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[The value of beta-2 transferrin analysis and MR cisternography for the diagnosis of cerebrospinal fluid fistulas].

The diagnosis of cerebrospinal fluid (CSF) fistula may require invasive techniques. Detection of CSF and perilymph-specific beta 2 transferrin and MR cisternography which greatly enhances the CSF signal are sensitive and noninvasive techniques which allowed a precise diagnosis in seven patients with suspected CSF fistula. We review the different diagnostic techniques used for CSF fistula, beta 2 transferrin analysis and MR cisternography appear to provide accurate and noninvasive methods for investigating CSF fistulae. They should replace invasive techniques such as CT cisternography.

Adult↗

Multiple sclerosis with uncommon cerebrospinal fluid findings.

AIM: To determine the frequency and clinical and laboratory features of patients with multiple sclerosis characterized by uncommon cerebrospinal findings, ie, negative oligoclonal band or increased number of mononuclear cells in cerebrospinal fluid. METHODS: The retrospective analysis included medical records of 233 patients (158 women and 75 men) admitted to the Department of Neurology, Ljubljana Medical Center, between January 1, 1990, and December 31, 1999 and discharged with the diagnosis of multiple sclerosis. We determined clinical features and cerebrospinal fluid parameters of patients with oligoclonal band-negative multiple sclerosis and > or =15 mononuclear cells/mm( 3) in cerebrospinal fluid and compared them with patients with oligoclonal band-positive multiple sclerosis and expected number of mononuclear cells in cerebrospinal fluid, respectively. There were 26 patients with oligoclonal band-negative finding and 26 with > or =15 mononuclear cells/mm(3) in cerebrospinal fluid. The two groups of patients did not overlap, except for one patient, who had 19 mononuclear cells/mm(3) and was oligoclonal band-negative. RESULTS: The diagnosis was delayed in oligoclonal band-negative multiple sclerosis patients, their cerebrospinal fluid contained less leukocytes, and lower concentration of IgG. The patients with > or =15 leukocytes/mm( 3) in cerebrospinal fluid were diagnosed earlier and had increased cerebrospinal fluid protein and IgG concentrations. CONCLUSION: Multiple sclerosis with negative oligoclonal band or increased count of leukocytes in cerebrospinal fluid were found in approximately 10% of patients with the disease. Because of the absence of oligoclonal band and less active cerebrospinal fluid, the diagnosis in these patients may be delayed.

Adult↗

Cerebrospinal fluid atrial natriuretic factor in intracranial disease.

We tested the hypothesis that the concentration of atrial natriuretic factor in the cerebrospinal fluid is an indicator of brain injury in patients with intracranial disease. Atrial natriuretic factor concentration was measured in 72 samples of cerebrospinal fluid from 28 patients with intraventricular drains and in nine samples from outpatient controls undergoing diagnostic lumbar puncture. Levels were correlated with diagnosis; systemic fluid administration; concentration of atrial natriuretic factor in the plasma; intracranial pressure; sodium, glucose, and protein concentrations, osmolality, and cell count in the cerebrospinal fluid; sodium concentration in the serum; and hemodynamics. Atrial natriuretic factor concentration was highest in cerebrospinal fluid from patients with intracerebral hematoma, followed by those with obstructive hydrocephalus and subarachnoid hemorrhage (19 +/- 2, 13 +/- 3, and 8 +/- 2 pg/ml, respectively); atrial natriuretic factor concentration was less than 4 pg/ml in the controls. Patients treated with fluid restriction had significantly higher atrial natriuretic factor levels than those receiving maintenance or high-volume fluids (16 +/- 3, 8 +/- 2, 10 +/- 1 pg/ml, respectively). The concentration of atrial natriuretic factor in the plasma was significantly elevated in patients with intracerebral hematoma and subarachnoid hemorrhage (155 +/- 38 and 92 +/- 20 pg/ml, respectively) and did not correlate with fluid administration or the concentration of atrial natriuretic factor in the cerebrospinal fluid. Neither cerebrospinal fluid nor plasma concentrations of atrial natriuretic factor correlated with intracranial pressure; cerebrospinal fluid sodium, glucose, or protein concentrations, osmolality, or cell count; serum sodium concentration; or hemodynamics. We conclude that the concentration of atrial natriuretic factor in the cerebrospinal fluid is a nonspecific indicator of brain injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Natriuretic Factor↗

[Cerebrospinal otorrhea--cerebrospinal rhinorrhea. The Salzburg concept of cerebrospinal fluid diagnosis].

