Cerebrospinal neuron-specific enolase, S-100 and myelin basic protein in neurological disorders

In this study levels of neuron-specific enolase (NSE), S-100 protein (S-100) and myelin basic protein (MBP) in cerebrospinal fluid (CSF) of children and adults with distinct neurological disorders were examined. A previous study from our department demonstrated age related reference values for these brain-specific proteins in CSF. The median concentration level of the 3 proteins in 17 different neurological disease groups versus the reference group was compared. Significantly higher MBP values were observed in patients with multiple sclerosis (MS), cerebrovascular accident (CVA), metabolic disorder and infection. Furthermore, significantly higher values were demonstrated for S-100 in CVA and for NSE in metabolic diseases. In CVA, the NSE and S-100 values were significantly related with MBP values, whereas in MS the NSE and S-100 were not related with MBP values.     

Myelin basic protein and creatine kinase BB isoenzyme as CSF markers of intracranial tumors and stroke

In patients with intracranial tumors (ICT) and acute cerebral infarctions (CI), both necrosis and reversible changes occur in central nervous system (CNS) tissue. The damaged CNS cells release specific substances into the cerebrospinal fluid (CFS). Radioimmunoassay (RIA)-determined myelin basic protein (MBP) and RIA-determined creatine kinase BB (CK-BB) are markers of damage to CNS specific structures. The elevated CSF level of MBP is considered a marker of myelin damage and the increased concentration of CSF CK-BB may be of combined neuronal and astrocytic origin. CSF was collected from 57 patients with the diagnosis of CI (n = 30) and ICT (n = 27) and the concentration of MBP and CK-BB were measured by RIA. Our study shows increased CSF levels of MBP and CK-BB in patients with CI and patients with ICT. We have also found a linear correlation between MBP and CK-BB in both CI and ICT, and for a given CK-BB level, MBP was significantly higher in patients with ICT than in patients with CI. These facts suggest that lesion markers behave differently in the different pathologic processes affecting the CNS.     

Sequential analyses of neurobiochemical markers of cerebral damage in cerebrospinal fluid and serum in CNS infections

OBJECTIVE: To elucidate the relation between release patterns and cerebrospinal fluid/serum concentrations of neurobiochemical markers of cerebral damage and their potential value as monitoring parameters in central nervous system infections. METHODS: We investigated protein S-100B and neuron-specific enolase (NSE) in 102 sequential cerebrospinal fluid (CSF)-serum-pairs in patients with bacterial (n = 11) or viral (n = 13) meningitis/meningoencephalitis and neuroborreliosis (n = 8) in comparison with controls (n = 13). RESULTS: Highest S-100B values in CSF and serum were found on admission and showed a significant decrease afterwards. Comparison between disease groups revealed significant differences between bacterial and viral meningitis and neuroborreliosis for S-100B and also when compared with controls. NSE was not significantly elevated. CONCLUSIONS: S-100B is altered in CNS infection but does not provide additional benefit in the differential diagnosis when compared with standard CSF parameters. Nevertheless, S-100B values might be used as an additional monitoring parameter especially when sequential lumbar punctures are contraindicated.     

A sensitive ELISA for glial fibrillary acidic protein: application in CSF of children.

In the present study we describe a sensitive ELISA for determination of glial fibrillary acidic protein (GFAP). To validate the method combined determinations of GFAP and S-100 protein were performed in cerebrospinal fluid (CSF) of normal children and children with autism. The GFAP ELISA is of sandwich type and uses the biotin-avidin system. Sensitivity was 16 pg/ml. Between-day precision was 0.079 (coeff. of variance). S-100 protein concentrations were measured using a commercially available ELISA kit. Normal CSF from children and young adults were analysed. The CSF levels of GFAP in normal children were low (16-163 pg/ml). Both GFAP and S-100 protein concentrations correlated with age (P < 0.01 and P < 0.05, respectively), but the GFAP increment was more pronounced, probably reflecting the age-dependent expansion of the fibrillary astrocytes in the central nervous system (CNS). GFAP levels in children with infantile autism were higher than those in normal children of the same age range. S-100 protein concentrations were similar in both groups. High levels of GFAP in combination with normal S-100 protein concentrations in CSF indicates reactive astrogliosis in the CNS. In conclusion, the sensitive ELISA described makes it possible to measure low levels of GFAP present in the CSF of children. Combined assays of GFAP and S-100 protein can be used to discriminate between acute and chronic brain disorders in children.     

