Tuberculous meningitis in South African urban adults.
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We retrospectively reviewed 56 adults with culture-proven tuberculous meningitis (TBM), investigating clinical signs, cerebrospinal fluid (CSF) findings and outcome. There were 50 patients, aged 18-59 years, 39 with and 11 without human immunodeficiency virus (HIV) infection. Six were aged 60 years or older. Neurological signs of TBM in 18-59-year-olds were unaffected by HIV serostatus while, compared to those > or = 60 years of age, there were more patients with meningism (86.0% vs. 33.3%; p = 0.011) and fewer with seizures (12.0% vs. 50.0%; p = 0.046). The HIV-infected 18-59-year-olds had significantly more extrameningeal tuberculosis compared to the non-HIV-infected (76.9% vs. 9.1%; p = 0.0001) and 23.1% had 'breakthrough' TBM. CSF analysis revealed 12 patients (21.4%) with acellular fluid (more common in those > or = 60 years of age, p = 0.016), of whom three had completely normal CSF. A neutrophil predominance was found in 22 patients (39.3%). Only three patients (5.4%) had a positive CSF smear for acid-fast bacilli. In-hospital mortality occurred in 39 patients (69.1%), was similar in all study groups, and was not related to neurological stage. The diagnosis of TBM can be masked by lack of meningism in the elderly and by atypical CSF findings. (+info)
Free sialic acid levels in the cerebrospinal fluid of patients with meningitis.
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The free and bound sialic acid content of cerebrospinal fluid from patients with positive evidence (by CSF culture) of pyogenic and tuberculous meningitis was determined. The free sialic acid content was significantly raised only in cases of pyogenic meningitis, but not in tuberculous or other types of the disease. (+info)
Tumor necrosis factor alpha is a determinant of pathogenesis and disease progression in mycobacterial infection in the central nervous system.
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The pathogenesis of tuberculous meningitis, a devastating complication of tuberculosis in man, is poorly understood. We previously reported that rabbits with experimental tuberculous meningitis were protected from death by a combination of antibiotics and thalidomide therapy. Survival was associated with inhibition of tumor necrosis factor alpha (TNF-alpha) production by thalidomide. To test whether cerebrospinal fluid (CSF) levels of TNF-alpha correlated with pathogenesis, the response of rabbits infected in the central nervous system (CNS) with various mycobacterial strains was studied. CNS infection with Mycobacterium bovis Ravenel, M. bovis bacillus Calmette-Guerin (BCG) Pasteur, and M. bovis BCG Montreal were compared. M. bovis Ravenel induced the highest levels of TNF-alpha in the CSF in association with high leukocytosis, protein accumulation, and severe meningeal inflammation. BCG Pasteur had intermediate effects, and BCG Montreal was the least virulent. In addition, M. bovis Ravenel numbers were highest in the brain and CSF and the bacilli also disseminated more efficiently to distant organs, compared with BCG Pasteur and BCG Montreal. In subsequent experiments, rabbits were infected with either recombinant M. bovis BCG Montreal (vector), or BCG Montreal expressing the murine gene for TNF-alpha (BCG mTNF-alpha). BCG Montreal was rendered virulent by the expression of murine TNF-alpha, as demonstrated by high CSF leukocytosis, high protein accumulation, severe meningeal inflammation, persistent bacillary load, and progressive clinical deterioration. Taken together, these results demonstrate that the level of TNF-alpha produced during mycobacterial CNS infection determines, at least in part, the extent of pathogenesis. (+info)
Magnetization transfer MR imaging in CNS tuberculosis.
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BACKGROUND AND PURPOSE: CNS tuberculosis may simulate other granulomas and meningitis on MR images. The purpose of this study was to improve the characterization of lesions in CNS tuberculosis and to assess the disease load using magnetization transfer (MT) imaging. METHODS: A total of 107 tuberculomas in seven patients with or without meningitis and 15 patients with tuberculosis meningitis alone were studied. Fifteen patients with cysticercus granulomas with T2 hypointensity, five patients each with viral and pyogenic meningitis, and two patients with cryptococcal meningitis were also studied. The MT ratios were calculated from tuberculomas, cysticercus granulomas, and thickened meninges in tuberculous, viral, pyogenic, and cryptococcal meningitis and were compared within each pathologic group and with the MT ratio of different regions of normal brain parenchyma. Detectability of lesions on T1-weighted MT spin-echo (SE) images was compared with that on conventional SE and postcontrast MT-SE images. RESULTS: Thickened meninges appeared hyperintense relative to surrounding brain parenchyma in the basal and supratentorial cisterns on precontrast MT-SE images in all 18 patients with tuberculosis meningitis. These meninges were not seen or were barely visible on conventional SE images, and enhanced on postcontrast MT-SE images. The MT ratio from the thickened meninges of tuberculous meningitis was significantly lower than that from the meninges in cryptococcal and pyogenic disease and significantly higher than the meninges in viral meningoencephalitis. The MT ratio from T2 visible and invisible tuberculomas appeared to be significantly lower than that of normal white matter. The MT ratio of T2 hypointense cysticercus granuloma was significantly higher than that of T2 hypointense tuberculoma. CONCLUSION: Precontrast MT-SE imaging helps to better assess the disease load in CNS tuberculosis by improving the detectability of the lesions. With the use of MT ratios, it may be possible to differentiate tuberculosis from similar-appearing infective lesions on MR images. (+info)
Predominance of Vgamma9/Vdelta2 T lymphocytes in the cerebrospinal fluid of children with tuberculous meningitis: reversal after chemotherapy.
