008), and BIS improved discriminations based on S100β (p < 10(-5)). Patients with S100β level above 0.03 μg/l and BIS below 5.5 had a 3.6-fold higher risk of poor neurological outcome (p < 0.0001). S100β and BIS predicted 6-month mortality (log-rank statistic: 50.41; p < 0.001)., Conclusions: Combined determination of serum level of S100β and BIS monitoring accurately predicts outcome after CA., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Neuron specific enolase (NSE) has repeatedly been evaluated for neurological prognostication in patients after cardiac arrest. However, it is unclear whether current guidelines for NSE cutoff levels also apply to cardiac arrest patients treated with hypothermia. Thus, we investigated the prognostic significance of absolute NSE levels and NSE kinetics in cardiac arrest patients treated with hypothermia., Methods: In a prospective study of 35 patients resuscitated from cardiac arrest, NSE was measured daily for four days following admission. Outcome was assessed at ICU discharge using the CPC score. All patients received hypothermia treatment for 24 hours at 33°C with a surface cooling device according to current guidelines., Results: The cutoff for absolute NSE levels in patients with unfavourable outcome (CPC 3-5) 72 hours after cardiac arrest was 57 μg/l with an area under the curve (AUC) of 0.82 (sensitivity 47%, specificity 100%). The cutoff level for NSE kinetics in patients with unfavourable outcome (CPC 3-5) was an absolute increase of 7.9 μg/l (AUC 0.78, sensitivity 63%, specificity 100%) and a relative increase of 33.1% (AUC 0.803, sensitivity 67%, specificity 100%) at 48 hours compared to admission., Conclusion: In cardiac arrest patients treated with hypothermia, prognostication of unfavourable outcome by NSE kinetics between admission and 48 hours after resuscitation may be superior to prognostication by absolute NSE levels.

Objective: Therapeutic hypothermia (TH) is a recommended treatment for survivors of cardiac arrest. Prognostication is complicated since sedation and muscle relaxation are used and established indicators of a poor prognosis are lacking. This prospective, observational study describes the pattern of commonly used prognostic markers in a hypothermia-treated cohort of cardiac arrest patients with prolonged coma., Methods: Among 111 consecutive patients, 19 died, 58 recovered, and 34 were in coma 3 days after normothermia (4.5 days after cardiac arrest), defined as prolonged coma. All patients were monitored with continuous amplitude-integrated EEG and repeated samples of neuron-specific enolase (NSE) were collected. In patients with prolonged coma, somatosensory evoked potentials (SSEP) and brain MRI were performed. A postmortem brain investigation was undertaken in patients who died., Results: Six of the 17 patients (35%) with NSE levels <33 μg/L at 48 hours regained the capacity to obey verbal commands. By contrast, all 17 patients with NSE levels >33 failed to recover consciousness. In the >33 NSE group, all 10 studied with MRI had extensive brain injury on diffusion-weighted images, 12/16 lacked cortical responses on SSEP, and all 6 who underwent autopsy had extensive severe histologic damage. NSE levels also correlated with EEG pattern, but less uniformly, since 11/17 with NSE <33 had an electrographic status epilepticus (ESE), only one of whom recovered. A continuous EEG pattern correlated to NSE <33 and awakening., Conclusions: NSE correlates well with other markers of ischemic brain injury. In patients with no other signs of brain injury, postanoxic ESE may explain a poor outcome.