Myelin basic protein and S-100 antigen in cerebrospinal fluid of patients with multiple sclerosis in the acute phase

It has previously been demonstrated that both Myelin Basic Protein (MBP) and S-100 are released in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients during acute phases of exacebation of the disease. In order to investigate the pathobiological significance of the release of these two proteins into the CSF, MBP and S-100 were assayed in 10 MS patients during the five weeks following onset of an acute exacerbation. MBP was detectable in CSF during the first three weeks after exacrebation, while S-100 was detectable during the entire period of observation, at least in some of the patients. MBP reached its highest CSF concentrations during the first two weeks while S-100 did so in the third week, decreasing thereafter. This difference in time of presence of MBP and S-100 in the CSF is probably due to the different biological origin, MBP being a marker of myelin sheath injury, and S-100, more probably, of astrocytic activity.

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Sommario È stato precedentemente dimostrato che sia la proteina basica della mielina (PBM) che la S-100 vengono liberate nel liquido cefalo-rachidiano (LCR) durante in periodi di esacerbazione della sclerosi multipla (SM). Al fine di approfondire ulteriormente il significato patobiologico della liberazione di queste due proteine nel LCR abbiamo eseguito uno studio quantitativo di PBM e S-100 in dieci malati di SM durante un periodo di 5 settimane successive ad una ricaduta. La PBM è risultata dosabile durante le prime tre settimane, mentre la S-100 è risultata essere presente nel LCR durante l'intero periodo di osservazione, almeno in alcuni dei pazienti. La PBM ha raggiunto i suoi maggiroi livelli durante le prime due settimane. La S-100, invece, durante la terza settimana, dopo di che vi è stata una netta riduzione dei suoi livelli liquorali. Questa differenza nei tempi di presenza di PBM ed S-100 nel LCR è probabilmente dovuta alla differente origine biological delle due proteine. La PBM, infatti, è marcatrice di lesione della guaina mielinica, la S-100 invece, con più probabilità, di attività dellule astrocitarie.

     

吉兰-巴雷综合征患者脑脊液中S-100b、MBP的检测及意义

目的 研究吉兰-巴雷综合征(green-barre syndrome,GBS)患者脑脊液中S-100 b和髓鞘碱性蛋白(MBP)的含量变化,探讨S-100 b及MBP在GBS发病过程中的作用以及与病情严重程度的关系.方法 采用酶联免疫吸附法(ELISA)测定32例不同临床分级的GBS患者(GBS组),30例其他神经系统...     

Normal CSF neuron-specific enolase and S-100 protein levels in patients with recent non-complicated tonic-clonic seizures

