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Chemokines in the cerebrospinal fluid of patients with meningitis.

Meningitis is accompanied by a differential immigration of leukocytes into the subarachnoid space. Since the mechanisms regulating leukocyte invasion are still incompletely understood, we studied the release of the neutrophil-attracting alpha-chemokines IL-8 and GRO-alpha and the mononuclear cell-attracting beta-chemokines MCP-1, MIP-1alpha, and RANTES during meningitis. In 48 paired CSF and serum samples from patients hospitalized for meningitic symptoms, high levels of IL-8, GRO-alpha, and MCP-1 were detected in the CSF during bacterial and abacterial meningitis. Elevated chemokine levels were not found in the blood serum samples taken in parallel. The release of MIP-1alpha or RANTES was below detection limits. The IL-8 and GRO-alpha levels significantly correlated with the number of immigrated granulocytes in the CSF of patients with bacterial meningitis. A similar correlation was found when MCP-1 levels and the mononuclear cell count were analyzed in abacterial meningitis. These findings suggest that the local production of the alpha-chemokines IL-8 and GRO-alpha and of the beta-chemokine MCP-1 represents the major chemoattractant stimulus for the differential recruitment of leukocytes into the subarachnoid space during meningitis.

Adolescent↗

Treatment of bacterial meningitis.

Bacterial meningitis remains a life-threatening infection at any age, and prompt, adequate treatment is of great prognostic importance. Due to the special features of the meninges as a site of infection, many problems are associated with antimicrobial therapy. Approximately 80% of the patients with bacterial meningitis belong to the pediatric age group, and the three principal pathogens are Haemophilus influenzae type b, Neisseria meningitidis and Streptococcus pneumoniae. The diagnostic requirements essential for satisfactory management are defined and the antibiotic therapy of meningitis is discussed in detail. Data obtained from both experimental and clinical meningitis are indicative that a minimum bactericidal titre of 1:10 should be achieved in the cerebrospinal fluid for optimal therapeutic results. Recommendations are given for specific antimicrobial treatment according to patient's age and causative organism, as well as guidelines for further lumbar punctures, duration of therapy and prophylaxis, with emphasis on the important role of the newer cephalosporin compounds in treatment of meningitis.

Humans↗

Pattern of meningitis in Al-Ain medical district, United Arab Emirates--a decadal experience (1990-99).

OBJECTIVES: Haemophilus influenzae vaccine was introduced in the United Arab Emirates in 1999. Our objective was to describe the pattern of meningitis in a health district in the decade before the introduction of the vaccine and compare it with the data from elsewhere. METHODS: For this retrospective study we included 128 meningitis cases reported from 1990 to 1999. Information on the cases was abstracted from the case notification forms and clinical and laboratory data from the hospital case notes. RESULTS: H. influenzae was the most common cause of bacterial meningitis (n=59, 46.1%) followed by Streptococcus pneumoniae (n=20, 15.6%). Meningitis was a disease primarily of infants and children and the median age was 15 months. One fifth of the patients (n=27) had neurological sequelae of which 33.3% had seizures and 25.9% developed deafness. 18.9% (10 out of 53) of H. influenzae isolates were resistant to ampicillin compared with 5.9% (3 out of 51) to chloramphenicol. 78.9% (15 out of 19) of S. pneumoniae isolates were susceptible to penicillin. CONCLUSIONS: The epidemiology of meningitis in our health district is similar to the epidemiology of meningitis during the pre-vaccine era in other countries.

Adolescent↗

[Significance of lactate level, lysozyme concentration and phosphohexose isomerase activity in the cerebrospinal fluid in the differential diagnosis of meningitis].

The significance of the measurement of lactate, lysozyme and PHI in CSF for differential diagnosis of meningitis was examined in 58 cases of viral, 36 of bacterial and 5 of tuberculous etiology. In the early phase of the illness CSF lactate was found to be the most sensitive parameter for distinction of viral from bacterial or tuberculous meningitis respectively. Except for one case CSF lactate exceeded 3.8 mmol/l in all cases of bacterial etiology, whereas this value was never reached in any case of viral meningitis. While lactate concentration was maximal on the day of admission and declined continuously thereafter, PHI activity reached its maximum on the third day after beginning of the therapy. At this time all patients with a bacterial or tuberculous meningitis had PHI activities about 50 U/l. This value wasn't exceeded in any case of viral meningitis. In a few cases some days after onset of therapy a distinction of bacterial meningitis from viral forms was still possible by PHI determination but not by lactate measurement. Determination of lysozyme also could be helpful in the later phase of the disease.

