Basic Protein In Cerebrospinal Fluid Research Articles

Diagnostic significance of the determination of myelin basic protein in cerebrospinal fluid in HIV-associated neurological diseases.

48 patients aged from 21 to 54 years, infected with human immunodeficiency virus (HIV) and presence of diseases of the central nervous system (CNS) were examined. CNS diseases included cerebral tuberculosis, viral encephalitis (caused by Epstein-Barr Virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV)), encephalitis of unspecified etiology, cerebral toxoplasmosis, fungal meningitis. 29 (60.4%) of the patients were discharged from the hospital with a clinical improvement, and 19 (39.6%) of the patients died as a result of CNS disease. Significant differences in the content of the myelin basic protein (MBP) in the cerebrospinal fluid (CSF), depending on the outcome of the disease, were determined. The Median of MBP in deceased patients was 2.9 times higher than in the survived patients - 4.00 (1.90-7.70) ng/ml vs. 1.40 (0.99-2.00) ng/ml (p=0.002 U). An inverse correlation between the content of MBP in the CSF and the time from the determination of the HIV status to the manifestation of neurologic symptoms (rs=-0.30, p<0.05) was found. According to the results of the ROC analysis, the high risk of unfavorable course of HIV-associated CNS diseases is predicted when the concentration of MBP in the cerebrospinal fluid increases by more than 2 ng/ml (68.4% sensitivity, 75.9% specificity, 72.9% accuracy). The highest level of this protein was observed in patients with fungal lesions of the central nervous system (6.6 (1.9-7.8) ng/ml), and the lowest MBP level – in the group of patients with unspecified encephalitis (0.99 (0.9-1.1) ng/ml), which correlated to more favorable outcomes of the disease. The MBP in cerebrospinal fluid can be an important diagnostic and prognostic marker of HIV-associated neurological diseases.

Is myelin basic protein a potential biomarker of brain cancer?

Myelin basic protein is a potential biomarker for the central nervous system diseases in which the myelin sheath is destroyed. Using pseudo-selected reaction monitoring and the method of standard additions, we have measured the myelin basic protein level in the cerebrospinal fluid of patients with neurotrauma (n = 6), chronic neurodegenerative diseases (n = 2) and brain cancer (n = 5). Myelin basic protein was detected only in four out of five cerebrospinal fluid samples of patients with brain cancer. The cerebrospinal fluid myelin basic protein level ranged from 3.7 to 8.8 ng ml-1. We suggest that monitoring of myelin basic protein in cerebrospinal fluid can serve as a diagnostic test for the brain cancer.

Clinical Classification of Delayed Encephalopathy after Carbon Monoxide Poisoning and Utility of Myelin Basic Protein in Cerebrospinal Fluid (S07.002)

Clinical Classification of Delayed Encephalopathy after Carbon Monoxide Poisoning and Utility of Myelin Basic Protein in Cerebrospinal Fluid (S07.002)

Optimisation of the quantification of glutamine synthetase and myelin basic protein in cerebrospinal fluid by a combined acidification and neutralisation protocol

The measurement of proteins in cerebrospinal fluid (CSF) by enzyme-linked immunosorbent assays (ELISAs) is becoming increasingly important in the diagnosis of many neurodegenerative diseases such as Alzheimer's Disease. However, detection of proteins in these immunoassays can be hampered by confounding factors either present in the sample matrix or inherent to the protein of interest. These confounding factors may, for example, include protein aggregation or binding to other proteins resulting in epitope masking. Furthermore, the pH of CSF may vary considerably amongst different samples which may limit standardisation of CSF analysis. Pre-treatment of CSF to liberate epitopes or optimise conditions for antibody binding may enhance protein detection. In the current study we investigated whether CSF acidification followed by neutralisation (in short: AFBN) or neutralisation alone prior to measurement might improve the detection of a panel of brain-specific proteins. We demonstrate that the AFBN pre-treatment protocol for CSF significantly enhances the measurement of glutamine synthetase (GS) and myelin basic protein (MBP) in CSF but does not affect detection of glial fibrillary protein (GFAP), amyloid β 42 (Aβ42), total tau (t-tau) or phosphorylated tau (p-tau). Neutralisation alone did not improve detection of any of the proteins tested. Based on our results, we suggest including the AFBN protocol in the evaluation of new biomarker development protocols to avoid confounders such as CSF pH or epitope-masking of the target protein.

