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Human cerebrospinal fluid acetylcholinesterase and butyrylcholinesterase. Evidence for identity between the serum and cerebrospinal fluid butyrylcholinesterase.

Human cerebrospinal fluid contained both acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8) and they were estimated in the presence of selective inhibitors. Butyrylcholinesterase of human cerebrospinal fluid was similar to human serum butyrylcholinesterase in its electrophoretic mobility, glycoprotein nature and tyramine activation of the aryl acylamidase (EC 3.5.1.13) activity exhibited by butyrylcholinesterase. Moreover antibody raised against human serum purified butyrylcholinesterase could completely immunoprecipitate butyrylcholinesterase from human cerebrospinal fluid without affecting acetylcholinesterase. It is suggested that a useful method for the precise determination of acetylcholinesterase in human cerebrospinal fluid would be removal of butyrylcholinesterase by immunoprecipitation using antibody raised against human serum butyrylcholinesterase.

Acetylcholinesterase↗

[Brain barriers. Part II. Blood/cerebrospinal fluid barrier and cerebrospinal fluid /brain tissue barrier].

Brain has its own unique and effective protection system that controls the process of active transport of chemical substances from blood to neurons and cerebrospinal fluid. The above mentioned system is called the blood brain barrier. As far as morphology is concerned the barrier consists of several membranes isolating the following compartments of the intracranial space: brain tissues, blood and cerebrospinal fluids. One of those membranes-blood/brain tissues barrier, has been described in the first part of this work. Structure and function of the blood/CSF barrier and CSF/brain tissues barrier are described in the second part.

Blood-Brain Barrier↗

Microdialysis sampling of carbamazepine, phenytoin and phenobarbital in subcutaneous extracellular fluid and subdural cerebrospinal fluid in humans: an in vitro and in vivo study of adsorption to the sampling device.

The purpose of the study was to determine if binding of the drugs to the sampling equipment during microdialysis would influence the results for carbamazepine, phenytoin and phenobarbital. In vitro experiments with microdialysis catheters and separate parts of catheters were performed to estimate the degree of drug binding to the dialysis equipment. A mathematical model to calculate drug binding and recovery is proposed. In vivo protein unbound carbamazepine concentrations in subcutaneous extracellular fluid at different flow rates (6 patients), unbound carbamazepine (1 patient) and unbound phenobarbital (I patient) in subdural cerebrospinal fluid and subcutaneous extracellular fluid were estimated and the in vivo data were compared to the in vitro results and data generated by the mathematical model. Binding to the soft outlet polyurethane tubing was extensive and variable for phenytoin, which precluded in vivo testing, but limited and more predictable for carbamazepine and phenobarbital. None of the three compounds bound to the hard internaltubing. Phenytoin and phenobarbital did not bind to the dialysis membrane, while a small degree of binding may be present for carbamazepine. In vivo estimates of carbamazepine protein unbound subcutaneous extracellular concentrations by microdialysis, adjusted for binding to the plastic tubing, were 81% of protein unbound plasma concentrations. In single case studies, subdural cerebrospinal fluid and subcutaneous extracellular levels of carbamazepine and phenobarbital were similar and when corrected for binding to the plastic tubings they were also close to protein unbound plasma concentrations. Microdialysis can be used for reliable estimations of protein unbound carbamazepine and possibly phenobarbital concentrations when drug binding to the plastic tubing is considered. Reliable estimation of unbound phenytoin is not possible at present.

Adult↗

Cerebrospinal fluid pressure monitoring after repair of cerebrospinal fluid leaks.

