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Identification of intranasal cerebrospinal fluid leaks by topical application with fluorescein dye.

The purpose of this paper is to describe a safe new technique for intraoperative identification of the site of cerebrospinal fluid rhinorrhea. Cerebrospinal fluid (CSF) rhinorrhea after intracranial or intranasal surgery is a known potential complication with significant morbidity and mortality. It is currently accepted that endoscopic intranasal management of CSF rhinorrhea is the preferred method of surgical repair, with higher success rates and less morbidity than intracranial surgical repair in selected cases. Accurate identification of the site of CSF leakage is necessary for a successful endoscopic surgical repair. Computer tomography (CT) with or without intrathecal contrast and preoperative nasal endoscopy are frequently used to preoperatively localize the site of the leak. Intrathecal fluorescein administered immediately before surgery has aided in the intraoperative identification of the site of CSF leak in 25-64% of patients undergoing endoscopic repair of CSF rhinorrhea in whom preoperative CT scanning and nasal endoscopy had not identified the site of CSF leak. Intrathecal fluorescein, however, has been associated with severe complications, such as lower extremity weakness, numbness, generalized seizures, opisthotonus, and cranial nerve deficits. We present three cases of CSF rhinorrhea in which fluorescein was applied intranasally during the endoscopic surgical repair. Ten percent fluorescein was applied to the nose with a cotton swab. Under endoscopic visualization the fluorescein changed its fluorescent color from amber/yellow to a dark green and was found streaming from high in the nasal cavity, which led to accurate identification of the site of the CSF leak.

Administration, Topical↗

Cerebrospinal fluid proteins in men with chronic encephalopathy after exposure to organic solvents.

Cerebrospinal fluid was examined for 23 patients with chronic toxic encephalopathy after heavy exposure to organic solvents and 23 healthy age-matched referents. No differences were found between the patients and referents with respect to the levels of albumin, immunoglobulin, prealbumin, alpha-1-antitrypsin, beta-2-microglobulin, haptoglobin, or the astroglial cell proteins S100 and glial fibrillary acidic protein in the cerebrospinal fluid. The albumin ratio was normal for both the patients and the referents. The patient group had had heavy exposure to organic solvents, but its members had not been exposed for at least one year before the study. It was concluded that, if exposure to organic solvents affects proteins in cerebrospinal fluid, such effects are probably reversible.

Adult↗

Autologous fibrin glue in the prevention of cerebrospinal fluid leak following acoustic neuroma surgery.

Postoperative cerebrospinal fluid (CSF) leak is a serious complication of acoustic neuroma surgery. The authors retrospectively reviewed the charts of 492 patients who underwent acoustic neuroma surgery to determine the efficacy of fibrin glue in preventing postoperative CSF leak. Thirteen of 92 patients (14%) undergoing retrosigmoid/transmeatal surgery experienced CSF leak when fibrin glue was used; 29 of 199 patients (15%) when it was not used. Nineteen of 85 patients (22%) experienced CSF leak when fibrin glue was used following translabyrinthine surgery; 23 of 116 patients (20%) when it was not used. No decrease was noted in the incidence of CSF leak following acoustic neuroma surgery with the use of autologous fibrin glue.

Cerebrospinal Fluid Otorrhea↗

Proteomic analysis of the cerebrospinal fluid of patients with schizophrenia.

We applied proteomics technologies to analyze the cerebrospinal fluid of patients with schizophrenia. Such an analysis can result in the identification of proteins, which may play a role in the disease progress and thus lead to the discovery of clues of the etiology of schizophrenia. Cerebrospinal fluid from patients and controls was analyzed by two-dimensional gels and the proteins were identified by matrix-assisted laser desorption ionization mass spectrometry (MS) in the MS and MS/MS mode. 54 different gene products were identified, which were mainly plasma proteins. The level of apolipoprotein A-IV was significantly decreased in the schizophrenic patients compared to that in the controls. Little is known about the function of this apolipoprotein in the central nervous system. The levels of certain other proteins, like haptoglobin, fibrinogen, complement component 3, and Gc-globulin, were altered in the disease group as well, however, the changes did not reach a statistical significance.

