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PubMed2006

Clusterin in cerebrospinal fluid: analysis of carbohydrates and quantification of native and glycosylated forms.

Clusterin is suggested to be involved in the pathogenesis of Alzheimer's disease. Clusterin expression is increased in brain tissue in affected regions of Alzheimer patients, and intense clusterin staining is found in both senile plaques and in neuronal and glia cells. In contrast, the cerebrospinal fluid level of clusterin in Alzheimer patients has, thus far, been found unchanged. Clusterin is a glycosylated protein, and an alteration of its glycosylation in Alzheimer's disease might influence accurate quantification in cerebrospinal fluid through interference of antibody binding to the protein. Using enzymatic deglycosylation of clusterin isolated from cerebrospinal fluid, we found that the carbohydrates attached to clusterin were of the N-linked type and sialic acids. Based on this finding, cerebrospinal fluid samples from Alzheimer patients (n=99) and controls (n=39) were analysed. The samples were treated with peptide: N-glycanase F, cleaving off N-linked carbohydrates, and clusterin was quantified before and after deglycosylation using a new sandwich enzyme-linked immunosorbent assay. Clusterin was significantly increased in Alzheimer patients, in both native (7.17+/-2.43 AU versus 5.73+/-2.09 AU; p=0.002), and deglycosylated samples (12.19+/-5.00 AU versus 9.68+/-4.38 AU; p=0.004). Deglycosylation led to increased measured levels of clusterin by 70% (p<0.001) in Alzheimer patients and 67% (p<0.001) in controls. These findings indicate that glycosylation of proteins may interfere with their quantification. The results show that clusterin is significantly increased in cerebrospinal fluid from Alzheimer patients as a group, supporting that clusterin might be involved in the pathogenesis of Alzheimer's disease. However, the individual clusterin levels overlap between the two groups, and thus cerebrospinal fluid clusterin measurement is not suitable as a biochemical marker in the diagnosis of Alzheimer's disease.

Aged↗
PubMed2005

Cerebrospinal fluid ACTH and cortisol in opsoclonus-myoclonus: effect of therapy.

Opsoclonus-myoclonus syndrome is one of a few corticotropin (ACTH)-responsive central nervous system disorders of childhood. We measured cerebrospinal fluid ACTH and cortisol in 69 children with opsoclonus-myoclonus and 25 age- and sex-matched control subjects to determine endogenous levels and look for hypothesized differential hormonal effects of ACTH and corticosteroid treatment. Cerebrospinal fluid cortisol was 10-fold higher with ACTH treatment (n = 26), but was unchanged with oral steroid treatment (n = 18) or no treatment (n = 25). It was significantly higher in children receiving daily high-dose ACTH than alternate day ACTH. In ACTH-treated children, cerebrospinal fluid and serum cortisol were highly correlated (r = 0.96, P = 0.0001), with a mean ratio of cerebrospinal fluid to serum cortisol of approximately 1:10. Cerebrospinal fluid ACTH concentration did not differ significantly between untreated opsoclonus-myoclonus and control subjects but was lower with ACTH (-29%) or steroid treatment (-36%), suggesting feedback inhibition of ACTH release. These data delineate differences in the central effects of ACTH and corticosteroid therapy, as well as between high and low ACTH doses, and support the integrity of the brain-adrenal axis in pediatric opsoclonus-myoclonus.

Adrenocorticotropic Hormone↗
PubMed1989

Increased endotoxin and interleukin-1 beta concentrations in cerebrospinal fluid of infants with coliform meningitis and ventriculitis associated with intraventricular gentamicin therapy.

Intraventricular gentamicin therapy in infants with gram-negative enteric bacillary meningitis and ventriculitis is associated with increased mortality. Therefore, endotoxin, interleukin-1 beta, and cachectin (tumor necrosis factor) concentrations in ventricular cerebrospinal fluid from 21 infants (11 received intravenous antibiotics alone and 10 received intraventricular gentamicin also) were determined and correlated with outcome and other ventricular cerebrospinal fluid indexes of inflammation. Mean interleukin-1 beta concentrations in ventricular cerebrospinal fluid correlated significantly with adverse outcome and with mean concentrations of endotoxin, white blood cells, and protein and inversely with glucose concentrations. Mean and peak endotoxin and interleukin-1 beta concentrations were significantly higher in infants who received intraventricular gentamicin and intravenous antibiotics than in infants given intravenous antibiotics alone. Intraventricular gentamicin may have caused release of endotoxin from gram-negative bacilli in ventricular cerebrospinal fluid, resulting in increased interleukin-1 beta concentrations and inflammation, which could have contributed to the poor outcome in these patients.

