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PubMed1987

Correlation of cerebrospinal fluid endotoxinlike activity with clinical and laboratory variables in gram-negative bacterial meningitis in children.

Detection of endotoxinlike activity in cerebrospinal fluid by Limulus amebocyte lysate gelation has been suggested as a useful technique for the diagnosis of gram-negative bacterial meningitis. We prospectively screened 1,503 cerebrospinal fluid specimens with a Limulus amebocyte lysate microassay. The limit of sensitivity of the assay was 0.01 ng/ml. All specimens that were positive for endotoxinlike activity were subjected to confirmatory retesting, after which 38 (86%) remained positive. Comparison with available culture results revealed that 33 of 38 specimens (86%) were culture positive; 3 of the 5 culture-negative specimens were from patients on therapy for gram-negative bacterial meningitis, and 1 was from a neonate. The overall specificity of confirmed positive tests was 99.5%, with a positive predictive value of 97.3%. There was one false-negative specimen, giving an overall sensitivity of 97.3% and a negative predictive value of 99.9%. Endotoxinlike activities of greater than or equal to 150 ng/ml correlated with present illness of less than 2 days' duration (P = 0.024), elevated cerebrospinal fluid protein (P less than 0.05), and seizures (P = 0.004); levels of greater than or equal to 3,000 ng/ml correlated with neutropenia (P = 0.032), and levels of greater than or equal to 3.2 X 10(6) ng/ml correlated with death (P = 0.001). We conclude that the Limulus amebocyte lysate microslide gelation test has prognostic value as a sensitive, specific, simple, inexpensive screening test for gram-negative bacterial meningitis.

Bacterial Infections↗
PubMedDate not supplied

[Matrix metalloproteinase-9 (MMP-9) activity in cerebrospinal fluid of amyotrophic lateral sclerosis patients].

Matrix metalloproteinase-9 (MMP-9) is a member of the family of zinc-dependent endopeptidases that degrade extracellular matrix proteins. It can be activated by serine proteinases or by superoxide radicals. The motor neurons in amyotrophic lateral sclerosis patients express significantly higher levels of MMP-9, suggesting a role in neurodegeneration. The aim of the study was to investigate MMP-9 in cerebrospinal fluid from amyotrophic lateral sclerosis patients. MMP-9 was measured by enzyme-linked immunosorbent assay ELISA in cerebrospinal fluid from 24 amyotrophic lateral sclerosis patients and 15 controls. The mean amyotrophic lateral sclerosis duration was 18 months. According to Munsat ALS Health State Scale, the patients were divided into four groups: mild, moderate, severe, terminal. The patients were also divided into groups with shorter (below 12 months) and longer (above 12 months) duration of the disease. MMP-9 level was insignificantly lower in the cerebrospinal fluid from amyotrophic lateral sclerosis patients compared with controls. MMP-9 level showed a tendency to decrease with clinical status worsening, however this correlation was not statistically significant. The difference between MMP-9 level in the cerebrospinal fluid between the groups of patients with shorter and longer duration of amyotrophic lateral sclerosis was not significant.

Aged↗
PubMed1977

Effects of probenecid on methotrexate exchange between the blood and the cerebrospinal fluid.

In rabbits anesthetized with urethane, only a small fraction of 3H-methotrexate administered by an i.v. infusion reached an artificial cerebrospinal fluid solution perfused through the cerebroventricular system. This movement was not altered significantly by probenecid administered either i.v. or in the perfusing artificial cerebrospinal fluid. When the 3H-methotrexate was perfused through the cerebroventricular system, one third of the amount normally lost during the perfusion was retained when probenecid was also added to the solution. Therefore, at least a portion of the apparent blood-brain barrier that exists for methotrexate is due to removal from the cerebrospinal fluid by a process that can be inhibited by probenecid.

Animals↗
PubMedDate not supplied

Value of a single-shot turbo spin-echo pulse sequence for assessing the architecture of the subarachnoid space and the constitutive nature of cerebrospinal fluid.

