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PubMed1979

Disproportionate elevation of the immunoglobulin G1 concentration in cerebrospinal fluids of patients with multiple sclerosis.

We determined immunoglobulin G (IgG) subclass concentrations and studied their distributions in the cerebrospinal fluids of patients suffering from multiple sclerosis, other inflammatory neurological diseases, and non-inflammatory diseases of the nervous system in comparison with a control group. In addition, the four subclass concentrations were measured in serum specimens of the multiple sclerosis and control groups. These data were correlated with the extent of local IgG synthesis in the subarachnoid spaces of the patients belonging to the different groups. We found a selective elevation of the IgG1 subclass in the cerebrospinal fluids of multiple sclerosis patients, and there was only a very small overlap of the IgG1 ranges of the multiple sclerosis and control groups. No major differences were detected between the IgG subclass distributions in different courses of multiple sclerosis nor between multiple sclerosis and control sera. The group with non-inflammatory diseases showed a uniform elevation of all four subclasses and a greater overlap with the normal range. This latter feature was combined with an elevated IgG1 concentration in the group with other inflammatory diseases. It is concluded that locally synthesized IgG in the cerebrospinal fluids of multiple sclerosis patients consists mainly of IgG1.

Humans↗
PubMed1983

Effect of mannitol infusions into the internal carotid artery on entry of two antibiotics into the cerebrospinal fluid and brains of normal rabbits.

The rapid infusion of hyperosmolar solutions into the internal carotid artery transiently disrupts the integrity of the blood-brain barrier, permitting entry of substances normally excluded from the nervous system. This study examined the effect of such an infusion on the penetration of vancomycin and tobramycin into the cerebrospinal fluid and brains of normal rabbits. Groups of five to seven animals were assigned either to control groups, receiving vancomycin or tobramycin alone, or to experimental groups, receiving these antibiotics with 40-s intracarotid infusions of 8.0 ml of 25% mannitol. Serum, cerebrospinal fluid, and brain specimens were obtained for assay 135 min after dosage. Concentrations of these antibiotics in serum were comparable in control and experimental groups; concentrations of the antibiotics in cerebrospinal fluid were significantly higher in the experimental groups. Mean (+/- standard deviation) concentrations of the antibiotics in cerebrospinal fluid were, respectively, less than 0.5 and 4.1 +/- 4.6 micrograms of vancomycin per ml and 0.6 +/- 0.5 and 3.4 +/- 2.4 micrograms of tobramycin per ml in the control and experimental groups. The concentrations of these antibiotics in brains were also higher in the experimental groups. This trend achieved statistical significance in the tobramycin studies, where control animals uniformly had tobramycin concentrations in brains of less than 0.1 microgram/g and experimental group animals had a mean concentration of 0.4 microgram/g. Additional studies with tobramycin indicated that intracarotid antibiotic administration immediately after the mannitol infusion further augmented antibiotic concentrations in brains.

Animals↗
PubMedDate not supplied

High resolution protein electrophoresis of 100 paired canine cerebrospinal fluid and serum.

This study was performed to investigate the diagnostic relevance of cerebrospinal fluid (CSF) high resolution electrophoresis. The laboratory technique was applied to 100 paired samples of canine CSF and serum, with paired samples tested during the same analytical run, as recommended in human medicine. Ninety four of the dogs had a neurological disease and 6 healthy dogs served as a control group. A strong linear correlation between CSF total protein concentration and the albumin quota (AQ) was found in the control group and in the inflammatory (infectious or noninfectious), neoplastic, and miscellaneous groups: AQ = 0.015 CSF total protein--0.102, r = 0.990. This correlation suggests that an increased CSF total protein concentration can be an indicator of blood brain barrier dysfunction. The highest median AQ value was found in the aseptic suppurative meningitis group, but no statistical differences were found between this and the other groups. The AQ, calculated with this technique, did not provide any additional information. Moreover, although unexpected, the electrophoretic profiles were not characteristic of any particular disease. In conclusion, this study did not confirm high resolution electrophoresis of paired CSF and serum samples to be a valuable ancillary diagnostic tool for canine neurological diseases.

