[Cerebrospinal fluid. Current methods and research results as a basis of interpretation of cerebrospinal fluid findings].
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The side chain oxidized oxysterol 24S-hydroxycholesterol (24-OH-chol) is formed almost exclusively in the brain, and there is a continuous passage of this oxysterol through the circulation to the liver. 27-Hydroxycholesterol (27-OH-chol) is produced in most organs and is also taken up by the liver. The 27-OH-chol-24-OH-chol ratio is about 0.1 in the brain and about 2 in the circulation. This ratio was found to be about 0.4 in cerebrospinal fluid (CSF) of asymptomatic patients, consistent with a major contribution from the circulation in the case of 27-OH-chol. In accordance with this, we demonstrated a significant flux of deuterium labeled 27-OH-chol from plasma to the CSF in a healthy volunteer. Patients with a defective blood-brain barrier were found to have markedly increased absolute levels (up to 10-fold) of both 27-OH-chol and 24-OH-chol in CSF, with a ratio between the two sterols reaching up to 2. There was a significant positive correlation between the levels of both oxysterols in CSF and the albuminCSF-albuminplasma ratio. The 27-OH-cholCSF-24-OH-cholCSF ratio was found to be about normal in patients with active multiple sclerosis and significantly increased in patients with meningitis, polyneuropathy, or hemorrhages. Results are discussed in relation to the possible use of 24-OH-cholCSF as a surrogate marker of central nervous system demyelination and/or neuronal death.
To gain insight of the underlying mechanisms of astroglial response to Alzheimer's disease (AD), the level of glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF) from controls and AD subjects were immunochemically determined, and the correlation between that level and dementia severity of AD patients was evaluated. Means and SD of CSF levels of GFAP for the young control group (from 1 to 25 years, mean +/- SD 14.2 +/- 5.0, n = 13) adult control (from 26 to 55 years, 41.6 +/- 10.1, n = 9) and senescent control (older than 56 years, 65.4 +/- 8.0, n = 8) were 2.96 +/- 1.04, 2.80 +/- 1.46 and 3.99 +/- 1.55 ng/ml, respectively, and the CSF level of GFAP was not dependent on age (ANOVA, p = 0.17). While that of the AD patient group (n = 27, 70.8 +/- 8.0 years) was 8.96 +/- 7.80 ng/ml, significantly higher than that of both the all-control (3.19 +/- 1.39 ng/ml, t test, p < 0.001) and age-matched senescent (3.99 +/- 1.55 ng/ml, t test, p < 0.005) control groups. The receiver-operator characteristic (ROC) curve revealed that the GFAP concentration at 5 ng/ml in CSF could serve as a cutoff value. The CSF level of GFAP in the moderately to severely demented patients (MMSE </= 17, 13.2 +/- 9.10 ng/ml, n = 9) was approximately by two-fold higher than that of the mildly to moderately demented patients (MMSE >/= 18, 6.85 +/- 5.76 ng/ml, n = 18; ANOVA, p < 0.05). These findings together with our previous report on an increase in the CSF level of apolipoprotein E suggest that degeneration and stimulation of astrocytes takes place concurrently in the AD brain.
BACKGROUND: Many neurological diseases are connected with the dysfunction of blood-CSF barrier. The quantitative determination of CSF proteins has already been used in the diagnosis of barrier impairments and inflammatory diseases of the central nervous system. PATIENTS: Serum and CSF, totaling 264 samples, were obtained from 15 controls and 117 patients with various diseases of the nervous system. Laurell's electroimmunoassay was used for estimation of albumin and IgG levels in serum and CSF. CSF-protein profile was evaluated according to Reiber's graph for the evaluation of the CSF-protein profile. RESULTS: The graph for the protein profile can be divided into 5 functionally different parts (1--normal range, 2, 3, 4--different types of barrier dysfunctions and 5--local humoral response in CNS without any barrier impairment). There was a good correlation of CSF-protein profiles and neurological diseases in our group of patients. CONCLUSIONS: According to our results, Reiber's graph was helpful for the diagnosis of blood-CSF-barrier dysfunctions. The graph has the following advantages: a) possibility of simultaneous assessment of the functional state of blood-CSF-barrier and the inflammatory response of the CNS, b)sensitivity for the determination of pathological local IgG-production in CNS and c) minimal number of protein assays necessary.
BACKGROUND: Hyaluronan (HA) was measured in cerebrospinal fluid (CSF) to ascertain the clinical significance of this substance in patients with spinal disorders, a topic that, to the best of our knowledge, has not previously been studied. METHODS: We examined correlations of CSF HA concentration with age, sex, height, body weight, and spinal disorders. By using a sandwich-binding protein assay, HA was measured in CSF samples obtained from 500 patients aged 12 to 104 years who underwent lumbar spinal anesthesia for surgery, myelography, or CSF examination. These patients were classified into 3 groups: (1) a control group (306 patients with injury or benign tumor of the lower limbs); (2) a cervical disorders group (84 patients with cervical disc herniation, cervical spondylotic myelopathy, or ossification of the posterior longitudinal ligament); and (3) a lumbar disorders group (110 patients with lumbar disc herniation, lumbar spinal canal stenosis tethered cord syndrome, lumbar fracture, or spondylolytic spondylolisthesis). RESULTS: CSF HA concentration was found to be positively correlated with age, and was significantly higher in patients with cervical spondylotic myelopathy, ossification of the posterior longitudinal ligament, or lumbar spinal canal stenosis tumor than in the control group. CONCLUSIONS: CSF HA concentration might be a secondary marker for inflammation in patients with spinal disease.
