Increase In Neuron-specific Enolase Research Articles

Medical Management of Acute Spinal Cord Injury with Aspiration pneumonia in a Kid

A two-month-old, non-descript female goat kid was brought to the Veterinary Clinical Complex, Veterinary College and Research Institute, Orathanadu, with a history of continuous high-pitched bleating, respiratory distress, and forelimb paresis over the past two days. The animal has appeared lethargic with an abnormal gait. Neurological examination revealed sluggish sensory and motor reflexes in the forelimbs and palpation elicited pain in the thoracic and dorsal spinal areas (C7-T2). Auscultation revealed exaggerated heart sounds and prolonged expiration. Radiographic examination ruled out spinal involvement but revealed left lung consolidation with pulmonary infiltration. Cerebrospinal fluid analysis showed an increase in neuron-specific enolase (NSE). The condition was tentatively diagnosed as acute spinal cord injury with aspiration pneumonia. Inj. Progesterone and intranasal Budesonide were administered along with a Progesterone patch applied to the lateral neck region. Successful medical management led to gradual clinical improvement observed from the seventh day and completely recovered after 15 days of treatment.

The effects of pentoxyphiline on neurocognitive functions and neurobiochemical markers in coronary artery bypass graft surgery

Aim: Neurocognitive dysfunction is a complication of cardiopulmonary bypass (CPB). Neuron-specific enolase (NSE) and S100ß protein are markers of cerebral injury. With its beneficial rheological and anti-inflammatory properties, pentoxyphiline (PTX) is an interesting agent in cardiac surgery patients. The study was designed to evaluate the influence of prophylactic use of PTX on cognitive function and S100ß and NSE in on-pump coronary artery bypass grafting (CABG) patients.Method: In this prospective study, 40 patients undergoing on-pump CABG and received either PTX (bolus of 5 mg kg-1) after induction of anesthesia or saline are included. Neurological examination and neuropsychologic tests, including the mini-mental state examination test (MMSET) and Benton visual retention test (BVRT), were obtained preoperatively and on the seventh postoperative day. Blood samples for analysis of S100ß and NSE were collected before anesthesia, at the end of CPB, at the 3rd hour and 24th hour postoperatively.Results: Demographic and perioperative data were similar for the two groups. Mean cross-clamping times were 67.86±22.22 and 66.32±27.84 min, respectively. In both groups, S100ß and NSE increased significantly (p<0.01) at the end of the CPB and remained slightly increased at T2 (at the CPB exit), and T3 (at the 3rd hour after surgery) than preoperative levels (p>0.05). MMSET and BVRT performances of the two groups were similar and did not change compared to preoperative scores.Conclusions: Coronary artery bypass surgery caused a significant increase in NSE and S100ß serum levels but with no deterioration in neuropsychological outcome assessed in the first postoperative week. Although it was reported that PTX could be a promising agent to prevent post-CPB organ dysfunction in elderly cardiac surgery patients, prophylactic use of PTX appeared to offer no advantage for cerebral protection in the age group involved in this study.

Association between Neuron-Specific Enolase, Memory Function, and Postoperative Delirium after Transfemoral Aortic Valve Replacement.

Although transfemoral aortic valve replacement (TAVR) is a safe treatment for elderly patients with severe aortic valve stenosis, postoperative microembolism has been described. In this secondary endpoint analysis of the POST-TAVR trial, we aimed to investigate whether changes in neuron-specific enolase (NSE)-a biomarker of neuronal damage-are associated with changes in memory function or postoperative delirium (POD). This was a prospective single-center study enrolling patients undergoing elective TAVR. Serum NSE was measured before and 24 h after TAVR. POD was diagnosed using CAM-ICU testing. Memory function was assessed before TAVR and before hospital discharge using the "Consortium to Establish a Registry for Alzheimer's Disease" (CERAD) word list and the digit span task (DST) implemented in "∆elta-App". Subjects' median age was 82 years (25th to 75th percentile: 77.5-85.0), 42.6% of subjects were women. CERAD scores significantly increased from pre- to post-TAVR, with p < 0.001. POD occurred in 4.4% (6/135) of subjects at median 2 days after TAVR. After TAVR, NSE increased from a median of 1.85 ng/mL (1.30-2.53) to 2.37 ng/mL (1.69-3.07), p < 0.001. The median increase in NSE was 40.4% (13.1-138.0) in patients with POD versus 17.3% (3.3-43.4) in those without POD (p = 0.17). Memory function improved after TAVR, likely due to learning effects, with no association to change in NSE. Patients with POD appear to have significantly higher postoperative levels of NSE compared to patients without POD after TAVR. This finding suggests that neuronal damage, as indicated by NSE elevation, may not significantly impair assessed memory function after TAVR.

