Neuron-specific Enolase Levels In Cerebrospinal Fluid Research Articles

Association of ultra-early diffusion-weighted magnetic resonance imaging with neurological outcomes after out-of-hospital cardiac arrest

BackgroundThis study aimed to investigate the association between ultra-early (within 6 h after return of spontaneous circulation [ROSC]) brain diffusion-weighted magnetic resonance imaging (DW-MRI) and neurological outcomes in comatose survivors after out-of-hospital cardiac arrest.MethodsWe conducted a registry-based observational study from May 2018 to February 2022 at a Chungnam national university hospital in Daejeon, Korea. Presence of high-signal intensity (HSI) (PHSI) was defined as a HSI on DW-MRI with corresponding hypoattenuation on the apparent diffusion coefficient map irrespective of volume after hypoxic ischemic brain injury; absence of HSI was defined as AHSI. The primary outcome was the dichotomized cerebral performance category (CPC) at 6 months, defined as good (CPC 1–2) or poor (CPC 3–5).ResultsOf the 110 patients (30 women [27.3%]; median (interquartile range [IQR]) age, 58 [38–69] years), 48 (43.6%) had a good neurological outcome, time from ROSC to MRI scan was 2.8 h (IQR 2.0–4.0 h), and the PHSI on DW-MRI was observed in 46 (41.8%) patients. No patients in the PHSI group had a good neurological outcome compared with 48 (75%) patients in the AHSI group. In the AHSI group, cerebrospinal fluid (CSF) neuron-specific enolase (NSE) levels were significantly lower in the group with good neurological outcome compared to the group with poor neurological outcome (20.1 [14.4–30.7] ng/mL vs. 84.3 [32.4–167.0] ng/mL, P < 0.001). The area under the curve for PHSI on DW-MRI was 0.87 (95% confidence interval [CI] 0.80–0.93), and the specificity and sensitivity for predicting a poor neurological outcome were 100% (95% CI 91.2%–100%) and 74.2% (95% CI 62.0–83.5%), respectively. A higher sensitivity was observed when CSF NSE levels were combined (88.7% [95% CI 77.1–95.1%]; 100% specificity).ConclusionsIn this cohort study, PHSI findings on ultra-early DW-MRI were associated with poor neurological outcomes 6 months following the cardiac arrest. The combined CSF NSE levels showed higher sensitivity at 100% specificity than on DW-MRI alone. Prospective multicenter studies are required to confirm these results.

Нейронспецифическая енолаза ликвора как объективный маркер когнитивных нарушений при ВИЧ-ассоциированной энцефалопатии

One of the main causes of cognitive dysfunction in a late stage of HIV infection is HIV-associated encephalopathy. The direct neurotropic impact of HIV creates the pathogenic basis for this clinical syndrome. The purpose — to evaluate the cognitive status and neuron-specific enolase (NSE) level in cerebrospinal fluid (CSF) in HIV-encephalopathy patients. Material and methods. 35 patients were included in the study. They were divided into two groups: 20 patients (9 females and 11 males) with cognitive dysfunction and confirmed diagnosis of HIV/AIDS and 15 patients (6 females and 9 males) were in comparison group. The cognitive status was investigated by mini-mental state examination (MMSE), international HIV-dementia scale (IHDS) and frontal assessment battery (FAB). CSF level of NSE were investigated by ELISA test. Results. Correlation between cognitive dysfunction severity and NSE level in CSF was determined in HIV-encephalopathy patients. Conclusion. NSE level changing in CSF is an objective indicator of clinical severity of HIV-encephalopathy and neurotropic impact of HIV.

