Cerebrospinal fluid adenosine deaminase activity for the diagnosis of tuberculous meningitis in adults

We studied adenosine deaminase (ADA) activity in cerebrospinal fluid (CSF) of 16 cases of tuberculous meningitis, 4 cases of cryptococcal meningitis, 5 cases of bacterial meningitis, 12 cases of eosinophilic meningitis, 26 cases of aseptic meningitis, 6 cases of carcinomatous meningitis and 108 cases with normal CSF. The mean CSF ADA values for the different groups were: 39.44 +/- 41.46, 13.00 +/- 7.43, 34.20 +/- 40.81, 3.17 +/- 4.82, 10.03 +/- 9.23, 8.67 +/- 13.60, and 2.58 +/- 2.90 U/I, respectively. Comparing the ADA activity between patients with tuberculous meningitis and non-tuberculous meningitis, the receiver-operating characteristic (ROC) curve identified a CSF ADA level of 15.5 U/I as the best cut-off value to differentiate between the two, with a sensitivity of 75% and a specificity of 93%, with an area under the curve of 0.92. When tuberculous meningitis was compared with aseptic and carcinomatous meningitis, the ROC curve identified a CSF ADA level of 19.0 U/I as the best cut-off value for differentiation, with a sensitivity of 69% and a specificity of 94%, with an area under the curve of 0.83. The level of CSF ADA may be useful as a complementary tool in the early diagnosis of tuberculous meningitis.     

腺苷脱氨酶诊断结核性脑膜炎价值Meta分析

目的通过Meta分析确定检测脑脊液(CSF)中腺苷脱氨酶(ADA)的含量是否有助于结核性脑膜炎的早期诊断。方法检索Medline,Embase,BIOSIS和Cochrane等数据库,检索时间为1995年1月至2009年12月,收集关于测定CSF中ADA以诊断结核性脑膜炎的相关英文文献,并用QUADAS标准进行质量评价,采用Metadisc1.4和SPSS13.0软件,用随机效应模型汇总各研究中ADA诊断结核性脑膜炎的敏感度、特异度以及其他指标,绘制汇总受试者工作特征曲线并探讨其诊断特性。结果最终有9项独立研究纳入本次Meta分析,ADA诊断结核性脑膜炎的总体敏感度0.77(95%CI 0.72～0.82);特异度0.91(95%CI 0.90～0.93);阳性似然比7.93(95%CI 5.85～10.76),阴性似然比0.28(95%CI 0.19～0.41),合并受试者工作特征曲线下面积为0.9129,但在结核性脑膜炎与化脓性脑膜炎的鉴别诊断中特异度降为0.75(95%CI 0.67～0.82)。结论 ADA诊断结核性脑膜炎的敏感度、特异度均较高,检测CSF中的ADA有助于结核性脑膜炎的诊断,但在与化脓性脑膜炎相鉴别时诊断效力下降,需参考其他检测指标。     

Diagnostic value of cerebrospinal fluid adenosine deaminase determination

We measured the activity of adenosine deaminase (ADA) in the cerebrospinal fluid of 3 patients with tuberculous meningitis, 38 with viral meningitis, 15 with bacterial meningitis, 5 with malignant lymphoma, 11 with cerebrovascular diseases and 13 with miscellaneous neurological disorders. The highest ADA activities were observed in patients with tuberculous meningitis (median 21.3 U/l, range 20.0-23.0) and lymphoma (13.0 U/l, range 4.0-25.0). The sensitivity of the test for diagnosing tuberculous meningitis was 100% and the specificity 99% when a cut-off value of 20.0 U/l was used. We conclude that determination of ADA in cerebrospinal fluid is useful for the diagnosis of tuberculous meningitis, but that high activity also can be seen in some other CNS disorders, e.g. lymphoma with meningeal involvement.     

Biopsy-proven tuberculous meningitis mimicking CNS sarcoidosis

We report a 31-year-old man with tuberculous meningitis (TM) mimicking CNS sarcoidosis. Although Mycobacterium tuberculosis (MTB) was not detected in CSF, the level of adenosine deaminase (ADA) in CSF was significantly raised. Brain biopsy showed caseous granuloma and a diagnosis of TM was made. The diagnosis of TM is often difficult and brain biopsy should be considered if MTB is not detected in the CSF. Evaluation of CSF ADA level could also strongly contribute to distinguishing TM from other meningitis. In addition to antituberculosis drugs, corticosteroid therapy was effective in our patient but careful reduction of its dosage was required.     

