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PubMed2003

Chemotactic activity of CXCL5 in cerebrospinal fluid of children with bacterial meningitis.

CXCL5 (epithelial-cell-derived neutrophil-activating protein (ENA-)78) is a CXC-chemokine that specifically acts on neutrophils. To obtain insight into the extent of local presence and action of CXCL5 during bacterial meningitis, we measured its concentrations in cerebrospinal fluid (CSF) of patients with culture-proven bacterial meningitis (n=14), aseptic meningitis (n=6), and controls (n=32) and compared these results with levels of other CXC-chemokines, CXCL8- (interleukin-8) and CXCL1-related oncogene (growth-related oncogene (GRO)-alpha). Patients with bacterial meningitis had profoundly elevated CSF concentrations of all three chemokines. CXCL5 was not detectable in patients with aseptic meningitis or control subjects. CSF from patients with bacterial meningitis exerted chemotactic activity towards neutrophils, which was partially inhibited by neutralizing antibodies against CXCL5 and CXCL8, but not CXCL1. CSF from controls exerted minor chemotactic activity, which could be strongly enhanced by the addition of recombinant CXCL5, CXCL8 or CXCL1. During bacterial meningitis, CXCL5 is elevated in CSF, where it is involved in the recruitment of neutrophils to the central nervous system.

Adolescent↗
PubMed1977

Difficulties in the diagnosis of bacterial meningitis. Evaluation of antibiotic pretreatment and causes of admission to hospital.

In 104 patients with bacterial meningitis admitted to departments of general medicine, the diagnosis before admission and the effect of previous antibiotic treatment were studied. Antibiotic therapy begun before admission in 30 patients did not affect the ability to make a bacteriological diagnosis. The duration of illness before admission was longer in the treated than in the untreated group. About 50% of the patients were admitted with diagnoses other than meningitis, although half these patients had distinct meningeal signs on arrival at hospital. In the whole series, 76% had meningeal signs on arrival. On the other hand, 95% of 108 patients with lymphocytic meningitis were admitted with a diagnosis of meningitis. The only significant clinical finding in the wrongly diagnosed group was a temperature higher than 40 degrees C on admission to hospital. The diagnosis before admission was not related to the treatment given. The findings illustrate the difficulties of diagnosing bacterial meningitis in the home.

Adult↗
PubMed1991

The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis.

BACKGROUND: In experimental models of meningitis and in children with meningitis, dexamethasone has been shown to reduce meningeal inflammation and to improve the outcome of disease. METHODS: We conducted a placebo-controlled, double-blind trial of dexamethasone therapy in 101 infants and children admitted to the National Children's Hospital, San José, Costa Rica, who had culture-proved bacterial meningitis or clinical signs of meningitis and findings characteristic of bacterial infection on examination of the cerebrospinal fluid. The patients were randomly assigned to receive either dexamethasone and cefotaxime (n = 52) or cefotaxime plus placebo (n = 49). Dexamethasone (0.15 mg per kilogram of body weight) was given 15 to 20 minutes before the first dose of cefotaxime and was continued every 6 hours thereafter for four days. RESULTS: The demographic, clinical, and laboratory profiles were similar for the patients in the two treatment groups. By 12 hours after the beginning of therapy, the mean opening cerebrospinal pressure and the estimated cerebral perfusion pressure had improved significantly in the dexamethasone-treated children but worsened in the children treated only with cefotaxime (controls). At 12 hours meningeal inflammation and the concentrations of two cytokines (tumor necrosis factor alpha and platelet-activating factor) in the cerebrospinal fluid had decreased in the dexamethasone-treated children, whereas in the controls the inflammatory response in the cerebrospinal fluid had increased. At 24 hours the clinical condition and mean prognostic score were significantly better among those treated with dexamethasone than among the controls. At follow-up examination after a mean of 15 months, 7 of the surviving 51 dexamethasone-treated children (14 percent) and 18 of 48 surviving controls (38 percent) had one or more neurologic or audiologic sequelae (P = 0.007); the relative risk of sequelae for a child receiving placebo as compared with a child receiving dexamethasone was 3.8 (95 percent confidence interval, 1.3 to 11.5). CONCLUSIONS: The results of this study, in which dexamethasone administration began before the initiation of cefotaxime therapy, provide additional evidence of a beneficial effect of dexamethasone therapy in infants and children with bacterial meningitis.