Neuroinflammation Process as a Key Etiopathogenetic Factor in the Evolution of Autism Spectrum Disorders in Child Patients

Background: the prevalence of autism spectrum disorders (ASD) is increasing every year, however, diagnostic and therapeutic options are still limited. Aim: identification the patterns of the neuroinflammation process in the etiopathogenesis of ASD of child patients. Patients and methods: clinical, anamnestic and laboratory data of 85 child patients with a confirmed ASD diagnosis. Each patient was assessed for the level of neurospecific proteins (neuron-specific enolase (NSE), S100b protein), the indices of the “Neuro-immuno-test” panel (leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) activity, autoantibodies to S100b protein and myelin basic protein) in the blood before and after a standardized three-month-course of treatment. The reference interval of the laboratory was taken as normal values. The clinical picture was assessed according to the Childhood Autism Rating Scale (CARS). The correlation calculations were carried out in the MS Excel program. Results: in this work we describe the dynamics of the neuroinflammation process parameters in children with autism-like syndrome and psycho-speech development delay on the basis of complex anti-inflammatory therapy. The results of the research prove the increase in NSE and S100b protein quantity among 85% of patients before the treatment. More than 60% of patients had the increase of the parameters of the Neuro-test panel. The severity levels of symptoms among patients according to the scales used specified moderate and severe autism. The quantity of neurospecific proteins and immunological parameters correlated with CARS scale scores. Positive dynamics of clinical symptoms and studied parameters decrease were observed while therapy. The use of the parameters allows to evaluate objectively the severity levels of the patient’s immunomitochondrial status and shows a congruent change on the basis of etiopathogenetic therapy.

Evaluation of the brain cellular damage during liver transplantations.

Neuroinflammation in patients undergoing major surgery can lead to neuronal damage, and neuronal damage can be detected through the measurement of biochemical markers of brain damage. S100 beta (S100 β), neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP) levels are considered good biomarkers to detect brain damage that emerged with neurotoxicity. To evaluate neuronal damage during liver transplantations. After approval of the ethics committee and patient consents, preoperative and postoperative cognitive functions of 33 patients undergoing liver transplantation were measured using the Mini Mental State Examination (MMSE), whereas simultaneous neuronal damage was evaluated through the measurement of S100β, NSE, and GFAP levels. There was no statistically significant difference between preoperative and postoperative MMSE. There was a statistically significant decrease in postoperative GFAP (P < 0.05) and a statistically significant increase in NSE (P < 0.05) compared to preoperative values. The decrease in S100β (P > 0.05) level was statistically insignificant. Neuroprotective approaches in anesthesia protocol protect patients from brain damage during liver transplantation and prevent the development of postoperative cognitive dysfunction. Since the significant increase in NSE levels during liver transplantations was deemed to have been associated with causes other than neuronal damage, NSE should not be evaluated as a marker of brain damage in these operations.

Beyond brain injury biomarkers: chemoattractants and circulating progenitor cells as biomarkers of endogenous rehabilitation effort in preterm neonates with encephalopathy.

