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Coagulation and fibrinolytic activity of cerebrospinal fluid.

Fibrin/fibrinogen degradation products (fragments D and E) were detected in cerebrospinal fluid in 23.4% of 252 patients admitted to a neurological/neurosurgical unit. Other coagulation proteins of low molecular weight (plasminogen and factor IX) were also present but larger proteins (fibrinogen and factor V) were not. These findings are consistent with protein leakage across a blood-CSF barrier damaged by inflammatory, vascular, or neoplastic disease. Fibrin/fibrinogen degradation products in cerebrospinal fluid after subarachnoid haemorrhage may not, therefore, be a reliable index of increased fibrinolytic activity in the subarachnoid space and may be misleading when selecting patients for fibrinolytic blockade.

Acute Disease↗

"Stat" measurements of L-lactate in whole blood and cerebrospinal fluid assessed.

A first-generation semi-automatic amperometric lactate analyzer (Yellow Springs Instrument Co.) was assessed for urgent ("stat"), rapid laboratory measurements in whole blood and cerebrospinal fluid. For whole blood, measured lactate concentration and hematocrit were linearly correlated. An improved equation is presented for estimating the concentration of lactate in plasma from measurements in whole blood. The 95% reference range for the concentration of lactate in paired samples of capillary and venous whole blood from 40 healthy laboratory adults was found to be 0.4-1.5 mmol/L and 0.3-1.5 mmol/L, respectively. The 95% ranges for lactate in whole blood from 24 uncomplicated vaginal deliveries at term were established for cord venous blood, 1.2-5.0 mmol/L; cord arterial blood, 1.6-5.5 mmol/L; and maternal venous blood, 1.7-6.6 mmol/L. The 95% paired ranges were established for 20 lumbar-anaesthetized urological patients without neurological disorders after induction of anaesthesia for venous whole blood and cerebrospinal fluid (venous blood, 0.5-1.3 mmol/L; cerebrospinal fluid, 1.1-2.4 mmol/L).

Adult↗

Measurement of prostaglandins in the cerebrospinal fluid in cat, dog, and man.

Prostaglandins are involved in the modulation of various central functions (neurotransmitters and hypothalamic hormone release, thermoregulation, cerebrovascular tone) and their levels increase in pathological situations [subarachnoid hemorrhage (SAH), stroke, convulsive disorders, etc.]. This study, using sensitive and specific antibodies, examined levels of four eicosanoids, prostaglandins E2 and F2 alpha (PGE2, PGF2 alpha); and the metabolites of PGI2, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and of thromboxane A2, thromboxane B2 (TxB2), in the cerebrospinal fluid (CSF) obtained atraumatically from three species (human, canine, and feline). An assessment of the methodologic procedures (extraction and radioimmunoassay) was carried out. Human lumbar cerebrospinal fluid was shown to contain PGF2 alpha (15-44 pg/ml), 6-keto-PGF1 alpha (undetectable to 39 pg/ml), and TxB2 (undetectable to 28 pg/ml), whereas PGE2 was undetectable (less than 18 pg) in all cases. In both animals species the eicosanoid concentrations were 3- to 30-fold higher than humans for every prostaglandin examined. Although the prostaglandin profile for a given species remained constant (cat, PGE2:6-keto-PGF1 alpha:TxB2:PGF2 alpha; dog, TxB2:PGE2:6-keto-PGF1 alpha:PGF2 alpha), the absolute levels were found to be lower in the pentobarbital-anesthetized animals than in conscious cats. The correspondence of the prostaglandin profiles found in cerebrospinal fluid with the profiles reported in the literature in brain homogenates for the same species supports the hypothesis that cerebrospinal fluid levels of prostaglandins reflect the relative rates of synthesis in neural tissue.

6-Ketoprostaglandin F1 alpha↗

Dexamethasone and ergonovine effects on cerebrospinal fluid pressure in conscious rats.