Neuron-specific enolase level is a useful biomarker for distinguishing amyotrophic lateral sclerosis from cervical spondylotic myelopathy

The current study aimed to evaluate whether cerebrospinal fluid (CSF) neuron-specific enolase (NSE) levels are elevated in amyotrophic lateral sclerosis (ALS) and are effective in distinguishing ALS from cervical spondylotic myelopathy (CSM). We retrospectively evaluated 45 patients with ALS, 23 with CSM, 28 controls, and 10 with Parkinson’s disease (PD) who underwent analysis of CSF NSE levels. The control group comprised patients aged above 45 years who underwent lumbar puncture because of suspected neurological disorders that were ruled out after extensive investigations. CSF NSE levels were evaluated using the electro-chemiluminescent immunoassay. The ALS group had significantly higher CSF NSE levels than the CSM and control groups (P < 0.001 for both comparisons). The CSM, control, and PD groups did not significantly differ in terms of CSF NSE levels. A receiver-operating characteristic curve analysis was performed to assess the diagnostic value of CSF NSE levels in distinguishing ALS from CSM. The area under the curve for CSF NSE levels was 0.86. The optimal cutoff value was 17.7 ng/mL, with a specificity of 87% and a sensitivity of 80%. Hence, CSF NSE levels are elevated in ALS and are effective in distinguishing ALS from CSM.

Meta-analysis of cerebrospinal fluid neuron-specific enolase levels in Alzheimer\u2019s disease, Parkinson\u2019s disease, dementia with Lewy bodies, and multiple system atrophy

BackgroundThis study examined the usefulness of cerebrospinal fluid (CSF) neuron-specific enolase (NSE) levels as a candidate biomarker of neurodegeneration in Alzheimer’s disease (AD), Parkinson’s disease (PD), PD with dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).MethodsWe performed a systematic search of PubMed, the Cochrane Library, Scopus, and Google Scholar to find studies that measured CSF NSE levels in AD, PD, DLB, and/or MSA. For each disease, we pooled all available data and performed a meta-analysis, and meta-regression analyses of age and sex were conducted if the main analysis found a significant association.ResultsTwenty studies were included (13 for AD, 8 for PD/PDD/DLB, and 4 for MSA). Significantly elevated CSF NSE levels were detected in AD (Hedges’ g = 0.822, 95% confidence interval [95% CI] 0.332 to 1.311, p = 0.0010), but the data exhibited high heterogeneity (I2 = 88.43%, p < 0.001). The meta-regression analysis of AD showed that age (p < 0.001), but not sex, had a significant effect on CSF NSE levels. A meta-analysis of the pooled data for PD/PDD/DLB did not show any significant changes in the CSF NSE level, but a sub-group analysis of PDD/DLB revealed significantly elevated CSF NSE levels (Hedges’ g = 0.507, 95% CI 0.020 to 0.993, p = 0.0412). No significant changes in CSF NSE levels were detected in MSA.ConclusionsThe CSF NSE level may be a useful biomarker of neurodegeneration in AD and PDD/DLB. Age was found to affect the CSF NSE levels of AD patients.

Neuron-specific enolase in cerebrospinal fluid as a biomarker of brain damage in infants with hypoxic-ischemic encephalopathy.

Neuron-specific enolase in cerebrospinal fluid as a biomarker of brain damage in infants with hypoxic-ischemic encephalopathy.

Relationship between YKL-40, neuron-specific enolase, tumor necrosis factor-a, interleukin-6, and clinical assessment scores in traumatic brain injury

Background and Objectives: The aim of the present study is to determine plasma and cerebrospinal levels of YKL-40, in combination with neuron-specific enolase (NSE), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and the clinical scales such as Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation a III, and MARSHALL classification in traumatic brain injury (TBI). Materials and Methods: This was a prospective study conducted on patient cohort of 27 patients with isolated severe TBI. Cerebrospinal fluid (CSF) and plasma were collected on the 24th and 96th h after trauma. CSF samples were obtained also from forensic autopsies of 29 adult healthy cadavers. Results: The CSF level of YKL-40 in TBI patients was higher compared to controls, while no significant change between CSF NSE levels in patients and controls was found. We determined a strong correlation between YKL-40 and NSE levels and TBI clinical assessment scores. The analysis of the influence of independent prognostic factors on the outcome of TBI patients showed that plasma NSE concentrations are the major independent variable which is associated with the survival of TBI patients. Still, changes in IL-6 and TNF-α levels could not be considered as reliable predictors of mortality. Conclusion: We present data for correlation of YKL-40 and NSE levels with clinical scores for assessment of trauma severity and the outcome of TBI patients. Even though further large-scale investigations are required to clarify and evaluate the clinical significance of both biomarkers, our findings suggest that YKL-40 and NSE might be implicated in the pathogenesis of TBI and could indicate the degree of neuroinflammation and brain damage.