Preclinical work and studies in adults have shown that endogenous regeneration efforts that involve mobilization of progenitor cells take place after brain injury. However, kinetics of endogenous circulating progenitor cells (CPCs) in preterm neonates is not well described, particularly their possible role regarding brain injury and regeneration. We aimed to assess the kinetics of CPCs in neonates with encephalopathy of prematurity in relation to brain injury biomarkers, chemoattractants and relevant antenatal and postanal clinical factors, in an effort to outline the related pathophysiology. 47 preterm neonates (of 28-33 weeks GA) were enrolled: 31 newborns with no or minimal brain injury (grade I IVH) and 16 prematures with encephalopathy (grade III or IV IVH, PVL or infarct). Peripheral blood samples obtained on days 1, 3, 9, 18 and 45 after birth were analyzed using flow cytometry, focusing on EPCs (early and late Endothelial Progenitor Cells), HSCs (Hematopoietic Stem Cells) and VSELs (Very Small Embryonic-Like Stem Cells). At the same time-points serum levels of S100B, Neuron-specific Enolase (NSE), Erythropoietin (EPO), Insulin-like growth factor-1 (IGF-1) and SDF-1 were also measured. Neonates were assessed postnatally with brain MRI, and with Bayley III developmental test at 2 years of corrected age. Preterms with brain injury proved to have significant increase of S100B and NSE, followed by increase of EPO and enhanced mobilization mainly of HSCs, eEPCs and lEPCs. IGF-1 was rather decreased in this group of neonates. IGF-1 and most CPCs were intense decreased in cases of antenatal or postnatal inflammation. S100B and NSE correlated with neuroimaging and language scale in Bayley III test, providing good prognostic ability. The observed pattern of CPCs' mobilization and its association with neurotrophic factors following preterm brain injury indicate the existence of an endogenous brain regeneration process. Kinetics of different biomarkers and associations with clinical factors contribute to the understanding of the related pathophysiology and might help to early discriminate neonates with adverse outcome. Timely appropriate enhancement of the endogenous regeneration effort, when it is suppressed and insufficient, using neurotrophic factors and exogenous progenitor cells might be a powerful therapeutic strategy in the future to restore brain damage and improve the neurodevelopmental outcome in premature infants with brain injury.

Neuron-specific enolase levels immediately following cardiovascular surgery is modulated by hemolysis due to cardiopulmonary bypass, making it unsuitable as a brain damage biomarker

Neuron-specific enolase (NSE) is one of the biomarkers used as an indicator of brain disorder, but since it is also found in blood cell components, there is a concern that a spurious increase in NSE may occur after cardiovascular surgery, where cardiopulmonary bypass (CPB) causes hemolysis. In the present study, we investigated the relationship between the degree of hemolysis and NSE after cardiovascular surgery and the usefulness of immediate postoperative NSE values in the diagnosis of brain disorder. A retrospective study of 198 patients who underwent surgery with CPB in the period from May 2019 to May 2021 was conducted. Postoperative NSE levels and Free hemoglobin (F-Hb) levels were compared in both groups. In addition, to verify the relationship between hemolysis and NSE, we examined the correlation between F-Hb levels and NSE levels. We also examined whether different surgical procedures could produce an association between hemolysis and NSE. Among 198 patients, 20 had postoperative stroke (Group S) and 178 had no postoperative stroke (Group U). There was no significant difference in postoperative NSE levels and F-Hb levels between Group S and Group U (p = 0.264, p = 0.064 respectively). F-Hb and NSE were weakly correlated (r = 0.29. p < 0.01). In conclusion, NSE level immediately after cardiac surgery with CPB is modified by hemolysis rather than brain injury, therefore it would be unreliable as a biomarker of brain disorder.

Effects of centrifugation prior to pneumatic tube system transport on routine biochemical and immunological tests of susceptibility to hemolysis

BackgroundPneumatic tube system (PTS) may be associated with preanalytical hemolysis. The objective of this study was to evaluate the effects of PTS on biochemical and immunological tests susceptible to hemolysis and try to find ways to reduce the result bias caused by PTS. MethodsLaboratory parameters were compared between PTS without centrifuging group, PTS after centrifuging group, PTS with serum group, and hand-delivered (HD) group. Studies were performed to access the influence of different PTS transport frequencies on laboratory assays. ResultsPTS transportation resulted in obviously increase in LDH (lactate dehydrogenase) and NSE (neuron-specific enolase) results (LDH: Bias = 17.95%, 95% confidence interval (CI) = −3.13–39.02; p < 0.001; NSE: Bias = 64.26%, 95% CI = −21.29–149.82; p < 0.001; respectively). After pre-centrifugation, no statistical difference was observed in LDH results (Bias = 2.83%, 95% CI = −13.00–18.65; p = 0.737). However, the bias of NSE still reach 19.16% (95% CI = −41.78–80.11), which exceeded the clinical acceptable range (p = 0.017). Both LDH(p = 0.931) and NSE(p > 0.999) show no statistical difference between PTS with serum group and HD group (LDH: Bias = −1.60%, 95% CI = −6.00–2.81; NSE: Bias = −3.68%, 95% CI = −11.35–3.99). ConclusionPTS can lead to falsely increased LDH and NSE test results. Only loading the centrifuged upper serum in new tubes during PTS transport can eliminate the results bias of NSE.