Objective: To conduct a pilot study to evaluate the blood levels of brain derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), neuron specific enolase (NSE) and S-100B as prognostic markers for neurological outcome 6 months after hypothermia treatment following resuscitation from cardiac arrest., Design: Prospective observational study., Setting: One intensive care unit at Uppsala University Hospital., Patients: Thirty-one unconscious patients resuscitated after cardiac arrest., Interventions: None., Measurements and Main Results: Unconscious patients after cardiac arrest with restoration of spontaneous circulation (ROSC) were treated with mild hypothermia to 32-34°C for 26h. Time from cardiac arrest to target temperature was measured. Blood samples were collected at intervals of 1-108h after ROSC. Neurological outcome was assessed with Glasgow-Pittsburgh cerebral performance category (CPC) scale at discharge from intensive care and again 6 months later, when 15/31 patients were alive, of whom 14 had a good outcome (CPC 1-2). Among the predictive biomarkers, S-100B at 24h after ROSC was the best, predicting poor outcome (CPC 3-5) with a sensitivity of 87% and a specificity of 100%. NSE at 96h after ROSC predicted poor outcome, with sensitivity of 57% and specificity of 93%. BDNF and GFAP levels did not predict outcome. The time from cardiac arrest to target temperature was shorter for those with poor outcome., Conclusions: The blood concentration of S-100B at 24h after ROSC is highly predictive of outcome in patients treated with mild hypothermia after cardiac arrest., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Neuron specific enolase (NSE) has been proven effective in predicting neurological outcome after cardiac arrest with a current cut off recommendation of 33 microg/l. However, most of the corresponding studies were conducted before the introduction of mild therapeutic hypothermia (MTH). Therefore we conducted a study investigating the association between NSE and neurological outcome in patients treated with MTH., Methods: In this prospective observational cohort study the data of patients after cardiac arrest receiving MTH (n = 97) were consecutively collected and compared with a retrospective non-hypothermia (NH) group (n = 133). Serum NSE was measured 72 hours after admission to ICU. Neurological outcome was classified according to the Pittsburgh cerebral performance category (CPC 1 to 5) at ICU discharge., Results: NSE serum levels were significantly lower under MTH compared to NH in univariate analysis. However, in a linear regression model NSE was affected significantly by time to return of spontaneous circulation (ROSC) and ventricular fibrillation rhythm but not by MTH. The model for neurological outcome identified NSE, NSE*MTH (interaction) as well as time to ROSC as significant predictors. Receiver Operating Characteristic (ROC) analysis revealed a higher cutoff value for unfavourable outcome (CPC 3 to 5) with a specificity of 100% in the hypothermia group (78.9 microg/l) compared to the NH group (26.9 microg/l)., Conclusions: Recommended cutoff levels for NSE 72 hours after ROSC do not reliably predict poor neurological outcome in cardiac arrest patients treated with MTH. Prospective multicentre trials are required to re-evaluate NSE cutoff values for the prediction of neurological outcome in patients treated with MTH.

Background: Sudden cardiac arrest (CA) is a leading cause of death in Europe. The victims of CA need immediate cardiopulmonary resuscitation (CPR). Patients resuscitated due to CA have high mortality rate. Prognostic evaluation based on clinical observation is uncertain and would benefit from the use of biochemical markers of hypoxic brain damage. Multiple factors of brain origin can be measured in blood., Objective: The purpose of this study was to validate the use of the serum neuron-specific enolase (NSE) and malondialdehyde (MDA) concentrations for predicting in-hospital death, after resuscitation from out-of-hospital CA. Neuronal damage and impairment of the blood-brain-barrier integrity can be detected by the release of NSE into cerebrospinal fluid and eventually into the blood. MDA represents a product of lipid peroxide decomposition reactions., Methods: In a prospective study of 35 consecutive survivors of out-of-hospital CA, serum samples were obtained within 24, 72 and 168 h after the CA. NSE and MDA concentrations were measured, relationship between concentration in group of in-hospital death and survived patients were examined. Results There was a significant difference in NSE concentration between survivors and dead group on 1st day of measurement, marginally significant difference on 3rd day and no statistically significant difference in NSE on 7th day of measurement. There was marginally significant difference in MDA levels in both groups in all days of measurements., Conclusion: Estimation serum concentrations of NSE but not MDA seems to be a predictor of fate of patients after CA. The exact nature of oxidative stress can only be resolved by further studies.

Introduction: Most patients with cardiac arrest (CA) admitted to hospitals after successful cardiopulmonary resuscitation (CPR) are discharged with various degree of neurological deficits. To determine predictor of neurological outcome early and accurately, and to determine cutoff values, serum levels of protein S-100B and neuron-specific enolase (NSE) within 24h after CA were assessed., Methods and Results: A multicenter prospective observational study was conducted between May 2007 and April 2008 at three medical institutions in Japan on 107 consecutive non-traumatic CA patients with return of spontaneous circulation after CPR. Based on "best-ever achieved" Glasgow-Pittsburgh cerebral performance categories (CPC) score within 6 months after CA, patients were classified into a "poor neurological outcome" group (CPC3 to CPC5) (n=67) and "favorable neurological outcome" group (CPC1 and CPC2) (n=13). Blood was sampled on admission, at 6 and 24h after CA. Serum S-100B and NSE in "poor outcome" group were higher than those in "favorable outcome" group (P<0.01). On ROC analysis, area under the curve of S-100B was 0.85, 0.94 and 1.0, respectively. These were greater than those of NSE at all sampling points. The "100%-specific" cutoff values of S-100B predictive of poor neurological outcome were 1.41, 0.21, and 0.05ng/mL, respectively. These values corresponded to sensitivities of 20.9%, 62.8%, and 100%, respectively, each of which was higher than those of NSE., Conclusions: S-100B is more reliable as an early predictor of poor neurological outcome within 24h after CA than NSE and can be applied clinically.