OBJECTIVE: To measure intracranial pressures (ICPs) via lumbar drains after surgical repair of cerebrospinal fluid (CSF) leaks. METHODS: We conducted a retrospective review of ICP measurements through lumbar drains during the immediate postoperative period after CSF leak repair. RESULTS: Eight patients with spontaneous CSF leaks underwent surgery and postoperative CSF pressures were measured via lumbar drains. ICP was elevated in 7/8 patients (mean, 32.5 cm H(2)O). Diuretics reduced ICP (mean, 10 cm H(2)O). Three traumatic CSF leaks patients served as controls (mean, ICP 14 cm H(2)O). CONCLUSION: Measurement of ICP through lumbar drains provides important information regarding the pathophysiology of CSF leaks that has an impact on subsequent medical and surgical treatment. Although the precise cause and mechanism of spontaneous CSF leaks are not fully understood, this study indicates that elevated ICP plays a role and that further medical or surgical treatment to correct the intracranial hypertension may be warranted.

Adult↗

Towards a high resolution separation of human cerebrospinal fluid.

Human cerebrospinal fluid is an ultrafiltrate of plasma that is largely produced by the choroid plexus. It consists of a mixture of anorganic salts, various sugars, lipids and proteins from the surrounding brain tissues. The predominant proteins in cerebrospinal fluid are isoforms of serum albumin, transferrin and immunoglobulins, representing more than 70% of the total protein amount. A rough overview of the protein compounds of human cerebrospinal fluid including their respective concentrations is given by Blennow et al. [Eur. Neurol. 33 (1993) 129]. In contrast, the aim of this work is to display the detailed protein composition of CSF by two-dimensional gel electrophoresis and to identify both high and low concentrated proteins using different mass spectrometry techniques. This extensive overview of proteins in human cerebrospinal fluid will be highly relevant for clinical research. Furthermore, the comparison of 2D gels will help to analyze the standard protein variability in CSF of healthy persons and detect specific protein variations of patients with various neurological diseases (e.g., Alzheimer's disease, Huntington's chorea). Sample preparation for two-dimensional gel electrophoresis must include concentration and desalting steps such as precipitation and ultrafiltration due to the high amount of salts, sugars and lipids and the low total amount of protein of 0.3-0.7 microg/microl present in human CSF. Up to now we were able to identify more than 480 spots from suchlike generated 2D gels using MALDI- and ESI-mass spectrometry.

Amino Acid Sequence↗

Management of traumatic cerebrospinal fluid fistula.

Cerebrospinal fluid fistulae present a common management problem for the surgeon managing craniofacial trauma. Controversies exist concerning various aspects of treatment. These controversial management issues include cerebrospinal fluid drainage, antibiotic prophylaxis, timing of surgical intervention, and techniques of repair. Although most cerebrospinal fluid fistulae cease spontaneously, some fistulae persist, resulting in the potential for life-threatening complications. A review of these issues is presented, together with a suggested management protocol.

Algorithms↗

Rate of cerebrospinal fluid formation, resistance to reabsorption of cerebrospinal fluid, brain tissue water content, and electroencephalogram during desflurane anesthesia in dogs.

Intracranial pressure (ICP) has been shown to increase dramatically during desflurane anesthesia, possibly as a result in part of an increase in the rate of cerebrospinal fluid (CSF) formation (Vf) or a decrease in the rate of CSF reabsorption. To examine this phenomenon, I designed a study to measure Vf, resistance to reabsorption of CSF (Ra), brain tissue water content, and the electroencephalographic activity (EEG) during desflurane anesthesia in dogs. Vf and Ra were determined using ventriculocisternal perfusion of mock CSF labeled with blue dextran. EEG activity was determined using aperiodic analysis. At the end of the study, brain tissue water contents of gray and white matter were determined by dry/wet weight ratios. Eighteen dogs were allocated into three groups. Group 1 (n = 6) was examined at five experimental conditions during normocapnia; group 2 (n = 6) was examined at five experimental conditions during hypocapnia. The experimental conditions for groups 1 and 2 were (a) baseline (halothane 0.5-1.0% inspired plus thiopental 12 mg.kg-1 i.v. given over 15 min followed by i.v. infusion at 12 mg.kg-1 x h-1), (b) 0.5 MAC (3.5 +/- 0.1% expired) and (c) 1.0 MAC (7.0 +/- 0.1% expired) desflurane at normal CSF pressure, and (d) and (e) 0.5 and 1.0 MAC desflurane at increased CSF pressure (> 30 cm H2O). Group 3 (n = 6), the control group, was examined over the same time period as groups 1 and 2. In the control group, desflurane was not administered; instead, the baseline condition (i.e., halothane plus thiopental) was maintained throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗

Histamine metabolites and pros-methylimidazoleacetic acid in human cerebrospinal fluid.

In cerebrospinal fluid, levels of the histamine metabolites, tele-methylhistamine and tele-methylimidazole-acetic acid, were higher in elderly than in young people, and women had higher levels than men. Therefore, age and gender should be considered in studies of histamine metabolites as exemplified by their measurements in cerebrospinal fluid of patients with Huntington's disease. Levels of pros-methylimidazoleacetic acid, an isomer of tele-methylimidazoleacetic acid and not a metabolite of histamine, were higher in cerebrospinal fluid of men than of women. Levels of pros-methylimidazoleacetic acid in cerebrospinal fluid were highly positively correlated with the severity of Parkinson's disease in a group of non-medicated, mildly to moderately affected patients.

Adult↗

Spontaneous cerebrospinal fluid leaks: from intracranial hypotension to cerebrospinal fluid hypovolemia--evolution of a concept.

Intracranial hypotension causes orthostatic headaches and diffuse pachymeningeal gadolinium enhancement on magnetic resonance imaging with or without subdural fluid collections or imaging evidence of descent of the brain. A review of the literature and my experience and investigations in the past decade reveal a broadening clinical and imaging spectrum of the syndrome. Besides the classic clinical-imaging syndrome of orthostatic headaches, diffuse pachymeningeal gadolinium enhancement, and low cerebrospinal fluid (CSF) pressure, several modes of presentation are recognized, including (1) the typical clinical-imaging syndrome with CSF pressures consistently within normal limits, (2) absence of diffuse pachymeningeal gadolinium enhancement with presence of low CSF pressures and typical clinical manifestations, and (3) absence of headaches despite low CSF pressures and presence of diffuse pachymeningeal gadolinium enhancement. Furthermore, in some patients with headaches, the orthostatic headaches may evolve into lingering chronic daily headaches, although they may be more prominent in upright positions. What determines the various clinical and imaging features of this syndrome seems to be the loss of CSF volume as the independent variable, while other manifestations, including clinical features, CSF pressures, and imaging abnormalities, are variables dependent on the CSF volume. The term CSF hypovolemia is proposed for this syndrome because the term intracranial hypotension no longer seems adequate to embrace all the variations that have emerged.

Cerebrospinal Fluid Pressure↗

Cerebrospinal fluid viral load, intrathecal immunoactivation, and cerebrospinal fluid monocytic cell count in HIV-1 infection.

To assess the association between cerebrospinal fluid (CSF) viral load, intrathecal immunoactivation, and immunosuppression in HIV-1-infected individuals with no antiretroviral treatment experience a cross-sectional study of stored frozen CSF and plasma samples were conducted. The study population included a total of 120 antiretroviral-naive HIV-1-infected patients, 110 neuroasymptomatic patients, and 10 with neurologic complications. HIV-1 RNA was quantified in cell-free CSF and plasma using polymerase chain reaction (PCR; Roche Amplicor HIV-1 Monitor version 1.5, Roche Diagnostic Systems, Hoffmann-La Roche, Inc., Base, Switzerland). Immunoactivation was measured by CSF-serum IgG index, CSF neopterin concentrations, and CSF monocytic cell count. The CSF HIV-1 RNA load did not differ significantly between patients with or without neurologic complications. In patients without neurologic symptoms, the CSF monocytic cell counts were correlated to the CSF viral load (r(s) = 0.40, p < .001), whereas IgG index and CSF neopterin concentrations were correlated to the viral load only in the subgroup of patients with CD4 counts > or =200 x 10(6) cells/L. In this subgroup of patients, the peripheral CD4 cell count was, as expected, inversely correlated to the CSF viral load (r. = -0.36, p < .01), whereas in patients with CD4 counts <200 x 10(6) cells/L, an unexpected, significant positive correlation (r(s) = 0.43, p < .01 ) was found. In HIV-1-infected patients with neurologic complications, no significant correlations were found between immune activation, CSF viral load, and immunosuppression.