Increased Neuron Specific Enolase in a Hypoxic Ischemia Rat Model

Introduction: Acute brain injury caused by cerebral ischemia, either due to stroke or ischemic hypoxic-ischemic encephalopathy (HIE), represents a major neurological cause of death and disability worldwide. Neuronal cell injury has been shown to correlate with a significant increase in neuron-specific enolase (NSE) levels in in vitro studies. This study aims to measure NSE levels in the blood serum of rats with HIE. Methods: This study used an experimental post-test design in which occlusion of the right common carotid artery (CCA) was performed on Wistar rats, which were then placed in a hypoxic chamber and reperfused after 60 minutes (treatment group). Neurological scores were collected over the first 24 hours. After 48 hours, experimental animals were sacrificed and their serum NSE levels were measured using ELISA. Statistical analysis using a T-test was performed for independent samples. Results: A total of 16 male rats were included in the study. Neurological scores indicated that all HIE group rats experienced hemiparesis to varying degrees. NSE levels in the treatment group were significantly higher than in the control group (p &lt; 0.05). The mean NSE level in the treatment group was higher than that in the other group. Conclusion: Consistent with in vitro studies, we found that NSE was higher in the HIE rat model than in controls. These data support future studies to assess the fitness of serum NSE as a biomarker of brain damage.

Clinical efficacy of combined therapy in children with stage 4 neuroblastoma

To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma. A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021. The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N-Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years. Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.

Differential Diagnosis of Seizure and Syncope by the Means of Biochemical Markers in Emergency Department Patients

Background:Seizure and syncope have similar clinical symptoms but different etiologies. Hence, differential diagnosis is crucial prior to intervention. This study evaluates the diagnostic importance of neuron specific enolase (NSE), creatine phosphokinase (CPK), and serum lactate dehydrogenase (LDH) for admitting patients with seizure medical history to emergency department (ED) in order for differential diagnosis between syncope and seizure.Methods:Patients with a short-lasting loss of consciousness admitted to the ED were recruited. All patients with a short-lasting loss of consciousness were eligible and EEG was conducted several times and was taken over a long period. Patients were then divided into two groups of seizure and syncope. The biochemical markers levels of all the eligible patients were measured by a reputable laboratory.Results:In order to define specificity and sensitivity of different levels of biomarkers and the optimal cut-off points, ROC curves for each biomarker of syncope and seizure patients admitted to ED were performed. AUC for NSE, CPK, and LDH were 0.973 ± 0.023, 0.827 ± 0.047, and 0.836 ± 0.043 respectively in 95% confidence level. Cut-off points for NSE, CPK, and LDH were determined 25.12, 218.09, and 193.88 respectively.Conclusions:It was concluded that NSE, CPK and LDH levels were different significantly in seizure patients compared to syncope ones. The seizure group showed an increase in NSE, CPK and LDH level.

Peripheral Polyneuropathy and Cognitive Impairment in Type II Diabetes Mellitus.

BackgroundNeuropathy is one of most common complications in diabetic patients. Diagnosis of diabetic neuropathy is essential for decreasing the rate of the disability and death. Neuron-specific enolase (NSE) is released from damaged neuronal cells and enters the blood circulation through an injured blood brain barrier. Therefore, serum NSE can reflect the damage of neurons and brain tissue.ObjectiveTo evaluate peripheral polyneuropathy and cognitive function in Type 2 Diabetes Mellitus (T2DM) and correlate them with NSE level as a possible biomarker of diabetic neuropathy.Subjects and MethodsForty five T2DM patients with polyneuropathy were randomly recruited in this study compared to 45 healthy age and sex matched subjects as a control. Patients group were divided into two subgroups, 24 diabetic patients with painful peripheral neuropathy and 21 with painless peripheral neuropathy. All were subjected to clinical assessment by diabetic neuropathy symptom score, Dyck neuropathy grading, Mini-Mental State Examination (MMSE), assessment of HbA1c, NSE biomarker and neurophysiological assessment (nerve conduction study (NCS), event related potential (P300wave) and somatosensory evoked potential (SSEP) of the right median nerve).ResultsThere were significant decrease in cognitive functions in diabetic patients compared to controls and a significant increase in NSE in diabetic patients. There were no significant difference between patients with painless and painful diabetic neuropathy as regard MMSE, HbA1c and NSE. There were significant correlation of P300 in diabetic patients with HbA1c and NSE.ConclusionNeurophysiological assessment of diabetic patients by NCS, SSEP and P300 have well evaluation of cognitive functions, painless, and painful diabetic polyneuropathy. NSE is a beneficial biomarker in diabetic patients to pick up neurological complications.