Three case history reports are presented to illustrate the value of the single-shot turbo spin-echo pulse sequence for assessment of the subarachnoid space. The use of the single-shot turbo spin-echo pulse sequence, which is a heavily T2-weighted sequence, allows for a rapid, noninvasive evaluation of the subarachnoid space by using the high signal from cerebrospinal fluid. This sequence can be completed in seconds rather than the several minutes required for a T2-fast spin-echo sequence. Unlike the standard T2-fast spin-echo sequence, a single-shot turbo spin-echo pulse sequence also provides qualitative information about the protein and the cellular content of the cerebrospinal fluid, such as in patients with inflammatory debris or hemorrhage in the cerebrospinal fluid. Although the resolution of the single-shot turbo spin-echo pulse sequence images is relatively poor compared with more conventional sequences, the qualitative information about the subarachnoid space and cerebrospinal fluid and the rapid acquisition time, make it a useful sequence to include in standard protocols of spinal magnetic resonance imaging.

Animals↗
PubMed1982

Cerebrospinal fluid rhinorrhea: evaluation with metrizamide cisternography.

Metrizamide computed tomographic cisternography was used to examine 27 patients (19 males and eight females, 14-59 years old) clinically suspected of having cerebrospinal fluid fistulae with rhinorrhea. Twenty-one fistulae were traumatic and six were spontaneous. Five to 6 ml of metrizamide (or lopamidol, two cases) were injected by lumbar puncture at a concentration of 185-200 mg I/ml for direct coronal and axial computed tomographic sections of the skull base. Cerebrospinal fluid rhinorrhea was present at the time of examination in 12 of 27 cases. Results were evaluated according to three criteria: (1) metrizamide passage through the bony and dural defect; (2) demonstrable site of the fracture and/or bony defect; and (3) metrizamide visualized within a paranasal sinus, nasal cavity, or cotton pledget. The examination was considered positive when criterion 1 alone was present and when 2 and 3 were associated. In 15 of 27 cases, cisternography was positive, with the exact site of cerebrospinal fluid leakage demonstrated in 10 patients. In six cases, the results were not definitive; only one of the criteria (2 or 3) was fulfilled. In six cases, cisternography was normal. Seventeen patients underwent surgery. The site of cerebrospinal fistulae was ethmoidal in nine cases, frontoethmoidal in seven, sphenoidal in two, and sphenoethmoidal in one. The relative value of metrizamide computed tomographic cisternography compared with other diagnostic studies, polytomography, positive or negative contrast studies, and radionuclides, is discussed. Diagnostic pitfalls include artifacts and partial volume effect.

Adolescent↗
PubMed1988

Cerebrospinal fluid lymphocytes from HIV-infected patients synthesize HIV-specific antibody in vitro.

Cerebrospinal fluid lymphocytes from six human immunodeficiency virus (HIV)-infected and three seronegative patients were studied for in vitro synthesis of HIV-specific antibody by means of Western blot analysis of lymphocyte culture supernatants. All the HIV-positive subjects showed in vitro production of HIV-specific IgG, regardless of neurological involvement, while no specific antibody synthesis was detected in seronegative individuals. These data provide the first direct evidence that HIV-specific antibody in cerebrospinal fluid is due to intrathecal synthesis.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Post-laminectomy cerebrospinal fluid fistula treated with epidural blood patch.

UNLABELLED: OBJECTIVES AND SUMMARY OF BACKGROUND DATA: Cerebrospinal fluid fistula after spinal surgery is associated with a definite risk of meningitis or discitis, and as a result, early active intervention usually is recommended. METHODS AND RESULTS: This report describes the successful use of an epidural blood patch after a more conventional intervention--namely, surgical re-exploration--had failed to control a postoperative cerebrospinal fluid leak. CONCLUSIONS: The techniques involved in performing a blood patch after spinal surgery may well differ from those usually recommended in the management of spinal headache resulting from other causes of dural puncture.

Aged↗
PubMed2001

Transforming growth factor beta concentrations and interferon gamma responses in cerebrospinal fluid of horses with equine protozoal myeloencephalitis.

