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Cerebrospinal fluid in critical illness.

OBJECTIVE: To detail the physiology, pathophysiology and recent advances in diagnostic analysis of cerebrospinal fluid (CSF) in critical illness, and briefly review the pharmacokinetics and pharmaco-dynamics of drugs in the CSF when administered by the intravenous and intrathecal route. DATA SOURCES: A review of articles published in peer reviewed journals from 1966 to 1999 and identified through a MEDLINE search on the cerebrospinal fluid. SUMMARY OF REVIEW: The examination of the CSF has become an integral part of the assessment of the critically ill neurological or neurosurgical patient. Its greatest value lies in the evaluation of meningitis. Recent publications describe the availability of new laboratory tests on the CSF in addition to the conventional cell count, protein sugar and microbiology studies. Whilst these additional tests have improved our understanding of the pathophysiology of the critically ill neurological/neurosurgical patient, they have a limited role in providing diagnostic or prognostic information. The literature pertaining to the use of these tests is reviewed together with a description of the alterations in CSF in critical illness. The pharmacokinetics and pharmacodynamics of drugs in the CSF, when administered by the intravenous and the intrathecal route, are also reviewed. CONCLUSIONS: The diagnostic utility of CSF investigation in critical illness is currently limited to the diagnosis of an infectious process. Studies that have demonstrated some usefulness of CSF analysis in predicting outcome in critical illness have not been able to show their superiority to conventional clinical examination. With further advances in our understanding of neurological function and refinement in biochemical analysis there remains the possibility of useful cerebrospinal fluid diagnostic and prognostic markers in the future.

Journal Article↗

Cerebrospinal fluid interleukin 8 concentrations and the subsequent development of postherpetic neuralgia.

PURPOSE: Other than age, the risk factors for postherpetic neuralgia are not well established. We studied whether the concentration of interleukin 8 in the cerebrospinal fluid is associated with the risk of postherpetic neuralgia. METHODS: We enrolled 170 patients more than 50 years old who had a typical painful and nontrigeminal herpetic rash. Patients were treated with acyclovir; no corticosteroids were given. Cerebrospinal fluid was taken for analysis of interleukin 8 during and at full crusting of the herpetic rash. Age, sex, comorbid conditions, prodromal pain, localization and severity of herpetic rash, number of skin lesions, and degree of pain were recorded. We used multivariate logistic regression modeling to identify significant predictive factors. Receiver operating characteristic (ROC) curves were evaluated to determine the contribution of each factor. RESULTS: Six months after healing, 31 patients (18%) had postherpetic neuralgia; 27 patients still had it after 1 year. Only three variables-age (odds ratio [OR] = 2.7 per 10-year increase; 95% confidence interval [CI]: 1.2 to 6.2), acute pain (OR = 1.8 per unit increase in visual analog scale; 95% CI: 1.2 to 2.8), and interleukin 8 concentration in the cerebrospinal fluid at full crusting of the herpetic rash (OR = 1.6 per 20-microg/L increase; 95% CI: 1.3 to 2.0)-were significant predictors of postherpetic neuralgia at 1 year. Interleukin 8 concentration also had the highest area under the ROC curve at these evaluation points (P <0.001). CONCLUSION: Our results suggest that interleukin 8 concentration in the cerebrospinal fluid at full crusting of herpetic rash may be useful for identifying patients who are likely to develop intractable postherpetic neuralgia.

Aged↗

Isolation of Inoue-Melnick virus from cerebrospinal fluid of patients with epidemic neuropathy in Cuba.

