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Copper, zinc, magnesium, and calcium in plasma and cerebrospinal fluid of patients with neurological diseases.

We investigated whether information on concentrations of some trace-mental concentrations in blood plasma or cerebrospinal fluid, or both, could be of value in diagnosis or management of various neurological diseases, and whether concentrations in plasma could serve as a means of estimating the protein or metal concentrations in cerebropsinal fluid. Samples of both from 82 patients were analyzed for copper, zinc, magnesium, and calcium by atomic absorption spectrophotometry. Protein concentrations in cerebrospinal fluid were also determined. Metal and protein concentrations in plasma and in cerebrospinal fluid were not strongly enough correlated to permit the estimation of one from the other. However, the correlation coefficients between calcium in plasma and cerebrospinal fluid (r = 0.41), magnesium and protein in cerebrospinal fluid (r = 0.40), magnesium in plasma and calcium in cerebrospinal fluid (r = 0.36), and magnesium and calcium in cerebrospinal fluid (r = 0.66) were statistically significant (P less than .01). Patients with cerebral infarctions had abnormally high copper concentrations in their plasma and cerebrospinal fluid. The ratio of plasma copper to plasma zinc was also significantly higher in cases of cerebral infarction.

Adolescent↗

Lymphocyte subpopulations in human cerebrospinal fluid.

Lymphocyte subpopulations in both human cerebrospinal fluid and peripheral blood were identified and compared by rosette techniques. In patients without neuroaxial disease, the percent distribution of Fc receptor and T-lymphocytes reflected peripheral blood values, although there was a significantly higher percentage of T cells in normal CSF. Alterations in lymphocyte cerebrospinal fluid populations were observed in various systemic and neurologic diseases.

B-Lymphocytes↗

Cerebrospinal fluid to serum glucose ratio in non-hypoglycorrhachic neurological conditions.

OBJECTIVE: To explore the relevance of cerebrospinal fluid to serum glucose ratio in non-hypoglycorrhachic conditions. DESIGN: Retrospective observational study. SETTING: Neurology ward, university teaching hospital, Hong Kong. PATIENTS: Adult patients with conditions unrelated to hypoglycorrhachia who underwent lumbar puncture. MAIN OUTCOME MEASURES: Cerebrospinal fluid and simultaneous serum glucose concentrations, and their ratio to each other. RESULTS: Between September 1998 and August 2003, 170 cerebrospinal fluid and serum glucose samples were collected from 138 patients. Mean cerebrospinal fluid to serum glucose ratio was 0.61 (standard deviation, 0.142; range, 0.21-1.00). With the exception of cerebrospinal fluid protein level, laboratory parameters were similar among different diseases. The glucose ratio was lower than 0.6 in 43% and lower than 0.5 in 19% of samples. Cases with a low glucose ratio appeared to have higher serum glucose concentrations (significant among groups with different glucose ratios, P<0.001). The mean glucose ratio (0.65) was also significantly higher in patients with serum glucose concentration of lower than 7.8 mmol/L compared with those with serum glucose concentration between 7.8 and 11.1 mmol/L (mean, 0.46), or higher than 11.1 mmol/L (mean, 0.46) [P<0.001]. There was a strong negative correlation between the glucose ratio and serum glucose concentration (r= -0.704, P<0.001). CONCLUSION: A lowered cerebrospinal fluid to serum glucose ratio is often seen in the absence of an appropriate disorder, especially when simultaneous serum glucose concentration is elevated. This may be explained by the saturation kinetics of glucose transportation in hyperglycaemia, and the time lag for cerebrospinal fluid and glucose to equilibrate when the blood level fluctuates.

Adult↗

Reduced cerebrospinal fluid 5-hydroxyindoleacetic acid and homovanillic acid in children with epilepsy.

Cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and probenecid were examined in 14 children with epilepsy (ages 6 months to 17 years) and 17 controls (ages 14 months to 16 years). The concentrations of amine metabolites were significantly correlated with probenecid concentrations in both groups of children. Cerebrospinal fluid concentrations of 5-HIAA were 63.6 ng per milliliter plus or minus 8.23 S.E.M. and 117 ng per milliliter plus or minus 11.6 S.E.M. for the epilepsy and control groups respectively. HVA averaged 89.1 ng per milliliter plus or minus 15.2 S.E.M in epilepsy and 172 ng per milliliter plus or minus 19.2 S.E.M. in the control group. These findings indicate a significant difference between epilepsy and control groups. Probenecid concentrations were similar in each group. The reduced cerebrospinal fluid amine metabolite concentrations in children with epilepsy were not related to age, anticonvulsant medication, cerebrospinal fluid folate or protein concentration, or cerebrospinal fluid cell count. Our findings suggest a relationship between brain amines and epilepsy.

