A comparison of clinical features between neurobrucellosis and tuberculous meningitis.

BACKGROUD: This study aims to compare the clinical manifestations, imaging findings, routine tests, biochemistry indicators and cerebrospinal fluid cytology between neurobrucellosis and tuberculous meningitis. The objective is to evaluate the similarities and differences of these two diseases and improve early diagnosis. METHODS: A comprehensive evaluation was conducted by comparing clinical data, imaging results, routine tests findings, biochemistry indicators and cerebrospinal fluid cytology of patients admitted to the Department of Neurology, the Second Hospital of Hebei Medical University from 2019 to 2021. Statistical analysis was applied to identify significant differences and similarities between the two diseases. RESULTS: Preliminary analysis demonstrated both diseases commonly present with symptoms such as fever, headache. However, there were no statistical differences between neurobrucellosis and tuberculous meningitis in early clinical data, imaging results, routine tests findings, biochemistry indicators. Further analysis indicates there is a statistically significantly difference in the lymphocyte ratio and neutrophil ratio in the cerebrospinal fluid between the two groups. CONCLUSIONS: Neurobrucellosis and tuberculous meningitis share similarities in early clinical manifestations, imaging findings and initial cerebrospinal fluid parametes, making early-stage differentiation challenging. The ratio of lymphocytes and neutrophil in the cerebrospinal fluid and a detailed medical history investigation can provide clues for early clinical diagnosis. So the examination of CSF cytology might be a potential to distinguish these two diseases and become a powerful tool in the future.

Chronic meningitis in adults: a comparison between neurotuberculosis and neurobrucellosis.

BACKGROUND: In regions endemic for tuberculosis and brucellosis, distinguishing between tuberculous meningitis (TBM) and brucella meningitis (BM) poses a substantial challenge. This study investigates the clinical and paraclinical characteristics of patients with TBM and BM. METHODS: Adult patients diagnosed with either TBM or BM who were admitted to two referral hospitals between March 2015 and October 2022, were included, and the characteristics of the patients were analyzed. RESULTS: Seventy patients formed the study group, 28 with TBM and 42 with BM, were included. TBM patients had a 2.06-fold (95% CI: 1.26 to 3.37, P-value: 0.003) higher risk of altered consciousness and a 4.80-fold (95% CI: 1.98 to 11.61, P-value: < 0.001) higher risk of extra-neural involvement as compared to BM patients. Cerebrospinal fluid (CSF) analysis revealed a significantly higher percentage of polymorphonuclear leukocytes (PMN) in TBM compared to BM (Standardized mean difference: 0.69, 95% CI: 0.18 to 1.20, P-value: 0.008). Neuroimaging findings indicated higher risks of hydrocephalus (P-value: 0.002), infarction (P-value: 0.029), and meningeal enhancement (P-value: 0.012) in TBM compared to BM. Moreover, TBM patients had a 67% (95% CI: 21% to 131%, P-value:0.002) longer median length of hospital stay and a significantly higher risk of unfavorable outcomes (Risk ratio: 6.96, 95% CI: 2.65 to 18.26, p < 0.001). CONCLUSIONS: Our study emphasizes that TBM patients displayed increased frequencies of altered consciousness, PMN dominance in CSF, extra-neural involvement, hydrocephalus, meningeal enhancement, and brain infarction. The findings emphasize the diagnostic difficulties and underscore the importance of cautious differentiation between these two conditions to guide appropriate treatment strategies.

Targeted sequencing from cerebrospinal fluid for rapid identification of drug-resistant tuberculous meningitis.