Association of the Plasma Long Non-coding RNA MEG3 With Parkinson's Disease.

Objective: To investigate the expression level of the maternally expressed gene-3 (MEG3) of the free long non-coding RNA (lncRNAs) in the plasma of Parkinson's disease (PD) patients and its relationship with the disease.Methods: Thirty PD patients (PD group) who treated at Xuanwu Hospital of Capital University of Medical Sciences between January 2017 and December 2019 were selected as the research objects and 30 healthy subjects were enrolled in the study during the same period as the control group. Cognitive function was assessed according to the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to evaluate cognitive function, Non-Motor Symptoms Scale (NMSS) was used to evaluate severity of non-motor symptoms. The relative expression of lncRNAs MEG3 in plasma was measured by PCR, and the levels of neuron-specific enolase (NSE), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in plasma were measured by ELISA, and the relationship with these all indexes was analyzed.Results: The NMSS score of PD group was significantly higher than that of the control group, while the MMSE and MoCA scores were significantly lower than that of the control group (P < 0.05); The relative expression of lncRNAs MEG3, NGF and BDNF levels of PD group were significantly lower than that of the control group, and NSE level was significantly higher than that of the control group (P < 0.05); The H&Y stage and NMSS score in PD group were negatively correlated with the relative expression of lncRNAs MEG3, the levels of NGF and BDNF (P < 0.05), and positively correlated with NSE (P < 0.05); The MMSE and MoCA scores in PD group were positively correlated with the relative expression of lncRNAs MEG3, NGF, BDNF levels (P < 0.05), and negatively correlated with NSE (P < 0.05); The relative expression of lncRNAs MEG3 in PD group was positively correlated with NGF, BDNF levels (P < 0.05), and negatively correlated with NSE (P < 0.05).Conclusion: The expression of lncRNAs MEG3 in the plasma of PD patients was downregulated compared to that of healthy control subjects, and its expression level was closely related to the aggravation of non-motor symptoms, cognitive decline, and PD stage. These associations may reflect the synergism of the increase of NSE and decrease of NGF and BDNF levels, highlighting plasma lncRNA MEG3 as a new candidate biomarker of PD.

Clinical features of neuroblastoma: an analysis of 44 children

Objective To study the clinical features of neuroblastoma (NB) and the factors influencing survival rate. Methods A total of 44 children with NB who were admitted from April 2016 to February 2020 were enrolled as research subjects. A retrospective analysis was performed on their medical data and follow-up data. Results The common clinical symptoms of these 44 children were fever (10/44, 23%), mass (9/44, 20%), abdominal pain (8/44, 18%), cough (7/44, 16%), pale complexion (3/44, 7%), claudication (2/44, 5%), and abnormal activity (2/44, 5%). According to the INSS stage, 2 children (4%) had stage I NB, 5 children (11%) had stage II NB, 5 children (11%) had stage III NB, and 32 children (73%) had stage IV NB. The mean follow-up time was (15.3±1.5) months, with a recurrence rate of 20% and an overall survival rate of 82%. Among the 44 children, 29 (66%) achieved event-free survival and 7 (16%) had survival with tumor. The univariate analysis showed that a pathological type of NB and an increase in serum neuron-specific enolase (NSE) decreased the overall survival rate of children with NB (P Conclusions The clinical symptoms of children with NB are not specific at the first visit. Fever, abdominal pain, and mass are common symptoms, and there is a high proportion of children in the advanced stage. The pathological type of NB and an increase in serum NSE may be associated with a reduction in the overall survival rate of children with NB.