Adolescent↗
PubMed1993

Concentrations of nucleotides, nucleosides, purine bases and urate in cerebrospinal fluid of children with meningitis.

The release of agents mediating inflammation in meningitis may bring about neuronal hypoxia, under which circumstances ATP concentrations decrease and its degradation products increase and are released into the cerebrospinal fluid. In this study of alterations in neuronal energy metabolism in meningitis, AMP, IMP, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine and urate were determined by high performance liquid chromatography in the cerebrospinal fluid of 54 children aged between 1 month and 13 years suffering from meningitis (25 viral, 24 bacterial and 5 tuberculous cases) and 63 controls. Compared to the controls, patients with viral meningitis exhibited high concentrations of IMP, adenosine, guanosine, adenine, guanine and xanthine; patients with bacterial meningitis exhibited high concentrations of IMP, inosine, guanosine, adenosine, hypoxanthine, xanthine and urate; and patients with tuberculous meningitis exhibited high concentrations of AMP, guanosine, xanthine and urate. Viral and bacterial cases did not differ significantly for any of the metabolites studied. AMP and urate concentrations were significantly higher in patients with tuberculous cases compared with viral or bacterial meningitis cases.

Adenosine Monophosphate↗
PubMed2006

Childhood meningitis in Kuwait: epidemiology of etiologic agents and the need for pneumococcal disease prevention.

OBJECTIVE: To investigate the epidemiology of the etiologic agents causing bacterial meningitis in Kuwait. SUBJECTS AND METHODS: This is a retrospective analysis of the medical records of children 1 month to 12 years old who had cerebrospinal fluid (CSF) findings consistent with meningitis. Patients were identified from the records of the Departments of Microbiology and Communicable Diseases in six regional hospitals during 2001. They were divided into bacterial and viral infective groups. RESULTS: Ninety children had CSF findings consistent with meningitis, 44 bacterial (23 culture proven, 21 probable) and 46 viral. Streptococcus pneumoniae and Neisseria meningitidis were the most frequently isolated organisms (44 and 30%, respectively). A 2-month-old child had Haemophilus influenzae and was the only mortality of this series. S. pneumoniae is the leading bacterial agent causing meningitis in children under the age of 1 year; 61% had bacterial meningitis compared to 37% with viral meningitis. Sequelae were encountered in 23% of bacterial cases. CONCLUSION: The results indicate that S. pneumoniae is the leading bacterial agent causing meningitis, indicating a need for the introduction of polyvalent pneumococcal vaccine.

Child↗
PubMed1977

Serum immunoglobulin levels in the course of bacterial meningitis in children.

Serum levels of 5 immunoglobulins (IgG, IgA, IgM, IgD and IgE) were determined at frequent intervals in the course of bacterial meningitis in children. 59 patients were examined; 27 with Haemophilus influenzae meningitis, 23 with meningococcal and 9 with pneumococcal meningitis. All 5 immunoglobulins increased during the 2-week course of bacterial meningitis. IgM was the immunoglobulin class responding most rapidly, regularly and intensively. IgG increased moderately. However, practically no rise of the IgG level was observed in children with H. influenzae meningitis. The elevation of the IgA and IgE levels possibly suggests that meningitis may also cause synthesis of IgA and IgE antibodies. The results of the study indicate that antibodies of all the 5 immunoglobulin classes are probably involved in the defense against the causative microbes in bacterial meningitis.

Bacterial Infections↗
PubMed1984

Treatment of acute bacterial meningitis with special emphasis on beta-lactam antibiotics.