The following experiment was performed to test the hypothesis that transforming growth factor beta (TGF-beta) concentration varies in the cerebrospinal fluid and serum of horses with EPM and to determine if cerebrospinal fluid (CSF) alters the interferon-gamma (IFN-gamma) rersponse of equine peripheral blood mononuclear cells (PBMCs). The concentration of transforming growth factor-beta (TGF-beta2) was investigated in the serum and cerebrospinal fluid (CSF) of 18 horses (9 normal, 9 affected with equine protozoal myeloencephalitis [EPM]). The TGF-beta2 assay was validated in a group of 6 normal horses. Intra-assay variability was 4.7%, and interassay variability was 10.7%. The slope of the curve of the unknown samples of various volumes demonstrated parallelism with a curve developed using equal volumes of assay kit standard. Assay of normal and EPM-affected horses found that TGF-beta2 was present in both the serum and CSF of all animals. However, the concentration of TGF-beta2 in the CSF was less (P = 0.03) in EPM-affected horses (144 pg/ml) than in normal horses (256 pg/ml). In addition, the effect of CSF from normal and EPM-affected horses on the production of interferon-gamma (IFN-gamma) by PHA-P stimulated PBMCs from normal horses was investigated using a bioassay. It was found that CSF from normal and EPM-affected horses enhanced IFN-gamma activity from PHA-P stimulated peripheral blood mononuclear cells (P < or = 0.05); however, the response to CSF from EPM-affected horses was no different than the response to CSF from normal horses. Treatment of cells with anti-TGF-beta2 monoclonal antibodies slightly increased the response when co-incubated with CSF from normal horses, and slightly decreased it when co-incubated with CSF from EPM-affected horses. These differences, however, did not achieve statistical significance (P > 0.05). Results of this study indicated that production of TGF-beta2 is altered in horses with EPM, and that CSF appears to contain substances which alter the inflammatory reaction to plant lectins. These findings confirm the immunomodulatory properties of CSF and suggest new techniques for future research regarding the pathophysiology of EPM.

Animals↗
PubMed1998

Cerebrospinal fluid measures of disease activity in patients with multiple sclerosis.

The potential of magnetic resonance imaging to serve as a surrogate marker of disease activity in patients with multiple sclerosis (MS) is increasingly recognised. In contrast, the use of cerebrospinal fluid analysis has received less attention. We analysed the correlation between clinical data and cerebrospinal fluid parameters in 75 patients with acute optic neuritis (ON) as a possible first symptom of MS, as a symptom of clinically definite MS, and in patients with an attack of MS other than ON. The samples were obtained within 30 days from the onset of an exacerbation. The concentration of myelin basic protein (MBP) in cerebrospinal fluid was significantly correlated with the visual acuity in patients with ON and the Kurtzke EDSS score in patients with MS. The concentration of MBP in CSF also correlated positively with the CSF leukocyte count, intrathecal IgG synthesis, and the CSF-serum albumin concentration quotient. The concentration of MBP in CSF correlated negatively with intrathecal IgA synthesis. The results support the use of the concentration of MBP in CSF as a surrogate marker of disease activity during acute exacerbations of MS; the data also link the presence of MBP in CSF to neuroimmunological parameters.

Adolescent↗
PubMed1981

Depression and cerebrospinal fluid citrate.

In relation to studies of calcium metabolism in manic-melancholic patients, the calcium binding metabolite citrate was analyzed in cerebrospinal fluid from 163 psychiatric and non-psychiatric patients. Patients with symptoms of depression, irrespective of whether the origin of the depression was endogenous or exogenous, had significantly higher cerebrospinal fluid citrate concentrations than non-psychiatric patients. Manic patients and other psychiatric patients without symptoms of depression were not significantly different from the non-psychiatric patients. When the mood was normalized after various treatments, cerebrospinal fluid citrate decreased in all groups of depressed patients.

Adult↗
PubMed1982

Relationships between the tubular system in the globules of the coronet cells of the saccus vasculosus and the cerebrospinal fluid in Gasterosteus aculeatus form leiurus (Teleostei).

In the stickleback, Gasterosteus aculeatus, the globules of the coronet cells in the saccus vasculosus contain a tubular system that most probably communicates permanently with the lumen of the saccus. Only very few openings were found in random ultrathin sections. Injecting peroxidase into the cerebrospinal fluid revealed the communication between this tubular system and the cerebrospinal fluid. As early a 1 h after peroxidase injection the tracer was detected in the tubular system. This system increases the potential exchange surface between the coronet cells and the content of the saccular lumen, and may also facilitate the access of components of the cerebrospinal fluid (CSF), even of high molecular weight, into the globules. It remains to be determined whether the intratubular condensations (granules) are, as often believed, of secretory origin or are formed by accumulation of components of the CSF.