Biomarkers of Neurological Outcome After Aneurysmal Subarachnoid Hemorrhage as Early Predictors at Discharge from an Intensive Care Unit

BackgroundSubarachnoid bleeding is associated with brain injuries and ranges from almost negligible to acute and life threatening. The main objectives were to study changes in brain-specific biomarker levels in patients after an aneurysmal subarachnoid hemorrhage (aSAH) in relation to early clinical findings, severity scores, and intensive care unit (ICU) outcome. Analysis was done to identify specific biomarkers as predictors of a bad outcome in the acute treatment phase.MethodsAnalysis was performed for the proteins of neurofilament, neuron-specific enolase (NSE), microtubule-associated protein tau (MAPT), and for the proteins of glial cells, S100B, and glial fibrillary acidic protein (GFAP). Outcomes were assessed at discharge from the ICU and analyzed based on the grade in the Glasgow Outcome Scale (GOS). Patients were classified into two groups: with a good outcome (Group 1: GOS IV–V, n = 24) and with a bad outcome (Group 2: GOS I–III, n = 31). Blood samples were taken upon admission to the ICU and afterward daily for up to 6 days.ResultsIn Group 1, the level of S100B (1.0, 0.9, 0.7, 2.0, 1.0, 0.3 ng/mL) and NSE (1.5, 2.0, 1.6, 1.2, 16.6, 2.2 ng/mL) was significantly lower than in Group 2 (S100B: 4.7, 4.8, 4.4, 4.5, 6.6, 6.8 ng/mL; NSE: 4.0, 4.1, 4.3, 3.8, 4.4, 2.5 1.1 ng/mL) on day 1–6, respectively. MAPT was significantly lower only on the first and second day (83.2 ± 25.1, 132.7 ± 88.1 pg/mL in Group 1 vs. 625.0 ± 250.7, 616.4 ± 391.6 pg/mL in Group 2). GFAP was elevated in both groups from day 1 to 6. In the ROC analysis, S100B showed the highest ability to predict bad ICU outcome of the four biomarkers measured on admission [area under the curve (AUC) 0.81; 95% CI 0.67–0.94, p < 0.001]. NSE and MAPT also had significant predictive value (AUC 0.71; 95% CI 0.54–0.87, p = 0.01; AUC 0.74; 95% CI 0.55–0.92, p = 0.01, respectively). A strong negative correlation between the GOS and S100B and the GOS and NSE was recorded on days 1–5, and between the GOS and MAPT on day 1.ConclusionOur findings provide evidence that brain biomarkers such as S100B, NSE, GFAP, and MAPT increase significantly in patients following aSAH. There is a direct relationship between the neurological outcome in the acute treatment phase and the levels of S100B, NSE, and MAPT. The detection of brain-specific biomarkers in conjunction with clinical data may constitute a valuable diagnostic and prognostic tool in the early phase of aSAH treatment.

Neuron-specific enolase has potential value as a biomarker for [18F]FDG/[68Ga]Ga-PSMA-11 PET mismatch findings in advanced mCRPC patients

