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[A method of membrane filtration of cells in the cerebrospinal fluid].

The authors discuss their assessment of the technique of membrane filtration of the cerebrospinal fluid based on an analysis of over 200 cytograms obtained using Milipore membrane filters. Filtration was done in Kistler's apparatus by the method of Kistler-Bischoff and the preparations were stained with hematoxylin and eosin. In the light of the obtained results and various envisaged possibilities of use the authors recommend this condensation technique as a method of choice in cytodiagnostic examinations of the cerebrospinal fluid.

Brain Neoplasms↗

In vitro changes in the transparency and pH of cerebrospinal fluid caused by adding midazolam.

The effects of adding midazolam and bupivacaine to human cerebrospinal fluid in glass test tubes were examined by looking for changes in pH and a reduction in the transparency of the solution. Midazolam (n = 6), 0.25% bupivacaine (n = 6), 5 mg of midazolam in 6 mL of 0.25% bupivacaine (n = 6) and 5 mg of midazolam in 10 mL of saline (n = 6) were added to 1.5-mL samples (n = 24) of cerebrospinal fluid taken at the time spinal anaesthesia was begun. Transparency and pH were checked after each increment. Cerebrospinal pH was decreased to below 7.0 by adding more than 3 mg of midazolam, more than 1.9 mL of 0.25% bupivacaine or 1.3 mL of the mixture. Cerebrospinal transparency was decreased by adding more than 0.7 mg of midazolam, 1.1 mL of 0.25% bupivacaine or 0.6 mL of the mixture. Midazolam in saline neither decreased the pH below 7.0 nor reduced transparency. These results do not suggest that clinically useful doses of intrathecal or epidural midazolam are neurotoxic.

Adjuvants, Anesthesia↗

Pseudo-cerebrospinal fluid rhinorrhea.

Because of its potentially serious sequelae, cerebrospinal fluid (CSF) leakage following surgery for lesions of the cranial base is given immediate attention by neurosurgeons. Despite a multitude of approaches used to prevent its occurrence, CSF leakage complicates up to 30% of difficult skull-base tumor operations. The authors describe the cases of 11 patients who developed a syndrome, not previously described in the literature, termed "pseudo-CSF rhinorrhea." This syndrome occurs after surgery of the cranial base, usually involving dissection or removal of the petrous or cavernous carotid artery, the greater superficial petrosal nerve, and the pericarotid sympathetic plexus. It is characterized by nasal stuffiness and nasal hypersecretion and is sometimes accompanied by facial flushing. The symptoms are characteristically exacerbated by exertion or by elevated ambient room temperatures. Lacrimation is typically absent ipsilateral to the pseudo-CSF rhinorrhea. It is believed that pseudo-CSF rhinorrhea developed in these patients because of a relative imbalance of the regulatory autonomic supply of the nasal mucosa.

Adult↗

Correlation of the ratio of S-adenosyl-L-methionine to S-adenosyl-L-homocysteine in the brain and cerebrospinal fluid of the pig: implications for the determination of this methylation ratio in human brain.

1. Pigs were maintained in air or in an atmosphere of nitrous oxide which dramatically changes the S-adenosyl-L-methionine to S-adenosyl-L-homocysteine ratio in neural tissues. Samples of cerebrospinal fluid, cortex, cerebellum and spinal cord were then extracted and analysed for S-adenosyl-L-methionine and S-adenosyl-L-homocysteine. Regression analyses were carried out on values obtained in cerebrospinal fluid and in neural tissues. 2. Highly significant correlations were obtained between levels of S-adenosyl-L-homocysteine (r2 = 0.42-0.69; P less than 0.001) and S-adenosyl-L-methionine/S-adenosyl-L-homocysteine ratios (r2 = 0.56-0.65; P less than 0.001) in cerebrospinal fluid and levels and ratios in cortex, cerebellum and spinal cord. The levels of S-adenosyl-L-methionine did not show a significant correlation. 3. We conclude that the ratio of these metabolites in the cerebrospinal fluid may reflect the ratio in the central nervous system and we suggest that this may also be true in human tissues. This finding will permit the determination of the probable methylation ratio in the central nervous system in human conditions, such as vitamin B12 deficiency and acquired immune deficiency syndrome, where a similar myelopathy occurs to that seen in the nitrous oxide-treated pig. All three myelopathies may arise from an inhibition of methyltransferases involved in the synthesis of myelin that would occur when the methylation ratio is reduced.