BACKGROUND: A mysterious disease spread over Cuba from 1991 to 1993, the cause of which has not been fully established. Major symptoms were the same in patients with the Cuban disease as in patients with subacute myelo-optico-neuropathy (SMON), which had occurred in Japan nearly 30 years ago and from which Inoue-Melnick virus (IMV) type 1 was first isolated. We investigated the presence of IMV in cerebrospinal fluid samples of patients with this epidemic neuropathy in Cuba. METHODS: The established method for detecting IMV in MRC-5 fibroblasts was used throughout the study, which was conducted in two independent laboratories, one in Buffalo, NY, and the other in Kyoto, Japan. The cerebrospinal fluid samples of 20 patients and four controls were provided by Cuban researchers. RESULTS: All cerebrospinal fluid specimens from 20 Cuban patients tested were positive for IMV type 2 (100%), and four cerebrospinal fluid specimens from Cuban controls were negative for IMV (0%). These clear-cut results were identical in both laboratories. CONCLUSION: Our study indicates an important association of IMV type 2 with patients of this Cuban epidemic. The etiologic role of IMV type 2 in the epidemic neuropathy in Cuba, along with weak cytopathic effect viruses isolated by the Cuban group, remains to be elucidated.

Animals↗

Thromboplastic activity of cerebrospinal fluid in neurological disease.

Estimates of thromboplastic activity in 1100 samples of cerebrospinal fluid indicate that an increased activity of this clotting factor is a nonspecific indicator of abnormality in the central nervous system, much like (e.g.) an increased count of mononuclear cells and an increased protein content. However, the proportion of abnormal results obtained by these three tests can differ markedly in different neurological disorders. Increased thromboplastic activity is about 14-fold more common in bacterial meningitis than in viral meningitis; thus the thromboplastin determination can be of value in discriminating between bacterial and viral meningitis.

Cerebrospinal Fluid↗

Cerebrospinal fluid and serum markers of inflammation in autism.

Systemic immune abnormalities have no known relevance to brain dysfunction in autism. In order to find evidence for neuroinflammation, we compared levels of sensitive indicators of immune activation: quinolinic acid, neopterin, and biopterin, as well as multiple cytokines and cytokine receptors, in cerebrospinal fluid and serum from children with autism, to control subjects with other neurologic disorders. In cerebrospinal fluid from 12 children with autism, quinolinic acid (P = 0.037) and neopterin (P = 0.003) were decreased, and biopterin (P = 0.040) was elevated, compared with control subjects. In sera from 35 persons with autism, among cytokines, only tumor necrosis factor receptor II was elevated compared with controls (P < 0.02). Decreased quinolinic acid and neopterin in cerebrospinal fluid are paradoxical and suggest dysmaturation of metabolic pathways and absence of concurrent infection, respectively, in autism. Alternatively, they may be produced by microglia but remain localized and not expressed in cerebrospinal fluid.

Adolescent↗

Bacterial meningitis in children whose cerebrospinal fluid contains polymorphonuclear leukocytes without pleocytosis.

A retrospective study was performed of 424 children who received diagnostic lumbar puncture for analysis of cerebrospinal fluid during evaluation of an acute illness. In 106 children, the CSF contained polymorphonuclear leukocytes without pleocytosis. Of these 106 patients, 90 percent had a CSF differential cell count with 20 percent or less PMN's and 88 percent had glucose and protein concentrations within the range of normal limits. All patients had a Gram-stained smear of CSF that revealed no organisms. In no instance was a CSF culture positive for a bacterial pathogen. In most instances, cerebrospinal fluid that contains total white cell count and glucose/protein concentrations within limits of normal, Gram-stained smear which reveals no organisms, and a differential cell count with less than 20 percent PMN's is not indicative of risk for bacterial meningitis. If the clinical situation warrants, the majority of children with this profile do not require hospitalization and initiation of empiric antibiotic therapy pending CSF culture results.

Cerebrospinal Fluid↗

[The effect of the cerebrospinal fluid from patients with manic and depressive syndromes on the social hierarchical relationships in a group of rats].