BackgroundPSMA-targeted radioligand therapy (PSMA-RLT) yielded impressive results in the metastasized castration-resistant prostate carcinoma (mCRPC) setting. High expression of PSMA is essential for successful PSMA-RLT. However, some patients develop [18F]FDG-avid lesions with low or no PSMA expression ([18F]FDG/[68Ga]Ga-PSMA-11 mismatch findings on PET/CT) in the course of treatment. Those lesions are not affected by PSMA-RLT and a change in therapy management is needed. To enable early mismatch detection, possible blood parameters as indicators for the occurrence of [18F]FDG/[68Ga]Ga-PSMA-11 mismatch findings on PET/CT were evaluated.MethodsRetrospective study of N = 66 advanced mCRPC patients with dual [68Ga]Ga-PSMA-11 and [18F]FDG PET/CT imaging within 4 weeks, who were referred for or received [177Lu]Lu-PSMA-617 radioligand therapy. Prostate-specific antigen (PSA), neuron-specific enolase (NSE), gamma-glutamyltransferase (GGT), and alkaline phosphatase (ALP) were tested as indicators for the occurrence of [18F]FDG/[68Ga]Ga-PSMA-11 mismatch findings. Additional to absolute values, relative changes (ΔPSA, ΔNSE, ΔGGT, ΔALP) over a period of 4 ± 1 weeks prior to [18F]FDG PET/CT were analyzed.ResultsIn total, 41/66 (62%) patients revealed at least one [18F]FDG/[68Ga]Ga-PSMA-11 mismatch finding on PET/CT. These mismatch findings were detected in 13/41 (32%) patients by screening for and in 28/41 (68%) patients during PSMA-RLT. NSE serum level (55.4 ± 44.6 μg/l vs. 18.5 ± 8 μg/l, p < 0.001) and ΔNSE (93.8 ± 124.5% vs. 2.9 ± 39.5%, p < 0.001) were significantly higher in the mismatch group than in the non-mismatch group. No significant differences were found for serum PSA (p = 0.424), ΔPSA (p = 0.417), serum ALP (p = 0.937), ΔALP (p = 0.611), serum GGT (p = 0.773), and ΔGGT (p = 0.971). For NSE and ΔNSE, the maximum value of the Youden index in ROC analysis was at a cut-off level of 26.8 μg/l (sensitivity 78%, specificity 96%) and at + 13.9% (sensitivity 84%, specificity 75%), respectively. An introduced scoring system of both parameters achieved a sensitivity of 90% and a specificity of 88% for the occurrence of [18F]FDG/[68Ga]Ga-PSMA-11 mismatch.ConclusionWe observed a significantly higher absolute serum concentration and a higher relative increase of NSE in advanced mCRPC patients with [18F]FDG-avid and insufficient PSMA expressing metastases ([18F]FDG/[68Ga]Ga-PSMA-11 mismatch findings on PET/CT) in our cohort. NSE might be used as a potential laboratory indicator for [18F]FDG/[68Ga]Ga-PSMA-11 mismatch findings, if this observation is confirmed in future, ideally prospective, studies in larger patient cohorts.

Neonatal neuron specific enolase, a sensitive biochemical marker of neuronal damage, is increased in preeclampsia: A retrospective cohort study

BackgroundPreeclampsia leads to chronic intrauterine hypoxia by interfering with placental blood supply. We aimed to investigate whether preeclampsia exposure has an influence on central nervous system of infants, as evaluated by analyzing neonatal serum neuron specific enolase (NSE). MethodsThis was a retrospective study including infants born in Nanfang hospital between Jan 2018 and Feb 2019 without asphyxia. They were divided into normotensive control group and preeclampsia group to compare the NSE levels. Furthermore, PE group was divided into five subgroups by lipstick of urine protein from 0 to 4+ to examine the relationship between urine protein and neonatal NSE. ResultsOf the 86 selected neonates, there were 40 in control group and 46 in preeclampsia group. The NSE levels were significantly higher in infants with preeclampsia exposure compared to those infants in control group (45.504 ± 17.926 vs 30.690 ± 4.475, P < 0.0001). Multiple regression analyses revealed that the preeclampsia (β coef = 0.394, p = 0.041), 4+ proteinuria (β coef = 0.558, p < 0.0001) and 3+ proteinuria (β coef = 0.356, p = 0.005) were significant independent variables predicting elevated serum NSE concentration. ConclusionFor the first time, this research has suggested the increase of neonatal NSE in preeclampsia, and the quantity of maternal proteinuria may be able to predict neonatal NSE elevation. Long-term neurodevelopmental follow-up and targeted preventive strategies are advised for this underrecognized high-risk population.

Neuron-Specific Markers and their Correlation with Neurological Scales in Patients with Acute Neuropathologies.

In predicting outcomes in patients with acute brain injury, current practice focuses special attention on neuron-specific proteins that reliably reflect the severity of the lesion. Further studies of molecular markers and their specificity and sensitivity could contribute to broadening the understanding of pathophysiological, diagnostic, and prognostic methods, which is vital to reducing the mortality and disability associated with these critical conditions. The purpose of this study was to assess the biomarkers of brain lesions and their correlative relations with the integral Glasgow Coma Scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) in predicting severity and treatment outcomes in patients with acute neuropathologies. Ninety patients were examined, including those with traumatic brain lesions (16.6%, n= 15), hemorrhagic stroke (52.2%, n= 47), and ischemic stroke (31.1%, n= 28). Patients were classified into two groups according to the outcome of the disease: those who survived (group I, 57.8%, n= 52) and those who died (group II, 42.2%, n= 38). In comparison with the survivors, the group of patients who died demonstrated an initial increase in neuron-specific enolase (NSE) by 1.23 and S100 by 6.45 times, and in dynamics by 1.5 and 7.4 times. A significant correlation with NIHSS and GCS was determined for NSE (r = 0.1149; P= 0.3073 and r = -0.0758; P= 0.5011) and for S100 (r = 0.3243; P= 0.0031 and r = -0.2661; P= 0.0163). The receiver operating characteristic (ROC) curves were 0.828 for S100 and 0.712 for NSE. The degree of sensitivity and specificity of the markers was studied. Increased levels of S100 and NSE correlated with NIHSS and GCS, with sensitivity of 80.77 and 63.46% and specificity of 42.11 and 73.68%, respectively, and were predictive of adverse disease outcome. The survival analysis showed that early detection of these biomarkers enables the timely prognostication of the progression of secondary brain injury and aids in implementing treatment.