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BACKGROUND: We analyzed the gammadelta T cell composition and responses in the peripheral blood and cerebrospinal fluid (CSF) of children affected by tuberculous meningitis (TBM) and in control children. MATERIALS AND METHODS: Peripheral blood and CSF samples were stimulated with different phosphoantigens and IL-2, and expansion of Vgamma9/Vdelta2 T cells assessed by FACS analysis. Vgamma9/Vdelta2 lines were obtained by culturing CSF or peripheral blood mononuclear cells (PBMC) in vitro with phosphoantigens and IL-2 for 2 months, and tested for proliferation and cytokine production in response to phosphoantigens. Vdelta2(D)Jdelta junctional sequence length was assessed by PCR. RESULTS: The repertoire of gammadelta T cells from the CSF of TBM patients was characterized by the predominance of Vgamma9/Vdelta2 T lymphocytes, which accounted for >80% of gammadelta T cells. Vgamma9/Vdelta2 cells from the CSF of TBM children responded to different synthetic and natural (mycobacterial) phosphoantigens and produced discrete amounts of IFN-gamma and TNF-alpha. The in vitro expansion of Vgamma9/Vdelta2 T cells from CSF and peripheral blood of TBM patients prominently decreased following chemotherapy, and similarly, the proportion of ex vivo unstimulated Vgamma9/Vdelta2 T cells in CSF of TBM patients decreased to levels detected in the CSF of control subjects. Vdelta2 CDR3 TCR analysis showed that the remaining Vdelta2 cells in the CSF of TBM patients were still polyclonal. CONCLUSIONS: These findings are consistent with an involvement of Vgamma9/Vdelta2 T cells in TBM. http://link. springer-ny.com/link/service/journals/00020/bibs/5n5p301. html (+info)
Diagnostic utility of ELISA test using antigen A60 in suspected cases of tuberculous meningitis in paediatric age group.
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The aim of the study was evaluation of the utility of ELISA test using antigen A60 for rapid diagnosis of tuberculous menigitis (TBM) in paediatric age group. ELISA test based on mycrobacterial antigen A60 (Anda biological, France) was used to estimate specific IgM and IgG antibodies in the sera and CSF of 20 suspected cases of TBM which were selected on the basis of numerous parameters and were smear negative on concentrated smear of CSF. Sera of 20 Montoux negative healthy children was taken as control by detecting IgM and IgG antibodies to A60 antigen. Response to anti-tubercular treatment was observed in all the suspected cases of TBM. This study showed that specificity for diagnosis of TBM by detecting IgM and IgG antibodies in sera was 90% and 80% respectively. Sensitivity of the test by detecting IgM and IgG antibodies in sera was 85% and 80% respectively with positive predictive value of 89.47% for IgM antibody and 80% for IgG antibody. In CSF IgM and IgG antibodies were found in 75% and 60% cases respectively. Both were positive only in 60% of cases. It is concluded from this study that 80-85% cases of TBM in paediatric age group have eigher IgM or IgG antibodies in sera whereas 60-75% have antibodies in CSF. (+info)
A diagnostic rule for tuberculous meningitis.
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Diagnostic confusion often exists between tuberculous meningitis and other meningoencephalitides. Newer diagnostic tests are unlikely to be available in many countries for some time. This study examines which clinical features and simple laboratory tests can differentiate tuberculous meningitis from other infections. Two hundred and thirty two children (110 tuberculous meningitis, 94 non-tuberculous meningitis, 28 indeterminate) with suspected meningitis and cerebrospinal fluid (CSF) pleocytosis were enrolled. Tuberculous meningitis was defined as positive CSF mycobacterial culture or acid fast bacilli stain, or basal enhancement or tuberculoma on computed tomography (CT) scan with clinical response to antituberculous treatment. Non-tuberculous meningitis was defined as positive CSF bacterial culture or Gram stain, or clinical response without antituberculous treatment. Thirty clinical/laboratory features of patients with tuberculous meningitis and non-tuberculous meningitis were compared by univariate and multiple logistic regression analysis. Five features were independently predictive of the diagnosis of tuberculous meningitis (p < 0.007): prodromal stage >/= 7 days, optic atrophy on fundal examination, focal deficit, abnormal movements, and CSF leucocytes < 50% polymorphs. When validated on another set of 128 patients, if at least one feature was present, sensitivity was 98.4% and, if three or more were present, specificity was 98.3%. This simple rule would be useful to physicians working in regions where tuberculosis is prevalent. (+info)
Rapid diagnosis of tuberculous meningitis by a dot immunobinding assay To detect mycobacterial antigen in cerebrospinal fluid specimens.
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In the present prospective study, a dot immunobinding assay (Dot-Iba) was standardized to measure the circulating mycobacterial antigen in cerebrospinal fluid (CSF) specimens for the laboratory diagnosis of tuberculous meningitis (TBM). Immunoglobulin G antibody specific for Mycobacterium tuberculosis in a CSF specimen from a patient with culture-proven TBM was isolated and was coupled with activated cyanogen bromide-Sepharose 4B. By immunosorbent affinity chromatography, a 14-kDa antigen was isolated from the culture filtrate of M. tuberculosis. Antibody to the 14-kDa mycobacterial antigen was raised in rabbits. The Dot-Iba in this study gave no false-positive results with CSF specimens from patients with nontuberculous neurological diseases. The assay gave positive results for all five patients with culture-proven TBM. The Dot-Iba described in the present report is simple, rapid, sensitive, specific, and, more importantly, suitable for routine application in laboratories in developing countries. (+info)