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The fibrinolytic activity of cerebrospinal fluid after subarachnoid hemorrhage.

Fibrinolytic activity of cerebrospinal fluid and peripheral blood was studied in 14 patients with subarachnoid hemorrhage during the high-risk period of subarachnoid rebleeding. Fibrinolytic activity of cerebrospinal fluid or peripheral blood could not be demonstrated. Determination of fibrin degradation products showed high levels in cerebrospinal fluid, being a result of meningeal irritation. The findings in this study--as well as other observations--suggest, that antifibrinolytic therapy should not be administered in patients with subarachnoid hemorrhage.

Antifibrinolytic Agents↗

Effect of endothelin on production of cerebrospinal fluid in rabbits.

BACKGROUND AND PURPOSE: Endothelin is a potent vasoconstrictor in several tissues, including the choroid plexus. The goal of this study was to determine whether endothelin affects the production of cerebrospinal fluid. METHODS: Ventriculocisternal perfusion was used to measure the production of cerebrospinal fluid in anesthetized rabbits. Changes in production of cerebrospinal fluid were examined in response to vehicle, intravenous endothelin (alone and in the presence of indomethacin), and intraventricular endothelin. RESULTS: Under control conditions, the reduction in production of cerebrospinal fluid in response to endothelin administered intravenously was only modestly greater than that during infusion of vehicle. Because endothelin releases cyclooxygenase products that attenuate the direct effects of endothelin in several tissues, effects of endothelin on the production of cerebrospinal fluid were also examined after inhibition of cyclooxygenase. Production of cerebrospinal fluid in response to 1 micrograms/kg i.v. endothelin was reduced more in animals treated with indomethacin than in untreated animals (-34 +/- 7% [mean +/- SEM] versus -14 +/- 6%, p less than 0.05). Thus, effects of endothelin on the production of cerebrospinal fluid are attenuated by cyclooxygenase products. Finally, responses to intraventricular endothelin were examined. Intraventricular endothelin produced a modest, but significant, reduction in the production of cerebrospinal fluid. CONCLUSIONS: In summary, endothelin may play a role in regulation of the brain fluid balance by affecting the rate of production of cerebrospinal fluid, and this effect is modulated by cyclooxygenase products.

Animals↗

Tegmen tympani cerebrospinal fluid leak repair.

OBJECTIVE: To describe the transmastoid approach for closing cerebrospinal fluid leaks in the tegmen tympani using autologous materials (temporal muscle fascia and abdominal fat) and heterologous materials (bovine collagen), together with its advantages and disadvantages. MATERIAL AND METHODS: We present the cases of three patients who underwent closure of spontaneous cerebrospinal fluid leaks in the tegmen tympani in which we used the transmastoid approach and autologous and heterologous materials. The three patients underwent canal wall-up mastoidectomy, posterior tympanotomy, removal of the malleus head and incus and, consequently, exposure of the tegmen tympani and the cerebrospinal fluid leak. Closure was performed using temporal muscle fascia, abdominal fat and bovine collagen, fixed in place with fibrin glue. A lumbar shunt was established, as is routine. RESULTS: The cerebrospinal fluid leak was closed in all patients using the technique described, with a minimum follow-up of 14 months. CONCLUSION: The technique presented herein is an excellent option in cases of cerebrospinal fluid leakage in the tegmen tympani; it is easy to perform and results in minimal risk to patients.

Adipose Tissue↗

Temporal physiochemical changes during in vitro relaxation time measurements: the cerebrospinal fluid.

Documented relaxation time measurements of body fluids such as cerebrospinal fluid (CSF) vary considerably. This may be largely due to lack of an appropriate method of maintaining the in vivo physiological and biochemical characteristics of the fluid. We have developed an in vitro technique that maintains the in vivo characteristics of body fluid samples for a sufficiently long period to establish the true relaxation times. To illustrate this we studied changes in CSF pH, pO2, and pCO2, first as it equilibrated with air and then under anaerobic conditions as found in vivo. Relaxation times of CSF were then studied under aerobic and anaerobic conditions. Under the particular aerobic conditions used the pH and pO2 of CSF increased quickly and pCO2 fell within the first 30 min. By 3-4 h equilibration with air was complete. The T1 and T2 relaxation times of CSF decreased by 14 and 16%, respectively, as a result of these physicochemical changes. It is important that such changes be considered when relaxation measurements of any body fluid are performed in vitro and efforts to maintain the in vivo milieu should not be neglected.