The three following cerebrospinal fluid (CSF) examinations make it possible to identify even the smallest amounts of CSF in case of CSF otorrhoea and rhinorrhoea. 1. Immunological identification of beta 2-transferrin (Oberascher/Arrer) 2. Laboratory fluorescein identification (Oberascher/Arrer) 3. Endoscopic fluorescein detection according to Messerklinger. For screening, and as the method of choice, beta 2-transferrin identification is always used as a first step if there is a suspicion of liquorrhoea. Depending on the result and on further measures, both fluorescein tests are used additionally in diagnosis. Basing on practical experience gained recently, special attention is given to test analysis, the various possibilities of taking samples, and their means of transport or mailing. A newly developed diagnostic step-by-step plan is intended to emphasise the clinical significance by means of practical examples. This concept represents the present state of the art in CSF diagnosis and demonstrates that a much mor precise range of indication is possible in surgery of fractures of the base of the skull and CSF leaks if it is combined with an appropriate x-ray examination.

Brain Concussion↗

Endoscopic endonasal approach for cerebrospinal fluid fistulae.

Different techniques have been proposed to repair cerebrospinal fluid rhinorrhea. Advances in nasal surgery led to a high success rate and low morbidity for the endonasal approach. It has become the favorite route for treating cerebrospinal fluid leaks of the anterior skull base. Better results have been obtained with the improvement of rigid endoscopes and intrathecal sodium fluorescein. In a prospective study, twenty-four patients with cerebrospinal fluid rhinorrhea were evaluated and treated by endoscopic endonasal surgery. In all cases intrathecal sodium fluorescein enabled a precise localization of the bone defect. The most common causes of CSF rhinorrhea were traumatic (8 cases, 33 %), spontaneous (6 cases, 25 %), and iatrogenic (5 cases, 20.8 %). Preoperative radiological evaluations (plane CT, CT cisternogram and MRI) showed the exact site and size of the defect in all patients. The most common site of leakage was the ethmoidal roof-cribriform plate. Primary closure was achieved in all patients. There were no major operative or postoperative complications. The endoscopic endonasal approach can be considered the first choice in the treatment of cerebrospinal fluid rhinorrhea.

Abdominal Fat↗

Features of the Sinushunt and its influence on the cerebrospinal fluid system.

OBJECTIVES: A new cerebrospinal fluid (CSF) shunt system, Sinushunt, has recently been introduced. CSF is shunted from the ventricles to the transverse sinus. The Sinushunt is not a classical differential pressure shunt; instead, it opens as soon as there is a positive pressure over the shunt and the flow is dependent on the resistance of the system, which is high compared with traditional CSF shunts. The objective of this study was to characterise the features of the Sinushunt and to evaluate its influence on the CSF system. METHODS: Five brand new Sinushunts with distal catheters were tested. An automated, computerised experimental apparatus based on regulation of pressure, built into an incubator at 37 degrees C, was used. Opening pressure, resistance, and anti-reflux properties were determined. RESULTS: The mean (SD) opening pressure was highly dependent on the pressure in the sinus: P(open) = 1.3 (0.6) mm Hg with Psinus = 0.0 mm Hg, and Popen = 7.5 (0.6) mm Hg for Psinus = 6.5 mm Hg. The mean (SD) resistance of the shunts was 7.9 (0.3) mm Hg/ml/min and not clinically significantly affected by the sinus pressure. In one shunt there was reflux, and in another two shunts there was a very small, but similar, tendency. CONCLUSIONS: This study confirms that the resistance of the Sinushunt is comparable to the physiological values in humans. However, the optimal post-operative resistance for different hydrocephalus types is unknown, and randomised clinical trials are needed to confirm improved outcome and reduced complication rate for the Sinushunt compared with traditional low resistance ventriculoperitoneal shunts. A weakness of the anti-reflux system of the Sinushunt must be suspected and has to be further investigated.

