Neuron-specific Enolase Values Research Articles

Diagnostic value of combined detection of serum neuron-specific enolase and homocysteine in patients with coronary atherosclerosis.

The aim of this paper was to investigate the diagnostic significance and severity assessment of serum neuron-specific enolase (NSE) combined with homocysteine (Hcy) for patients with coronary atherosclerosis (coronary artery disease, CAD). Two hundred sixty-three patients with coronary artery disease were selected as the research group, and 400 healthy individuals who underwent physical examination during the same period were taken as the control group. Electrochemiluminescence immunoassay and biochemical analyzer were employed to detect the serum NSE and Hcy levels of all subjects. The diagnostic value of combined and individual serum NSE and Hcy detection for the combined group was analyzed using the ROC curve. The serum NSE (19.91±9.98 vs. 11.17±2.35) and Hcy levels (15.76±5.37 vs. 10.17±3.71) in the research group were significantly higher than those in the control group, with a statistically significant difference (P<0.05). The serum NSE (16.67±4.02 vs. 18.63±5.49 vs. 20.29±5.87) and Hcy levels (13.28±2.49 vs. 15.56±2.67 vs. 16.66±3.94) gradually increased across groups A, B, and C, and inter-group comparisons showed statistically significant differences (P<0.05). The AUC value of combined serum NSE and Hcy detection for CAD patients was higher (0.879 vs. 0.724 vs. 0.827) than individual NSE and Hcy testing. The specificity of Hcy for the diagnosis of CAD was the highest, reaching 90.3%. The sensitivity of combined NSE and Hcy (82.9%) was higher than the individual testing sensitivity of the two groups. The combined detection of serum NSE and Hcy has high diagnostic efficacy for CAD and provides reference value in assessing the severity of the disease.

Prognostic Value of Neuron-Specific Enolase (NSE) Biomarker in Neonates with Encephalopathy: Review Article

Prognostic Value of Neuron-Specific Enolase (NSE) Biomarker in Neonates with Encephalopathy: Review Article

Normal value of neuron-specific enolase for predicting good neurological outcomes in comatose out-of-hospital cardiac arrest survivors.

Research on prognostic factors for good outcomes in out-of-hospital cardiac arrest (OHCA) survivors is lacking. We assessed whether normal levels of normal neuron-specific enolase (NSE) value would be useful for predicting good neurological outcomes in comatose OHCA survivors treated with targeted temperature management (TTM). This registry-based observational study with consecutive adult (≥18 years) OHCA survivors with TTM who underwent NSE measurement 48 hours after cardiac arrest was conducted from October 2015 to November 2022. Normal NSE values defined as the upper limit of the normal range by the manufacturer (NSE <16.3 μg/L) and guideline-suggested (NSE < 60 μg/L) were examined for good neurologic outcomes, defined as Cerebral Performance Categories ≤2, at 6 months post-survival. Among 226 OHCA survivors with TTM, 200 patients who underwent NSE measurement were enrolled. The manufacturer-suggested normal NSE values (<16.3 μg/L) had a specificity of 99.17% for good neurological outcomes with a very low sensitivity of 12.66%. NSE <60 μg/L predicted good outcomes with a sensitivity of 87.34% and specificity of 72.73%. However, excluding 14 poor-outcome patients who died from multi-organ dysfunction excluding hypoxic brain injury, the sensitivity and specificity of normal NSE values were 12.66% and 99.07% of NSE < 16.3 μg/L, and 87.34% and 82.24% of NSE < 60 μg/L. The manufacturer-suggested normal NSE had high specificity with low sensitivity, but the guideline-suggested normal NSE value had a comparatively low specificity for good outcome prediction in OHCA survivors. Our data demonstrate normal NSE levels can be useful as a tool for multimodal appropriation of good outcome prediction.

The predictive value of delta-like3 and serum NSE in evaluating chemotherapy response and prognosis in patients with advanced small cell lung carcinoma: An observational study.

