Serum Neuron-specific Enolase Research Articles

Association of Serum Neuron-Specific Enolase and C-Reactive Protein With Disease Location and Endoscopic Inflammation Degree in Patients With Crohn's Disease.

Objective: The objective of this study was to explore the association between serum markers neuron-specific enolase (NSE) and C-reactive protein (CRP) with intestinal lesion location and degree of inflammation in patients with Crohn's disease (CD).Design: The levels of serum NSE, CRP, and fecal calprotectin (FC) in patients with CD were analyzed retrospectively. The severity of inflammatory lesions in the intestinal wall was accessed using the Simple Endoscopic Score for Crohn's disease (SES-CD).Results: The levels of NSE in patients with CD were higher than those of healthy individuals (14.87 vs. 12.68 ng/ml, P < 0.001). The levels of CRP in patients with CD were higher than those of healthy individuals (12.30 vs. 3.40 mg/l, P < 0.001). The FC levels in patients with CD were higher than those of patients with non-inflammatory bowel disease (1,143.90 vs. 114.21 μg/g, P < 0.05). The levels of NSE in CD with ileal lesions and simultaneous ileal and colon lesions were significantly higher than those in patients with CD with colonic lesions. However, the CRP was higher in patients with colonic lesions than those with ileal lesions. The levels of NSE in patients with severe inflammation were higher than those in patients with moderate inflammation (15.95 vs. 13.89 ng/ml, P < 0.05). Similarly, the NSE levels in patients with CD with severe inflammation were higher than those in patients with CD with mild inflammation (15.95 vs. 13.53 ng/mL, P < 0.05). The levels of CRP in severe inflammation were higher than those in moderate inflammation (29.80 vs. 19.60 mg/l, P < 0.05). In addition, the CRP levels in severe inflammation were higher than those in mild inflammation (29.80 vs. 5.86 mg/l, P < 0.05). ROC curve analysis showed that when NSE was combined with CRP for distinguishing between patients with CD and those without CD, sensitivity increased to 80.41%, specificity increased to 74.66%, and a highest AUC was equal to 0.843.Conclusion: Our study shows that serum NSE and CRP can be used to assess the severity of CD as well as the location of intestinal involvement. Therefore, NSE and CRP could be used as the non-invasive tests in detecting the location and severity of disease in patients with CD in daily routine practice.

Prognostic value of neuron-specific enolase in patients with advanced and metastatic non-neuroendocrine non-small cell lung cancer.

Background: Increased serum neuron-specific enolase (NSE) level was found in a substantial proportion (30–69%) of patients with non-small-cell lung cancer (NSCLC), but little was known about the clinical properties of NSE in NSCLC.Objective: We aimed to assess the level of serum NSE to predict prognosis and treatment response in patients with advanced or metastatic non-neuroendocrine NSCLC.Methods: We retrospectively analyzed 363 patients with advanced and metastatic NSCLC between January 2011 and October 2016. The serum NSE level was measured before initiation of treatment.Results: Patients with high NSE level (≥26.1 ng/ml) showed significantly shorter progression-free survival (PFS) (5.69 vs 8.09 months; P=0.02) and significantly shorter overall survival (OS) than patients with low NSE level (11.41 vs 24.31 months; P=0.01).NSE level was an independent prognostic factor for short PFS (univariate analysis, hazard ratio [HR] = 2.40 (1.71–3.38), P<0.001; multivariate analysis, [HR] = 1.81 (1.28–2.56), P=0.001) and OS (univariate analysis, [HR] = 2.40 (1.71–3.37), P<0.001; multivariate analysis, [HR] = 1.76 (1.24–2.50), P=0.002).Conclusion: The survival of NSCLC patients with high serum NSE level was shorter than that of NSCLC patients with low serum NSE levels. Serum NSE level was a predictor of treatment response and an independent prognostic factor.

Protective effect and mechanism of Angong Niuhuang pill in sepsis-associated brain dysfunction of rats