Animals↗
PubMed1992

Changes in piglet auditory brainstem response amplitudes without increases in serum or cerebrospinal fluid neuron-specific enolase.

We studied the relationship between changes in auditory brainstem responses (ABR) and serum and cerebrospinal fluid levels of neuron-specific enolase (NSE) in hyperbilirubinemic 2- to 8-d-old piglets. Infusion of a stabilized solution of bilirubin resulted in serum bilirubin levels of 571.1 +/- 48.8 mumol/L (mean +/- SEM) after 6 h. ABR were obtained at baseline and then hourly until the piglets were killed. We measured peak amplitudes and latencies for waves I-V, as well as latency for the post-V trough. Changes in amplitudes and latencies were analyzed as slopes because of heterogeneous variances. Over time, a significant reduction was observed in peak II-V amplitudes of bilirubin-infused piglets, but not in those of corresponding controls. No change was observed in latencies. NSE was analyzed by RIA. Serum NSE remained stable throughout the experiment (means 5.1-6.6 micrograms/L) and did not differ between the groups. Cerebrospinal fluid NSE values also remained stable, and no differences that could be ascribed to hyperbilirubinemia were detected. We conclude that hyperbilirubinemia induced significant changes in piglet ABR amplitudes without concomitant evidence of severe neuronal compromise, as might have been indicated by significant increases in serum and/or cerebrospinal fluid NSE levels. This provides further support to the clinical impression that early ABR changes during hyperbilirubinemia may be reversible.

Animals↗
PubMed1997

Frontal brain and leptomeningeal biopsy specimens correlated with cerebrospinal fluid outflow resistance and B-wave activity in patients suspected of normal-pressure hydrocephalus.

OBJECTIVE: Normal-pressure hydrocephalus (NPH) is a potentially treatable syndrome with abnormal cerebrospinal fluid dynamics. Meningeal fibrosis and/or obliteration of the subarachnoid space has been suggested as the pathoanatomic basis. The purpose of the present study was to investigate whether meningeal fibrosis causes increased resistance to cerebrospinal fluid outflow (R(out)) and/or increased B-wave activity and whether pathological changes in the brain parenchyma after brain compliance, causing increased B-wave activity. METHODS: The study involved a group of 38 consecutively studied patients with clinical and radiological evidence of idiopathic NPH, for whom a frontal brain biopsy was obtained. For 29 patients, hydrodynamic criteria of NPH were fulfilled and a ventriculoperitoneal shunt was performed. RESULTS: Meningeal fibrosis was found in 12 of 25 biopsies containing arachnoid tissue, but no correlation with R(out) or B-waves was found. Pathological parenchymal changes, most often Alzheimer's disease (10 cases) or vascular changes (10 cases), were found in 21 biopsies, but no correlation with B-waves or R(out) was found. CONCLUSION: The results suggest that leptomeningeal fibrosis is not the only pathoanatomic basis of increased R(out) and/or B-wave activity in patients with NPH and that various degenerative changes in the parenchyma may be responsible for the altered cerebrospinal fluid dynamics characteristic of NPH.

Adult↗
PubMed1986

Evaluation of adenosine deaminase activity and antibody to Mycobacterium tuberculosis antigen 5 in cerebrospinal fluid and the radioactive bromide partition test for the early diagnosis of tuberculosis meningitis.