Aerobiosis↗

[Cerebrospinal fluid prealbumins in children with subacute sclerosing panencephalitis].

In the cerebrospinal fluid of 26 children with SSPE the levels of prealbumins and total proteins were determined and electrophoretic separation of proteins was done. The usefulness is discussed of the percent proportion of prealbumins in the cerebrospinal fluid as a criterion indicating damage to the blood-cerebrospinal fluid barrier with increased penetration of proteins in SSPE. It is concluded that in diseases in which biosynthesis occurs of proteins in the central nervous system the percent proportion of prealbumins fails to reflect the integrity of the brain-cerebrospinal fluid barrier.

Adolescent↗

Net transport of glucose from blood to cerebrospinal fluid in the cat.

The net transport of glucose from blood to the cerebrospinal fluid compartment of cats was measured by ventriculocisternal perfusion to determine over a large range of serum glucose concentrations the influence of serum glucose levels and their changes on the net transport rate. Changes in serum glucose levels were followed within minutes by corresponding changes in cerebroventricular effluent fluid glucose concentration. At mean values of serum glucose concentration of 6.2 mM and cerebrospinal fluid formation rate of 24.3 microliter/min, the net glucose influx rate was 1.6 mmol/min. The effluent fluid-to-serum glucose concentration ratio was 0.25 and decreased when serum glucose was greater than 11.1 mM. The rate of glucose transport from blood to effluent fluid during ventricular perfusion was saturable, and approached a maximum of 3.5 mumol/min at serum glucose levels above 22 mM. From the cerebrospinal fluid formation and net glucose influx rates the calculated glucose concentration of nascent cerebrospinal fluid was 6.5 mM and higher than the corresponding serum glucose of 5.6 mM. It is concluded that during perfusion over a wide range of serum glucose concentrations, a saturable mediated glucose transport mechanism can be demonstrated. Changes in serum glucose are rapidly reflected in corresponding effluent fluid glucose levels. From effluent fluid-to-serum glucose concentration ratios and calculations of the glucose in newly formed cerebrospinal fluid, the technique, however, overestimates the glucose influx rates at normal serum glucose levels.

Animals↗

Steady-state pharmacokinetics of indinavir in cerebrospinal fluid and plasma among adults with human immunodeficiency virus type 1 infection.

To characterize steady-state indinavir pharmacokinetics in cerebrospinal fluid and plasma, 8 adults infected with human immunodeficiency virus underwent intensive cerebrospinal fluid sampling while receiving indinavir (800 mg every 8 hours) plus nucleoside reverse transcriptase inhibitors. Nine and 11 serial cerebrospinal fluid and plasma samples, respectively, were obtained from each subject. Free indinavir accounted for 94.3% of the drug in cerebrospinal fluid and 41.7% in plasma. Mean values of cerebrospinal fluid peak concentration, concentration at 8 hours, and area under the concentration-time profile calculated over the interval 0 to 8 hours [AUC(0-8)] for free indinavir were 294 nmol/L, 122 nmol/L, and 1616 nmol/L x h, respectively. The cerebrospinal fluid-to-plasma AUC(0-8) ratio for free indinavir was 14.7% +/- 2.6% and did not correlate with indexes of blood-brain barrier integrity or intrathecal immune activation. Indinavir achieves levels in cerebrospinal fluid that should contribute to control of human immunodeficiency virus type 1 replication in this compartment. The cerebrospinal fluid-to-plasma AUC(0-8) ratio suggests clearance mechanisms in addition to passive diffusion across the blood-cerebrospinal fluid barrier, perhaps by P-glycoprotein-mediated efflux.

Acquired Immunodeficiency Syndrome↗

Transnasal endoscopic repair of cerebrospinal fluid rhinorrhea and skull base defects: a review of twenty-nine cases.