Intravenous Hydrogen Therapy With Intracisternal Magnesium Sulfate Infusion in Severe Aneurysmal Subarachnoid Hemorrhage.

Poor-grade subarachnoid hemorrhage still has a poor prognosis. This randomized controlled clinical trial evaluated intracisternal magnesium sulfate infusion combined with intravenous hydrogen therapy in patients with poor-grade subarachnoid hemorrhage. Thirty-seven patients with poor-grade subarachnoid hemorrhage were randomized to Mg+H2, Mg, and control groups. Mg and Mg+H2 groups received intracisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days. Mg+H2 group also received intravenous hydrogen-rich solution infusion for 14 days. Primary outcome measures were occurrence of delayed cerebral ischemia and cerebral vasospasm. Secondary outcome measures were modified Rankin Scale and Karnofsky performance status at 3 and 12 months, Barthel index at 12 months, and serum and cerebrospinal fluid malondialdehyde and neuron-specific enolase. Serum neuron-specific enolase levels were significantly lower in the Mg+H2 group from days 3 to 14 than in the control group. Cerebrospinal fluid neuron-specific enolase levels were also significantly lower in the Mg+H2 group from days 3 to 7 than in the control group. Incidences of cerebral vasospasm and delayed cerebral ischemia were significantly higher in the control group than in other groups. Modified Rankin Scale and Karnofsky performance status did not significantly differ between the three groups at 3 months. Modified Rankin Scale scores 0 to 2 were more common in the Mg and Mg+H2 groups at 1 year. Barthel index was higher in the Mg+H2 group than in the control group. Intracisternal magnesium sulfate infusion started immediately after surgery reduces the incidence of cerebral vasospasm and delayed cerebral ischemia and improves clinical outcomes without complications in patients with poor-grade subarachnoid hemorrhage. Intracisternal magnesium sulfate infusion combined with intravenous hydrogen therapy decreases serum malondialdehyde and neuron-specific enolase and improves Barthel index, indicating hydrogen has additional effects. Registration: URL: https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000014696.

Abstract 348: Impact of Low and High Partial Pressure of Carbon Dioxide on Neuron Specific Enolase Derived from Serum and Cerebrospinal Fluid in Patients Who Underwent Targeted Temperature Management After Out-of-hospital Cardiac Arrest: A Retrospective Study

Aim: In a previous study, low and high-normal arterial carbon dioxide tension (PaCO 2 ) were not associated with serum neuron specific enolase (NSE) in cardiac arrest survivors. We assessed the effect of PaCO 2 on NSE in cerebrospinal fluid (CSF) and serum. Methods: This was a retrospective study. PaCO 2 for the first 24 h was analysed in four means, qualitative exposure state (qES), time-weighted average (TWA), median, and minimum-maximum (Min-Max). These subgroups were divided into low (LCO 2 ) and high PaCO 2 (HCO 2 ) groups defined as PaCO 2 ≤35.3 and PaCO 2 &gt;43.5 mmHg, respectively. NSE was measured at 24, 48, and 72 h (sNSE 24,48,72 and cNSE 24,48,72 ) from return of spontaneous circulation (ROSC). The primary outcome was the association between PaCO 2 and the NSE measured at 24 h after ROSC. Results: Forty-two subjects (male, 33; 78.6%) were included in total cohort. PaCO 2 in TWA subgroup was associated with cNSE 24,48,72 , while PaCO 2 in the other subgroup were only associated with cNSE 24 . PaCO 2 and cNSE in qES subgroup showed good correlation (r= -0.61; p&lt; 0.01), and in TWA, Median, and Min-Max subgroup showed moderate correlations (r= -0.57, r= -0.48, and r= -0.60; p&lt; 0.01). Contrastively, sNSE was not associated and correlated with PaCO 2 in all analysis. Poor neurological outcome in LCO 2 was significantly higher than HCO 2 in qES, TWA, and Median subgroups ( p&lt; 0.01, p&lt; 0.01, and p= 0.02). Conclusion: Association was found between NSE and PaCO 2 using CSF, despite including normocapnic ranges; TWA of PaCO 2 may be most strongly associated with CSF NSE levels. A prospective, multi-centre study is required to confirm our results.