A number of different biochemical and serological tests have been described recently for the early and accurate diagnosis of tuberculous meningitis. None of these tests has yet gained widespread acceptance in clinical medicine or in microbiology laboratories. To investigate this problem we evaluated adenosine deaminase activity (ADA), an enzyme linked immunosorbent assay (ELISA) that detects antibody to antigen 5 of Mycobacterium tuberculosis, and the radioactive bromide partition test (BPT) in the cerebrospinal fluid (CSF). Cerebrospinal fluid specimens from children with tuberculous, pyogenic, and viral meningitis as well as from patients with pulmonary tuberculosis without meningitis and from controls with normal CSFs were included inn the study. In addition, we estimated ADAs in serum samples from selected children in these groups. The sensitivity and specificity of the three tests evaluated in the CSF were: ADA assay 73% and 71%; BPT 92% and 92%; and ELISA for antibody to antigen 5, 53% and 90%, 40% and 94%, and 27% and 100%, respectively, at tires of more than or equal to 1:20, 1:40, and 1:80. The serum ADA was lower (11.0 +/- 6.15 IU/l) in children with tuberculous meningitis when compared with those with pulmonary tuberculosis alone (25.8 +/- 20.9 IU/l). The BPT was found to be the most reliable test in the early differentiation of tuberculous from other causes of meningitis and remained abnormal for a period of up to five months after the beginning of treatment. Accordingly, we believe that the BPT should be used in conjunction with bacterial and fungal antigen detection systems for the initial differentiation of clinically suspicious tuberculous meningitis from Gram or culture negative cases, or both, of bacterial and fungal meningitis.

Adenosine Deaminase↗
PubMed1989

The effect of cerebrospinal fluid pressure on dural venous pressure in young rats.

In order to study cerebrospinal fluid (CSF) absorption across the dural sinus wall, the effect of CSF pressure (recorded from the cisterna magna) on dural venous pressure (recorded from the transverse sinus) was investigated in groups of rats at 2, 10, 20, and 31 days after birth and in adulthood. At normal resting pressures there was no positive pressure gradient between the CSF and sinus venous blood in 2-, 10-, and 20-day-old rats, but in 31-day-old and adult rats there was a positive gradient of 16 and 12 mm H2O, respectively. A series of constant-rate infusions of artificial CSF was made into the cisterna magna, and subsequent plateaus in both CSF and venous blood were recorded. The gradient of a plot of plateau pressure against infusion rate gave the overall resistance to absorption of the CSF for each age group, which was higher in 2- and 10-day-old rats than at three older ages. The effect on dural venous pressure was age-related, with the largest increase at 2 days, the smallest at 20 days, and no effect at 31 days or in adults. The pressure difference between CSF and sinus blood has been used to calculate resistance to absorption across the sinus wall. This showed that the high overall resistance to drainage in young rats can be largely accounted for by the rise in sinus pressure. It is concluded that drainage of CSF into the sinuses is greatly restricted in young animals.

Absorption↗
PubMed1997

Cerebrospinal fluid findings in children with Lyme disease-associated facial nerve palsy.

OBJECTIVE: To determine the relative frequency of abnormal cerebrospinal fluid (CSF) findings in children with Lyme disease-associated facial nerve palsy. DESIGN: A clinical series. A prospective evaluation was undertaken of the condition of children seen between 1988 and 1996 at a single medical center in a Lyme disease endemic area. PATIENTS: Forty children (24 boys and 16 girls, aged 3-19 years) with new onset facial nerve palsy who met the Centers for Disease Control and Prevention case definition of Lyme disease. INTERVENTIONS: Neurologic examinations. Cerebrospinal fluid analysis. MAIN OUTCOME MEASURES: Rates of abnormal CSF findings: white blood cell count, protein level, and Borrelia burgdorferi-specific CSF assays. RESULTS: Cerebrospinal fluid white blood cell count, protein level, or both were abnormal in 27 (68%) of the children. Thirty-six (90%) of the 40 children had a CSF abnormality consistent with central nervous system infection or immune involvement by B burgdorferi. Of the 22 children with CSF pleocytosis, only 7 (32%) had headache and none had meningeal signs. CONCLUSIONS: Most children with Lyme disease-associated facial nerve palsy have CSF abnormalities. Our studies indicate that, in endemic areas, facial nerve palsy in children may be a marker of Lyme disease and occult meningitis. When Lyme disease is suspected, CSF should be examined; in some cases, it may be helpful to expand beyond routine CSF studies to look at a battery of B burgdorferi-specific assays.

