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Pharmacokinetics of fluconazole in cerebrospinal fluid and serum in human coccidioidal meningitis.

The pharmacokinetics of fluconazole, a new oral azole, were evaluated in cerebrospinal fluid and sera of eight patients with coccidioidal meningitis. At a dose of 50 mg/day, peak concentrations of 2.5 to 3.5 and 2.0 to 2.3 micrograms/ml occurred at 2 to 6 and 4 to 8 h in serum and cerebrospinal fluid, respectively. At 100 mg/day, peak concentrations of 4.5 to 8.0 and 3.4 to 6.2 micrograms/ml occurred at 2 to 4 and 4 to 12 h, respectively. The mean ratios of the concentration in cerebrospinal fluid to that in serum were 73.8% at 50 mg/day and 88.7% at 100 mg/day. Results suggested that there was a prolonged half-life in both cerebrospinal fluid and serum and that it was slightly longer in the former. Minimal toxicity was noted in 34 patient months of therapy (12 months on 50 mg daily; 22 months on 100 mg daily). After a mean of 4.5 months of therapy, five patients responded to therapy and three were unevaluable. The penetration of fluconazole into cerebrospinal fluid was substantial, toxicity was minimal, and early clinical experience was encouraging. Fluconazole holds promise as the sole or adjunctive therapy for fungal meningitis.

Adult↗

Cytology of cerebrospinal fluid: technical and diagnosis considerations.

The usefulness of cerebrospinal fluid cytology in the diagnosis of malignancy has been enhanced in recent years by the development of new techniques for increasing cellular yield. Micropore filters and a specially adapted cytocentrifuge have been used for this purpose with a resulting increase in cell concentration and in diagnostic accuracy. Cerbrospinal fluid examination has been found to be of particular value in the diagnosis of metastatic carcinoma, lymphomatous and leukemic involvement of the meninges and certain primary central nervous system tumors. Cytologic criteria for the differential diagnosis of the principal types of tumors encountered in cerebrospinal fluid are discussed.

Astrocytoma↗

Abnormal alkaline phosphatase of hepatic type in cerebrospinal fluid of a patient with intracranial metastasis from lung cancer.

High alkaline phosphatase (ALP) activity was found in the cerebrospinal fluid of a patient with intracranial metastases from adenocarcinoma of the lung. On agarose gel electrophoresis of the major ALP isoenzyme found in the cerebrospinal fluid, its mobility was different from those of the usual serum ALP isoenzymes. This abnormal mobility might be due to the linked glycan phosphatidylinositol anchor in the ALP molecule, as the mobility became the same as that of the common liver type ALP after treatment with phosphatidylinositol specific phospholipase. The immunochemical antigenicity of the cerebrospinal fluid ALP was identical with that of the common serum liver type ALP, but its sugar moiety was similar to the membranous liver-type ALP rather than the serum liver type ALP. The molecular size of the cerebrospinal fluid ALP was 140 kilodaltons, 12 less than the common serum liver type ALP, suggesting that the ALP in the patient's cerebrospinal fluid was derived from the intracranial metastatic carcinoma.

Alkaline Phosphatase↗

Cerebrospinal fluid ascites complicating a ventriculoperitoneal shunt.

An unusual case of intermittent cerebrospinal fluid ascites complicating a ventriculoperitoneal shunt is presented. The patient developed hydrocephaly secondary to blockage of the third ventricle by a recurrent craniopharyngioma. The ascites responded to paracenteses and on several occasions resolved spontaneously. There was no satisfactory explanation for the "rejection" of the cerebrospinal fluid by the peritoneal cavity. The ascites was resolved without conversion of the ventriculoperitoneal shunt to a ventriculoatrial shunt being required.

Ascites↗

Cerebrospinal fluid tau and beta-amyloid 42 proteins identify Alzheimer disease in subjects with mild cognitive impairment.