Cerebral Ventricles↗
PubMed1983

[Encephalomyelitis syndrome in the cerebrospinal fluid in correlation to disease course criteria in multiple sclerosis].

Basing on a classification of the dynamic forms of multiple sclerosis according to prognostic-social aspects and in view to different degrees of defect the incidence of the five possible syndromes of cerebrospinal fluid were subjected to a correlation in 345 cases. In moderate till severe grades of neurologic disturbances and courses of illness an immunoreactive syndrome of cerebrospinal fluid - typically complete to incomplete - was doing found (in ca 40%). The slighter forms of the disease predominantly presented the whole spectrum of possible findings of cerebrospinal fluid; in it the syndromes with unimportant deviations were prevailing. In the course of multiple sclerosis alterations in the constellation of cerebrospinal fluid in manner of a retrograde tendency were scarcely noted. An increase of pathologic parameters in cerebrospinal fluid did rather show the slighter forms, in the severe progredient courses the syndromes turned out to be comparatively constant.

Cerebrospinal Fluid↗
PubMed1982

Pathogenesis of non-traumatic cerebrospinal fluid rhinorrhea.

15 consecutive patients with non-traumatic cerebrospinal fluid rhinorrhea were studied. 13 operations were performed on 10 patients. In 8 transcranial operations, an assumed defect in the anterior fossa was plugged with muscle, but only 3 operations were successful. In 4 operations, either transcranial or transsphenoidal, the sella was packed with muscle and rhinorrhea ceased immediately. Based on radiological and operative findings, 3 groups of patients appeared (1) 9 patients had pathology related to the pituitary gland or the sella turcica: enlarged sella, empty sella, pituitary tumour, intrasellar cyst or erosion of the sellar osseous border. (2) 2 patients had rhinorrhea from extrasellar origin. (3) In 4 patients no abnormality could be found. Prior to the rhinorrhea, 6 patients (5 from group 1 and 1 from group 3) had experienced episodes of neurological symptoms, compatible with a pituitary apoplexy. It is suggested that non-traumatic cerebrospinal fluid rhinorrhea in most cases is the result of a spontaneous necrosis in a pituitary adenoma, which has caused sellar bony erosion.

Adolescent↗
PubMed1981

Concomitant appearance of antibodies to two viruses in cerebrospinal fluid of an infant with acute encephalitis.

Acute encephalitis developed in a 5 1/2-month-old infant with a previous history of uncomplicated measles at 4 months of age. The patient survived his acute illness with resultant severe neurological sequelae. The serum complement fixing antibody titer for herpes simplex virus in the early phase of the illness was less than 1:4, and increased significantly to 1:64 in the convalescent phase. Antibody was also demonstrated in the cerebrospinal fluid. Antimeasles antibody was found in the cerebrospinal fluid in the early convalescent stage and remained at a detectable level for at least 1 month. Moreover, at least 71% of the total protein in the cerebrospinal fluid was IgG. Although brain biopsy for viral isolation was not performed, the most probable diagnosis was herpes simplex virus encephalitis, and the concomitant appearance of measles antibody in the cerebrospinal fluid may have been due to leakage of measles antibody from the blood into the cerebrospinal fluid due to disturbance of the blood-brain barrier.

Acute Disease↗
PubMed1995

Influx of nonactivated T lymphocytes into the cerebrospinal fluid during relapse of multiple sclerosis.

T lymphocytes were analyzed in the cerebrospinal fluid of 17 patients with multiple sclerosis during and 2 months after an exacerbation. The percentage of activated (HLA-DR+) T lymphocytes was decreased in the cerebrospinal fluid during the relapse but returned thereafter to the level comparable to that in patients with noninflammatory neurological diseases, whereas no fluctuation in the total number of these cells was found. This suggests an influx of nonactivated T lymphocytes into the cerebrospinal fluid at the beginning of the relapse.