Mortality from tuberculous meningitis (TBM) remains around 30%, with most deaths occurring within 2 months of starting treatment. Mortality from drug-resistant strains is higher still, making early detection of drug resistance (DR) essential. Targeted next-generation sequencing (tNGS) produces high read depths, allowing the detection of DR-associated alleles with low frequencies. We applied Deeplex Myc-TB-a tNGS assay-to cerebrospinal fluid (CSF) samples from 72 adults with microbiologically confirmed TBM and compared its genomic drug susceptibility predictions to a composite reference standard of phenotypic susceptibility testing (pDST) and whole genome sequencing, as well as to clinical outcomes. Deeplex detected Mycobacterium tuberculosis complex DNA in 24/72 (33.3%) CSF samples and generated full DR reports for 22/24 (91.7%). The read depth generated by Deeplex correlated with semi-quantitative results from MTB/RIF Xpert. Alleles with <20% frequency were seen at canonical loci associated with first-line DR. Disregarding these low-frequency alleles, Deeplex had 100% concordance with the composite reference standard for all drugs except pyrazinamide and streptomycin. Three patients had positive CSF cultures after 30 days of treatment; reference tests and Deeplex identified isoniazid resistance in two, and Deeplex alone identified low-frequency rifampin resistance alleles in one. Five patients died, of whom one had pDST-identified pyrazinamide resistance. tNGS on CSF can rapidly and accurately detect drug-resistant TBM, but its application is limited to those with higher bacterial loads. In those with lower bacterial burdens, alternative approaches need to be developed for both diagnosis and resistance detection.

Evaluation of seegene anyplex MTB/NTM real-time detection assay for diagnosis of tuberculous meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is a common central nervous system infectious disease. Polymerase chain reaction (PCR) assay is a useful method for the rapid diagnosis of TBM. The Seegene Anyplex MTB/NTM real-time detection assay has good sensitivity and specificity for detection of tuberculosis in respiratory specimens, though, data regarding other specimens are lacking. This study aims to define the diagnostic role of Seegene Anyplex MTB/NTM real-time detection assay in TBM in adults. METHODS: This was a retrospective study of 367 adults with symptomatic community acquired meningitis between December 2013 and December 2019. Cerebrospinal fluid (CSF) had been sent for conventional diagnosis, including culture to identify Mycobacterium tuberculosis, and Seegene Anyplex MTB/NTM real-time detection assay. Other diagnostic examinations were performed as necessary. RESULTS: Of the 367 patients in the study, 37 were diagnosed with TBM (14 with definite TBM and 23 with probable TBM). Between the total TBM cases (n = 37) and non-TBM cases (n = 330), clinical sensitivity was 32.4% and specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 93.0%. Between the definite TBM cases (n = 14) and non-TBM cases (n = 330), clinical sensitivity was 50.0% and specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 97.9%. CONCLUSION: Due to lack of sensitivity, we suggest Seegeen Anyplex MTB/NTM real-time detection assay should not be used to rule out TBM but is useful for definite diagnosis.

Combined cerebrospinal fluid metabolomic and cytokine profiling in tuberculosis meningitis reveals robust and prolonged changes in immunometabolic networks.

Much of the high mortality in tuberculosis meningitis (TBM) is attributable to excessive inflammation, making it imperative to identify targets for host-directed therapies that reduce pathologic inflammation and mortality. In this study, we investigate how cytokines and metabolites in the cerebral spinal fluid (CSF) associate with TBM at diagnosis and during TBM treatment. At diagnosis, TBM patients (n = 17) demonstrate significant increases of cytokines and chemokines that promote inflammation and cell migration including IL-17A, IL-2, TNFα, IFNγ, and IL-1ß versus asymptomatic controls without known central nervous system pathology (n = 20). Inflammatory immune signaling had a strong positive correlation with immunomodulatory metabolites including kynurenine, lactic acid, and carnitine and strong negative correlations with tryptophan and itaconate. Inflammatory immunometabolic networks were only partially reversed with two months of effective TBM treatment and remained significantly different compared to CSF from controls. Together, these data highlight a critical role for host metabolism in regulating the inflammatory response to TBM and indicate the timeline for restoration of immune homeostasis in the CSF is prolonged.