Lung cancer is one of the most malignant tumors with fastest morbidity and mortality. Small cell lung cancer (SCLC) is the most malignant pathological type of lung cancer with early metastasis and poor prognosis. At present, there is a lack of effective indicators to predict prognosis of SCLC patients. Delta-like 3 protein (DLL3) is selectively expressed on the surface of SCLC and is involved in proliferation and invasion. Neuron-specific enolase (NSE) is an enolase isoenzyme that is generally regarded as a biomarker for SCLC and may correlate with stage of SCLC, prognosis and chemotherapy response. NSE can be influenced by different types of factors. To explore the associations between expression levels of DLL3 in tumor tissues with platinum/etoposide chemotherapy response, and assess the prognostic values of DLL3, NSE and other potential prognostic factors in advanced SCLC patients were herein studied. Ninety-seven patients diagnosed with SCLC in Zhongda Hospital from 2014 to 2020 were enrolled in the study. Serum NSE levels were tested using ELISA methods before any treatment. The expression of DLL3 in tumor tissue was detected by Immunohistochemistry (IHC). We investigated the relationship of DLL3 expression with chemotherapy and survival. Progression free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Multivariate Cox-proportional hazard regression was used to identify predictors of PFS and OS. DLL3 was detected in 84.5% (82/97) of all patients' tumor samples by IHC, mainly located on the surface of SCLC cells. Lower DLL3 expression was associated with longer PFS and better chemotherapy response. OS had no significant differences. Multivariate analysis by Cox Hazard model showed that, high DLL3 expression and maximum tumor size >5 cm were independent risk factors for PFS, where NSE < 35 ng/mL and age < 70 were independent prognostic factors for OS. Early stage was independent prognostic factors for PFS and OS (P < .05 log-rank). DLL3 was expressed in the most of SCLCs. DLL3 expression level in the tumor and NSE level in the serum may be useful biomarkers to predict the prognosis of SCLC. DLL3 may be a potential therapeutic target for SCLC in the future.

Differences in clinical features according to survival and gender in patients admitted for cardiac arrest

Abstract Funding Acknowledgements None. Introduction Cardiac arrest (CA) is a condition with poor vital and neurological prognosis. Although there are widely known clinical features modifying prognosis –such as time to return of spontaneous circulation (ROSC) and neuron-specific enolase values-, there is uncertainty around whether gender, ischemic etiology or classic cardiovascular risk factors may influence in the management and prognosis. Purpose The aim of this study was to analyze the differences in baseline characteristics and management between survivors and non survivors, among patients admitted for CA in an Intensive Cardiac Care Unit. Methods A prospective unicentric registry was performed from January 2010 to December 2021, including all consecutive cardiac arrest patients admitted to an intensive cardiac care unit of a university hospital. Patients were classified into survivors –to hospital discharge- and non-survivors –deceased during hospital admission, irrespective of time of death. Univariate analysis were performed using Chi-square and Student t tests, and logistic regression was used for a multivariate analysis to compare both groups. Results A total of 324 patients were included, mean age 59.7 (DE 12.2) years, 17.9% were women. In-hospital mortality was 42% (136 patients) and 188 patients survived to hospital discharge. Survivors were significantly younger (mean of 57,37 vs 62,98 years) and had less prevalence of diabetes (17 vs 33%) and previous myocardial infarction (15 vs 25%) than non-survivors. Among survivors, there was a higher prevalence of in-hospital CA (26,6 vs 12,5%), CA due to acute coronary syndrome (68,62 vs 57,78%) and shockable first rhythm (90,43 vs 72,06%). They also had shorter ROSC (mean 22,13 vs 34,25 minutes) and no flow times (mean 2,54 vs 5,67 minutes). Gender, arterial hypertension, dyslipidemia and smoking habit did not modify prognosis. When comparing genders, women had significantly less prevalence of smoking habit and previous ischemic heart disease, their time to ROSC was lower and they received less coronary angiographies than men. The multivariate analysis showed significant in-hospital mortality risk increase with age (OR 1,04 per year), ROSC (OR 1,04 per minute) and no-flow (OR 1,09 per minute) times, out of hospital CA (OR 2,26) and non shockable rhythm. Conclusions In a consecutive cohort of 324 patients admitted after cardiac arrest, survivors were significantly younger, and had less prevalence of diabetes mellitus and previous myocardial infarction. In-hospital arrest, shockable rhythm, and shorter ROSC and no-flow times were associated with better survival. No differences in survival were found between genders, although women had significantly shorter resuscitation times.Univariate analysisMultivariate analysis

