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.

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.

Longitudinal cerebrospinal fluid assessment in a patient with tuberculous meningitis-A case report.

BACKGROUND: Dynamic assessment of cerebrospinal fluid (CSF) is essential for diagnosis, treatment, and prognosis of tuberculous meningitis, one of the most severe forms of central nervous system (CNS) infection. CASE PRESENTATION: A 45-year-old man sought care as he developed confusion, clonic convulsion, and coma. Longitudinal, comprehensive analyses of cytological, biochemical, and microbial changes in CSF specimen were assessed for this patient. On day 1 of hospitalization, modified Ziehl-Neelsen staining of CSF identified positive acid-fast bacilli, cytological analysis revealed neutrophilic-predominant pleocytosis (neutrophils 77%), and adenosine deaminase (ADA) was substantially elevated. Therefore, tuberculous meningitis was diagnosed and first-line standard anti-tuberculosis treatment was initiated. Interestingly, after 7-day treatment, the patient was greatly improved, and CSF disclosed a dominant percentage of lymphocytes (82%) as well as macrophages engulfing Mycobacterium tuberculosis. Later, the dose of dexamethasone was reduced, large number of neutrophils (57%) was present and protein level was immediately elevated in CSF specimen, indicating a possible relapse of tuberculous meningitis. Since the clinical condition of the patient was not worsening, the patient was stick to reduced dose of dexamethasone and standard anti-tuberculosis agents. He was discharged from the hospital on day 34, with 1-year continuation standard anti-tuberculosis therapy, and was clinically resolved from tuberculous meningitis. CONCLUSION: Detailed analyses of cellular composition, biochemical results, and microbial tests of CSF specimen provide the physician direct evidence of the immune surveillance status during tuberculous meningitis, which facilitates early diagnosis, optimal treatment, and improved prognosis.

A case with neurological abnormalities caused by Rickettsia raoultii in northwestern China.

BACKGROUND: The number of new rickettsial species are rapidly increasing, and increasing numbers of Rickettsia raoultii (R. raoultii) infection cases have been detected in humans. However, neurological abnormalities caused by R. raoultii are rarely reported, especially in northwestern China. CASE PRESENTATION: A 36-year-old Kazakh shepherd with an attached tick on part temporalis, presented with right eyelid droop, lethargy, fever, headache, fever (38.0-41.0 °C) and erythematous rash. The examination of cerebrospinal fluid (CSF) showed cerebrospinal pressure of 200 mm H2O, leukocyte count of 300.0 × 106/L, adenosine deaminase of 2.15 U/L, and total protein concentration of 0.93 g/L. The diagnosis of R. raoultii infection was confirmed by six genetic markers, and semi-quantified by enzyme-linked immunosorbent assay for rickettsial antigen. The patient gradually recovered after treatment with doxycycline and ceftriaxone. R. raoultii DNA was found both in a tick detached from this patient and in 0.18% (2/1107) of blood samples collected from local shepherds. CONCLUSIONS: This is the first reported case with neurological abnormalities caused by R. raoultii in northwestern China. It is vital to detect rickettsial agents both in blood and CSF for tick bite patients with neurological abnormalities. Public health workers and physicians should pay attention to neurological abnormalities caused by Rickettsia.

Development of a clinical prediction rule for tuberculous meningitis in adults in Lima, Peru.