Taking into account socio-oriented symptoms of affective disorders, a method of zoosocial hierarchy of rats was used for biological testing of the cerebrospinal fluid of patients with manic and depressive syndromes. Cerebrospinal fluid and its fractions were administered before and after treatment by trypsin into suboccipital cistern of "dominants" and "subordinates" of the community. A change of behaviour was observed, the character of which depended on the phase of donor's psychosis. Low-molecular fraction of the cerebrospinal fluid possessed specific activity, which disappeared after the treatment by trypsin, what allowed to suggest oligopeptide nature of the active factors.

Adult↗

[Gasometric studies and lactic acid determinations in arterial blood and cerebrospinal fluid in brain infarction].

In 54 cases of brain infarction and 17 control cases the gasometric parameters and lactic acid level were determined in arterial blood and cerebrospinal fluid. Metabolic acidosis was demonstrated in the arterial blood and cerebrospinal fluid. Respiratory acidosis compensated partly metabolic acidosis. Changes in the cerebrospinal fluid were more frequent and more pronounced, especially in cases with fatal outcome. Deep disturbances of acid-base balance complicated with hypoxia may have prosnostic significance while moderate rise in lactic acid level is without this significance.

Aged↗

[Development and current possibilities of cerebrospinal fluid diagnosis in the routine laboratory. 1. Cytological and microbiological studies and methods of chemical analysis].

Although there are many precisely working procedures for diagnostic examinations of cerebrospinal fluid, very often methods are used which do not fulfill conditions of adequate quality. The aim of this survey of several cytological and chemical methods, of their development during the past 80 years, of their advantages or disadvantages, and of the various difficulties is to contribute to a discussion on improvement of quality and on unification of laboratory methods regarding diagnostic examinations of cerebrospinal fluid. Several procedures to separate protein fractions or single proteins in cerebrospinal fluid will be discussed in the second part of this paper.

Central Nervous System Diseases↗

Cerebrospinal fluid tumour markers in patients treated for meningeal malignancy.

The results of cerebrospinal fluid (CSF) biochemical markers were compared with conventional CSF cytology in patients treated for leptomeningeal metastases from extra cranial malignancies. For lumbar CSF, before treatment, no statistically significant difference of the probabilities of being positive was found between CSF cytology and a classification by linear discriminant analysis, based on patient's age, of beta-glucuronidase and beta 2-microglobulin. During treatment, classification by linear discriminant analysis was found more often positive than cytology. Possible mechanisms for this difference are discussed. For ventricular CSF a correlation was found between CSF cytology and beta-glucuronidase for solid tumours, and between CSF cytology and beta 2-microglobulin for haematological malignancies. Reference values for ventricular protein, CEA beta-glucuronidase and beta 2-microglobulin were obtained for cytological negative samples.

Adult↗

Ventricular cerebrospinal fluid eosinophilia in children with ventriculoperitoneal shunts.

To determine the significance of cerebrospinal fluid (CSF) eosinophilia, the charts of 106 patients treated with shunt-related procedures during the calendar year 1985 were reviewed. Sixty-nine patients presented for a shunt revision; their charts were retrospectively reviewed from the time of shunt insertion until January, 1988. The remaining 37 patients had a ventriculoperitoneal shunt inserted during the study period and were subsequently followed to January, 1988. A total of 558 shunt-related procedures were performed on these patients during the study period, with a mean follow-up period of 6.9 years. The infection rate was 3.8%. Eosinophilia was diagnosed when eosinophils accounted for 8% or more of the total CSF white blood cell count. Ventricular CSF eosinophilia occurred in 36 patients sometime during their clinical course. These 36 patients required a mean of 8.5 shunt revisions, while the remaining patients required a mean of 2.5 revisions (p less than 0.001). Shunt infections were also more frequent in patients with eosinophilia (p less than 0.01). In no case was peripheral eosinophilia or a parasitic infection present. This study demonstrates that CSF eosinophilia is common in children with shunts. Children with this laboratory finding will experience more shunt failures. In addition, the new appearance of eosinophilia in the CSF of a patient with a shunt in place suggests the possibility of a shunt infection.

Brain Diseases↗

Vascular components of cerebrospinal fluid compensation.