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Our investigations concerned the blood-brain barrier (b.b.b.) in patients with acute bacterial purulent meningitis. For that purpose concentrations of proteins, which are synthesized beyond the central nervous system and in normal cerebrospinal fluid (CSF) exist only in slight amounts, were determined in CSF and in blood serum. Albumin was examined in the CSF of 59 patients and in the serum of 35 of them, transferrin of 40 and 32 patients, respectively. Etiological verification was obtained in 84.7% of patients. The control group consisted of 20 persons. Quantitative analytical tests were carried out by means of immunochemical, turbidimetric methods. High levels of albumin and transferrin in CSF and low in serum of patients with meningitis were observed. The obtained results, confirmed by statistical analysis, demonstrate that in the acute phase of purulent meningitis b.b.b is impaired, what leads to the transfer of the proteins from the blood serum into the cerebrospinal fluid and that transferrins a better indicator of the damage to blood-brain barrier than albumin.
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A soluble form of the intercellular adhesion molecule-1 (sICAM-1) was measured in paired cerebrospinal fluid (CSF)/blood samples from 123 patients with different neurological diseases. Mean levels of circulating ICAM-1 in the blood were mean +/- SD = 423 +/- 184.6 ng ml-1 (range 44-1115 ng ml-1). Considerable differences of sICAM-1 in the CSF of patients were observed between disease groups. In acute bacterial meningitis, sICAM-1 levels as high as 1/5 of the serum concentration were detected in the CSF (n = 24; mean +/- SD = 33.0 +/- 23.7 ng ml-1; range: 4.8-93.9 ng ml-1). These changes coincided with a severe blood-CSF barrier dysfunction as indicated by a high CSF/blood ratio for albumin (mean +/- SD = 46.7 +/- 52.2; range: 16.8-249.3). In patients with polyradiculitis (n = 9; mean +/- SD = 14.5 +/- 11.9 ng ml-1; range: 2.6-43.7 ng ml-1) a similar covariation between the albumin and sICAM CSF/blood ratios was detected. In patients with multiple sclerosis (n = 9; mean +/- SD = 5 +/- 4.3; range: 0-12.7 ng ml-1) or HIV infection with neurological symptoms (n = 18; mean +/- SD = 4.9 +/- 3.2; range; 1-11.9 ng ml-1) low levels of sICAM-1 were detected in the CSF associated with intact blood-CSF barrier function in most patients. Among 13 patients with viral meningitis, only four had detectable levels of sICAM-1 in their CSF (mean +/- SD = 1.0 +/- 1.5 ng ml-1; range: 0-3.7).(ABSTRACT TRUNCATED AT 250 WORDS)
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BACKGROUND: This report describes the sensitivity and specificity of glucose detection using Glucostix test strips and computed tomography (CT) of the skull base for confirming cerebrospinal fluid (CSF) fistulae in patients with persistent rhinorrhoea or otorrhoea, and comparing them with the beta-2 transferrin assay as the gold standard for CSF detection. METHODS: Fluid samples from the nose were collected from 18 patients with suspected CSF fistulae. The samples were assayed for beta-2 transferrin using the Western blotting and immunostaining technique. CT (5mm axial slice) of the skull base was performed for evidence of skull base fracture. The glucose levels and Glucostix results were compared. RESULTS: Out of the 18 samples, 15 were positive for beta-2 transferrin adn the leaks were validated surgically in 10 patients. Give leaks healed spontaneously with conservative management. Glucostix tests produced three false positive results from blood and nasal mucus contaminated fluid. Glucostix failed to detect another three CSF leaks resulting from false negative tests because of low CSF glucose levels. The Glucostix glucose test was nonspecific and insensitive compared with the beta-2 transferrin assay. CT failed to detect three of the 15 beta-2 transferrin-positive leaks but there were no false positive results. CT produced six negative results, of which three were false negatives. CONCLUSIONS: Glucose detection using Glucostix test strips is not recommended as a confirmatory test due to its lack of specificity and sensitivity. In the presence of a skull bas fracture on CT and a clinical CSF leak, there is no need for a further confirmatory test. In cases where a confirmatory test is needed, the beta-2 transferrin assay is the test of choice because of its high sensitivity and specificity.
RATIONALE AND OBJECTIVES: To investigate and measure temporal and amplitude aspects of blood and cerebrospinal fluid (CSF) flow waveform relations. METHODS: A cine phase-contrast magnetic resonance imaging pulse sequence was used to measure blood and CSF flow in 16 healthy subjects aged 27 +/- 4 years. A semiautomated segmentation algorithm was developed to study CSF flow. RESULTS: Standard deviations of the aqueductal and cervical flow measurements carried out by five observers were 1% and 4%, respectively. The peak systolic arterial flow was 1087 +/- 169 mL/min, and the peak cervical CSF flush (173 +/- 59 mL/min) occurred at 5% +/- 3% of the cardiac cycle after the internal carotid systolic peak flow. Peak aqueductal flush flow (13 +/- 5 mL/min) occurred at 21% +/- 7% of the cardiac cycle after the internal carotid systolic peak flow. CONCLUSIONS: The CSF segmentation algorithm is reproducible. Brain expansion was quickly regulated by a major extracerebral CSF flush flow, whereas ventricular CSF made only a very small contribution.
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