Serum Neuron-specific Enolase Concentrations Research Articles

Serum neuron-specific enolase levels are upregulated in patients with acute lymphoblastic leukemia and are predictive of prognosis.

We explored the relationship between neuron-specific enolase (NSE) levels and the clinical features of acute lymphoblastic leukemia (ALL). Seventy ALL patients and forty-two healthy controls were enrolled in this study, and their serum NSE levels were measured using an electrochemiluminescence assay. The serum NSE concentration was higher in ALL patients than in healthy controls. In ALL patients, the mean serum NSE level declined after complete remission (CR) but increased with relapse. In addition, the mean serum NSE level was lower in the CR group than in the non-CR group. High NSE levels were associated with poorer progression-free and overall survival than low NSE levels. Serum NSE levels closely correlated with several clinical features, including the immunophenotype, risk stratification and serum lactate dehydrogenase levels. Multivariate analysis revealed that high NSE expression was an independent prognostic factor in adult ALL patients. NSE mRNA levels were also higher in ALL cell lines and bone marrow mononuclear cells from ALL patients than in control cells. These results suggested that NSE could be a clinical prognostic factor and a potential therapeutic target in ALL.

Neuron-specific enolase as a novel biomarker reflecting tuberculosis activity and treatment response.

Background/Aims:It is not clear which tests are indicative of the activity and severity of tuberculosis (TB). This study aimed to investigate the predictive value of neuron-specific enolase (NSE) and to determine the origin of NSE in TB patients.Methods:A single-center retrospective analysis was conducted on newly diagnosed TB patients between January and December 2010. Patients were categorized into one of two disease groups (focal segmental or extensive) based on chest X-ray. Pre- and post-treatment NSE concentrations were evaluated. To determine the origin of serum NSE concentration, NSE staining was compared with macrophage-specific CD68 staining in lung tissues and with a tissue microarray using immunohistochemistry and immunofluorescence.Results:A total of 60 newly diagnosed TB patients were analyzed. In TB patients, NSE serum concentration was significantly increased and NSE level decreased after treatment (p < 0.001). In proportion to serum high-sensitivity C-reactive protein concentration, the mean serum concentration of NSE in the extensive group (25.12 ng/mL) was significantly higher than that in the focal segmental group (20.23 ng/mL, p = 0.04). Immunohistochemical staining revealed a large number of macrophages that stained positively for both NSE and CD68 in TB tissues. In addition, NSE signals mostly co-localized with CD68 signals in the tissue microarray of TB patients.Conclusions:Our results suggest that NSE may be a practical parameter that can be used to monitor TB activity and treatment response. Elevated serum NSE level originates, at least in part, from macrophages in granulomatous lesions.

Effect of goal-directed fluid therapy on postoperative cognitive function in patients undergoing intracranial tumor resection

Objective To evaluate the effect of goal-directed fluid therapy (GDFT) on postoperative cognitive function in the patients undergoing intracranial tumor resection. Methods One hundred patients of both sexes, aged 45-64 yr, weighing 50-70 kg, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, scheduled for elective cerebral glioma or meningioma resection, were randomly divided into 2 groups(n=50 each) using a random number table: GDFT group (group G) and conventional fluid therapy group (group C). The mean arterial pressure was maintained at 65-110 mmHg, urine volume >0.5 ml·kg-1·h-1, and central venous pressure at 8-12 cmH2O in group C. In group G, GDFT was performed using FloTrac/Vigileo system, and the cardiac index was maintained at 2.5-4.0 L·min-1·m-2, stroke volume variation≤13%, mean arterial pressure at 65-110 mmHg, and stroke volume index at 35-47 ml/m2.The requirement for crystalloid and colloid, urine volume, blood loss, and requirement for vasoactive agents were recorded during operation.Before induction of anesthesia (baseline), when the dura of brain was opened, at the end of tumor removal, at the end of operation, and at 24 h after operation (T0-4), venous blood samples were taken to determine the concentrations of serum neuron-specific enolase (NSE) and S100β protein by enzyme-linked immunosorbent assay.The patient′s cognitive function was assessed using Mini-Mental State Examination at T0 and 7 days after operation (T5). Results Compared with the baseline value at T0, the serum NSE and S100β protein concentrations were significantly increased at T2-4 in the two groups (P 0.05). Conclusion GDFT based on FloTrac/Vililgeo system can reduce the damage to brains after operation, but it has no significant effect on postoperative cognitive function in the patients undergoing intracranial tumor resection. Key words: Fluid therapy; Cognition disorders; Neurosurgical procedures