Prior work showed that intracerebroventricular (i.c.v.) infusions of artificial cerebrospinal fluid (aCSF), at a rate of 8 microliters/min x 10 min, elevated CSF pressure (CSFp) of conscious rats after a 2-hour delay. The rise was associated with an increased resistance to outflow and decreased intracranial compliance. When maintained by a continuous infusion of 0.25 microliter/min into each lateral ventricle, CSFp recordings can be made for 24 h and a higher CSFp occurs. Here, we pretreated rats with ergonovine or dexamethasone to determine their effects on the delayed CSFp rise. Ergonovine (0.5 mg/kg i.p.) pretreatment, in a 6-hour protocol using only the 10-min infusion, slightly reduced CSFp (p < 0.05, one-tail test) but the time course of the delayed rise in CSFp was unchanged (p > 0.05). Ergonovine increased intracranial compliance (p < 0.05) 20 min after infusion when CSFp was normal, but not when CSFp was elevated at 4 h (p > 0.05). Dexamethasone (40 micrograms i.m.) pretreatment was tested in the 24-hour protocol. It reduced (p < 0.05) normal CSFp during the 2-hour lag after infusion and the CSFp rise was reduced (p < 0.05) for about 8 h. However, the time course and ending CSFp were unchanged (p > 0.05). Thus, prior cerebral vasoconstriction or a steroidal anti-inflammatory drug have partial efficacy in reducing CSFp, but do not prevent the unknown events that precede the delayed CSFp rise after i.c.v. infusions.

Animals↗

Plasma, red cell and cerebrospinal fluid concentrations of mannitol and sorbital in patients with severe chronic renal failure.

The concentrations of mannitol and sorbitol in plasma, red cells, cerebrospinal fluid and urine were determined in 24 patients with chronic renal failure; 10 of them were on conservative treatment and 14 were haemodialysed three times weekly. The mannitol concentration was significantly increased in the plasma and the cerebrospinal fluid of the uraemic patients compared with the controls. In six out of ten uraemic patients mannitol clearance values exceeded creatinine clearance values. The plasma concentration of sorbitol was undetectable or very low in all patients and control subjects. Red-cell and cerebrospinal fluid concentrations of sorbitol showed a large individual variation in the uraemic patients on conservative treatment and did not correlate with kidney function. During dialysis the mannitol concentration decreased, leading to a small osmotic gradient between the plasma and the red cells. The changes in the concentration of mannitol during dialysis showed no connection with the symptoms of central nervous disturbance which appeared during dialysis treatment. The red cell sorbitol concentration during dialysis increased by about 20%. There was a correlation (p less than 0.05) between t,e increase in sorbital in cereemic patients.

Creatinine↗

Automated counting of white and red blood cells in the cerebrospinal fluid.

The objective of this study was to examine to what extent the automated method of the Bayer H*2 instrument could replace the visual counting of white and red blood cells in cerebrospinal fluid. The number of white blood cells as well as the percentage of mononuclear and polymorphonuclear cells were counted in the 'Baso channel' (Research screen 3) whereas the number of red cells were registered as the 'R-count' (Research screen 1). All automated cell counts were compared to visual estimates. The automated count yielded reliable results down to 5 x 106 white blood cells/l and 5 x 108 red blood cells/l. In some samples 'noise' was present in the Baso channel. A correct white blood cell count could then be obtained by counting the cells directly as dots on the screen. It was possible to differentiate between polymorphnuclear cells and mononuclear cells at all WBC concentrations. The automated counting of cerebrospinal fluid can be performed without changing thresholds or sample volumes of the instrument. Thus, in the routine practice it will be possible to alternate between automated counting of whole blood samples and cerebrospinal fluid samples.

Adult↗

The clinical, cerebrospinal fluid, and histopathologic effects of epidural ketorolac in dogs.