Bacterial Infections↗

Tumor necrosis factor alpha in cerebrospinal fluid during bacterial, but not viral, meningitis. Evaluation in murine model infections and in patients.

To evaluate the potential role of cachectin/TNF-alpha in the pathogenesis of bacterial and viral meningitis, concentrations and kinetics of TNF-alpha were determined in cerebrospinal fluid (CSF). After intracerebral, but not systemic, infection with Listeria monocytogenes in mice, TNF-alpha was detected as early as 3 h after infection reaching maximum titers after 24 h. However, TNF-alpha was not found in serum during the course of Listeria infection. In contrast to bacterial meningitis, no TNF-alpha was detected at any time in CSF of mice suffering from severe lymphocytic choriomeningitis induced by intracerebral infection with lymphocytic choriomeningitis virus. This difference is striking since both model infections led to a massive infiltration of polymorphonuclear and mononuclear leukocytes into the meninges and CSF. The results found for the two model infections were paralleled by findings in humans; CSF from three out of three patients with bacterial meningitis examined during the first day of hospitalization showed significant levels of TNF-alpha; none of the CSF obtained later than 3 d after hospitalization was positive. In addition, similarly to what was found in mice with viral meningitis, zero out of seven patients with viral meningitis had detectable TNF-alpha in CSF.

Adolescent↗

Proton nuclear magnetic resonance-based metabonomics for rapid diagnosis of meningitis and ventriculitis.

BACKGROUND: Reduction of mortality associated with bacterial meningitis and postsurgical cerebral ventriculitis is dependent on early diagnosis and institution of appropriate therapy. Metabonomics rapidly defines metabolic profiles of biological fluids through the use of high-throughput analytical techniques combined with statistical pattern recognition tools. METHODS: Proton nuclear magnetic resonance (1H NMR)-based metabonomics was applied to (1) lumbar cerebrospinal fluid samples collected prospectively from a cohort of patients with bacterial, fungal, or viral meningitis and from control subjects without neurological disease and (2) ventricular cerebrospinal fluid samples from patients with ventriculitis associated with an external ventricular drain and from control subjects. 1H NMR spectra were analyzed by the unsupervised statistical method of principal components analysis. RESULTS: Metabonomic analysis clearly distinguished patients with bacterial or fungal meningitis (11 patients) from patients with viral meningitis (12) and control subjects (27) and clearly distinguished patients with postsurgical ventriculitis (5) from postsurgical control subjects (10). Metabolites of microbial and host origin that were responsible for class separation were determined. Metabonomic data also correlated with the onset and course of infection in a patient with 2 episodes of bacterial ventriculitis and with response to therapy in another patient with cryptococcal meningitis. CONCLUSIONS: Metabonomic analysis is rapid, requires minimal sample processing, and is not targeted to specific microbial pathogens, making the platform potentially suitable for use in the diagnostic laboratory. This pilot study indicates that metabonomic analysis of cerebrospinal fluid is feasible and a potentially more powerful diagnostic tool than conventional rapid laboratory indicators for distinguishing bacterial from viral meningitis and for monitoring therapy. This should have important implications for early management, reduced empirical use of antibiotics, and treatment duration.

Adolescent↗

Hearing alterations following meningitis. 1. Hearing improvement.

In ten patients suffering from hearing loss following meningitis or meningoencephalitis, hearing recovery was observed. Eight of the cases had suffered from purulent meningitis, five cases had Haemophilus influenzae meningitis, 1 had coli meningitis, and 1 had meningococcal meningitis. In one case, the ethiologic agent remained unknown. Two other cases had suffered from viral meningoencephalitis. Postmeningitis hearing loss was observed in 19 ears. In eight ears, the hearing loss was profound, and in eleven, it was slight to moderate. Recovery of hearing occurred in 16 ears and was complete in eight ears and partial in eight ears. Approximately one-fourth of all patients with meningitis hearing loss do recover partially or completely in both ears or only in one ear.

Adult↗

Differences in the epidemiology of childhood community-acquired bacterial meningitis between two ethnic populations cohabiting in one geographic area.

