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Cerebrospinal fluid abnormalities in acute posterior multifocal placoid pigment epithelialopathy.

Two patients with acute posterior multifocal placoid pigment epithelialopathy also had cerebrospinal fluid pleocytosis and elevated protein levels. A 24-year-old white women had visual acuity of counting fingers in each eye. The cerebrospinal fluid contained 56 lymphocytes per cubic millimeter and a protein level of 48 mg/100 ml. When the retinopathy resolved, visual acuity returned to R.E.: 6/60 (20/200), AND L.E.: 6/9 (20/30). A 22-year-old white man had visual acuity of counting fingers bilaterally. The initial lumbar puncture showed 70 lymphocytes and a protein level of 76 mg/100 ml. A second cerebrospinal tab showed 64 lymphocytes and a protein level of 86 mg/100 ml. Final visual acuity was R.E.: 6/15 (20/50), and L.E.: 6/6 (20/20). Neither patient received treatment for this disorder. The findings of cerebrospinal fluid cells and elevated protein levels in acute posterior multifocal placoid pigment epithelialopathy probably represent a mild viral meningitis as part of a systemic viral infection that also involves the retinal pigment epithelium or choriocapillaris.

Acute Disease↗

Aminoterminal propeptides of type III procollagen in human cerebrospinal fluid.

The concentrations of aminoterminal propeptides of procollagen type III were determined by radioimmunoassay in the cerebrospinal fluids of 64 patients with various neurological disorders, including 4 infant patients (less than 1 year). In cerebrospinal fluids of adult patients with normal composition (protein, glucose, cell count), adult patients with pathologic composition, and infant patients the peptide levels (mean value +/- S.D.) were 4.07 +/- 1.26 micrograms/l, 8.15 +/- 6.78 micrograms/l, and 56.9 +/- 31.0 micrograms/l, respectively. The concentrations ranged from 1.96 to 265 micrograms/l and were independent of the respective serum propeptide levels. No statistic correlation with other parameters was found. Gel chromatography revealed a high degree of molecular weight heterogeneity, a substantial portion of immunoreactive material was eluted even with the void volume of Sephacryl S 300. Different slopes of radioimmunoinhibition curves indicate heterogenous antigenicity among the propeptides from various patients. Interaction of the propeptides with fibronectin and/or heparin is probably not responsible for the heterogeneity. The diagnostic potential of cerebrospinal fluid propeptide levels for local connective tissue (collagen) turnover remains to be elucidated.

Adult↗

Increased cerebrospinal fluid glycine: a biochemical marker for a leukoencephalopathy with vanishing white matter.

Recently, a new disease entity has been defined: the disease of vanishing white matter. This leukoencephalopathy has an autosomal-recessive mode of inheritance. No cause or biochemical marker is known. We studied cerebrospinal fluid amino acids in five patients with the disease and found a consistent, moderate elevation of cerebrospinal fluid glycine in all. The ratio of cerebrospinal fluid to plasma glycine was elevated in four patients, in two patients reaching the level considered diagnostic for nonketotic hyperglycinemia. The activity of the glycine cleavage system was found to be normal in lymphoblasts in two patients. The elevation of cerebrospinal fluid glycine in the disease of vanishing white matter is either caused by a primary disturbance of glycine metabolism or is secondary to excitotoxic brain damage.

Adolescent↗

Relative increase of inflammatory CD4+ T cells in the cerebrospinal fluid of multiple sclerosis patients and control individuals.

Of three patients with multiple sclerosis (MS) and two non-MS individuals a large number of CD4+ T cell clones was obtained from the cerebrospinal fluid and peripheral blood by direct limiting dilution. The CD4+ T cell clones from cerebrospinal fluid and peripheral blood lymphocytes were compared for their cytotoxic activity and lymphokine production. Cytotoxic capacity of cloned T cells was analysed with the use of anti-CD3 antibodies and target cells bearing Fc receptors for murine IgG. Recently, we demonstrated the existence of two different subsets of human CD4+ T cell clones by phenotypic and functional criteria. One type of CD4+ T cell with anti-CD3 mediated cytotoxic activity, in analogy with murine studies, is the inflammatory or TH1 subtype, the main producer of interleukin (IL-2), interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF)-alpha, -beta, whereas the other type of CD4+ T cell clone lacked anti-CD3 mediated cytotoxicity and produced minimal amounts of IL-2 concomitant with reduced levels of IFN-gamma and TNF-alpha, -beta. The present study demonstrates that among three MS patients, relatively more inflammatory CD4+ T cell clones with cytotoxic activity and IFN-gamma and TNF-alpha, -beta production were derived from the cerebrospinal fluid as compared with peripheral blood lymphocytes. Also among control individuals more inflammatory CD4+ T cell clones could be obtained from the cerebrospinal fluid as from the peripheral blood. The enrichment of inflammatory CD4+ T cells, therefore, appears to be physiological rather than associated with the disease.