Acute bacterial meningitis still represents a therapeutic problem. Successful management depends on early administration of large doses of bactericidal antibiotics and adequate treatment of complications, i.e. shock, acute cerebral edema, consumption coagulopathy, convulsions and electrolyte disturbances. Meningitis caused by Neisseria meningitidis or Streptococcus pneumoniae should be treated with benzylpenicillin. If benzylpenicillin cannot be given, chloramphenicol has remained the best substitute. However, cefuroxime or ceftriaxone now seems to offer an alternative to chloramphenicol. The prevalence of beta-lactamase-producing Haemophilus influenzae strains is increasing and chloramphenicol has replaced ampicillin in the treatment of H. influenzae meningitis. Recent studies indicate that cefuroxime, ceftriaxone or moxalactam may be as effective as chloramphenicol in this type of meningitis. In neonatal meningitis, cefotaxime or moxalactam may constitute alternatives to the present regimens with ampicillin-gentamicin, gentamicin-chloramphenicol, cotrimoxazole or gentamicin. Promising results have also been obtained with cefotaxime or moxalactam in elderly patients with meningitis due to Gram-negative enteric bacilli. However, more extensive studies are needed to determine the role of the newer cephalosporins in the treatment of acute bacterial meningitis.

Anti-Bacterial Agents↗
PubMed1996

[A score for the differential diagnosis of bacterial and viral meningitis].

The purpose of this study was to verify the statistical validity of the score proposed by Thomé et al. for the differential diagnosis between bacterial and viral meningitis and to study the utility of two new parameters (CRP and the patient's age). A retrospective review of 136 consecutive cases of meningitis was made. The cases were classified into three groups according to the culture results and the use or not of intravenous antibiotics. There were 20 cases of bacterial meningitis, 60 non-bacterial and 56 cases of meningitis of uncertain etiology. Considering only the patients in the first two groups, the capacity for differential diagnosis between bacterial and non-bacterial meningitis of the 8 parameters in the original score, the CRP and the patient's age was analyzed with a numeric value of 0, 1, or 2 assigned to each parameter. Finally, the results of applying the score that includes the two new parameters with the original score are compared. We found that all parameters showed statistical significance for the differential diagnosis between bacterial and viral meningitis. The resulting score can be used in order to decide the need for intravenous antibiotic therapy, with only a few cases being uncertain. The score with the two new parameters correctly classified 78 of the 80 cases, while leaving only two case uncertain as compared to the four that remained unclassified with the original score. We conclude that the score is a useful instrument in the differential diagnosis between bacterial and viral meningitis. Furthermore, the introduction of CRP and the patient's age improves the diagnostic value of the test.

Adolescent↗
PubMed2000

Inhibition of glutamine synthetase in rabbit pneumococcal meningitis is associated with neuronal apoptosis in the dentate gyrus.

Apoptosis of dentate granular cells in the hippocampal formation during bacterial meningitis may be mediated by glutamate toxicity. For this reason, we studied the relationship between glutamine synthetase activity and regional neuronal apoptosis in rabbits with experimental pneumococcal meningitis. The duration of meningitis was 24 h, and the treatment was started 16 h after infection. Significant increases of glutamine synthetase protein concentration (P < 0.05) were found in the frontal cortex of rabbits with meningitis (n = 7) and rabbits with meningitis receiving ceftriaxone treatment (n = 12) as compared to the control animals (n = 14). No significant differences were seen in the hippocampal formation. The enzymatic activity of glutamine synthetase also was elevated in the frontal cortex (P < 0.05), but not in the hippocampal formation of rabbits with meningitis. After intravenous administration of L-methionine sulfoximine (specific inhibitor of glutamine synthetase) in rabbits with meningitis treated with ceftriaxone (n = 10), the concentration of neuron-specific enolase in CSF (P = 0.025) and the density of apoptotic neurons in the dentate gyrus quantified with the in-situ tailing reaction (P = 0.043) were higher than in meningitic animals receiving only ceftriaxone (n = 10). In conclusion, the inability of hippocampal glutamine synthetase to metabolize excess amounts of glutamate may contribute to neuronal apoptosis in the hippocampal formation during meningitis.

Animals↗
PubMed1992

Meningeal arteries in rhesus macaques (Macaca mulatta): implications for vascular evolution in anthropoids.