Animals↗

Pharmacokinetics of methotrexate in cerebrospinal fluid and serum after osmotic blood-brain barrier disruption in patients with brain lymphoma.

OBJECTIVE: To evaluate the pharmacokinetics of methotrexate in ventricular cerebrospinal fluid and serum after osmotic blood-brain barrier disruption and intra-arterial administration compared with intravenous or simple intra-arterial infusion in patients with primary central nervous system lymphoma. METHODS: Serum and ventricular cerebrospinal fluid were sampled after methotrexate administration in 12 patients. Blood-brain barrier disruption was induced on 2 sequential days by mannitol (25%) infusion delivered to the vertebral or internal carotid artery territories followed by intra-arterial methotrexate (dose, 1.4 g/m2; 47 treatments). Sixteen treatments were given without barrier disruption by intravenous (3.5 g/m2; nine treatments) or intra-arterial (2.8 g/m2; seven treatments) infusion. RESULTS: Ventricular cerebrospinal fluid-methotrexate peak levels after blood-brain barrier disruption of the vertebral and the internal carotid arteries territories were 19.3 +/- 2.9 and 8.5 +/- 0.7 micromol/L (P < .001), and the area under the curve from time 0 to infinity was 178.0 +/- 21.3 and 110.0 +/- 12.4 [micromol/L x h, respectively (P < .01). No significant differences were observed in serum levels. After intra-arterial infusion was performed without disruption, the serum peak level was higher than that achieved by intravenous treatment (518.2 +/- 67.7 versus 180.6 +/- 31.8 micromol/L; P < .001). No differences were observed in cerebrospinal fluid concentrations, which dropped below 1 micromol/L at 6 hours. The cerebrospinal fluid/serum ratio [AUC(%)] of methotrexate after blood-brain barrier disruption was three to four times greater than that by systemic administration. CONCLUSION: Enhanced methotrexate delivery to the central nervous system can be attained by intra-arterial administration combined with osmotic disruption of the blood-brain barrier compared with simple intra-arterial or intravenous administration.

Adult↗

Distal aortic perfusion and cerebrospinal fluid drainage for thoracoabdominal and descending thoracic aortic repair: ten years of organ protection.

OBJECTIVE: To report the long-term results of our experience using cerebrospinal fluid drainage and distal aortic perfusion in descending thoracic and thoracoabdominal aortic repair. SUMMARY BACKGROUND DATA: Repair of thoracoabdominal and thoracic aortic aneurysm by the traditional clamp-and-go technique results in a massive ischemic insult to several major organ systems. Ten years ago, we began to use distal aortic perfusion and cerebrospinal fluid drainage (adjunct) to reduce end-organ ischemia. METHODS: Between January 1991 and February 2003, we performed 1004 thoracoabdominal or descending thoracic repairs. Adjunct was used in 741 (74%) of 1004. Multivariable data were analyzed by Cox regression. Number needed to treat was calculated as the reciprocal of the risk difference. RESULTS: Immediate neurologic deficit was 18 (2.4%) of 741 with adjunct and 18 (6.8%) of 263 without (P < 0.0009). In high-risk extent II aneurysms, the numbers were 11 (6.6%) of 167 with adjunct, and 11 (29%) of 38 without. Long-term survival was improved with adjunct (P < 0.002). The long-term survival results persisted after adjustment for age, extent II aneurysm, and preoperative renal function. CONCLUSION: Use of adjunct over a long period of time has produced favorable results; approximately 1 neurologic deficit saved for every 20 uses of adjunct overall. In extent II aneurysms, where the effect is greatest, this increases to 1 saved per 5 uses. Adjunct is also associated with long-term survival, which is consistent with mitigation of ischemic end-organ injury. These long-term results indicate that cerebrospinal fluid drainage and distal aortic perfusion are safe and effective adjunct for reducing morbidity and mortality following thoracic and thoracoabdominal aortic repair.

Actuarial Analysis↗

Study of cerebrospinal fluid in Salmonella typhi meningitis.