CD4-Positive T-Lymphocytes↗

Alpha-melanocyte-stimulating hormonelike immunoreactivity is increased in cerebrospinal fluid of patients with Parkinson's disease.

We measured alpha-melanocyte-stimulating hormonelike immunoreactivity in cerebrospinal fluid of 12 healthy control subjects and nine patients with Parkinson's disease, four of whom had never been treated. Mean cerebrospinal fluid alpha-melanocyte-stimulating hormonelike immunoreactivity concentration was two-fold greater in parkinsonian patients (44.1 +/- 9.3 [SD] pg/mL) as compared with control subjects (21.8 +/- 10.0 pg/mL). No significant correlation was found between cerebrospinal fluid alpha-melanocyte-stimulating hormonelike immunoreactivity concentrations and patient age, disease severity, or duration of disease. These results suggest a functional relation between dopaminergic and melanotropinergic systems in the human brain.

Aged↗

Fluconazole in cats: pharmacokinetics following intravenous and oral administration and penetration into cerebrospinal fluid, aqueous humour and pulmonary epithelial lining fluid.

The pharmacokinetics of fluconazole following intravenous (i.v.) and oral (p.o.) administration and the penetration of fluconazole into cerebrospinal fluid, aqueous humour and epithelial lining fluid (ELF) of the lungs were evaluated in adult male cats. Pharmacokinetic parameters were calculated from serum concentration-time data obtained following i.v. and p.o. administration of 50 mg per cat using a cross-over study design. Fluconazole concentrations were measured using a high-performance liquid chromatography assay. Mean total body clearance of fluconazole was 37.7 mL/h.kg, mean volume of distribution at steady state was 1.14 L/kg, mean residence time was 31.0 h and mean half-life of elimination was 25 h as derived by non-compartmental analysis of data. Absorption was complete. Mean ratios of fluid:serum fluconazole concentrations following administration of 50 mg fluconazole per day for 8 days were as follows: cerebrospinal fluid, 0.88; aqueous humour 0.79; ELF, 1.20. Fluconazole concentrations in cerebrospinal fluid, aqueous humour and ELF exceeded reported minimum inhibitory concentrations of fluconazole for pathogenic fungi. Results of this study suggest fluconazole can effectively be administered to cats at 50 mg per cat per day.

Administration, Oral↗

[Haptoglobin levels in the serum and the cerebrospinal fluid patients with multiple sclerosis].

In 47 patients with multiple sclerosis and 10 with other diseases of the nervous system determinations of haptoglobin were performed in the serum and cerebrospinal fluid by the method of Owen et al. The Hp level in the serum of multiple sclerosis patients was normal. Its level in the cerebrospinal fluid was higher in multiple sclerosis patients than in cases of other nervous system diseases (statistically significant difference, p less than 0.001). Raised value of the Hp/IgG index in the cerebrospinal fluid of multiple sclerosis patients points to increased permeability of the blood-brain barrier. The so called normal Hp/IgG index was found in multiple sclerosis patients with high Hp and IgG level. Low Hp/IgG index suggested the possibility of IgG synthesis in the brain of patients with this disease. The comparison of the protein level and protein indexes showed that raised IgG level in the cerebrospinal fluid was present in 80% of multiple sclerosis cases, raised Kabat index in 50%, and low Hp/IgG index in 48%.

Haptoglobins↗

Detection of cytomegalovirus in cerebrospinal fluid autopsy specimens from AIDS patients.

Cytomegalovirus (CMV) is a common opportunistic pathogen infecting AIDS patients. Polymerase chain reaction (PCR) and antigen capture ELISA were used to detect CMV in 40 cerebrospinal fluid autopsy specimens from patients with AIDS. CMV DNA was detected by PCR in 70% of samples. Of the 21 samples from patients with systemic CMV infection, 57% had CMV encephalitis, while 81% had virus in cerebrospinal fluid detectable by PCR. Of the 24 samples from patients with no histologic evidence of CMV encephalitis, 58% had CMV DNA in cerebrospinal fluid detected by PCR. These results suggest that PCR of cerebrospinal fluid sensitively detects systemic CMV infection but is not specific for brain infection in autopsy specimens of AIDS patients.