A comparison of the epidemiology of community-acquired bacterial meningitis between Jewish and Bedouin populations cohabiting one geographical area is reported here. During the years 1981 to 1985, 100 children younger than 13 years old with community-acquired bacterial meningitis were hospitalized. Seventy-one patients were younger than 12 months. The principal bacteria isolated were Haemophilus influenzae 42%; Streptococcus pneumoniae 29% and Neisseria meningitidis 20%. The case fatality rate was 12%. The chance of acquiring meningitis during the first 5 years of life was twice as common among Bedouins than among Jews (328/100,000 vs. 173/100,000, respectively; P less than 0.0001). The most common cause of meningitis during the first year of life was S. pneumoniae among Bedouins and H. influenzae among Jews. Meningitis caused by H. influenzae and S. pneumoniae was usually associated with respiratory morbidity during fall and winter among Jews, but with diarrheal morbidity during summer and fall among Bedouins. Since the most prevalent type of morbidity among Jews results from respiratory infections and among Bedouins from diarrhea, our findings suggest that community-acquired bacterial meningitis is associated with the type of morbidity most prevalent in the community at any given season rather than with a specific type of infection.

Child↗

Cerebrospinal fluid lysozyme in bacterial and viral meningitis.

The concentration of lysozyme (LZM) in cerebrospinal fluid was determined in 25 patients with bacterial meningitis, in 18 patients with viral meningitis and in 25 control patients who had other fibrile illnesses. The concentration of LZM was less than 1.5 microgram/ml in all control patients, and slightly to markedly raised in 10 patients with viral meningitis and in 11 out of 13 patients with untreated bacterial meningitis. The concentration of LZM was significantly different in the viral and bacterial meningitis patients (p less than 0.001). Most raised concentrations of cerebrospinal fluid LZM persisted for at least one week after the start of antibiotic treatment. The concentrations of LZM correlated well with concentrations of lactic dehydrogenase. These results show that the determination of cerebrospinal fluid LZM is a useful tool in the differential diagnosis of meningitis, particularly when the prehospital treatment with antibiotics may be responsible for a diagnostically misleading negative bacterial culture of the cerebrospinal fluid and altered cerebrospinal fluid cytology.

Diagnosis, Differential↗

Free amino acid pattern of cerebrospinal fluid in meningeal pathology.

Free amino acid concentrations of CSF were measured in bacterial meningitis, aseptic meningitis, meningoradiculitis Garin-Bujadoux-Bannwarth, multiple sclerosis, carcinomatous meningitis, and controls. Almost all CSF amino acids were highly elevated in bacterial but not in aseptic meningitis, meningoradiculitis Garin-Bujadoux-Bannwarth or carcinomatous meningitis thus providing a laboratory tool for their differential diagnosis. In carcinomatous meningitis the amino acid pattern indicates metabolic activity of tumor cells. Minimal alterations were found in multiple sclerosis which have no diagnostic value.

Adult↗

Neuraminidase activity in bacterial meningitis.

The relation of neuraminidase to morbidity and mortality was examined in patients with Haemophilus influenzae, meningococcal, and pneumococcal meningitis. Ten strains of H. influenzae and eight strains of meningococci from infected cerebrospinal fluid (CSF) did not elaborate neuraminidase. Each of 27 strains of pneumococci from infected CSF elaborated both neuraminidase and N-acetylneuraminic acid (NANA) aldolase. There was no correlation between amount of neuraminidase secreted in vitro and survival of patients. Values for free and total NANA concentrations were derived from admission CSF samples of 63 patients with meningitis; 18 patients infected with Neisseria meningitidis, 10 with H. influenzae and 35 with Diplococcus pneumoniae. Mean values for total NANA were elevated in each type of bacterial meningitis; however, abnormal concentrations of free CSF NANA were detected only in 17 patients with pneumococcal meningitis. 11 of 18 patients with pneumococcal meningitis showing normal free CSF NANA concentrations were cured, whereas only 4 patients with abnormal free NANA levels survived without residua. Both coma and bacteremia occurred significantly more often among patients with elevated concentrations of free CSF NANA. The association of elevated concentrations of free CSF NANA with coma and with an adverse prognosis suggested that neuraminidase may be a factor in the pathogenesis of penumococcal meningitis.

Cerebrospinal Fluid Proteins↗

Study of the aetiologic agents of meningitis in Kumasi, Ghana, with special reference to Cryptococcal neoformans.