The present study was designed to study the cerebrospinal fluid of Salmonella typhi meningitis cases. All the 12 cases (100%) showed increase in the lymphocyte count (range 6-24 cells/cmm, mean 15.40 cells/cmm) and increase in protein concentration (range 80-125 mg.Dl, mean 86.25 mg/dl), while glucose concentration remained normal (range 56-80 mg/dl, mean 64.25 mg/dl). These changes in CSF may resemble viral meningitis, from which Salmonella typhi meningitis can only be differentiated by culture of CSF.

Adolescent↗

Characterisation of the pro opiocortin family of peptides in human cerebrospinal fluid.

Chromatography under acid dissociating conditions in conjunction with radioimmunoassay has been employed to investigate the nature of peptides related to opiocortin in human cerebrospinal fluid. Samples of cerebrospinal fluid (CSF) were collected for chromatography from 15 patients prior to air encephalography. 2 patients had pituitary dependent Cushing's disease, 3 non-endocrine neurological disease and 10 non-ACTH related pituitary disease. The column fractions were assayed for N- and C-terminal beta-lipotropin, N-terminal ACTH and gamma-MSH immunoreactivity. Elution profiles obtained from chromatography on Sephadex G-50 demonstrated peaks of immunoreactivity corresponding to the elution positions of synthetic human beta-endorphin, highly purified beta-lipotropin and highly purified gamma-lipotropin in all CSF samples. A peak of a large molecular weight material with N and C terminal beta-lipotropin immunoreactivity was also detected. Chromatography of CSF on Sephadex G-75 showed this large molecular weight peak to be comprised of peptides eluting in the positions of a 31K molecular weight marker with beta-lipotropin and ACTH immunoreactivity and a 16K molecular weight marker with gamma-MSH immunoreactivity. This suggests the presence of the common precursor to ACTH and LPH in the CSF.

Chromatography, Gel↗

Sequential changes of cerebrospinal fluid sodium during the development of hypertension in Dahl rats.

The role of sodium retention and consequent changes in cerebrospinal fluid sodium concentration in the genesis of hypertension in Dahl rats was evaluated. Dahl salt-sensitive (DS, n = 7), Dahl salt-resistant (DR, n = 7), and Sprague-Dawley (n = 6) rats were housed in metabolic cages and instrumented with a stainless steel cannula in the cisterna magna and a femoral arterial catheter. A blood sample was drawn daily (200 microliters), and cerebrospinal fluid was collected by continuous 24-hour withdrawal (200 microliters/day). Daily sodium, potassium, and water balances were also determined. Rats were studied sequentially on 0.4%, 4%, and 8% sodium diets (7 days per sodium level). Mean arterial pressure increased with 4% NaCl from 107 to 120 mm Hg (p less than 0.05) over 24 hours in DS rats and remained at about that level until the NaCl was increased to 8%, which resulted in a gradual rise of mean arterial pressure over the next 7 days to 135 mm Hg. Cerebrospinal fluid sodium was unchanged in DR and Sprague-Dawley rats fed 4% or 8% sodium, but in DS rats rose from 152.3 to 155.2 +/- 0.6 meq/l on the third day at 4% sodium and remained elevated over the next 2 weeks of study. Blood sodium was unchanged throughout the study in all groups. On the first day only of the 4% and 8% sodium diets, both DS and DR rats exhibited a similar net retention of sodium, which was greater than the Sprague-Dawley rats (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Isoflurane and cerebrospinal fluid pressure--a study in neurosurgical patients undergoing intracranial shunt procedures.

The effect of isoflurane 1.0% and 1.5% with nitrous oxide on ventricular cerebrospinal fluid pressure was studied in 17 patients who underwent intracranial shunt procedures. Isoflurane at both concentrations caused significant increases in cerebrospinal fluid pressure during normocapnic ventilation, but these could be prevented by simultaneous hyperventilation or by the prior induction of hypocapnia. Decreases in mean arterial pressure occurred also, and resulted in a significant reduction in cerebral perfusion pressure in normocapnic patients.

Adolescent↗

Diagnostic value of cerebrospinal fluid anti-myelin basic protein in patients with multiple sclerosis.