Adult↗
PubMed1990

[Disorders of the cerebrospinal fluid dynamics in young children with pathology of the nervous system].

Two groups of patients with abnormalities of the cerebrospinal fluid dynamics were examined. There were 40 children with the hypertensive hydrocephalic syndrome and 67 with active hydrocephalus that had occurred before two years of age. A study was made of the anamnestic, clinical, ultrasonic and computer-aided tomographic parallels of those conditions. In the first group, computer-aided tomography of the brain revealed a moderate enlargement of the cerebrospinal fluid space. Two-dimensional ultrasonic examination of the brain via the open large fontanel also demonstrated the widening of the frontal cornua of the lateral ventricles and of the III ventricle. The second group children manifested an appreciable enlargement of the cerebrospinal fluid system, while the occlusive character of cerebrospinal fluid abnormalities required surgical treatment (drainage via the shunting system). A table of the differential diagnosis of the clinical and preclinical symptoms recorded in the two patients' groups is presented.

Brain Injuries↗
PubMed1996

Modified latex agglutination test for rapid detection of Streptococcus pneumoniae and haemophilus influenzae in cerebrospinal fluid and direct serotyping of Streptococcus pneumoniae.

A modified latex agglutination test was designed and evaluated for the rapid detection of Streptococcus pneumoniae and haemophilus influenzae type b capsular antigens, and for direct serotyping of Streptococcus pneumoniae in the cerebrospinal fluid. Reagents were prepared by sensitizing latex particles with Omniserum (against 83 capsular serotypes of pneumococci) and Haemophilus influenzae type b burro antiserum. For serotyping reagents, latex particles were similarly coated with nine pneumococcal pool (a to I) antisera and 46 individual pneumococcal serogroup/serotype specific antisera. The test was performed on cerebrospinal fluid from 298 patients with suspected meningitis. Serotyping was done directly on untreated cerebrospinal fluid samples showing positive reactions with the Omniserum reagent. Pneumococcal or Haemophilus influenzae type b antigens were detected in 41 patients; in 32 of these the etiology was established by culture and in 2 by smear examination. Five of the remaining seven cases were judged clinically and by cytological examination of cerebrospinal fluid to have partially treated bacterial meningitis. In two cases the test was false positive. The overall sensitivity and specificity of the latex agglutination test for the detection of Streptococcus pneumoniae and Haemophilus influenzae type b antigens was 100% and 96.8% respectively. The commonest pneumococcal serotypes were type 1 (30%), types 6 and 19 (10% each). The latex agglutination test is rapid and simple to perform, yielding serotype data directly by testing of cerebrospinal fluid.

Adult↗
PubMed1975

Enzymes in the cerebrospinal fluid in diagnosis of brain death.

The increase of enzymes in the cerebrospinal fluid is shown to indicate an adverse prognosis, with the implication of irreversibility. The massive increase of glutamate-oxaloacetate transaminase and lactate dehydrogenase and the appearance of alkaline phosphatases in a sample of cerebrospinal fluid in which the cytology is normal constitute an easy and reliable test for brain death. The increase in lactate dehydrogenase fraction V and lysozyme in cerebrospinal fluid supports the macrophagic origin of these enzymes.

Alkaline Phosphatase↗
PubMed1999

Reduced cerebrospinal fluid levels of alpha-secretase-cleaved amyloid precursor protein in aged rats: correlation with spatial memory deficits.

