Differential Diagnosis Of Tuberculous Meningitis Research Articles

Identification of protein biomarkers in host cerebrospinal fluid for differential diagnosis of tuberculous meningitis and other meningitis.

Background and purposeThe diagnosis of tuberculous meningitis (TBM) is difficult due to the lack of sensitive methods. Identification of TBM-specific biomarkers in the cerebrospinal fluid (CSF) may help diagnose and improve our understanding of TBM pathogenesis.Patients and methodsOf the 112 suspected patients with TBM prospectively enrolled in the study, 32 patients with inconclusive diagnosis, non-infectious meningitis, and long-term treatment with hormones and immunosuppressants were excluded. The expression of 8 proteins in the CSF was analyzed using ELISA in 22 patients with definite TBM, 18 patients with probable TBM, and 40 patients with non-TBM.ResultsSignificant differences in the expression of 7 proteins were detected between the TBM and non-TBM groups (P < 0.01). Unsupervised hierarchical clustering (UHC) analysis revealed a disease-specific profile consisting of 7 differentially expressed proteins for TBM diagnosis, with an accuracy of 82.5% (66/80). Logistic regression with forward stepwise analysis indicated that a combination of 3 biomarkers (APOE_APOAI_S100A8) showed a better ability to discriminate TBM from patients with non-TBM [area under the curve (AUC) = 0.916 (95%CI: 0.857–0.976)], with a sensitivity of 95.0% (95%CI: 83.1–99.4%) and a specificity of 77.5% (95%CI: 61.5–89.2%).ConclusionOur results confirmed the potential ability of CSF proteins to distinguish TBM from patients with non-TBM and provided a useful panel for the diagnosis of TBM.

The association between serum sodium level and tuberculous meningitis compared with viral and bacterial meningitis

We evaluated the association between hyponatremia and tuberculous meningitis (TBM) with the aim of providing additional information for differential diagnosis from other types of infectious meningitis, especially viral meningitis (VM). Cross-sectional and longitudinal data involving 5026 participants older than 18 years were analyzed in the total population and a propensity-matched population. The initial and lowest sodium levels and longitudinal changes in TBM, bacterial meningitis (BM), and VM patients were compared. Participants in the TBM group were enrolled when they were diagnosed as possible, probable, or definite TBM according to the Marais’ criteria. The initial serum sodium level was significantly lower in TBM patients than in BM and VM patients (136.9 ± 5.9 vs. 138.3 ± 4.7 mmol/L, p < 0.001 for TBM vs. BM, and 139.0 ± 3.1, p < 0.001 for TBM vs. VM), and it decreased significantly more steeply to lower levels in both the TBM and BM patients compared with VM patients. The lowest serum sodium level was in the order of TBM < BM < VM patients, and the change was statistically significant in all subgroups (131.8 ± 6.4, 133.1 ± 5.1, 137.4 ± 3.7, respectively, p < 0.001). Participants with lower serum sodium level were more likely to have a diagnosis of TBM rather than VM, and this association was more pronounced for the lowest sodium level than the initial sodium level [OR 4.6 (95% CI 2.4–8.8, p < 0.001)]. These findings indicate that baseline and longitudinal evaluation of serum sodium level can provide information for differential diagnosis of TBM from BM or VM.

Glucocorticoids in the treatment of patients with tuberculous meningitis — two sides of one medal (current trends, clinical case)

Corticosteroids have long been used as an adjunct to the treatment of tuberculous meningitis. In addition, glucocorticoid therapy is an integral aspect of the management of patients with systemic connective tissue diseases, which is due to the high effectiveness of these drugs in reducing disease activity. Immunological defects in systemic connective tissue diseases, a high total dose of corticosteroids in therapy cause the activation of latent tuberculosis infection and the rapid development of the disease when infected with mycobacterium tuberculosis.The results of presented clinical case have shown that doctors of different specialties should be tuned to the probability of developing tuberculous meningitis in patients with immunosuppression, even in the absence of meningeal symptoms (rigidity of the occipital muscles, the symptom of Kernig) against the background of the use of glucocorticoids in the treatment of other diseases. At the same time, corticosteroids should be prescribed to patients as an adjuvant for anti‑TB therapy (despite immunosuppressive effects), but the regimen should be developed for each patient according to the individual severity of the disease. A molecular genetic method G‑Xpert demonstrated considerable molecular diagnostic value for the diagnosis of tuberculous meningitis. The method allows not only detect Mycobacterium tuberculosis in the cerebrospinal fluid in 2 hours but also determine the presence of multiple drug resistance, which contributes to the immediate administration of adequate etiotropic therapy which prevents the development of severe neurological disorders and death. Neuroimaging is essential for the diagnosis and monitoring of tuberculous meningitis.In cases of differential diagnosis of tuberculous meningitis, physicians should refrain from using broad‑spectrum drugs from fluoroquinolones and aminoglycosides, as this may cause untimely detection of a correct diagnosis.