PURPOSE: Increased concentrations of the nervous-system-specific proteins neuron-specific enolase (NSE) and S-100 protein (S-100) have been measured with lesions in the CNS. Elevated levels of serum NSE (s-NSE) have been found in status epilepticus, but also after single epileptic seizures. Because larger studies addressing cerebrospinal fluid (CSF) levels of NSE or S-100 have not been performed, we measured CSF NSE and S-100 after tonic-clonic seizures to search for evidence of neuronal and glial damage. METHODS: 22 consecutive patients with single, previously undiagnosed and untreated tonic-clonic seizures were studied. Serum and CSF samples were collected within 24 h after seizure. 18 serum and CSF samples were measured from a control group. RESULTS: The mean CSF NSE was 8.9 ng/ml (range 0-28 ng/ml) and s-NSE 8.2 ng/ml (range 5-15 ng/ml) in the patient group. The mean concentrations in the control group were 13.1 ng/ml (range 3-24 ng/ml) and 8.0 ng/ml (range 5-12 ng/ml) respectively. The mean CSF S-100 was 3.17 microg/l (range 1.45-7.02 microg/l) and serum S-100 0.05 microg/l (range 0-0.32 microg/l), and in controls 3.19 microg/l (range 1.52-5.13 microg/l) and 0.08 microg/l (range 0-0.28 microg/l). CONCLUSION: There were no significant differences between the mean concentrations of NSE or S-100 in CSF and serum between the epileptic group and controls. These results do not confirm the previous observation of elevated NSE-levels after tonic-clonic seizures, which argues against neuronal or glial damage after uncomplicated tonic-clonic seizures in unmedicated patients.     

急性脑外伤患者脑脊液髓鞘碱性蛋白水平与其损伤类型的关系

目的 探讨急性脑外伤患者脑脊液髓鞘碱性蛋白(CSF-MBP)水平与其损伤类型的关系。 方法 采用放射免疫测定法(RIA)对42例急性脑外伤患者的CSF-MBP进行测定,并测定26例非神经系统疾病患者作对照。结果 严重脑内原发性损伤患者CSF-MBP平均水平显著高于轻中度脑内原发性损伤和单纯颅内血肿者(P<0.01),单纯颅内血肿患者CSF-MBP仅伤后第5天增高;弥漫性脑损伤组CSF-MBP水平显著高于局灶性脑损伤组(P<0.01),伤后1周内持续处于高水平状态。结论 CSF-MBP的测定有助于急性脑外伤患者损伤程度及类型的判定。     

Brain and plasma proteins in spinal fluid as markers for brain damage and severity of stroke

Forty well-defined acute stroke patients were investigated for some cerebro-spinal fluid (CSF) markers of cerebral damage. Myelin-basic protein (MBP), tau-fraction, albumin, IgG and transferrin were analyzed on two early occasions after onset of clinical symptoms. Patients with transitory ischaemic attack (TIA) had normal values for MBP both at first and second lumbar puncture. Patients with cerebral infarction and haemorrhage had mean MBP concentrations higher than normal at both lumbar punctures. In cerebral infarction there was a significant increase in MBP from the first to the second lumbar puncture. Patients with intracerebral haemorrhage showed the highest mean MBP values and MBP was markedly elevated already at the first lumbar puncture, suggesting different mechanisms of destruction of nervous tissue in cerebral infarction and bleeding. The amount of MBP was also significantly correlated to the visibility of the cerebral lesion at CT-scan and to the short-term outcome of the patients. The tau-fraction, indicating damage to grey matter, was higher than normal in the majority of patients with cerebral infarction and TIA. The concentration of MBP increases with the extent of brain lesion and a high value indicates a poor short-term prognosis for the patient. This study shows that the brain specific MBP in CSF is a useful marker of cerebral damage in acute cerebrovascular disease.     

The S-100 protein in cerebrospinal fluid: a simple ELISA method

A simple ELISA method is described for determinations of S-100 protein concentrations in CSF. The assay has a useful range of 200-3200 pmol/l. The precision of the ELISA was estimated using a pool of CSF. The coefficient of variation was 0.18 within assay, 0.17 between assay and 0.17 between day. The S-100 protein is stable in the CSF as no measurable differences in S-100 concentrations were observed in samples stored at room temperature for 2 days. No correlation between age and S-100 concentration was found when determinations were performed in CSF from neurologically healthy males. Furthermore, no changes of S-100 was observed in a lumbocisternal CSF gradient from patients with normal pressure hydrocephalus. Thus, the described ELISA represents an easy to handle and reliable method, well suited for routine determinations of S-100 protein concentration in the CSF.     