OBJECTIVE: To evaluate the clinical, cerebrospinal fluid (CSF), and histopathologic effects of epidural ketorolac. STUDY DESIGN: Blinded, randomized, placebo controlled study. ANIMALS: Twenty-two adult mixed breed dogs with 16 treatment and 6 control dogs, weighing 14.4 to 29.8 kg. METHODS: Dogs were anesthetized and epidural catheters were placed at the lumbosacral space. Catheter placement was evaluated fluoroscopically. Ketorolac (0.4 mg/kg) or placebo (5% ethanol) was administered epidurally over a 52-hour period, with 5 injections given at 12-hour intervals. At 1, 2, 4, or 8 hours after the first and last injection of ketorolac, dogs were anesthetized and CSF was obtained. Control dogs had CSF sampled 1 hour after the first and last ethanol injection. Neurologic function and pain responses were evaluated before and during the study. Selected dogs were then killed and necropsies performed. RESULTS: None of the dogs exhibited any clinical or neurologic abnormalities during the study. No statistical difference was noted in pain response or CSF analysis between treatment and control dogs. Gross necropsy revealed gastrointestinal ulceration of varying degrees in all treatment dogs. Histopathologic analysis of the spinal cord and meninges revealed minimal focal leptomeningeal phlebitis in 2 of 8 treatment dogs and minor subdural inflammation in 1 control dog. No changes to the neural structures were noted in any dogs. CONCLUSIONS: Epidural administration of ketorolac did not cause clinical signs, alteration in CSF values, or pathologic changes to the spinal cord when used for short duration. Gastrointestinal ulceration was common when ketorolac was administered epidurally at 0.4 mg/kg every 12 hours for 5 treatments. CLINICAL RELEVANCE: This study documented the neurologic safety of epidural ketorolac in dogs before an efficacy trial can be performed. Gastrointestinal ulceration may limit use to short duration or a single injection.

Anesthesia, Epidural↗

[Indications for the intrathecal infusion test in disorders of cerebrospinal fluid dynamics].

Indications for and results of the intrathecal infusion test including 50 patients with chronic disturbances of the circulation of the cerebrospinal fluid are presented and discussed. The computer-aided infusion test permits in 93 per cent a reliable differentiation between patients with a normal-pressure hydrocephalus and those with cerebro-atrophic processes. Functional checking of the valve systems is a further indication for the intrathecal infusion test. In patients with a classical pressure hydrocephalus or subdural hygromas, however, we do not see an indication for this invasive examination procedure.

Adolescent↗

Temperature-dependent variations of 5-hydroxyindoles in ventricular cerebrospinal fluid--an in vivo voltammetric study.

The in vivo voltammetric signal of 5-OH-indoles increased or decreased in the ventricular cerebrospinal fluid when body temperature was artificially increased or decreased in rats in acute experiments. The increase of the signal occurring after raising the body temperature was facilitated by premedication with the monoamine oxidase inhibitor pargyline. It was not abolished by pretreatment with the serotonin synthesis inhibitor para-chlorophenylalanine, although the latter caused an 85% decrease of ventricular 5-OH-indole level. No similar effects were demonstrable in the 5-OH-indole signal of the caudate nucleus recorded simultaneously. An increase of the 5-OH-indole peak was found also in animals chronically implanted with voltammetric electrodes when the ambient temperature was increased in their cages. According to the results of in vitro experiments, a direct physical effect of changes in brain temperature on the sensitivity of the voltammetric electrodes cannot account for changes found in the cerebrospinal fluid. These data, therefore, demonstrate that the increase of body temperature is followed by an increase of 5-OH-indole concentration in the ventricular cerebrospinal fluid. The in vivo voltammetric technique appears to be a suitable method for studying the serotonergic mechanisms involved in thermoregulatory processes.

Animals↗

Cerebral dysfunction in fibromyalgia: evidence from regional cerebral blood flow measurements, otoneurological tests and cerebrospinal fluid analysis.

