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Long-term growth in vitro of human cerebrospinal fluid T lymphocytes.

Investigations of central nervous system cellular immune reactivity in human disease, as reflected in the responses of cerebrospinal fluid lymphocytes, have been limited primarily due to the low numbers of cerebrospinal fluid lymphocytes available during routine diagnostic lumbar punctures in normal individuals and most patients with demyelinating diseases. We report the use of a T-cell growth factor generated by by phytochemagglutinin-stimulated, irradiated normal peripheral blood lymphocytes to maintain long-term proliferating cultures of human cerebrospinal fluid lymphocytes. Cerebrospinal fluid lymphocytes. Cerebrospinal fluid T-cell cultures were initiated from 10 to 14 cerebrospinal fluid samples with up to 5000-fold expansion of initial cell numbers. Few, if any, macrophage or surface immunoglobulin-bearing cells were present, while 80 to 90% of the cultured cells were T cells as demonstrated by rosette formation with sheep red blood cells. Mixed lymphocyte cultures with cultured cerebrospinal fluid T cells and irradiated, freshly isolated allogeneic peripheral blood lymphocytes yielded a positive response in four of the five cultures tested.

Cerebrospinal Fluid↗

Effects of enflurane and isoflurane on resistance to reabsorption of cerebrospinal fluid in dogs.

Using the technique of ventriculocisternal perfusion, resistance to reabsorption of cerebrospinal fluid (Ra) was calculated from determinations of the rate of reabsorption of cerebrospinal fluid (Va) at differing cerebrospinal fluid pressures in dogs. Ra was examined during prolonged anesthesia (5.0-6.0 h) with enflurane (2.2%, end expired) or isoflurane (1.4%, end expired). Compared with previously reported normal values for Ra in dogs (220-224 cmH2O . ml-1 . min), enflurane increased Ra to 274 +/- 4 cmH2O . ml-1 . min (mean +/- SEM), and isoflurane decreased Ra to 104 +/- 1 cmH2O . ml-1 . min. The alterations of cerebrospinal fluid (CSF) dynamics caused by enflurane, namely increase of both Ra and the rate of production of cerebrospinal fluid (Vf), may contribute to the sustained increase of intracranial pressure observed during prolonged anesthesia with enflurane. In contrast, the different alterations of CSF dynamics caused by isoflurane, namely decrease of Ra with no change in Vf, may explain, in part, why minimal increase of intracranial pressure is observed during prolonged anesthesia with isoflurane. Because decreased Ra improves spatial compensation by cerebrospinal fluid volume for increased intracranial pressure, isoflurane may offer an advantage over enflurane in patients at risk because of increased intracranial pressure.

Absorption↗

Anatomic details of intradural channels in the parasagittal dura: a possible pathway for flow of cerebrospinal fluid.

OBJECTIVE: The absorption of cerebrospinal fluid occurs primarily by means of arachnoid granulations (AG) in the superior sagittal sinus (SSS) and the lacunae laterales (LL) in the parasagittal dura. Previous descriptions of this region suggest a network of intradural channels, but finer details of extent and relationship between channels and AG were not addressed. Therefore, we undertook an anatomic study of cadaveric parasagittal dura. METHODS: The SSS and parasagittal dura of 20 formalin-fixed adult cadavers and 15 autopsy specimens from patients ranging in age from 18 weeks of gestation to 80 years were studied by use of a light microscope, a scanning electron microscope, and corrosion casting. Intradural injections into the parasagittal region were performed in two formalin-fixed and four autopsy specimens from adults by use of normal saline and corrosion casting. RESULTS: Extensive networks of intradural channels from 0.02 to 2.0 mm in diameter were noted in all of the specimens. Channels either were connected to the SSS at intervals along the side wall or drained directly into the LL, which extended up to 3 cm from midline. Channels lined with endothelium stained positive for Factor VIII, as did the endothelium of the LL and SSS. In some places, the network of channels seemed to coalesce to form LL. The underside of the dura was coarse and trabeculated where the channels were abundant, and AG were interdigitated between these trabeculae. In regions of the dura where channels were sparse or absent, the dural underside was smooth and lacked AG. Underlying cortical veins opened directly into the SSS and were unrelated to intradural channels. Intradural parasagittal injections from the epidural side accessed the SSS by way of channels using pressures between 0 and 20 cm H2O at 1.5 ml/min. CONCLUSION: These channels may represent a pathway for the flow of cerebrospinal fluid from AG to the SSS.

Adolescent↗

Endoscopic repair of cerebrospinal fluid rhinorrhea.