Lactic acid, neuron-specific enolase, and blood–brain barrier index after a severe traumatic brain injury: a prospective study

Objective To explore the clinical significance of dynamic monitoring of cerebrospinal fluid (CSF) and serum Lactic acid（Lac), neuron-specific enolase (NSE), and the blood–brain barrier (BBB) index in evaluating the condition and prognosis after a severe traumatic brain injury (TBI). Methods A total of 52 severe TBI patients admitted to the Department of Neurosurgery within 24 hours after injury were dynamically monitored. CSF and serum samples were collected on the 1st, 3rd, and 7th day after a severe TBI to monitor the changes in Lac, NSE, and the BBB index. Intracranial pressure (ICP), Glasgow coma scale (GCS), and 6-month Glasgow outcome scale-extended (GOS-E) were tested. According to the results of GOS-E, the patients were divided into two groups (i.e. the poor prognosis group and good prognosis group). Statistical analysis was conducted to investigate the clinical significance of dynamic monitoring of CSF and serum Lac, NSE, and BBB index after a severe TBI. Results After a severe TBI, the levels of Lac, NSE, and BBB in CSF and serum were significantly higher than those in the normal range. Lac, NSE, and the BBB index did not correlate with ICP (except serum Lac) but had correlations with GCS and post-injury 6 months post-injury (except serum Lac). Moreover, the correlations between Lac, NSE, and BBB index were statistically significant (p < 0.05): CSF Lac and CSF NSE; CSF Lac and serum NSE; Lac and BBB index of CSF; Lac and BBB index of CSF; NSE and CSE of serum; CSF NSE and BBB index; and serum NSE and BBB index. Additionally, serum NSE is correlated with NSE in CSF (p < 0.05). Conclusion After a severe TBI, dynamic monitoring of CSF and serum Lac, NSE, and BBB index has the potential to assess the condition, predict the prognosis, and have clinical significance.

Impact of low and high partial pressure of carbon dioxide on neuron-specific enolase derived from serum and cerebrospinal fluid in patients who underwent targeted temperature management after out-of-hospital cardiac arrest: A retrospective study

AimIn a previous study, low and high-normal arterial carbon dioxide tension (PaCO2) were not associated with serum neuron-specific enolase (NSE) in cardiac arrest survivors. We assessed the effect of PaCO2 on NSE in cerebrospinal fluid (CSF) and serum. MethodsThis was a retrospective study. PaCO2 for the first 24 h was analysed in four means, qualitative exposure state (qES), time-weighted average (TWA), median, and minimum–maximum (Min–Max). These subgroups were divided into low (LCO2) and high PaCO2 (HCO2) groups defined as PaCO2 ≤ 35.3 and PaCO2 > 43.5 mmHg, respectively. NSE was measured at 24, 48, and 72 h (sNSE24,48,72 and cNSE24,48,72) from return of spontaneous circulation (ROSC). The primary outcome was the association between PaCO2 and the NSE measured at 24 h after ROSC. ResultsForty-two subjects (male, 33; 78.6%) were included in total cohort. PaCO2 in TWA subgroup was associated with cNSE24,48,72, while PaCO2 in the other subgroup were only associated with cNSE24. PaCO2 and cNSE in qES subgroup showed good correlation (r = −0.61; p < 0.01), and in TWA, median, and Min–Max subgroup showed moderate correlations (r = −0.57, r = −0.48, and r = −0.60; p < 0.01). Contrastively, sNSE was not associated and correlated with PaCO2 in all analysis. Poor neurological outcome in LCO2 was significantly higher than HCO2 in qES, TWA, and median subgroups (p < 0.01, p < 0.01, and p = 0.02). ConclusionAssociation was found between NSE and PaCO2 using CSF, despite including normocapnic ranges; TWA of PaCO2 may be most strongly associated with CSF NSE levels. A prospective, multi-centre study is required to confirm our results.

