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PubMed1996

Detection of both herpes simplex and varicella-zoster viruses in cerebrospinal fluid from patients with encephalitis.

Cerebrospinal fluid (CSF) samples from 46 patients with encephalitis were studied for the presence of herpes simplex virus (HSV) types 1 and 2 and/or varicella zoster virus (VZV)-specific DNA sequences by the polymerase chain reaction (PCR) assay. Patients were studied because of detection of intrathecal production of IgG antibody to HSV alone (10 patients, Group A) or to both HSV and VZV (11 patients, Group B) or because of the presence of specific anti-HSV IgG in CSF without evidence of intrathecal antibody production (25 patients, Group C). CSF samples taken between days 1 and 10 from onset of encephalitis were available from all patients, and follow-up samples (taken after 10 days from onset) were obtained from some of them. Positive PCR results were obtained in a total of 13 patients. Four patients (three from Group A and one from Group B) gave amplification of HSV type 1 DNA alone, two patients (both from Group B) showed amplification of VZV DNA alone, and seven patients (all from Group B) gave dual amplification of both HSV type 1 and VZV DNA sequences in CSF. All CSF samples from patients in Group C were negative by PCR. Ten patients with CSF samples positive by PCR lacked a prior history of herpetic cutaneous lesions. In seven patients, serum antibody tests (specific IgM detection and specific IgG avidity assays) identified both primary and recurrent infections. The results suggest that the dual presence of IgG antibody to both HSV and VZV in CSF from patients with encephalitis may reflect in some cases a dual infection of the central nervous system caused by both agents.

Adult↗
PubMed1982

Effect of folic acid and vitamin B12 deficiencies on 5-hydroxyindoleacetic acid in human cerebrospinal fluid.

Indoles were measured in cerebrospinal fluid (CSF) from control patients, from patients suffering from folate deficiency, and from patients with vitamin B12 deficiency. The folate-deficient patients were classified according to whether they exhibited a neuropsychiatric syndrome, consisting of organic mental changes, polyneuropathy, and depression, which responded to folate administration. CSF 5-hydroxyindoleacetic acid was low in the vitamin B12-deficient patients and in those folate-deficient patients whose symptoms were not related to folate deficiency. CSF 5-hydroxyindoleacetic acid returned to normal with folate treatment in the patients exhibiting folate-responsive neuropsychiatric signs. The data indicate a close association between folate-responsive neuropsychiatric symptoms and changes in 5-hydroxytryptamine metabolism in the central nervous system.

Adolescent↗
PubMed1993

Bambuterol and terbutaline in human cerebrospinal fluid and plasma.

Concentrations in cerebrospinal fluid (CSF) and plasma of bambuterol and its active metabolite, the beta 2-adrenoceptor agonist terbutaline, were measured in man after four once-daily doses of 30 mg bambuterol hydrochloride (Bambec). Nine patients scheduled for orthopaedic surgery under spinal anaesthesia completed the study. The concentrations of both substances were much lower in CSF than in plasma, the ratio CSF/plasma being 0.09 for bambuterol and 0.19 for terbutaline, at apparent steady state. While the rank order of the ratios was expected from the fractions of unbound bambuterol and terbutaline in plasma, their absolute values were only about 1/6 (bambuterol) and 1/4 (terbutaline) of those predicted from diffusion equilibria between plasma and CSF. Thus, the rates of transport of bambuterol and terbutaline from plasma into the central nervous system appear to be slow relative to transport out of the system, e.g. by outflow of CSF. The findings are in agreement with animal experiments and suggest that bambuterol and terbutaline are less likely than lipophilic beta 2-adrenoceptor agonists to interact with central receptors.

Aged↗
PubMed1993

Concentration gradients for monoamine metabolites in lumbar cerebrospinal fluid.