AIDS Dementia Complex↗

Tubal and tympanic openings of the peritubal cells: implications for cerebrospinal fluid otorhinorrhea.

Cerebrospinal fluid otorhinorrhea after surgery for cerebellopontine angle tumors may persist despite obliteration of the mastoid, middle ear, and tympanic orifice of the eustachian tube. In this study, histologic sections of 120 adult temporal bones were examined by light microscopy to determine the incidence of peritubal pneumatization and to demonstrate the frequency of tubal and tympanic openings of the peritubal cells. The results of this study suggest that the pathway for these persistent cerebrospinal fluid leaks may be via the peritubal cells that open directly into the eustachian tube anterior to its tympanic orifice. Peritubal pneumatization was present in 78 (65%) of the temporal bones. Of the 57 specimens in which the openings of the peritubal cells could be identified, in 52 (91%), the cells opened into the eustachian tube anterior to its tympanic orifice, and in only five (9%), they opened into the middle ear. The overall incidence of tubal openings in this study was 59%. In 13 temporal bones (21%), the tubal opening were at a distance of > 5 mm anterior to the tympanic orifice of the eustachian tube. Therefore, cerebrospinal leak may persist through these tubal openings despite obliteration of the mastoid, middle ear, and tympanic orifice of the eustachian tube. A case of persistent cerebrospinal fluid leak in which extensive peritubal pneumatization was demonstrated by computed tomography scan is presented. Successful control of the leak was obtained only after the tubal openings of these cells several millimeters anterior to the tympanic orifice were obliterated.

Cerebrospinal Fluid Rhinorrhea↗

Continuous cerebrospinal fluid drainage using a lumbar subarachnoid catheter for cerebrospinal fluid rhinorrhea after functional endoscopic sinus surgery.

Anesthesiologists are frequently consulted for performing lumbar cerebrospinal fluid (CSF) drainage to facilitate surgery or manage complications. Functional endoscopic sinus surgery (FESS) is a common treatment for chronic sinus diseases. Cerebrospinal fluid (CSF) leakage is a serious complication following FESS and is typically treated with an endonasal free or rotational mucoperichondrial flap. Continuous drainage of CSF with a lumbar subarachnoid catheter has been used in patients who have undergone neurosurgery but it is seldom used in the treatment of post-FESS CSF rhinorrhea. We present a 71-year-old male patient who suffered from CSF rhinorrhea after FESS, and was treated successfully with continuous lumbar CSF drainage. We are of the opinion that continuous CSF drainage with a lumbar subarachnoid catheter is an effective and safe modality of treatment for post-FESS CSF leakage.

Aged↗

Cerebrospinal fluid tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and interleukin-8 as diagnostic markers of cerebrospinal fluid infection in neurosurgical patients.