To observe the protective effect of Angong Niuhuang pill on brain function of rats with sepsis, explore its protective mechanism, and provide the experimental basis for clinical application of Angong Niuhuang pill in the treatment of sepsis-associated encephalopathy (SAE). Thirty male Sprague-Dawley (SD) rats were divided into sham operation group, sepsis model group and Angong Niuhuang pill group according to random number table method, with 10 rats in each group. The sepsis model was established by cecal ligation and puncture (CLP); rats in sham operation group received open and closed abdomen. The rats in the Angong Niuhuang pill group were given Angong Niuhuang pill (0.3 g/kg) by gastric irrigation daily for 3 days before CLP, and the drugs were administrated 12 hours after modeling again. After 24 hours of CLP, the neuroreflex scores were evaluated, white blood cell count (WBC), the levels of serum neuron-specific enolase (NSE) and S100β were detected. Then the brain tissue was harvested. After hematoxylin-eosin (HE) staining, the pathological changes of brain tissue were observed under the light microscope. The mRNA expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in brain tissue were detected by polymerase chain reaction. Compared with the sham operation group, the total score of neuroreflex scores in the sepsis model group and the Angong Niuhuang pill group were significantly reduced (4.43±1.40, 6.57±1.90 vs. 9.40±0.84, both P < 0.05), WBC, serum NSE, S100β were significantly increased [WBC (×109/L): 8.07±1.32, 5.84±0.94 vs. 3.60±0.32; NSE (μg/L): 1.04±0.14, 0.61±0.07 vs. 0.16±0.04; S100β (ng/L): 255.624±30.25, 97.72±15.41 vs. 46.88±12.03, all P < 0.05], and the mRNA expressions of IL-6 and TNF-α in brain tissue were significantly increased [IL-6 mRNA (2-ΔΔCt): 5.668±2.195, 3.605±1.014 vs. 0.997±0.329; TNF-α mRNA (2-ΔΔCt): 18.996±0.913, 1.746±0.710 vs. 0.674±0.132, all P < 0.05]. Compared with the sepsis model group, the total score of neuroreflex scores in the Angong Niuhuang pill group was significantly increased (6.57±1.90 vs. 4.43±1.40, P < 0.05), WBC, serum NSE, S100β concentration, and the mRNA expressions of IL-6 and TNF-α in the brain were significantly reduced [WBC (×109/L): 5.84±0.94 vs. 8.07±1.32, NSE (μg/L): 0.61±0.07 vs. 1.04±0.14, S100β (ng/L): 97.72±15.41 vs. 255.62±30.25, IL-6 mRNA (2-ΔΔCt): 3.605±1.014 vs. 5.668±2.195, TNF-α mRNA (2-ΔΔCt): 1.746±0.710 vs. 18.996±0.913, all P < 0.05]. Brain histopathological observation showed that the hippocampal neurons in the sepsis model group were disordered arrangement, a large number of neuronal nuclei were contracted, and the tissue was loose with obvious edema. Compared with the sepsis model group, the Angong Niuhuang pill group had less nuclear shrinkage and tissue edema. The pretreatment of the Angong Niuhuang pill can improve the brain dysfunction of septic rats and reduce the expression of pro-inflammatory cytokines in the brain. It is speculated that the Angong Niuhuang pill can protect the brain function in sepsis by inhibiting the inflammatory reaction in the brain.

Optimized Clustering Algorithm for Comparative Analysis of Different Prenatal Corticosteroid Neurological Deficits in Premature Infants through Magnetic Reasoning Imaging (MRI).

Objective This study aimed to explore the application of different prenatal corticosteroids in the assessment of neurological deficits and prognosis in premature infants through Magnetic Reasoning Imaging (MRI) under optimized cluster algorithm. Methods 100 pregnant women with threatened preterm labor were retrospectively analyzed, in which 38 pregnant women with lasting threatened preterm labor (group A) were treated with multiple courses of antenatal corticosteroids (dexamethasone treatment) and 62 cases of pregnant women with threatened preterm labor (group B) were treated with single course of dexamethasone treatment. Craniocerebral MRI images based on optimal clustering algorithm were used to examine neonates. Neonatal hypoxic-ischemic encephalopathy (HIE) rate, serum neuron-specific enolase (NSE) concentration, neonatal behavioral neurological score (NBNA), respiratory distress syndrome (RDS) rate, perinatal mortality, neonatal birth weight, and maternal complications rate of two groups were compared. Results Compared with other traditional image segmentation algorithms, this algorithm had the best segmentation effect, the shortest running time (1.43 s), the least number of iterations (5 times), and the highest segmentation accuracy (97.98%). There was no significant difference in the HIE rate, serum NSE concentration, NBNA score, RDS score, and perinatal mortality in group A and group B (P > 0.05). Compared with group B, neonates' body weight in group A was decreased, while the maternal complication rate in group A was increased (P < 0.05). Conclusion MRI images based on optimized clustering algorithm can be used in the diagnosis of neonatal hypoxic-ischemic encephalopathy. There is no significant difference in the application of different antenatal corticosteroids affecting premature nerve function defect and prognosis, but multiple courses of antenatal corticosteroids can affect neonatal body mass and increased maternal complications to a certain extent; therefore, before threatened premature delivery treatment, the pros and cons of multiple courses of antenatal corticosteroids should fully be considered and in the treatment, measures should be actively taken to alleviate the side effect.