Chronic subdural haematoma and arachnoid cyst in autosomal dominant polycystic kidney disease (ADPKD).

We present the unusual association between chronic subdural haematoma (CSDH), intracranial arachnoid cyst and autosomal dominant polycystic kidney disease (ADPKD) in a 27-year-old man. CSDH is a documented complication of intracranial arachnoid cyst, the incidence of which is increased in patients with ADPKD. Awareness of this association may lead to earlier diagnosis of ADPKD and treatment of its systemic complications, including renal insufficiency, systemic hypertension and previously unsuspected intracranial saccular aneurysm. Surgery for CSDH associated with intracranial arachnoid cyst may be complicated by over-drainage of cerebrospinal fluid due to communication between the cyst and the cisternal subarachnoid space, as illustrated in the present case, and the development of epidural haemorrhage.     

Cerebrospinal fluid/serum gradient of IgG is associated with disability at acute attacks of neuromyelitis optica

Increased blood-brain barrier (BBB) disruption can be found in patients with neuromyelitis optica (NMO); however, its clinical implication and association with disability at acute attack remains obscure. The purpose of the study was to evaluate the clinical significance of BBB disruption and the subsequent cerebrospinal fluid (CSF)/serum IgG gradient in NMO. Retrospective analysis was made of acute-stage CSF samples from NMO (n = 40) and multiple sclerosis (MS; n = 26) patients. The CSF/serum IgG gradient (QIgG), albumin ratio (Qalb), and IgG index were calculated. Multivariate regression analysis was used to identify clinical and CSF variables associated with disability at acute attacks (extended disability scale score, EDSS) in both groups. The EDSS was significantly associated with the QIgG (p < 0.001), Qalb (p = 0.012), and number of cumulative attacks (p = 0.012) in NMO but not in MS with univariate analysis. Length of spinal cord involvement was also associated with EDSS in NMO (p = 0.030). However, multivariate analysis revealed that the QIgG was only significantly associated with EDSS in NMO (0.580; 95% CI -0.257, 0.961; p = 0.002). The QIgG was also highly associated with the Qalb in NMO (p < 0.001). The QIgG may reflect systemic IgG leakage into the CNS and is strongly associated with disability at acute attacks in NMO, suggesting that BBB disruption can aggravate disease activity by facilitating systemic IgG infiltration into the CNS.     

Cerebrospinal fluid biomarkers showing neurodegeneration in dogs with GM1 gangliosidosis: possible use for assessment of a therapeutic regimen

The present study investigated cerebrospinal fluid (CSF) biomarkers for estimating degeneration of the central nervous system (CNS) in experimental dogs with GM1 gangliosidosis and preliminarily evaluated the efficacy of long-term glucocorticoid therapy for GM1 gangliosidosis using the biomarkers identified here. GM1 gangliosidosis, a lysosomal storage disease that affects the brain and multiple systemic organs, is due to an autosomal recessively inherited deficiency of acid beta-galactosidase activity. Pathogenesis of GM1 gangliosidosis may include neuronal apoptosis and abnormal axoplasmic transport and inflammatory response, which are perhaps consequent to massive neuronal storage of GM1 ganglioside. In the present study, we assessed some possible CSF biomarkers, such as GM1 ganglioside, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), neuron-specific enolase (NSE) and myelin basic protein (MBP). Periodic studies demonstrated that GM1 ganglioside concentration, activities of AST and LDH, and concentrations of NSE and MBP in CSF were significantly higher in dogs with GM1 gangliosidosis than those in control dogs, and their changes were well related with the months of age and clinical course. In conclusion, GM1 ganglioside, AST, LDH, NSE and MBP could be utilized as CSF biomarkers showing CNS degeneration in dogs with GM1 gangliosidosis to evaluate the efficacy of novel therapies proposed for this disease. In addition, we preliminarily treated an affected dog with long-term oral administration of prednisolone and evaluated the efficacy of this therapeutic trial using CSF biomarkers determined in the present study. However, this treatment did not change either the clinical course or the CSF biomarkers of the affected dog, suggesting that glucocorticoid therapy would not be effective for treating GM1 gangliosidosis.     