Objective: To characterize the pattern of serum biochemical markers of central nervous system injury (neuron-specific enolase [NSE], S-100B, plasminogen activator inhibitor-1 [PAI-1]) after pediatric cardiac arrest and determine whether there is an association between biomarker concentrations and neurologic outcome., Design: Prospective, observational study., Setting: Urban, tertiary care children's hospital., Patients: Cardiac arrest survivors, n = 35., Interventions: Serial blood sampling, pediatric cerebral performance category, and standardized neurologic examination., Measurements and Main Results: Serial serum NSE and S-100B concentrations over 96 hrs and PAI-1 at 24 hrs were measured in children (age <18 yrs) who had return of spontaneous circulation following cardiac arrest. Neurologic outcome was prospectively categorized as poor if the change in pre- to postarrest pediatric cerebral performance category was > or =2. Biomarker concentrations were compared between outcome groups and between survival groups using longitudinal analysis correcting for multiple comparisons. Median levels (25th, 75th percentiles) are reported. Receiver operating characteristic analyses were performed at all time points. Biomarker concentrations showed statistically significant differences. Of the 35 patients, neurologic outcomes were poor in 19, with 15 deaths. Median NSE concentrations differed by outcome when measured at > or =48 hrs, and by survival at > or =24 hrs. S-100B concentrations were not significantly associated with neurologic outcome. S-100B levels were associated with survival outcome at > or =48 hrs. PAI-1 levels were not significantly associated with either neurologic or survival outcomes., Conclusions: The timing, intensity, and duration of serum NSE and S-100B biomarker concentration patterns are associated with neurologic and survival outcomes following pediatric cardiac arrest. Serum NSE concentrations at > or =48 hrs are associated with neurologic outcome, whereas serum S-100B levels at > or =48 hrs are associated with survival. Prospective analysis of these markers may help to predict outcomes and guide postresuscitative therapies.

Aim: To assess the prognostic value of repetitive serum samples of neuron specific enolase (NSE) and S-100B in cardiac arrest patients treated with hypothermia., Methods: In a three-centre study, comatose patients after cardiac arrest were treated with hypothermia at 33 degrees C for 24h, regardless of cause or the initial rhythm. Serum samples were collected at 2, 24, 48 and 72h after the arrest and analysed for NSE and S-100B in a non-blinded way. The cerebral performance categories scale (CPC) was used as the outcome measure; a best CPC of 1-2 during 6 months was regarded as a good outcome, a best CPC of 3-5 a poor outcome., Results: One centre was omitted in the NSE analysis due to missing 24 and 48h samples. Two partially overlapping groups were studied, the NSE group (n=102) and the S-100B group (n=107). NSE at 48h >28microg/l (specificity 100%, sensitivity 67%) and S-100B >0.51microg/l at 24h (specificity 96%, sensitivity 62%) correlated with a poor outcome, and so did a rise in NSE of >2microg/l between 24 and 48h (odds ratio 9.8, CI 3.5-27.7). A majority of missing samples (n=123) were from the 2h sampling time (n=56) due to referral from other hospitals or inter-hospital transfer., Conclusion: NSE was a better marker than S-100B for predicting outcome after cardiac arrest and induced hypothermia. NSE above 28microg/l at 48h and a rise in NSE of more than 2microg/l between 24 and 48h were markers for a poor outcome.