Concentration gradients in lumbar cerebrospinal fluid (CSF) for the monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA) and 4-hydroxy-3-methoxyphenylglycol (HMPG) were studied in 9 healthy controls and 47 neuropsychiatric patients without diseases causing disturbed CSF circulation. In a serial sampling of the first 24 ml of CSF, steep concentration gradients between the first (0-4th ml) and last (21st-24th ml) portions of CSF were found for HVA (99 +/- 59% increase; p < 0.001) and 5-HIAA (88 +/- 54% increase; p < 0.001), while the concentration gradient was slight for HMPG (11 +/- 7% increase; p < 0.001). The existence of marked concentration gradients for the monoamine metabolites HVA and 5-HIAA gives further evidence for an active transport system for these metabolites and indicates that the lumbar CSF-HVA and 5-HIAA levels reflect the dopamine and serotonin metabolism in the brain. Moreover, the existence of pronounced concentration gradients for HVA and 5-HIAA stresses the importance of making analyses on a standardized volume of CSF.

Adolescent↗
PubMed1990

Cerebrospinal fluid markers in neurological disorders.

Cerebrospinal fluid (CSF) markers are a useful tool for determining disease progression or activity in some neurological disorders which need parameters both for evaluating treatments and investigating pathobiological evolution in research-oriented follow-up. A number of CSF proteins are reviewed with data on biological properties, analytical methods, clinical usefulness of: myelin basic protein, S-100 protein, glial fibrillary acidic protein, neural-cell adhesion molecule, neuron-specific enolase and others.

Biomarkers↗
PubMed1998

Levels and proteolytic processing of chromogranin A and B and secretogranin II in cerebrospinal fluid in neurological diseases.

Human cerebrospinal fluid (CSF) contains chromogranin A and B and secretogranin II which represent peptides secreted from neuronal large dense core vesicles. Within these vesicles these precursor peptides are at least partly processed to smaller peptides. We analysed the CSF levels of chromogranins/secretogranin by radioimmunoassay using specific antisera. The degree of their processing was characterized by molecular sieve column chromatography followed by radioimmunoassay. As previously shown secretogranin II is fully processed to smaller peptides including the peptide secretoneurin, whereas processing of chromogranin A was more limited. For chromogranin B we found in this study a high degree of processing comparable to that of secretogranin II. An analysis of CSF from patients with multiple sclerosis, essential tremor, Alzheimer and Parkinson disease, did not reveal any differences in proteolytic processing of chromogranins/secretogranin when compared to control CSF. We conclude that in the four diseases investigated there is no change in the proteolytic processing of the chromogranins/secretogranin within the large dense core vesicles. The absolute levels of chromogranins/secretogranin varied in CSF collected in different hospitals, however their relative ratios were remarkable constant. We suggest to use this ratio as a parameter to standardise CSF levels of other peptides, e.g. neuropeptides. In Parkinson patients the chromogranin A/secretogranin II ratio was significantly increased whereas in Alzheimer patients and those with essential tremor and multiple sclerosis no change of the ratios was observed. Apparently there are only limited changes in the biosynthesis, processing, secretion and CSF clearance of these peptides in pathological conditions.

Adult↗
PubMed2002

Low Cerebrospinal Fluid Pressure Headache.