Animals↗
PubMed1992

Intrathecal 4-hydroperoxycyclophosphamide: neurotoxicity, cerebrospinal fluid pharmacokinetics, and antitumor activity in a rabbit model of VX2 leptomeningeal carcinomatosis.

Dissemination of tumor to the leptomeninges and cerebrospinal fluid represents a common pattern of metastasis for many cancers; however, few chemotherapeutic agents are available for intrathecal (i.t.) use and treatment results are often poor. We studied the neurotoxicity and pharmacokinetics of i.t. 4-hydroperoxycyclophosphamide (4-HC) in the rabbit and the activity of i.t. 4-HC in a VX2 rabbit model of leptomeningeal carcinomatosis to evaluate the potential use of 4-HC in the treatment of leptomeningeal tumors. Toxicity studies examined 4-HC doses ranging from 0.5 to 6.0 mumol administered by intraventricular injection weekly for 4 to 8 weeks. Clinical or histological neurotoxicity was not observed in rabbits treated with < 1.0 mumol 4-HC for 4 weeks. Clinical toxicity, characterized by lethargy, weight loss, seizures, or death, was apparent at doses > 2.0 mumol. Vasculitis of superficial arteries was observed in rabbits treated with > 1.0 mumol 4-HC. In cerebrospinal fluid pharmacokinetic studies, the mean drug half-life after intraventricular or intralumbar administration was 24.3 and 18.2 min. Regional inequities in drug exposure were apparent as area under the clearance curve values for cerebrospinal fluid distant from the injection site were lower than those of proximate sites (P < 0.001). Weekly intraventricular treatment of VX2 leptomeningeal tumor-bearing rabbits with 0.5 or 1.0 mumol of 4-HC resulted in an increased life span of 22.5 and 35%, respectively. These results indicate that i.t. 4-HC, at doses lower than those producing neurotoxicity in the rabbit, is effective treatment for VX2 leptomeningeal carcinomatosis.

Animals↗
PubMed2001

[Endothelin in the plasma and cerebrospinal fluid of patients after head injury].

UNLABELLED: Endothelin (ET) is identified as a potent vasoconstrictor peptide. It can cause a cerebral vasospam after subarachnoid hemorrhage. Its long-lasting vasoconstricting activity has been well documented. The role of ET in response to head injury is not clear. ET can participate in astrocyte activation and oxidative stress after trauma. The aim of this presentation was to investigate ET in the plasma and cerebrospinal fluid of patients after head injury and estimation of relation between the ET csf level and clinical condition of the patients and also relation of ET csf level and changes in the CT-scan and usefulness of ET as independent prognostic factor. We examined 30 patients at Day 1 after trauma (28 male, 2 female, aged 19-34 y, mean 30, 4, GCS ranged 8-15). CT-examination showed post-traumatic changes in 19 cases (11 with brain edema only, 8 with brain contusion). We measured ET by immunoenzymatic method using standard kits (Biomedica). The ET plasma level reached 1.12 +/- 0.63 fmol/ml (in the control group--0.44 +/- 0.19 fmol/ml) and c ET csf level 1.03 +/- 0.49 (in the control group--0.07 +/- 0.09 fmol/ml). W confirmed the correlation between the ET level and patients consciousness (by GCS) (p < 0.01). The ET csf level was highest in the patients with brain contusion in CT-scan (p < 0.02). Using multivariate analyses, we showed that ET can be used as a prognostic factor of results of treatment (p < 0.02). CONCLUSIONS: The ET level is elevated in the plasma of patients after head injury. ET is also present and strongly elevated in the cerebrospinal fluid of the same patients. The ET level in cerebrospinal fluid is associated with clinical condition of patients and elevated in cases with brain edema and structural brain damage. The ET level in cerebrospinal fluid is related to post-traumatic changes of the brain such as oedema and structural damage present in the CT-scan. ET can be used as a prognostic factor of results of treatment.

Adult↗
PubMedDate not supplied

Alterations of plasma and cerebrospinal fluid glutamate levels in rats treated with the N-methyl-D-aspartate receptor antagonist, ketamine.