OBJECTIVES: Diagnosis of tuberculous meningitis (TM) is a challenge in countries with a high burden of the disease and constrained resources and clinical prediction rules (CPRs) could be of assistance. We aimed at developing a CPR for diagnosis of TM in a Latin American setting with high tuberculosis incidence and a concentrated HIV epidemic. METHODS: We enrolled adult patients with clinical suspicion of TM attending two hospitals in Lima, Peru. We obtained information on potential anamnestic, clinical and laboratory predictive findings that are easy to collect and promptly available. We independently diagnosed TM according to a composite reference standard that included a series of microbiological tests. We performed bivariate analysis and constructed a logistic regression model to select the predictive findings associated with TM. With the selected predictors included in the model, we developed a score-based CPR. We assessed its internal validity and diagnostic performance. RESULTS: Of 155 analysed patients, 59 (38%) had TM. The CPR we derived includes three predictors: cough for 14 days or more, 10-500 cells in CSF and adenosine deaminase ≥ 6 U/l in CSF. It classifies patients into high-, moderate- or low-score groups and has an overall area under the ROC curve of 0.87. 59% of patients were assigned to either the high- or the low-score group, permitting prompt decision-making. In patients in the high-score group, it attains a positive likelihood ratio for TM of 10.6 and in patients with low scores, a negative likelihood ratio of 0.10. Bootstrap analysis indicated high internal validity. CONCLUSION: This CPR could support decision-making in patients with clinical suspicion of TM. External validation and further assessment of its clinical impact are necessary before application in other settings.

Study of Central Nervous System Tuberculosis.

Aims and Objective: To assess the clinical features, complications and outcome in patients with central nervous system tuberculosis (CNS TB) and to correlate the clinical, laboratory and radiological findings of CNS TB. Materials and Methods: In a cross sectional study, total 50 diagnosed cases of CNS TB (either TB meningitis or tuberculoma) were studied. The data on demographic factors, clinical features, complications and laboratory findings, details of treatment and outcome were recorded and analyzed. Follow up was done during hospital stay and at the end of six months after completion of chemotherapy. Results: Out of 50, 42 patients had TBM (tuberculous meningitis) and 8 patients had tuberculoma. Mean age of patients was 33.5 yrs with male preponderance (M: F = 6.2:1), 66% patients had duration of symptoms more than 4 weeks. Common symptoms were fever (100%), headache (70%) and vomiting (64%). CSF staining for AFB was positive in 8% patients, mean CSF protein was 157 mg%, 32 patients had CSF lymphocytosis, (count >90%), CSF PCR was positive in 92.85%, CSF ADA levels were high (> 10 U/L) in 90.47%. On neuroimaging, 62 % patients had meningeal enhancement and 8 patients had tuberculomas. 10 patients were in stage I of disease, 24 in stage II and 16 in stage III. 30% mortality was observed, more in HIV positive patients with stage III disease. On followed up after 6 months of discharged patients (n=35), 10 patients had full recovery and 17 had recovery with neurological deficit, however 8 patients lost follow up. Conclusion: Diagnosis of CNS TB should be based on clinical features and 3 or more supportive criteria rather than CSF positivity on staining or culture. Rapid and early diagnosis by positive CSF PCR and CT/MRI findings should replace CSF AFB staining and culture in further for the diagnosis of CNS TB.

The dubious value of cerebrospinal fluid adenosine deaminase measurement for the diagnosis of tuberculous meningitis.

BACKGROUND: The diagnosis of tuberculous meningitis (TBM) can be extremely difficult in the absence of culture confirmation. Cerebrospinal fluid (CSF) adenosine deaminase (ADA) can potentially assist in this regard, although its current value remains unclear. The literature on the usefulness of CSF ADA in TBM diagnosis is inconsistent, especially from an analytical point of view. METHODS: A retrospective analysis of clinical and laboratory data relating to all CSF ADA requests during 2009 and 2010 in a South African quaternary healthcare setting was performed. A CSF ADA cut-off for TBM diagnosis was calculated using receiver operating characteristic curve analysis. The performance of CSF ADA in different infective and non-infective categories was assessed. RESULTS: In total, 3548 CSF ADA requests were considered over the 2-year period. Of these, 1490 were for patients for whom both a CSF ADA and a mycobacterial culture were requested. The optimal cut-off was calculated at 2.0 U/L (AUC = 0.86; 95% CI = 0.82 - 0.89; p-value < 0.01; sensitivity of 85.9% (95% CI of 77.0 - 92.3) and specificity of 77.7% (95% CI of 75.4 - 79.8%); positive likelihood ratio = 3.85 and negative likelihood ratio = 0.18). At this cut-off 13 TBM cases were missed. CONCLUSION: An optimal cut-off for routine use could not be established as too many TBM cases were missed. Specimen integrity, lack of ADA assay standardisation and overlap in performance of the assay in different diagnostic categories affect interpretation.

