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At least 271 records · Page 15Linked to original sources

Spontaneous canine hydrocephalus: cerebrospinal fluid dynamics.

Cerebrospinal fluid dynamics were studied in 14 dogs with spontaneous hydrocephalus. In nine of the dogs aqueductal obstruction was observed and the remainder had a `communicating type' hydrocephalus. The major histological findings consisted of severe ependymal destruction, spongy changes in the periventricular white matter, increased density of capillaries in this area, and varying degrees of thickening, fibrosis, and fusion of the choroid villi. The formation and absorption of CSF were studied by perfusion of the cerebral ventricles. The rate of formation of CSF was found to decrease with perfusion pressure by V(f) = 0·02595-0·00022 P ml./min (P = pressure in cm H(2)O). The absorption of spinal fluid was found to increase linearly with pressure by V(a) = 0·0165 + 0·00050 P. The various factors influencing the formation and absorption of the spinal fluid are discussed. The meaning and attainment of `arrest' of the hydrocephalic process in terms of the measured rates of CSF formation and absorption in these animals are considered.

Animals↗

Multiple sclerosis cerebrospinal fluid biomarkers.

Cerebrospinal fluid (CSF) is the body fluid closest to the pathology of multiple sclerosis (MS). For many candidate biomarkers CSF is the only fluid that can be investigated. Several factors need to be standardized when sampling CSF for biomarker research: time/volume of CSF collection, sample processing/storage, and the temporal relationship of sampling to clinical or MRI markers of disease activity. Assays used for biomarker detection must be validated so as to optimize the power of the studies. A formal method for establishing whether or not a particular biomarker can be used as a surrogate end-point needs to be adopted. This process is similar to that used in clinical trials, where the reporting of studies has to be done in a standardized way with sufficient detail to permit a critical review of the study and to enable others to reproduce the study design. A commitment must be made to report negative studies so as to prevent publication bias. Pre-defined consensus criteria need to be developed for MS-related prognostic biomarkers. Currently no candidate biomarker is suitable as a surrogate end-point. Bulk biomarkers of the neurodegenerative process such as glial fibrillary acidic protein (GFAP) and neurofilaments (NF) have advantages over intermittent inflammatory markers.

Biomarkers↗

Immunoreactive calcitonin in human cerebrospinal fluid.

The cerebrospinal fluid (CSF) of 123 male subjects was studied by RIA for the presence of immunoreactive calcitonin (CT). The hormone could be detected in the CSF of 75% of 63 subjects at a mean (+/- SE) concentration of 11.1 +/- 1.3 pg/ml, with a range of less than 2 to 55 pg/ml. In 31 subjects, simultaneous measurements were made of CSF and plasma CT and there was not significant correlation between them. Column chromatography of a lyophilized pool of CSF from 60 of the subjects demonstrated that most of the CT immunoreactivity eluted with or after radioiodinated human CT. Our studies demonstrate the presence of immunoreactive CT in human CSF but do not provide any direct evidence regarding the source of the immunoreactivity.

Calcitonin↗

Pregnancy-specific beta 1-glycoprotein-like material in human cerebrospinal fluid.

Human cerebrospinal fluid (CSF) from 34 unselected neurological patients was studied for pregnancy-specific beta 1-glycoprotein (SP1) activity because of the recent finding of SP1 production by cultured glial cells. An organic central nervous system lesion was diagnosed in 9 patients, but not in the other 25. Low levels of SP1 immunoreactivity were found in CSF by RIA, and the adsorption of anti-SP1 antiserum with concentrated CSF abolished the positive immunohistochemical staining of placental tissue obtained with the unadsorbed antiserum. By means of immunoadsorption using monoclonal anti-SP1 antibodies, it was possible to isolate SP1 immunoreactive material from CSF and to demonstrate that it had the same electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis as purified placental SP1. These results show that CSF contains SP1-like material that is closely related, if not identical, to placental SP1. The amount of SP1 in CSF has no direct correlation to an organic central nervous system lesion or to abnormality of the CSF.

Adenocarcinoma↗

Ascending meningitis secondary to traumatic cerebrospinal fluid leaks.