Fractional anisotropy in the centrum semiovale as a quantitative indicator of cerebral white matter damage in the subacute phase in patients with carbon monoxide poisoning: correlation with the concentration of myelin basic protein in cerebrospinal fluid

Carbon monoxide (CO) poisoning leads to demyelination of cerebral white matter (CWM) fibers, causing chronic neuropsychiatric symptoms. To clarify whether fractional anisotropy (FA) from diffusion tensor imaging in the centrum semiovale can depict demyelination in the CWM during the subacute phase after CO inhalation, we examined correlations between FA in the centrum semiovale and myelin basic protein (MBP) in cerebrospinal fluid. Subjects comprised 26 adult CO-poisoned patients ≤60 years old. MBP concentration was examined for all patients at 2 weeks after CO inhalation. The mean FA of the centrum semiovale bilaterally at 2 weeks was also examined for all patients and 21 age-matched healthy volunteers as controls. After these examinations, the presence of chronic symptoms was checked at 6 weeks after CO poisoning. Seven patients displayed chronic symptoms, of whom six showed abnormal MBP concentrations. The remaining 19 patients presented no chronic symptoms and no abnormal MBP concentrations, with MBP concentrations undetectable in 16 patients. The MBP concentration differed significantly between patients with and without chronic symptoms. The mean FA was significantly lower in patients displaying chronic symptoms than in either patients without chronic symptoms or controls. After excluding the 16 patients with undetectable MBP concentrations, a significant correlation was identified between MBP concentration and FA in ten patients. The present results suggest that FA in the centrum semiovale offers a quantitative indicator of the extent of demyelination in damaged CWM during the subacute phase in CO-poisoned patients.

557 Myelin basic protein in malignant brain tumour – source of increased myelin basic protein in cerebrospinal fluid

557 Myelin basic protein in malignant brain tumour – source of increased myelin basic protein in cerebrospinal fluid

Myelin basic protein in cerebrospinal fluid: a predictive marker of delayed encephalopathy from carbon monoxide poisoning

This study was designed to investigate whether myelin basic protein (MBP) in cerebrospinal fluid (CSF) can be a predictive marker of delayed encephalopathy from carbon monoxide (CO) poisoning. Five patients with CO poisoning were included in the study. The CSF was serially sampled to determine the MBP concentration. All patients were classified into group DE or group non-DE according to whether delayed encephalopathy developed or not. In all 3 patients in group DE, the MBP levels in the CSF were markedly elevated preceding the clinical manifestations of delayed encephalopathy. In both group non-DE patients, the MBP concentrations in the CSF were never elevated. Elevated MBP concentrations in the CSF may represent a predictive marker of delayed encephalopathy from CO poisoning, leading to a more appropriate triage of patients with CO poisoning.

Acute Ascending Motoric Paraplegia Following Intrathecal Chemotherapy for Treatment of Acute Lymphoblastic Leukemia in Children: Case Reports and Review of the Literature

Severe side effects of chemotherapy in pediatric patients with acute lymphoblastic leukemia are rare, but well-known. We present two pediatric patients who developed ascending motoric paraplegia (AMP) following intrathecal chemotherapy. Both patients suffered from progressive weakness of their lower extremities, neurogenic bladder dysfunction, autonomous neural dysregulation and minor sensory deficits. Despite an initially similar clinical picture, progression and outcome were fairly different. There is convincing evidence that AMP is caused by spinal cord toxicity of intrathecally applied toxic agents such as cytarabin and/or methotrexate leading to spinal demyelinisation as demonstrated by elevated myelin basic protein in cerebrospinal fluid.

Neuron-specific enclose and myelin basic protein in cerebrospinal fluid of patients with first episode schizophrenia

In order to study whether patients with schizophrenia have cerebral injury, neuron-specific enolase (NSE) and myelin basic protein (MBP)in cerebrospinal fluid (CSF) of 33 patients with first episode schizophrenia and 9 from the control group were determined by double antibody sandwich enzyme immunoassay method. The results showed that there was significant difference in the NSE contents between the experimental group and control group (P<0.01). The NSE contents in CSF in the experimental group were positively correlated with MBP in schizophrenia patients (P< 0. 05). These findings suggested that patients with schizophrenia had cerebral injury.