OBJECTIVE: To evaluate the importance of Cryptococcus neoformans, an opportunistic in meningitis, in healthy and HIV infected patients in Kumasi, Ghana. DESIGN: A prospective study; isolating the aetiologic agents of meningitis from cerebrospinal fluid (CSF) using standard methods. SETTING: Kumasi city, Ashanti region of central Ghana. SUBJECTS: One thousand five hundred and seventy patients suspected of meningitis, including 28 HIV infected and AIDS patients. MAIN OUTCOME MEASURE: The pattern and distribution of the main etiologic agents of meningitis in Kumasi, Ghana shown. RESULTS: Of the 1570 CSF samples examined, 1256 (80%) showed no abnormality. Of the 314 (20%) with abnormalities, 147 were bacterial, and 167 diagnosed aseptic. No cryptococcal cells were found. CONCLUSION: There is a paucity of cryptococcal meningitis in Kumasi, Ghana, and it is not recommended to screen routinely for the fungus in meningitis investigations.

AIDS-Related Opportunistic Infections↗

Limulus lysate test for gram-negative bacterial meningitis. Bedside application.

The limulus lysate on cerebrospinal fluid was evaluated in 335 infants and children as a method for the rapid diagnosis of Gram-negative bacterial meningitis. Positive limulus tests were obtained within one hour in 33 of 34 cases of Hemophilus influenzae meningitis; four additional patients with Gram-negative meningitis also showed positive limulus lysate tests. Conversely, 13 patients with Gram-positive bacterial meningitis all yielded negative limulus assays. All 48 cases of aseptic meningitis and 236 children with no meningitis showed negative limulus assays. Antibiotic therapy prior to hospitalization did not vitiate the validity of the test. A bedside adaptation of the limulus test, performed by house officers and medical students, showed approximately 98% agreement with the laboratory assay.

Arachnida↗

Subcortical low intensity on MR images of meningitis, viral encephalitis, and leptomeningeal metastasis.

BACKGROUND AND PURPOSE: Subcortical low-intensity lesion on T2-weighted images is an uncommon manifestation of ischemia, multiple sclerosis, and Sturge-Weber disease. This study was performed to determine whether subcortical low signal intensity is an MR feature of meningitis, viral encephalitis, or leptomeningeal metastasis and to investigate a cause of subcortical low intensity. METHODS: We retrospectively reviewed MR images of 117 patients with meningitis, encephalitis (viral or unknown), or leptomeningeal metastasis for the presence of subcortical low intensity, meningeal enhancement, signal intensity change of cortex, and change in subcortical low intensity on follow-up images. Diffusion-weighted (DW) images and apparent diffusion coefficient (ADC) maps were obtained in 55 patients. Subcortical low-intensity lesions were also quantitatively analyzed on T2-weighted, fluid-attenuated inversion recovery (FLAIR), and DW images. RESULTS: Subcortical low intensity was found in nine (23.7%) of 38 patients with encephalitis (viral, 31; unknown origin, 7), five (24%) of 21 with leptomeningeal metastasis, and five (9%) of 58 with meningitis. Leptomeningeal enhancement was observed in 100% and cortical hyperintensity in 14 (74%) of 19 patients with subcortical low intensity. Leptomeningeal enhancement was seen in 46 (47%) and cortical hyperintensity in 33 (34%) of 98 patients without subcortical low intensity. Subcortical low intensity disappeared or decreased in extent on follow-up MR images in all seven patients who underwent follow-up. ADC of subcortical low-intensity lesions was lower than that of the contralateral area and decreased by 9.3 +/- 11.4%. CONCLUSION: Subcortical low intensity was uncommonly found in meningitis, viral encephalitis, and leptomeningeal metastasis. It is a nonspecific MR sign of various meningeal and cortical diseases. Although the cause of subcortical low intensity remains uncertain, free radical formation may play a role as a causative factor.

Adolescent↗

Entry of ciprofloxacin into cerebrospinal fluid during bacterial, viral and tuberculous meningitis.