Tuberculous and brucellosis meningitis differential diagnosis.

The Thwaites and Lancet scoring systems have been used in the rapid diagnosis of tuberculous meningitis (TBM). However, brucellar meningoencephalitis (BME) has similar characteristics with TBM. The ultimate aim of this study is to infer data to see if BME should be included in the differential diagnosis of TBM when these two systems suggest the presence of TBM. BME and TBM patients from 35 tertiary hospitals were included in this study. Overall 294 adult patients with BME and 190 patients with TBM were enrolled. All patients involved in the study had microbiological confirmation for either TBM or BME. Finally, the Thwaites and Lancet scoring systems were assessed in both groups. The Thwaites scoring system more frequently predicted BME cases (n=292, 99.3%) compared to the TBM group (n=182, 95.8%) (P=0.017). According to the Lancet scoring system, the mean scores for BME and TBM were 9.43±1.71 and 11.45±3.01, respectively (P<0.001). In addition, TBM cases were classified into "probable" category more significantly compared to BME cases, and BME cases were categorized into the "possible" category more frequently. When the Thwaites or Lancet scoring systems indicate TBM, brucellar etiology should also be taken into consideration particularly in endemic countries.

Validation of thwaites' diagnostic scoring system for the differential diagnosis of tuberculous meningitis and bacterial meningitis.

To compare the clinical features of patients with tuberculous meningitis (TBM) and bacterial meningitis (BM) and to validate Thwaites' diagnostic scoring system for the differential diagnosis of TBM and BM, a retrospective review of 211 patients with TBM or BM who were admitted to Huashan Hospital, Fudan University, from 2007 to 2012 was conducted. The clinical characteristics and laboratory data were compared, and Thwaites' diagnostic scores were assessed at the time of admission for the differential diagnosis of TBM and BM. Significant differences were observed between the 2 groups in general information, clinical features, and cerebrospinal fluid characteristics. The sensitivity and specificity of Thwaites' diagnostic scoring system for the differential diagnosis of TBM and BM were found to be 98.2% and 43.6%, respectively, with positive and negative predictive values being 65.9% and 95.8%, respectively. The sensitivity and specificity for the differential diagnosis of TBM and initially treated BM were 98.2% and 82.9%, respectively, but were only 98.2% and 24.2% for that of TBM and partially treated BM, respectively. Thus, Thwaites' diagnostic scoring system was found to be highly effective for the differential diagnosis of TBM and initially treated BM but was found to be less effective for that of TBM and partially treated BM.

Clinical and Laboratory Factors in the Differential Diagnosis of Tuberculous and Cryptococcal Meningitis in Adult HIV-negative Patients

Objective It is difficult to make the differential diagnosis between tuberculous meningitis (TBM) and cryptococcal meningitis (CM) when the smear is negative. The objective of this study was to create a diagnostic rule for differentiating TBM from CM in adult HIV-negative patients based on clinical and laboratory features. Methods The clinical and laboratory data of 219 adult HIV-negative patients satisfying the diagnostic criteria for tuberculous (n=100) and cryptococcal (n=119) meningitis hospitalized at the Third Affiliated Hospital of Sun Yat-Sen University during the period 2000-2009 were retrospectively analyzed. Features found to be independently predictive of tuberculous meningitis were modeled using a multivariate logistic regression to create a diagnostic rule. The performance of the diagnostic rule was assessed using a prospective test data method. Results Six factors were found to be predictive of a diagnosis of tuberculous meningitis: gender, mental disorders, vision and/or hearing damage, proteins in the cerebrospinal fluid, the total cerebrospinal fluid white cell count and the coexistence of tuberculosis in peripheral organs. The diagnostic rule developed using these features exhibited 78.0% sensitivity, 95.2% specificity, 92.9% positive predictive value and 84.4% negative predictive value. The corresponding values for the diagnostic rule were 70.0% and 88.0% using prospective test data. Conclusion Clinical and laboratory features can be helpful in the differential diagnosis of tuberculous meningitis and cryptococcal meningitis in adult HIV-negative patients.