The automated processing algorithm to correct the test result of serum neuron-specific enolase affected by specimen hemolysis.

IntroductionSerum neuron‐specific enolase (NSE) is an important tumor marker for small cell lung cancer and neuroblastoma. However, the test of serum NSE compromised by specimen hemolysis is presented as a falsely higher result, which seriously disturbs clinical decision. This study aimed to establish a solution integrated with laboratory information system to clear the bias from hemolysis on serum NSE test.MethodsThe reference range of serum hemolysis index (HI) was first established, and specimen hemolysis rate was compared between HI test and visual observation. NSE concentration in serum pool with normal HI was spiked with serial diluted lysates from red blood cells to deduce individual corrective equation. The agreement between individual corrective equation and original NSE test was assayed by Bland and Altman plots.ResultsThe high HI existed in 32.6% of specimens from patients. The NSE median of hemolyzed specimens was significant higher than the baseline (p = 0.038), while the corrected NSE median had no difference compared with the baseline (p = 0.757). The mean difference of corrected NSE and initial NSE was 1.92%, the SD of difference was 5.23%, and furthermore, the difference was independent of tendency of HI (Spearman r = −0.069, p = 0.640). The 95% confidence interval of mean difference (from −8.33% to 12.17%) was less than the acceptable bias range (±20%).ConclusionThe agreement between individual correction equation and NSE assay was satisfied. Our automated processing algorithm for serum NSE could provide efficient management of posttest data and correct positive bias from specimen hemolysis.

Circulating progastrin-releasing peptide in the diagnosis of Small Cell Lung Cancer (SCLC) and in therapeutic monitoring

Introduction: Progastrin-releasing peptide (proGRP), a precursor of GRP, has been recently reported as a putative circulating biomarker for differential diagnosis between non–small cell lung cancer (NSCLC) and SCLC. We evaluated the diagnostic effectiveness of proGRP to differentiate patients with NSCLC and SCLC and the usefulness of combined measurement of proGRP and neuron-specific enolase (NSE) for diagnosing SCLC.&#x0D; Methods: Serum proGRP, NSE, cytokeratin 19 fragment 21-1 (CYFRA 21.1), squamous cell carcinoma antigen (SCC Ag) and carcinoembryonic antigen (CEA) were prospectively collected and measured in patients with a new diagnosis of lung cancer. Serum proGRP was also measured in healthy subjects. The serum proGRP, NSE, CYFRA 21.1 and CEA concentrations were determined by an electrochemiluminescence immunoassay and the serum SCC Ag concentration was determined by an automated immunofluorescence assay. Differences between proGRP and NSE in patients with SCLC and NSCLC were evaluated and compared using Mann-Whitney test.&#x0D; Results: A total of 77 patients affected by SCLC (n = 17) and NSCLC (n = 60) were enrolled in the present study. Moreover, 50 cases of healthy subjects were analyzed for proGRP. SCLC patients showed a significantly higher proGRP (1,484 pg/mL; range 168-3,777) levels compared to NSCLC patients (45 pg/mL; range 31.7-60.6), p&lt;0.0001. In healthy subjects the median proGRP level was 36.1 (28.8-43.5) pg/mL, significantly lower than SCLC patients. ProGRP showed a higher specificity when compared to NSE, with a difference in proportion of 47.5% (95% confidence interval 32.5% to 62.5%, p&lt;0.001). Serial measurements of proGRP in SCLC patients showed a decrease in responsive chemotherapy patients.

Effect of acupuncture combined with rehabilitation on cognitive and motor functions in poststroke patients.

The aim of the study was to explore the effect of acupuncture combined with rehabilitation on cognitive and motor functions in poststroke patients. All patients were divided into Group A and Group B based on different interventions (Group A: acupuncture + conventional rehabilitation, Group B: conventional rehabilitation alone). Acupuncture was conducted once a day, five times a week for 8 weeks, and rehabilitation (including physical therapy and occupational therapy) was conducted for 2 hr per session, once a day, five times a week for 8 weeks. Mini-mental State Examination (MMSE) and Fugl-Meyer Assessment (FMA) were used to assess the motor and cognitive functions at baseline and the end of 8 weeks. After the intervention, FMA and MMSE scores were improved significantly in the two groups (p <.05), compared with the scores prior to intervention. After 8 weeks of intervention, a statistically significant difference in the FMA and MMSE scores was observed between the Group A and the Group B. The results suggested that the combined intervention is more effective than the conventional rehabilitation alone in improving cognitive and motor functions in poststroke patients.