The branching patterns of meningeal arteries are reported for 200 endocast hemispheres representing rhesus monkeys (Macaca mulatta) of known cranial capacity. We detect five basic patterns for the branching of the anterior division of the middle meningeal artery and its relationship with the anterior meningeal artery. These results confirm and elaborate trends published for much smaller samples that were based on direct dissections of rhesus monkey arterial patterns. The most common pattern is that in which the anterior meningeal artery dominates the blood supply above the rostral part of the middle cranial fossa. Analysis of cranial capacities reveals that presence of this pattern on both sides of endocasts is associated with increased cranial capacity. When studied in light of published reports of anatomical dissections of cranial arteries in apes and human embryological data, the anterior meningeal artery in rhesus monkeys appears to be a possible homologue of the lacrimal meningeal artery in apes and the anterior branch of the middle meningeal artery in humans. This finding provides a step towards understanding cranial vasculature homologies that may be useful for accurately scoring the branching patterns of the meningeal arteries in monkeys, apes, and humans.

Animals↗
PubMed1980

Meningeal gliomatosis: a review of 12 cases.

Diffuse or multifocal invasion of the leptomeninges by malignant glioma (meningeal gliomatosis) is believed to be rare. From 1971 through 1977, 11 of 52 patients with intracranial malignant gliomas examined at autopsy were found to have meningeal gliomatosis, and 1 additional patient was diagnosed clinically without autopsy (12 cases total). Eight of the 12 patients were diagnosed antemortem with positive cerebrospinal fluid (CSF) cytology, while the other 4 patients were diagnosed at autopsy only. All 11 autopsied patients had multifocal or diffuse meningeal tumor distant from the primary site; 8 patients had spinal subarachnoid seeding with tumor encroachment of cauda equina and spinal nerve roots, and 9 patients had tumor invasion into the lateral ventricles. Three patients had symptomatic spinal cord compression at the thoracic or lumbar level, and 10 patients had hydrocephalus. These 12 patients with meningeal gliomatosis were compared with the other 41 autopsied malignant glioma patients without the complication (controls); the patients with meningeal gliomatosis were significantly younger (mean age, 40 versus 57 years; p less than 0.005). Patients with meningeal gliomatosis lived somewhat longer (median, 49 weeks) compared to controls (35 weeks), but the difference was not statistically significant. With the advance of chemotherapy, patients with malignant glioma are living longer and the incidence of meningeal gliomatosis may rise. The diagnosis of meningeal gliomatosis can be suspected, especially if hydrocephalus is present, and can often be confirmed by CSF cytology.

Adolescent↗
PubMed1975

Cyclic adenosine-3',5-monophosphate concentration and enzyme activities of cerebrospinal fluid in meningitis of children.

The concentration of cyclic adenosine-3',5'-monophosphate (cAMP) and the activities of some enzymes of 29 children were measured from cerebrospinal fluid (CSF) and plasma at various stages of meningitis. The CSF cAMP values in acute untreated phase of aseptic and purulent meningitis were equal, but significantly higher than those of convalescent children with no pathological clinical or laboratory findings. During the whole course (up to 2 weeks) of antimicrobial treatment of the purulent meningitis CSF cAMP concentration was higher than in the convalescent phase. Of the CSF enzymes studied, the lactic dehydrogenase activity seemed to be the best indicator of changing stages of meningitis. It was clearly elevated in the acute, untreated phase of purulent meningitis then decreasing during the course of treatment. In aseptic meningitis this activity was at the normal level and the activities of creatine kinase and acid phosphatase behaved similarly. The plasma cAMP concentrations in the acute phase of purulent meningitis were in the same range as in the CSF. During the treatment no significant changes were seen. The enzyme activities in the plasma were normal. The CSF cAMP level seems to be a sensitive indicator of metabolic disturbances in meningitis and may serve as a diagnostic aid.

Acid Phosphatase↗
PubMedDate not supplied

Brain meninges tumor formation by in vivo-selected metastatic B16 melanoma variants in mice.