Effect of recombinant human erythropoietin on brain injury in patients undergoing cardiac valve replacement with cardiopulmonary bypass

Objective To evaluate the effect of recombinant human erythropoietin (rHuEPO) on brain injury in the patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB). Methods Forty-five patients with chronic valvular heart disease, aged 36-62 yr, weighing 42-92 kg, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, with New York Heart Association of Ⅱ or Ⅲ, undergoing cardiac valve replacement with CPB, were randomly divided into 3 groups (n=15 each) using a random number table: control group (group C), and different doses of rHuEPO groups (EPO1 group, EPO2 group). In EPO1 and EPO2 groups, rHuEPO 40 and 80 IU/kg were injected intravenously before anesthesia induction, respectively.Before anesthesia induction (T0, baseline value), immediately after endotracheal intubation (T1), immediately after aortic cannulation (T2), immediately after cannulation of superior and inferior vena cava (T3), immediately after the beginning of CPB (T4), when each index was decreased to the minimal value during CPB (T5), after rewarming to 36.5 ℃ (T6), immediately after termination of CPB (T7), and at 1 h after termination of CPB (T8), regional cerebral oxygen saturation (rSO2), tissue hemoglobin index (THI), and changes in concentrations of oxyhemoglobin(△O2Hb), deoxyhemoglobin (△HHb) and total hemoglobin (△cHb) in bilateral frontal lobes were recorded.The patients whose minimal rSO2 ≤50% and decrease in minimal rSO2 ≥20% of the baseline value (△rSO2) were recorded.At T0, T8 and 2 h after termination of CPB (T9), venous blood samples were taken for determination of serum concentrations of S100 protein and neuron-specific enolase (NSE) by ELISA.At 1 day before surgery and 8 days after surgery, the patient's cognitive function was assessed using Mini-Mental State Examination, the Digit Span subtest of the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the Digit Symbol subtest of the WAIS-R, the Trailing Making Test (Part A) and the Stroop Color Word Interference Test, while depression and anxiety were assessed by Zung Self-Rating Depression Scale and Zung Self-Rating Anxiety Scale, respectively.The occurrence of postoperative cognitive dysfunction was recorded. Results There was no significant difference among the three groups in bilateral rSO2 and △cHb, incidence of bilateral rSO2 ≤50% and postoperative cognitive dysfunction, Zung Self-Rating Depression Scale score, and Zung Self-Rating anxiety Scale score at each time point (P>0.05). Compared with group C, the incidence of left △rSO2≥20% was significantly decreased, the right △O2Hb was increased at T6, 8, the serum NSE concentrations were decreased at T9, the serum S100 protein concentrations were decreased at T8, and the number of the Digit Symbol subtest of the WAIS-R completed was increased in group EPO1, and right THI was significantly decreased at T2, T3, T5, T7 and T8, right △HHb was increased at T2 and T3, and the completion time of Stroop color word interference test B was shortened at 8 days after surgery in group EPO2 (P<0.05 or 0.01). Compared with group EPO1, the incidence of left △rSO2≥20% was significantly increased, the right THI was decreased at T2-4 and T6-8, and the left △O2Hb at T6-7 and right △O2Hb at T8 were decreased in group EPO2 (P<0.05). Conclusion rHuEPO 40 IU/kg injected intravenously before induction of anesthesia can mitigate brain injury in the patients undergoing cardiac valve replacement with CPB. Key words: Erythropoietin, recombinant; Brain injuries; Cardiopulmonary bypass; Heart valve prosthesis implantation

Neuron-specific enolase in nasal secretions as a novel biomarker of olfactory dysfunction in chronic rhinosinusitis.