Measurements of regional cerebral blood flow (rCBF), analysis of cerebrospinal fluid, auditory brain stem responses (ABR) and oculomotor tests were performed in 19 patients with fibromyalgia. The results from the rCBF measurements showed a normal flow level with slight but significant focal flow decreases in dorsolateral frontal cortical areas of both hemispheres. The ABR results showed signs of dysfunction at least at the brain stem level and the oculomotor tests showed high frequency of pathology. The cerebrospinal fluid analysis showed discrete changes in the cell differential count. Possible explanations for the involvement of the central nervous system in fibromyalgia are discussed.

Adult↗

Quantitative analysis of cerebrospinal fluid flow in patients with cervical spondylosis using cine phase-contrast magnetic resonance imaging.

OBJECTIVE: To investigate changes in the cerebrospinal fluid flow in patients with cervical spondylosis using cine phase-contrast magnetic resonance (MR) imaging. METHODS: The participants included 44 healthy volunteers, 11 asymptomatic patients with evidence of degenerative changes of the cervical spine revealed by MR imaging but no neurological symptoms referable to those abnormalities, and 23 symptomatic patients with myelopathy who underwent surgery. Cervical spondylotic myelopathy was evaluated using the Japanese Orthopedic Association scores, and the percentage reduction of the transverse cord area at the level of maximum cord compression was measured on T1-weighted magnetic resonance images. A cine phase-contrast MR pulse sequence with peripheral gating was used to measure the cerebrospinal fluid flow direction and velocity in the ventral subarachnoid spaces at the C1 and T1 levels. RESULTS: The velocity waveforms produced by plotting flow velocity at 16 intervals during one cardiac cycle significantly differed among the healthy volunteers, asymptomatic patients, and preoperative symptomatic patients. However, velocity waveforms did not differ between the healthy volunteers and the postoperative patients at the C1 level. Decreases of flow velocity were significantly correlated with the severity of myelopathy and the percentage reduction of cord area. Patients with severe myelopathy (Japanese Orthopedic Association score of 0-9 points) or greater than 30% reduction of cord area showed significantly decreased flow velocity compared with those with mild myelopathy (Japanese Orthopedic Association score of 10-17 points) or less than 30% reduction of cord area. Changes in flow velocity were not correlated with multiplicity of the lesion or the level of maximum cord compression. Postoperative improvement of flow velocity was not correlated with neurological recovery. CONCLUSION: Cine phase-contrast MR imaging allows quantitative and noninvasive assessment of changes in cerebrospinal fluid flow in patients with cervical spondylosis.

Adult↗

Determination of 3,4-dihydroxyphenylalanine (DOPA) in plasma and cerebrospinal fluid by high performance liquid chromatography with electrochemical detection.

We report a reliable method for determining DOPA levels in plasma and cerebrospinal fluid. The method is based on complete conversion of DOPA to dopamine and quantification by HPLC-ECD of the dopamine formed. Lower limit of detection was 0.5 nmol/l. No differences in plasma DOPA levels were found between normal children (0-15 yr, n = 60), normal adults (n = 39) and patients with essential hypertension (n = 40) or Parkinson's disease (no DOPA therapy, n = 30). In normal individuals and in patients with essential hypertension venous plasma levels were higher than arterial levels (10.2 vs 9.3 nmol/l, p less than 0.001, V/A ratio 1.11 (SD 0.08), n = 15). Sympathetic stimuli (standing, tilting, bicycle exercise, tyramine) did not influence DOPA levels. In untreated depressed patients (n = 10) and in non-parkinsonian neurological patients (n = 12) cerebrospinal fluid levels of DOPA were 4.5 (SD 2.4) and 5.2 (SD 1.3) nmol/l respectively. A direct method for the measurement of DOPA by HPLC-ECD after deproteinization of plasma is also described and compared with the conversion method. Good agreement was found when plasma DOPA levels exceeded 0.25 mumol/l (y(conversion method) = 0.943x (direct method) + 0.118; n = 60; r = 0.985). The direct method, because of greater simplicity and the possibility of simultaneous measurement of the DOPA metabolite 3-O-methyldopa, is the method of choice with plasma samples from DOPA-treated patients. In non-DOPA treated individuals the conversion method is superior and has proved to be an accurate and sensitive method for the determination of DOPA levels in plasma and cerebrospinal fluid.