OBJECT: The aim of the study was to assess how cerebrospinal fluid (CSF) pressure-volume compensation depends on cerebrovascular tone. METHODS: In 26 New Zealand White rabbits, intracranial pressure (ICP), arterial blood pressure, and basilar artery blood flow velocity were measured continuously. Saline was infused into the cranial subarachnoid space to assess CSF compensatory parameters: the resistance to CSF outflow, the elastance coefficient, and the amplitude of the ICP pulsatile waveform. Infusions were repeated on two different levels of CO2 concentration in the arterial blood (PaCO2), at normotension and hypotension, and after the death of the animal. An increase in PaCO2 from a mean of 27 to 48 mm Hg was accompanied by an 18% increase in the resistance to CSF outflow (p<0.005) and a 64% increase (p<0.05) in the elastance coefficient. A decrease in arterial blood pressure from a mean of 100 to 51 mm Hg caused a 25% decrease in CSF outflow resistance (p<0.01) but did not affect the elastance coefficient. Postmortem, a 23% decrease in the CSF outflow resistance was associated with a 102% decrease in the elastance coefficient. CONCLUSIONS: Cerebrovascular parameters have a limited but significant impact on CSF infusion studies. The vascular component of ICP may be identified as a significant factor contributing to this phenomenon. During infusion studies, physiological parameters influencing vascular conditions should be maintained as stable as possible.

Animals↗

Vitronectin may mediate staphylococcal adhesion to polymer surfaces in perfusing human cerebrospinal fluid.

Prosthetic devices are frequently used for temporary or permanent drainage of cerebrospinal fluid (CSF), i.e., ventricular catheters with or without external monitoring devices and shunts. Infections constitute a serious complication in the use of biomaterials in contact with CSF; coagulase-negative staphylococci (CNS) are the most common aetiological agents. In the present study, polyvinylchloride (PVC) and PVC with endpoint-attached heparin were exposed to human CSF under perfusion to mimic conditions in vivo. Adhesion of strains of CNS isolated from patients with or without biomaterial-associated infection was determined: (i) after pre-incubation with fibronectin (Fn) or vitronectin (Vn) to block bacterial surface binding structures; and (ii) after preincubation of biomaterials with antibodies to Fn or Vn to block exposure of bacteria-binding domains on these host proteins. Pre-incubation of bacterial cells with Vn significantly reduced subsequent adhesion to polystyrene precoated with Vn 0.5 microg/well. When PVC pre-exposed to CSF was incubated with antibodies to Vn, subsequent bacterial adhesion of a Vn-binding strain, S. epidermidis 5703, was significantly reduced. The study shows that Vn may mediate adhesion of CNS in the presence of CSF. However, strains retrieved from biomaterials did not express binding of Vn or Fn to a higher extent than non-biomaterial-associated strains. Expression of heparin binding under static conditions did not correlate with staphylococcal adhesion to heparinised polymers under perfusion with CSF. The extent of adhesion of staphylococci to heparinised PVC was either reduced or the same as to unheparinised PVC.

Antibodies↗

Cerebrospinal fluid monoamine metabolites in alcoholic patients who attempt suicide.

Reduced cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid have been reported to be commonly associated with suicidal behaviour. Alcoholics are known to often manifest suicidal behaviour. Therefore, we compared cerebrospinal fluid levels of monoamine metabolites in alcoholics who had (n = 20) and had not (n = 108) attempted suicide and healthy volunteers (n = 30). There were no significant differences among the 3 groups for CSF levels of either 5-hydroxyindoleacetic acid, the dopamine metabolite homovanillic acid, norepinephrine, or the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol.

Adult↗

6-Hydroxydopamine-induced turning behaviour in the rat: the significance of acetylcholinesterase in cerebrospinal fluid.