Markers of brain injury in patients with aneurysmal subarachnoid hemorrhage

Aim To investigate the correlation of serum changes and markers of brain injury (BI) in cerebrospinal fluid (CSF) with postoperative cognitive dysfunction (POCD) in patients with cerebral aneurysmal subarachnoid haemorrhage (aSAH). Methods 120 patients diagnosed with aSAH were included. 3 months after surgery, these patients were divided into a normal cognition group and a cognitive dysfunction (CD) group relying on the Montreal Cognitive Assessment (MoCA) Scale. Results The correlations were analysed between the serological changes and the levels of BI markers, such as neurofilament-light (NF-L) protein, Ubisquitin C-terminal hydrolase L1(UCH-L1), Glial Fibrillary Acidic Protein (GFAP), and neuron specific enolase (NSE) in patients after surgery. Hunt-Hess grading standard was employed to determine the severity of aSAH in patients. The mean values of NF-L, UCH-L1, GFAP, and NSE were (8.2 ± 4.3) pg/mL, (0.7 ± 0.3) ng/mL, (2.2 ± 0.4) ng/mL, and (48.5 ± 10.9) ng/mL in patients with severe aSAH, which were remarkably higher than those in patients with mild aSAH [(3.5 ± 0.7) pg/mL, (0.5 ± 0.2) ng/mL, (1.3 ± 0.7) ng/mL, (30.7 ± 8.2) ng/mL]. The sensitivity, specificity, and accuracy of the combined prediction of four detections for POCD were 90.80%, 84.20%, and 82.80%, respectively, which were greatly higher than those of four independent predictions (p < 0.05). The combined prediction effect of the four items, with the area under the curve (AUC) of 0.938 and the 95% confidence interval (CI) of 0.851-0.926. Conclusions BI markers NF-L, UCH-L1, GFAP, and NSE could be utilized as predictors of POCD in patients with aSAH, deserving a reference value.

Prospective analysis of optic nerve diameter and NSE values in patients with refractory headaches

Purpose: This study aims to investigate the usability of ultrasonographic optic nerve diameter measurement and plasma neuron-specific enolase (NSE) levels in detecting secondary causes of headaches in patients with refractory headaches in emergency department.&#x0D; Materials and Methods: The study was conducted in a university-based adult emergency department over 3 years. Sixty-six consecutive patients presenting to the emergency department with refractory headaches and 50 healthy volunteers for the control group were included. Information recorded included the duration of complaints, type and location of headache, symptoms, co-morbidities, results of imaging studies, optic nerve diameters, results of lactate, arterial blood gas and NSE levels.&#x0D; Results: A total of 66 patients were included, comprising 33 females. The mean age was 43.05 ± 17.06 years. Secondary causes of headache were identified in 45 patients (68.2%). Evaluation of ultrasonographic optic nerve diameter revealed that 17 (25.8%) right and 21 (31.8%) left optic nerve diameters were ≥5 mm. Optic nerve diameter values were significantly higher in patients diagnosed with secondary headache compared to those with primary headache, with no statistically significant difference observed in NSE values. Lactate levels in patients with secondary headaches were significantly higher than those in patients with primary headaches.&#x0D; Conclusion: In patients admitted to the emergency department with refractory headaches and normal imaging, ultrasonographic optic nerve diameter measurement may be preferred as an easily accessible method to guide the detection of secondary causes. NSE was not an effective in the early selection of patients with secondary headaches.

Prognostic value of tumor markers ProGRP, NSE and CYFRA 21-1 in patients with small cell lung cancer and chemotherapy-induced remission.

Despite successful response to first line therapy, patients with small-cell lung cancer (SCLC) often suffer from early relapses and disease progression. To investigate the relevance of serum tumor markers for estimation of prognosis at several time points during the course of disease. In a prospective, single-center study, serial assessments of progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), cytokeratin-19 fragments (CYFRA 21-1) and carcino-embryogenic antigen (CEA) were performed during and after chemotherapy in 232 SCLC patients, and correlated with therapy response and overall survival (OS). ProGRP, NSE and CYFRA 21-1 levels decreased quickly after the first chemotherapy cycle and correlated well with the radiological response. Either as single markers or in combination they provided valuable prognostic information regarding OS at all timepoints investigated: prior to first-line therapy, after two treatment cycles in patients with successful response to first-line therapy, and prior to the start of second-line therapy. Furthermore, they were useful for continuous monitoring during and after therapy and often indicated progressive disease several months ahead of radiological changes. The results indicate the great potential of ProGRP, NSE and CYFRA 21-1 for estimating prognosis and monitoring of SCLC patients throughout the course of the disease.

Meta-analysis of evaluating neuron specific enolase as a serum biomarker for sepsis-associated encephalopathy

