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PubMed1995

Cerebrospinal fluid zinc concentrations in febrile convulsions.

Zinc modulates the activity of glutamic acid decarboxylase, the rate limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter. Low cerebrospinal fluid GABA values have been reported in association with several seizure disorders, including febrile convulsions. It is also known that fever and/or infections may cause a reduction in serum zinc concentrations. In this study the hypothesis that febrile convulsions are related to low cerebrospinal fluid zinc was tested. Cerebrospinal fluid zinc concentrations were measured in 66 febrile children: 32 with febrile convulsions, 18 with fever but without convulsions, and 16 with aseptic (viral) meningitis. There was no statistically significant difference in the cerebrospinal fluid zinc between the three groups of children, and the mean concentration was 26.2 micrograms/l. No significant relationship was found between either age, gender, maximal temperature, type of infection, or time of performance of the lumbar puncture and cerebrospinal fluid zinc concentration. These results do not support the hypothesis that febrile convulsions are related to reduced cerebrospinal fluid zinc concentrations.

Age Factors↗
PubMed2000

Reduced long-term potentiation in hippocampal slices prepared using sucrose-based artificial cerebrospinal fluid.

Sucrose-based artificial cerebrospinal fluid (aCSF) is sometimes used to prepare brain slices for in vitro electrophysiological experiments. This study compared the effect of preparing brain slices using chilled sucrose-based aCSF versus the conventional method using chilled aCSF on hippocampal synaptic plasticity. Brain slices from each treatment group were transferred to normal aCSF before electrophysiological recordings were made. The stimulus-response relationship of field excitatory postsynaptic potentials (fEPSPs) in the CA1 region was indistinguishable between the two treatment groups. However, the amount of LTP induced by either a &theta;-burst (four stimuli at 100 Hz repeated ten times at 200 ms intervals) or tetanic stimulation (100 Hz for 1 s) was significantly reduced in slices that had been prepared using sucrose-based aCSF. This was associated with reduced facilitation of the fEPSPs during the high frequency stimulus, reduced post-tetanic potentiation and short-term potentiation. In sucrose-cut slices the fEPSPs were slightly shorter in duration (29%, P<0.01), and during paired-pulse stimulation the broadening of the second fEPSP was enhanced. The LTP deficit in sucrose-cut slices was reversed by blocking GABA(A) receptor function with picrotoxin. These data suggest that the use of sucrose based aCSF better preserves GABA-mediated synaptic transmission, which limits the induction of LTP in hippocampal brain slices.

Action Potentials↗
PubMed1998

Surgical treatment of spontaneous spinal cerebrospinal fluid leaks.

OBJECT: Spontaneous spinal cerebrospinal fluid (CSF) leaks are an increasingly recognized cause of intracranial hypotension and may require neurosurgical intervention. In the present report the authors review their experience with the surgical management of spontaneous spinal CSF leaks. METHODS: Between 1992 and 1997, 10 patients with spontaneous spinal CSF leaks and intracranial hypotension were treated surgically. The mean age of the seven women and three men was 42.3 years (range 22-61 years). Preoperative imaging showed a single meningeal diverticulum in two patients, a complex of diverticula in one patient, and a focal CSF leak alone in seven patients. Surgical exploration in these seven patients demonstrated meningeal diverticula in one patient; no clear source of CSF leakage could be identified in the remaining six patients. Treatment consisted of ligation of the diverticula or packing of the epidural space with muscle or Gelfoam. Multiple simultaneous spinal CSF leaks were identified in three patients. CONCLUSIONS: All patients experienced complete relief of their headaches postoperatively. There has been no recurrence of symptoms in any of the patients during a mean follow-up period of 19 months (range 3-58 months; 16 person-years of cumulative follow up). Complications consisted of transient intracranial hypertension in one patient and leg numbness in another patient. Although the disease is often self-limiting, surgical treatment has an important role in the management of spontaneous spinal CSF leaks. Surgery is effective in eliminating the headaches and the morbidity is generally low. Surgical exploration for a focal CSF leak, as demonstrated on radiographic studies, usually does not reveal a clear source of the leak. Some patients may have multiple simultaneous CSF leaks.