Olfactory dysfunction is a diagnostic criterion for chronic rhinosinusitis (CRS). During chronic inflammation and olfactory neuronal damage in CRS, it is likely that neuron-specific enolase (NSE) can leak into nasal secretions (NS) and serum. Therefore, we postulated that NSE levels in NS and in circulation may be indicative of olfactory dysfunction in CRS. To evaluate the relationship between the NS and serum concentrations of NSE with olfactory dysfunction in subjects with CRS. The patients with CRS were classified into two groups, depending on the presence of polyps: CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP). A group of age- and sex-matched healthy volunteers served as controls. Olfactory function assessment was performed by using Sniffin' Sticks. NSE concentrations in serum and NS were analyzed by using the enzyme immunometric assay kit specific for the γ subunit. The study included 46 patients with CRSsNP, 25 women (54.3%) and 21 men (45.7%), mean (standard deviation [SD]) age, 34.1 ± 12.3 years; and 54 patients with CRSwNP, 24 women (44.4%) and 30 men (55.6%), mean (SD) age, 37.9 ± 17.5 years. A group of 40 healthy volunteers who were matched for age and sex served as controls. Significantly higher serum and NS levels of NSE were measured in patients with CRS compared with healthy controls (p < 0.001). In the CRSwNP group, both mean (SD) serum (83.5 ± 37.6 ng/mL) and mean (SD) NS (6.1 ± 2.3 ng/mL) levels of NSE were significantly higher than in the CRSsNP group (46.4 ± 7.3 ng/mL [p < 0.001] and 1.7 ± 0.5 ng/mL [p < 0.001], respectively). In both the CRSsNP and CRSwNP groups (but not in the healthy controls), significant negative correlations between NS NSE levels and TDI scores (r = -0.63, p < 0.001 for the CRSwNP group, and r = -0.51, p < 0.001 for CRSsNP group) were observed, which meant that higher NSE was associated with worse olfactory function. The study demonstrated a contribution of CRS to NSE and olfactory dysfunction.

Serum carcinoembryonic antigen, neuron-specific enolase as biomarkers for diagnosis of nonsmall cell lung cancer.

To investigate the clinical efficacy of serum carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) as biomarkers for diagnosis of nonsmall cell lung cancer (NSCLC). Forty-six cytology or pathology confirmed nonsmall cell lung patients and 33 cases of benign lung disease (BLD) were retrospective reviewed in our hospital from February 2013 to January 2016. The serum concentrations of CEA and NSE were measured by chemiluminescent assay. The sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve (area under the curve) of serum CEA and NSE as biomarkers for diagnosis of lung cancer were analyzed by SPSS version 17.0 software. The serum CEA and NSE concentration were 30.69 ± 14.11 ng/mL, 52.36 ± 49.68 ng/mL for NSCLC patients and 12.69 ± 8.87 ng/mL, 5.32 ± 4.66 for BLD patients, respectively with statistical difference (P < 0.05); the diagnostic sensitivity and specificity were 58.66% and 76.48% for serum CEA at the cutoff value of 5.74 ng/mL and 66.67% and 78.69% for serum NSE at the cutoff value of 19.35 ng/mL; the diagnostic area under the ROC curve was 0.81 and 0.76 for CEA and NSE, respectively as biomarkers for diagnosis of NSCLC. Serum CEA and NSE are potential biomarker for NSCLC diagnosis.

Hydrogen sulfide improves neural function in rats following cardiopulmonary resuscitation.

The alleviation of brain injury is a key issue following cardiopulmonary resuscitation (CPR). Hydrogen sulfide (H2S) is hypothesized to be involved in the pathophysiological process of ischemia-reperfusion injury, and exerts a protective effect on neurons. The aim of the present study was to investigate the effects of H2S on neural functions following cardiac arrest (CA) in rats. A total of 60 rats were allocated at random into three groups. CA was induced to establish the model and CPR was performed after 6 min. Subsequently, sodium hydrosulfide (NaHS), hydroxylamine or saline was administered to the rats. Serum levels of H2S, neuron-specific enolase (NSE) and S100β were determined following CPR. In addition, neurological deficit scoring (NDS), the beam walking test (BWT), prehensile traction test and Morris water maze experiment were conducted. Neuronal apoptosis rates were detected in the hippocampal region following sacrifice. After CPR, as the H2S levels increased or decreased, the serum NSE and S100β concentrations decreased or increased, respectively (P<0.0w. The NDS results of the NaHS group were improved compared with those of the hydroxylamine group at 24 h after CPR (P<0.05). In the Morris water maze experiment, BWT and prehensile traction test the animals in the NaHS group performed best and rats in the hydroxylamine group performed worst. At day 7, the apoptotic index and the expression of caspase-3 were reduced in the hippocampal CA1 region, while the expression of Bcl-2 increased in the NaHS group; and results of the hydroxylamine group were in contrast. Therefore, the results of the present study indicate that H2S is able to improve neural function in rats following CPR.