Apolipoproteins A↗

Subtotal petrosectomy in the treatment of cerebrospinal fluid fistulae of the lateral skull base.

Cerebrospinal fluid (CSF) fistulae almost invariably lead to meningitis, even in the absence of other clinically obvious sequelae of the fistula such as a CSF fluid leak. The only effective means of reducing the risk of meningitis is surgical closure of the fistula. If surgery is to be recommended to patients with CSF fistulae even if they are currently asymptomatic, the morbidity of the procedure must be a principal determinant of the chosen technique. Recovery after the extracranial approach to a CSF fistula is much more rapid than after an intracranial procedure. The extracranial route is also free of the long-term risk of epilepsy which accompanies a craniotomy. The principal disadvantage of the lateral extracranial approach, failure of treatment, has been largely eliminated following studies into the obliteration of simple bony cavities using free adipose grafts. This paper describes our use of the extracranial approach to closure of CSF fistulae of the lateral skull base.

Adult↗

Interferon-gamma secretion by in vivo activated cytotoxic T lymphocytes from the blood and cerebrospinal fluid during mumps meningitis.

Functional studies of cerebrospinal fluid T lymphocytes during acute viral infections of the nervous system are rare. Recently, we had the opportunity to investigate the requirements for interferon-gamma (IFN-gamma) production of human in vivo activated (primary) cytotoxic T lymphocytes (CTL) generated during acute viral meningitis. Two HLA-B7-restricted, CD4-, CD8+ CTL clones from cerebrospinal fluid of one patient with mumps meningitis were studied. Although lytic activity was restricted by HLA-B7, the clones produced similar amounts of IFN-gamma when stimulated with HLA-matched and mismatched mumps virus-infected target cells. In addition, peripheral blood mononuclear cells of infected patients secreted significant amounts of IFN-gamma when incubated with autologous or allogeneic (HLA-A/B-mismatched) mumps virus-infected target cells. T cells capable of lytic activity and IFN-gamma secretion could only be isolated from venous blood during the initial phase of the infection. We suggest that the ability of human in vivo activated CTL to secrete INF-gamma early during the course of inflammation and in a HLA-unrestricted fashion is important for the elimination of viruses invading the central nervous system.

Child, Preschool↗

Reference values for cerebrospinal fluid glutamine concentration in infants.

We measured cerebrospinal fluid glutamine concentration in a reference group of 85 newborn to 30-month-old infants. All of the spinal taps were performed for the diagnosis of illnesses unrelated to hyperammonemia or hepatic encephalopathy. We also analyzed samples from patients with meningitis or cerebral hemorrhage, or who were receiving total parenteral nutrition. The mean glutamine concentration in cerebrospinal fluid in the reference group was somewhat lower than values reported for older children and adults. Values were significantly higher in patients with meningitis or cerebral hemorrhage and in those infants receiving total parenteral nutrition.

Age Factors↗

Effects of ritonavir on indinavir pharmacokinetics in cerebrospinal fluid and plasma.

Therapeutic control of human immunodeficiency virus type 1 (HIV-1) in peripheral compartments does not assure control in the central nervous system. Inadequate drug penetration may provide a sanctuary from which resistant virus can emerge or allow development of psychomotor abnormalities. To characterize the effect of ritonavir on indinavir disposition into cerebrospinal fluid, seven HIV-infected adults underwent intensive sampling at steady-state while receiving twice-daily indinavir (800 mg) and ritonavir (100 mg). Serial cerebrospinal fluid and plasma samples were obtained at 10 time points from each subject. Free indinavir accounted for 98.6% of drug in cerebrospinal fluid and 55.9% in plasma. Mean cerebrospinal fluid C(max), C(min), and area under the concentration-time curve from 0 to 12 h (AUC(0-12)) values for free indinavir were 735 nM, 280 nM, and 6502 nM h(-1), respectively, and the free levels exceeded 100 nM in every sample. The cerebrospinal fluid/plasma AUC(0-12) ratio for free indinavir was 17.5% +/- 6.4%. This ratio was remarkably similar to results obtained in a previous study in which subjects received indinavir without ritonavir, indicating that ritonavir did not have a substantial direct effect on the barrier to indinavir penetration into cerebrospinal fluid. Low-dose ritonavir increases cerebrospinal fluid indinavir concentrations substantially more than 800 mg of indinavir given thrice daily without concomitant ritonavir, despite a lower total daily indinavir dose.