Raised adenosine deaminase in the cerebrospinal fluid: A tool for the diagnosis of tuberculous meningitis in developing countries.

CONTEXT: The rapid diagnosis followed by the early treatment of tuberculous meningitis (TBM) is important in preventing fatal outcomes. The mainstay of diagnosis lies in cerebrospinal fluid (CSF) analysis, radiological investigations, and clinical findings. AIM: The present study was conducted to determine the efficacy, sensitivity, and specificity of raised adenosine deaminase (ADA) level in CSF to differentiate TBM from non-TBM cases as a rapid, cost-effective, and noninvasive test. PATIENTS AND METHODS: This was a retrospective study conducted over a 1-year period in a tertiary teaching institute of Malwa region, India. A total of 143 patients presented with symptoms and signs of meningitis were included and divided into TBM and non-TBM groups on the basis of the diagnostic criteria. CSF ADA estimation was drafted and analyzed by using ≥10 U/L as a cutoff value. A statistical comparison of the ADA levels between the study groups was made by using unpaired Student's t-test. RESULTS: Out of the 143 cases, 40 were TBM, and 103 were non-TBM. The mean ADA level in TBM and non-TBM cases was 17.18 ± 9.59 and 6.33 ± 2.48, respectively, and the difference was statistically significant. Using a cutoff level ≥10 U/L, CSF ADA had a sensitivity of 92.5% and a specificity of 89.32%. Positive and negative likelihood ratios of the test were 8.66 and 0.08, respectively, and positive and negative predictive values, were 77.08 and 96.84%, respectively. CONCLUSION: The present study reflects the importance of a CSF ADA level ≥10 U/L in the diagnosis of TBM. Thus, it can be used as an adjunctive diagnostic tool to differentiate TBM from other non-TBM cases, when there is a diagnostic dilemma.

[Cerebrospinal fluid adenosine deaminase and its dynamic changes in tuberculous meningitis].

Objective: To explore the diagnostic value of cerebrospinal fluid (CSF) adenosine deaminase (ADA) level in tuberculous meningitis. Methods: We retrospectively analyzed 139 patients (73 males, 66 females) who visited Beijing Chest Hospital for suspected TBM from January 2010 to June 2015. Of them, 99 patients were diagnosed to have TBM, with 45 males and 54 females, and a mean age of (33±15) years. Forty patients were diagnosed as having Non-TBM, with 28 males and 12 females, and a mean age of (35±18) years. All patients underwent lumbar puncture, and CSF ADA, routine, biochemical and bacteriological tests were performed. Thirty-five TBM patients reviewed CSF ADA test after treatment for 4 weeks, 8 weeks and 6 months. Results: The level of CSF ADA in TBM group was higher than that in the non-TBM group, the difference being statistically significant (5.6 U/L vs 2.3 U/L, P=0.000). When the cut-off value of the CSF ADA was 3.8 U/L , the sensitivity and specificity for diagnosis of TBM were 60.6% (95%CI 50.3%-70.1%) and 87.5% (95%CI 72.4%-95.3%), respectively, and the area under the ROC curve was 0.734.The CSF ADA level was (6.7±4.2) U/L in the 35 cases of TBM before treatment. After 4 weeks, 8 weeks and 6 months of anti-tuberculosis treatment, the CSF ADA levels were (4.5±3.3) U/L, (3.7±2.7) U/L and (2.0±1.5) U/L, respectively; all significantly decreased as compared to that before treatment (P<0.001). There was no significant change in the ADA level between 8 weeks and 4 weeks (P=0.128). After 6 months of treatment, the level of CSF ADA was significantly lower than those after 4 and 8 weeks' treatment (P<0.001). Conclusions: CSF ADA in TBM patients was significantly higher than in non-TBM patients. The sensitivity of CSF ADA level in the diagnosis of TBM was poor, but the specificity was better. CSF ADA was significantly reduced and showed dynamic changes with effective anti-tuberculosis treatment and maybe helpful in evaluating the effect of treatment.