Serum NSE and S100B protein levels for evaluating the impaired consciousness in patients with acute carbon monoxide poisoning.

The aim of this study was to investigate the associations between the levels of neuron-specific enolase (NSE) and S100B protein and coma duration, and evaluate the optimal cut-off values for prediction coma duration ≥ 72 hours in patients with acute carbon monoxide poisoning (ACOP).A total of 60 patients with ACOP were divided into 3 following groups according to their status of consciousness and coma duration at admission: Awake group [Glasgow Coma Scale score (GCS score) ≥ 13 points], Coma < 72 hours group (GCS score < 13 points and coma duration < 72 h), and Coma ≥ 72 hours group (GCS score < 13 points and coma duration ≥ 72 h). The levels of serum NSE and S100B protein were measured after admission.There were significant differences in GCS score, carbon monoxide (CO) exposure time, NSE, and S100B levels between the Coma ≥ 72 h group and the Awake group, and between the Coma < 72 h group and the Awake group. Significant differences in GCS score, NSE, and S100B levels were also found between Coma ≥ 72 h group and Coma < 72 h group. Correlation analysis showed that NSE and S100B were positively correlated (rs = 0.590, P < .01); NSE and S100B were negatively correlated with GCS score (rs = -0.583, rs = -0.590, respectively, both P < .01). The areas under the curve (AUCs) of NSE, S100B, and GCS score to predict the coma duration ≥ 72 hours were 0.754, 0.791, and 0.785, respectively. Pairwise comparisons did not show differences among the 3 groups (all P > .05). The sensitivity and specificity of NSE prediction with a cut-off value of 13 μg/L were 80% and 64%, respectively, and those of S100B prediction with a cut-off value of 0.43 μg/L were 70% and 88%, respectively.The NSE and S100B protein levels were significantly correlated with the degree of impaired consciousness and had the same clinical value in predicting coma duration of ≥ 72 hours in patients with ACOP.

Clinical effects of medical ozone autologous blood transfusion combined with Xingnaojing in the treatment of septic encephalopathy in burns

Objective: To investigate the clinical effects of medical ozone autologous blood transfusion combined with Xingnaojing in the treatment of septic encephalopathy in burns. Methods: The retrospective cohort study was conducted. From August 2015 to May 2019, 90 patients with burn septic encephalopathy and conforming to the inclusion criteria were admitted to Zhengzhou First People's Hospital. Forty-six patients (25 males and 21 females, aged (35±4) years ) treated with Xingnaojing were included in Xingnaojing alone group, and forty-four patients (20 males and 24 females, aged (34±5) years) treated with medical ozone autologous blood transfusion combined with Xingnaojing were included in ozone autologous blood transfusion+Xingnaojing group. Heart rate, body temperature, mean arterial pressure, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score and Glasgow coma score (GCS) of patients in 2 groups were recorded before treatment and on 7 d after treatment. The blood-brain barrier injury markers including occludin, nitric oxide synthase (NOS), neuron-specific enolase (NSE), central nervous system specific protein S100β, glial fibrillar acidic protein (GFAP), and excitatory amino acid (EAA) in serum of patients in 2 groups were detected before treatment and on 1, 3, and 7 d after treatment. Computer tomography perfusion imaging for brain was performed in patients of 2 groups to calculate the region of interest cerebral blood flow (rCBF), region of interest blood volume (rCBV), and region of interest mean transit time (rMTT) before treatment and on 1, 3, and 7 d after treatment. Data were statistically analyzed with chi-square test, analysis of variance for repeated measurement, independent sample t test, and Bonferroni correction. Results: On 7 d after treatment, heart rate, body temperature, and mean arterial pressure of patients in 2 groups were decreased compared with those before treatment, heart rate of patients in ozone autologous blood transfusion+Xingnaojing group was obviously higher than that in Xingnaojing alone group (t=2.886, P<0.01), body temperature of patients in ozone autologous blood transfusion+Xingnaojing group was obviously lower than that in Xingnaojing alone group (t=5.020, P<0.01), and mean arterial pressure of patients in 2 groups were close (t=0.472, P>0.05). On 7 d after treatment, APACHEⅡ score of patients in ozone autologous blood transfusion+Xingnaojing group was obviously lower than that in Xingnaojing alone group (t=3.797, P<0.01), and GCS of patients in ozone autologous blood transfusion+Xingnaojing group was obviously higher than that in Xingnaojing alone group (t=4.934, P<0.01). On 3 and 7 d after treatment, the levels of occludin, NOS, NSE, S100β, GFAP, and EAA in serum of patients in ozone autologous blood transfusion+Xingnaojing group were significantly lower than those in Xingnaojing alone group (t=2.100, 2.090, 2.691, 2.013, 2.474, 2.635, 2.225, 4.011, 3.150, 2.691, 3.145, 2.781, P<0.05 or P<0.01). On 1, 3, and 7 d after treatment, rCBF and rCBV of patients in ozone autologous blood transfusion+Xingnaojing group were significantly increased compared with those in Xingnaojing alone group (t=3.127, 3.244, 3.883, 7.274, 3.661, 2.777, P<0.01). On 7 d after treatment, rMTT of patients in ozone autologous blood transfusion+Xingnaojing group was (3.02±0.57) s, which was significantly lower than (3.11±1.20) s in Xingnaojing alone group (t=2.409, P<0.05). Conclusions: Transfusion of medical ozone autologous blood combined with Xingnaojing therapy can effectively relieve brain injury and improve cerebral blood perfusion in patients with burn septic encephalopathy, which is with safety and credibility.