Follow-up investigations of tau protein and S-100B levels in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease

BACKGROUND: S-100B and tau protein have a high differential diagnostic potential for the diagnosis of Creutzfeldt-Jakob disease (CJD). So far there has been only limited information available about the dynamics of these parameters in the cerebrospinal fluid (CSF). However, there is a special interest in finding biochemical markers to monitor disease progression for differential diagnosis and treatment. PATIENTS AND METHODS: We analyzed CSF of 45 patients with CJD and of 45 patients with other neurological diseases for tau protein and S-100B in a follow-up setting. All diagnoses of CJD were later neuropathologically verified. A ratio between tau protein differences and the time between lumbar puncture was calculated. The same was done for S-100B. RESULTS: Tau protein levels of 34 cases were above the cut-off level for CJD (>1,300 pg/ml) in the first CSF sample. In 7 of 11 patients with lower tau levels in the first CSF sample, tau levels rose. The above-mentioned ratio was significantly higher in the CJD group than in the group with other neurological diseases. Similar results were obtained for S-100B. CONCLUSION: We conclude that follow-up investigations and calculation of ratios is a useful tool in the differential diagnosis of CJD. Variations in this pattern were observed in single cases.     

14-3-3 protein, neuron-specific enolase, and S-100 protein in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease

We explored simultaneously 14-3-3 protein, neuron-specific enolase (NSE), and one astroglial protein, S-100, recently proposed as Creutzfeld-Jakob disease (CJD) markers, in the cerebrospinal fluid (CSF) of 129 patients with suspected CJD. Cutoff values for NSE and S-100 were established at 25 and 2.5 ng/ml, respectively. The highest sensitivity was observed for S-100 (94.2%) followed by 14-3-3 (89.8%) and NSE (79.7%), while the highest specificity in CJD diagnosis was obtained with 14-3-3 protein (100%) as compared with NSE (91.5%) and S-100 (85.4%). No influence of sex, genotype at codon 129 of the prion protein gene, time between sampling, and death or disease duration has been found. Based on 90 cases initially referred as 'probable' or 'possible' CJD, with 14-3-3, NSE, or S-100 we could correctly discriminate between 'CJD' or 'non-CJD' categories in 94.4, 86.5, and 90% of the cases, respectively. When limited to 'possible CJD' cases, diagnosis based on one of the three CSF proteins was accurate in 98, 90.7 and 87.3%, respectively. In view of the fact that the CSF 14-3-3 protein test alone has the highest specificity and good sensitivity, it appears that there is no additional advantage at the moment to include NSE and/or S-100 protein in the exploration of clinically suspected CJD cases.     

复方黄芪注射液对急性重型颅脑损伤患者血清NSE，MBP和S-100B含量的影响

目的观察复方黄芪注射液对急性重型颅脑损伤患者血清神经元特异性烯醇化酶（NSE），髓鞘碱性蛋白（MBP）和S-100蛋白B（S-100B）含量的影响。方法按标准选取急性重型颅脑损伤患者196例，随机分成常规治疗组和黄芪治疗组两组。黄芪治疗组在常规治疗基础上加用复方黄芪注射液治疗。治疗前和治疗后不同时间点分别检测患者血清NES、MBP和S-100B浓度,并行GCS评分，3个月后行GOS评分；同时检测96例健康成人血清的NES、MBP和S-100B的浓度，然后对所得资料进行统计学分析。结果急性重型颅脑损伤患者血清的NES、MBP和S-100B的浓度均显著高于健康成年人（P〈0．05）。治疗后黄芪治疗组血清NSE、MBP和S-100B均低于常规治疗组，差异均有显著性意义（P〈0．05）。黄芪治疗组在入院时的GCS评分与常规治疗组比较无显著性差异（P〉0．05），但治疗后1周和2周其GCS评分显著高于常规治疗组（P〈0．05）。治疗3月后其GOS评分显著高于常规治疗组（P〉0．05）。结论黄芪能降低急性重型颅脑损伤患者血清NSE，MBP，S-100B含量，并能改善患者的预后。     