Adolescent↗
PubMed2004

Presence of HTLV-I Tax protein in cerebrospinal fluid from HAM/TSP patients.

Infection with human T-cell lymphotropic virus type I (HTLV-I) have been associated with the development of the HTLV-I-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP). The disease affects the pyramidal tract at the distal segments of spinal cord, generating a spastic paraparesis. We studied the presence of Tax protein in cerebrospinal fluid cells and spinal fluid (CSF) of 35 Chilean patients: 22 HAM/TSP patients (15 HTLV-I-seropositives, and 7 seronegatives), and 13 controls (9 PSP and 4 CJD non-infected patients). Tax antigens were evaluated with monoclonal antibodies reacting with Tax by immunofluorescence and ELISA assays in cerebrospinal fluid cells and CSF, respectively. Proviral was evaluated by PCR of tax gene in cerebrospinal fluid cells. Tax antigen was detected in CSF and lymphocytes of CSF from 4 and 12 HAM/TSP patients, respectively. Lymphocytes of CSF of 8 HAM/TSP (6 seropositives and 2 seronegatives) showed the presence of tax gene. These results show that cells of CSF from HAM/TSP patients are able to express and export Tax protein towards the CSF. This is the first report of the presence of Tax protein in cerebrospinal fluid cells and CSF from HAM/TSP HTLV-I seronegative patients.

Adult↗
PubMed1978

Hormones, electrolytes, and cerebrospinal fluid proteins in manic-melancholic patients.

The concentrations of insulin and thyroid hormones, tryptophan, electrolytes, urea, plasma proteins in the cerebrospinal fluid, and glucose in blood and cerebrospinal fluid in manic-melancholic patients were studied. As control groups served patients suffering from other psychiatric disorders as well as neurological and orthopedic patients. Apart from the blood values of thyroid hormones, the results showed no differences between the various diagnostic groups, neither in the abnormal states nor when recovered. For blood thyroxine and free thyroxine index, a statistically significant differences was seen in unipolar (melancholic) patients, namely a decrease concomitant with the clinical improvement. A tendency in the opposite direction of the thyroxine values was found in bipolar (melancholic) patients. In the manic group a marked decrease in the thyroxine values was obtained in the lithium-treated patients.

Adolescent↗
PubMed1981

Melatonin concentrations in human serum, ventricular and lumbar cerebrospinal fluids as an index of the secretory pathway of the pineal gland.

Melatonin was extracted from human sera, ventricular and lumbar cerebrospinal fluids taken within an hour from 25 patients undergoing neurosurgical operations such as ventricular shunts and craniotomy. Using a radioimmunoassay procedure, it was possible to measure the melatonin concentrations in 3 groups of patients: (a) those with obstructive hydrocephalus, (b) those with communicating hydrocephalus, and (c) those with normal cerebrospinal fluid flow. It was demonstrated that melatonin levels were higher in sera compared with those in lumbar and ventricular cerebrospinal fluids thus supporting the view that melatonin is primarily secreted into the bloodstream.

Cerebral Ventricles↗
PubMed2000

[The value of the polymerase chain reaction in cerebrospinal fluid for the diagnosis of herpetic encephalitis: a report of 2 cases and a review of the literature].

Brain biopsy has been considered the gold-standard test for the diagnosis of herpetic encephalitis. However, because of its cruence, other non invasive methods have been developed for its diagnosis. In recent years polymerase chain reaction (PCR) in cerebrospinal fluid has been employed for the diagnosis of herpetic encephalitis (HE). We report two cases of clinically suspected HE in which DNA of herpes simplex virus was amplified by PCR from cerebrospinal fluid, and review the role of this method for the diagnosis of HE. Two patients were admitted to the emergency room presenting clinical pictures and cerebrospinal fluid samples suggestive of lymphocytic meningoencephalitis. Both were admitted in the intensive care unit because of altered level of consciousness, beginning empiric treatment with intravenous acyclovir as HE was suspected. Clinical outcomes were favourable in both cases, being confirmed the presence of herpes simplex DNA in cerebrospinal fluid by PCR in the two patients. We have reviewed in the literature the value of PCR for the diagnosis of HE in comparison with other ancillary tests as brain biopsy and serology. PCR could reach according with some authors a sensibility of 98% and a specificity of 94%.