Adolescent↗

Enzyme-linked immunosorbent assay with a monoclonal antibody for detecting group A meningococcal antigens in cerebrospinal fluid.

Hybridomas were produced from spleen cells of BALB/c mice immunized with a membrane preparation from Neisseria meningitidis group A strain 4402 and S194/5.XXOBU.14 myeloma cells. The hybridomas were screened for secretion of antibodies suitable for an enzyme-linked immunosorbent assay (ELISA) diagnostic for group A meningococcal meningitis. One hybridoma antibody, 3G7, was directed against the pilus protein. This antibody bound to all six lipopolysaccharide and protein group A meningococcal serotyping strains, as well as to meningococcal strains from serogroups C, W135, and Y, but not to a strain of Escherichia coli, Haemophilus influenzae type b, or to two or more strains of Streptococcus pneumoniae, Neisseria gonorrhoeae, and Salmonella typhi. The ELISA used on antibody, antigen, antibody-conjugate sandwich. Rabbit anti-meningococcal serum was the coating antibody for the antibody sandwich, cerebrospinal fluids contained the bacterial antigens, and 3G7-alkaline phosphatase conjugate was the detecting antibody. The monoclonal antibody conjugate ELISA system was able to detect group A meningococcal antigens in 21 of 25 cerebrospinal fluid specimens that were positive in an immune rabbit serum conjugate ELISA; cerebrospinal fluid samples from patients with Haemophilus meningitis served as the controls. Counterimmunoelectrophoresis detected meningococcal antigens in 16 of the same 25 cerebrospinal fluid samples.

Antibodies, Monoclonal↗

Age-related changes in cerebrospinal fluid gamma-aminobutyric acid concentration.

The purpose of this study was to clarify the effect of aging on brain gamma-aminobutyric acid metabolism. We measured the cerebrospinal fluid gamma-aminobutyric acid concentration in subjects of various ages, including healthy volunteers and patients without neurological or psychiatric disease. The cerebrospinal fluid gamma-aminobutyric acid concentration was determined by radiolabelled receptor assay using [3H]gamma-aminobutyric acid. Cerebrospinal fluid gamma-aminobutyric acid was significantly higher in the control group (20s and 30s) than in the groups of subjects in their 50s, 60s, 70s and 80s. There was a significant negative correlation between cerebrospinal gamma-aminobutyric acid concentration and age (p less than 0.01). These data suggest that dysfunction of brain gamma-aminobutyric acid metabolism increases with age, and that the various symptoms caused by abnormal gamma-aminobutyric acid metabolism in the brain are therefore more likely to appear in elderly people.

Adult↗

[Evaluation of the activity of various lysosomal enzymes in the cerebrospinal fluid and blood in cases of brain concussion].

The results of determinations of lysosomal enzymes: mannosidase, b-galactosidase and b-glucosidase, in the cerebrospinal fluid and blood are presented in 72 patients with severe brain trauma. The determinations were carried out at different times after the trauma. The study demonstrated a significantly lower level and in a smaller degree expressed variability of enzymes in the cerebrospinal fluid in relation to blood. It seems that the level of b-glucosidase in the cerebrospinal fluid depends on the level of this enzyme in the blood, while no such evident correlation was found for the remaining enzymes.

Adolescent↗

Molecular monitoring of cerebrospinal fluid can predict clinical relapse in acute lymphoblastic leukemia with eosinophilia.