Prognostic value of cerebrospinal fluid neuron-specific enolase and S-100b protein in Guillain-Barré syndrome

We measured the cerebrospinal fluid (CSF) concentrations of neuron-specific enolase (NSE) and S-100b protein (S-100b) using enzyme immunoassay methods, in 24 patients with Guillain-Barré syndrome and 46 controls, and examined their prognostic values. Sixteen of 24 patients showed elevated levels (> the mean + 2SD levels of controls) of NSE, S-100b, or both, and in those with higher NSE or S-100b levels there was a rather longer duration of disease, whereas 8 patients with the normal levels showed an early recovery. Further, NSE or S-100b levels were significantly correlated with months to recovery. Thus, NSE and S-100b in CSF may be useful markers for predicting the outcome of Guillain-Barré syndrome.     

Arachnoid cyst rupture with subdural hygroma: report of three cases and literature review

INTRODUCTION: Arachnoid cysts are believed to account for about 1% of all intracranial expansive lesions, some remain inactive throughout life, others lie dormant for many years before clinical manifestation. In a few cases, arachnoid cysts have ruptured after cranial trauma or more rarely, spontaneously, with resultant subdural haemorrhage or CSF collection. CASE REPORT: We report three cases with traumatic rupture of arachnoid cyst into the subdural space in children, which is an extremely unusual complication. DISCUSSION: A review of the literature revealed only 18 previously reported cases.     

Human myelin basic protein peptide 69-89: immunochemical features and use in immunoassays of cerebrospinal fluid

The characteristics and heterogeneity of the myelin basic protein (MBP)-like material appearing in cerebrospinal fluid (CSF) after acute central nervous system (CNS) myelin injury are unresolved. Antigenic material containing an epitope in the carboxyl-terminal portion of human MBP peptide 45-89 (from the intact molecule of 170 residues) is a prominent species of the MBP-like material present. In an effort to define further the MBP-like material in CSF and to enhance its detection, a modified double-antibody radioimmunoassay has been developed using a radioligand of human MBP synthetic peptide 69-89. This assay is more sensitive with results paralleling those of previously used MBP assays for CNS myelin damage. Results with this assay provide additional confirmation of the presence of an epitope of MBP in the decapeptide of MBP 80-89 but in a conformation simulating that of intact MBP in CSF after CNS myelin injury. Unexpected buffer effects were noted to influence the immunochemical behavior of some of the small peptides of MBP.     

CSF antibodies to myelin basic protein and oligodendrocytes in multiple sclerosis and other neurological diseases

Cerebrospinal fluid (CSF) from 18 multiple sclerosis (MS) patients, 13 subacute sclerosing panencephalitis (SSPE) patients, 22 other neurological disease (OND) patients, and 7 neurotic patients as controls were tested in an 125I-labeled anti-human F(ab')2 binding assay for the presence of antibodies to normal human brain cells from tissue culture, human fibroblasts, plasma membranes of MS and normal human brain, myelin basic protein (MBP) and bovine oligodendrocytes. Antibodies to MBP and to oligodendrocytes were found in the CSF of MS, SSPE and OND patients. Absorption of CSF with bovine CNS myelin significantly diminished binding activity to oligodendrocytes. Antibodies in the CSF against MBP and oligodendrocytes, on which some myelin determinants are expressed, seem to be a common feature of diseases in which demyelination is a component.