The management of cerebrospinal fluid rhinorrhea has historically plagued the neurosurgeon and the otolaryngologist-head and neck surgeon. Intracranial repair is still favored at many institutions, despite its inherent morbidity. Extracranial nonendoscopic techniques have been previously described but have not gained wide acceptance. More recently, several reports have been published describing a variety of endoscopic techniques in limited patient series used to manage cerebrospinal fluid rhinorrhea. We present our series of 29 patients with cerebrospinal fluid rhinorrhea, treated with endoscopic techniques between December 1989 and June 1993, with follow-up ranging from 3 to 43 months. This represents the largest reported series to date of patients treated with this technique. Our technique has evolved during this time period but centers around the use of free tissue grafts from various donor sites. The causes of the skull base defects in this series included neurosurgical procedures (9), functional endoscopic sinus surgery (8), and trauma (3). Defects occurred spontaneously in 9 cases. The fovea ethmoidalis and sphenoid sinus were the site in 11 and 12 cases, respectively, and the cribriform plate was involved in 6 cases. Cerebrospinal fluid rhinorrhea was documented by nasal endoscopy with or without intrathecal fluorescein, laboratory studies, computed tomography with or without contrast cisternography, and radioisotope cisternography in various combinations. Resolution of cerebrospinal fluid rhinorrhea was achieved in 22 of 29 patients (75.9%) with one endoscopic procedure and 25 of 29 patients (86.2%) after a second attempt. Four patients required neurosurgical intervention for recurrent cerebrospinal fluid rhinorrhea. Complications were minimal and were related primarily to the original pathology or procedure. Cerebrospinal fluid rhinorrhea can be managed safely and effectively with endoscopic techniques in a majority of cases, and the morbidity of open procedures can be avoided.

Adult↗

Cerebrospinal fluid lactate level in childhood purulent meningitis.

Cerebrospinal fluid lactate was determined in 54 pediatric patients by means of enzymatic method of Marbach and Weil. The mean value of cerebrospinal fluid lactate in 13 purulent meningitis patients was 80.4 mg/dl, in 9 clinical purulent meningitis patients was 72.7 mg/dl, in 18 non-purulent meningitis patients and 14 controls were 17.0 and 11.8 mg/dl respectively. The present study demonstrated that a cerebrospinal fluid lactate level of 35 mg/dl may be used as a cut off point to differentiate bacterial from non-bacterial infection of the central nervous system. It should served as a supplementary aid to clinical examinations and conventional methods to diagnose bacterial meningitis.

Child, Preschool↗

Laboratory testing on cerebrospinal fluid. A reappraisal.

555 consecutive cases in which cerebrospinal fluid (CSF) was sent for cell count were reviewed to determine which cerebrospinal-fluid tests affect diagnosis or therapy. Among 334 cases (60%) with a normal opening pressure, cell count, and protein, 1385 additional tests were done, but such tests were useful in only 3 patients (0.9%) with multiple sclerosis. Among 148 consecutive cases of bacterial, chronic infectious, and malignant meningitis the opening pressure, cell count, or protein was abnormal in all but 3 (2 childhood bacterial meningitis and 1 cryptococcal meningitis in a patient with the acquired immunodeficiency syndrome). If the opening pressure, cell count, and protein are normal, no additional CSF tests are needed in most instances; however, in immunocompromised patients and in those with possible multiple sclerosis or childhood bacterial meningitis additional tests may be indicated.

Adolescent↗

Electrophoresis of normal lumbar cerebrospinal fluid proteins in the African.

Lumbar cerebrospinal fluid obtained from Zambian patients suspected of suffering from central nervous system conditions was concentrated over a hundred-fold and subjected to small-scale cellulose acetate electrophoresis (Millipore). The percentage of each protein fraction was determined by scanning. Only twenty samples were considered normal out of a total of 150 studies. These normal values were not statistically different from those of published data on Europeans and North American Caucasians. The high serum gamma globulin in African subjects is not reflected in the cerebrospinal fluid.

Adolescent↗

Cellular lining of the sheep pineal recess studied by light-, transmission-, and scanning electron microscopy: morphologic indications for a direct secretion of melatonin from the pineal gland to the cerebrospinal fluid.