Prevalence and titer of total, free, and bound cerebrospinal fluid anti-myelin basic protein (MBP) antibodies as well as free/bound ratios were determined in four groups of patients with multiple sclerosis (MS) and three groups of controls. All patients with clinically active MS have elevated levels of total anti-MBP, which may be present in either free or bound form. Patients whose disease is in remission have undetectable anti-MBP levels, and some patients with clinically stable disease with residual disability may have detectable antibody titers. Chronically progressive MS is usually associated with high levels of antibody in the bound rather than the free form, resulting in a low or normal free/bound ratio. In contrast, MS exacerbations are characterized by relatively high levels of free anti-MBP in the cerebrospinal fluid, resulting in a high free/bound antibody ratio. Bound anti-MBP was also detected in elevated levels in 1 patient with subacute sclerosing panencephalitis and 2 of 8 patients with postinfectious encephalomyelitis. Although elevated levels of cerebrospinal fluid anti-MBP are not specific for MS, they are strongly associated with disease activity and may be involved in the pathogenesis of demyelination in patients with MS.

Autoantibodies↗

Direct analysis of tetrahydrobiopterin in cerebrospinal fluid by high-performance liquid chromatography with redox electrochemistry: prevention of autoxidation during storage and analysis.

Measurement of tetrahydrobiopterin in cerebrospinal fluid requires careful handling of samples during storage and analysis. Addition of dithioerythritol and deoxygenation of the mobile phase with helium prevents breakdown of tetrahydrobiopterin during chromatography. Tetrahydrobiopterin in cerebrospinal fluid is unstable at room temperature, 100% being lost within 3.5 h, this breakdown does not generate equivalent quantities of dihydrobiopterin and biopterin. Addition of dithioerythritol and diethylenetriaminepenta-acetic acid to cerebrospinal fluid prevents breakdown of tetrahydrobiopterin for 6 mth at -70 degrees C and for up to 5 h at 4 degrees C. At room temperature less than 5% of tetrahydrobiopterin was lost after 2 h.

Biopterins↗

Effect of methylprednisolone on entry of ampicillin and gentamicin into cerebrospinal fluid in experimental pneumococcal and Escherichia coli meningitis.

The influence of methylprednisolone on the passage of ampicillin and gentamicin into and activity within cerebrospinal fluid was examined in two models of experimental meningitis. Steroid pretreatment reduced the concentrations of these drugs in purulent cerebrospinal fluid of rabbits with experimental pneumococcal and Escherichia coli meningitis (P less than 0.05). However, the resultant mean concentrations of these antibiotics in cerebrospinal fluid still exceeded the minimal bactericidal concentrations of the infecting organisms. The rate of bactericidal effect in vivo was unaffected by steroid therapy in each model. Methylprednisolone did not have deleterious effects on the course of treated experimental meningitis under these short-term (24-h) experiments.

Ampicillin↗

The predictive value of cerebrospinal fluid dynamic tests in patients with th idiopathic adult hydrocephalus syndrome.

OBJECTIVE: To evaluate the predictive value of the cerebrospinal fluid (CSF) tap test and CSF outflow conductance in the selection of patients with the idiopathic adult hydrocephalus syndrome, defined exclusively on a clinical basis, for shunt surgery. DESIGN: A prospective, consecutive case series. All patients were assessed before surgery and at 3 months after shunt placement. Preoperatively, CSF pressure, conductance, and CSF formation rate were assessed by a constant-pressure infusion method. Improvement in gait and cognitive functions after removal of CSF was noted (ie, with the CSF tap test). Postoperatively, the infusion method was used to evaluate shunt function. SETTING: Tertiary, academic referral center. PATIENTS: Thirty-five patients with idiopathic adult hydrocephalus (normal-pressure hydrocephalus) syndrome based on conservative clinical criteria. No predictive tests were used for inclusion. All patients had a typical gait disturbance and a communicating hydrocephalus. Twenty-eight patients also had dementia or incontinence, or both. INTERVENTION: The CSF diversion (Cordis, [Orbis-Sigma]) valve, six patients; Hakim's standard system (Cordis Hakim standard system), 29 patients. OUTCOMES OF SURGERY: Serial videotaping of gait, a comprehensive neuropsychologic battery, and the Bartel index of activities of daily life. RESULTS: Gait was improved in 25 (72%) of the 35 patients, whereas the Bartel index remained unchanged. The conditions of five of seven patients with gait disturbance as the sole symptom improved. The spatial function (37% improved) and the findings from the Fuld object memory tests (29% improved) were significantly improved. Shunt dysfunction could not explain the lack of effect of an operation in the remaining patients. It should be noted that these results obtained at 3 months postoperatively may not be applicable in a long-term perspective. The CSF outflow conductance or CSF tap test were not able to identify those patients who would or would not benefit from a CSF diversion procedure. However patients had a lower conductance and a higher CSF pressure than did control subjects. CONCLUSIONS: Considerable improvement in gait was seen, but cognitive function was little affected. The CSF tap test or conductance does not provide additional information that is necessary to distinguish between patients whose conditions will or will not respond to shunting, when selection for surgery is based on conservative clinical criteria.