In a patient with precursor B-cell acute lymphoblastic leukemia (ALL) associated with eosinophilia that completely responded to induction chemotherapy, we assayed serial remission cerebrospinal fluid and bone marrow specimens for minimal residual disease using a quantitative polymerase chain reaction assay to assess for clone-specific immunoglobulin heavy-chain gene cluster (IGH) gene rearrangement. Cerebrospinal fluid eosinophilia and minimal residual disease were detected on day 406, preceding the morphologic diagnosis of central nervous system relapse on day 578. By day 841, the bone marrow had 35% blasts. Despite aggressive therapy, including unrelated umbilical cord blood transplantation, the patient developed testicular and bone marrow relapses and died of disease. We conclude that increasing levels of minimal residual disease in cerebrospinal fluid can predict recurrence of ALL prior to clinical and morphologic relapse. Furthermore, we demonstrate a novel translocation in this tumor, the t(5;9)(q31;p24), that possibly led to fusion of the interleukin-3 (IL3) (5q31) and JAK2 (9p24) genes and may explain the concomitant appearance of eosinophilia and ALL.

Cerebrospinal Fluid↗

[Determination of morphine in the vitreous and cerebrospinal fluid by radioimmunoassay (author's transl)].

In 12 cases of fatal poisoning with morphine or heroin a radioimmunological determination of morphine was carried out in vitreous humor, cerebrospinal fluid and urine. The concentrations varied between 30 and 350 ng of morphine-equivalents/ml in the cerebrospinal fluid and between 45 and 280 ng/ml in the vitreous humor (urine concentrations: 120-100.000 ng/ml). The counts per minute differed significantly for samples with and without prior ingestion of morphine, when vitreous and cerebrospinal fluids were tested by the morphine (3H) radioimmunoassay. Thereby it was clearly demonstrated, that radioimmunoassay is a valuable screening procedure for the rapid identification of morphine in corpses, even when urine is not available.

Heroin↗

Cerebrospinal fluid levels of catechols in patients with neurogenic orthostatic hypotension.

In multiple system atrophy (MSA) and pure autonomic failure (PAF), orthostatic hypotension (OH) results from deficient noradrenaline release from sympathetic nerves during standing. Post-mortem findings have indicated loss of central noradrenergic cells in both diseases. The present study sought in vivo neurochemical evidence for central noradrenergic deficiency in patients with OH due to MSA or PAF. A total of 28 patients with OH (18 with MSA; 10 with PAF) had cerebrospinal fluid and blood sampled for levels of noradrenaline and its neuronal metabolite dihydroxyphenylglycol. A control group of 44 subjects included 10 elderly normal volunteers, 10 patients with Alzheimer's disease, 18 patients with dysautonomia (postural tachycardia syndrome or neurocardiogenic syncope) and six patients with MSA in the absence of OH. Patients with OH had lower cerebrospinal fluid concentrations of noradrenaline (0.53+/-0.07 nmol/l) and dihydroxyphenylglycol (6.52+/-0.46 nmol/l) than did control subjects (0.90+/-0.09 and 9.64+/-0.46 nmol/l respectively; P =0.0001). The MSA+OH group had higher plasma levels of both catechols (noradrenaline, 1.31+/-0.16 nmol/l; dihydroxyphenylglycol, 5.08+/-0.43 nmol/l) than did the PAF group (noradrenaline, 0.38+/-0.08 nmol/l; dihydroxyphenylglycol, 2.53+/-0.30 nmol/l; P <0.001), despite similarly low cerebrospinal fluid levels. Among MSA patients, those with OH had lower cerebrospinal fluid levels of noradrenaline and dihydroxyphenylglycol than those without OH (noradrenaline, 1.71+/-0.64 nmol/l; dihydroxyphenylglycol, 10.41+/-1.77 nmol/l respectively; P =0.006). The findings are consistent with central noradrenergic deficiency in both MSA+OH and PAF. In MSA, central noradrenergic deficiency seems to relate specifically to OH.

Aged↗

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