The amyloid precursor protein undergoes proteolysis at several sites to yield a number of functionally relevant peptides, including beta-amyloid and the soluble amyloid precursor protein derivatives alpha-soluble amyloid precursor protein and beta-soluble amyloid precursor protein. beta-Amyloid is the primary constituent of senile plaques associated with Alzheimer's disease, while a-soluble amyloid precursor protein promotes synaptogenesis and plays a role in neuroprotective processes. We tested for age-related alterations in these amyloid precursor protein proteolytically derived peptides by measuring the levels of alpha-soluble amyloid precursor protein, total soluble amyloid precursor proteins (alpha- and beta-soluble amyloid precursor protein combined) and beta-amyloid in cerebrospinal fluid from three-, 13- and 23-month-old Fischer-344 rats. Western blot analysis using selective antibodies revealed 50% less total soluble amyloid precursor protein and a-soluble amyloid precursor protein in cisternal cerebrospinal fluid from 23-month-old rats compared with three- and 13-month-old animals. Mass spectrometric analysis indicated, however, that beta-amyloid in cerebrospinal fluid was not different between the three age groups. In a second group of young (five to six months of age) and aged (24-25 months of age) rats, spatial working and reference memory were assessed in a water maze followed by collection of cerebrospinal fluid. As a group, the aged rats consistently performed below the young rats in both working and reference memory tests. The aged rats also had 49% less cerebrospinal fluid alpha-soluble amyloid precursor protein than did their younger counterparts. There was a positive correlation (r= 0.52-0.57, P < 0.001) between performance in spatial memory tasks and cerebrospinal fluid alpha-soluble amyloid precursor protein in these young and aged rats. These results suggest that there is a positive association between cerebrospinal fluid levels of alpha-soluble amyloid precursor protein and cognitive performance in rats, and that alpha-soluble amyloid precursor protein may be involved in the spatial learning and memory changes that accompany ageing.

Aging↗
PubMed1984

Spontaneous cerebrospinal fluid otorrhea and rhinorrhea coexisting in a patient with meningitis.

Congenital (spontaneous) cerebrospinal fluid fistulae are uncommon, potentially dangerous, pathological conditions. Most present in childhood with repeated bouts of meningitis, although presentation in adulthood with an asymptomatic nasal mass has been well documented. Radiologic work-up of the patient will usually reveal an abnormality in either the labyrinth or the base of the skull. A patient is presented who had both spontaneous cerebrospinal fluid otorrhea and rhinorrhea. Three anatomic defects were identified as potentially accountable: a round window fistula, a meningoencephalocele and an empty sella turcica.

Cerebrospinal Fluid Otorrhea↗
PubMed2000

An enzyme-linked immunosorbent assay to quantify 14-3-3 proteins in the cerebrospinal fluid of suspected Creutzfeldt-Jakob disease patients.

The detection of 14-3-3 protein by Western immunoblot is a sensitive and specific cerebrospinal fluid marker of Creutzfeldt-Jakob disease (CJD). We developed a quantitative enzyme-linked immunosorbent assay (ELISA) that reliably detects 14-3-3 in cerebrospinal fluid. In a prospective study of 147 cerebrospinal fluid samples, the mean 14-3-3 concentration among pathologically confirmed CJD patients (28.0+/-20.6 ng/ml, n = 41) is significantly higher than the mean in the cerebrospinal fluid of those with other neurological disorders (3.1+/-2.9 ng/ ml, n = 84). At a cutoff value of 8.3 ng/ml, the ELISA has a sensitivity of 92.7% and a specificity of 97.6%. The 14-3-3 ELISA supports a diagnosis of CJD in patients who fulfill clinical criteria for possible CJD.

14-3-3 Proteins↗
PubMed1975

Blood and cerebrospinal fluid catecholamines in the chronic obstructive bronchopneumopathy.

In our research we have aimed at studying the blood- and cerebrospinal fluid catecholamines' behaviour by means of von Euler-Floding's method, in a group of 30 patients, between 33 and 83 years, with chronic obstructive bronchopneumopathy, evolving from over ten years (even in younger persons). The total catecholamines in the cerebrospinal fluid have double values as against those in the blood, corresponding to the proportion found in a group of healthy subjects. On the contrary, the catecholamine fractions, occurring both in the blood and in the cerebrospinal fluid, have a diffent behaviour as against the normals, the adrenaline percentage exceeding by far the value of 23% recorded by these latter, going up to 46.95% in the blood and up to 47.68 in the cerebrospinal fluid. The increase of the adrenaline percentage may represent a pathogenetical factor, added to the other metabolic and hemodynamic factors, in the genesis of the chronic cardiopneumopathy; and the noxious effect acting on the whole myocardium supports the thesis according to which, earlier or later, in chronic obstructive bronchopneumopathy the left ventricle starts to suffer, as an integrant part of the clinico-morphological image.