Activities of Daily Living↗

Epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidural opioids (part 1): differences among opioids.

BACKGROUND: The pharmacokinetics of epidurally administered drugs has been the subject of many studies, yet drug concentration in the epidural space has never been measured. This study was undertaken to characterize the epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidurally administered opioids on the basis of measurement of drug concentration in each of these compartments after epidural administration. METHODS: Morphine plus alfentanil, fentanyl, or sufentanil were administered epidurally in anesthetized pigs. Microdialysis was used to sample the epidural space and the cerebrospinal fluid for measurement of opioid concentration over time. Plasma samples were obtained from the central venous plasma and the epidural venous plasma. These data were used to calculate relevant pharmacokinetic parameters, including mean residence time, elimination half-lives, areas under the concentration versus time curves, clearance, and volume of distribution for each opioid in each compartment. RESULTS: Some of the more important findings were that the cerebrospinal fluid and plasma pharmacokinetics of the opioids did not parallel their epidural pharmacokinetics and that their hydrophobic character governed multiple aspects of their lumbar epidural pharmacokinetics. CONCLUSIONS: The findings indicate that the spinal pharmacokinetics of these drugs are complex and, in some ways, counterintuitive. Also, the bioavailability of opioids in the cerebrospinal fluid and epidural space is determined primarily by their hydrophobicity, with less hydrophobic drugs having greater bioavailability.

Adipose Tissue↗

Endoscopic management of cerebrospinal fluid leak associated with the use of bone wax in skull-base surgery.

OBJECTIVE: To alert otolaryngologists to consider the possibility that bone wax may be associated with cerebrospinal fluid leaks that occur immediately after skull-base craniotomy approaches. STUDY DESIGN AND SETTING: Clinical report from surgical experience in a tertiary care setting. RESULTS: Three patients presented with brisk cerebrospinal fluid leak after craniotomy. Sinus endoscopy revealed bone wax within a small parasphenoid defect in all 3 cases. CONCLUSIONS: Bleeding from areas of the skull base adjacent to the paranasal sinuses during craniotomy can signal a small breach of the skull base. Bone wax may control bleeding from edges of transected bone but also stent the skull-base defect open, preventing fibrin deposition and spontaneous healing and closure. SIGNIFICANCE: Otolaryngologists repairing a cerebrospinal fluid leak after a skull-base craniotomy approach should consider the possibility of encountering bone wax and be able to identify it to better treat their patient.

Adult↗

Cerebrospinal fluid seepage through polyglactin 910 dura substitute manifested as spinal extradural collection of fluid.

Following excision of pilocytic astrocytoma, a 12-year-old girl underwent posterior cranial fossa synthetic duraplasty with polyglactin 910 mesh. On the 8th postoperative day, unusual extradural collection was diagnosed by spinal magnetic resonance imaging. On the 14th postoperative day, cerebrospinal fluid leakage in the upper part of the postoperative wound was noticed. Unusual extradural collection detected by spinal magnetic resonance imaging was assumed to be the consequence of cerebrospinal fluid seepage and a warning sign of cerebrospinal fluid leakage following synthetic posterior fossa duraplasty. This case shows that polyglactin 910 mesh may be ineffective when used for posterior cranial fossa duraplasty in children, although it is considered as valuable as autologous tissue.

Astrocytoma↗