In the sheep, the pineal hormone melatonin displays nocturnal levels 20 times as high in the cerebrospinal fluid of the third ventricle as in the jugular blood. Moreover, in the pineal recess, the evagination of the third ventricle into the pineal stalk, the levels of melatonin in the cerebrospinal fluid are even higher than in the ventral part of the third ventricle. This finding suggests melatonin to be secreted directly from the pineal gland to the ventricular lumen of the pineal recess of this species. We have, therefore, studied the interface between the sheep pineal gland and the cerebrospinal fluid by light-, scanning-, and electron microscopy of the pineal recess, as well as the permeability of the interface by tracer injections into the third ventricle. First, we show that the classic ependymal lining of the third ventricle disappears in the superior part of the recess. In this area, bulging pinealocytes, displaying immunoreactivity for serotonin, directly appose the cerebrospinal fluid. This pineal-cerebrospinal fluid interface of the sheep is large compared with other species, especially rodent species. Intraventricular injections of horseradish peroxidase and fluorescein isothiocyanate showed that both these tracers could permeate from the pineal recess into the sheep pineal parenchyma. This permeation was due to the presence of gap and intermediate junctions connecting the pinealocytes apposing the ventricular lumen. Thus, our results show that endocrine cells in this specialized area of the ventricular system are in direct contact with the cerebrospinal fluid. This finding supports the physiological concept of a direct secretion of melatonin into the cerebrospinal fluid of the sheep pineal recess.

Animals↗

Increased concentrations of cholestanol and apolipoprotein B in the cerebrospinal fluid of patients with cerebrotendinous xanthomatosis. Effect of chenodeoxycholic acid.

We investigated the effect of chenodeoxycholic acid on cerebrospinal fluid sterol and protein composition in six patients with cerebrotendinous xanthomatosis, a progressive neurologic disease, and in 11 control subjects. In the cerebrospinal fluid from the controls, the mean (+/- SD) levels of cholesterol and cholestanol were 400 +/- 300 and 4 +/- 7 micrograms per deciliter, respectively. The levels were almost 1.5 and 20 times higher in cerebrospinal fluid from untreated patients with cerebrotendinous xanthomatosis. Cholestanol levels were also markedly elevated in the plasma of untreated patients, but their plasma cholesterol levels (215 +/- 61 mg per deciliter) were not different from control values. Treatment with chenodeoxycholic acid reduced cerebrospinal fluid cholesterol by 34 percent and cholestanol threefold. Plasma cholestanol levels also decreased sharply. Normal cerebrospinal fluid contained small quantities of albumin, apolipoproteins, and lecithin:cholesterol acyltransferase. In cerebrospinal fluid from untreated patients with cerebrotendinous xanthomatosis, immunoreactive apolipoprotein B or apolipoprotein B fragment was increased about 100-fold and albumin about 3.5-fold; apolipoprotein AI, apolipoprotein D, and lecithin:cholesterol acyltransferase were 1.5 to 3 times more concentrated. Apolipoprotein AIV and apolipoprotein E concentrations were comparable to those in controls, and apolipoprotein AII was considerably decreased. During treatment, the concentrations of albumin and apolipoproteins AI and B declined. These results suggest that increased cerebrospinal fluid sterols are derived from plasma lipoproteins by means of a defective blood-brain barrier in patients with cerebrotendinous xanthomatosis. Therapy with chenodeoxycholic acid reestablished selective permeability of the blood-brain barrier and normalized the concentrations of sterol and apolipoprotein in the cerebrospinal fluid.

Albumins↗

Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using 111indium-DTPA ventriculography.

Cerebrospinal fluid flow dynamics were evaluated by 111Indium-diethylenetriamine pentaacetic acid (111In-DTPA) ventriculography in 27 patients with neoplastic meningitis. Nineteen patients (70 percent) had evidence of cerebrospinal fluid flow disturbances. These occurred as ventricular outlet obstructions, abnormalities of flow in the spinal canal, or flow distrubances over the cortical convexities. Tumor histology, physical examination, cerebrospinal fluid analysis, myelograms, and computerized axial tomographic scans were not sufficient to predict cerebrospinal fluid flow patterns. These data indicate that cerebrospinal fluid flow abnormalities are common in patients with neoplastic meningitis and that 111In-DTPA cerebrospinal fluid flow imaging is useful in characterizing these abnormalities. This technique provides insight into the distribution of intraventricularly administered chemotherapy and may provide explanations for treatment failure and drug-induced neurotoxicity in patients with neoplastic meningitis.