Acute Disease↗
PubMed1993

Ureaplasma urealyticum in the cerebrospinal fluid of a premature infant.

A premature infant, born at 28 weeks' gestation, was found to be colonized with Ureaplasma urealyticum and developed intraventricular hemorrhage and progressive hydrocephalus during the first weeks of life. The organism was isolated from the infant's cerebrospinal fluid in the absence of marked cerebrospinal fluid pleocytosis, but meningitis was suspected on the basis of low glucose and high protein content. Since this organism was resistant to erythromycin by clinical criteria, the infant was treated with chloramphenicol for 20 days. Cerebrospinal fluid sterilization was demonstrated; hydrocephalus, however, was persistent and made intraventricular shunt placement necessary.

Chloramphenicol↗
PubMed1992

Cerebrospinal fluid neurochemistry in children and adolescents with obsessive-compulsive disorder.

Cerebrospinal fluid hormones, monoaminergic metabolites, and dynorphin A (1-8 sequence) were examined in 43 children with severe, primary obsessive-compulsive disorder. Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid were positively correlated with one of eight obsessive-compulsive disorder severity ratings and three of seven measures of improvement following 5 weeks of treatment with clomipramine hydrochloride. Arginine vasopressin concentration was significantly and negatively correlated with several ratings of obsessive-compulsive disorder symptom severity, while oxytocin concentration was positively correlated with depressive symptoms. The ratio of arginine vasopressin to oxytocin was also negatively correlated with obsessive-compulsive disorder and depressive symptoms. Comorbid affective disorder was associated with decreased arginine vasopressin concentrations, while concomitant anxiety disorder was associated with increased oxytocin. Dynorphin A (1-8 sequence), homovanillic acid, corticotropin, 3-methoxy-4-hydroxyphenylglycol, and corticotropin releasing hormone were not significantly related to obsessive-compulsive disorder symptoms. These results seem to indicate that arginine vasopressin may be related to obsessive-compulsive disorder symptom severity, while 5-hydroxyindoleacetic acid might be associated with drug response.

Adolescent↗
PubMed1989

Cerebrospinal fluid indices of blood-brain barrier permeability following adrenal-brain transplantation in patients with Parkinson's disease.

Cerebrospinal fluid (CSF) and serum or plasma concentrations of albumin, IgG and carbidopa were measured before and after adrenal-brain transplantation in patients with Parkinson's disease to indirectly assess blood-brain barrier (BBB) integrity. Previous studies in animals have suggested that the BBB is compromised by cerebral transplantation. CSF and plasma levodopa was also measured to permit comparison with the carbidopa values, recognizing that levodopa readily crosses the BBB via facilitated transport. Our patients underwent adrenal-brain transplantation in accordance with the method of Madrazo et al. (I. Madrazo, R. Drucker-Colin, V. Diaz, J. Martinez-Mata, C. Torres, and J. J. Becerril, 1987, N. Engl. J. Med. 316: 831-834) in which adrenal medullary pieces are implanted in the head of the caudate nucleus, in contact with the cerebrospinal fluid. All patients were maintained on oral carbidopa/levodopa therapy after surgery. CSF albumin/serum albumin and CSF IgG/serum IgG ratios were initially elevated above the preoperative baseline 6 weeks after the surgery; however, these values returned to the preoperative baseline by 6 months following the operation in six of seven patients. This suggested that the BBB was sufficiently intact to exclude these larger protein molecules from the CSF of these six patients. On the other hand, exogenously administered carbidopa, which normally is largely excluded from the cerebrospinal fluid by the BBB, was modestly increased in the CSF in four of the five patients in which it was measured. This suggests that the transplant BBB might be partially patent to small molecules for at least 6 months after the surgery. Whether increased passage of carbidopa into CSF and perhaps the transplant is of clinical significance has yet to be determined. Median CSF levodopa did not increase after surgery, probably because a limited defect in the BBB would be likely to be overshadowed by the effects of facilitated transport. CT scans performed following intravenous iothalamate meglumine contrast failed to reveal enhancement (dye leakage) near the transplantation site; however, artifact from the metal surgical clips used in the Madrazo procedure prevented good visualization of the area.