Detection of myelin basic protein in cerebrospinal fluid

Radioimmunoassay for myelin basic protein in cerebrospinal fluid is commonly used as a biochemical marker of demyelination in multiple sclerosis patients. A sensitive enzyme-linked immunosorbent assay for myelin basic protein has been recently developed, which can make a clinical evaluation of myelin basic protein in cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases. Most multiple sclerosis patients with acute exacerbation had markedly high myelin basic protein. Longitudinal studies of multiple sclerosis patients showed that myelin basic protein in CSF increases rapidly in agreement with acute relapse and then rapidly declines and disappears. Significantly higher cerebrospinal fluid myelin basic protein levels in human T-cell lymphotropic virus Type I-associated myelopathy/tropical spastic paraparesis patients were also detected. This enzyme-linked immunosorbent assay system can be used routinely to measure myelin basic protein in cerebrospinal fluid as a useful diagnostic indicator, not only for central active demyelination as in multiple sclerosis but, also for spinal cord demyelination as in human T-cell lymphotropic virus Type I-associated myelopathy/tropical spastic paraparesis.

Detection of myelin basic protein in cerebrospinal fluid and serum from patients with HTLV-1-associated myelopathy/tropical spastic paraparesis

BackgroundHuman T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) is a chronic inflammatory disease that primarily affects the spinal cord and may be a neurological syndrome that is clinically similar to multiple sclerosis (MS). Myelin basic protein (MBP) in the cerebrospinal fluid (CSF) of MS patients is generally measured by radio-immunoassay. We have recently established a sensitive enzyme-linked immunosorbent assay (ELISA) and measured the MBP concentrations in CSF and serum of HAM/TSP patients. MethodsA sensitive two-site ELISA capable of measuring MBP at a concentration as low as 30pg/mL in serum and CSF samples was used. ResultsSignificantly higher CSF MBP concentrations were detected in 61% of HAM/TSP patients than in patients with non-neurological diseases. Serum MBP concentrations were also higher in 9% of HAM/TSP patients compared with patients with non-neurological diseases or healthy controls. ConclusionsUsing our ELISA system, we detected MBP in CSF and serum not only in patients with central active demyelination as in MS, but also in patients with spinal cord demyelination as in HAM/TSP

Detection of myelin basic protein in cerebrospinal fluid and serum from patients with HTLV-1-associated myelopathy/tropical spastic paraparesis.

Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) is a chronic inflammatory disease that primarily affects the spinal cord and may be a neurological syndrome that is clinically similar to multiple sclerosis (MS). Myelin basic protein (MBP) in the cerebrospinal fluid (CSF) of MS patents is generally measured by radioimmunoassay. We have recently established a sensitive enzyme-linked immunosorbent assay (ELISA) and measured the MBP concentrations in CSF and serum of HAM/TSP patients. A sensitive two-site ELISA capable of measuring MBP at a concentration as low as 30 pg/mL in serum and CSF samples was used. Significantly higher CSF MBP concentrations were detected in 61% of HAM/TSP patients than in patients with non-neurological diseases. Serum MBP concentrations were also higher in 9% of HAM/TSP patients compared with patients with non-neurological diseases or healthy controls. Using our ELISA system, we detected MBP in CSF and serum not only in patients with central active demyelination as in MS, but also in patients with spinal cord demyelination as in HAM/TSP.

Clinical and Analytical Evaluation of an Enzyme Immunoassay for Myelin Basic Protein in Cerebrospinal Fluid