Adult↗
PubMed1990

Reappraisal of the mechanism for cerebrospinal fluid hypertension during aortic surgery.

Cerebrospinal fluid (CSF) hypertension during aortic surgery is a poorly understood, multifactorial event that may increase the risk of spinal cord injury. To assess the factors that may contribute to changes in CSF pressure during aortic surgery, measurements of ascending arterial and CSF pressures were made in 17 anesthetized mongrel dogs. Changes in CSF patterns were monitored under several conditions tested in random sequence. These included systemic hypertension produced by an infusion of phenylephrine, cross-clamping of the descending thoracic aorta, and manual, superior displacement of the transverse aortic arch (arch elevation), either alone or in conjunction with the cross-clamp. Hypertension, cross-clamping, and cross-clamping combined with arch elevation all produced significant increases in ascending mean arterial pressure (204 +/- 20, 170 +/- 8, and 158 +/- 11 mm Hg, respectively, vs. 117 +/- 8 mm Hg [control]; (p less than 0.01). Small, nonsignificant increases in CSF pressure were detected in the cross-clamp group, but none were detected with hypertension alone, despite significant increases in ascending arterial blood pressure in both groups. Thus, neither arterial hypertension nor cross-clamping alone could be demonstrated directly to cause significant CSF hypertension. However, when aortic elevation (displacement) was combined with cross-clamping, the rise in CSF pressure increased to significant levels, even though the ascending arterial hypertension was least severe in this group. In contrast, arch elevation alone did not produce any significant increase in ascending arterial pressure but did produce an approximately 114% increase in CSF pressure (15.2 +/- mm Hg vs. 7.7 +/- 1 mm Hg [control]; p less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

Induction of cell death in rat brain by a gliotoxic factor from cerebrospinal fluid in multiple sclerosis.

The cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients contains a 17 kDa glycoproteic factor with gliotoxic properties in vitro. In order to study the physiopathological role of this gliotoxic factor in vivo, we have injected a partially purified preparation and appropriate controls in rat CSF and investigated whether it induces cell death in the rat central nervous system (CNS), 10 days and 3 months after injection. We used the TUNEL assay in association with specific immunohistochemistry to characterize dying cells in the gliotoxic factor- treated rat CNS. At 10 days post-injection, TUNEL-positive cells were observed in the whole rat CNS. They were particularly numerous in the choroid plexus, ependymal epithelium, cerebral white matter, cerebral vascular endothelium, arachnoid spaces and less frequent in the gray matter of brain and spinal cord. The predominant type of TUNEL-positive cells observed at 10 days post-injection was astrocytes, in white matter, gray matter, occasionnally around damaged endothelial cells in periventricular and subpial spaces. Other TUNEL-positive cells were identified as oligodendrocytes by an oligodendrocyte specific RIP immunostaining, at 10 days post-treatment with the gliotoxic factor. Interestingly, demyelination and death of oligodendrocytes were more important 3 months post-injection: TUNEL-RIP positive oligodendrocytes were generally associated with multifocal demyelinating areas. Clearly, the 17 kDa gliotoxic factor injection in rat CSF triggers demyelination and may be used as a new animal model for MS. Also, our results suggest a new possible scenario for MS pathogenesis: death of oligodendrocytes and astrocytes, stimulated by the MS gliotoxic factor causes the breakdown of the blood-brain barrier (BBB) and the demyelinating cascade.

Animals↗
PubMed1994

Analysis of human cerebrospinal fluid by capillary electrophoresis with laser-induced fluorescence detection.