AIDS-Related Opportunistic Infections↗

Superficial siderosis of the brain: roles for cerebrospinal fluid circulation, iron and the hydroxyl radical.

Superficial siderosis is associated with chronic blood loss into the cerebrospinal fluid. The pattern of hemosiderin deposition and clinical signs in superficial siderosis suggest that cerebrospinal fluid is recirculated into the ventricular system. Patterns of deposition of corpora amylacea and findings in normopressure communicating hydrocephalus also support the recirculation theory. 'Free' iron with excess production of hydroxyl radicals is the probable mechanism of tissue damage. The arachnoid villus-superior saggital sinus theory of cerebrospinal fluid circulation should be abandoned.

Brain Diseases↗

Acetylcholinesterase--a specific marker for cerebrospinal fluid.

An oedematous pre-eclamptic patient received lumbar epidural analgesia during labour. Clear fluid leaked from the skin puncture site for 4 days. The fluid was analysed using protein electrophoresis for cholinesterase enzymes and was found not to contain the cerebrospinal fluid specific form of the enzyme, acetylcholinesterase. The sensitivity of this test was explored using serial dilutions of cerebrospinal fluid. It is now possible to say that the leaking fluid did not contain cerebrospinal fluid.

Acetylcholinesterase↗

Acute changes in the dynamics of the cerebrospinal fluid system during experimental subarachnoid hemorrhage.

Early changes in intracranial pressure (ICP), ICP volume index, and resistance to absorption of cerebrospinal fluid induced by experimental subarachnoid hemorrhage were studied in cats. After SAH, the ICP was slightly elevated, and there was a decrease in the buffering capacity of the intracranial space and a sharp rise in outflow resistance. During infusion of blood into the cisterna magna with a constant infusion rate, an extensive increase in ICP could be demonstrated in contrast to the infusion of saline, which caused only slight elevation of ICP. Furthermore, during blood infusion, the ICP level did not reach a plateau phase of pressure, as was demonstrated during infusion of saline. It is suggested that the marked increase in ICP during blood infusion into the subarachnoid space is caused by intracranial volume loading and the simultaneous increase in cerebrospinal fluid outflow resistance. It is concluded that the reported relationship between increased cerebrospinal fluid outflow resistance and increased ICP supports the hypothesis of a strong increase in ICP during subarachnoid hemorrhage in human subjects.

Animals↗

Impermeability of the blood-cerebrospinal fluid barrier for angiotensin II in rats.

1. Anaesthetized, nephrectomized rats were infused intravenously with unlabelled angiotensin II (AII) or with [3H]angiotensin II (3H-labelled AII). The brain ventricular system was perfused with artificial cerebrospinal fluid. The perfusate was collected from the cisterna magna and analysed for AII by radioimmunological and biochemical methods. 2. No increase of immunoreactive AII in cerebrospinal fluid could be shown during intravenous infusion of AII. 3. During intravenous infusions of 3H-labelled AII at pressor doses small amounts of radioactivity were found in cerebrospinal fluid perfusate. 4. The radioactivity of cerebrospinal fluid outflow could not be related to AII.

Angiotensin II↗

Morphological indications for considerable diffuse reabsorption of cerebrospinal fluid in spinal meninges particularly in the areas of meningeal funnels. An electronmicroscopical study including tracing experiments in rats.