Cerebrospinal fluid (CSF) leakage may cause immediate or delayed complications, such as ascending meningitis and brain abscess, potentially lethal complications that may appear years or decades after the trauma. Thus, the initial treatment of a CSF fistula may decisively influence long-term outcome. In a retrospective study including 1036 consecutive patients presenting with severe cranial trauma from May 1990 to March 1996, we identified 27 patients (2.6%) with CSF fistulas. Patients with a post-traumatic CSF leak were most commonly males between 15 and 40 years involved in a motor vehicle accident. The most common sites of injury were the frontal area and anterior skull base for those patients with rhinorrhea and the temporal bone for those patients with otorrhea. A transcranial repair was used for large cranial base defects (n = 10), while conservative treatment, comprised of bedrest, lumbar drainage, and medications, was used for smaller fistulas (n = 17). Four patients (40%) initially treated with a transcranial repair, and five patients (29%) initially treated conservatively, developed a meningitis. Therefore, neither the conservative approach nor the transcranial repair was able to prevent this considerable incidence of ascending meningitis. We believe that the high incidence of meningitis is not acceptable; thus, we are now evaluating early intervention using endoscopic techniques for the identification and/or repair of post-traumatic fistulas.

Adolescent↗

Immunoelectroosmophoresis (IEOP) for detection of bacterial antigens in cerebrospinal fluid.

365 cerebrospinal fluid specimens from 259 patients were tested by the immunoelectroosmophoretic (IEOP) method to detect bacterial antigens. 25 patients had bacterial meningitis. The bacterial agent was identified by IEOP in 16 of 21 cases with aetiological agents detectable with the antisera employed. No false positive reactions occurred. The test gave true negative results in 340 instances. The rapidity, simplicity, sensitivity, reliability and low cost are emphasized.

Adolescent↗

Tardive dyskinesia and neurotransmitters: effects of sodium valproate, cyproheptadine, oxypertine, hydroxyzine pamoate and Ca-hopantenate on monoamine metabolites, cyclic nucleotides and gamma-aminobutyric acid in human cerebrospinal fluid.

Lumbar cerebrospinal fluid (CSF) homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), cyclic AMP (cAMP) and cyclic GMP (cGMP) were measured in chronic schizophrenics with tardive dyskinesia before and three weeks after the initial treatment with sodium valproate (VPA), cyproheptadine, oxypertine or hydroxyzine pamoate. HVA levels significantly decreased after the administration of VPA, cyproheptadine or oxypertine. Cyclic GMP levels significantly increased after the administration of VPA or cyproheptadine. Elevation of the cAMP level was observed after the administration of VPA, cyproheptadine or oxypertine. An elevation of the MHPG level was observed during oxypertine treatment and a reduction of the 5-HIAA level was observed during hydroxyzine pamoate treatment. Decreases in HVA and increases in cGMP levels during treatment might be indicative of normalization of the dopaminergic-cholinergic imbalance in the brain. Lumbar CSF HVA and gamma-aminobutyric acid (GABA) were also measured in patients with tardive dyskinesia before and eight weeks after Ca-hopantenate treatment. No significant changes were observed before or after this treatment. The hypothesis is discussed that the pathogenesis of tardive dyskinesia may involve functional disorders not only of the dopaminergic or cholinergic system but also of the norepinephrinergic, serotoninergic and GABA-ergic systems.

Adult↗

The effect of carbonic anhydrase inhibitors and other drugs on sodium entry to cerebrospinal fluid.

Single cerebrospinal fluid (CSF) samples, taken 7 min after the i.v. administration of tracer 22Na+, provided data for calculation of rate constants for entry of Na+ into CSF from plasma. Four carbonic anhydrase (CA) inhibitors and certain other drugs were studied in terms of 1) ability to reduce the entry of Na+ into CSF and 2) level of drug in plasma. Dose-response curves were generated for the CA inhibitors. Complete CA inhibition in this system is defined by kin 0.017 to 0.019 min-1, a reduction of about 35% from the control kin for Na+. Acetazolamide, ethoxzolamide and methazolamide were fully inhibitory at 20 mg/kg. Significant decreases, approximately 19%, were caused by 2 mg/kg of acetazolamide or ethoxzolamide; methazolamide unaccountably was less effective at this dose. Benzolamide was relatively inactive, but gave full effect at 150 mg/kg. The diuretics furosemide and bumetanide and the steroid dexamethasone showed no activity against Na+ entry. In considering these responses, attention is given to drug affinity for CA and to properties affecting access of inhibitors to CSF-secreting sites. There is a well recognized correlation between the movement of Na+ from plasma into CSF and the secretion of CSF. These data may, therefore, be taken as indicators of the relative ability of the drugs to decrease CSF flow.