OBJECTIVE: To evaluate whether cerebrospinal fluid concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, or IL-8 may be used as diagnostic markers for the differential diagnosis of aseptic vs. bacterial meningitis and/or ventriculitis in neurosurgical patients. DESIGN: Prospective, observational study. SETTING: University teaching hospital. SUBJECTS: A total of 112 cerebrospinal fluid samples from 14 asymptomatic patients with normal cerebrospinal fluid after neurosurgery, 27 asymptomatic and 19 symptomatic patients with postneurosurgical aseptic meningitis, 32 patients with postneurosurgical cerebrospinal fluid infection, and 20 with severe subarachnoid and/or cerebral hemorrhage. MEASUREMENTS AND MAIN RESULTS: Specific ELISA kits were used to analyze TNF-alpha, IL-1beta, IL-6, and IL-8 concentrations on cerebrospinal fluid samples. Elevations in cerebrospinal fluid concentrations of TNF-alpha, IL-1beta, IL-6, and IL-8 were induced by different diseases or neurosurgical procedures, but cerebrospinal fluid bacterial infection induced the highest concentrations. To discriminate between aseptic cerebrospinal fluid pleocytosis and cerebrospinal fluid infection with a specificity of 95%, cerebrospinal fluid leukocyte count >1700/mL, TNF-alpha >150 pg/mL, and IL-1beta >90 pg/mL showed sensitivities of 51%, 74%, and 90%, respectively. Sufficiently sensitive and specific cutoff points could not be found for cerebrospinal fluid IL-6 or IL-8. CONCLUSION: Cerebrospinal fluid IL-1beta appears to be the best biochemical marker of cerebrospinal fluid infection in neurosurgical patients.

Adolescent↗

[IgG determination in the cerebrospinal fluid--correlation of these results with other cerebrospinal fluid values].

IgG determined by means of quantitative radial immunodiffusion in the cerebrospinal fluid of 225 neurological patients correlates in a statistically significant manner (p less than 0.001) with the gamma-globulin determined by the acetate foil electrophoresis. The indication of the IgG as a percentage of the total protein (limiting value of 10 per cent) is suitable for an orientating assessment in the diagnosis of inflammatory-immunoreactive diseases of the central nervous system. The IgG-values exceeding 10 per cent of the total protein correlate in 260 fluids examined in the respect with the percental value of the lymphocyte content which also lies above the reference range (p less than 0.001). For the assessment of the presence of a barrier disturbance, a comparison with the serum values should be carried out, either in the form of the frequently used fluid/serum quotients of the immunglobulin or the electrophoretically separated protein fraction.

Cerebrospinal Fluid Proteins↗

Dose-related changes in the rate of cerebrospinal fluid formation and resistance to reabsorption of cerebrospinal fluid following administration of thiopental, midazolam, and etomidate in dogs.

The rate of cerebrospinal fluid (CSF) formation (Vf) and resistance to reabsorption of CSF (Ra) were determined in dogs at four doses of thiopental (6, 12, 18, and 24 mg.kg-1.h-1), midazolam (0.5, 1.0, 1.5, and 2.0 mg.kg-1.h-1), and etomidate (0.86, 1.72, 2.58, and 3.44 mg.kg-1.h-1). Results were compared within and between groups and to previously reported normal values for Vf (0.030-0.054 ml/min) and Ra (220-240 cmH2O.ml-1.min) in dogs. At the two lower doses of thiopental, midazolam, or etomidate Vf was not significantly different than previously reported normal values. At the two higher doses of each drug Vf was 0.019-0.024 ml/min, significantly reduced compared to Vf at the two lower doses of each drug. The pattern of Ra data was more varied. With thiopental Ra was elevated at the lowest dose, (354 +/- 17 cmH2O.ml-1.min, mean +/- SD) reduced at the highest dose (156 +/- 19 cmH2O.ml-1.min), and not significantly different than previously reported normal values at the two intermediate doses. With midazolam Ra was elevated at the lowest and highest doses (332 +/- 25 and 378 +/- 18 cmH2O.ml-1.min) and normal at the two intermediate doses. With etomidate Ra was normal at the three lower doses and reduced at the highest dose (187 +/- 13 cmH2O.ml-1.min). It is concluded that CSF volume may be increased and the CSF pressure at which CSF volume contracts may be increased by doses of thiopental or midazolam that increase Ra, but not increased by etomidate.

Absorption↗