Rational application of adenosine deaminase activity in cerebrospinal fluid for the diagnosis of tuberculous meningitis.

PURPOSE: Tuberculous meningitis (TBM) is one of the most serious and difficult to diagnose manifestations of TB. An ADA value >9.5 IU/L has great sensitivity and specificity. However, all available studies have been conducted in areas of high endemicity, so we sought to determine the accuracy of ADA in a low endemicity area. METHODS: This retrospective study included 190 patients (105 men) who had ADA tested in CSF for some reason. Patients were classified as probable/certain TBM or non-TBM based on clinical and Thwaite's criteria. Optimal ADA cutoff was established by ROC curves and a predictive algorithm based on ADA and other CSF biochemical parameters was generated. RESULTS: Eleven patients were classified as probable/certain TBM. In a low endemicity area, the best ADA cutoff was 11.5 IU/L with 91 % sensitivity and 77.7 % specificity. We also developed a predictive algorithm based on the combination of ADA (>11.5 IU/L), glucose (<65 mg/dL) and leukocytes (≥13.5 cell/mm(3)) with increased accuracy (Se: 91 % Sp: 88 %). CONCLUSIONS: Optimal ADA cutoff value in areas of low TB endemicity is higher than previously reported. Our algorithm is more accurate than ADA activity alone with better sensitivity and specificity than previously reported algorithms.

Cerebrospinal Fluid Parameters Predicting Contralateral Isolated Lateral Ventricle in Adult Tuberculous Meningitis with Hydrocephalus Post-Ventriculoperitoneal Shunt.

OBJECTIVE: Hydrocephalus, a major complication in tuberculous meningitis (TBM) patients, often necessitates treatment via ventriculoperitoneal shunt (VPS). However, post-VPS, some patients develop a complication called contralateral isolated lateral ventricle (CILV), leading to persistent hydrocephalus symptoms. This study aims to evaluate cerebrospinal fluid (CSF) parameters in predicting CILV occurrence post-VPS in adult TBM patients. METHODS: A retrospective analysis was conducted, focusing on the relationship between preoperative CSF parameters and the development of CILV in 40 adult TBM patients who underwent VPS. The study compared CSF parameters from lumbar puncture after admission with those from ventricular CSF post-external ventricular drainage tube insertion. RESULTS: CILV was observed in 6 of the 40 patients following VPS. Statistical analysis showed no significant difference between the CSF parameters obtained via lumbar and ventricular punctures. Notably, the mean CSF glucose level in patients with CILV was significantly lower (1.92 mmol/L) compared to the non-CILV group (3.03 mmol/L). Conversely, the median adenosine deaminase (ADA) level in the CILV group was higher (5.69 U/L) compared to the non-CILV group (3.18 U/L). The optimal cutoff values for CSF glucose and ADA levels were 1.90 mmol/L and 4.80 U/L, respectively, with a sensitivity of 66.67% and 83.33% and a specificity of 88.24% and 79.41%. CONCLUSIONS: The study identified elevated ADA levels and decreased glucose levels in CSF as potential risk factors for CILV development in adult TBM patients post-VPS. These findings suggest the necessity for more tailored surgical approaches, in patients with altered CSF parameters to mitigate the risk of CILV.

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.

[A comparative study for adenosine deaminase and anti-antigen A-60 antibodies detection for the diagnosis of tuberculous meningitis]. / Comparación de adenosina deaminasa y detección de anticuerpos anti-antígeno A60 para el diagnóstico de meningitis tuberculosa.