Animals↗

Nitric oxide synthase is present in the cerebrospinal fluid of patients with active multiple sclerosis and is associated with increases in cerebrospinal fluid protein nitrotyrosine and S-nitrosothiols and with changes in glutathione levels.

Nitric oxide (NO) is hypothesized to play a role in the immunopathogenesis of multiple sclerosis (MS). Increased levels of NO metabolites have been found in patients with MS. Peroxynitrite, generated by the reaction of NO with superoxide at sites of inflammation, is a strong oxidant capable of damaging tissues and cells. Inducible NO synthase (iNOS) is up-regulated in the CNS of animals with experimental allergic encephalomyelitis (EAE) and in patients with MS. In this study, Western blots of cerebrospinal fluid (CSF) from patients with MS demonstrated the presence of iNOS, which was absent in CSF from control subjects. There was also NOS activity present in both MS and control CSF. Total NOS activity was increased (by 24%) in the CSF from MS patients compared with matched controls. The addition of 0.1 mM ITU (a specific iNOS inhibitor) to the samples did not change the activity of the control samples but decreased the NOS activity in the MS samples to almost control levels. The addition of 1 mM L-NMMA (a nonisoform specific NOS inhibitor), completely inhibited NOS activity in CSF from control and MS subjects. Nitrotyrosine immunostaining of CSF proteins was detectable in controls but was greatly increased in MS samples. There were also significant increases in CSF nitrate + nitrite and oxidant-enhanced luminescence in MS samples compared with controls. Additionally, a significant decrease in reduced glutathione and significant increases in oxidized glutathione and S-nitrosothiols were found in MS samples compared with controls. Parallel changes in NO metabolites were observed in the plasma of MS patients, compared with controls, and accompanied a significant increase of reduced glutathione. These data strongly support a role for nitrosative stress in the pathogenesis of MS and indicate that therapeutic strategies focussed on decreasing production of NO by iNOS and/or scavenging peroxynitrite may be useful in alleviating the neurological impairments that occur during MS relapse.

Adult↗

[Relation between the clinical and cerebrospinal fluid parameters in multiple sclerosis, with special reference to subjects without oligoclonal IgG in the cerebrospinal fluid].

120 patients with clinically definite or probable Multiple Sclerosis (MS) were studied by Isoelectric focusing of cerebrospinal fluid and serum proteins. Of the 62 patients with definite MS, 56 (90%) had IgG oligoclonal bands only in CSF, while in the group with probable MS 44 patients over 58 (75,8%) showed the same finding. The group of 20 patients with normal IgG profile has been compared with a group of 22 patients selected by random out of the 100 with IgG oligoclonal bands. No statistically significant difference was discovered between these groups but a tendency to present an higher age at onset and a longer duration of the disease in the group with a normal IgG pattern than in the patients with oligoclonal bands was pointed out.

Blood Proteins↗

Lactoferrin, C-reactive protein, alpha-1-antitrypsin and immunoglobulin GA in cerebrospinal fluid in meningitis.

Cerebrospinal fluid measurements of lactoferrin and alpha-1-antitrypsin showed significant elevation in bacterial meningitis in children. 8 of 10 lactoferrin values and 6 of 11 alpha-1-antitrypsin values were above the upper range of controls. Both proteins correlated well with the total number of leukocytes in the cerebrospinal fluid. C-reactive protein, measured by either agglutination or radial immunodiffusion in the cerebrospinal fluid, failed to demonstrate any usefulness in diagnosing bacterial meningitis. Neither elevated serum C-reactive protein in cases of bacterial meningitis, nor sepsis, gave detectable concentrations of C-reactive protein in the cerebrospinal fluid.

Adolescent↗