Acetazolamide↗

Spinal and cranial contributions to total cerebrospinal fluid transport.

In this study, we quantified cerebrospinal fluid (CSF) transport from the cranial and spinal subarachnoid spaces separately in sheep and determined the relative proportion of total CSF drainage that occurred from both CSF compartments. Cranial and spinal CSF systems were separated by placement of an extradural ligature over the spinal cord between C(1) and C(2). In one approach, two different radiolabeled human serum albumins (HSA) were introduced into the appropriate CSF compartment by a perfusion system (method 1) or as a bolus injection (method 2). Plasma tracer recoveries in conjunction with a mass balance equation were used to estimate CSF transport. In method 3, catheters connected to reservoirs filled with artificial CSF were introduced into the cranial and spinal CSF compartments. Incremental CSF pressures were established in each CSF system, and the corresponding steady-state flow rates were measured. Total CSF drainage ranged from 0.51 to 0.75 ml. h(-1). cmH(2)O(-1). Expressed as a percentage of the total CSF transport, the ratios of cranial-to-spinal clearance estimated from methods 1, 2, and 3 were 75:25, 88:12, and 75:25, respectively. Primarily on the basis of the data derived from methods 1 and 3, we conclude that the spinal subarachnoid compartment has an important role in CSF clearance and is responsible for approximately one-fourth of total CSF transport.

Animals↗

[Cholinesterase in plasma and cerebrospinal fluid in patients with viral meningitis].

Pseudocholinesterase activity (PChE) in human plasma and cerebrospinal fluid was determined in 30 patients; in 15 patients with acute viral meningitis and in 15 patients with meningism. Concentration of total proteins in cerebrospinal fluid was also determined. PChE activity and protein concentration in cerebrospinal fluid of patients with meningitis is significantly higher than in control group (P < 0.001). Relationship of PChE activity and protein concentrations in cerebrospinal fluid of patients with meningitis does not differ from that in the control group patients. Thus, the increase of PChE activity in the cerebrospinal fluid of patients with viral meningitis suggests an alteration in the blood-brain barrier, leading to an increase in the passage of serum components.

Acute Disease↗

Does the secretion and circulation of the cerebrospinal fluid really exist?

The secretion and circulation of cerebrospinal fluid have been studied in anaesthetized cats by means of a plastic cannula introduced into the aqueduct of Sylvius and by inspection of free escape of cerebrospinal fluid out of the end of the cannula. The fact that during the 120-minute period of observation not a single drop of CSF escaped out of the cannula, at physiological pressure, indicates that cerebrospinal fluid does neither secrete nor circulate.

Animals↗

Endothelin immunoreactivity in cerebrospinal fluid of patients with subarachnoid haemorrhage.

A radioimmunoassay method for endothelin was developed. Antisera raised against endothelin 1 showed significant crossreaction with endothelin 2 and 3 (45 and 13%, respectively). Considerable endothelin immunoreactivity was shown to be present in the cerebrospinal fluid of patients with a subarachnoid hemorrhage, ranging from 0.3 pmol/l cerebrospinal fluid to 4.5 pmol/l cerebrospinal fluid, though no endothelin immunoreactivity was observed in the cerebrospinal fluid of controls and patients with cerebral infarction, subdural haematoma or brain tumours. Endothelin immunoreactivity was also observed in two out of five cerebrospinal fluid samples from patients with cerebral bleeding. Reverse phase high performance liquid chromatography showed that the main immunoreactive component in cerebrospinal fluid appeared to elute at the same position. There was, however, an immunoreactive component which eluted at the same position as endothelin 3. These results may support the idea that endothelin immunoreactivity in the cerebrospinal fluid originate mainly from endothelial and neural tissues and that endothelin may contribute to the generation of the vasospasm often observed in subarachnoid hemorrhage, a conclusion based on the exceptionally high endothelin immunoreactivity in cerebrospinal fluid observed in patients with subarachnoid haemorrhage.

Aged↗

Evaluation of cerebrospinal fluid in Southeast Asian refugees with reactive serologic tests for syphilis.