Primary Diffuse Leptomeningeal Gliomatosis Mimicking Meningeal Tuberculosis

Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare condition, with only 45 cases recorded to date, characterized by infiltration of the meninges by glial cells without evidence of primary tumor in the brain or spinal cord parenchyma. Here, we describe a patient with PDLG who was managed with tuberculostatic drugs owing to multiple findings that were suggestive of tuberculous meningitis. A 19-year-old woman presented with headaches and behavioral changes. A sudden decrease in visual acuity with papilledema, bilateral sixth nerve palsies, and neck stiffness developed. Lumbar puncture showed elevated opening pressure (50 cm H2O). Cerebrospinal fluid (CSF) analysis showed glucose 30 mg/dL, protein 26.5 mg/dL, white blood cell count 150 (60% lymphocytes, 40% neutrophils). The second sample of CSF provided adenosine deaminase activity 21.9 U/L. Polymerase chain reaction for Koch's bacillus was positive in the third CSF sample. Magnetic resonance imaging revealed meningeal thickening of the quadrigeminal cistern, tentorium cerebelli, cerebral convexity, and spinal cord, with gadolinium enhancement in nodular lesions. The patient died 22 weeks after symptom onset owing to brainstem infarction. Postmortem pathologic studies revealed PDLG. This entity should be included in the differential diagnosis of tuberculous meningitis that does not respond to treatment with antituberculous drugs. Surgical biopsy should be considered in contrast-enhanced areas in magnetic resonance imaging.

Thwaites’ Diagnostic Scoring and the Prediction of Tuberculous Meningitis

Objective: This study was conducted to investigate the applicability of Thwaites’ diagnostic criteria in order to differentiate tuberculous from bacterial meningitis. Material and Methods: The study was done retrospectively in HIV-negative patients (n = 126) with meningitis. Of the 126 patients, 103 had bacterial meningitis and 23 patients had tuberculous meningitis. The diagnosis was confirmed microbiologically in 59 and 12 patients with bacterial and tuberculous meningitis, respectively. The prediction of tuberculous meningitis was determined by Thwaites’ diagnostic scoring using parameters such as age, history of illness, white blood cell count, total cerebrospinal fluid (CSF) white cell count and the percent of neutrophils in CSF. The diagnostic value of the model was assessed by calculating the area under the receiver operating characteristic (ROC) curves. Results: The sensitivity and the specificity of Thwaites’ diagnostic scoring were 95.6% (22/23) and 70.8% (73/103), respectively. In microbiologically proven cases the sensitivity and the specificity were 91.7% (11/12), 79.7% (57/59), respectively. The area under the ROC curve value for the diagnostic scoring was 0.92. Conclusions: Thwaites’ diagnostic score was found to be helpful in differential diagnosis of tuberculous meningitis, however, the usefulness of diagnostic scoring should be validated in large series especially in patients with viral meningitis and low CSF glucose levels.

Proton MR CSF analysis and a new software as predictors for the differentiation of meningitis in children

This article describes proton MR spectroscopic analysis of cerebrospinal fluid of 167 children suffering from meningitis and 24 control cases. Quantification of 12 well-separated and commonly observed cerebrospinal fluid metabolites viz., beta-hydroxybutyrate, lactate, alanine, acetate, acetone, acetoacetate, pyruvate, glutamine, citrate, creatine/creatinine, glucose (total) and urea was carried out using Bruker's NMRQUANT software with respect to a known concentration of sodium-3-(trimethylsilyl)-2,2,3,3-d4-propionate (TSP), serving as an external reference. The assignment of urea in CSF is reported for the first time by NMR. The presence of cyclopropane, observed for the first time in tuberculous meningitis overall in 85.1% of cases, acts as a finger-print marker for the differential diagnosis. Multivariate discriminant function analysis was carried out for the proton MR-detected metabolite information and the clinical symptoms data of the meningitis and control cases to find the important descriptors for classification, followed by a re-validation of the entire database. It was found that the control could be differentiated from the disease group with a success rate of 96.4%, followed by the differential diagnosis of tuberculous meningitis with a corresponding value of 77.2%. Excluding the presence of cyclopropane, bacterial meningitis could be classified 84.4% correct and viral meningitis with a rate of 83.3%. It is proposed that the NMR spectroscopic information, along with other routine clinical features, may serve as an additional diagnostic tool for the differential diagnosis of meningitis in children.