Cerebrospinal fluid levels of neuron-specific enolase predict the severity of brain damage in newborns with neonatal hypoxic-ischemic encephalopathy treated with hypothermia.

To investigate whether cerebrospinal fluid levels of neuron-specific enolase (CSF-NSE) during the first 72 hours correlate with other tools used to assess ongoing brain damage, including clinical grading of hypoxic-ischemic encephalopathy (HIE), abnormal patterns in amplitude integrated electroencephalography (aEEG), and magnetic resonance imaging (MRI), as well as with the neurodevelopmental outcomes at two years of age. Prospective observational study performed in two hospitals between 2009 and 2011. Forty-three infants diagnosed with HIE within 6 hours of life were included. HIE was severe in 20 infants, moderate in 12, and mild in 11. Infants with moderate-to-severe HIE received whole-body cooling. Both the HIE cohort and a control group of 59 infants with suspected infection underwent measurement of CSF-NSE concentrations at between 12 and 72 hours after birth. aEEG monitoring was started at admission and brain MRI was performed within the first 2 weeks. Neurodevelopment was assessed at 24 months. The HIE group showed higher levels of CSF-NSE than the control group: median 70 ng/ml (29; 205) vs 10.6 ng/ml (7.7; 12.9); p <0.001. Median levels of CSF-NSE in infants with severe, moderate, and mild HIE were 220.5 ng/ml (120.5; 368.8), 45.5 ng/ml (26, 75.3), and 26 ng/ml (18, 33), respectively. CSF-NSE levels correlated were significantly higher in infants with seizures, abnormal aEEG, or abnormal MRI, compared to those without abnormalities. Infants with an adverse outcome showed higher CSF-NSE levels than those with normal findings (p<0.001), and the most accurate CSF-NSE cutoff level for predicting adverse outcome in the whole cohort was 108 ng/ml and 50ng/ml in surviving infants. In the era of hypothermia, CSF-NSE concentrations provides valuable information as a clinical surrogate of the severity of hypoxic-ischemic brain damage, and this information may be predictive of abnormal outcome at two years of age.

Cerebrospinal fluid neuron specific enolase, interleukin-1β and erythropoietin concentrations in children after seizures.

In the present study, the levels of neuron-specific enolase (NSE), interleukin-1β (IL-1β), and erythropoietin (EPO) in cerebrospinal fluid (CSF) in children with idiopathic epilepsy were measured to illuminate the relationships between these markers with idiopathic epilepsy. Eighty-five children from 6 months to 12.5 years of age with single, previously undiagnosed, and untreated idiopathic epilepsy were participated in this study. The concentrations of CSF NSE, 1L-1β, and EPO were measured by specific ELISA methods. The mean concentrations of CSF NSE, IL-1β, and EPO in the epileptic groups showed a significant increase (P < 0.01) compared with those in the control groups. Besides, the mutual correlations of NSE, 1L-1β, and EPO were also analyzed. Results showed that there were positive correlations between the levels of IL-1β, NSE, and EPO. The changes of NSE, 1L-1β, and EPO level in CSF may be beneficial for the pathophysiology study of epileptic seizures and the identification and diagnosis of a seizure clinically.