CONTEXT: Cerebrospinal fluid tau protein and beta-amyloid 42 (Abeta42) protein are altered even in very mild Alzheimer disease (AD). So far, few data exist for subjects with mild cognitive impairment (MCI). OBJECTIVE: To investigate the potential of cerebrospinal fluid tau and Abeta42 for predicting progression from MCI to AD in a longitudinal study of 28 patients with MCI who received follow-up for 18 months. DESIGN: An 18-month prospective study. SETTING: Clinical follow-up study of community-residing subjects with MCI. MAIN OUTCOME MEASURES: Cerebrospinal fluid tau and Abeta42 concentrations were measured using enzyme-linked immunosorbent assay at baseline. The potential of both biomarkers was evaluated to predict the progression to dementia, the end point of this study, using multiple logistic regression analysis. RESULTS: Of 28 subjects with MCI, 12 progressed to dementia (2 to frontotemporal dementia; 10 to AD). Six subjects had progressive MCI, and 10 subjects showed stable MCI. Cerebrospinal fluid tau levels were significantly elevated in patients who progressed to probable AD (P =.002) and subjects with progressive MCI (P =.003) compared with subjects who had stable MCI. Cerebrospinal fluid Abeta42 levels were significantly lower in patients who progressed to probable AD (P =.007) and those with progressive MCI (P =.04) than in subjects with stable MCI. Logistic regression analysis identified elevated tau protein level as a predictor of cognitive deterioration (P =.02), whereas a delayed verbal recall score at baseline was significantly associated with the development of probable AD (P =.03). CONCLUSION: Our results indicate that altered tau and Abeta42 concentrations may be detectable in subjects who are clinically diagnosed as having MCI but demonstrate the pathological changes of AD.

Aged↗

The effect of cerebrospinal fluid dilution of isobaric 0.5% bupivacaine used for spinal anaesthesia.

A prospective study was conducted to see the effect on spinal anaesthesia of the dilution of isobaric 0.5% bupivacaine with cerebrospinal fluid. Sixty patients were randomly allocated to three groups. In group 1, patients received 3 ml isobaric 0.5% bupivacaine intrathecally without aspirating cerebrospinal fluid. In groups 2 and 3, cerebrospinal fluid 1 ml and 2 ml was aspirated respectively and mixed with 3 ml isobaric 0.5% bupivacaine. A total volume of 4 ml in group 2 and 5 ml in group 3 was administered. Thus, the volume of cerebrospinal fluid remained unchanged. Pinprick analgesia and motor block was evaluated from induction until recovery. No differences in onset time, duration and 'two segments regression' were noticed. The only statistical difference was the time to reach complete motor block, which was shorter in group 1 as compared to groups 2 and 3 (6.9 SD 1.4 min versus 11.3 SD 3.0 and 13.5 SD 3.9 min respectively). The mean value of maximum decrease in systolic blood pressure was small, being less than 15% of the pre-operative value for each group. In conclusion, the effect of diluting isobaric 0.5% bupivacaine with cerebrospinal fluid, 1 ml and 2 ml, is minimal and it is an unnecessary procedure with limited clinical effect.

Adult↗

Studies of activated microglial cells and macrophages using Alzheimer's disease cerebrospinal fluid in adult rats with experimentally induced lesions.

Previous investigations have shown that cerebrospinal fluid from Alzheimer's disease patients contains antibodies that recognize the amoeboid microglia--a nascent and active form of microglia in the developing rat brain [McRae et al. (1991) Neuroscience 41, 739-752]. The present study extended this to show that the same cerebrospinal fluid from Alzheimer's disease patients also labeled the activated microglia and macrophages induced experimentally in adult central nervous system. Thus, in the spinal cord, activated microglia were elicited following the destruction of the motor neurons by the toxic lectin, Ricinus communis agglutinin, injected into the sciatic nerve. The activated microglia which were closely associated with the soma of the degenerating neurons were intensely immunostained with the cerebrospinal fluid from Alzheimer's disease patients. The labeling pattern was comparable to some known monoclonal antibodies including OX-42, OX-18 and OX-6 that mark microglia. The microglia cells on the contralateral normal side remained unstained. In the cerebrum, activated microglia and neural macrophages were induced following an epidural application of the excitotoxin, kainic acid or cryolesion. Immunoelectron microscopy of these cells showed that the immunoreactivity was localized at the plasma membrane and its derivatives suggesting that these are the sites where the antigens are associated. The results obtained in this investigation suggest that these experimental models may be a means to gain further insight to antigens recognized by antibodies in the cerebrospinal fluid of Alzheimer's disease patients.