MO445BRAIN AND GUT AXIS IN CHRONIC KIDNEY DISEASE: FOCUS ON SPECIFIC BIOMARKERS, AND TIGHT JUNCTION PROTEINS

Abstract Background and Aims Chronic kidney disease (CKD) is a progressive systemic disease that affect the microvascular permeability of the blood-brain barrier (BBB) and intestinal barrier leading to increased morbidity, mortality and central nervous system symptoms. In this study we examined the relationship of blood brain and intestinal barrier dysfunction in relation to uraemic environment and increased risk of developing neurologic complications and mortality. In addition, potential proteins conferring the junctional communications were assessed. Method The study included serum samples from 216 prevalent haemodialysis (HD), 80 peritoneal dialysis (PD) and 80 healthy subjects. Permeability of the BBB was evaluated by measuring serum concentrations for brain-specific biomarkers S100B, NSE (neuron specific enolase), BDNF (brain-derived neurotrophic factor), GFAP (glial fibrillary acidic protein) using ELISA. TMAO (trimethylamine-N-Oxide) as a surrogate of gut generated uraemic toxins was analysed by mass spectrophotometry. Subcutaneous fat tissues with identified microvessels from 10 kidney transplant recipients and 11 donors were examined for expression of tight junction proteins claudin-5, occludin and JAM-1 (junction adhesion molecule-1) by immunohistochemical staining. Results HD and PD groups showed elevated cholesterol, triglyceride, creatinine, hsCRP and lower BMI, and P-albumin compared to healthy controls. BDNF serum concentrations were lower in both HD (14.0 ng/mL, IQR 8.7-19.2) and PD (17.9 ng/mL, IQR 14.4-23.4) vs controls (20.2 ng/mL, IQR 16.7-25.7). Similarly, S100B serum concentrations were lower in both HD (31.6 pg/mL, IQR 9.4-186) and PD (49.4 pg/mL, IQR 9.8-118) vs control (87.3 pg/mL, IQR 13.3-749). Conversely, NSE serum concentrations were higher in both HD (5.3 ng/mL, IQR 4.4-6.6) and PD (4.0 ng/mL, IQR 3.6-4.7) vs controls (3.5 ng/mL, IQR 2.9-4.3). Finally, TMAO serum concentration were also higher in both HD (6.4 ng/μL, IQR 4.0-11.2) and PD (3.8 ng/μL, IQR 2.2-6.3) vs controls (0.4 ng/μL, IQR 0.3-0.6). No significant sex differences in biomarker concentration were found, except for TMAO in healthy controls. Immunohistochemistry studies of endothelial tight junction proteins in microvessels, within the subcutaneous fat tissues, showed reduced expression of claudin-5 (5%), occludin (6%) and JAM-1 (5%) in kidney transplant patients vs donors (7%, 8% and 8%, respectively), and ongoing studies are indicating a trend for altered expression of tight junction proteins after ex vivo stimulation with TMAO. Conclusion We report that CKD5 patients showed disruption of BBB and intestinal barrier resulting in altered circulating serum levels of brain-specific biomarkers, secondary to a disruption in the tight junction protein markers in microvasculature of adipose tissue. These findings imply that it is important to continuously monitor cognitive function(s) in CKD. Further studies are needed to assess direct effect of TMAO on tight junction proteins which confer vascular permeability.