Differential diagnosis of tuberculous meningitis from partially-treated pyogenic meningitis by cell ELISA

BackgroundTuberculous meningitis (TBM) is a major global health problem, and it is sometimes difficult to perform a differential diagnosis of this disease from other diseases, particularly partially-treated pyogenic meningitis (PTPM). In an earlier study, we demonstrated the presence of a 30-kD protein antigen in cerebrospinal fluid (CSF) of TBM patients. We have also shown that lymphocytes from CSF of TBM patients respond differently to this antigen than do those from PTPM patients. The purpose of this study was to develop an assay that can discriminate between TBM and PTPM.MethodsWe developed a cell enzyme-linked immunosorbant assay (Cell ELISA) to quantitatively measure production of antibodies against the 30-kD protein in B cells from CSF of TBM and PTPM patients.ResultsThe cell ELISA yielded 92% (11/12) sensitivity and 92% (11/12) specificity for the differential diagnosis of TBM from PTPM.ConclusionWhen induced with the 30-kD protein antigen, B cells derived from CSF of TBM patients respond to IgG production within 24 h while those derived from PTPM patients do not respond.

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.

Immunodiagnosis of tuberculous meningitis: rapid detection of mycobacterial antigens in cerebrospinal fluid by reverse passive hemagglutination assay and their characterization by Western blotting.

Tuberculous meningitis (TBM) is one of the commonest chronic infections of the central nervous system (CNS). Diagnosis of TBM has been a problem as it causes various clinical manifestations which can be confused with those of other chronic infections of the CNS such as neurocysticercosis (NCC), neurobrucellosis and cryptococcal meningitis, that are prevalent in many underdeveloped and developing countries. Differential diagnosis of TBM can be made by detecting circulating mycobacterial antigens in CSF by immunoassays. In this study, a reverse passive hemagglutination (RPHA) has been developed using rabbit antimycobacterial IgG for detection of circulating mycobacterial antigens in CSFs from chronic infections of the CNS in order to develop a rapid, simple, sensitive and cost-effective method. Circulating mycobacterial antigens were characterized by immunoblot assay. The sensitivity limit of RPHA was 400 ng ml(-1). RPHA was specific as antimycobacterial IgG did not show any reaction with porcine Cysticercus cellulosae which was used as a control antigen. RPHA could detect mycobacterial antigens in CSF at a sensitivity level of 94.11% with a specificity of 99.0%. Immunoblot analysis of RPHA positive CSFs revealed predominantly 30-32 kDa and 71 kDa antigens whilst 6, 86, 120, 96 and 110 kDa showed varied degree of reactivity. Antigens of masses 30-32 and 71 kDa were absent in culture filtrate of Mycobacterium tuberculosis H37Rv grown in Proskeur-Beck liquid medium. RPHA is a rapid, simple and sensitive immunological method with a long shelf life of 6-8 weeks if stabilized coated erythrocytes are stored at +4 degrees C. RPHA could be used as an additional immunodiagnostic tool in both differential diagnosis and prognosis of TBM. Immunoblot results indicate that 30-32 kDa and 71 kDa antigens are cell wall derived.

Immunodiagnosis of tuberculous meningitis: rapid detection of mycobacterial antigens in cerebrospinal fluid by reverse passive hemagglutination assay and their characterization by Western blotting

Tuberculous meningitis (TBM) is one of the commonest chronic infections of the central nervous system (CNS). Diagnosis of TBM has been a problem as it causes various clinical manifestations which can be confused with those of other chronic infections of the CNS such as neurocysticercosis (NCC), neurobrucellosis and cryptococcal meningitis, that are prevalent in many underdeveloped and developing countries. Differential diagnosis of TBM can be made by detecting circulating mycobacterial antigens in CSF by immunoassays. In this study, a reverse passive hemagglutination (RPHA) has been developed using rabbit antimycobacterial IgG for detection of circulating mycobacterial antigens in CSFs from chronic infections of the CNS in order to develop a rapid, simple, sensitive and cost-effective method. Circulating mycobacterial antigens were characterized by immunoblot assay. The sensitivity limit of RPHA was 400 ng ml −1. RPHA was specific as antimycobacterial IgG did not show any reaction with porcine Cysticercus cellulosae which was used as a control antigen. RPHA could detect mycobacterial antigens in CSF at a sensitivity level of 94.11% with a specificity of 99.0%. Immunoblot analysis of RPHA positive CSFs revealed predominantly 30–32 kDa and 71 kDa antigens whilst 6, 86, 120, 96 and 110 kDa showed varied degree of reactivity. Antigens of masses 30–32 and 71 kDa were absent in culture filtrate of Mycobacterium tuberculosis H37Rv grown in Proskeur–Beck liquid medium. RPHA is a rapid, simple and sensitive immunological method with a long shelf life of 6–8 weeks if stabilized coated erythrocytes are stored at +4°C. RPHA could be used as an additional immunodiagnostic tool in both differential diagnosis and prognosis of TBM. Immunoblot results indicate that 30–32 kDa and 71 kDa antigens are cell wall derived.