Objective: To investigate the prognostic value of serum neuron specific enolase (NSE) and S100 protein in evaluation of brain damage in patients resuscitated from cardiac arrest (CA)., Methods: According to whether the patients regained consciousness after 6 months or not, 25 patients after cardiopulmonary resuscitation (CPR) were divided into 2 groups, and blood samples were obtained for determination of NSE and S100 protein at 2, 12, 24, 48 and 72 hours after recovery of spontaneous circulation (ROSC), then the values at each time point were compared between 2 groups and also with that of 7 healthy volunteers. Receiver operator characteristic (ROC) curves of serum NSE and S100 protein were depicted and used area under curve (AUS) to scale the ability in evaluating the state of consciousness in patients after CPR., Results: (1)The levels of serum NSE at 12, 48 and 72 hours and S100 protein at 2, 12, 48 and 72 hours were significantly higher in patients who did not regain consciousness compared with patients who regained consciousness (all P<0.01). (2)Compared with healthy volunteers, the levels of NSE at 12 and 24 hours and S100 protein at 12 hours were higher in patients who regained consciousness (all P<0.05), the levels of NSE at all time points and S100 protein at 12, 48 and 72 hours were significantly higher in patients who did not regain consciousness (P<0.05 or P<0.01). (3)Area under curve AUC(NSE) =0.848 (P=0.000), AUC(S100) =0.896 (P=0.000), therefore both serum NSE and S100 protein had diagnostic value for predicting whether patients resuscitated from CA could regain consciousness or not. Serum S100 protein cut-off was 0.165 microg/L, with a sensitivity of 94.4%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 80% and an accuracy of 95.5% at 2 hours after ROSC. Serum NSE cut-off was 45.6 microg/L, all values reached 100% 48 hours after ROSC., Conclusion: Measurement of serum NSE and S100 protein concentrations can help judge the degree of brain damage and whether patients can regain consciousness after CPR. It will be more valuable to prognosticate a serious and continuous brain damage with dynamic observation of the serum NSE together with S100 protein.

Predicting the neurological outcome after resuscitation and a return of spontaneous circulation of resuscitated patients still remains a difficult issue. Over the past decade numerous studies have been elaborated to provide the physician with tools to assess as early as possible the neurological outcome of patients with cardiac arrest and return of spontaneous circulation and to decide about further therapeutic management. We summarise the most important ones, giving special focus to three biochemical markers (neuron specific enolase, a protein soluble in 100% ammonium sulfate and interleukin-8), which, when combined with standard neuro-functional and imaging techniques, can serve as potent predictors of neurological outcome in these patients. Despite current limitations about the prognostic significance of these markers - their inferior sensitivity, the different cut-off levels used by several investigators and their variable unequal rise over time - they can give useful information about short and long-term neurological outcome. A comprehensive set of clinical, electrophysiological, biochemical and imaging measures, obtained in a uniform manner in a cohort of patients without limitations in care, could provide a more objective set of comprehensive prognostic indicators.

Objective: To determine the prognostic accuracy of biochemical, clinical, electrophysiological, and neuropsychological investigations in predicting outcomes after cardiac arrest., Design: Prospective study., Setting: Intensive care unit of the Hamburg-Eppendorf University Medical Center, Hamburg, Germany., Patients: A total of 80 patients (mean age, 63.79 +/- 15.85 yrs) after cardiopulmonary resuscitation., Interventions: Serial blood samples (days 2-4), clinical examinations (days 2 and 4), sensory-evoked potentials (day 4), and neuropsychological assessments (

Objectives: High oxygen concentration in blood may be harmful in the reperfusion phase after cardiopulmonary resuscitation. We compared the effect of 30 and 100% inspired oxygen concentrations on blood oxygenation and the level of serum markers (NSE, S-100) of neuronal injury during the early post-resuscitation period in humans., Methods: Patients resuscitated from witnessed out-of-hospital ventricular fibrillation were randomised after the return of spontaneous circulation (ROSC) to be ventilated either with 30% (group A) or 100% (group B) oxygen for 60 min. Main outcome measures were NSE and S-100 levels at 24 and 48 h after ROSC, the adequacy of oxygenation at 10 and 60 min after ROSC and, in group A, the need to raise FiO(2) to avoid hypoxaemia. Blood oxygen saturation <95% was the threshold for this intervention., Results: Thirty-two patients were randomised and 28 (14 in group A and 14 in group B) remained eligible for the final analysis. The mean PaO(2) at 10 min was 21.1 kPa in group A and 49.7 kPa in group B. The corresponding values at 60 min were 14.6 and 46.5 kPa. PaO(2) values did not fall to the hypoxaemic level in group A. In another group FiO(2) had to be raised in five cases (36%) but in two cases it was returned to 0.30 rapidly. The mean NSE at 24 and 48 h was 10.9 and 14.2 microg/l in group A and 13.0 and 18.6 microg/l in group B (ns). S-100 at corresponding time points was 0.21 and 0.23 microg/l in group A and 0.73 and 0.49 microg/l in group B (ns). In the subgroup not treated with therapeutic hypothermia in hospital NSE at 24h was higher in group B (mean 7.6 versus 13.5 microg/l, p=0.0487)., Conclusions: Most patients had acceptable arterial oxygenation when ventilated with 30% oxygen during the immediate post-resuscitation period. There was no indication that 30% oxygen with SpO(2) monitoring and oxygen backup to avoid SpO(2)<95% did worse that the group receiving 100% oxygen. The use of 100% oxygen was associated with increased level of NSE at 24h in patients not treated with therapeutic hypothermia. The clinical significance of this finding is unknown and an outcome-powered study is feasible.