Adult↗

Tau protein in the cerebrospinal fluid is a marker of brain injury after aortic surgery.

BACKGROUND: Tau is a protein localized primarily in neurons, especially in the axonal compartment. Cerebrospinal fluid tau levels are elevated in acute stroke and head traumas. The purpose of this study is to elucidate the alterations of cerebrospinal fluid tau levels in patients with or without neurologic complication after aortic surgery. METHODS: Twenty-eight patients undergoing descending thoracic (n = 8) or thoracoabdominal (n = 20) aortic surgery were enrolled. Cerebrospinal fluid tau levels were measured before operation and at seven time points up to the 72nd postoperative hour, and were compared with cerebrospinal fluid S100B levels. RESULTS: Two patients developed brain infarction, including the one with paraplegia. In these patients, 20-fold to 100-fold tau elevation was observed, but S100B elevation was less evident in the patient without paraplegia. Three other patients developed spinal cord injury. Additional three patients suffered from temporary neurologic dysfunction of the brain. Tau levels in the latter three patients showed tenfold elevation and were higher than those in the three patients with spinal cord injury or those in the patients without neurologic complication up to 24 postoperative hours. The S100B levels were also higher in the three patients with temporary neurologic dysfunction of the brain than in the patients without neurologic complication at the conclusion of surgery. From 6 to 24 postoperative hours, they were higher in the three patients with spinal cord injury than in the patients without neurologic complication. CONCLUSIONS: These preliminary results suggest that cerebrospinal fluid tau levels reflect brain injury. Because tau levels may separate the patients with temporary neurologic dysfunction, they may serve as a useful marker of brain injury.

Adult↗

Effect of meningitis and probenecid on the penetration of vancomycin into cerebrospinal fluid in rabbits.

This study examined the effects of experimental pneumococcal meningitis and probenecid administration on the penetration of parenterally administered vancomycin into cerebrospinal fluid in rabbits. Bacterial killing was also examined in infected animals. Meningitis was induced by intracisternal inoculation of Streptococcus pneumoniae. Vancomycin was administered in a loading dose followed by a continuous intravenous infusion for 6 h. Serum and cerebrospinal fluid samples were obtained at 0, 2, 4, and 6 h for antibiotic assays and quantitative cultures. Meningitis significantly enhanced the penetration of vancomycin into cerebrospinal fluid, but probenecid administration had no effect. In normal rabbits, at 6 h the mean percent penetration (cerebrospinal fluid concentration/serum concentration x 100%) +/- the standard deviation was 1.9 +/- 0.9% in the nonprobenecid group (n = 10) and 1.9 +/- 1.1% in the probenecid group (n = 9). In rabbits with experimental pneumococcal meningitis, the mean percent penetration at 6 h was 3.9 +/- 2.6% in the nonprobenecid group (n = 11) and 4.3 +/- 2.1% in the probenecid group (n = 9). Mean bacterial titers in the cerebrospinal fluid of infected animals decreased by more than 3.0 log 10 colony-forming units per ml in both the nonprobenecid and the probenecid groups.

Animals↗

Serum procalcitonin and cerebrospinal fluid cytokines level in children with meningitis.

AIMS: To determine the level of serum procalcitonin and cerebrospinal fluid cytokines in children with bacterial or viral meningitis and to document the use of these parameters in differential diagnosis. RESULTS: Before the start of antibiotic treatment, serum procalcitonin and tumor necrosis factor alpha levels were found to be higher in acute bacterial meningitis compared with viral meningitis and with the control group. Similarly, cerebrospinal fluid interleukin-6 levels were found to be significantly higher in children with acute bacterial meningitis compared with viral meningitis. However, no significant difference was determined between groups in respect to the cerebrospinal fluid interleukin-8 level. CONCLUSION: Serum procalcitonin and cerebrospinal fluid tumor necrosis factor alpha levels can be used in the early diagnosis of bacterial meningitis. Similarly, they may be useful adjuncts in differential diagnosis of bacterial and viral meningitis.