Rifampicin and protein concentrations in paired spinal versus ventricular cerebrospinal fluid samples of children with tuberculous meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is the most lethal form of TB. To study the disease, drug concentrations in samples obtained from the spinal CSF are usually used to reflect brain concentrations. Emerging data suggest that transport of substances across capillaries in the brain (ventricular CSF) and spinal cord may differ. METHODS: We examined paired, time-linked samples of ventricular CSF (VCSF) and lumbar CSF (LCSF) of 28 patients with TBM and analysed these for rifampicin and total protein concentrations. Clinically indicated samples from procedures to determine the level of CSF block were collected from children being treated for TBM and hydrocephalus. Total protein concentrations were determined using the bicinchoninic acid (BCA) or turbidimetry assay, and rifampicin concentrations were determined using a validated LC coupled with tandem MS method. A paired Wilcoxon signed-rank test was used to determine significance. RESULTS: TBM was confirmed in 19 cases (68%) using TB culture or GeneXpert Mtb/Rifampicin assay. All other cases were classified as probable. The median total protein concentration in LCSF was 6.0 g/L and in VCSF was 1.3 g/L. The median rifampicin concentration in LCSF was 299 ng/mL and 133 ng/mL in VCSF. The median ratio of LCSF/VSCF for protein was 4.23 and 1.57 for rifampicin. CONCLUSIONS: Total protein and rifampicin concentrations differed significantly between the two compartments, both being higher in LCSF than in VCSF samples (P < 0.0001 for total protein and P = 0.0046 for rifampicin). Further studies are required to explore the causative reasons for the observed differences.

Development and validation of a new model for the early diagnosis of tuberculous meningitis in adults based on simple clinical and laboratory parameters.

BACKGROUND: The differential diagnosis between tuberculous meningitis (TBM) and viral meningitis (VM) or bacterial meningitis (BM) remains challenging in clinical practice, particularly in resource-limited settings. This study aimed to establish a diagnostic model that can accurately and early distinguish TBM from both VM and BM in adults based on simple clinical and laboratory parameters. METHODS: Patients diagnosed with TBM or non-TBM (VM or BM) between January 2012 and October 2021 were retrospectively enrolled from the General Hospital (derivation cohort) and Branch Hospital (validation cohort) of Ningxia Medical University. Demographic characteristics, clinical symptoms, concomitant diseases, and cerebrospinal fluid (CSF) parameters were collated. Univariable logistic analysis was performed in the derivation cohort to identify significant variables (P < 0.05). A multivariable logistic regression model was constructed using these variables. We verified the performance including discrimination, calibration, and applicability of the model in both derivation and validation cohorts. RESULTS: A total of 222 patients (70 TBM and 152 non-TBM [75 BM and 77 VM]) and 100 patients (32 TBM and 68 non-TBM [31 BM and 37 VM]) were enrolled as derivation and validation cohorts, respectively. The multivariable logistic regression model showed that disturbance of consciousness for > 5 days, weight loss > 5% of the original weight within 6 months, CSF lymphocyte ratio > 50%, CSF glucose concentration < 2.2 mmol/L, and secondary cerebral infarction were independently correlated with the diagnosis of TBM (P < 0.05). The nomogram model showed excellent discrimination (area under the curve 0.959 vs. 0.962) and great calibration (P-value in the Hosmer-Lemeshow test 0.128 vs. 0.863) in both derivation and validation cohorts. Clinical decision curve analysis showed that the model had good applicability in clinical practice and may benefit the entire population. CONCLUSIONS: This multivariable diagnostic model may help clinicians in the early discrimination of TBM from VM and BM in adults based on simple clinical and laboratory parameters.

Diagnostic value of the cerebrospinal fluid lipoarabinomannan assay for tuberculous meningitis: a systematic review and meta-analysis.