Capillary electrophoresis with laser-induced fluorescence detection is used to analyze 10 microL samples of human cerebrospinal fluid. Primary amine-containing compounds in untreated cerebrospinal fluid are labeled with 3-(4-carboxybenzoyl)-2-quinolinecarboxaldehyde prior to analysis, producing fluorescent isoindoles. Electropherograms containing approximately 50 peaks are obtained in less than 35 min from cerebrospinal fluid samples. Ten peaks in the electropherograms have been identified and quantitated: arginine, glutamine, threonine, valine, gamma-amino-n-butyric acid, serine, alanine, glycine, glutamic acid, and aspartic acid. Detection limits for these 10 amino acids range from 0.29 nM for gamma-amino-n-butyric acid to 100 nM for threonine, and separation efficiencies as high as 190,000 theoretical plates are obtained for these analytes. Electropherograms of cerebrospinal fluid samples from patients with Alzheimer's disease and from children with different neurological disorders are compared to those of healthy controls. Differences in individual amino acid levels are observed between the patient groups, and these differences appear to be disease and age related. These results indicate that analysis of cerebrospinal fluid by capillary electrophoresis will be useful as a selective, rapid, and sensitive tool for both diagnosis of central nervous system disorders and for study of the mechanisms of these disorders.

Adult↗
PubMed1985

Guanidino compounds in plasma, urine and cerebrospinal fluid of hyperargininemic patients during therapy.

The concentrations of guanidino compounds were determined in urine, plasma and cerebrospinal fluid of two patients with hyperargininemia during dietary therapy. alpha-Keto-delta-guanidinovaleric acid, N-alpha-acetylarginine, argininic acid and gamma-guanidinobutyric acid were increased in urine. In plasma, these compounds together with creatine, guanidinoacetic acid, arginine and homoarginine were also increased. In cerebrospinal fluid, only arginine, homoarginine and argininic acid were increased. Trace amounts of alpha-keto-delta-guanidinovaleric acid were found in cerebrospinal fluid of the patient treated with only a low-arginine diet. The concentrations of guanidinosuccinic acid are decreased in urine, plasma and cerebrospinal fluid. During a low-arginine diet, together with sodium benzoate therapy, the plasma and cerebrospinal fluid arginine values returned to normal. There was also a normalization of plasma guanidinoacetic acid and a marked decrease in plasma N-alpha-acetylarginine and argininic acid.

Adolescent↗
PubMed2002

Calpain inhibition by cerebrospinal fluid and effects of calpain on intrathecal nerve tissue.

STUDY DESIGN: The effects of calpain on intrathecal nerve tissue in the rabbit were investigated. OBJECTIVE: To evaluate the chemonucleolytic side effect of calpain on nerve tissue in the event of accidental intrathecal calpain injection. SUMMARY OF BACKGROUND DATA: Calpain has a degradative effect on proteoglycans, and as previously shown, it is associated with chemonucleolytic action in the rabbit. However, its effect on nerve tissue in the event of accidental intrathecal injection is not clear. METHODS: The inhibitory activity of cerebrospinal fluid against calpain was measured in human cerebrospinal fluid using mu-calpain, and in different cerebrospinal fluid fractions separated by molecular filtration. The presence of the endogenous calpain inhibitor, calpastatin, in human cerebrospinal fluid was examined by Western blotting with anticalpastatin antibody. After intrathecal application of calpain in rabbits, the spinal cord nerve tissue was examined by light microscopy. RESULTS: Cerebrospinal fluid inhibited the enzyme reaction of calpain at its normal concentration. Immunoblotting with anticalpastatin antibody did not yield positive staining. After the intrathecal application of calpain, there was no evidence of degeneration in the nerve tissue of the spinal cord. CONCLUSIONS: This study suggests that in the event of accidental intrathecal injection of calpain for chemonucleolysis, the enzyme activity of calpain will be neutralized by cerebrospinal fluid, and the calpain should not cause unwanted side effects in chemonucleolysis.