Automation↗

Choroid plexus papilloma: hydrocephalus and cerebrospinal fluid dynamics.

Dynamics of the cerebrospinal fluid were measured pre- and postoperatively in a patient with a choroid plexus papilloma associated with hydrocephalus. The production rate was 0.35 ml/min, absorption 0.0057 ml/min H2O, and the critical opening pressure 196 mm H2O. Following removal of the tumor, these values were 0.32 ml/min, 0.0053 ml/min/mm H2O, and 105 mm H2O, respectively. It was concluded that no over-production of cerebrospinal fluid was present in this case. The hydrocephalus was due solely to obstruction of the fourth ventricle.

Adult↗

Cultivation and characterization of spirochetes from cerebrospinal fluid of patients with Lyme borreliosis.

Attempts were made to culture spirochetes from cerebrospinal fluid samples of 105 patients suspected of having Lyme borreliosis with neurological complications. At the final evaluation, only 38 patients fulfilled the criteria of neuroborreliosis. Spirochetes were cultured from cerebrospinal fluid samples of four of these patients. All four patients had pleocytosis in their cerebrospinal fluid and a history of neurological symptoms of only 4 to 10 days in duration. Two of them had no detectable antibodies against any of the isolated spirochetes in their cerebrospinal fluid, both when tested with an enzyme-linked immunosorbent assay and when tested by immunoblotting. An antibody reaction against the homologous isolate that was distinctly stronger than that against the heterologous isolates was found in the serum and cerebrospinal fluid samples from one patient. The cells of the isolates were morphologically similar and showed a very similar protein pattern when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cells of all isolates reacted with the monoclonal antibodies H5332 and H9724, which also react with Borrelia burgdorferi B31, the type strain. One isolate lost a major protein of 23 kilodaltons after subcultivation for 4 months. We conclude that isolation of spirochetes from cerebrospinal fluid might prove successful in clinically selected cases of Lyme borreliosis.

Adult↗

Presence of aldosterone-like immunoreactivity in cerebrospinal fluid in normotensive subjects.

Accumulating evidence, including a wide distribution of specific receptors for aldosterone in the brain, has revealed a potential role of aldosterone in the central nervous system. However, whether or not aldosterone is present in cerebrospinal fluid remains unclear. We attempted to detect aldosterone in cerebrospinal fluid in 14 normotensive subjects. Cerebrospinal fluid was obtained by lumbar puncture. Aldosterone-like immunoreactivity was detected in cerebrospinal fluid (163 +/- 5 pmol/l, range 139-211 pmol/l) and was found to significantly correlate to both plasma aldosterone (r = 0.70, p less than 0.01) and plasma renin activity (r = 0.68, p less than 0.01). However, no significant relationship was found between aldosterone-like immunoreactivity in cerebrospinal fluid and the level of sodium or potassium in cerebrospinal fluid or mean blood pressure. Although we confirmed the presence of aldosterone-like immunoreactivity in cerebrospinal fluid of normotensive subjects, the physiological role of aldosterone in cerebrospinal fluid has yet to be elucidated. Further study will thus be needed to determine the role of cerebrospinal fluid aldosterone.

Adult↗

Cerebrospinal fluid to serum glucose ratios in diabetes mellitus and bacterial meningitis.

Although calculation of the cerebrospinal fluid to serum glucose ratio is widely recommended as a way to identify pathologic hypoglycorrhachia, few data are available to document its accuracy. In order to provide a better basis for interpretation of this quotient, simultaneous cerebrospinal fluid and serum glucose concentrations from patients with diabetes mellitus and noninflammatory cerebrospinal fluid and patients with acute bacterial meningitis were compared. Cerebrospinal fluid to serum glucose ratios were significantly lower in the patients with meningitis (Mann-Whitney U Test, p less than 0.001). A ratio of 0.31 provided the best differentiation between the two groups. Ratios were below this level in 25 of 64 patients with meningitis, including 10 in whom the absolute cerebrospinal fluid glucose concentration was not below 40 mg/dl. In 35 of 36 uninfected diabetic subjects, ratios were 0.31 or greater. In the sole exception, concentrated glucose solution had been given intravenously shortly before lumbar puncture, Use of the cerebrospinal fluid to serum ratio, in addition to the absolute cerebrospinal fluid glucose concentration, increases sensitivity in detecting pathologic hypoglycorrhachia with little loss in specificity.