Objective: This systematic review aims to evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) lipoarabinomannan (LAM) assays in detecting tuberculous meningitis (TBM). Methods: A systematic review search was conducted in PubMed and five other databases up to April 2023. Studies that evaluated the diagnostic accuracy of CSF LAM assays were included with either definitive or composite reference standard used as the preferred reference standard. The quality of the included studies was assessed using the QUADAS-2 tool. We performed a bivariate random-effects meta-analysis and calculated the summary diagnostic statistics. Results: A total of six studies, including a sample size of 999, were included in the final analysis. The pooled sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of CSF LAM for diagnosing TBM were determined to be 0.44 (95% CI: 0.31-0.58), 0.89 (95% CI: 0.81-0.93), and 0.76 (95% CI: 0.73-0.80), respectively. Significant heterogeneity was observed in both sensitivity (Q = 73.82, p < 0.01; I2 = 86.45, 95%CI: 79.64-93.27) and specificity (Q = 95.34, p < 0.01; I2 = 89.51, 95% CI: 84.61-94.42). Regression analysis indicated that the study design (retrospective vs. prospective) was associated with the heterogeneity of pooled sensitivity and specificity (all p < 0.05). Conclusion: Although more prospective studies are required to validate the role of the CSF LAM assay, current evidence supports that the performance of the CSF LAM assay is unsatisfactory for the TBM diagnosis. Additionally, the optimization of the CSF LAM assay (e.g., improvements in CSF collection and preparation methods) should be considered to improve its performance.

Clinical characteristics of tuberculous meningitis in older patients compared with younger and middle-aged patients: a retrospective analysis.

BACKGROUND: Few studies have analyzed the clinical characteristics and adverse factors affecting prognosis in older patients with tuberculous meningitis (TBM). This study aimed to compare the clinical characteristics of TBM in older patients with those in younger and middle-aged patients. METHODS: This single-center retrospective study extracted data on the clinical features, cerebrospinal fluid changes, laboratory results, imaging features, and outcomes of patients with TBM from patient medical records and compared the findings in older patients (aged 60 years and older) with those of younger and middle-aged patients (aged 18-59 years). RESULTS: The study included 197 patients with TBM, comprising 21 older patients aged 60-76 years at onset, and 176 younger and middle-aged patients aged 18-59 years at onset. Fever was common in both older (81%) and younger and middle-aged patients (79%). Compared with younger and middle-aged patients, older patients were more likely to have changes in awareness levels (67% vs. 40%), peripheral nerve dysfunction (57% vs. 29%), changes in cognitive function (48% vs. 20%), and focal seizures (33% vs. 6%), and less likely to have headache (71% vs. 93%), neck stiffness on meningeal stimulation (38% vs. 62%), and vomiting (47% vs. 68%). The Medical Research Council staging on admission of older patients was stage II (52%) and stage III (38%), whereas most younger and middle-aged patients had stage I (33%) and stage II (55%) disease. Neurological function evaluated on the 28th day of hospitalization was more likely to show poor prognosis in older patients than in younger and middle-aged patients (76% vs. 25%). Older patients had significantly higher red blood cell counts and blood glucose levels, and significantly lower serum albumin and sodium levels than those in younger and middle-aged patients. The cerebrospinal fluid protein levels, nucleated cell counts, glucose levels, and chloride levels did not differ significantly by age. CONCLUSION: In patients with TBM, older patients have more severe clinical manifestations, a higher incidence of hydrocephalus and cerebral infarction, and longer hospital stays than younger and middle-aged patients. Older patients thus require special clinical attention.

Role of vascular endothelial growth factor in tuberculous meningitis: A prospective study from a tertiary care center in North India.