It has been reported that the repeated administration of a sub-anesthetic dose of an N-methyl-D-aspartate receptor antagonist, ketamine, can produce an animal model of schizophrenia. Since no information is available on the alterations of the amino acid levels in ketamine-treated rats, we investigated the amino acid composition in the plasma and cerebrospinal fluid of rats that were repeatedly administered with ketamine for 5 consecutive days (30 mg/kg/day). The plasma and cerebrospinal fluid amino acid compositions in the fifth week after cessation of repeated ketamine administration were determined by highperformance liquid chromatography with fluorescence detection using a pre-column fluorescence reagent, i.e. 4-fluoro-7nitro-2,1,3-benzoxadiazole. Among the amino acids investigated in the present study, the level of plasma glutamic acid increased significantly (p < 0.05), while that of the cerebrospinal fluid glutamic acid decreased significantly in the ketamine-treated rats as compared with these levels in control rats injected with saline (p < 0.05, n = 7). These alterations in the glutamic acid level in the plasma and cerebrospinal fluid resemble those in schizophrenic patients, suggesting that ketamine-treated rats may be a useful model for performing research on the pathophysiology of schizophrenia.

Animals↗
PubMed1984

Heterogeneous models for blood-cerebrospinal fluid barrier permeability to serum proteins in normal and abnormal cerebrospinal fluid/serum protein concentration gradients.

Cerebrospinal fluid (CSF)/serum concentration gradients (Q) of individual proteins (albumin, IgG, alpha 2-macroglobulin) have been studied in controls and in patients in whom the lumbar CSF flow is altered (medullary compression) or the blood-CSF barrier (BCB) function impaired (acute idiopathic polyneuropathy and acute meningoencephalitis). The analysis of relationships among protein Q has been performed by total and multiple regressions and the actual BCB permeability to individual proteins has been interpreted according to the accepted theoretical porous or vesicular BCB models. The exponential Q-IgG vs. Q-albumin total regression, and the poor Q-alpha 2-macroglobulin vs. Q-albumin regression found in controls, together with the different multiple regressions among proteins and the high Q-IgG vs. Q-albumin partial regression coefficients found in medullary compression, acute idiopathic polyneuropathy and acute meningoencephalitis, indicated that different permeability mechanisms can be postulated. Heterogeneous, fairly independent permeability BCB mechanisms maintain the normal CSF/serum protein concentration gradient. Pinocytotic vesicles or pores of radius exceeding 1000-1500 A, probably located at the capillary endothelium, account for the main serum-derived CSF protein fraction(s) with large hydrodynamic radius (R). A more selective endothelial vesicular transport with a radius of 250 A transfers a negligible amount of protein from serum into CSF. Proteins with small R also enter the CSF through a set of selective pores of radius 120 A, probably at the level of the choroidal epithelium. Pinocytotic vesicles with a radius of 250 A and increased rate of formation induce the accumulation of proteins below an obstruction of lumbar CSF flow. An increased formation rate of vesicles with a radius of 450 A can explain the increased capillary permeability in nerve roots in acute idiopathic polyneuropathy. Loss of selectivity was the main feature of BCB in acute meningoencephalitis, and it seemed to be due to pores or vesicles with a radius larger than 1000-1500 A. The heterogeneity of BCB mechanisms must be taken into account when the intrathecal synthesis of a protein, also derived from serum (for example IgG), has to be measured.

Blood Proteins↗
PubMed2006

Identification of glycoproteins in human cerebrospinal fluid with a complementary proteomic approach.

Biomarkers are pressingly needed to assist with the clinical diagnosis of neurodegenerative diseases and/or the monitoring of disease progression. Glycoproteins are enriched in bodily fluids such as human cerebrospinal fluid (CSF), an ideal source for discovering biomarkers due to its proximity to the central nervous system (CNS), and consequently can serve as diagnostic and/or therapeutic markers for CNS diseases. We report here an in-depth identification of glycoproteins in human CSF using a complementary proteomic approach which integrated hydrazide chemistry and lectin affinity column for glycoprotein enrichment, followed by multidimensional chromatography separation and tandem mass spectrometric analysis. Using stringent criteria, a total of 216 glycoproteins, including many low-abundance proteins, was identified with high confidence. Approximately one-third of these proteins was already known to be relevant to the CNS structurally or functionally. This investigation, for the first time, not only categorized many glycoproteins in human CSF but also expanded the existing overall CSF protein database.

Adult↗