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PubMed1986

Abnormal proteins in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.

We studied more than 300 cerebrospinal fluid proteins from 21 patients with Creutzfeldt-Jakob disease. We also examined cerebrospinal fluid from 100 normal controls and more than 400 patients with various neurologic disorders other than Creutzfeldt-Jakob disease. Four abnormal proteins that were identified in the patients with Creutzfeldt-Jakob disease were absent in the normal persons. Two of these proteins (Mr [relative molecular mass], 40,000; pl [isoelectric point], 5.7 and Mr 40,000; pl 5.9) were also present in some patients with multiple sclerosis, herpes simplex encephalitis, schizophrenia, Parkinson's disease, or Guillain-Barré or Behçet's syndrome. Two proteins (Mr 26,000; pl 5.2 and Mr 29,000; pl 5.1) were present in all patients with Creutzfeldt-Jakob disease and in 5 of 10 patients with herpes simplex encephalitis, but in none of the other control groups. A subsequent blinded study of these cerebrospinal fluid proteins from patients with Creutzfeldt-Jakob disease, Alzheimer's disease, Huntington's disease, multi-infarct dementia, parkinsonism dementia of Guam, or the specific dementia of the acquired immunodeficiency syndrome resulted in the ability to distinguish all cases of Creutzfeldt-Jakob disease from the other types of dementia. Although the identity and origin of the abnormal spinal fluid proteins are not yet known, these preliminary results suggest that their presence may help in the diagnosis of Creutzfeldt-Jakob disease.

Cerebrospinal Fluid Proteins↗
PubMed1984

Two-dimensional electrophoresis of cerebrospinal fluid and ventricular fluid proteins, identification of enriched and unique proteins, and comparison with serum.

The proteins of cerebrospinal fluid (CSF) and ventricular fluid have been analyzed by two-dimensional electrophoresis (2DE) and the patterns compared with autologous serum. Fourteen proteins were specifically identified by immunoprecipitation followed by 2DE, or by blotting 2DE gels to nitrocellulose and detection by peroxidase staining. Proteins in CSF and serum with high and low affinity for the ligands, protein A, Cibacron Blue, and concanavalin A, were also characterized by 2DE. The 2DE profiles of CSF and serum proteins were similar and indicated that a relatively nonselective filtration mechanism based on protein size is the major determinant for the overall pattern of CSF proteins. The classic CSF-enriched or CSF-specific proteins, beta-trace, prealbumin, transferrin, and beta-2-microglobulin, were identified according to 2DE coordinates. Charge differences between CSF and serum for transferrin and prealbumin were identified. In addition, a large number of additional CSF-enriched or CSF-specific proteins of high, intermediate, and low molecular weight, all predominantly anodic in mobility, were identified. Three acidic protein complexes, heterogeneous in charge and molecular weight, were characterized as constituents of normal CSF, and two of these are increased in patients with inflammatory diseases of the CNS. All three proteins and several other proteins unique to CSF bound to Cibacron Blue-Sepharose. The use of 2DE in conjunction with affinity chromatography and sensitive protein stains enlarged the number of proteins previously identified as unique to CSF. By a modified 2DE and silver staining procedure, most of these proteins were visible without prior concentration of CSF.

Adult↗
PubMed2002

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.

Adolescent↗
PubMed2000

Prospective validation of a diagnosis model as an aid to therapeutic decision-making in acute meningitis.

The aim of this study was to validate a diagnosis model that provides pABM, the probability of bacterial versus viral meningitis, based on four parameters collected at the time of first lumbar tap: cerebrospinal fluid protein level, cerebrospinal fluid polymorphonuclear cell count, blood glucose level, and leucocyte count. The model was evaluated prospectively as an aid to therapeutic decision-making in 109 consecutive patients with acute meningitis and negative cerebrospinal fluid Gram stain. In each case pABM was computed before a therapeutic decision and three diagnoses were established successively: (i) clinical evaluation, i.e. before pABM computation (bacterial meningitis, viral meningitis, or meningitis of undetermined origin); (ii) computation of pABM (viral meningitis if pABM< 0.1, bacterial meningitis otherwise); and (iii) determination of definitive diagnosis (bacterial meningitis: positive cerebrospinal fluid culture; viral meningitis: negative cerebrospinal fluid culture, no other aetiology and no treatment; meningitis of undetermined origin: cases fitting neither of the first two diagnoses). The computed diagnosis was viral meningitis in 78 of the 80 cases diagnosed definitively as viral meningitis, and bacterial meningitis in four of the five cases diagnosed definitively as bacterial meningitis. Negative and positive predictive values and accuracy of the model were 98.7%, 66.7%, and 96.5%, respectively. The clinical diagnosis was undetermined in 22 cases, 15 of which were diagnosed definitively as viral cases; in all of these 15 cases, the computed diagnosis was viral meningitis, leading the physician to refrain from starting antibiotics in all of them. The results confirm that the model evaluated is reliable and aids in the identification of patients in whom antibiotics can be safely avoided.

Acute Disease↗