Adolescent↗
PubMed1985

Cerebrospinal fluid beta-glucuronidase activities in patients with central nervous system metastases.

beta-Glucuronidase activities were determined in cerebrospinal fluid from 249 patients suffering from various neurological diseases. Reference values were established as 9-27 mU/l. Marked elevations of cerebrospinal beta-glucuronidase activities were observed in patients with bacterial and carcinomatous meningitis. Slight elevations of cerebrospinal beta-glucuronidase activities were observed in epidural and parenchymal metastases from solid tumours. Comparison was made with the determination of total protein, glucose and lactate dehydrogenase in cerebrospinal fluid. Cerebrospinal beta-glucuronidase activity appeared the most useful test in monitoring patients at risk in developing meningeal metastases from solid primary tumours.

Adolescent↗
PubMed1998

Control of proximal hypertension during aortic cross-clamping: its effect on cerebrospinal fluid dynamics and spinal cord perfusion pressure.

Postoperative paraplegia remains the most devastating complication of surgery of the descending and thoraco-abdominal aorta. Control of the proximal hypertension that follows cross-clamping of the thoracic aorta to repain aneurysms of the descending and thoraco-abdominal aorta is necessary to prevent left ventricular failure, myocardial infarction, and hemorrhagic cerebral events. Both pharmacological and mechanical modalities used to control central hypertension during aortic occlusion affect cerebrospinal fluid dynamics and spinal cord perfusion pressure. Sodium nitroprusside (doses >5 microg/kg/min), the most widely used pharmacological agent, decreases spinal cord perfusion pressure because it increases cerebrospinal fluid pressure and decreases blood pressure distal to the aortic cross-clamp. This effect cannot be prevented by drainage of cerebrospinal fluid. Nitroglycerin also decreases spinal cord perfusion pressure, but its effects on cerebrospinal fluid dynamics can be countered by drainage of cerebrospinal fluid. Active distal perfusion with left atrial-femoral artery bypass can provide adequate perfusion of the circulation distal to the aortic cross-clamp while simultaneously reducing cerebrospinal fluid pressure. This approach can maintain mesenteric and spinal cord blood flow, therefore preventing the multiple organ dysfunction syndrome caused by release of cytokines from the splanchnic district and decreasing the incidence of postoperative paraplegia from spinal cord ischemia. In cases of limited retroperfusion, partial exsanguination and cerebrospinal fluid drainage can be used in conjunction with left atrial-femoral artery bypass to prevent rises in cerebrospinal fluid pressure and maintain spinal cord blood flow above the threshold necessary to prevent neurological injury. The use of oxygenated perfluorocarbons in the subarachnoid space to provide passive oxygenation of the spinal cord during aortic occlusion remains experimental and requires further investigation.

Antihypertensive Agents↗
PubMed1990

[Electrophoresis of cholinesterases of the cerebrospinal fluid in the Guillain-Barré syndrome].

Polyacrylamide gel electrophoresis of cholinesterase from cerebrospinal fluid was performed in 22 patients with Guillain-Barré syndrome. Fifteen of these patients had an abnormal cerebrospinal fluid with emergence of a second electrophoretic migration band corresponding to non-specific cholinesterase. Among 182 patients with a variety of diseases who served as controls, only one presented with this abnormality. From these data the sensitivity and specificity of cerebrospinal fluid cholinesterase electrophoresis were calculated at 68 and 99 percent respectively. The second migration band seems to appear early in the course of the disease and disappears when the patient is cured. Moreover, the occurrence of this band is correlated with the severity of the condition, as shown by a greater number of patients under artificial ventilation and by a longer stay in intensive care unit. Cerebrospinal fluid electrophoresis could be used as a prognosis factor.

Adolescent↗
PubMed1990

Endoscopic management of cerebrospinal fluid leaks and cephaloceles.