Blood Glucose↗

Hydrocephalus-induced changes in the composition of cerebrospinal fluid.

Studies reporting the composition of cerebrospinal fluid obtained from hydrocephalic humans have been critically reviewed. Hydrocephalus-induced alterations in the cerebrospinal fluid concentrations of neurotransmitters and peptide neuromodulators, products of glycolysis and nucleotide metabolism, neural cell-derived proteins and enzymes, and serum-derived proteins have been documented. The data are interpreted with reference to experimental studies. The reported changes suggest that in the hydrocephalic brain there are disturbances of oxidative metabolism and neurotransmission, and perhaps damage to periventricular cells particularly when intracranial pressure is elevated. Although no assays have provided and entirely useful guide to aid decisions regarding shunt therapy, they have provided in vivo information regarding the pathophysiology of hydrocephalus.

Cerebrospinal Fluid Proteins↗

Dopamine beta-hydroxylase immunoreactivity in human cerebrospinal fluid: properties, relationship to central noradrenergic neuronal activity and variation in Parkinson's disease and congenital dopamine beta-hydroxylase deficiency.

1. Dopamine beta-hydroxylase is stored and released with catecholamines by exocytosis from secretory vesicles in noradrenergic neurons and chromaffin cells. Although dopamine beta-hydroxylase enzymic activity is measurable in cerebrospinal fluid, such activity is unstable, and its relationship to central noradrenergic neuronal activity in humans is not clearly established. To explore the significance of cerebrospinal fluid dopamine beta-hydroxylase, we applied a homologous human dopamine beta-hydroxylase radioimmunoassay to cerebrospinal fluid, in order to characterize the properties and stability of cerebrospinal fluid dopamine beta-hydroxylase, as well as its relationship to central noradrenergic neuronal activity and its variation in disease states such as hypertension, renal failure, Parkinsonism and congenital dopamine beta-hydroxylase deficiency. 2. Authentic, physically stable dopamine beta-hydroxylase immunoreactivity was present in normal human cerebrospinal fluid at a concentration of 31.3 +/- 1.4 ng/ml (range: 18.5-52.5 ng/ml), but at a 283 +/- 27-fold lower concentration than that found in plasma. Cerebrospinal fluid and plasma dopamine beta-hydroxylase concentrations were correlated (r = 0.67, P = 0.001). Some degree of local central nervous system control of cerebrospinal fluid dopamine beta-hydroxylase was suggested by incomplete correlation with plasma dopamine beta-hydroxylase (with an especially marked dissociation in renal disease) as well as the lack of a ventricular/lumbar cerebrospinal dopamine beta-hydroxylase concentration gradient. 3. Cerebrospinal fluid dopamine beta-hydroxylase was not changed by the central alpha 2-agonist clonidine at a dose that diminished cerebrospinal fluid noradrenaline, nor did cerebrospinal fluid dopamine beta-hydroxylase correspond between subjects to cerebrospinal fluid concentrations of noradrenaline or methoxyhydroxyphenylglycol; thus, cerebrospinal fluid dopamine beta-hydroxylase concentration was not closely linked either pharmacologically or biochemically to central noradrenergic neuronal activity. 4. Cerebrospinal fluid dopamine beta-hydroxylase was not changed in essential hypertension. In Parkinson's disease, cerebrospinal fluid dopamine beta-hydroxylase was markedly diminished (16.3 +/- 2.9 versus 31.3 +/- 1.4 ng/ml, P < 0.001) and rose by 58 +/- 21% (P = 0.02) after adrenal-to-caudate chromaffin cell autografts. In congenital dopamine beta-hydroxylase deficiency, lack of detectable dopamine beta-hydroxylase immunoreactivity in cerebrospinal fluid or plasma suggests absent enzyme (rather than a catalytically defective enzyme) as the origin of the disorder. 5. We conclude that cerebrospinal fluid dopamine beta-hydroxylase immunoreactivity, while not closely linked to central noradrenergic neuronal activity, is at least in part derived from the central nervous system, and that its measurement may be useful in both the diagnosis and treatment of neurological disease.