Alterations in cerebrospinal fluid (CSF) pressure lead to neurologic symptoms, the most common clinical manifestation of which is headache. Typically, the headache is orthostatic and related to traction on pain-sensitive intracranial and meningeal structures, distention on periventricular pain-sensitive areas, and direct pressure on pain conveying cranial nerves. Low CSF headache is a distinct and familiar syndrome that is seen most frequently following lumbar puncture. In this clinical scenario, the diagnosis and proposed plan of treatment are obvious. Over the past decade, however, an emerging syndrome of spontaneous intracranial hypotension (SIH) is being recognized with increasing frequency. Most of these patients are found to have spontaneous CSF leaks and have unique, clinically distinct imaging findings, which confirm the diagnosis leading to appropriate treatment. Spontaneous intracranial hypotension is a relatively benign and usually self-limiting syndrome of orthostatic headache in association with one or more of numerous symptoms including nausea, vomiting, horizontal diplopia, unsteadiness or vertigo, altered hearing, neck pain/stiffness, interscapular pain, and occasionally visual field cuts. The headache itself, while often orthostatic, may initially be non-positional, may lose its orthostatic features, or rarely or never be orthostatic. It may be gradual, subacute, or thunderclap in onset. There may be a history of minor, antecedent trauma. By very definition, the opening CSF pressure is low, below 60 mm H(2)O, and often a "dry" tap is encountered. However, the pressure may be normal, especially with intermittent leaks and may vary tap to tap. Fluid analysis is normal. Brain (and occasionally spinal) MRI studies, with gadolinium enhancement should be undertaken. In patients with SIH, studies typically reveal diffuse pachymeningeal enhancement, frequently in association with "sagging"of the brain, tonsilar descent, and posterior fossa crowding. Spinal MRI is an up and coming investigational technique, which may be helpful even in the case of a normal brain MRI. Computed tomography myelography is the diagnostic study of choice and may follow radiocisternography, which often shows absence of activity over the convexities and early appearance of activity in the renal/urinary tract. Although conservative measures are often undertaken first, epidural blood patch (EBP) is the treatment of choice. For those who fail EBP, surgery may need to be undertaken in those cases with clearly identified leaks.

Journal Article↗
PubMed1976

The bacteriological diagnosis of pyogenic meningitis from cerebrospinal fluid dried on filter paper.

Cerebrospinal fluid from patients with pyogenic meningitis in two rural hospitals in Nigeria was dried on filter paper and sent by post for analysis in a reference laboratory. Microbial antigens were detected by counter-current immunoelectrophoresis in 78 of the 142 specimens (55%). This method of detecting antigens deserves further application for epidemiological and diagnostic work in developing countries.

Antigens, Bacterial↗
PubMed1982

Cerebrospinal fluid hydroxylase cofactor in schizophrenia.

Cerebrospinal fluid levels of pterin cofactor were measured in off-medication schizophrenic patients and normal control subjects as one aspect of monoamine physiology in schizophrenia. Pterin cofactor is essential for the hydroxylation of several substances including tyrosine, the rate-limiting step in the synthesis of dopamine and norepinephrine. No significant differences were found. Platelet monoamine oxidase activity correlated significantly with pterin levels in male schizophrenic and in female control subjects.

Adult↗
PubMed1989

Antibodies to myelin-associated glycoprotein (MAG) in the cerebrospinal fluid of multiple sclerosis patients.

Cerebrospinal fluids (CSF) and sera from patients with multiple sclerosis (MS), other neurological diseases (ONDs) and healthy controls were tested for antibodies to myelin-associated glycoprotein (MAG) by several different assays. Using a very sensitive, solid-phase radioimmunoassay with radioiodinated protein A, a statistically significant elevation of anti-MAG antibodies was detected in MS CSFs in comparison to those from ONDs and healthy controls. The antibodies reacted with human MAG, but not with rat MAG, and appeared to be directed towards carbohydrate determinants in the glycoprotein. The CSFs from high IgG producers had significantly greater anti-MAG antibody levels than those from low IgG producers, even though the assays were done on CSF samples that had been normalized to the same IgG concentration. The elevated antibodies were not detected when the same samples were tested with a liquid-phase radioimmunoassay or an enzyme-linked immunosorbent assay, and the antibodies in the MS CSF also could not be detected by Western blotting. An elevated level of antibodies was not found in sera from MS patients by any of the assays, possibly because these samples gave higher and more variable background. The results suggest that there is a low level of humoral immunity to MAG in MS patients that can only be detected by the most sensitive assays. This weak immune response to MAG may be secondary to the demyelinating process, but could play a role in the progression of the disease.

Antibodies↗
PubMedDate not supplied

Elevated cerebrospinal fluid histidine in alcohol withdrawal.