Alzheimer Disease↗

Value of cerebrospinal fluid analysis in the differential diagnosis of meningitis: a study in 710 patients with suspected central nervous system infection.

A prospective study to determine the value of cerebrospinal fluid analysis in the differential diagnosis of meningitis was performed in 710 consecutively observed patients, both children and adults, who underwent lumbar puncture due to suspected central nervous system infection. Diagnoses included acute or presumed bacterial meningitis (n = 79), acute or presumed viral meningoencephalitis (n = 218), acute unclassified meningitis (n = 6), other infections of the central nervous system (n = 37), non-infectious neurological diseases (n = 76) and control patients (n = 294). The sensitivity, specificity and predictive values were determined for cerebrospinal fluid white blood cell count, total protein, lactate, glucose and C-reactive protein levels as well as the blood/cerebrospinal fluid glucose ratio. Determination of cerebrospinal fluid levels of lactate (greater than or equal to 3.5 mmol/l) was found to be superior to the other tests. The C-reactive protein level gave no additional diagnostic information when the lactate level was determined. The white blood cell count, and total protein and glucose levels were often unreliable tools for differential diagnosis, largely due to low sensitivity at realistic discriminatory limits. The study confirms that no cerebrospinal fluid test is fully reliable in distinguishing bacterial meningitis from other forms of meningitis.

Adolescent↗

The significance of neuron specific enolase levels in cerebrospinal fluid and serum after experimental traumatic brain damage.

In the posttraumatic period, measurement of neural tissue enzymes in serum and cerebrospinal fluid gives quantitative information about the severity of the head injury. In our study, we evaluated the relationship between the serum and cerebrospinal fluid levels of neuron specific enolase and the severity of trauma. Head traumas at different severity were applied experimentally (Mild 0.038 N, Moderate 0.057 N, Severe 0.3 N). Serum and cerebrospinal fluid levels of neuron specific enolase were measured in trauma and control groups of rats. Only in the severe trauma group, the neuron specific enolase levels of cerebrospinal fluid were significantly increased. There was no statistically significant difference between the groups when serum neuron specific enolase levels were evaluated. Our data leads us to conclude that trauma, causing significant neural damage, results in an increase in cerebrospinal fluid neuron specific enolase levels, however the serum neuron specific enolase levels do not seem to run parallel with that increase.

Animals↗

Cerebrospinal fluid shunting for hydrocephalus in the adult: factors related to shunt revision.

Cerebrospinal fluid shunting procedures are widely employed in the treatment of hydrocephalus and other disturbances of the dynamics of cerebrospinal fluid. In spite of its popularity, this operation frequently requires surgical revision. A retrospective analysis of a series of 356 adults who underwent the insertion of a cerebrospinal fluid shunt between January 1970 and December 1988 was performed. The incidence of revision was analyzed, and an attempt was made to identify possible causal factors. The overall incidence of surgical revisions was 28.65%; the number of revisions in the same patient ranged between one and eight. The most frequent causes of revision were distal malposition, obstruction, and infection. A statistically significant difference (P less than 0.05) was found in both the risk of revision in patients who had undergone previous operations and those who had not and in the incidence of revision before and after January 1985. Meticulous surgical technique as well as perioperative antibiotic prophylaxis appear responsible for the latter. The differences in the incidence of revision among patients treated with different types of shunts and valves, though remarkable, is not statistically significant.

Adolescent↗

2',5'-Oligoadenylate synthetase activity and T cell subset in the cerebrospinal fluid and peripheral blood of aseptic meningitis.