Calcitonin↗

Comparison of Phadebact coagglutination tests with counterimmunoelectrophoresis for the detection of bacterial antigens in cerebrospinal fluid.

One hundred and seventeen specimens of cerebrospinal fluid from 94 patients were examined for the presence of pneumococcal and Haemophilus influenzae type b antigens using counterimmunoelectrophoresis and coagglutination tests. The coagglutination method using Phadebact reagents was as sensitive as counterimmunoelectrophoresis, but culture was a more sensitive diagnostic procedure than either test. A meningococcus coagglutination reagent, included in a prototype meningitis diagnostic kit, was also found to be as sensitive as counterimmunoelectrophoresis when tested on culture-positive cerebrospinal fluid specimens. Coagglutination tests for the detection of bacterial antigen are useful supportive tests when used in conjunction with direct microscopy and culture for bacterial pathogens.

Agglutination Tests↗

Neurological outcome after out-of-hospital cardiac arrest. Prediction by cerebrospinal fluid enzyme analysis.

The prognostic value of cerebrospinal fluid (CSF) and serum neuron-specific enolase and brain-type creatine kinase isozyme (CK-BB) measurements was studied in 75 consecutive victims of out-of-hospital cardiac arrest. All patients with a CSF neuron-specific enolase level of more than 24 ng/mL 24 hours after cardiac arrest remained unconscious and died. The CSF CK-BB level was as reliable as an index of brain injury. Cerebrospinal fluid neuron-specific enolase, CSF CK-BB and serum neuron-specific enolase levels correlated with the neurological outcome at 3 months. Thus, the analysis of these enzymes in CSF seems to be useful in the early prognostic assessment of cardiac arrest victims.

Adult↗

Penetration of cefoxitin into human cerebrospinal fluid: comparison with cefamandole, ampicillin, and penicillin.

Single, intravenously administered doses of cefoxitin and cefamandole did not penetrate into cerebrospinal fluid of normal humans. Multiple-dose administration with or without probenecid facilitated penetration of both antibiotics into the cerebrospinal fluid. Preliminary data showed that cefoxitin penetrated into cerebrospinal fluid of patients with inflamed meninges even when administered in a single dose without probenecid. However, the concentrations of cefoxitin in the cerebrospinal fluid of the individuals studied were not within the therapeutic range.

Administration, Oral↗

A prospective randomized study of cerebrospinal fluid drainage to prevent paraplegia after high-risk surgery on the thoracoabdominal aorta.

This article is concerned with the study of the effect of several variables, principally that of cerebrospinal fluid drainage, on the incidence of neurologic deficit in a prospective randomized series of patients with extensive aneurysms of the descending thoracic and abdominal aorta (thoracoabdominal type I and II). Forty-six patients had cerebrospinal fluid drainage, and 52 were controls, with a total of 98 available for study. Cerebrospinal fluid pressure was continuously monitored in the former group and pressure maintained less than or equal to 10 mm Hg in 20, less than or equal to 15 mm Hg in 20, and greater than 15 mm Hg in 6 patients during period of aortic clamping. The method of treatment including reattachment of intercostal and lumbar arteries (p = 0.2), temporary atriofemoral bypass during aortic occlusion (p = 0.3), and spinal fluid drainage (p = 0.8) were not statistically significant in reducing the incidence of neurologic deficits. Thus cerebrospinal fluid drainage as we used it, was not beneficial in preventing paraplegia. On appropriate statistical analysis we found that the only significant predictor of delayed deficits was postoperative hypotension (p = 0.006).

Aortic Dissection↗

Assessment of tumor markers in cerebrospinal fluid.

In clinical practice, the examination of cerebrospinal fluid from patients with primary or metastatic brain tumors is commonly limited to cytomorphologic and routine chemistry analysis. The relative lack of sensitivity and specificity of these tests has led to a search for markers that can detect nervous system involvement by neoplasms at an earlier stage and even predict the site of origin of the neoplasms. This article summarizes recent investigators of biochemical tumor markers and cytoplasmic and cell surface markers in cerebrospinal fluid from patients with nervous system tumors.