Endoscopic repair of cerebrospinal fluid rhinorrhea is a promising alternative to traditional repair techniques. This article reports our experience with 21 cases (10 spontaneous, 8 iatrogenic, and 3 traumatic). Various diagnostic radiographic modalities were used, including computer-aided techniques. Most repairs were accomplished with a free fascial graft positioned in the epidural space. Postoperative lumbar drainage was used in 15 cases. Initial repair was successful in 18 cases (85.7%). In all 3 failures, the surgeon had difficulty with proper graft placement. Additionally, 2 of these cases were confounded by early inadvertent removal of the lumbar drain. All patients in whom the procedure failed underwent a second successful endoscopic repair. There were no major complications. In our experience endoscopic repair of cerebrospinal fluid rhinorrhea is a safe and effective approach that can be improved with computer-aided localization devices. Proper graft placement is critical, and lumbar drainage is an important adjunct in selected cases.

Adult↗

Serotonin in body fluids: characterization of human plasmatic and cerebrospinal fluid pools by means of a new HPLC method.

A new HPLC technique for the analysis of picomolar amounts of serotonin (5HT) in plasma and cerebrospinal fluid (CSF) is described. Bufotenin is used as internal standard. Detection is achieved electrochemically or fluorimetrically. The detection limit can be estimated as 50 pg 5HT/mL of either fluid (0.3 picomolar). The method is used to characterize a non-particulate pool of 5HT which is clearly distinct of the platelet pool. Administration of parachlorophenylalanine (PCPA) 300 mg/kg to rats leads to a 90% reduction in the plasmatic pool whereas platelet 5HT is only slightly decreased (3rd day after PCPA) or even increased (7th day after PCPA). Human concentration (n = 15) of 5HT in plasma is 2.6 +/- 0.9 ng/mL (X +/- S.D.). The application of the method to CSF of neurological patients reveals 5HT concentrations ranging from 93 to 962 pg/mL.

Animals↗

[Hydro-osmotic activity of the cerebrospinal fluid in fetuses, children and adults].

The hydroosmotic activity of the cerebrospinal fluid in 38 persons of different ages and in 2 fetuses was investigated. In the fetal cerebrospinal fluid the hydroosmotic activity was undetectable. The highest hydroosmotic activity was observed in the cerebrospinal fluid of children aged 0 to 3 years (24.320 +/- 3530 microhydroosmotic units (mHOU/ml). The activity significantly decreased in the cerebrospinal fluid of children 7 to 10 years of age (13.184 +/- 2112 mHOU/ml, p < 0.01). The above activity was detected in 40% of the adult patients with different diseases and in all the cases of idiopathic diabetes insipidus. The hydroosmotic activity of both children and adults was sensitive to trypsin digestion. The data obtained suggest the presence of a basic peptide, probably arginine-vasotocin, in the cerebrospinal fluid studied. If this hypothesis is right, vasotocin occurres in the cerebrospinal fluid only after birth and decreases with age, with the exception of some cases of pathology.

Adult↗

Treatment of cerebrospinal fluid shunt infections: a decision analysis.

BACKGROUND: Cerebrospinal fluid shunts transfer cerebrospinal fluid (CSF) from the lateral ventricles in the brain to the peritoneum (ventriculoperitoneal shunt) or the right atrium (ventriculoatrial shunt) via subcutaneous Silastic tubing. As with any implanted foreign body, infection is a serious complication. Although there are several therapeutic modalities currently used for the treatment of shunt infections, controversy remains as to which is best given that there has been only one randomized trial comparing their effectiveness. OBJECTIVE: To determine which treatment modality is most effective by using decision analysis to compare three approaches with regard to cure rate, morbidity and mortality. METHODS: We constructed a decision tree to map out the different treatment modalities and assigned probability values obtained from previously published studies. A utility value was assigned to each treatment outcome, ranging from 0 to 1.0, with a higher score indicating a more favorable outcome. Calculations were performed using Decision Analysis TreeAge computer software. RESULTS: The removal of an infected shunt with establishment of external ventricular drainage or ventricular taps and administration of antibiotics leads to the highest expected value, 0.86. Removal of an infected shunt followed by immediate replacement and administration of antibiotics is less effective, with an expected value of 0.76. The use of antibiotics alone results in the lowest expected value, 0.61. Sensitivity analysis showed the above findings to be robust with respect to clinically relevant changes for the baseline probabilities and utility values. CONCLUSION: A protocol of shunt removal, external ventricular drainage placement or ventricular taps and antibiotics, followed by creation of a new shunt when CSF sterility is achieved, is the most effective method of treatment for CSF shunt infection.

Anti-Bacterial Agents↗

Advances in the analysis of cerebrospinal fluid.