RIA of myelin basic protein (MBP) in cerebrospinal fluid (CSF) is commonly used as a biochemical marker of demyelination in patients with multiple sclerosis (MS). Our aim was to develop a sufficiently sensitive ELISA for MBP and evaluate it clinically in patients with MS. The ELISA used anti-bovine MBP antibody coated on plates and biotinylated anti-MBP antibody. The bound antibody complex was quantified with streptavidin-horseradish peroxidase. MBP was determined in CSF from 84 MS patients and 55 patients with other neurological diseases. The respective within- and between-assay CVs were 4.7% and 7.2% at 200 ng/L, and 6. 3% and 8.8% at 2000 ng/L. The detection limit was 30 ng/L. Most of the MS patients with acute exacerbations had markedly increased MBP in the CSF. Longitudinal studies of six MS patients with recurrent exacerbation confirmed this observation. MBP concentrations from 78 MS patients, as tested with our ELISA, correlated well with those obtained by RIA (r = 0.9; P: <0.01), but the detection limit of the ELISA was much lower than that of the RIA. This convenient ELISA with higher sensitivity than the existing assays is a suitable routine assay that provides a diagnostic indicator of myelin breakdown in the central nervous system; moreover, it is an excellent indicator of MS disease activity.

Myelin basic protein in cerebrospinal fluid and other body fluids.

Myelin basic protein (MBP) or a fragment thereof may enter cerebrospinal fluid (CSF) and other body fluids in an etiologically nonspecific fashion to provide information about the status of central nervous system (CNS) myelin damage. MBP immunochemically detected is referred to as MBP-like material (MBPLM). The clinical utility of the assay for MBPLM in CSF is to document the presence, continuation, or resolution of CNS myelin injury. The analysis of CSF for MBPLM is subject to many variables, among which are the antisera and the form of the assay utilized. The dominant epitope of CSF MBPLM is in the decapeptide of 80-89 from the intact MBP molecule of 170 residues. Normally, CSF has no detected MBPLM. Following an acute relapse of MS, MBPLM rises quickly in the range of ng/ml and rapidly declines and disappears. The presence of MBPLM in CSF in chronic and progressive phases of the disease is unusual, but it may sometimes be detected in low levels, depending on the assay used for detection. The level of CSF MBPLM is related to both the mass of CNS myelin damage and how recently it occurred. The level of CSF MBPLM rarely is elevated in optic neuritis. The level of CSF MBPLM is unrelated to CSF protein level, level of IgG, presence of oligoclonal bands or pleocytosis. CSF MBPLM has the potential of serving as a marker of therapeutic effectiveness in MS and does have predictive value for response to glucocorticoids given for worsening of disease. The detection of MBPLM in body fluids other than CSF would be of great value because of the resulting improved feasibility for objectively monitoring the natural history of MS and response to therapy. Studies on blood have yet to produce a valid assay of MBPLM. Urinary MBPLM, though different in its features from that in CSF, may provide a correlate, not with acute demyelination in MS as is the case for CSF, but with progression of disease.

Myelin basic protein in cerebrospinal fluid and other body fluids

Myelin basic protein in cerebrospinal fluid and other body fluids

Enzyme immunoassay for myelin basic protein in cerebrospinal fluid

Myelin basic proteins (MBPs) are a set of proteins making up about 30% of the protein content of the central nervous system myelin. Four human isoforms have been identified [11]. The most abundant is a highly conserved 18.5 kDa polypeptide. For this species, the amino acid sequence homologies between human and monkey or human and chick are 98.2% and 71.1%, respectively [11]. As a consequence, there is a very good immunological cross-reactivity between the mammalian MBP. This protein has been extensively used to induce experimental allergic encephalomyelitis (EAE) in numerous animals [1, 4, 10]. The evolution of chronic EAE in animal is similar to that of multiple sclerosis (MS), a demyelinating human pathology, and chronic EAE is considered to be an animal model of MS [1, 10]. In demyelinating pathologies, MBP concentration in the cerebrospinal fluid (CSF) is considered to be a good marker of demyelination [7, 9, 14–16]. MBP concentration, in biological fluids, is generally determined by radioimmunoassay (RIA) [3, 8, 9]. The RIA technique currently used is highly sensitive (0.1–2.5 ng/ml) [2, 14]but has the drawback of requiring the handling of radioactivity and frequent labelling of MBP [2, 14]. So we developed a new enzyme immunoassay (EIA) technique. Our technique has the same sensitivity as RIA, needs only small volumes of CSF (50 μl) and the enzyme-labelled MBP tracer is stable for at least 12 months. © 1997 Elsevier Science B.V. All rights reserved.