The murine melanoma subline B16-F1 of low brain- and lung-colonizing potential has been used to obtain brain-colonizing variant sublines by sequential selection in vivo for their abilities to form brain meningeal tumors. After fourteen and fifteen selections in syngeneic C57BL/6 mice sublines B16-B14b and B16-B15b, respectively, were established in culture. These were then assayed in vivo by injection of single tumor cell suspensions into the tail vein (i.v.), left ventricle of the heart (i.c.) or left common carotid artery (i.a.), and the resulting tumors were examined histologically. Injection of subline B16-B14b or B16-B15b resulted in brain meningeal tumor formation in the dura mater and leptomeninges with invasion into underlying brain parenchyma and also some brain ventricular tumors at the sites of i.a. injection. Lung colonization ability remained in the brain-selected sublines, although it was remarkably reduced in i.a. tumor cell-injected animals. The brain meningeal tumors that formed were of three types: intravascular, nodular or infiltrative. Injection of tumor cells i.v. resulted mainly in the establishment of the intravascular type of brain meningeal tumors with eventual perivascular invasion, while injection i.a. or i.c. resulted mostly in nodular or infiltrative type brain meningeal tumors. The B16-B14b brain meningeal tumors formed were small (less than 1 mm in diameter) and usually nonpigmented, while B16-B15b tumors were generally large (up to 7 mm in diameter) and pigmented. Host reactions towards B16-B14b and B16-B15b tumors at meningeal sites differed. The former B16 subline was characterized by extensive fibrosis with some immunocytic cell infiltration in and around the meningeal tumors, while the latter subline did not elicit such host reactions. In contrast, tumors in brain parenchyma failed to evoke observable host reactions, and there was little evidence of immunocyte cell infiltration or glial cell alterations.

Animals↗
PubMed1996

Recurrent bacterial meningitis.

UNLABELLED: To characterize recurrent bacterial meningitis in children, we reviewed the charts of all patients treated for more than one episode of bacterial meningitis at the Würzburg University Children's Hospital from 1980 to June 1995. Twenty-five children suffered 2-13 episodes of bacterial meningitis. Most patients were referred from other hospitals to our paediatric neurosurgical service. No immunodeficiency was found. In all patients, the cause of recurrent meningitis was an anatomical lesion with 13 intracranial defects including encephaloceles, skull fractures, Mondini dysplasias, neurenteric cyst, fibrous dysplasia, persistent craniopharyngeal duct, and 12 lumboscral defects with a dermoid cyst within the lumbosacral spine. A first episode of meningitis at school age did not exclude a congenital defect. In total, 84 episodes of meningitis were treated, a pathogen was isolated in 77%. The most common pathogen was Streptococcus pneumoniae, followed by Escherichia coli, Staphylococci and others. The pathogen isolated often gave a clue to the location of the defect. Personal history was often unrewarding and in some cases the search for the anatomical lesion required repeated imaging and explorative surgery. In 24 of 25 cases, final treatment of recurrent meningitis was by surgical intervention. CONCLUSION: In recurrent bacterial meningitis, excessive diagnostic and therapeutic procedures are indicated. An anatomical defect is a very probable cause.

Algorithms↗
PubMed1991

Interactions between meningeal cells and astrocytes in vivo and in vitro.

At the interface between the meninges and the central nervous system there is a characteristic structure known as the glia limitans, consisting of many fine interdigitating astrocyte processes which contain both GFAP and vimentin, and a basal lamina. A similar structure is set up after brain injury where meningeal cells invade the lesion. We have experimentally put astrocytes and meningeal cells in contact with one another, both in vivo and in vitro, to see whether this results in the formation of a glia limitans. Cultured meningeal cells were injected into the hippocampus of adult rats, and from 1 to 12 weeks later brains were stained were stained for GFAP and vimentin. One week after injection there was a widespread astrocytic reaction stretching up to 2 mm from the injection, the cells being stained intensely for both GFAP and vimentin. Over the next 4-6 weeks this widespread reaction subsided, the only remaining vimentin stained astrocytes, apart from those at the normal glia limitans, being in contact with the injected meningeal cells, or with meningeal cells which had migrated into the injection needle track. In vitro a structure reminiscent of the glia limitans formed where patches of astrocytes abutted meningeal cells; the astrocytes formed a layer of fine interdigitating processes all running parallel to the interface between the two cell types, and there was heavy staining for laminin and fibronectin. We conclude that a glia limitans forms wherever astrocytes and meningeal cells come into contact.

Animals↗
PubMed2002

The possible role of cerebrospinal fluid adenosine deaminase activity in the diagnosis of tuberculous meningitis in adults.