Antibodies, Monoclonal↗

[Ventriculo-lumbar gradient of concentration of total cerebrospinal fluid proteins: 1 - mechanisms of origin].

In normal conditions there is a concentration gradient of proteins along the neuraxis. From a low level in the ventricles, ranging from 5 to 15 mg/10C ml, to an intermediate level in the cisterna magna, the protein content reaches its highest level in the lumbar sac, 12 to 44 mg/100 ml. Several mechanisms were considered to elucidate the origin of this gradient but many investigators think that the progressive increase of the protein concentration is best explained by the transfer of proteins from serum to the cerebrospinal fluid due to the relatively raised permeability of blood-cerebrospinal fluid barrier in the spinal subarachnoid space. This paper presents a study of the protein concentrations in cisternal and lumbar cerebrospinal fluid samples of patients with neurocysticercosis in activity. The 11 patients of the first group had free subarachnoid space communication between the cisterna magna and the lumbar sac; the 6 patients of the second group had a complete block of the subarachnoid space between these two levels. In every cerebrospinal fluid specimen the quantitative complement fixation test for cysticercus was performed and the titer determined in order to make an assessment of the central nervous system humoral immune response. The analysis of the data of this investigation shows that the concentration gradient of proteins is evident in the cerebrospinal fluid of patients with patency of the spinal subarachnoid space, and the ratio of concentrations of protein contents in simultaneous cisternal and lumbar samples was similar to that one observed in normal individuals. This gradient is also detected when the intensity of the humoral immune response is determined by quantitative complement fixation test for cysticercus in simultaneous cisternal and lumbar specimens. After the onset of spinal subarachnoid block, the confront of the results of the tests in cerebrospinal fluid samples, obtained before and after the blockage, shows a large increase both in the total protein content as well as the intensity of the humoral immune response, in the lumbar level. The similar increases both in protein concentration and titer of cysticercus complement fixation test in the lumbar fluid, in comparison with the cisternal fluid, in patients with patent spinal subarachnoid space, and the large simultaneous and similar increases in both protein content and titer of the cysticercus complement fixation test in the lumbar fluid of patients with spinal subarachnoid block are in disagreement with the usual explanation of the origin mechanisms of the gradient.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibody Formation↗

Randomized trial of cerebrospinal fluid shunt valve design in pediatric hydrocephalus.

OBJECTIVE: Forty percent of standard cerebrospinal fluid shunts implanted for the treatment of pediatric hydrocephalus fail within the first year. Two new shunt valves designed to limit excess flow, particularly in upright positions, were studied to compare treatment failure rates with those for standard differential-pressure valves. METHODS: Three hundred-forty-four hydrocephalic children (age, birth to 18 yr) undergoing their first cerebrospinal fluid shunt insertion were randomized at 12 North American or European pediatric neurosurgical centers. Patients received one of three valves, i.e., a standard differential-pressure valve; a Delta valve (Medtronic PS Medical, Goleta, CA), which contains a siphon-control component designed to reduce siphoning in upright positions; or an Orbis-Sigma valve (Cordis, Miami, FL), with a variable-resistance, flow-limiting component. Patients were monitored for a minimum of 1 year. Endpoints were defined as shunt failure resulting from shunt obstruction, overdrainage, loculations of the cerebral ventricles, or infection. Outcome events were assessed by blinded independent case review. RESULTS: One hundred-fifty patients reached an endpoint; shunt obstruction occurred in 108 (31.4%), overdrainage in 12 (3.5%), loculated ventricles in 2 (0.6%), and infection in 28 (8.1%). Sixty-one percent were shunt failure-free at 1 year and 47% at 2 years, with a median shunt failure-free duration of 656 days. There was no difference in shunt failure-free duration among the three valves (P = 0.24). CONCLUSION: Cerebrospinal fluid shunt failure, predominantly from shunt obstruction and infection, remains a persistent problem in pediatric hydrocephalus. Two new valve designs did not significantly affect shunt failure rates.

Adolescent↗