Adult↗

Management options for cerebrospinal fluid leak after vestibular schwannoma surgery and introduction of an innovative treatment.

OBJECTIVE: To review the management of cerebrospinal fluid leak after vestibular schwannoma removal reported in the literature and to present a novel approach to management of recalcitrant cases. DATA SOURCES: MEDLINE and PubMed literature search using the terms "cerebrospinal fluid leak" or "cerebrospinal fluid fistula" and "acoustic neuroma" or "vestibular schwannoma" covering the period from 1985 to present in English. A review of bibliographies of these studies was also performed. STUDY SELECTION: Criteria for inclusion in this meta-analysis consisted of the availability of extractable data from studies presenting a defined group of patients who had undergone primary vestibular schwannoma removal and for whom the presence and absence of cerebrospinal fluid leakage was reported. Studies reporting combined approaches were excluded. No duplications of patient populations were included. Twenty-five studies met the inclusion criteria. DATA EXTRACTION: Quality of the studies was determined by the design of each study and the ability to combine the data with the results of other studies. All of the studies were biased by their retrospective, nonrandomized nature. DATA SYNTHESIS: Significance (p < 0.05) was determined using the chi test. CONCLUSIONS: Incisional cerebrospinal fluid leakage responded well to local management and lumbar drainage. Rhinorrhea often necessitated surgical intervention. No specific reoperation techniques correlated exclusively with better reoperation outcomes. The transaural/transnasal approach presents an alternative for surgical management of cerebrospinal fluid rhinorrhea.

Adult↗

The ontogenetic development of concentration differences for protein and ions between plasma and cerebrospinal fluid in rabbits and rats.

1. The purpose of this study was to study in rats and rabbits the ontogenetic development of the blood-brain barrier to macromolecules and the ontogenetic development of concentration differences between plasma and cerebrospinal fluid for ions which are known to be transported actively across the choroid plexus and the blood-brain barrier.2. By comparing the development of concentration differences for ions with the development of the blood-brain barrier to macromolecules we wanted to evaluate an eventual relationship between the development of these two functions of the blood-brain barrier.3. The concentration of protein in cerebrospinal fluid and plasma was measured in foetal, juvenile and adult rabbits and in new-born, juvenile and adult rats. The concentration of protein was similar in rabbit foetuses at 23 days of gestational age (term at 31 days) and in new-born rats, and the ratio decreases at approximately the same rate in the two species.4. The high concentration of proteins in cerebrospinal fluid might reflect either a high rate of entry of protein into the brain or a low production rate of cerebrospinal fluid. Injection of Diamox(R) (100 mg/kg) 2 hr before sampling of cerebrospinal fluid did not change the concentration of protein in cerebrospinal fluid in new-born rats whereas it increased the concentration in older rats. This finding suggests that new-born rat produces little (if any) cerebrospinal fluid suggesting that the high concentration of protein in cerebrospinal fluid in new-born rats reflect a low rate of turnover of cerebrospinal fluid.5. The concentration of sodium, potassium, chloride and magnesium in plasma and cisternal cerebrospinal fluid was measured in rabbits of different age, from 23 days of gestation until adulthood, and in rats of different ages from birth until adulthood.6. Concentration differences between plasma and cerebrospinal fluid for these were established in the youngest animals examined, indicating that the active transport mechanisms for these ions were functioning at an age where the concentration of protein in cerebrospinal fluid was very high.7. The maintenance of concentration differences for ions at a time where the concentration of proteins in cerebrospinal fluid is high, is difficult to explain if the high concentration of proteins in cerebrospinal fluid is due to a leakiness of the intercellular junctions between cerebral endothelial cells. However, the findings might be explained either by a low rate of production of cerebrospinal fluid in the youngest animals and/or by a pinocytotic transfer of proteins across the blood-brain barrier in these animals.8. In rats concentration gradients for ions are established at an age (new-borns) with a low or absent bulk formation of cerebrospinal fluid and at an age where the capillaries are still not enveloped by astrocytic foot processes. These facts suggest that the active transport mechanisms for the ions must be located in the cerebral endothelial cells.