Cerebral Ventriculography↗

Percutaneous computer tomography-guided technique to close postsurgical cerebrospinal fluid fistulas of the frontal sinus.

BACKGROUND: The occurrence of cerebrospinal fluid fistulas of the frontal sinus after anterior skull base surgery is not rare. The extracerebral techniques to repair cerebrospinal fluid fistulas are often used, especially because they avoid open-air surgical operations. METHODS: A percutaneous CT-guided technique to close postsurgical cerebrospinal fluid fistulas of the frontal sinus in three patients after anterior skull base surgery is presented in this report. Ten millimeters of human fibrin glue was injected into the frontal sinus through one of the burr holes of the bone flap by an 18-gauge spinal needle. RESULTS: After an average follow-up period of 2.8 years, all three patients are in excellent general and neurological conditions and have not shown any further signs of rhinoliquorrhea. CONCLUSIONS: The presented percutaneous CT-guided technique can be considered a valid and harmless solution to closer small or moderate cerebrospinal fluid fistula that occurred after anterior skull base surgery.

Adult↗

The effects of human serum and cerebrospinal fluid on retroviral vectors and packaging cell lines.

Human serum is known to inactivate many retroviruses, including murine leukemia viruses (MLV). Exposure of vectors based on MLV to human serum components would presumably decrease the efficiency of gene transfer in vivo. Human serum also lyses xenogeneic cells, which would affect the survival of retroviral vector packaging cells in vivo. The effects of other body fluids, such as cerebrospinal fluid (CSF), on MLV vectors and packaging lines have not been studied. We have found that retroviral vectors packaged in ecotropic, amphotropic, and gibbon ape leukemia virus (GALV) envelope proteins were all inactivated by human sera, and human sera also lysed mouse NIH-3T3 cells and the retroviral vector packaging cells derived from them. Human fibroblasts producing amphotropic vector particles were resistant to lysis, but the particles produced by them were inactivated. In contrast, CSF did not inactivate MLV vectors, nor did it lyse murine retrovirus packaging cells. Our results suggest that exposure to human serum may prevent in vivo gene transfer by MLV vectors and xenogeneic packaging lines, but gene transfer within the central nervous system should be more successful.

3T3 Cells↗

Incidence of cerebrospinal fluid leak after microsurgical removal of vestibular schwannomas.

OBJECTIVES: Cerebrospinal fluid (CSF) leak still remains an unresolved problem after microsurgical removal of vestibular schwannomas (VS). METHODS: 14 (6%) Cases of cerebrospinal fluid rhinorrhea and 3 cases with subcutaneous retro-auricular CSF collection, occurring in a series of 224 patients operated on by the senior author (JMG) on VS between 1989-2000 via the suboccipital retrosigmoidal approach were studied retrospectively. Prophylaxis of CSF leak was usually attempted by packing the unroofed posterior wall of internal acoustic meatus with muscle. The mastoid air cells were packed first with collagen then with muscle and bone dust. RESULTS: All CSF leaks were diagnosed within 2-7 days after surgery. We found no relation to tumour size. Treatment was initiated in all patients with continuous external lumbar cerebrospinal fluid drainage (CELCFD) for 7 days. In 11 cases with CSF rhinorrhea and all cases with retro-auricular CSF collection, the CSF leak was stopped. However, in 3 cases the CSF leak persisted despite the lumbar drain. These patients were operated on again with sealing the IAM and the mastoid cells again with muscle and collagen. No recurrence of CSF leak was noted after the second operation. There was no case of late onset CSF leak during the follow-up of one year. CONCLUSION: Although CSF leak is a common complication (6%) after vestibular schwannoma removal, aggressive treatment is required only in a few cases (1%). Most of the cases are successfully treated by (CELCFD). The suboccipital approach offers an advantage of opening only a part of mastoid air cells, which are in our opinion the second most common site of CSF leakage.

Bone Transplantation↗