BACKGROUND: Diagnosis of tuberculous meningitis (TBM) is hampered by the lack of rapid and accurate diagnostic tools. We evaluated the immunological response to Mycobacterium tuberculosis anti-A60 antibodies in cerebrospinal fluid (CSF) in comparison to adenosine deaminase (ADA) determination, for the diagnosis of TBM. METHODS: A total of 63 CSF samples were analyzed by indirect ELISA for the detection of anti- A60 IgG, IgM and IgA. These include samples from 17 patients with confirmed TBM and 46 control patients with other infections. RESULTS: The mean individual anti-A60 IgM, IgG and IgA CSF antibody titers were significantly higher in TBM in comparison with control groups (p < 0.01). The best discriminatory CSF antibody for confirming TBM diagnosis was IgM, with an area under the receiver operating characteristic curve of 0.928 (95%CI 0.834-0.978), compared to 0.863 (95% CI: 0.752-0.936) for ADA testing (p = NS). The sensitivity of anti- A60 IgM CSF antibody titers (cutoff > 0.06 U/ml) was 94.1% compared to 88.2% for ADA (cutoff > 6.2 U/ml), p = NS. Both anti A60 IgM and ADA showed the same moderate specificity (80.4%). Two cases of TBM were correctly identified by anti-A60 IgM but missed by ADA. CONCLUSION: The ELISA test for anti-antigen A60 antibodies (IgM) is a rapid and sensitive tool for the rapid diagnosis of TBM that can be a complement to ALDA determination. The specificity of both tests is still a limitation in TBM diagnosis.

Study of cerebrospinal fluid levels of lactate, lactate dehydrogenase and adenosine deaminase in the diagnosis and outcome of acute meningitis.

BACKGROUND: Meningitis is a serious clinical health issue in most developing countries. Late diagnosis and treatment result in significant morbidity and mortality. This research aims to study the utility of CSF lactate, lactate dehydrogenase (LDH), and adenosine deaminase (ADA) as diagnostic markers in acute meningitis, and to differentiate among varied aetiologies of acute meningitis and their outcomes. METHOD: A cross-sectional observational case-control study was conducted in 30 patients of suspected meningitis of varied aetiologies and 30 controls without any pre-existing neurological disorder and who underwent lumbar puncture during spinal anesthesia. A fresh CSF sample was collected in a heparinized vial following an aseptic lumbar puncture. The levels of lactate, LDH and ADA were estimated and recorded. RESULT: CSF lactate was significantly elevated in bacterial meningitis (BM) and cryptococcal meningitis, with 100% sensitivity when compared to controls. Elevated LDH was found only in BM, hence elevated LDH levels may strongly signify bacterial etiology. Significantly elevated ADA levels were noted in tuberculous meningitis. Significantly elevated levels of lactate and ADA were suggestive of slower clinical recovery and a prolonged hospital stay (p < 0.001). CONCLUSION: Estimation of CSF lactate, LDH, and ADA levels is a rapid, inexpensive and simple procedure and can play a major role in the early differentiation of bacterial, viral, tuberculous, and fungal meningitis. This would facilitate the initiation of appropriate treatment as early as possible, thereby decreasing mortality and complications.

Cerebrospinal fluid C reactive protein and adenosine deaminase in meningitis in adults.

OBJECTIVES: To assess the utility of C-reactive protein (CRP) levels and adenosine deaminase (ADA) activity in the cerebrospinal fluid (CSF) as rapid screening tests to differentiate various types of meningitis in adults and to establish a cut off level for ADA. METHODS: CSF samples were obtained from 50 patients who presented to the emergency room and out-patient of Sri Siddhartha Medical Hospital, Tumkur during the period between August 2006 and September 2008. Diagnosis of meningitis was based on the clinical presentation and CSF analysis. RESULTS: Out of a total of 50 patients who were enrolled in the study, 24 were diagnosed as tubercular meningitis (TBM) based on the clinical features and CSF analysis. The mean Adenosine deaminase (ADA) activity was 14.14 +/- 7.44 U/l in the TBM group. The sensitivity and specificity was 73.9% and 92.6% respectively when a cut-off value of ADA of 10U/l was used, with an accuracy of 84%. CSF-C Reactive protein (CRP) was significantly higher in pyogenic meningitis compared to non-pyogenic meningitis. The sensitivity and specificity of the test was 83.3% and 100% respectively with an accuracy of 98%. CONCLUSIONS: 2 rapid screening tests- CRP and ADA activity in the CSF can help in the differential diagnosis of pyogenic from non-pyogenic meningitis and tubercular from viral meningitis respectively. CRP being elevated in pyogenic meningitis and ADA activity noted to be higher in TBM. The levels of ADA and CRP were found to be low in viral meningitis.