IntroductionBrain dysfunction in sepsis is known as Sepsis-associated encephalopathy (SAE), which often results in severe cognitive and neurological sequelae and increases the risk of death. Neuron specific enolase (NSE) may serve as an important neurocritical biomarker for detection and longitudinal monitoring in SAE patients. Our Meta-analysis aimed to explore the diagnostic and prognostic value of serum NSE in SAE patients. Currently, no systematic Review and Meta-analysis have been assessed that NSE as a biomarker of SAE. MethodsThe study protocol was registered in the PROSPERO database (CRD42023398736) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We conducted a systematic review and Meta-analysis to evaluate the serum NSE’s diagnostic accuracy for SAE and prognostic strength for probability of death of septic patients. We systematic searched electronic bibliographic databases from PubMed, MEDLINE, Web of Science, Embase, Cochrane databases, CNKI, CQVIP, and WFSD. QUADAS-2 assessment tool was used to evaluate quality and risk of bias of the selected studies. Subgroup analyses, funnel plots, sensitivity analyses were also carried out. Review Manager version 5.4 and Stata16.0. was used for statistical analysis. ResultsThis Meta-analysis included 22 studies with 1361 serum samples from SAE patients and 1580 serum samples from no-encephalopathy septic (NE) patients. The Meta-analysis showed that individuals with SAE had higher serum NSE level than NE controls (SMD 1.93 (95 % CI 1.51–2.35), P < 0.00001). In addition, there are 948 serum samples from survival septic patients and 446 serum samples from non-survival septic patients, septic patients with survival outcomes had lower serum NSE levels than those with death outcomes (SMD −1.87 (95 % CI −2.43 to −1.32), P < 0.00001). ConclusionOur Meta-analysis reveals a significant association between elevated NSE concentrations and the increased likelihood of concomitant SAE and mortality during septic patients. This comprehensive analysis will equip ICU physicians with up-to-date insights to accurately identify patients at risk of SAE and implement appropriate intervention strategies to mitigate morbidity and improve neurological outcomes. However, it is important to note that the presence of substantial heterogeneity among studies poses challenges in determining the most effective discrimination cutoff values and optimal sampling collection time.

Early systemic insults following traumatic brain injury: association with biomarker profiles, therapy for intracranial hypertension, and neurological outcomes—an analysis of CENTER-TBI data

PurposeWe analysed the impact of early systemic insults (hypoxemia and hypotension, SIs) on brain injury biomarker profiles, acute care requirements during intensive care unit (ICU) stay, and 6-month outcomes in patients with traumatic brain injury (TBI).MethodsFrom patients recruited to the Collaborative European neurotrauma effectiveness research in TBI (CENTER-TBI) study, we documented the prevalence and risk factors for SIs and analysed their effect on the levels of brain injury biomarkers [S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and protein Tau], critical care needs, and 6-month outcomes [Glasgow Outcome Scale Extended (GOSE)].ResultsAmong 1695 TBI patients, 24.5% had SIs: 16.1% had hypoxemia, 15.2% had hypotension, and 6.8% had both. Biomarkers differed by SI category, with higher S100B, Tau, UCH-L1, NSE and NfL values in patients with hypotension or both SIs. The ratio of neural to glial injury (quantified as UCH-L1/GFAP and Tau/GFAP ratios) was higher in patients with hypotension than in those with no SIs or hypoxia alone. At 6 months, 380 patients died (22%), and 759 (45%) had GOSE ≤ 4. Patients who experienced at least one SI had higher mortality than those who did not (31.8% vs. 19%, p < 0.001).ConclusionThough less frequent than previously described, SIs in TBI patients are associated with higher release of neuronal than glial injury biomarkers and with increased requirements for ICU therapies aimed at reducing intracranial hypertension. Hypotension or combined SIs are significantly associated with adverse 6-month outcomes. Current criteria for hypotension may lead to higher biomarker levels and more negative outcomes than those for hypoxemia suggesting a need to revisit pressure targets in the prehospital settings.

The Correlation Between Serum Tumor Markers and Liver Metastasis of Lung Cancer

Purpose: To investigate the relationship between the changes of lactate dehydrogenase (LDH), neuron‐specific enolase (NSE), keratin‐19 fragment antigen 21‐1 (cyfra21‐1), and liver metastases of lung cancer.Methods: Eighty patients who had lung cancer that had spread to their liver diagnosed in our hospital from October 2021 to October 2023 (Group A), 80 individuals with advanced lung cancer who have metastasized to other sites (Group B), and 80 individuals with lung cancer who have not spread (control group) were selected as the study objects. LDH, NSE, and serum cyfra21‐1 levels of patients in the three groups were detected, and pathological results were used as the diagnostic gold standard. ROC curves were drawn to examine the clinical value of NSE, cyfra21‐1, and LDH levels in the distinct types of lung cancer identification of liver metastases.Results: There was no remarkable variation in pathological types among the three groups (p &gt; 0.05), but there were remarkable variations in TNM stage and lymph node metastasis among the three groups (p &lt; 0.05). The levels of cyfra21‐1, NSE, and LDH in Group A and Group B were greater compared to those in the control group (p &lt; 0.05), and the levels of cyfra21‐1, NSE, and LDH in Group A were greater compared to those in Group B (p &lt; 0.05). The critical value, sensitivity, specificity, and area under the curve (AUC) of serum cyfra21‐1 in the distinct identification of liver metastasis of lung cancer were 8.22 ng/mL, 37.42%, 65.18%, and 0.508, respectively. The critical value, sensitivity, specificity, and AUC of NSE for distinct types of lung cancer identification of liver metastases were 23.96 ng/mL, 64.56%, 81.23%, and 0.723, respectively. The critical value, sensitivity, specificity, and AUC of LDH for differential diagnosis of liver metastasis of lung cancer were 304.78 U/L, 75.65%, 85.73%, and 0.821.Conclusion: The serum levels of NSE, cyfra21‐1, and LDH in patients with liver metastasis of lung cancer were remarkably greater compared to patients without liver metastasis, which can be useful as a clinical auxiliary in determining lung cancer metastasis.