The laboratory examination of cerebrospinal fluid (CSF) continues to play an important role in the clinical diagnosis and treatment of various disorders of the central nervous system (CNS). The major conditions currently include, as they have in the past, infectious diseases, neoplastic processes, multiple sclerosis, other demyelinating disorders, and intracerebral hemorrhage. Recent publications suggest a variety of new laboratory tests that may be useful in the evaluation of patients with both primary and metastatic malignancies, Alzheimer's disease, Creutzfeld-Jacob disease, global ischemia, various psychiatric disorders, CSF otorrhea and rhinorrhea, and in the differential diagnosis of cortical vs lacunar stroke, among others. Examples of these recent developments and their possible clinical usefulness are discussed.

Amines↗

Cerebrospinal fluid analysis.

Accurate interpretation of cerebrospinal fluid (CSF) changes can only be made in the context of the differential diagnosis for each case. The routine analysis of CSF cell number and type as well as CSF total protein can provide information that suggests a specific mechanism or disease, but is often inconclusive. Further information obtained from CSF protein electrophoresis and immunoglobulin determination and calculation of an albumin quota and IgG index can lend additional support for the suspected mechanism of disease. Paired serum and CSF antibody titers for specific organisms can be useful to confirm the presence of a systemic or nervous system infection. Current research on detecting antibodies against nervous tissue components in CSF should result in better diagnostic capabilities and understanding of the pathophysiology of certain disorders in the future.

Animals↗

Composition of cerebrospinal fluid in healthy adult llamas.

Cerebrospinal fluid and serum were obtained from 17 adult, healthy llamas (9 males, 1 castrated male, and 7 females). Osmolality; activities of lactate dehydrogenase and creatine kinase; and concentrations of glucose, sodium, chloride, potassium, total protein, and albumin were determined in serum and CSF. Total and differential cell counts were determined in CSF, and electrophoresis of CSF proteins was performed. Total nucleated cell count was low, 0 to 3/microliters, which is lower than that reported for other domestic species and is similar to values in healthy people. Differential leukocyte percentages were disparate depending on the degree of blood contamination. Blood contamination influenced the percentage of neutrophils and eosinophils in CSF. Samples with few erythrocytes had differential leukocyte distribution similar to that of other species: mostly lymphocytes, fewer monocytoid cells, and scant neutrophils. Older llamas had a few eosinophils in the CSF. Total protein, albumin, and gamma-globulin concentrations in llamas were similar to values in cattle and were higher than values in most domestic species. Glucose concentration in CSF was approximately 40% of the value in serum (nonruminant animals and peoply typically have CSF glucose concentration that is approximately 60 to 80% of the serum glucose concentration). Sodium and Cl concentrations in CSF were higher than those in serum, whereas K concentration was lower in CSF, compared with serum. Activities of creatine kinase and lactate dehydrogenase in CSF were markedly lower than those in serum, and the ranges of values in this group of healthy llamas were narrow.

Animals↗

The fidelity and dynamic response of fluid-filled catheter systems for direct measurement of lumbar cerebrospinal fluid pressure.

OBJECTIVE: The purpose of this study was to determine the fidelity of pressure signals transmitted through long, narrow (epidural) catheters inserted into the lumbar intrathecal space. METHODS: Using a model of the spinal canal we tested three epidural catheters: 20-gauge Arrow, 20-gauge Abbott, 21-gauge Portex. We (1) determined the damping coefficient and natural frequency of the three catheters, (2) correlated the static pressures measured using the three catheters compared to the true pressure in the intrathecal space, and (3) compared the response time of the three catheters connected to transducers vs U-tube manometers. RESULTS: The three catheters had high damping coefficients (alpha) (Arrow, 0.75; Abbott, 0.85; Portex, 1.10) and low natural frequencies (Arrow, 15.23 Hz; Abbott, 12.83 Hz; Portex, 9.09 Hz). The dynamic response characteristics of the catheter with the largest internal diameter (20-gauge Arrow) were adequate to reproduce pulsatile cerebrospinal fluid pressure reliably. Smaller catheters tracked the mean pressure, although oscillations were damped. Static pressure measurements from all three catheters showed good correlation with test pressures (r = 0.99; p < 0.001). Using the U-tube manometer, it required 170, 140, and 130 minutes for the Portex, Abbott, and Arrow catheters, respectively, to equilibrate with a test pressure of 30 cm H2O. The rate of rise in the U-tube manometer pressure was limited by the rate of fluid flow through the catheters. CONCLUSIONS: We found that a catheter of at least 20 gauge connected to a transducer could record pressures in the cerebrospinal fluid compartment with a high degree of fidelity. The prolonged time to reach equilibrium made U-tube manometry unsuitable for clinical use.

Catheterization↗

False positive serology in cerebrospinal fluid associated with a spinal cord tumor.