Adult↗
PubMed1996

Immunoglobulin G avidity testing in serum and cerebrospinal fluid for analysis of measles virus infection.

We studied a variety of patients with measles virus infection by using avidity testing for measles virus-specific immunoglobulin G (IgG) in serum and cerebrospinal fluid samples. For the avidity testing, an Enzygnost measles IgG enzyme-linked immunosorbent assay kit was used with an 8 M urea denaturing method. With this method, low-avidity IgG (acute primary infection, avidity of < 30% within 15 days of the onset of rash) and high-avidity IgG (subacute sclerosing panencephalitis, avidity of > 75%) could be clearly distinguished by using serum samples. One patient, who developed a typical course of measles despite a previous vaccination, showed a positive IgM response with an initial low titer of measles virus-specific IgG of low avidity, but a later sample revealed a high titer of IgG of intermediate (40%) avidity, suggesting previous immunological priming. Two patients with breakthrough infection (secondary vaccine failure), both having central nervous system involvement, showed a positive IgM response with initial high titers of serum IgG of high avidity. In addition, one of the patients had a detectable level of measles-specific IgG in cerebrospinal fluid. In this patient, the avidity of both serum and cerebrospinal fluid IgG decreased during the short follow-up period. This phenomenon has never before been reported. In subacute sclerosing panencephalitis patients, the avidity of cerebrospinal fluid IgG was consistently lower than that of serum IgG. The difference in avidity between cerebrospinal fluid and serum IgG may be used as a direct indicator of intrathecal production of IgG. In conclusion, the avidity testing is simple to perform, reliable, and highly informative in the analysis of measles virus infection.

Adolescent↗
PubMed1987

Cerebrospinal fluid findings in neurological manifestations of Lyme disease.

The cerebrospinal fluid (CSF) findings in 21 patients with different manifestations of Lyme disease are presented. 15 patients exhibited CSF changes including a lymphoplasmocytic pleocytosis and a CSF protein profile indicating a barrier leakage combined with an intrathecal immunoglobulin synthesis. Six patients-mainly suffering from cranial neuritis-had a normal CSF.

Adolescent↗
PubMedDate not supplied

Anticardiolipin antibodies and interleukin-6 in cerebrospinal fluid and blood of Chinese patients with neuro-Behçet's syndrome.

Anticardiolipin antibodies of the IgG, IgM and IgA isotypes and soluble IL-6 were measured in paired serum and cerebrospinal fluid samples from five patients with neuro-Behçet's syndrome. Another five patients with non-inflammatory neurological diseases were also studied as a control group. Anticardiolipin antibodies, especially the IgM isotype, and IL-6 were highly elevated in the cerebrospinal fluid of patients with neuro-Behçet's. Levels of both IgM isotype anticardiolipin antibodies and IL-6 in the cerebrospinal fluid dropped after disease activity subsided. These results suggest that the increase in IgM isotype anticardiolipin antibodies and IL-6 in cerebrospinal fluid may be involved in the immune response of neuro-Behçet's within the central nervous system. Serial measurements of IgM isotype anticardiolipin antibodies and IL-6 in the cerebrospinal fluid may be useful in evaluating disease activity in neuro-Behçet's.

Adult↗
PubMed1987

Bacterial meningitis presenting with normal cerebrospinal fluid.

At a large children's hospital cases of bacterial meningitis with normal initial cerebrospinal fluid determinations other than culture or antigen detection assays were reviewed in an attempt to determine clinical or other laboratory findings accompanying this presentation. During a 5-year period from January, 1980, through December, 1985, 7 of 261 pediatric meningitis patients (2.7%) fulfilled these criteria. Ages ranged from 3 weeks to 18 months. All 7 patients were hospitalized for observation with all but 1 begun on empiric antibiotic therapy. Laboratory parameters such as a complete blood count, sedimentation rate or C-reactive protein did not influence decisions for management. Cerebrospinal fluid antigen detection assays were negative in all but one patient with pneumococcal meningitis. Review of these cases did not reveal unique indicators for bacterial meningitis. The results emphasize that the physician must rely on clinical judgment in initiating empiric antimicrobial therapy once apparently normal cerebrospinal fluid parameters are observed.

Antigens, Bacterial↗