Effect of sevoflurane on brain injury in pigs with hemorrhagic shock

Objective To evaluate the effect of sevoflurane on brain injury in pigs with hemorrhagic shock (HS). Methods Twenty-four adult male Bama miniature pigs, aged 6 months, weighing 22–25 kg, were equally and randomly divided into 3 groups using a random number table: sham operation group (group Sham), group HS, and sevoflurane group (S group). In group Sham, the bilateral femoral arteries and internal jugular vein were only punctured. The animals were anesthetized with iv propofol 3.0 mg/kg, tracheostomized and mechanically ventilated. The right femoral artery was cannulated for blood-letting.HS was induced by blood-letting (40% blood volume within 15 min), and it was then maintained for 1 h after the end of blood-letting to induce brain injury. In group S, 2% sevoflurane was inhaled for 30 min after successful establishment of the model. Immediately before establishment of the model (T0), and at 30, 60, 90, 120, 180 and 240 min after HS (T1-6), blood samples were collected from the internal jugular vein for determination of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) concentrations in serum (by enzyme-linked immunosorbent assay), and neuron-specific enolase (NSE) and S-100β protein concentrations in serum (using double antibody sandwich method). Results Compared with group Sham, the serum IL-1β, TNF-α, NSE and S-100β protein concentrations were significantly increased at T2-6 in HS and S groups (P<0.05). Compared with group HS, the serum IL-1β, TNF-α, NSE and S-100β protein concentrations were significantly decreased at T3-6 in group S (P<0.05). Conclusion Sevoflurane can mitigate brain injury in pigs with HS, and the mechanism is associated with inhibition of inflammatory responses. Key words: Anesthetics, inhalation; Shock, hemorrhagic; Brain injuries

S100B and NSE serum concentrations after simulated diving in rats.

The purpose of this study was to assess whether one could detect S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) in serum of rats after a simulated dive breathing air, with the main hypothesis that the serum concentrations of S100B and NSE in rats will increase above pre-exposure levels following severe decompression stress measured as venous gas emboli (VGE). The dive group was exposed to a simulated air dive to 700 kPa for 45 min. Pulmonary artery was monitored for vascular gas bubbles by ultrasound. Pre- and postdive blood samples were analyzed for S100B and NSE using commercially available Elisa kits. There was no increase in serum S100B or NSE after simulated diving and few of the animals were showing high bubble grades after the dives. The present study examined whether the protein biomarkers S100B and NSE could be found in serum from rats after exposure to a simulated dive to 700 kPa for 45 min breathing air. There were no differences in serum concentrations before versus after the dive exposure. This may be explained by the lack of vascular gas bubbles after the dives.

Brain function in children with untreated epilepsy: Relationship to biomarkers of brain damage