Retracted: Related Factors and a Threshold of the Maximum Neuron-Specific Enolase Value Affecting the Prognosis of Patients with Aneurysmal Subarachnoid Hemorrhage

Retracted: Related Factors and a Threshold of the Maximum Neuron-Specific Enolase Value Affecting the Prognosis of Patients with Aneurysmal Subarachnoid Hemorrhage

In-hospital and long term neurological outcome prognostication using an algorithm based on the analysis of ventricular fibrillation from the EKG of patients with sudden cardiac death (AWAKE)

Abstract Background Sudden cardiac death (SCD) is a leading cause of mortality and carries a dismal neurological outcome (NO) among patients admitted alive to acute cardiac care units (ACCU). A big share of SCD are found in ventricular fibrillation (VF). VF waveform is dynamic and it can be characterized by spectral analysis at the very time of ACCU admission. Purpose To validate in a multicenter cohort an algorithm based on spectral variables of VF waveform to early predict neurological outcome at hospital discharge and follow-up, and to compare its performance with currently established prognostic tools. Methods Multicenter study in which 5 hospitals recruited patients, resuscitated from SCD due to VF whose EKG was available, and admitted to ACCU with expertise in SCD. EKG tracings were scanned and analyzed with a custom MATLAB script delivering spectral variables to be entered in an algorithm to predict NO. NO was assessed by Cerebral Performance Category (CPC) during admission and after a minimum 6-month follow-up period. The primary endpoint was favorable neurological outcome (FNO, defined as CPC 1 and 2) during hospital admission, and the secondary endpoint was FNO at long-term follow-up. Statistical data were analyzed with SPSS and EPIDAT. Results We included 168 patients out of 678 screened in participant hospitals among admissions from 2007 to 2022. The main cause of exclusion was a rhythm different from VF at the time of medical assistance (n=329, 48%) or VF EKG unavailable (n=151, 22%). Ninety-five patients (57%) were admitted in comatose status (Glasgow &amp;lt;9). Baseline characteristics are depicted in Picture 1. FNO during admission was documented in 136 patients (81%). Twenty-nine patients (17%) died during hospitalization. A spectral-based model using VF tracings early predicted FNO with an area under the curve (AUC) value of 0.85 (CI95% 0.77-0.93). There was overlap with the predictive performance obtained with the peak value of neuron-specific enolase (NSE) (0.85; CI95% 0.74-0.95) (Picture 2, A). Other prognostic tools showed similar or lower diagnostic yield and results were obtained at a later time after admission (Picture 2, B,D). Long-term follow-up was obtained for 166 cases (2 foreign patients were impossible to retrieve). Patients discharged alive were followed for 17 (± standard deviation 21) months. FNO was present in 136 (82%). The spectral-based model predicted FNO with AUC 0.83 (CI95% 0.74-0.92), similar to NSE (AUC 0.87, CI95% 0.77-0.97) (Picture 2, C). Other tools performed in follow-up similar to during admission (Picture 2, D). CONCLUSION A model based on VF spectral analysis predicts neurological outcome after SCD with an accuracy similar to current validated tools, but with no requirement for drug withdrawal or waiting period in comatose patients. This model estimates outcomes at the earliest moment of hospital admission and its predictions remain valid in the long run.Baseline characteristicsDiagnostic yield of model vs other tools

Abstract 296: Comparison of Prognostic Performance Using Quantitative Analysis of Head Computed Tomography and Apparent Diffusion Coefficient Imaging Before Target Temperature Management in Out-of-Hospital Cardiac Arrest Survivors