Neuron-specific enolase serum levels in COVID-19 are related to the severity of lung injury

The multifunctional role of neuron-specific enolase (NSE) in lung diseases is well established. As the lungs are greatly affected in COVID-19, we evaluated serum NSE levels in COVID-19 patients with and without dyspnea. In this study, we evaluated both SARS-CoV-2-infected and uninfected patients aged >18 years who were referred to hospitals in Catanzaro, Italy from March 30 to July 30, 2020. Epidemiological, clinical, and radiological characteristics, treatment, and outcome data were recorded and reviewed by a trained team of physicians. In total, 323 patients (178 men, 55.1% and 145 women, 44.9%) were enrolled; of these, 128 were COVID-19 patients (39.6%) and 195 were control patients (60.4%). Westergren’s method was used to determine erythroid sedimentation rate. A chemiluminescence assay was used for measurement of interleukin-6, procalcitonin, C-reactive protein, and NSE. We detected significantly higher NSE values (P<0.05) in COVID-19 patients than in controls. Interestingly, within the COVID-19 group, we also observed a further significant increase in dyspnea (Dyspnea Scale and Exercise score: 8.2 ± 0.8; scores ranging from 0 to 10, with higher numbers indicating very severe shortness of breath). These data provide the background for further investigations into the potential role of NSE as a clinical marker of COVID-19 progression.

Effect of abiraterone combined with prednisone on serum CgA and NSE in metastatic castration-resistant prostate cancer without previous chemotherapy

Purpose: To investigate the influence of a combination of abiraterone and prednisone on serum chromogranin A (CgA) and neuron-specific enolase (NSE) in patients with metastatic castrationresistant prostate cancer (mCRPC) without previous chemotherapy, so as to provide reference data for drug therapy of prostate cancer.&#x0D; Methods: A total of 103 mCRPC patients without chemotherapy from January 2013 to March 2017 were included in this retrospective study. Seventy-one (71) patients received prednisone combined with abiraterone (study group), while 32 patients accepted prednisone (control group). The CgA, NSE and prostate-specific antigen (PSA) in the two groups were monitored, while PSA progression-free survival (PSA-PFS), radiographic PFS (rPFS), and overall survival (OS) were determined during follow-up.&#x0D; Results: PSA-PFS, rPFS and OS in the study group were significantly higher than those in the control group (p &lt; 0.05). The increased proportion of CgA or NSE in the study group was significantly lower than that in the control group at 6 months of treatment (p &lt; 0.05). The occurrences of NED before treatment and 6 months after treatment were both independent predictors of PSA and radiographic progression in the study group (p &lt; 0.05).&#x0D; Conclusion: The combination of prednisone and abiraterone is helpful for prognosis in mCRPC patients that are not on chemotherapy. The occurrence of NED predicts mostly poor prognosis of mCRPC patients on a combination of abiraterone and prednisone

Can we delineate brain injury in full-term neonates using serum biomarkers?

ABSTRACT OBJECTIVE: Early identification of neonates at risk of neurological impairment is particularly important for the bedside clinician. Clinical value of S100b and neuron-specific enolase in neonates has not been yet established. We investigated their kinetics and possible early clinical utility in neonatal encephalopathy (NE). STUDY DESIGN: 36 full-term neonates (13 with moderate/severe encephalopathy, 11 with mild encephalopathy, 12 controls) were enrolled and studied prospectively. Serum S100b and neuron-specific enolase (NSE) were measured serially on days(d) 1, 3, 9 and 18 of life. Brain MRI and long-term neurodevelopmental outcome were also assessed. RESULT: Neonates with moderate/severe encephalopathy had significantly increased S100b (d1) and NSE levels (d1, d3, d9) compared to controls. Neuron-specific enolase significantly correlated with the degree of encephalopathy, and a cutoff of 38.8 μg/l (d1) accurately predicted moderate/severe encephalopathy. S100b (d1) cutoff points of 1.6 μg/l and 11.4 μg/l prognosticated severe encephalopathy and death/cerebral palsy, respectively. Both biomarkers correlated well with neuroimaging and Bayley-III scores. CONCLUSION: Combined clinical, laboratory, imaging and neurodevelopmental data indicate that serum S100b and NSE can be useful biomarkers for the diagnosis and prognosis of neonatal brain injury, providing useful information to the bedside clinician.