Serum neuron-specific enolase measurement for neuro-prognostication post out-of-hospital cardiac arrest: Determination of the optimum testing strategy in routine clinical use.

Background Measurement of serum neuron-specific enolase (NSE) for neuro-prognostication post out-of-hospital cardiac arrest (OHCA) is recommended by international guidelines. There is, however, a lack of consensus regarding the cut-offs and time points to use. In addition, NSE is particularly susceptible to haemolysis interference. This study aimed to define the optimum NSE testing strategy to support the intensive care unit (ICU). Methods Patients admitted to ICU post-OHCA over 16 months had NSE measured. The outcome was survival to ICU discharge. NSE at 0 h, 24 h, 48 h, 72 h and change in NSE (ΔNSE) were assessed for prognostic accuracy using receiver operator characteristic curve analysis. The magnitude of haemolysis interference was quantified by spiking haemolysate into paired serum. Results There is a consistent linear increase in NSE with increasing haemolysis, independent of baseline NSE concentration. A haemolysis index acceptance threshold was defined as 20. There were 142 patients, and 82 survived to ICU discharge. The NSE parameter with best predictive performance was ΔNSE at 48 h, which had an area under the receiver operator characteristic curve of 0.91. A cut-off of &gt;0 μg/L at this time point had sensitivity of 80% and specificity of 97% for predicting death on ICU. When patients who died of non-neurological causes were removed, the sensitivity increased to 91%. Conclusions Application of a stringent haemolysis interference threshold and measurement of NSE at two time points enabled us to achieve excellent discrimination. Increasing NSE over the first 48 h, suggestive of an ongoing reperfusion injury to the brain, is a strong predictor of poor outcome.

Analysis of the neuronal damage severity and cognitive status in patients after operations on the aortic arch

Aim. To assess the neuronal damage severity and cognitive status in conditions of unilateral antegrade cerebral perfusion through the brachiocephalic trunk during surgical reconstruction of the thoracic aorta. Material and methods. The study included 144 patients with aneurysm and dissection of the thoracic aorta. Patients underwent reconstructive surgery under cardiopulmonary bypass, unilateral antegrade cerebral perfusion and circulatory arrest. Before and after the intervention, a cognitive status analysis was performed using the Montreal Cognitive Assessment (MoCA), Amatinu test and Schulte tables. The dynamics of neuron-specific enolase (NSE), a marker of neuronal damage, was determined perioperatively. Results. The duration of cardiopulmonary bypass was 155 [115; 201] min, cardioplegic arrest — 100 [72; 150] min, unilateral perfusion — 20 [15; 51] min,circulatory arrest — 20 [15; 30]min.Hospital mortality was 7% (10 cases). Neurological complications were noted in 12 (8%) cases. All patients in the postoperative period (within 24 hours) showed an increase in NSE compared with baseline values (3,3 μg/L and 2,07 μg/L, respectively, p=0,0003), but not exceeding the upper limit of normal (9,9 μg/l). According to the results of psychometric tests, which were carried out upon admission to the hospital and 2 weeks after the operation, there were no negative changes (MoCA test: 24 [21; 26] points — 26 [24; 27] points, p=0,00001; Schulte tables: 288 [240; 368] s — 278 [241; 328] s, p=0,01; Amatuni sample 264 [216; 297] s — 254 [221; 280] s, p=0,57). Conclusion. Based on the analysis of the perioperative dynamics of neuronspecific enolase and cognitive tests, unilateral cerebral perfusion through the brachiocephalic trunk is effective and relatively safe. This method of perfusion protection of the brain helps to minimize postoperative neurological complications during operations on the thoracic aorta.