Cerebrospinal fluid (CSF) histidine concentration was significantly elevated in seven patients early in the alcohol withdrawal syndrome (206.3 +/- 74.4 (SEM) nanomols/ml CSF). When these same patients were restudied an average of six days later when alcohol withdrawal was clinically resolved, their mean CSF histidine concentration continued to be significantly elevated (164.7 +/- 24.7) when compared to normal (12.0 +/- 0.5 nanomols/ml CSF). Other amino acids (aspartic acid, serine, alanine, methionine, leucine, tyrosine, phenylalanine, lysine and arginine) showed no definite changes from normal, and no change during the course of alcohol withdrawal. Possible reasons for these high concentrations and the extreme variability (especially early in alcohol withdrawal) are discussed.

Adult↗
PubMed2000

Current antipsychotic dose correlates to mononuclear cell counts in the cerebrospinal fluid of psychotic patients.

Elevated cerebrospinal fluid (CSF) angiotensin I-converting enzyme (ACE) levels have been evidenced in patients with schizophrenia who have been treated with antipsychotics. In order to explore a possible mononuclear cell origin of CSF ACE, the authors determined CSF ACE and CSF mononuclear cell counts from 25 acutely psychotic patients, who had been drug-free for at least 4 months but started on conventional antipsychotic medication within a few days before sampling. No correlations were found between CSF to serum ACE ratio and CSF mononuclear cell counts. However, CSF total mononuclear cell count, CSF lymphocyte count, and CSF mononuclear phagocyte count evidenced significant positive correlations with current dose of antipsychotic medication expressed as chlorpromazine equivalents. The authors conclude that no indication of a relationship between mononuclear cells and CSF ACE activity was found. Surprisingly, a relationship between chlorpromazine dose and CSF mononuclear cell counts was found, which may indicate drug-related changes in cell-mediated immunity. This finding needs replication and further corroboration in well-designed studies.

Acute Disease↗
PubMed2000

Cerebral trypsinogen expression in human and rat cerebrospinal fluid.

Trypsinogen was identified in cerebrospinal fluid (CSF), where it has not previously been reported and its activation state in experimental subarachnoid haemorrhage (SAH) in rats and in neurosurgical patients was determined. Trypsinogen activation peptide (TAP) release provided an equimolar marker for trypsinogen. Total TAP was significantly reduced to 26% of the baseline level (P<0.02) following experimental SAH in 15 rats but not in ten sham operated controls (P=0.3). TAP was also measured in patients with ruptured (n=11) and unruptured (n=9) aneurysms who underwent craniotomy to clip an aneurysm. Postoperatively there was a significant fall in TAP concentration (P<0.005) in both groups. Trypsinogen, as identified by CSF levels of TAP, is activated by SAH in rats and by craniotomy for aneurysmal clipping in patients.

Animals↗
PubMed1989

Rapid diagnosis of bacterial meningitis by an enzyme immunoassay of cerebrospinal fluid.

A total of 250 cerebrospinal fluid (CSF) specimens were analyzed using a rapid enzyme immunoassay (Pharmacia Meningitis EIA-Test) (EIA) for the detection of antigens of Haemophilus influenzae type b, Neisseria meningitidis (serogroups A,B,C) and Streptococcus pneumoniae (25 selected types). The test is performed in less than 1 h and read by the naked eye. EIA and coagglutination (CoA) were compared with a constructed reference that comprised samples which were either positive by culture and/or on direct microscopy (DM), or in which there were positive results with both EIA and CoA for the bacteria covered by the assays. Using this reference for CSF samples assayed in a period between two meningococcal meningitis epidemics, the sensitivity was 0.86 for EIA and 0.69 for CoA, the specificity 0.95 (EIA) and 0.97 (CoA), the predictive value for a positive result 0.81 (EIA) and 0.87 (CoA) and, the predictive value for a negative result 0.96 (EIA) and 0.93 (CoA). Antibiotics had been given to 54% of the patients before admission. All of the 56 samples that were positive in any of the tests taken during an epidemic of group A meningococcal disease were detected by EIA; CoA was negative in 45% and culture/DM was negative in 32%. Sequential dilutions of two CSF samples from which H. influenzae type b had been isolated, showed the EIA to be 16-32 times more sensitive than CoA. With both technical feasibility and good sensitivity and specificity, the EIA seems to be useful and reliable for the rapid diagnosis of bacterial meningitis, especially in situations where pretreatment with antibiotics are likely.