To determine the prevalence of cerebrospinal fluid abnormalities in Southeast Asian refugees with reactive serologic tests for syphilis, we evaluated 65 patients, 36 prospectively and 29 retrospectively, in a primary care clinic. Information was collected on history of treponemal infections, neurologic symptoms and signs, and total protein concentration, leukocyte count, and the VDRL test in the cerebrospinal fluid. Neurologic symptoms were reported by all patients for whom data were available. Abnormal neurologic signs were found or noted in medical records in 15 (42%) prospectively evaluated patients and 9 (64%) of 14 retrospectively evaluated patients for whom data were available. No patient had evidence of congenital or non-neurologic sequelae such as cutaneous or cardiovascular manifestations of syphilis. No patient had a positive cerebrospinal fluid VDRL test, 1 had more than 5 x 10(6) leukocytes per liter (5 leukocytes per mm3), and 6 (9%) had elevated total protein levels in the cerebrospinal fluid. Previous therapy for syphilis was not associated with lower serum VDRL reactions, neurologic symptoms and signs, or cerebrospinal fluid findings. In the absence of other indications, routine examination of the cerebrospinal fluid in seropositive Southeast Asian refugees who have nonspecific neurologic symptoms has a low yield, perhaps because of the high prevalence of yaws in this population, and may not be warranted.

Adolescent↗

Aujeszky's disease (pseudorabies) virus detection in cerebrospinal fluid in experimentally infected pigs.

The presence of Aujeszky's disease virus in cerebrospinal fluid of experimentally infected pigs was studied using the techniques of virus isolation and PCR. Pigs, some of which were previously vaccinated against Aujeszky's disease, were inoculated with different doses of the Aujeszky's disease NIA-3 strain. At the time of death or sacrifice, a sample of cerebrospinal fluid was taken and tested for the presence of virus using the mentioned techniques. Virus was isolated only from one sample, while it was detected by PCR in most of them. The higher sensitivity of the PCR technique and the possible presence of antiviral antibodies in the cerebrospinal fluid are reasons that can be argued to explain this fact. By PCR, the virus was detected more efficiently when digested cerebrospinal fluid cells were used as DNA source than when using whole cerebrospinal fluid, suggesting that the virus could be cell-associated. Aujeszky's disease virus could not be detected by PCR in pigs which survived the acute phase of the infection and were euthanased at 8 weeks post-inoculation, when they were latently infected. This indicated that the cerebrospinal fluid is not an adequate sample for the diagnosis of latency. Since Aujeszky's disease virus was detected from most of the tested samples, we believe that this could be an adequate procedure for the quick diagnosis of Aujeszky's disease.

Animals↗

[Cerebrospinal fluid eosinophilia preceding central nervous system leukemia].

Cerebrospinal fluid eosinophilia are an uncommon finding that is most often the result of a helminthic infection of the central nervous system. Information from the recorded literature suggests the differential diagnosis of this clinical observation is relatively limited. This is a report of a girl with acute lymphoblastic leukemia who developed central nervous system relapse of leukemia following 3 years of remission. She showed marked eosinophilia in the cerebrospinal fluid 6 weeks preceding central nervous system leukemia. No cause for the eosinophilia was identified. The gradual accumulation of case reports of eosinophilia in the cerebrospinal fluid with or without blood eosinophilia in patient with leukemia suggests that this finding is of some importance.

Brain Neoplasms↗

New lumbar method for monitoring cerebrospinal fluid pressure in rats.

OBJECTIVE: Monitoring cerebrospinal fluid pressure or intracranial pressure (ICP) is crucial in the study of neurosurgical disorders. In the present study, we report a new lumbar method for monitoring ICP in rats. METHODS: A PE10 catheter connected to a pressure transducer was placed into the subarachnoid space of L5 through the duramater after laminectomy to record lumbar cerebrospinal fluid pressure (lumbar-ICP). ICP at the cisterna magna (cisterna-ICP) was recorded simultaneously via a catheter in the subarachnoid space at the cisterna magna. Eighteen anesthetized adult male S-D rats were subjected to baseline recording followed by either experimental subarachnoid hemorrhage (SAH) induced by intravascular puncture method or experimental intracerebral hemorrhage (ICH) induced by blood injection with a stereotaxic system. RESULTS: Baseline lumbar-ICP and cisterna-ICP varied between 6 and 8 mmHg, and respiratory variation could be detected. A similar acute response to SAH was recorded in both the lumbar-ICP and cisterna-ICP in all rats. In rats subjected to SAH, the lumbar catheter continuously and accurately monitored lumbar-ICP, and reliable pressure tracings were obtained for up to 24 h after SAH. However, continued cisterna-ICP monitoring was abandoned in two rats in the cisterna magna method due to obstruction of the catheter by blood clots (hematoma). CONCLUSION: This new lumbar-ICP method is simple, safe, easy, and reliable in rats. Continued lumbar-ICP measurements provided monitoring for up to 24 h after experimental manipulation.