A case of idiopathic hypertrophic pachymeningitis with high adenosine deaminase in cerebrospinal fluid.

Adenosine deaminase (ADA) in cerebrospinal fluid (CSF) has been reported as useful to diagnose tuberculous meningitis and hypertrophic pachymeningitis (HP). The case of a 59-year-old woman with impaired vision and an auditory disturbance due to massive intracranial HP is presented. Although acid-fast bacillus cultures and polymerase chain reaction tests for Mycobacterium tuberculosis in the CSF were negative, tuberculous HP was diagnosed clinically because of the high ADA in CSF, and anti-tuberculosis drugs were administered with prednisolone because idiopathic HP (IHP) could not be ruled out. Since the impaired vision worsened with prednisolone reduction despite the continuation of anti-tuberculosis drugs, a dural biopsy was performed, and the patient was diagnosed with IHP. ADA is associated with lymphocyte proliferation and differentiation and increased by activation of cell-mediated immunity. Elevated CSF-ADA might be caused by lymphocyte infiltration in the thickened dura mater.

Rapid diagnosis of tuberculous meningitis by T cell-based assays on peripheral blood and cerebrospinal fluid mononuclear cells.

BACKGROUND: The role of the new Myocbacterium tuberculosis-specific enzyme-linked immunosorbent spot (ELISPOT) assay for diagnosis of tuberculous meningitis (TBM) has not yet been fully assessed. Here, we conducted a prospective, blinded, observational study to evaluate the diagnostic accuracy of this assay, compared with the conventional tests, for diagnosing TBM. METHODS: All adult patients with suspected TBM were enrolled at a tertiary care hospital (Seoul, South Korea) during a 12-month period. ELISPOT assays were performed on peripheral mononuclear cells and mononuclear cells from cerebrospinal fluid (CSF). RESULTS: Eighty-nine patients with suspected TBM were enrolled. Of these, 31 (35%) were classified as having TBM (10 confirmed, 6 highly probable, and 15 probable cases), and 55 (62%) were classified as not having active tuberculosis. The remaining 3 (3%) with possible TBM were excluded from the final analysis. The sensitivities and specificities, respectively, of the tested methods for diagnosing TBM were as follows: CSF adenosine deaminase level >5.8 U/L, 89% (95% confidence interval [CI], 69%-98%) and 73% (95% CI, 58%-84%); peripheral mononuclear cells ELISPOT, 71% (95% CI, 51%-86%) and 57% (95% CI, 42%-70%); and CSF mononuclear cells ELISPOT assay, 59% (95% CI, 36%-79%) and 89% (95% CI, 72%-98%). The combined sensitivity of an adenosine deaminase level >5.8 U/L or a positive peripheral mononuclear cells ELISPOT assay result was 94% (95% CI, 79%-99%), conferring a negative likelihood ratio of 0.14 (95% CI, 0.03-0.55) when both test results were negative. CONCLUSION: ELISPOT assays using peripheral mononuclear cells and CSF mononuclear cells are useful adjuncts to the current tests for diagnosing TBM, particularly when used in combination with the assessment of adenosine deaminase level in CSF.

Adenosine deaminase and tuberculous meningitis--a systematic review with meta-analysis.