Aim: We compared head computed tomography (HCT) and diffusion-weighted magnetic resonance imaging (DW-MRI) findings before target temperature management (TTM) to predict neurological outcomes in out-of-hospital cardiac arrest survivors. Methods: Using prospectively collected data from a TTM registry, we included patients who underwent HCT and DW-MRI within 6 h of return of spontaneous circulation (ROSC). We examined the gray-to-white matter ratio (GWR) on HCT and apparent diffusion coefficient (ADC) values obtained through voxel-based analysis of DW-MRI. We analyzed the mean ADC value and the % voxels of ADC thresholds (percentage of voxels below ADC thresholds per total voxel) at 50-step intervals ranging from 200 to 1200 х 10 -6 mm/s, identifying thresholds that differentiate between good and poor neurological outcomes. Additionally, we analyzed the combination of pupillary light reflex (PLR) and neuron-specific enolase (NSE) values acquired at the same time points to predict the neurological outcomes. The primary outcome measure was the dichotomized cerebral performance category (CPC) at six months, defined as good (CPC 1-2) or poor (CPC 3-5). Results: Of 131 patients (26% female), 74 (57%) had poor outcomes. The time from ROSC to HCT and DW-MRI scans was 1.7h and 3.2h, respectively. The group with a good outcome had higher GWR (1.26 vs. 1.20) and mean ADC (787.10 vs. 697.49) values, but lower values in all ranges (250-1150) of ADC values (all P&lt;0.001). Mean ADC and ADC values in the range of 350-650 demonstrated better predictive performance for poor outcomes than the GWR (P &lt; 0.05). The mean ADC value had the highest sensitivity of 51.3% (95% CI 39.4-63.1; cutoff value ≤ 739.2 х 10 –6 mm 2 /s) when the false positive rate (FPR) was 0%. Furthermore, when combined with PLR and NSE values, the prognostic performance was significantly improved compared to using Mean ADC alone (0.83 vs 0.92; P&lt;0.01). Conclusions: In this cohort study, early voxel-based quantitative ADC analysis after ROSC (i.e., before TTM) was associated with poor neurological outcomes 6 months after cardiac arrest. We found that the Mean ADC value showed the highest sensitivity when the FPR was 0% and that combining the NSE and PLR values resulted in an even better prognostic performance.

Abstract 110: Brain Injury Biomarkers Are Associated With Poor Neurological Outcomes Within 24 Hours After Refractory VT/VF Cardiac Arrest Requiring Extracorporeal Cardiopulmonary Resuscitation

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) is an emerging method that improve survival after refractory VF/VT cardiac arrest. Neuron-specific enolase (NSE) and S-100B are used to predict neurological outcome; however, it is unclear the reliability and earliest time point during ECPR. Methods: Single-center, retrospective cohort study included OHCA patients who underwent ECPR at the University of Minnesota between December 2015 and January 2023. NSE and S100B levels were obtained at admission, at 12 and 24h after ROSC in a total of 361 unconscious patients. The primary outcome was poor neurological outcome (defined as CPC 3-5) at hospital discharge. We evaluated the optimal cut-off levels for NSE and S100B by maximizing the Youden index and ROC analyses for poor clinical results. Finally, NSE and S100B at 12h and 24h were added to a multivariable logistic model (age, sex, bystander and witnessed). Results: Of 361 patients, 170 survived to hospital admission. Of these 85% (145/170) survived neurologically favorable. Mean (SD) NSE (ng/mL) values were significantly higher in the CPC 3-5 group at every time point, 52.3 (53) vs 21.1 (12) on admission; 92.8 (92) vs 20 (10) after 12h; 107.1(94.4) vs 21.5 (12.9) after 24h; p&lt;0.01 at all time points. Again, mean (SD) S100B (ng/L) values were significantly higher in the CPC 3-5 group at every time point 3912 (990) vs 986 (920) on admission; 3975 (4972) vs 272.2 (209) after 12h; 4454 (7300) vs 192 (239) after 24h; p&lt;0.01 at all time points. At 24h, NSE and S100B significantly predicted poor neurological outcome with AUC 0.92; 95%CI:0.87-0.95 (optimal NSE cut-off value of 47) and 0.91; 95%CI: 0.87-0.95 (optimal cut-off S100B value of 354), respectively. High concentrations of both biomarkers at 24h (NSE: odds ratio [OR] 2.4 per 1 ng/mL, p&lt;0.001; S100B: odds ratio [OR] 1.1 per 1 ng/L, p&lt;0.05) were independent for poor outcome in a multivariate analysis. Additionally, the combination of both markers (AUC, 0.94; 95%CI: 0.91-0.97) showed significantly higher predictive performance than when using them individually. Conclusions: By using serial measurements, high NSE and S100B levels may help early predict progression to poor neurological outcome in OHCA survivors requiring ECPR in the first 24h after ROSC.