In the substantia nigra, acetylcholinesterase may have a novel function related not to cholinergic transmission, but to the homeostasis of dopaminergic nigrostriatal neurones. The initial aim of this study was thus to see whether, in the rat, release of the enzyme into cerebrospinal fluid would reflect turning behaviour following unilateral 6-hydroxydopamine lesions of varying severity. It was found that acetylcholinesterase levels, lower than those in the cerebrospinal fluid of control rats, were accompanied by marginal circling behaviour and a small loss of striatal dopamine: on the other hand, elevated acetylcholinesterase activity was observed in the cerebrospinal fluid of rats displaying vigorous turning behaviour and with large depletion of striatal dopamine. It has already been demonstrated that exogenous acetylcholinesterase, applied locally to nigral neurones, has both electrophysiological and behavioural effects reminiscent of dopamine agonists. Hence it is possible that exogenous acetylcholinesterase could modify turning behaviour resulting from unilateral striatal dopamine depletion. Purified acetylcholinesterase, administered by cisternal puncture, attenuated circling behaviour for up to 7 days. The possible mechanisms are discussed by which endogenous acetylcholinesterase in cerebrospinal fluid could serve as an index of dopamine depletion in the nigrostriatal pathway and how exogenous enzymes might alleviate the accompanying motor dysfunction.

Acetylcholinesterase↗

Abdominal cerebrospinal fluid pseudocyst.

A case of an abdominal cerebrospinal fluid (CSF) pseudocyst in a patient with a ventriculoperitoneal shunt is reported to illustrate this known but rare complication. In the setting of a VP shunt, the frequency of abdominal CSF pseudocyst formation is approximately 3.2%, often being precipitated by a recent inflammatory or infective process or recent surgery. Larger pseudocysts tend to be sterile, whereas smaller pseudocysts are more often infected. Ultrasound and CT each have characteristic findings.

Adolescent↗

Immunohistochemical characterization of the amyloid deposits and quantitation of pertinent cerebrospinal fluid proteins in hereditary cerebral hemorrhage with amyloidosis.

Cystatin C, a protein inhibitor of lysosomal cysteine proteinases, was demonstrated by immunohistochemical techniques to be present in the birefringent amyloid deposits of the small arteries in the cerebrum, cerebellum, and leptomeninges of 10 Icelandic individuals with hereditary cerebral hemorrhage with amyloidosis. Specimens from other organs were investigated in one of the patients, and amyloid angiopathy characterized by an immunoreactivity of cystatin C was found in a submandibular lymph node. No immunoreactivity of amyloid fibril protein AA, kappa or lambda immunoglobulin light chain, or prealbumin was observed. Significantly low cerebrospinal fluid concentrations of cystatin C were found in all 9 investigated individuals with hereditary cerebral hemorrhage with amyloidosis. The concentrations of beta 2-microglobulin, albumin, and IgG in the cerebrospinal fluid were within normal limits. Isoelectric focusing showed that cystatin C from the cerebrospinal fluid of 9 patients with hereditary cerebral hemorrhage with amyloidosis had an isoelectric point identical to that of normal individuals. This investigation demonstrates that hereditary cerebral hemorrhage with amyloidosis may be diagnosed by two laboratory methods: immunohistochemical investigation of cystatin C in brain tissue specimens and quantitation of cystatin C in cerebrospinal fluid.

Adult↗

beta-N-acetylhexosaminidases in human cerebrospinal fluid and serum of patients with multiple sclerosis.

Beta-N-Acetylhexosaminidase activity and isoenzyme have been investigated in normal human cerebrospinal fluid and that of patients with multiple sclerosis. beta-N-acetylhexosaminidase activity in normal cerebrospinal fluids has been resolved into five components. The major component was in a form that eluted from DEAE cellulose at the same salt concentration as hexosaminidase As, the isoenzyme previously identified in human serum. Cerebrospinal fluid from patients exhibited a different isoenzyme profile, showing a remarkable increase in a form having a pI which was more acidic than that of As. These changes have a potential use in the diagnosis and further biochemical characterization of multiple sclerosis.

Chromatography, Ion Exchange↗