Biologic false positive serology in cerebrospinal fluid has been reported as exceedingly rare. In a patient with a spinal cord tumor and elevated cerebrospinal fluid protein, the cerebrospinal fluid was reactive to VDRL and fluorescent treponemal antibody absorption (fta-abs) tests, but became nonreactive with removal of the tumor. This biologic false positive reaction may be related to the elevated cerebrospinal fluid protein, as similar false positive reactions have occurred in blood with abnormal or elevated proteins. Cerebrospinal fluid reactive to the VDRL and FTA-ABS tests does not always indicate neurosyphilis.

Cerebrospinal Fluid Proteins↗

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↗

Cerebrospinal fluid shunt infections in children.

Infections of cerebrospinal fluid shunts continue to be a substantial source of mortality and morbidity in children with hydrocephalus. Although several therapeutic modalities are currently used for the treatment of shunt infections, there are no clear guidelines for treatment. The purpose of this study was to determine the common pathogens of cerebrospinal fluid shunt infections and evaluate the success of our management. Thirty-five children treated for ventriculoperitoneal shunt infections over the past 9 years were reviewed. The management protocol consisted of the removal of the infected shunt, the application of ventricular taps or reservoir placement, intraventricular antibiotic treatment, and the placement of a new shunt when cerebrospinal fluid sterility was achieved. Four patients were treated with antibiotics alone. Most episodes occurred within 4 months of shunt placement. The most common causative microorganism identified was Staphylococcus epidermidis, followed by S. aureus, and S. warneri. Three patients died from complications of shunt infections, 2 patients had a recurrent shunt infection, while the remaining 29 patients remained free from shunt-related complications. In agreement with the evidence published in the literature, our findings suggest that the above management protocol is effective for the treatment of cerebrospinal fluid shunt infections.

Anti-Bacterial Agents↗

[Method and clinical significance of cerebrospinal fluid spectrophotometry].

The results of the spectrophotometric analysis of 932 cerebrospinal fluid specimens are presented. The specimens were obtained from 95 patients with subarachnoid and intracerebral hemorrhages, 75 patients with traumatic head injuries, 40 patients with infectious diseases of the central nervous system, 302 patients with cerebrovascular accidents and 302 patients suffering from a variety of diseases such as multiple sclerosis, herniated intervertebral discs and vasomotor headache. Normal cerebrospinal fluid is colourless and shows a spectrophotometric absorption characterized by a flat curve with decreasing absorption from 350 to 650 nm. In disease states Oxy-Hemoglobin, Met-Hemoglobin and Bilirubin can be identified in cerebrospinal fluid. These pigments, when present in cerebrospinal fluid, change the spectrophotometric curve due to their specific absorption spectra. According to the quantitative relationship between the pigments and their chronological order of appearance in the cerebrospinal fluid, typical spectrophotometric patterns have been delineated. The spectrophotometric absorption curve of a hemorrhage due to rupture differs from that of a diapedetic hemorrhage. Moreover, tap bleeding results in an absorption curve which can be differentiated early from that of a subarachnoid hemorrhage. Finally, artifacts due to desinfectants can easily be identified. It is concluded that the spectrophotometric analysis of cerebrospinal fluid gives helpful information in subarachnoidal-hemorrhage, subdural and intracerebral hematoma, in contusions of the brain, carcinomatosis of the leptomeninx, spinal tumor and meningoencephalitis of unknown origin.

Bilirubin↗

Levels of transforming growth factor alpha (TGF-alpha) in human cerebrospinal fluid.

In this study, we investigated cerebrospinal fluid of patients with various neurological symptoms for the presence of transforming growth factor alpha (TGF-alpha). 41 samples of cerebrospinal fluid were collected by lumbar puncture performed routinely due to the clinical suspicion of neurological disease from 22 females (age 15-80 years, median 42 years) and from 19 males (age 18-82 years, median 48 years). A highly sensitive and specific radioimmunoassay was used to determine the concentration of TGF-alpha in the samples. The detection limit of the assay was about 200 pg TGF-alpha. There was no cross-reactivity to human EGF. We showed CSF indeed does contain TGFalpha. As TGF-alpha was detected in all 41 samples investigated, this growth factor appears to be a constant component of CSF. The mean concentration was 5.5 ng TGF-alpha (S.D. +/- 2.7 pg/ml, range 1.1 to 13.9 pg/ml). There was no significant correlation between TGF-alpha concentration in CSF and age (r = -0.006) and there was no significant difference between females (mean 5.8+/-3.10 pg/ml) and males (mean 5.2+/-1.96 pg/ml). No diagnosis was over represented in patients with TGF-alpha concentrations above or below 1 S.D. off the mean. However, highest concentrations of TGF-alpha were found in the group of patients with peripheral neurological sensory dysfunctions and polyneuropathy. We conclude that TGF-alpha is not only a constant component of human cerebrospinal fluid in adults but could also be significantly involved in the pathophysiology of various neurological diseases. The earlier hypothesis that TGF-alpha could mainly have a role in brain development needs hence to be re-evaluated.

Adolescent↗