Many studies have reported cognitive and behavioral abnormalities with recurrent seizures in adults. Similar evidence from the pediatric population is scarce and controversial. We aimed to investigate the effect of recurrent seizures on the developing brain. Included were 42 children with epilepsy (mean age 14.1±1.72 yr) and 30 healthy children for comparison. Patients had recurrent untreated epilepsy (generalized or focal). Negative attitudes and misconceptions about epilepsy are common in developing countries, often resulting in neglect of medical services and treatment. Epilepsy is greatly misunderstood by the public, and is attributed to spiri- tual causes such as the devil or mistaken as odd behavior or daydreaming. Another misconception is that medications will harm the child. Intelligence quotient (IQ) and cognition were examined using Wechsler Intelligence Scale for Children and Stanford Binet Subsets Test version 4 (SBST4). Serum levels of neuron-specific enolase (NSE) and S100s proteins, sensitive markers of neuronal and glial cell damage were measured. Compared to controls, patients had lower mean score of full scale IQ on the Wechsler Intelli- gence Scale for Children (P = 0.045), particularly performance IQ scores (P <0.01), and comprehension, pattern analysis, quantita- tion, bead memory and memory for sentences of SBST4 (P = 0.045; P =0 .013,P = 0.007, P = 0.002; P = 0.035), but not for NSE or S100s. Severe epileptogenic (EEG) records were observed in children with lower IQ. Serum concentrations of NSE and S100s were lower in children with higher seizure frequency but did not reach significance compared to controls. Significant correlation was observed between full scale IQ and duration of illness (r = �0.430, P = 0.035), number of seizures (r = �0.580, P = 0.005) and sever- ity of electroencephalography changes (r = �0.450, P = 0.052), but not with S100s or NSE levels. Lower intelligence and poor cog- nitive performance were common with recurrent childhood epilepsy. Functional brain abnormalities without structural brain injury may likely be the cause. It seems that serum levels of NSE and S100s are not sensitive markers for structural or minimal brain damage in children with untreated epilepsy. Thus, early recognition and optimal seizure control is necessary to prevent the subse- quent damaging effects on the brain due to prolonged and recurrent seizures and subclinical epileptiform activity. Looking for addi- tional, more specific markers of brain injury is necessary, elevated serum levels of NSE and S100s were not detected.

Serum neuron specific enolase - a novel indicator for neuropsychiatric systemic lupus erythematosus?

Neuropsychiatric (NP) lupus, a common manifestation of systemic lupus erythematosus (SLE), is still insufficiently understood, in part, because of the lack of specific biomarkers. Neuron specific enolase (NSE), an important neuronal glycolytic enzyme, shows increased serum levels following acute brain injury, and decreased serum levels in several chronic disorders of the nervous system, including multi infarct dementia, multiple sclerosis and depression. The aim of the study was to evaluate serum NSE levels in SLE patients with and without nervous system involvement, and in healthy controls, and to assess the correlation of NSE serum levels of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) with clinical parameters. The study comprised 47 SLE patients and 28 controls. SLE activity was assessed using the Systemic Lupus Activity Measure (SLAM). A neurologist and a psychiatrist examined all patients. NP involvement was diagnosed according to strict NPSLE criteria proposed by Ainiala and coworkers, as modification to American College of Rheumatology (ACR) nomenclature and case definitions. NSE serum levels were determined by use of an immunoassay. Mean NSE serum concentrations in patients with NPSLE were significantly lower than in non-NPSLE patients (6.3 ± 2.6 µg/L vs. 9.7 ± 3.3 µg/L, p < 0.01) and in controls (8.8 ± 3.3 µg/L, p < 0.05). There were significant negative correlations between NSE serum levels and SLE activity (r = -0.42, p < 0.05) and the number of NPSLE manifestations diagnosed (-0.37; p = 0.001). Decreased serum concentrations of NSE may reflect chronic neuronal damage with declined metabolism of the nervous tissue in patients with NPSLE.

Prognostication of outcome after cardiac arrest and targeted temperature management