Transmission and scanning electron microscopical observations in the rat indicate a considerable capacity of the spinal meninges to reabsorb cerebrospinal fluid. The density of blood vessels and lymphatics in the duramater is extremely high, particularly in the areas of meningeal funnels and spinal nerve root sleeves. Arterioles with closely related unmyelinated nerve fibres, many fenestrated capillaries and venules predetermine these areas as sites where absorption processes could take place. At certain sites of the meningeal angle region, the arachnoid membrane, mostly multilayered, is reduced to only three or four layers. Intercellular discontinuities and cytoplasmic fenestrations occurring in the arachnoid lining cell layer result in direct communications between the subarachnoid space and cisterns of the arachnoid "reticular layer". These cisterns are partly fluid-filled, partly occupied by a net of collagen fibre bundles. Some cisterns harbour macrophages that often project filiform processes through the lining cell layer into the subarachnoid space, contacting cerebrospinal fluid. Desmosomes and gap junctions are present in all layers of the arachnoid. However, tight junctions and the continuous electrondense intercellular gap, known to occur normally within the "arachnoid barrier layer", were not seen in many sites of the meningeal angle region. Numerous arachnoid cells display a high degree of vesiculation. Cationized ferritin, introduced in vivo into the rat subarachnoid space, passes inter- and intracellularly from the cerebrospinal fluid compartment through the arachnoid membrane, reaching dural blood vessels and lymphatics. Tracer could be visualized both in the cytoplasm of the endothelium and on the luminal surface of the cells. Tracer also passed through pial cell layers into pial vessels, through leptomeningeal sheaths into vessels crossing the subarachnoid space, into the connective tissue compartment and into vessels of spinal dorsal root ganglia. In the angle region, a particularly large number of macrophages can be found on the surface of leptomeninges, within the arachnoid reticular layers, and in close relation to dural and epidural capillaries, venules and lymphatics. Their possible role in the process of cerebrospinal fluid reabsorption is discussed.

Absorption↗

Experimental determination of time of intracranial hemorrhage by spectrophotometric analysis of cerebrospinal fluid.

A method for determining the time elapsed after a cerebrovascular accident by examination of the cerebrospinal fluid (CSF) is described. Hemorrhagic intracranial trauma was simulated in dogs by injecting blood into the subarachnoid space. Daily samples of cerebrospinal fluid were gathered during the subsequent 14 days, and the concentrations of oxyhemoglobin and bilirubin were measured using spectrophotometric methods. The hemoglobin coefficient (HC), defined as the ratio of the oxyhemoglobin concentration to the sum of the concentrations of the cerebrospinal fluid pigments, and the hemoglobin-bilirubin index (HBI), the ratio of the oxyhemoglobin and the bilirubin concentrations, are found to permit accurate calculation of the time elapsed after the hemorrhage.

Animals↗

Diagnosis and treatment of spontaneous cerebrospinal fluid otorrhea.

Two consecutively operated-on adult cases with spontaneous cerebrospinal fluid otorrhea were reviewed. Three meningoencephaloceles through tegmental defects were found. Each cele was peduculated through a small dural dehiscence partially obstructed by herniated brain. The otic capsule was normal in both cases. Bipolar cautery was used to reduce the size of the meningoencephalocele and to allow this tissue to assist in the closure of the defect. Conchal cartilage was placed through the tegmental defect to act as a self maintaining intracranial repair of the bony dehiscence. These cases and the literature suggest that fistulization of dura is more frequently the cause of spontaneous cerebrospinal fluid otorrhea in adults than is a defect in the otic capsule. Thus, direct surgical inspection of these areas is required.

Adult↗

[Antifibrinolytic therapy of subarachnoid hemorrhage. Permeation of oral paraaminomethylbenzoic acid in the cerebrospinal fluid].

Studies of the permeation of PAMBA in the cerebrospinal fluid of patients with intact or disturbed BBB function after oral administration of 6 g and withdrawal of the spinal fluid after 120 minutes exclusively showed concentrations which were below the identification threshold of the method using 1 micron per millilitre. Patients suffering from subarachnoidal haemorrhages mainly showed a permeation of PAMBA in the cerebrospinal fluid which, however, only rarely reached the lower therapeutically necessary concentration.

4-Aminobenzoic Acid↗

Cerebrospinal fluid shunt complications: an emergency medicine perspective.

Shunt malfunction and shunt infections are the most significant complications associated with cerebrospinal fluid shunts. Most cases of shunt infection are due to S. epidermidis or S. aureus. Seventy percent of all shunt infections present within two months of the shunt surgery. The most common factor associated with shunt infection is age under three months. Even fever may not be a consistent sign of shunt infection. A high index of suspicion for shunt infection or malfunction must be maintained when evaluating the patient with a cerebrospinal fluid shunt. There are many types of shunt systems in use today. An understanding of current shunt systems and their associated problems should allow physicians to promptly diagnose and initiate treatment for patients with cerebrospinal fluid shunts. Prompt neurosurgical consultation is mandatory whenever shunt malfunction or infection is suspected.

Anti-Bacterial Agents↗