The excellent visualization and atraumatic surgical techniques of endoscopic sinus surgery have been applied to the management of five cerebrospinal fluid leaks and two nasal cephaloceles. In all cases, the exact site of the lesion was identified. Four cerebrospinal fluid leaks were grafted with a free or pedicled septal mucosal graft. The fifth cerebrospinal fluid leak came from a narrow sphenoethmoid recess and stopped after the mucosa was abraded. The two cephaloceles were reduced intranasally and covered with bone and mucosal grafts. Not all cases seen in the same time period were treated endoscopically; two additional cerebrospinal fluid leaks were treated with conventional techniques because of severe nasal inflammatory disease and intracranial complications. The technique and indications for endoscopic management of cerebrospinal fluid leaks and cephaloceles are discussed.

Adult↗
PubMed2001

Detection of oligoclonal immunoglobulins in the cerebrospinal fluid by immunofixation electrophoresis.

Many disorders of the central nervous system are associated with increased concentration of cerebrospinal fluid protein due to either an increase in the permeability of blood-brain barrier or the synthesis of immunoglobulins within the central nervous system. Immunofixation electrophoresis was used to detect the immunoglobulins in sera and cerebrospinal fluid in patients with different central nervous system disorders. A strong oligoclonal band, or a single weak monoclonal band, observed in the cerebrospinal fluid but not in the serum, indicates the endogenous immunoglobulin synthesis. In 17 cases of non-infectious central nervous system diseases, we diagnosed one case of progressive multifocal leukoencephalopathy, one case of multiple sclerosis, one case of Guillain-Barre syndrome, and one case of epilepsy. A weak band was observed in both serum and cerebrospinal fluid samples in two cases of cerebral trauma. Out of 25 cases of infectious central nervous system diseases, two cases of nervous system syphilis were positive only in cerebrospinal fluid samples, and 23 cases were negative in both samples. Compared with the standard immunofixation, the application of an enzyme-labeled antibody can significantly increase the sensitivity of the method.

Adult↗
PubMed1998

Evaluation of a commercially available reverse transcription-PCR assay for diagnosis of enteroviral infection in archival and prospectively collected cerebrospinal fluid specimens.

A commercially available reverse transcription (RT)-PCR method (AMPLICOR EV; Roche Diagnostic Systems, Inc., Branchburg, N.J.) was evaluated for detection of enteroviruses in cerebrospinal fluid from patients with neurological disease. This assay was compared with virus isolation in cell culture and an in-house RT-PCR method designed with a nonoverlapping region of the enteroviral genome. A panel of 200 cerebrospinal fluid specimens prospectively collected from patients with a wide variety of neurological symptoms, including 50 patients involved in three different outbreaks of acute aseptic meningitis, was assayed. A second panel of 97 archived cerebrospinal fluid specimens, stored for 2 to 5 years, from patients with aseptic meningitis associated with several enterovirus outbreaks was also studied. From the first panel, enteroviruses were detected in 13 of 50 specimens by cell culture (26%), in 43 of 50 specimens by AMPLICOR EV (86%), and in 46 of 50 specimens by the in-house assay (92%) from patients with aseptic meningitis associated with outbreak and 1 of 29, 3 of 29, and 4 of 29 specimens, respectively, from sporadic cases of aseptic meningitis. The remaining 121 cerebrospinal fluid specimens from patients with other neurological syndromes were negative by all tests. From the second panel, enteroviral RNA was detected by the AMPLICOR test (31 of 97 specimens, 32%) and the in-house assay (39 of 97 specimens, 40%). According to our results, patients with aseptic meningitis should be analyzed for enteroviral infection in cerebrospinal fluid by RT-PCR methods, and the AMPLICOR EV test is a suitable tool for performing such studies. Archival cerebrospinal fluid specimens are less suitable for evaluation of the performance of RT-PCR methods designed for enterovirus detection.

Central Nervous System Diseases↗
PubMed1997

Cerebrospinal fluid lactate and glutamine are reduced in multiple sclerosis.