The vast majority of cardiac arrest (CA) survivors remain comatose at hospital arrival. Around one-half of these patients suffer from severe hypoxic encephalopathy leading to death or unresponsive wakefulness. Early outcome prognostication may reduce futile intensive care and suffering for next of kin. Several early prognostic markers have shown high positive predictive value for poor outcome in patients treated at normothermia, but results may be altered by targeted temperature management (TTM). Most prominently, absent motor response to painful stimuli 3 days after CA and a serum concentration of neuron-specific enolase (NSE) above 33 ng/ml do not predict poor outcome reliably in these patients [1,2]. Sedation during TTM is a relevant confounder for motor response and corneal reflexes [3]. Bilaterally absent pupillary light reaction 3 days after CA is a reliable predictor of poor outcome (sensitivity 20%) [1]. Eye diseases and medication are potential confounders. A threshold for poor outcome prediction by NSE has not been established after TTM. Above a level of 80 to 100 ng/ml 72 hours after CA good outcome has rarely been reported. The NSE levels may vary with different test kits, and NSE producing tumors, acute brain diseases and severe hematological diseases/hemolysis are confounders. Bilateral absence of cortical median nerve SSEP remains a reliable predictor, but single cases with recovery were reported [4] and inter-rater reliability is not perfect. Preserved spinal SSEP and low cortical noise levels are important prerequisites. The sensitivity of absent SSEP for poor outcome prediction is around 40% [1]. EEG can be a valuable predictive tool when interpreted by experienced neurophysiologists and indicates (subclinical) status epilepticus [5]. The influence of medication on EEG needs to be considered. Recently, a revised EEG classification has been proposed [6]. A reduced contrast between gray and white matter in brain computed tomography is associated with poor outcome. It can be quantified as gray–white-matter ratio and values below 1.1 predict poor outcome with high specificity [7]. Additional studies are needed to establish this threshold more firmly. MRI emerges as a prognostic parameter because of high spatial resolution and high sensitivity for cytotoxic brain edema with DWI/ADC imaging [8]. However, access is limited and quantification of early changes needs to be established in larger cohorts. To date, most authors argue for a multiparameter prognostication approach including repeated neurological examination, SSEP, NSE, EEG and imaging (CT or MRI) combined with a waiting period for potential recovery of several days after cardiac arrest.

Should an increase in cerebral neurochemicals following head kicks in full contact karate influence return to play?

Cerebral neurochemicals are markers of traumatic brain injury (TBI). The aim of the study was to determine whether kicks to the head (KTH) in full contact karate significantly increased serum concentrations of protein S-100B, and neurone specific enolase (NSE). Kicks to the body (KTB) were also quantified to asses muscle tissue injury. Muscle damage was assessed by analysis of serum total creatine kinase (CK). Twenty-four full contact karate practitioners were observed and filmed during actual competition and divided into two main groups post event: (1) Kicks to the head and body group (KTH): n = 12; mean ± SD; age, 30.4 ± 6.7 years; height, 1.74 ± 0.1 m; weight, 79.1 ± 2.1 kg; and (2): Kicks to the body group (KTB): n = 12; mean ± SD; age, 28.2 ± 6.5 years; height, 1.75 ± 0.1 m; weight, 79.2 ± 1.7 kg. The KTH group received direct kicks to the head, while group KTB received kicks and punches to the body. Blood samples were taken before and immediately post-combat for analysis of serum S-100B, NSE, CK and cardiac troponin. Significant increases in serum concentrations of S-100B (0.12 ± 0.17 vs. 0.37 ± 0.26, µg.L(-1)) and NSE (11.8 ± 4.1 vs. 20.2 ± 9.1 ng.mL(-1)) were encountered after combat in the KTH group and CK (123 ± 53 vs. 184 ± 103 U.L(-1)) in the KTB group (all P <0.05). Head kicks in full contact karate cause elevation of neurochemical markers associated with damaged brain tissue. The severity of injury is related to the early post-traumatic release of protein S-100B and NSE. The early kinetics and appearance post injury can reflect intracranial pathology, and suggest S-100B and NSE are extremely sensitive prognostic markers of TBI.

Prognostic value of neuron-specific enolase after cardiac arrest and targeted temperature management

The serum concentration of neuron-specific enolase (NSE) has been established as a highly specific predictor of poor outcome after cardiac arrest. Recent studies have indicated that patients treated with targeted temperature management at 33°C for 24 hours may have good outcome despite NSE serum concentrations considerably higher than the cutoff established for normothermic patients. The threshold above which survival with good outcome becomes very unlikely, its positive predictive value and sensitivity for prediction of poor outcome have not been established in this patient group. Furthermore, a threshold below which hypoxic encephalopathy may be largely excluded has not been determined.