Quantitative analysis of early apparent diffusion coefficient values from MRIs for predicting neurological prognosis in survivors of out-of-hospital cardiac arrest: an observational study

BackgroundThis study aimed to quantitatively analyse ultra-early brain diffusion-weighted magnetic resonance imaging (DW-MRI) findings to determine the apparent diffusion coefficient (ADC) threshold associated with neurological outcomes in comatose survivors of out-of-hospital cardiac arrest (OHCA).MethodsThis retrospective study included adult survivors of comatose OHCA who underwent DW-MRI imaging scans using a 3-T MRI scanner within 6 h of the return of spontaneous circulation (ROSC). We investigated the association between neurological outcomes and ADC values obtained through voxel-based analysis on DW-MRI. Additionally, we constructed multivariable logistic regression models with pupillary light reflex (PLR), serum neuron-specific enolase (NSE), and ADC values as independent variables to predict poor neurological outcomes. The primary outcome was poor neurological outcome 6 months after ROSC, determined by the Cerebral Performance Category 3–5.ResultsOverall, 131 patients (26% female) were analysed, of whom 74 (57%) showed poor neurological outcomes. The group with a poor neurological outcome had lower mean whole brain ADC values (739.1 vs. 787.1 × 10–6 mm/s) and higher percentages of voxels with ADC below threshold in all ranges (250–1150) (all P < 0.001). The mean whole brain ADC values (area under the receiver operating characteristic curve [AUC] 0.83) and the percentage of voxels with ADC below 600 (AUC 0.81) had the highest sensitivity of 51% (95% confidence interval [CI] 39.4–63.1; cut-off value ≤ 739.2 × 10−6 mm2/s and > 17.2%, respectively) when the false positive rate (FPR) was 0%. In the multivariable model, which also included PLR, NSE, and mean whole brain ADC values, poor neurological outcome was predicted with the highest accuracy (AUC 0.91; 51% sensitivity). This model showed more accurate prediction and sensitivity at an FPR of 0% than did the combination of PLR and NSE (AUC 0.86; 30% sensitivity; P = 0.03).ConclusionsIn this cohort study, early voxel-based quantitative ADC analysis after ROSC was associated with poor neurological outcomes 6 months after cardiac arrest. The mean whole brain ADC value demonstrated the highest sensitivity when the FPR was 0%, and including it in the multivariable model improved the prediction of poor neurological outcomes.

Correlation Between Quantitative Background Suppression on EEG and Serum NSE in Patients With Hypoxic-ischemic Encephalopathy.

We evaluated the correlation between quantitative background activities on electroencephalography (EEG) and serum neuron specific enolase (NSE) in patients with hypoxic-ischemic encephalopathy as well as a diagnostic value of prognostication. This retrospective cohort study enrolled patients with return of spontaneous circulation after cardiac arrest from March 2010 to March 2020. The inclusion criteria were (1) older than the age of 16 years and (2) patients who had both EEG and NSE. The median time for EEG and NSE were 3 days (interquartile range 2-5 days) and 3 days (interquartile range 2-4 days), respectively. The quantification of background activity was conducted with the suppression ratio (SR). We used a machine learning (eXtreme Gradient Boosting algorithm) to evaluate whether the SR could improve the accuracy of prognostication. We enrolled 151 patients. The receiver operating characteristic analysis revealed a cut-off value of serum NSE and the SR for poor outcome, serum NSE (>31.9 μg/L, area under curve [AUC] = 0.88), and the SR (>21.5%, AUC = 0.75 in the right hemisphere, >34.4%, AUC = 0.76 in the left hemisphere). There was a significant positive correlation between the severity of SR and the level of NSE (ρ = 0.57, p < 0.0001 for the right hemisphere, ρ = 0.58, p < 0.0001 for the left hemisphere). The SR showed an excellent diagnostic value for predicting poor outcome (93% specificity, 60% sensitivity in the right hemisphere and 93% specificity, 58% sensitivity in the left hemisphere). With machine learning analysis, there was an increment in distinguishing the neurological outcome by adding SR on clinical factors. The SR showed a positive correlation with the level of serum NSE. The diagnostic value of the SR for predicting poor outcome was excellent, suggesting that it can be a possible biomarker for neuroprognostication in patients with hypoxic-ischemic encephalopathy.