Background and Purpose: Patients resuscitated from cardiac arrest are at risk of subsequent death or poor neurological outcome up to a persistent vegetative state. We investigated the prognostic value of several epidemiological and clinical markers and two neuroproteins, neuron-specific enolase (NSE) and S-100 protein (S-100), in 97 patients undergoing cardiopulmonary resuscitation (CPR) after non-traumatic cardiac arrest between 1998 and 2002., Results: 52.6% of the patients died, 28.8% survived with severe, moderate or without neurological disorders, and 18.6% remained in a persistent vegetative state. Unconsciousness>48 h after CPR predicted a 60.6-fold (95% CI 14.3287-257.205, p=0.001) and a Glasgow Coma Scale (GCS)<6 points after 72 h a 11.2-fold (CI 95%, 3.55-36.44, p<0.001) risk of poor neurological outcome. Serum levels>or=65 ng/ml for NSE and >or=1.5 microg/l for S-100 increased the risk of death and persistent vegetative state 16.8 (95% CI 2.146-131.520)- and 12.6 (95% CI 1.1093-99.210)-fold, respectively. By combination of the GCS with elevated serum concentrations of both neuroproteins above the cut off levels on third day after CPR a poor neurological outcome was predicted with a specificity of 100%., Conclusion: The combination of GCS with the serum levels of both neuroproteins at 72 h after CPR permit a more reliable prediction of outcome in post arrest coma than the single markers alone, independent of the application of anaesthetic agents.

Background and Purpose: High serum levels of neuron-specific enolase (NSE) and S-100B protein are known to be associated with ischemic brain injury and poor outcome after cardiac arrest. Therapeutic hypothermia has been shown to improve neurological outcome after cardiac arrest. The aim of this study was to evaluate the effect of therapeutic hypothermia on levels of serum NSE and S-100B protein, their time course, and their prognostic value in predicting unfavorable outcome after out-of-hospital cardiac arrest., Methods: Seventy patients resuscitated from ventricular fibrillation were randomly assigned to hypothermia of 33+/-1 degrees C for 24 hours or to normothermia. Serum NSE and S-100B were sampled at 24, 36, and 48 hours after cardiac arrest. Neurological outcome was dichotomized into good or poor at 6 months after cardiac arrest., Results: The levels of NSE (P=0.007 by analysis of variance for repeated measurements) but not S-100B were lower in hypothermia- than normothermia-treated patients. A decrease in NSE values between 24 and 48 hours was observed in 30 of 34 patients (88%) in the hypothermia group and in 16 of 32 patients (50%) in the normothermia group (P<0.001). The decrease in NSE values was associated with good outcome at 6 months after cardiac arrest (P=0.005), recovery of consciousness (P<0.001), and survival for at least 6 months after cardiac arrest (P=0.012)., Conclusions: Decreasing levels of serum NSE but not S-100B over time may indicate selective attenuation of delayed neuronal death by therapeutic hypothermia in victims of cardiac arrest.