Serum Neuron-Specific Enolase Levels Associated with Connectivity Alterations in Anterior Default Mode Network after Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is the most prevalent neurological insult and leads to long-lasting cognitive impairment. Neuroimaging studies have discovered abnormalities in brain network connectivity following mTBI as the underlying neural basis of cognitive deficits. However, the pathophysiologic mechanisms involved in imaging alterations remain elusive. Proteins neuron-specific enolase (NSE) and ubiquitin C terminal hydrolase 1 are reliable markers for neuronal cell-body damage, both of which have been demonstrated to be increased in serum following mTBI. Therefore, we conducted a longitudinal study to examine relationships between abnormal brain network connectivity and serum neuronal biomarkers and their associations with cognitive recovery following mTBI. Sixty patients were followed-up at 1 week and 3 months post-injury and 41 controls were recruited. Resting-state functional magnetic resonance imaging was used to build a functional connectivity matrix within large-scale intrinsic networks, and their topological properties were analyzed using graph theory measures. We found that, compared with controls, mTBI patients showed significant decreases in a number of nodal characteristics in default mode network (DMN), salience network, and executive network (p < 0.05, false discovery rate corrected) at 3 months post-injury. Linear regression analysis found elevated serum NSE in acute phase could predict lower efficiency and degree centrality of anterior DMN at 3 months post-injury. In addition, efficiency and degree centrality of anterior DMN were negatively associated with working memory. Our study showed neuronal injury was associated with alterations in brain network connectivity after mTBI. These findings can facilitate capability to predict the brain functional outcomes and cognitive recovery in mTBI.

Changes in NSE and S-100β during the perioperative period and effects on brain injury in infants with biliary atresia undergoing parent donor liver transplantation.

The present study aimed to investigate the effects of parental donor liver transplantation on the perioperative changes of serum calcium-binding protein β (S-100β) and neuron-specific enolase (NSE) levels, two markers of brain injury, and on postoperative cognitive function. The present study was a prospective observational study of infants with congenital biliary atresia who underwent selective liver transplantation in 2017 at Tianjin First Central Hospital (Tianjin, China). Blood samples were collected prior to, during and following surgery, and S-100β and NSE levels were measured using ELISA. The pediatric patients were assessed using the Bayley Scales of Infant Development 1 day prior to and 3 months after surgery. Additionally, the pediatric anesthesia emergence delirium scores were evaluated. The results demonstrated that serum NSE and S100β were increased during and after surgery compared with prior to surgery (P<0.05). Furthermore, serum S-100β and NSE levels peaked 1 h after the neohepatic phase compared with prior to surgery (P<0.05). Compared with 1 day before surgery, mental development index (MDI) and psychomotor development index (PDI) were decreased 3 months after surgery (MDI, 87.7±8.4 vs. 84.5±8.5, P=0.015; PDI, 82.9±8.7 vs. 79.6±8.8, P=0.016). In conclusion, parental donor liver transplantation may cause a certain degree of brain injury in pediatric patients with end-stage liver disease, as revealed by increased serum NSE and S100β levels.

Significance of serum neuron-specific enolase in transient global amnesia

Neuron-specific enolase (NSE) is a glycolytic enzyme, which is associated with neuronal cell dysfunction in the brain. This study evaluated the role of serum NSE levels of patients with transient global amnesia (TGA). In addition, the relationship between serum NSE levels and the clinical features of TGA was explored. Forty-eight patients with TGA were prospectively included, and their serum NSE levels were measured. We investigated serum NSE levels in patients with TGA. In addition, we analyzed the differences in clinical characteristics between patients with elevated and normal serum NSE levels. Of the 48 patients with TGA, 16 patients (33.3%) had elevated serum NSE levels (25.0 ± 11.5 ng/mL), whereas 32 patients (66.7%) showed normal serum NSE levels (12.8 ± 2.1 ng/mL). The patients with elevated serum NSE levels exhibited higher levels of cognitive impairment than those with normal serum NSE levels (4/16 vs. 1/32, p = 0.036). The serum NSE levels showed a relatively high discrimination (AUC 0.684) between patients with and without cognitive impairment, with 80.0% sensitivity and 74.4% specificity at a cut-off value 17.3 ng/mL. A third of all patients with TGA carry elevated serum NSE levels, which suggests that the neuronal cell dysfunction could be associated with TGA pathogenesis. In addition, it might be correlated with cognitive impairment.

Using Out-of-Hospital Cardiac Arrest (OHCA) and Cardiac Arrest Hospital Prognosis (CAHP) Scores with Modified Objective Data to Improve Neurological Prognostic Performance for Out-of-Hospital Cardiac Arrest Survivors.