Increased Neuron-Specific Enolase Level Predicts Symptomatic Intracranial Hemorrhage in Patients with Ischemic Stroke Treated with Endovascular Treatment

Neuron-specific enolase (NSE), which is a highly specific marker for neurons, could be a predictor for prognosis in patients with symptomatic intracranial hemorrhage (sICH) with acute ischemic stroke who are receiving endovascular treatment (EVT). This study aimed to investigate the relationship between NSE and sICH in patients with acute anterior circulation stroke undergoing EVT. A total of 215 consecutive patients with acute stroke treated with EVT were included. Patients with stroke and acute anterior circulation occlusion, receiving EVT treated at our hospital, were enrolled between January 2017 and August 2021. NSE level was measured on arrival at the neurology intensive care unit after EVT. The patients were divided into 2 groups according to whether sICH was present. Univariate and multivariate analyses were performed. NSE level was also incorporated into the TAG score (modified Thrombolysis in Cerebral Infarction score, Alberta Stroke Program Early CT Score, and glucose level), which was developed as a scoring system to predict sICH, and the prediction capability was compared with the TAG score alone. Causal inference was performed using the package DoWhy in Python to evaluate the causal relationship between NSE and sICH. The area under the curve (AUC) value of NSE showed moderate accuracy, with an AUC value of 0.729 (95% confidence interval, 0.655-0.795; P < 0.001). The NSE cutoff value was set at 23.88 ng/mL. When the NSE level ≥23.88 ng/mL, the sensitivity was 58.33% and the specificity was 78.72% (P < 0.001). The AUC for the TAG+ NSE score was 0.801 compared with an AUC of 0.632 for the TAG score (Z= 2.034; P= 0.042). A causal inference model using the DoWhy library shows a proportional relationship between NSE and the diagnosis of sICH. This study is the first to show that increased NSE level is an independent predictor of sICH in patients with acute anterior circulation stroke who are undergoing endovascular treatment.

Clinical value of combined serum CA125, NSE and 24-hour urine VMA for the prediction of recurrence in children with neuroblastoma

BackgroundIn this study, we intend to retrospectively analyze the clinical data of postoperative neuroblastoma children, including the results of follow-up examinations and laboratory tests, to explore the clinical value of combined serum Carbohydrate antigen 125 (CA125), neuron-specific enolase (NSE) and 24-hour urine vanillylmandelic acid (VMA) levels at baseline for the prediction of recurrence in children with neuroblastoma.Methods265 children with neuroblastoma were successfully followed up, including 163 cases without recurrence (non-recurrence group) and 102 cases with recurrence (recurrence group). The levels of 24-hour urine VMA were determined using spectrophotometric methods. Additionally, the serum levels of CA125 and NSE were measured using electrochemiluminescence immunoassay.ResultsThe serum CA125, NSE and 24-hour urine VMA levels were significantly higher in the recurrence group than in the non-recurrence group. It demonstrated a significant positive correlation between the levels of serum CA125, NSE, and 24-hour urine VMA in all children with neuroblastoma. All children in stage IV of neuroblastoma had the highest level of serum CA125, NSE and 24-hour urine VMA and vice versa. The combined CA125, NSE and VMA had significantly better sensitivity and specificity than an individual marker.ConclusionsCombined serum CA125, NSE and 24-hour urine VMA had the potential to predict neuroblastoma recurrence more effectively.

Prognosticating acute traumatic spinal cord injury using Neurofilament (NF), Neuron Specific Enolase (NSE), Matrix Metalloproteinases (MMPs), and S-100B as biomarkers.

Spinal cord injury (SCI) can result in lifelong disability. Currently, the literature suggests that biomarkers are helpful in prognosticating SCI, but there is no specific biomarker to date. This is the first study that predicted the prognosis dynamically using biomarkers. To elucidate the role of biomarkers in prognosticating acute traumatic SCI. Blood samples were obtained from 35 patients of acute traumatic SCI at presentation, immediate post-op, and at 6 weeks. At 6 months follow-up, patients were divided into two groups, i.e, improved and non-improved based on the improvement in the ASIA grade compared to presentation. A non-parametric test was used for comparing mean NSE, MMP-2, S100-B, and NF serum levels at presentation, immediate post-op, and 6 weeks post-op follow-up between the two groups. There was a significant difference (p = 0.03) in the NF values at presentation between the two groups. The difference of NSE values at 6 weeks was also significant(p = 0.016) between the two groups. S-100B levels were also significantly different between both groups at presentation (p=0.016), and at the immediate post-op stage (p=0.007). MMP-2 levels neither displayed any specific trend nor any significant difference between the two groups. Higher NF values at presentation, and higher S-100B levels at presentation and immediate post-operative period correlated with poor outcome. Also, increased NSE valuesafter surgery are indicativeof no improvement. These levels can be used at various stages to predict the prognosis. However, further studies are required on this topic extensively to know the exact cut-off values of these markers to predict the prognosis accurately. REF/2020/01/030616.