Antigens, Bacterial↗
PubMed1999

Low calcitonin gene-related, peptide-like immunoreactivity in cerebrospinal fluid from chronic pain patients.

Cerebrospinal fluid (CSF) levels of calcitonin gene-related peptide-like activity (CGRP-LI), were determined in 35 patients with painful orthopaedic disorders and the activity was compared to that of 12 healthy controls without pain. Fourteen patients had pain from osteoarthritis of the hip or the knee, 11 had rhizopathic pain due to a herniated lumbar disc and 10 had pain from a hip fracture. In all patients, decreased CGRP-LI was observed in CSF compared to the controls. The lowest values were found in the patients with osteoarthritis, while there was less, but still significant, reduction of CGRP-LI in the patients with herniated lumbar disc and those with a hip fracture. In most of the patients, CGRP-LI was also analysed at a second lumbar puncture after operative treatment, when pain had subsided or was reduced. However, the CGRP-LI remained low after treatment, which may suggest the influence of factors other than pain.

Adult↗
PubMed1992

Survival of Trypanosoma brucei brucei in cerebrospinal fluid.

Different compositions of artificial cerebrospinal fluid (CSF) and the CSF from sleeping sickness patients both with and without late-stage [i.e. central nervous system (CNS)] involvement were evaluated for their abilities to support survival of Trypanosoma brucei brucei. Artificial CSF, containing the major electrolytes, amino acids and carbohydrate components of healthy fluid, was equivalent to the CSF from patients without CNS involvement (survival time 20 hours). Normal CSF does not therefore contain substances which deter the parasite. The CSF from the late-stage patients did not support survival for longer than 10 hours, probably because it contained increased numbers of lymphocytes and antibodies.

Animals↗
PubMed1985

Chemotactic activity of cerebrospinal fluid in experimental cryptococcal meningitis.

Cerebrospinal fluid from rabbits with chronic cryptococcal meningitis was tested for its chemotactic activity towards polymorphonuclear cells and monocytes. CSF chemotactic activity was present; it peaked 5-8 days after infection, coinciding with the time when the number of inflammatory cells in CSF was greatest. However, little chemotactic activity could be found in the early stages of infection, during the initial ingress of inflammatory cells. The chemotactic activity appeared to be host-derived, with characteristics consistent with lymphokine(s) or C5a. Treatment with cortisone significantly reduced the CSF chemotactic activity for both cell types; this reduction may contribute to the severe CSF leukopenia observed in cortisone-treated animals, which are unable to eradicate this yeast infection. Modulation of CSF chemotactic activity may be important to the success or failure of the host central nervous system response to Cryptococcus neoformans.

Animals↗
PubMed2000

GDNF but not BDNF is increased in cerebrospinal fluid in amyotrophic lateral sclerosis.

Cerebrospinal fluid from 15 patients with ALS and 11 controls without neurological disease were analysed for levels of the neurotrophic factors BDNF and GDNF. Analyses were performed using a sensitive sandwich immunoassay (ELISA). There was no significant difference in BDNF levels between the ALS patients and the control subjects studied. Measurable levels of GDNF were found in 12 out of 15 ALS samples. GDNF was not detected in CSF from any of the control subjects. The finding of increased CSF levels of GDNF in ALS compared to controls, together with earlier findings of increased expression of GDNF mRNA in muscle in ALS, indicates that the capacity to synthesize GDNF is enhanced in this disorder.

Adult↗