Cells secreting antibodies to myelin basic protein in cerebrospinal fluid of patients with Lyme neuroborreliosis

An autoimmune response to myelin basic protein (MBP) has been proposed to participate in the development of the chronic neurologic manifestations that may accompany Borrelia burgdorferi-induced Lyme disease. Using an immunospot assay, we counted cells secreting antibodies to MBP. Anti-MBP IgG antibody-secreting cells were detected in CSF from eight of 13 consecutive patients with Lyme neuroborreliosis irrespective of stage of disease. The numbers were between 1/370 and 1/5,000 CSF cells (mean, 1/1,250 in the 13 patients). The highest numbers were encountered in two patients with severe signs of CNS involvement. The numbers decreased in parallel with clinical improvement after treatment. Anti-MBP IgG antibody-secreting cells were also observed in the CSF from patients with a variety of other inflammatory diseases of the nervous system, and their role in the development of tissue damage remains unsettled. Anti-MBP IgG antibody-secreting cells were not detected in the patients' blood, reflecting accumulation of this autoantibody response to CSF.

Antimyelin basic protein and antimyelin antibody‐producing cells in multiple sclerosis

The B-cell response to myelin and myelin basic protein was studied in patients with multiple sclerosis and in patients with acute aseptic meningoencephalitis by using a nitrocellulose immunospot assay. This method allows detection of single cells producing antibodies. Twenty-seven (79%) of 34 patients with multiple sclerosis had cells producing IgG antibodies against myelin, and 11 (57%) of 19 had cells producing IgG antibodies against myelin basic protein in cerebrospinal fluid (CSF), with mean values of 30 and 14 per 10(4) mononuclear cells, respectively. Total numbers of IgG-producing cells occurred at a mean number of 75 per 10(4) CSF cells. Cells producing antimyelin or anti-myelin basic protein antibodies of IgA or IgM isotypes were rarely found in CSF. Patients with acute aseptic meningoencephalitis less frequently showed CSF cells producing IgG antibodies against myelin and myelin basic protein. No cells producing antibodies against myelin or myelin basic protein were detected in peripheral blood of patients with multiple sclerosis or meningoencephalitis. Thus, a majority of patients with multiple sclerosis had CSF cells that produced IgG antibodies against myelin and myelin basic protein. These cells comprised a large proportion of the total IgG-producing cells. A pronounced B-cell response against autoantigens produced at the target for immune attack might be important in the pathogenesis of multiple sclerosis.

Measurement of myelin basic protein in cerebrospinal fluid

Annals of NeurologyVolume 25, Issue 1 p. 107-107 Letter Measurement of myelin basic protein in cerebrospinal fluid Steven R. Cohen MD, PhD, Steven R. Cohen MD, PhD Suncoast Medical Clinic St Petersburg, FLSearch for more papers by this authorGuy M. McKhann MD, Guy M. McKhann MD Department of Neurology The Johns Hopkins University Baltimore, MDSearch for more papers by this author Steven R. Cohen MD, PhD, Steven R. Cohen MD, PhD Suncoast Medical Clinic St Petersburg, FLSearch for more papers by this authorGuy M. McKhann MD, Guy M. McKhann MD Department of Neurology The Johns Hopkins University Baltimore, MDSearch for more papers by this author First published: January 1989 https://doi.org/10.1002/ana.410250121Citations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume25, Issue1January 1989Pages 107-107 RelatedInformation

Experimental allergic encephalomyelitis in mice: presence of myelin basic protein in cerebrospinal fluid

The concentration of myelin basic protein (MBP) in cerebrospinal fluid (CSF) correlates with the development of experimental allergic encephalomyelitis following intradermal injection with encephalitogen in adjuvant; MBP is absent in controls inoculated with adjuvants only. The presence of MBP is a sensitive indicator of disease inasmuch as CNS-inoculated mice with neurologic signs had an average of 0.29 ng/μl of MBP in their CSF and controls, including normal or adjuvants only, had an average of 0.03 ng/μl. The amount present per μl of CSF, as well as the absolute amount, obtained from an individual mouse do not always reflect the severity of disease as indicated by clinical signs and the pathology observed in a sampling of the neuraxis. The presence of MBP does correlate with demyelination, although the extent of pathology observed by light microscopy in the mouse model is minimal, associated only with the inflammatory response, and does not extend beyond the zone of the perivascular cuff.