We studied an adenosine deaminase (ADA) activity in the cerebrospinal fluid (CSF) of 182 patients with meningitis. The patients were subdivided into four groups, (1) 36 cases of tuberculous meningitis; (2) 130 cases of viral or aseptic meningitis; (3) nine cases of bacterial meningitis; (4) seven cases of cryptococcal meningitis. Mean+/-S.D. ADA activity was 12.76+/-7.53 U/l in group 1; 2.58+/-2.37 U/l in group 2; 7.38+/-3.27 U/l in group 3; 7.42+/-4.38 U/l in group 4. Comparing the ADA activity in each group with the other groups, the difference is significant (P<0.001), except between groups 3 and 4. The sensitivity of the test for group 1 compared with group 2 was 0.83 and the specificity was 0.95 when a cut-off value of 7 U/l was used. When group 1 was compared with groups 3 and 4, the sensitivity was 0.58 and the specificity was 0.89 and 0.71 with groups 3 and 4, respectively, when a cut-off value of 10 U/l was used. Values >15 U/l were not observed in any of the non-tuberculous meningitis patients; therefore, ADA activity >15 U/l could be a strong indication of tuberculous meningitis. We conclude that a determination of CSF ADA can aid in the early differential diagnosis of tuberculous meningitis.

Adenosine Deaminase↗
PubMed2000

[Meningitis after locoregional spinal anesthesia].

OBJECTIVE: Meningitis is a severe and an uncommon complication of both spinal and epidural anaesthesia. This review summarizes the knowledge on epidemiology, clinical and microbiological diagnosis and the ways to prevent them. DATA SOURCES: Articles published in English and French language since 1989 has been collected on Medline database, using "meningitis", "spinal anaesthesia" and "epidural anaesthesia" as keywords. DATA SYNTHESIS: Bacterial meningitis are usually in relation with Gram positive bacterias which is a clue for an exogenous contamination. Another unusual ways of contamination are blood circulating bacterias and spreading of local infection. Aseptic meningitis has been described, in relation to introduction of irritant agents in subarachnoid space. Lumbar puncture must be done each time meningitis suspected so that it can assert the diagnosis and guide antibiotherapy. Easy hygienic guidelines has been widely published to prevent meningitis. Usually, antibiotherapy alone is sufficient to treat meningitis but with an unjustified cost and sometimes severe persistent neurologic sequelae. CONCLUSION: The unexpected appearance of meningitis during the wearing-off of a spinal anesthesia is exceptional; the possibility of death or serious sequela must be taken into account. The sources of contamination are quite frequently exogenous, the germs coming most often from the patient's cutaneous flora or the anesthetist's ENT flora. Prevention of this risk involves a rigorous respect for cutaneous disinfection and hygiene procedures. The anesthetist's medico-legal responsibilities will be called upon in case of exogenous contamination.

Adolescent↗
PubMed1997

Acute otitis media and otitis media with effusion in children with bacterial meningitis.

Acute otitis media and otitis media with effusion (OME) have often been observed in children with bacterial meningitis. OME has also been proposed as the mechanism of reversible hearing loss after meningitis. In this controlled study, children with acute bacterial meningitis were studied using auditory brainstem responses (ABR), otoacoustic emissions, tympanometry and otoscopy. An age- and sex-matched control was recruited for each patient and the incidence of acute otitis media and OME was compared between the two groups. One hundred and twenty-four children with meningitis were studied. Ninety-two children (74 per cent) had meningococcal meningitis. Five patients (4 per cent) had conductive hearing loss (ABR threshold > or = 30 dB HL) at the time of discharge from hospital. None of the patients or controls had acute otitis media. Patients and controls were well matched for risk factors for OME and the prevalence of middle ear effusion in patients and controls was 7.2 per cent and 11.3 per cent respectively. The relative risk of OME in the children with meningitis was 0.64 (95 per cent confidence interval 0.29 to 1.42). After nine months, three of the five children with meningitis and conductive hearing loss had regained normal hearing. In contrast to previous reports, there was no relationship between bacterial meningitis and acute otitis media or OME in this study. Nevertheless, coincidental conductive hearing defects were identified as the cause of reversible hearing loss in three patients.

Acute Disease↗