OBJECTIVES: To analyse various metabolites in human cerebrospinal fluid from healthy controls and patients with multiple sclerosis. PATIENTS AND METHODS: Cerebrospinal fluid was obtained from patients by lumbar puncture, frozen, redissolved, and analysed for metabolites by proton nuclear magnetic resonance spectroscopy. RESULTS: Significantly lower values for lactate and glutamine were found in patients with multiple sclerosis in comparison with controls. No significant differences were found between patients with the relapsing-remitting and chronic progressive forms of the disease for any of the metabolites measured. CONCLUSION: There is a concomitant reduction in both lactate and glutamine in the cerebrospinal fluid of patients with multiple sclerosis compared to controls. This may be related to altered astrocytic metabolism during the disease. The results clearly show the diagnostic potential of magnetic resonance spectroscopy in diseases such as multiple sclerosis.

Adolescent↗
PubMed1985

Comparison of serum and cerebrospinal fluid levels of methotrexate in man during high-dose chemotherapy for aggressive non-Hodgkin's lymphoma.

The relationship between plasma and cerebrospinal fluid levels of methotrexate was studied in five patients, four with aggressive non-Hodgkin's lymphoma and one with mixed epithelial mesothelial tumour, who were treated with high-dose methotrexate (1.5 g/m2) as part of combination chemotherapy. Cerebrospinal fluid was sampled for 24 h via a permanent indwelling lumbar catheter. No complications were observed with this technique. In two patients with central nervous system involvement adequate "cytotoxic" levels (greater than 10(-6) M) were obtained for greater than 12 h. The remaining three patients, with no direct evidence of central nervous system involvement, never attained adequate cytotoxic methotrexate levels in the cerebrospinal fluid. Serum levels were therapeutic in all patients. These results suggest that patients with central nervous system tumour involvement may receive adequate doses of methotrexate in the cerebrospinal fluid. Patients with occult central nervous system tumour involvement may not attain adequate cerebrospinal fluid levels. A 24-h serum methotrexate level of greater than 10(-5) M may indicate that patients have achieved therapeutic cerebrospinal fluid levels of methotrexate. Cranial irradiation following chemotherapy is still recommended in this tumour group until adequate cytotoxic levels of methotrexate can be obtained in all patients for prolonged periods.

Adult↗
PubMed2007

Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood-brain barrier.

Patients receiving trastuzumab for HER2-overexpressing metastatic breast cancer seem to suffer from an increased risk of brain metastases, even in cases with responsive disease. To evaluate whether trastuzumab is able to penetrate the blood-brain barrier, we measured trastuzumab levels in the serum and in cerebrospinal fluid of metastatic breast cancer patients with brain metastases receiving trastuzumab for HER2-overexpressing metastatic breast cancer. In a pilot study, metastatic breast cancer patients with brain metastases and HER2-overexpressing tumors (HercepTest; Dako, Copenhagen, Denmark) were included. At different time points, trastuzumab levels in the serum and cerebrospinal fluid were measured using a newly developed immunoenzymatic test for trastuzumab. Six out of eight patients were evaluable for determination of trastuzumab level in the serum and cerebrospinal fluid. Before radiotherapy, median trastuzumab level in the serum was 52 054 ng/ml compared with 124 ng/ml in cerebrospinal fluid (ratio 420 : 1). After completion of radiotherapy, median trastuzumab level was 20 185 ng/ml in the serum and 226 ng/ml in cerebrospinal fluid, respectively (ratio 76 : 1). With concomitant meningeal carcinomatosis, trastuzumab level in the serum after radiotherapy was 17 431 and 356 ng/ml in cerebrospinal fluid (ratio 49 : 1). For the first time, we present clinical evidence that trastuzumab levels in cerebrospinal fluid are increased under conditions of an impaired blood-brain barrier such as meningeal carcinomatosis or radiotherapy. This evidence supports the concept of continuing trastuzumab therapy in patients with brain metastases treated by radiotherapy. Monitoring of trastuzumab levels in the serum and cerebrospinal fluid may enable individualized therapy strategies in metastatic breast cancer patients with brain metastases, and lead to a better understanding of trastuzumab pharmacokinetics in the cerebrospinal fluid and serum.

Adult↗