The level of neuron-specific enolase and S-100 protein in the cerebrospinal fluid of patients with acute bacterial meningitis

Aim. To evaluate the diagnostic and prognostic role of neuron-specific enolase (NSE) and S-100 protein levels in cerebrospinal fluid (CSF) of patients with acute bacterial meningitis in the course of the disease.Materials and Methods. 54 cases of acute bacterial meningitis were analyzed, among them – 26 with pneumococcal and 28 with meningococcal etiology. Patients were divided into groups depending on the severity and etiology of disease. In addition to routine laboratory methods, we analyzed the CSF levels of S-100 protein and NSE at admission and after 10 – 12 days of treatment. 12 patients with acute respiratory infections and meningism were examined as a comparison group.Results. In all patients with acute bacterial meningitis CSF NSE and protein S-100 levels were significantly higher than in the control group (P <0,05). CSF neuro specific proteins level was in direct dependence on severity of the disease, and in patients with severe disease was significantly higher than in patients with moderate severity and in the control group (P <0,01). After 10 – 12 days of treatment, the level of the NSE and S-100 protein decreased, but in severe cases was still higher than in the control group (P <0,05).Conclusions. Increased cerebrospinal fluid NSE and S – 100 protein levels shows the presence and value of neurons and glial cells damage in patients with acute bacterial meningitis. CSF S-100 protein and neuron-specific enolase levels help to determine the severity of neurons destruction and glial cells in patients with acute bacterial meningitis. Level of neurospecific protein is in direct proportion to the severity of the disease and is the highest in patients with severe cases (P<0,05). It confirms the diagnostic and prognostic value of CSF neurospecific protein determination in patients with bacterial meningitis.

Neuron-specific enolase in cerebrospinal fluid as a neurochemical marker for brain damage in acute lymphoblastic leukemia

Background Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer with a cure rate approaching 80%. Neuron-specific enolase (NSE) is known to be a cell-specific isoenzyme of the glycolytic enzyme enolase. The expression of NSE is a late event in neural differentiation, thus making it a useful index of neural maturation. It is a highly specific marker for neurons and peripheral neuroendocrine cells. NSE in cerebrospinal fluid (CSF) is a reliable marker of neuronal damage. It is believed to signal for brain damage after hypoxic-ischemic and traumatic injury. Objective and methods This study aimed to measure CSF levels of NSE as a neurochemical marker for brain damage in response to chemotherapy at diagnosis and during induction using the enzyme-linked immunosorbent assay method. Thirty newly diagnosed ALL patients were enrolled in this study, comprising 19 male and 11 female patients. Results NSE level in the CSF samples increased from 9.3 ± 2.1 μg/l on day 0 (before the start of treatment) to 14.9 ± 1.85 μg/l on day 7 and then gradually decreased to 11.4 ± 1.46 μg/l on day 28. The increase in NSE levels in CSF on days 7 and 28 was considered highly significant when compared with those measured on day 0 (before induction therapy). Conclusion We concluded that the increase in NSE in CSF during induction therapy in children with ALL can be interpreted as an early sign of brain damage.

Elevated levels of cerebrospinal fluid neuron-specific enolase (NSE), but not S100B in major depressive disorder

Objectives. Alterations in neuronal and glial integrity are considered to be of pathogenic impact on major depressive disorder (MDD). For MDD, data on cerebrospinal fluid (CSF) levels of neuron-specific enolase (NSE) are lacking and scarce for glial protein S100B. Methods. We measured CSF levels of NSE and S100B in 31 patients with MDD and 32 mentally healthy controls using electrochemiluminescence immunoassays (ECLIA). Results. Adjusted means of NSE were significantly elevated in the MDD patients (11.73 ng/ml (9.95–13.52 95% CI) compared to the controls (6.17 ng/ml (4.55–7.78), F = 9.037, P = 0.004. Effect size for adjusted mean group difference of 5.57 ng/ml was found invariably high (Cohen’s d = 1.23). Differentiating MDD from controls, a NSE cut-off of 7.94 ng/ml showed sensitivity of 81% (95% CI 63.7–90.8) and specificity of 75% (95% CI 57.9–86.7). Adjusted levels of S100B did not differ significantly between the two groups (1.12 ng/ml (0.77–1.48) in MDD, 0.97 ng/ml (0.64–1.30) in controls). Conclusions. Our results of elevated CSF-NSE levels support neuronal pathology in MDD and the potential use of CSF-NSE as marker in clinical diagnostics. Missing group differences in S100B do not promote a specific glial pathology in depressive disorders.