Acetazolamide↗

Nerve growth factor levels in cerebrospinal fluid from patients neurologic disorders.

Nerve growth factor levels were measured in the cerebrospinal fluid from 73 patients with neurologic disorders and non-neurologic acute illnesses by a two-site enzyme immunoassay. Elevated nerve growth factor levels in cerebrospinal fluid were demonstrated in 2 of 7 patients with bacterial meningitis, 7 of 14 patients with viral meningitis or encephalitis, and 1 with multiple sclerosis. Follow-up examinations of the 3 patients (1 with bacterial meningitis, 1 with viral meningitis, and 1 with multiple sclerosis) at convalescent stage showed diminished nerve growth factor levels in cerebrospinal fluid. None of the other patients showed elevation of nerve growth factor levels in cerebrospinal fluid. Nerve growth factor levels in cerebrospinal fluid were not correlated with cell numbers in patients with meningitis or encephalitis. No relationship was observed between nerve growth factor levels and outcome in patients with viral meningitis or encephalitis and bacterial meningitis. Nerve growth factor in cerebrospinal fluid may play a role in neuronal recovery or function as an immunomodulator in children with inflammatory and immune-mediated neurologic disorders.

Adolescent↗

[Complement 3 level in the cerebrospinal fluid in multiple sclerosis].

Using the test of radial diffusion the absolute (mg%) and relative (% of albumin, % of total protein in cerebrospinal fluid) levels of the C3 component of the complement were determined in the cerebrospinal fluid and serum in a group of 61 cases of multiple sclerosis, and similar determinations were carried out in the control groups of patients with neurosis and organic diseases of the central nervous system. The absolute and relative levels of the C3 component in the cerebrospinal fluid in cases of multiple sclerosis were significantly lower (p < 0,001) and were independent of the levels of total protein and albumin in the cerebrospinal fluid. The low level of C3 in the cerebrospinal fluid was due to its low level in the serum in the same cases of multiple sclerosis, and the correlation coefficient of C3 levels in the cerebrospinal fluid and serum in this disease was r = 0.816. The C3 index studied in this work was statistically insignificantly lower in the group of multiple sclerosis with low C3 level in the cerebrospinal fluid as compared with the cases of this disease with normal C3 level in the cerebrospinal fluid. This shows that no data were obtained indicating a local consumption of complement components within the central nervous system in cases of multiple sclerosis. The possibility of a temporarily reduced complement consumption in the areas of demyelination cannot be excluded.

Albumins↗

Diffusion of ketoprofen into the cerebrospinal fluid of young children.

BACKGROUND: The objective was to examine whether or not ketoprofen enters the cerebrospinal fluid after a single oral dose of 1 mg.kg-1 syrup, and to find out what is the lowest plasma concentration that will achieve a measurable level in the cerebrospinal fluid. METHODS: We measured ketoprofen concentrations both in plasma and cerebrospinal fluid of 10 young and healthy children (aged 9-86 months) after surgery with spinal anaesthesia. Samples of cerebrospinal fluid were collected 30 min after drug administration, at the same time as venous blood samples. A validated high-performance liquid chromatography method with a lower limit of 0.02 microg x ml(-1) was used to detect ketoprofen concentrations in cerebrospinal fluid and plasma. RESULTS: Ketoprofen was detectable in the cerebrospinal fluid only in the child who had the highest plasma concentration, 7.4 microg x ml(-1), while at plasma concentrations 6.5 microg x ml(-1) or less, cerebrospinal fluid (CSF) concentrations remained unmeasurable. The detected CSF/plasma ratio was 0.008. CONCLUSIONS: These results indicate that ketoprofen at a dose of 1 mg x kg(-1) is too low to produce measurable CSF levels within 30 min of oral administration.

Administration, Oral↗