INTRODUCTION: The status of vascular endothelial-derived growth factor (VEGF) in the pathogenesis of tuberculous meningitis (TBM) remains far from clear. We prospectively evaluated the role of serum and cerebrospinal fluid (CSF) VEGF in TBM. PATIENTS AND METHODS: This prospective study was conducted at a tertiary care center in North India from January 2018 to June 2019. Consecutive drug-naive patients (n = 82) of TBM diagnosed on the basis of modified Ahuja's criteria were included in the study. The results were compared with 49 control subjects (n = 49). Serum and CSF VEGF were done in all the cases and controls. Follow-up serum VEGF levels were done in 34 patients after 3 months of completion of antitubercular therapy. The VEGF levels were estimated using the human VEGF enzyme-linked immunosorbent assay kit. RESULTS: The mean age was 29.9 ± 13.1 years. The study group consisted of 33 (40.2%) men and 49 (59.8%) women. BACTEC MGIT960 was positive in 15 (18%) patients while multiplex tuberculosis polymerase chain reaction was positive in 73 (89%) patients. Levels of VEGF in serum and CSF of TBM patients were not elevated when compared to controls. There was no association between final outcome in TBM and decrease in serum levels of VEGF at follow-up. CONCLUSION: VEGF may not be playing a significant role in the pathogenesis of TBM. Future studies with larger sample size may clarify the status of VEGF further in TBM.

Study of the Role of Cerebrospinal Fluid C-reactive Protein and Adenosine Deaminase to differentiate Various Types of Meningitis.

OBJECTIVE: (1) To study cerebrospinal fluid (CSF) adenosine deaminase (ADA) and CSF C-reactive protein (CRP) levels in the differentiation of viral, pyogenic, and tuberculous meningitis (TBM). (2) To estimate the borderline levels of CRP in CSF in viral, pyogenic, and TBM. METHODS: A prospective and cross-sectional study was conducted at the Department of Medicine, SRN Hospital, Prayagraj, Uttar Pradesh, India, between August 2016 and September 2018. In this study, a total of 100 patients with meningitis were included applying specific inclusion and exclusion criteria after proper ethical approval. RESULTS: Out of 100 patients, 61 were TBM, 31 were pyogenic meningitis, and eight were viral meningitis (VM). CSF CRP level was significantly increased in pyogenic meningitis (1.05 ± 0.36 mg/dL) compared to nonpyogenic meningitis [TBM (0.42 ± 0.13 mg/dL) and VM (0.37 ± 0.09 mg/dL)]. At the cut-off level of CRP in CSF > 0.6 mg/dL, its diagnostic sensitivity in pyogenic meningitis was 93.55% and specificity 94.20%. While CSF ADA levels were higher in the TBM group (13.32 ± 3.21 U/L) compared to the other two groups [pyogenic meningitis (6.15 ± 1.27 U/L) and VM (4.86 ± 0.88 U/L)]. At a cut-off, CSF ADA level of >10 U/L, its diagnostic sensitivity for TBM was 91.67% and specificity 90%. CONCLUSION: Cerebrospinal fluid (CSF) CRP levels were found to be raised in pyogenic meningitis, and CSF ADA was found to be elevated in TBM. While both ADA level and CRP level in CSF are found low in VM.

Interferon-γ release assay and mantoux response in infants with tuberculous meningitis in low and intermediate burden countries.

AIM: Until now, the performance of interferon-γ release assay (IGRA) and Mantoux tests remains unclear in infant tuberculous meningitis (TBM). Therefore, a systematic review is performed to evaluate the sensitivity of IGRA and Mantoux tests for the diagnosis of infant TBM in low and intermediate tuberculosis (TB) burden countries, while following PRISMA. METHODS: Several databases, including PubMed, EBSCO, Embase, Scopus, Web of Science, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials, were searched. Articles describing the results of IGRA or Mantoux tests among infant TBM were included for analysis. Data, such as age, sex, Mantoux test or IGRA, and cerebrospinal fluid (CSF) microbiological examinations (such as acid-fast bacilli (AFB) smear, TB PCR, and TB culture), were extracted from each study. RESULTS: A total of 31 articles were enrolled for further analysis, including 48 cases. The mean age was 9.4 ± 5.8 months and boys accounted for 57.1% of infants (24/42). Mantoux test was positive in 57.4% (27/47) of tested infants and IGRA was positive in 77.8% (7/9) of infants. In addition, among the infants with confirmed TB, 18 (52.9%, 18/34) of them have positive Mantoux responses and 7 (20.0%, 7/35) have positive IGRA results. CONCLUSIONS: In low or intermediate TB burden countries, the Mantoux test has a poor performance for diagnosing TBM among infants, and IGRAs appear to have a moderate sensitivity for the diagnosis of infant TBM.