The effect of therapeutic hypothermia after cardiopulmonary resuscitation on ICAM-1 and NSE levels in sudden cardiac arrest rabbits

Purpose: To assess the effects of hypothermia and normothermia treatments for sudden cardiac arrest (SCA) on brain injury recovery in rabbit models. Methods: Cardiopulmonary resuscitation (CPR) was implemented on apnea-induced SCA rabbit models. Fifty survived rabbits were then randomly received hypothermia (n = 25, 32–34°C) or normothermia treatment (n = 25, 39–39.5°C) for 12 hours. The expected body temperatures were achieved within the first two hours, maintained for ten hours and then rewarmed. The physiological parameters, neurologic function, and the levels of adhesion molecule ICAM-1 and neuron-specific enolase (NSE) were monitored. Results: Hypothermia-treated rabbits had lower heart rate when achieving hypothermia (p < 0.0001) and higher SjvO2 after hypothermia maintenance (p = 0.038). The hypothermia group achieved better brain recovery performance according to the neurological deficit grading scale. ICAM-1 and NSE levels in both serum and CSF of the hypothermia group were lower than the normothemia group (all p < 0.0001) during hypothermia maintenance. Conclusion: Hypothermia treatment after CPR provides better outcome than normothermia treatment in SCA rabbits. Hypothermia can reduce the ICAM-1 and NSE levels in both serum and cerebrospinal fluid (CSF). This study supports the clinical implementation of hypothermia treatment for SCA and reveals that ICAM-1 and NSE are involved in the recovery of brain function after resuscitation.

The role of oxidative stress in perinatal hypoxic-ischemic brain injury

The pathogenesis of perinatal hypoxic-ischemic brain damage is highly complex. The aim of this study was to assess the role of oxidative stress in hypoxic-ischemic brain injury and subsequent abnormal neurological outcome in infants with perinatal hypoxic-ischemic encephalopathy (HIE). We estimated perinatal oxidative brain damage measuring activity of glutathione peroxidase (GPX) in cerebrospinal fluid (CSF) as an indirect biomarker of free radical production during cerebral hypoxia-ischemia in correlation with the level of intracellular enzyme neuron specific enolase (NSE) in CSF as a biomarker of extend of brain injury. Ninety neonates (>32 GA) with perinatal HIE were enrolled prospectively. HIE was categorized into three stages according Sarnat and Sarnat clinical scoring system and changes seen on amplitude integrated EEG. CSF for GPX analysis and NSE analysis was taken in the first 72 hours of life. Neurodevelopment outcome was assessed at 12 months of corrected gestational age. GPX activity in CSF was in good relation with clinical stage of HIE (p < 0.0001) and GA (p < 0.0001) and significantly corresponded with subsequent neurodevelopment outcome (p < 0.001). GPX activity in CSF showed a strong correlation with NSE levels in CSF (p < 0.001) as the biomarker of extent of brain injury. Our results suggest that oxidative stress might be important contributing factor in perinatal hypoxic-ischemic brain damage, particularly in preterm neonates.

Prognostic value of biochemical markers of brain damage and oxidative stress in post-surgical aneurysmal subarachnoid hemorrhage patients

The aim of this study is to determine effective biochemical markers and optimal sampling timing for prediction of neurological prognosis in post-surgical aneurysmal subarachnoid hemorrhage (SAH) patients. Subjects were a sequential group of SAH patients admitted to our centre who underwent aneurysm clipping before Day 3 and who received a cerebrospinal fluid (CSF) drain. CSF samples from 32 patients were collected on Days 3, 7, and 14. Neurological outcome was assessed by neurosurgeons using the Glasgow outcome scale (GOS) at 6 months after onset. CSF levels of neuron-specific enolase (NSE), S100B, and glial fibrillary acidic protein (GFAP) were determined using enzyme-linked immunosorbent assay, and the CSF concentrations of malondialdehyde (MDA) were determined using spectrophotometric assay. In univariate analysis, S100B on Days 3 and 14, GFAP on Days 3 and 7, and MDA on Day 14 were significantly higher in the poor outcome group (GOS 1–4) than in the good outcome group (GOS 5). In multivariate analysis, only MDA on Day 14 was identified as a significant predictor of poor neurological outcome at 6 months after onset. The area under the receiver-operating characteristic (ROC) curve for MDA on Day 14 was 0.841. For a threshold of 0.3 μM, sensitivity and specificity were 0.875 and 0.750, respectively. Our findings suggest that these biochemical markers, especially MDA, show significant promise as predictors of neurological outcome in clinical practice.