Adrenal Medulla↗
PubMed1978

[Phosphocreatine kinase activity in the cerebrospinal fluid in different types of stroke].

In 45 patients with brain strokes (thrombosis, embolus, intracerebral haemorrhages) and subarachnoid haemorrhages the CPK activity was determined in the cerebrospinal fluid. In most cases a significant rise was observed in CPK activity in the cerebrospinal fluid as compared to the control group. In two cases the dynamics of CPK activity changes were studied in the cerebrospinal fluid during the stroke. It seems that a significant rise in CPK activity develops in the initial phase of the stroke when the area of nervous tissue softening develops and spreads.

Cerebrovascular Disorders↗
PubMed1984

Neuronotrophic activities in cerebrospinal fluid of head trauma patients.

Neuronotrophic factors (NTFs) are agents required for neurons to survive in tissue culture. In this study, we investigated the presence of NTFs in cerebrospinal fluid (CSF) of patients with central nervous system (CNS) injury. Cerebrospinal fluid was collected from 15 patients with acute CNS lesions in whom ventricular catheters had been placed to monitor and to facilitate the control of intracranial pressure. Neuronotrophic activity within the CSF was assayed using cultures of neurons derived from fetal rat hippocampus and embryonic chick cerebral cortex. Cerebrospinal fluid from all 15 patients contained NTFs which supported the survival of rat hippocampal neurons. Survival of chick cortex neurons was supported by eight of nine CSF samples. In the 11 patients from whom consecutive CSF samples were available, NTF activity assayed in rat hippocampal cultures tended to decrease during the first several days after CNS injury. In CSF collected from three patients by lumbar puncture for diagnosis of "nontraumatic" conditions, no NTFs were detectable. NTFs supporting hippocampal neurons were also detected in extracts of blood clot obtained from normal volunteers. Neuronotrophic activity in the CSF was heat sensitive, nondialyzable, and macromolecular, suggesting its association with a protein(s). These observations suggested that (i) NTFs are detectable in human CSF after CNS injury, (ii) NTFs appear in response to the injury itself, and (iii) at least some human NTFs can support the survival in culture of nonhuman CNS neurons.

Animals↗
PubMed1989

Determination of homovanillic acid, 5-hydroxyindoleacetic acid and pressure in the cerebrospinal fluid of collie dogs following administration of ivermectin.

Twelve adult Collie dogs were studied to determine the effects of ivermectin on neurotransmitter metabolites released from the brain into the cerebrospinal fluid (CSF) and on CSF pressure. Ten of the 12 Collies were given ivermectin orally at a concentration of 200 micrograms/kg body weight. Three of these 10 Collies showed clinical signs of ivermectin-induced toxicosis which progressed into a state of unresponsive recumbency in 2 dogs. Cerebrospinal fluid pressures and neurotransmitter metabolite concentrations in cisterna magna CSF were analysed 49 to 50 hours after administration of ivermectin in 6 of the 10 treated dogs, and in the 2 untreated control Collies. Cerebrospinal fluid pressures were within normal limits in all dogs. However, compared to the CSF concentrations in the 2 untreated and 3 non-reactive Collies, the 2 ivermectin-reactive Collies still in recumbency had elevated CSF concentrations of homovanillic acid (HVA), a metabolite of dopamine, and 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of serotonin. These findings suggest an association between altered neurotransmission and severe ivermectin-induced neurological abnormalities. No evidence of elevated intracranial pressure was found.

Animals↗