[The effect of surgical treatment of tuberculous abscesses and tuberculoma of the brain on the dynamics of neurological symptoms]. / Vliyanie khirurgicheskogo lecheniya tuberkuleznykh abstsessov i tuberkulem golovnogo mozga na dinamiku nevrologicheskoi simptomatiki.

OBJECTIVE: To evaluate the efficacy of surgery in reducing neurological symptoms in patients with focal brain tuberculosis. MATERIAL AND METHODS: Seventy-four patients with tuberculosis meningoencephalitis were studied. Among them, 20 people with a life expectancy of at least 6 months were identified, in whom foci with a ring-shaped accumulation of contrast along the periphery were determined during MSCT of the brain. Formed tuberculomas and abscesses were removed from 7 patients (group 1) under neuronavigation control. Indications for the operation were: the absence of a reduction in size for 3-4 months, the limitation of the lesion to 1-2 foci with reduction of perifocal edema according to MSCT and normalization of cerebrospinal fluid. Six patients had contraindications or refusals from operations (group 2). In 7 patients, there was a decrease in formations by the control period (group 3). Neurological symptoms in the groups at the beginning of the observation were similar. The duration of observation was 6-8 months. RESULTS: In group 1, patients were discharged with improvement, postoperative cysts were determined in all of them at discharge. In group 2, 67% died. In group 3, 43% of patients had a complete reduction of foci during conservative treatment, in 57% cysts formed in place of foci. Neurological symptoms decreased in all groups, with the most decrease in group 1. However, statistical analysis did not show significant differences between the groups regarding the reduction of neurological symptoms. A significant difference in the mortality criterion between groups 1 and 2 was obtained. CONCLUSION: Despite the absence of a significant effect on the reduction of neurological symptoms, the high survival rate of operated patients shows the need to remove tuberculosis formations in all the cases.

Cerebrospinal fluid adenosine deaminase for the diagnosis of tuberculous meningitis.

Background: A consensus on the diagnostic utility of cerebrospinal fluid adenosine deaminase (ADA) for tuberculous meningitis (TBM) is lacking. Methods: Patients aged ≥12 years admitted with CNS infections were enrolled prospectively. ADA was measured with spectrophotometry. Results: We enrolled 251 TBM and 131 other CNS infections. The optimal cutoff of ADA was calculated at 5.5 U/l against microbiological reference standard with area under curve 0.743, sensitivity 80.7%, specificity 60.3%, positive likelihood ratio 2.03 and negative likelihood ratio 3.12. The widely used cutoff value 10 U/l had specificity 82% and sensitivity 50%. The discriminating power was higher for TBM versus viral meningoencephalitis than bacterial or cryptococcal meningitis. Conclusion: Cerebrospinal fluid ADA has a low-to-modest diagnostic utility.

The diagnosis of tuberculosis (TB) of the brain is mainly made by testing cerebrospinal fluid, a clear liquid that flows in and around the brain and spinal cord. Adenosine deaminase (ADA) is a protein whose production and activity are increased in many diseases, such as TB. ADA testing in cerebrospinal fluid is widely used for the diagnosis of brain TB. However, the experts have split opinions regarding its confirmatory role. This study explores ADA measurement in cerebrospinal fluid for differentiating TB from other brain infections. The report says that this simple and inexpensive test can be helpful, but it cannot make or refute the diagnosis of brain TB and should only be considered along with other tests.