Effects of dexmedetomidine on postoperative cognitive dysfunction in elderly patients undergoing general anesthesia

Objective To evaluate the effects of dexmedetomidine on postoperative cognitive dysfunction (POCD) in the elderly patients undergoing general anesthesia.Methods Ninety ASA physical status Ⅱ or Ⅲ patients,aged 65-76 yr,weighing 49-78 kg,scheduled for elective surgery under general anesthesia,were randomly assigned into 3 groups (n =30 each):control group (group C) and different doses of dexmedetomidine groups (D1 and D2 groups).Anesthesia was induced with midazolam,cisatracurium besilate,sufentanil and propofol.Dexmedetomidine 0.5 μg/kg was then intravenously infused over 15 min,followed by infusion at a rate of 0.50 μg· kg-1 · h-1 (group D1) or 0.75 μg· kg-1 · h-1 (group D2) until the end of surgery.Group C received the equal volume of normal saline.At 1 day before surgery and 1,3 and 7 days after surgery,venous blood samples were obtained for determination of serum concentrations of C-reactive protein (CRP) and neuron-specific enolase (NSE).The cognitive function was evaluated by Mini-Mental State Examination (MMSE) at the time points mentioned above.The development of POCD was recorded.Results Compared with group C,the MMSE scores were significantly increased and serum concentrations of CPR and NSE were decreased in groups D1 and D2,and no significant differences were found in the indexes mentioned above between D1 and D2 groups.The incidence of POCD was 30％,7％ and 7％ in C,D1 and D2 groups,respectively.The incidence of POCD was significantly higher in group C than in D1 and D2 groups,and there was no significant difference between D1 and D2 groups.Conclusion Dexmedetomidine is helpful in preventing the development of POCD in the elderly patients undergoing general anesthesia. Key words: Dexmedetomidine ; Cognition disorders; Aged

Neuron specific enolase and c-reactive protein levels in stroke and its subtypes: correlation with degree of disability.

Stroke is an emergency which threatens life and third leading cause of death and long term disability in developed countries. The use of biomarkers in diagnosing stroke and assessing prognosis is an emerging and rapidly evolving field. The study aimed to investigate the predictive value of biochemical marker of brain damage neuron-specific enolase (NSE) and systemic inflammatory marker C-reactive protein (CRP) with respect to degree of disability at the time of admission and short term in stroke patients. We investigated 120 patients with cerebrovascular stroke who were admitted within 72h of onset of stroke in the Department of Neurology at Sri Aurobindo Institute of Medical Sciences, Indore, India. NSE and CRP were analyzed by solid enzyme linked immunosorbent assay using analyzer and micro plate reader from Biorad 680. In all patients, the neurological status was evaluated by a standardized neurological examination and the National Institutes of Health Stroke Scale on admission and on day 7. Serum NSE and CRP concentration were found significantly increased in acute stroke cases as compared to control in present study (<0.05 and <0.001 respectively). The maximum serum NSE and CRP levels within 72h of admission were significantly higher in patients with greater degree of disability at the time of admission. Both biomarkers were found significantly correlated with neurological disability and short term outcome. Our study showed that serum biomarkers NSE and CRP have high predictive value for determining severity and early neurobehavioral outcome after acute stroke.

Blast-induced traumatic brain injury of goats in confined space

Objective:To study blast-induced traumatic brain injury (bTBI) characteristics in confined space.Methods:The goats were placed at the column-like buildings with trinitrotoluene (TNT) as the source of the blast wave. The pressure was recorded at 2–8 m from the explosion center. The systemic physiology, electroencephalogram (EEG), serum level of S-100beta, and neuron specific enolase (NSE) were determined pre and post the exposure. Neuroanatomy and neuropathology were observed 4 hours after the exposure.Results:The blast waveform was composed of two peaks from the incident and reflection wave with a range of pressure–duration from 555/913 kPa–0·663 milliseconds at 2 m to 45/71 kPa–2·7/2·367 milliseconds at 8 m. At 2 m, the goats experienced brain depression while the heart rate and respiratory rate concomitantly increased with bloody foam fluid emission from the nose and the mouth. Of the goats, 88·89% were burned. The distinctive gross neuroanatomical changes were congestive expansion of surface vessels on the hemisphere cerebellum and brainstem along with subarachnoid hemorrhage on the frontal lobe, mesencephalon, and brainstem. Subarachnoid hemorrhage, enlarged perivascular space, vascular dilatation and congestion, and parenchymal hemorrhagic could be easily observed microscopically. High amplitude and low frequency of waveforms appeared in the EEG. The serum concentration of S-100beta and NSE were elevated. Although these pathophysiological changes diminished with increasing distance from the explosive center, these changes existed for the 8 m subjects.Conclusions:Blast-induced traumatic brain injury can be induced by a complex blast wave with a pressure and duration of 45/71 kPa and 2·7/2·367 milliseconds. Its severity is related to the features and waveforms of the blast.