This study aimed to determine whether accuracy and sensitivity concerning neurological prognostic performance increased for survivors of out-of-hospital cardiac arrest (OHCA) treated with targeted temperature management (TTM), using OHCA and cardiac arrest hospital prognosis (CAHP) scores and modified objective variables. We retrospectively analyzed non-traumatic OHCA survivors treated with TTM. The primary outcome was poor neurological outcome at 3 months after return of spontaneous circulation (cerebral performance category, 3–5). We compared neurological prognostic performance using existing models after adding objective data obtained before TTM from computed tomography (CT), magnetic resonance imaging (MRI), and biomarkers to replace the no-flow time component of the OHCA and CAHP models. Among 106 patients, 61 (57.5%) had poor neurologic outcomes. The area under the receiver operating characteristic (AUROC) curve for the OHCA and CAHP models was 0.89 (95% confidence interval (CI) 0.81–0.94) and 0.90 (95% CI 0.82–0.95), respectively. The prediction of poor neurological outcome improved after replacing no-flow time with a grey/white matter ratio measured using CT, high-signal intensity (HSI) on diffusion-weighted MRI (DWI), percentage of voxel using apparent diffusion coefficient value, and serum neuron-specific enolase levels. When replaced with HSI on DWI, the AUROC and sensitivity of the OHCA and CAHP models were 0.96 and 74.5% and 0.97 and 83.8%, respectively (100% specificity). Prognoses concerning neurologic outcomes improved compared with existing OHCA and CAHP models by adding new objective variables to replace no-flow time. External validation is required to generalize these results in various contexts.

Prognostic performance of serum neuron specific enolase (NSE) in comatose cardiac arrest survivors: a multiple thresholds meta-analysis (1634)

Prognostic performance of serum neuron specific enolase (NSE) in comatose cardiac arrest survivors: a multiple thresholds meta-analysis (1634)

Comparison of Prognostic Performance between Neuron-Specific Enolase and S100 Calcium-Binding Protein B Obtained from the Cerebrospinal Fluid of Out-of-Hospital Cardiac Arrest Survivors Who Underwent Targeted Temperature Management.

We compared the prognostic performances of serum neuron-specific enolase (sNSE), cerebrospinal fluid (CSF) NSE (cNSE), and CSF S100 calcium-binding protein B (cS100B) in out-of-hospital cardiac arrest (OHCA) survivors. This prospective observational study enrolled 45 patients. All samples were obtained immediately and at 24 h intervals until 72 h after the return of spontaneous circulation. The inter- and intragroup differences in biomarker levels, categorized by 3 month neurological outcome, were analyzed. The prognostic performances were evaluated with receiver operating characteristic curves. Twenty-two patients (48.9%) showed poor outcome. At all-time points, sNSE, cNSE, and cS100B were significantly higher in the poor outcome group than in the good outcome group. cNSE and cS100B significantly increased over time (baseline vs. 24, 48, and 72 h) in the poor outcome group than in the good outcome group. sNSE at 24, 48, and 72 h showed significantly lower sensitivity than cNSE or cS100B. The sensitivities associated with 0 false-positive rate (FPR) for cNSE and cS100B were 66.6% vs. 45.5% at baseline, 80.0% vs. 80.0% at 24 h, 84.2% vs. 94.7% at 48 h, and 88.2% (FPR, 5.0%) vs. 94.1% at 72 h. High cNSE and cS100B are strong predictors of poor neurological outcome in OHCA survivors. Multicenter prospective studies may determine the generalizability of these results.

Role of the ratio of NSE serum concentration in evaluating the therapeutic effect on metastatic neuroendocrine neoplasms of the liver.

Neuron-specific enolase (NSE) is one of the biomarkers of neuroendocrine neoplasms (NEN). Its level of evidence is significantly lower than some other biomarkers. However, the ratio of NSE serum concentration (NSE ratio) before and after the treatment cycle may be a good tool for evaluating the therapeutic effect of metastatic neuroendocrine neoplasms of the liver (MNENOL). We collected clinical cases of NEN with liver metastases, calculating the ratio of NSE in each case before and after the treatment cycle, using thin-slice computed tomography or magnetic resonance imaging as a reference to evaluate the therapeutic effect. We analyzed the correlation between NSE ratio and NSE serum concentration and curative effect, and then compared the evaluation performance of the two. We found that increase in the NSE ratio is a risk factor for the progression of MNENOL. Compared with NSE, NSE ratio has a greater advantage in evaluating the effect of MNENOL. NSE ratio is related to the curative effect of NEN, and the correlation is better than that of NSE. When judging whether NEN has new metastasis, the NSE ratio shows a similar effect to NSE, and there is no significant difference between the two. NSE ratio is more effective than NSE in evaluating the therapeutic effect of MNENOL, but it is not significantly different from NSE in terms of predicting new metastases.