Animals↗

Quantification of cerebrospinal fluid proteins in children by high-resolution agarose gel electrophoresis.

Physiologic alterations in cerebrospinal fluid proteins occur inter alia with aging. Agarose gel electrophoresis discriminates many cerebrospinal fluid proteins and in addition quantifies concentration alterations. This study aimed to investigate the time course of these alterations in children and to establish normative values for cerebrospinal fluid protein properties. In 202 children without diseases known to alter cerebrospinal fluid, normative protein properties were quantified using nephelometry, ultrafiltration, high-resolution electrophoresis, and Gaussian curve fit densitometry. Total protein and protein concentrations (albumin and gamma-globulins) decreased from birth until 7 months age, and, from then on, increased slightly (transthyretin, albumin, and alpha2-proteins) or strongly (gamma-globulins). Protein proportions (transthyretin and transferrin) increased until about 3 years of age and decreased from then on. These normative values for children as quantified by high-resolution agarose gel electrophoresis are presented in a significance-structured percentile table. The time courses of these cerebrospinal fluid properties reflect physiologic alterations of the blood-brain barrier function during childhood.

Adolescent↗

Acid-base and gas tension of cerebrospinal fluid in Nigerians and tetanus patients.

The acid-base balance and gas tension of the cerebrospinal fluid of eight tetanus patients and twelve control subjects were studied. Tetanus patients had metabolic acidosis which was severely reflected in the cerebrospinal fluid. While the cerebrospinal fluid pH is lower than that of the arterial blood there was no difference between the acid-base and gas tension of the cerebrospinal fluid of Nigerians and the causasians. The severe metabolic acidosis of the cerebrospinal fluid of tetanus patients might be one of the causes of sudden deaths seen in these patients.

Acid-Base Imbalance↗

Clinical pharmacokinetics of cerebrospinal fluid.

The distribution of drugs into the cerebrospinal fluid has long been considered a challenging field of investigation in 2 major respects: (a) understanding how the physicochemical properties (molecular weight, pKa, plasma protein binding) of various molecules influence their movements across such a specific structure as the blood-brain barrier; and (b) defining the relationship between cerebrospinal fluid concentrations of various drugs and their central (side) effects. An attempt has been made to review the very dispersed information presently available to offer a clinically orientated picture of this area of pharmacokinetics. Drugs acting on the central nervous system (benzodiazepines, tricyclic antidepressants, anticonvulsants, opioids), antibacterial agents, cardiovascular drugs (beta-adrenoceptor blockers and digoxin), antineoplastic drugs (mainly methotrexate), and other miscellaneous agents (corticosteroids, cimetidine, methylxanthines) are reviewed. The available evidence seems to support the conclusion that only for methotrexate and antibacterial agents does knowledge of cerebrospinal fluid pharmacokinetics have direct therapeutic implications, while the mosaic of information available for other drugs does little more than provide a partially satisfactory picture.

Anti-Infective Agents↗

DNA synthesis and intracellular calcium elevation in porcine cerebral arterial smooth muscle cells by cerebrospinal fluid from patients with subarachnoid haemorrhage.

To understand the molecular mechanism of the pathogenesis of cerebral vasospasm following subarachnoid haemorrhage, we analysed the effect of cerebrospinal fluid from patients with subarachnoid haemorrhage on DNA synthesis and cytosolic-free calcium elevation in cultured porcine cerebral smooth muscle cells. Cerebrospinal fluid from patients on day 2 after subarachnoid haemorrhage induced transient elevation in cytosolic-free calcium levels. In contrast, the maximal elevation of cytosolic-free calcium levels induced by cerebrospinal fluid from control patients (without subarachnoid haemorrhage) was significantly lower than that induced by cerebrospinal fluid from patients with subarachnoid haemorrhage. In cultured porcine cerebral arterial smooth muscle cells, cerebrospinal fluid from patients with subarachnoid haemorrhage promoted levels of [3H]-thymidine incorporation (DNA synthesis) more than 2.5-fold higher than that promoted by cerebrospinal fluid from control patients without subarachnoid haemorrhage. However, in cultured aortic smooth muscle cells, there was no significant difference in [3H]-thymidine incorporation between cerebrospinal fluid from patients with subarachnoid haemorrhage and that by control cerebrospinal fluid. From these results in cerebral arterial smooth muscle cells, cerebrospinal fluid from patients following subarachnoid haemorrhage may play not only constrictive functions, evidenced by cytosolic-free calcium elevations, but also proliferative functions, demonstrated by promotion of [3H]-thymidine incorporation. The relevance of these factors to vasospasm will be discussed.

Animals↗