Clinical characteristics and prognostic factors of prostate cancer with liver metastases

Liver metastasis from prostate cancer is uncommon and remains poorly understood. We computer searched the clinical records of all our patients registered into a database to identify patients that presented or developed liver metastases. A total of 27 prostate cancer patients with ultrasound or CT/MR imaging evidence of liver metastases were included in our analysis. The liver metastasis rate from metastatic prostate cancer was 4.29%. Eight (29.63%) patients had previously untreated, hormone-naive prostate cancer (synchronous liver metastases at diagnosis of prostate cancer), whereas 19 (70.37%) patients had already been diagnosed as having hormone-refractory prostate cancer. In the hormone-naive group, the median overall survival after liver metastases diagnosis was 38 months and half of the patients were still alive at the latest follow-up, whereas only 6 months in the hormone-refractory group (p = 0.003). High concentration of serum neuron-specific enolase and previous chemotherapy were associated with a significantly poor overall survival after liver metastases in the hormone-refractory group using Kaplan–Meier curves and logrank tests for univariate analysis.

Individualized correction of neuron-specific enolase (NSE) measurement in hemolyzed serum samples

BackgroundAccuracy of serum neuron-specific enolase (NSE) measurement is paramount, particularly in the context of neurological outcome prognostication. However, NSE measurements are compromised by even slight hemolysis, as it is abundant in red blood cells (RBCs). We derived and validated an individualized hemolysis correction equation in an attempt to reduce the current rejection rate of 14% at our institution. MethodsIntracellular NSE was measured in RBC lysates to determine concentration variability. A correction equation was derived, accounting for both RBC-derived NSE false-elevation and hemoglobin-derived signal quenching. The performance of this individualized correction was evaluated in intentionally hemolyzed samples and accuracy was compared to a generalized correction. ResultsSignificant inter-individual variability of RBC NSE was observed, with an almost two-fold range (15.7–28.5ng NSE/mg Hb, p<0.001); intra-individual variability was insignificant. The individualized hemolysis correction equation derived: NSEcorr=NSEmeas−(Hbserum)(NSERBCs/Hb)+0.0844(Hbserum)+1.1 corrected 95% of the intentionally hemolyzed samples to within ±5ng/ml of corresponding baseline NSE concentrations, compared to 74% using a generalized formula. ConclusionsThe individualized hemolysis correction provides increased accuracy in the estimation of true serum NSE concentrations for hemolyzed samples, compared to a generalized approach, by accounting for inter-individual RBC NSE variability. Incorporating this correction should reduce sample rejection rates and overall health care costs.

Prognostic Assessment Always Requires Several Parameters

An important point of criticism regarding the cited studies is the fact that the prognostic parameters under investigation are further used in decisions about stopping therapy. This entails the possibility of a self-fulfilling prophecy. In the study by Bouwes et al., for example, therapy was immediately ended or limited in 40 out of 42 patients with lacking somatosensory evoked potentials (SEP) (1). We have repeatedly cared for patients who woke up again in spite of concentrations of neuron-specific enolase (NSE) >97 µg/L. The biggest impression was left by the case of a patient with a neuroendocrine tumor, whose NSE rose to >1000 µg/L. In assessing the NSE, malignant tumors should be regarded as confounders. In our opinion, the key message “Elevated serum concentrations of neuron-specific enolase have to be above 97 µg/L to serve as a safe indicator of an unfavorable prognosis” is therefore problematic in this abbreviated form. We think that the factually equating the bilateral absence of the pupillary light response or the corneal reflex with reliable indicators of a poor prognosis is equally problematic, because of possible examiner bias. Especially absent corneal reflexes should be assessed with a great deal of caution. Bouwes and Samaniego described 2 of 23, and 2 of 22, patients whose outcome was good in spite of absent corneal reflexes (1, 3). A high degree of certainty in the prognostic assessment is possible only by basing it on several parameters, rather than a single one. We treat most patients for seven days before we limit their treatment according to an interdisciplinary prognostic algorithm, on the basis of several consistent parameters for a poor prognosis (2).