Tuberculous meningitis (TBM) is a severe infection of the central nervous system, particularly in developing countries. Prompt diagnosis and treatment are necessary to decrease the high rates of disability and death associated with TBM. The diagnosis is often time and labour intensive; thus, a simple, accurate and rapid diagnostic test is needed. The adenosine deaminase (ADA) activity test is a rapid test that has been used for the diagnosis of the pleural, peritoneal and pericardial forms of tuberculosis. However, the usefulness of ADA in TBM is uncertain. The aim of this study was to evaluate ADA as a diagnostic test for TBM in a systematic review. A systematic search was performed of the medical literature (MEDLINE, LILACS, Web of Science and EMBASE). The ADA values from TBM cases and controls (diagnosed with other types of meningitis) were necessary to calculate the sensitivity and specificity. Out of a total of 522 studies, 13 were included in the meta-analysis (380 patients with TBM). The sensitivity, specificity and diagnostic odds ratios (DOR) were calculated based on arbitrary ADA cut-off values from 1 to 10 U/l. ADA values from 1 to 4 U/l (sensitivity >93% and specificity <80%) helped to exclude TBM; values between 4 and 8 U/l were insufficient to confirm or exclude the diagnosis of TBM (p = 0.07), and values >8 U/l (sensitivity <59% and specificity >96%) improved the diagnosis of TBM (p < 0.001). None of the cut-off values could be used to discriminate between TBM and bacterial meningitis. In conclusion, ADA cannot distinguish between bacterial meningitis and TBM, but using ranges of ADA values could be important to improve TBM diagnosis, particularly after bacterial meningitis has been ruled out. The different methods used to measure ADA and the heterogeneity of data do not allow standardization of this test as a routine.

[Value of assaying adenosine deaminase level in patients with neuromeningeal tuberculosis]. / Intérêt du dosage de l'adénosine désaminase dans les infections tuberculeuses neuro-méningées.

Neuromeningeal tuberculosis is a rare extrapulmonary location in France. Delayed diagnosis can lead to therapeutic failure and severe sequels. However early diagnosis is a major challenge that requires the proper epidemiological, clinical, radiological and biological resources. Problems related to diagnosis of mycobacteria infection and to shortcomings in certain healthcare systems can hinder early diagnosis. The purpose of this review was to describe the diagnostic value of assaying adenosine deaminase activity in cerebrospinal fluid from patients with neuromeningeal tuberculosis. Evidence from studies published over the last 25 years indicate that the sensitivity and specificity of measuring adenosine deaminase activity range from 36 to 92% and 71 to 100% respectively depending of cutoff values used. Before performing this assay, it is necessary to rule out obvious or frequent etiologies such as purulent bacterial meningitis or cryptococcosis in HIV patients. Taken together these studies show that this simple, inexpensive technique is a valuable tool for early diagnosis and management of tuberculosis patients and that it can be easily implemented in hospital labs regardless of technical or financial resources.

Determination of cerebrospinal fluid adenosine deaminase activity cut-off for the diagnosis of tuberculous meningitis in Hong Kong.

AIMS: Tuberculous meningitis (TBM) is a severe infection which may lead to serious complication and mortality. Prompt diagnosis and treatment are essential. There is a need for a simple and fast laboratory test to differentiate TBM from other causes. METHODS: Retrospective review was conducted for cerebrospinal fluid adenosine deaminase (CSF-ADA) activity which was measured at the Chemical Pathology Laboratory of Princess Margaret Hospital, the sole centre providing such service in Hong Kong, for 51 patients with suspected meningitis from nine local hospitals between June 2014 and July 2017. TBM diagnosis was defined by positive culture and/or nucleic acid amplification test result of Mycobacterium tuberculosis complex in CSF. RESULTS: CSF-ADA activity was significantly higher in the TBM group (8.6±2.1 IU/L, n=8) than that of the non-TBM group (2.8±5.9 IU/L, n=43). The optimal clinical cut-off of 5.1 U/L for TBM diagnosis in our laboratory yielded 100% sensitivity, 91% specificity, positive likelihood ratio of 10.8 and negative likelihood ratio of 0. In rare circumstance, false elevation may be seen in non-tuberculous cause, such as central nervous system lymphoma and fungal infection. CONCLUSIONS: We recommend the use of CSF-ADA activity, which is a simple, fast and robust test for early differentiation of TBM from other causes, to facilitate timely initiation of antituberculous treatment and potentially improve patients' outcome.