Microbiological diagnosis and mortality of tuberculosis meningitis: Systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) which is caused by Mycobacterium tuberculosis poses a significant public health global treat. Tuberculosis meningitis (TBM) accounts for approximately 1% of all active TB cases. The diagnosis of Tuberculosis meningitis is notably difficult due to its rapid onset, nonspecific symptoms, and the difficulty of detecting Mycobacterium tuberculosis in cerebrospinal fluid (CSF). In 2019, 78,200 adults died of TB meningitis. This study aimed to assess the microbiological diagnosis TB meningitis using CSF and estimated the risk of death from TBM. METHODS: Relevant electronic databases and gray literature sources were searched for studies that reported presumed TBM patients. The quality of included studies was assessed using the Joanna Briggs Institute Critical Appraisal tools designed for prevalence studies. Data were summarized using Microsoft excel ver 16. The proportion of culture confirmed TBM, prevalence of drug resistance and risk of death were calculated using the random-effect model. Stata version 16.0 was used perform the statistical analysis. Moreover, subgroup analysis was conducted. RESULTS: After systematic searching and quality assessment, 31 studies were included in the final analysis. Ninety percent of the included studies were retrospective studies in design. The overall pooled estimates of CSF culture positive TBM was 29.72% (95% CI; 21.42-38.02). The pooled prevalence of MDR-TB among culture positive TBM cases was 5.19% (95% CI; 3.12-7.25). While, the proportion of INH mono-resistance was 9.37% (95% CI; 7.03-11.71). The pooled estimate of case fatality rate among confirmed TBM cases was 20.42% (95%CI; 14.81-26.03). Based on sub group analysis, the pooled case fatality rate among HIV positive and HIV negative TBM individuals was 53.39% (95%CI; 40.55-66.24) and 21.65% (95%CI;4.27-39.03) respectively. CONCLUSION: Definite diagnosis of TBM still remains global treat. Microbiological confirmation of TBM is not always achievable. Early microbiological confirmation of TBM has great importance to reduce mortality. There was high rate of MDR-TB among confirmed TBM patients. All TB meningitis isolates should be cultured and drug susceptibility tested using standard techniques.

Adenosine deaminase from the cerebrospinal fluid for the diagnosis of tuberculous meningitis: A meta-analysis.

OBJECTIVE: To comprehensively evaluate the diagnostic efficacy of adenosine deaminase in cerebrospinal fluid (CSF) for tuberculous meningitis (TBM), and the potential influence of patients' age groups and cutoffs of measured adenosine deaminase. METHODS: Systematic review and meta-analysis of relevant studies retrieved from PubMed, Embase, and Web of Science databases. Pooled sensitivity and specificity were calculated with a random-effect model. RESULTS: Overall, 43 studies with 1653 patients with TBM and 3417 controls without were included. Pooled results showed that adenosine deaminase in CSF is associated with satisfactory diagnostic efficacy for TBM, with a pooled sensitivity of 0.86 (95% confidence interval [CI]: 0.82-0.90), specificity of 0.89 (95% CI: 0.86-0.91), positive likelihood ratio of 7.70 (95% CI: 6.16-9.63), and negative likelihood ratio of 0.15 (95% CI: 0.12-0.20). The pooled receiver operating characteristic (AUC) was 0.94 (95% CI: 0.91-0.96), suggesting good performance. Subgroup analyses showed good diagnostic efficacies of adenosine deaminase in CSF for both adults (AUC 0.95) and children (AUC 0.96) with TBM. AUCs indicating the diagnostic accuracies of adenosine deaminase in CSF for TBM were 0.93 for studies with cutoffs <10 U/L and and 0.94 for a cutoff =10 U/L, but only 0.90 for studies with cutoffs >10 U/L. CONCLUSIONS: Measuring adenosine deaminase of CSF shows satisfactory diagnostic efficacy for TBM in children and adults, particularly if using a cutoff ≤10 U/L.