We studied the entry of ciprofloxacin into the cerebrospinal fluid (CSF) in 37 patients with various types of meningitis (bacterial meningitis 10 patients, viral 12 patients, tuberculous 7 patients). Eight patients were in the control group with normal CSF finding. Mean ciprofloxacin concentrations in the CSF 50-60 minutes after 200 mg of ciprofloxacin was given in infusion were 0.20 +/- 0.12 mg/L in patients with bacterial meningitis, which was significantly higher than in other tested groups (p = 0.0325). Ciprofloxacin achieved concentrations in the CSF 6.5-39% of serum (mean value 15% +/- 9%) in the bacterial meningitis group, while in the groups with viral and tuberculous meningitis the levels were significantly lower (approximately 9% of serum) but still higher than in the control group (approximately 5% of serum). Our data suggest that ciprofloxacin should be very cautiously used in selected patients with bacterial meningitis caused by multiple resistant strains of gram negative bacteria.

Adult↗

Gd-DTPA-enhanced MR imaging of the brain in patients with meningitis: comparison with CT.

Plain and Gd-DTPA-enhanced MR images of the brain were obtained in 18 consecutive patients with meningitis (eight with tuberculous, five with bacterial, three with viral, and two with fungal infections); the MR images were compared with CT scans. MR images were obtained on a 2.0-T superconducting unit with both T1- and T2-weighted pulse sequences before injection and with a T1-weighted sequence after injection of Gd-DTPA (0.1 mmol/kg) in all patients. In tuberculous meningitis, MR imaging depicted ischemia/infarct, hemorrhagic infarct of basal ganglia, meningeal enhancement at either basal cistern or convexity surface of brain, and associated small granulomas in a few more patients than CT did. In bacterial meningitis, primary foci of extracranial inflammation (i.e., mastoid, paranasal sinuses) and adjacent intracranial lesions including localized dural inflammation, subdural fluid collection, and/or brain parenchymal lesions were demonstrated much better on MR than on CT. Otherwise, MR images generally matched the CT scan. Although the plain MR images, both T1- and T2-weighted, were the most sensitive in delineating ischemia/infarct, hemorrhage, and edema, they were not as specific as Gd-DTPA-enhanced T1-weighted images and postcontrast CT scans in defining the active inflammatory process of the meninges and focal lesions precisely. We conclude that if Gd-DTPA is used, MR imaging appears to be superior to CT in the evaluation of patients with suspected meningitis. Precontrast MR is needed to delineate ischemia/infarct, edema, and subacute hemorrhage.

Adolescent↗

Changing Epidemiology of Bacterial Meningitis in the United States.

Bacterial meningitis is an important cause of morbidity and mortality in the United States and throughout the world. Over the past 20 years, there have been significant changes in the epidemiology of bacterial meningitis. The most important change is the decrease in the frequency of Haemophilus influenzae type b as the most common etiologic agent of bacterial meningitis, since the H. influenzae type b conjugate vaccine was introduced. Streptococcccus pneumoniae is now the major cause of bacterial meningitis in the US and bacterial meningitis is now a disease predominantly of adults, rather than of infants and children. Emergence of antimicrobial resistance in S. pneumoniae has also altered the approach to antimicrobial therapy in patients with pneumococcal meningitis, indicating the need to use preventive strategies to reduce the frequency of this serious infection. Recent licensure of the heptavalent pneumococcal conjugate vaccine will likely decrease the overall incidence of pneumococcal meningitis.

Journal Article↗

Acute Meningitis.

Recent major epidemiologic trends in bacterial meningitis include a dramatic decline in the incidence of Haemophilus influenzae meningitis since the introduction of the protein-conjugated H. influenzae vaccines, and a worldwide increase in infections with antibiotic-resistant strains of bacterial pathogens. Cases of meningitis caused by resistant strains require an alternative therapeutic strategy. Animal studies have identified inflammatory mediators, eg, chemokines, excitatory amino acids, and endothelins, which are involved in the pathophysiology of bacterial meningitis. There is increasing evidence that reactive oxygen species (ROS), reactive nitrogen species, peroxynitrite, and matrix metalloproteinases contribute to brain damage during bacterial meningitis. The cytotoxic effects of ROS and peroxynitrite include the initiation of lipid peroxidation and the induction of DNA single-strand breakage. Damaged DNA activates poly(ADP-ribose) polymerase (PARP). Recent experimental data suggest that lipid peroxidation and PARP activation play a role in the development of meningitis-associated intracranial complications and brain injury. Agents that interfere with the production of ROS and peroxynitrite, and interfere with lipid peroxidation and PARP activation, may represent novel, therapeutic strategies by which meningitis-associated brain damage can be limited, therefore improving the outcome of this serious disease.

Journal Article↗