Elevation of neuron-specific enolase and S-100β protein level in experimental acute spinal cord injury

We evaluated the protein levels of neuron-specific enolase (NSE) and S-100β in serum and cerebrospinal fluid (CSF) in an animal model of acute spinal cord injury and ascertained their relevance. Spinal cord injury was induced at the T8 level in rats. Enzyme-linked immunosorbent assay was used to measure the protein levels of NSE and S-100β in both serum and CSF at different time points (30 min, 2 h, 6 h, 12 h and 24 h after induction of spinal cord injury). There existed a significant correlation between neurological deficits and the severity of spinal cord injury ( p < 0.05). Compared with the control group, the protein levels of NSE and S-100β in serum and CSF significantly increased from 2 h after injury ( p < 0.05) and reached a maximum at 6 h. Within a certain time window, the protein levels of NSE and S-100β in serum and CSF were closely related to the severity of injury level ( p < 0.05). The protein levels of NSE and S-100β in serum and CSF significantly increased after experimental spinal cord injury in a time-dependent manner and thus may be considered specific biomarkers for acute spinal cord injury.

Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults

To study the occurrence of relapse of herpes simplex encephalitis (HSE) and to find out whether soluble activity markers in cerebrospinal fluid (CSF) indicate direct viral or immune- mediated events. A consecutive series of 32 adult survivors of HSE were followed to determine the incidence of clinical relapse of HSE. Four patients had neurological deterioration interpreted as relapsing HSE. Four non-relapsing HSE cases were selected as matched controls. Fifty nine batched, paired CSF and serum samples from the eight HSE patients were analysed for soluble activity markers, predominantly cytokines and mediators (interferon-gamma, soluble CD8, tumour necrosis factor-alpha, and interleukin-10), amount of HSV-DNA and markers of glial and neuronal destruction (neurofilament protein, glial fibrillary acidic protein, S-100-beta, and neuron specific enolase). Relapse of HSE was diagnosed in 3 of 26 (12 %) acyclovir-treated patients (5 episodes during 6.1 years of followup) and in 1 of 6 vidarabine-recipients. All relapses occurred from 1 to 4 months after acute HSE, except for a second relapse after 3.3 years in one patient. Computer tomography at relapses revealed few abnormalities apart from those found during the primary disease. Intravenous acyclovir and corticosteroids were given for 7-21 days in all the relapse patients. All relapse patients seemed to recover to the pre-relapse condition. HSV-DNA was demonstrated in CSF in all patients during the acute stage but not in any of 13 CSF samples taken during relapse phases. The HSV viral load during the acute stage of HSE was not higher or of longer duration in the relapsing patients than in the non-relapsing HSE controls. The levels of sCD8 were increased in nearly all CSF samples tested with peaks of sCD8 at one month of acute HSE. In all episodes of relapse, sCD8 peaks were detected during the first week at high levels. CSF levels of neuron-specific enolase, S-100 and glial fibrillary acidic protein were markedly lower at relapse than at the acute stage of HSV-1 encephalitis. The lack of demonstrable HSV DNA in CSF, the lack of acute CSF signs and the lack of signs of neural and glia cells destruction indicate that a direct viral cytotoxicity is not the major pathogenic mechanism in relapse. Instead, the pronounced CSF proinflammatory immunological response and the relative lack of CSF anti-inflammatory cytokine IL-10 response suggest immunologically-mediated pathogenicity.