Background and Purpose: patients with cardiac arrest have a high mortality and the long-term outcome is doubtful. The prognosis is mainly dependent on clinical parameters. S-100 and neurone specific enolase (NSE) are established biochemical markers of central nervous system (CNS) injury. The purpose of this study was to validate the use of serum determinations of S-100 and NSE with neurological investigations in regard to brain damage and long-term outcome after cardiac arrest., Methods: neurological examinations were performed on 66 patients after cardiac arrest. Serum levels of S-100 and NSE were determined during the first 3 days of post arrest, using commercial luminescent immunoassays (LIAs). The main outcome variable was the Glasgow Outcome Scale (GOS), while secondary variables were the activity of daily living (ADL) index and mini mental state examination (MMSE). Outcome was determined at 1 year., Results: the serum levels of S-100 and NSE were increased during the first 3 days after the arrest and were related to coma depth, time of anoxia and abnormal brain stem reflexes. High levels predicted a poor outcome, according to the GOS (death, vegetative state and severe disability). The prognostic value of the brain damage markers was comparable with that of traditional clinical parameters. None of the secondary outcome variables (ADL and MMSE) was strongly associated with S-100 or NSE., Discussion: the serum levels of S-100 and NSE increased after cardiac arrest due to the anoxic brain damage. The determination of S-100 and NSE can be used as an adjunct to predict long-term outcome after cardiac arrest.

Objective: To examine the prognostic value of serum neuron-specific enolase for early prediction of outcome in patients at risk for anoxic encephalopathy after cardiac arrest., Design: Prospective study., Setting: Coronary intensive care unit of the University of Heidelberg., Patients: Forty-three patients (66.8 +/- 12.7 [SD] yrs, range 33 to 85) who had had either primary or secondary cardiac arrest, followed by cardiopulmonary resuscitation (CPR)., Interventions: Serial blood samples and clinical examinations., Measurements and Main Results: Serum neuron-specific enolase concentrations were determined after CPR on 7 consecutive days. Twenty-five patients remained comatose and subsequently died; 18 patients survived the first 3 months and had no relevant functional deficit at 3-month follow-up. Neuron-specific enolase concentrations were correlated with neurologic outcome. Concentrations of >33 ng/mL predicted persistent coma with a high specificity (100%) and a positive predictive value of 100%. Overall sensitivity was 80%, with a negative predictive value of 78%. Serum concentrations of neuron-specific enolase exceeded this cutoff value no more than 3 days after cardiac arrest in 95% of patients in whom these concentrations had exceeded 33 ng/mL., Conclusions: In patients who have been resuscitated after cardiac arrest, serum neuron-specific enolase concentrations of >33 ng/mL predict persistent coma with a high specificity. Values below this cutoff level do not necessarily indicate complete recovery, because this method has a sensitivity of 80%.

Creatine kinase (CK) and its brain-specific isoenzyme (CK-BB), neuron-specific enolase (NSE), neural cell adhesion molecule (NCAM) and the ions sodium, potassium, chloride and calcium were measured both in CSF and serum and inorganic phosphate in CSF in order to assess their prognostic value in total brain ischemia due to cardiac arrest. The samples were collected at 4, 28 and 76 h after resuscitation. Twenty consecutive patients resuscitated from ventricular fibrillation or asystole were included in the study. Nine of the patients recovered consciousness (recovered) but eleven remained comatose (disabled). The follow-up period was 2 years after which only one patient was still alive. The earliest statistically significant differences between neurologically recovered and disabled patient groups were seen in CSF inorganic phosphate (P = 0.030) already at 4 h and CK-BB (P = 0.046) and NSE (P = 0.020) activity at 28 h. Later, at 76 h after the resuscitation CSF NSE differentiated the groups most clearly (P = 0.014). The values were higher in the disabled patients. A negative correlation between CSF parameters and Glasgow Coma scores was also seen at these timepoints. Statistically significant differences between the groups were seen in both CSF and blood pCO2, pO2, base excess (BE) and actual bicarbonate (HCO3-). CSF or serum NCAM has no prognostic value in anoxic-ischemic coma. The results suggest that in CSF CK-BB and NSE are useful prognostic indicators of hypoxic brain injury when measured 28-76 h after cardiac arrest whereas blood samples have no prognostic value.

The prognostic value of cerebrospinal fluid (CSF) and serum neuron-specific enolase and brain-type creatine kinase isozyme (CK-BB) measurements was studied in 75 consecutive victims of out-of-hospital cardiac arrest. All patients with a CSF neuron-specific enolase level of more than 24 ng/mL 24 hours after cardiac arrest remained unconscious and died. The CSF CK-BB level was as reliable as an index of brain injury. Cerebrospinal fluid neuron-specific enolase, CSF CK-BB and serum neuron-specific enolase levels correlated with the neurological outcome at 3 months. Thus, the analysis of these enzymes in CSF seems to be useful in the early prognostic assessment of cardiac arrest victims.