2',5'-oligoadenylate synthetase activity, which is assumed to be induced by interferon, is reported to be one of the useful markers reflecting interferon activity. The enzyme activity of patients with aseptic meningitis and febrile convulsion were compared in order to evaluate interferon activity as one of the local immuno-defense mechanisms of aseptic meningitis. The surface antigen of mononuclear cells in cerebrospinal fluid and peripheral blood of some patients with aseptic meningitis was also measured. The enzyme activity of patients with aseptic meningitis was 191.4 pmol/dL in the cerebrospinal fluid and 395.8 pmol/dL in the serum during the acute phase, while that of patients with febrile convulsion was 45.2 pmol/dL in the cerebrospinal fluid and 326.0 pmol/dL in the serum. The enzyme activity of the former patients significantly decreased during the recovery phase in both the cerebrospinal fluid and serum. CD3 positive cells in the peripheral blood were 56.3% of the total mononuclear cells during the acute phase and 65.2% during the recovery phase, whereas in the cerebrospinal fluid mononuclear cells, they were 87.1 and 85.5%, respectively. During the acute phase, CD4 positive cells were the predominant T lymphocyte subset in the cerebrospinal fluid cells, while CD8 positive cells were predominant during the recovery phase. The relative proportions of CD4 positive and CD8 positive cells during the acute and recovery phase in the cerebrospinal fluid mononuclear cells were quite high compared to the recovery phase, although that ratio of peripheral blood mononuclear cells was not changed throughout the course. It was concluded that T lymphocytes and increased 2',5'-oligoadenylate synthetase activity in the cerebrospinal fluid may be one of the important components in the local inflammatory process independent of the systemic host defense mechanism in aseptic meningitis.

2',5'-Oligoadenylate Synthetase↗

N-acetylaspartic acid (NAA) and N-acetylaspartylglutamic acid (NAAG) in human ventricular, subarachnoid, and lumbar cerebrospinal fluid.

N-Acetylaspartic and N-acetylaspartylglutamic acid concentrations in human ventricular, subarachnoid and lumbar cerebrospinal fluid were measured by combined gas chromatography-mass spectrometry using selected ion monitoring with deuterated internal standards. N-Acetylaspartate concentrations were in the range 55, 9, and 1 microM, respectively; N-acetylaspartylglutamate concentrations in the same fluids were in the range 8, 3 and 4 microM, respectively. There did not appear to be any difference in lumbar fluid concentrations of either compound between control subjects, schizophrenic patients, Alzheimer's disease patients and a pooled group of patients with neurological degeneration. Ventricular concentrations of both compounds were greatly increased in deceased patients suggesting that maintenance of their intracellular concentrations is probably energy dependent. The concentrations of these compounds in lumbar cerebrospinal fluid from living, and ventricular cerebrospinal fluid from deceased subjects were weakly correlated with one another. In lumbar fluid neither compound appeared to be correlated with age. Analysis of serially collected lumbar samples from two subjects showed a weak concentration gradient for both compounds. Neither antipsychotic medication nor the acid transport inhibitor probenecid had any effect on lumbar concentrations of either compound. Attempts to use anion exchange high pressure liquid chromatography with UV detection for measurement of the low concentrations of N-acetylaspartate found in cerebrospinal fluid from living subjects were unsuccessful.

Adult↗

Vasopressin in fetal cerebrospinal fluid.

Vasopressin concentrations were measured in the cerebrospinal fluid in two hydrocephalic fetuses at 33 and 34 weeks of gestation. The vasopressin concentrations in cerebrospinal fluid were 0.8 and 0.6 pg/ml, and in amniotic fluid 0.4 and 1.0 pg/ml, respectively. Previously measured vasopressin concentrations in amniotic fluid of the normal fetuses have been of the same magnitude.

Female↗

Liquid chromatographic assay for cerebrospinal fluid normetanephrine.

A method for quantitation of normetanephrine in human cerebrospinal fluid is described. An amine-specific reagent, sulfosuccinimidyl propionate, is used to obtain the lipid soluble N-propionyl derivative of normetanephrine, which can be separated and quantitated in presence of other biogenic amines by liquid chromatography with electrochemical detection. The method is reproducible, linear, and precise at the relatively low concentrations of unconjugated normetanephrine occurring in human cerebrospinal fluid. Hospitalized, drug-free, alcoholic patients were found to have cerebrospinal fluid unconjugated normetanephrine concentrations in the 0.5-1.5 nanomolar range. The practical limit of sensitivity for the method is about 0.025 pmole per ml of CSF.

Acylation↗

Cerebrospinal fluid rhinorrhea and intraventricular pneumocephalus due to intermittent shunt obstruction.

Cerebrospinal fluid rhinorrhea and intraventricular pneumocephalus occurred in an adolescent with aqueduct stenosis whose ventriculoperitoneal shunt occluded repeatedly due to a faulty on-off control. The possible mechanisms are discussed, the urgency of treatment is stressed, and the risk of pneumocephalus when a shunt is used to treat cerebrospinal fluid rhinorrhea is pointed out.

Adolescent↗