结核性和非结核性脑膜炎患者脑脊液中ADA及NSE表达水平的对比分析

目的探讨脑脊液腺苷脱氨酶（ADA）及神经元特异性烯醇化酶（NSE）表达水平在结核性脑膜炎（TBM）患者诊断中的应用价值。方法利用免疫学技术对TBM患者、无菌性脑膜炎患者及非中枢神经系统病患者脑脊液中的ADA、NSE含量及血清NSE含量进行测定。结果 TBM患者脑脊液中ADA含量明显高于无菌性脑膜炎组及对照组（P〈0.01）,无菌性脑膜炎患者脑脊液中的ADA含量与对照组比较没有明显变化（P〉0.05）。TBM组脑脊液/血清NSE比值比与对照组比较差异有统计学意义（P=0.001）。结论脑脊液ADA含量测定有助于TBM的诊断。脑脊液/血清NSE比值比可能成为一个早期诊断结核性脑膜炎的参数。     

4种指标在腹水鉴别诊断中的意义

目的探讨腺苷脱氨酶（ADA）、乳酸脱氢酶（LDH）、癌胚抗原（CEA）及血清-腹水白蛋白梯度（SAAG）在不同病因腹水中的临床意义。方法检测139例腹水患者腹水中ADA、LDH、CEA和SAAG等4种指标,用受试者工作特征曲线（ROC）对它们在腹水病因鉴别诊断中的临床价值进行评估。结果ADA水平以结核性腹水组为最高,恶性腹水组次之;LDH以恶性腹水组最高,结核性腹水组次之,门脉高压性腹水组最低;CEA含量以恶性腹水组为最高,其余3组含量相当;SAAG以门脉高压性腹水组和肝硬化伴自发性腹膜炎组为最高。结论联合检测腹水ADA、LDH、CEA及SAAG对腹水病因的鉴别诊断有重要的临床价值。     

Diagnostic value of adenosine deaminase in nontuberculous lymphocytic pleural effusions.

Adenosine deaminase (ADA) can aid in the diagnosis of tuberculous pleural effusions, but false-positive findings from lymphocytic effusions have been reported. The purpose of this study is to assess the ADA levels in nontuberculous lymphocytic pleural effusions (lymphocyte count > 50%) of different aetiologies. Altogether, 410 nontuberculous lymphocytic pleural fluid samples were consecutively selected. These included malignant effusions (n = 221), idiopathic effusions (n = 76), parapneumonic effusions (n = 35), postcoronary artery bypass graft surgery effusions (n = 6), miscellaneous exudative effusions (n = 21) and transudative effusions (n = 51). The ADA level reached the diagnostic cut-off for tuberculosis (40 U x L(-1)) in seven of the 410 cases (1.71%). The negative predictive value of ADA for the diagnosis of pleural tuberculosis was 99% (403 of 407 cases) in the group of lymphocytic pleural effusions. In five of these seven patients ADA1 and ADA2 were measured, and in all these cases (100%) ADA1/ADA(p) correctly classified these lymphocytic effusions as nontuberculous (ratio < 0.42). This prospective study provides additional evidence that adenosine deaminase levels in nontuberculous lymphocytic pleural effusions seldom exceed the cut-off set for tuberculous effusions. The pleural fluid adenosine deaminase levels were significantly higher in different types of exudative effusions than in transudates. An adenosine deaminase level < 40 IU x L(-1) virtually excluded a diagnosis of tuberculosis in lymphocytic pleural effusions. Adenosine deaminase1/adenosine deaminase(p) correctly classified all nontuberculous lymphocytic pleural effusions with high adenosine deaminase levels.     

Adenosine deaminase activity in pleural fluid--a diagnostic test of tuberculous pleural effusion.

Adenosine deaminase (ADA) activity in pleural fluids was studied in 47 patients with pleural effusion of different etiology. Patients were divided into two groups: Group I - Tuberculous pleural effusion (21 patients): Group II - Non tuberculous effusion (26 patients) and these included malignant pleural effusion (9 cases), synpneumonic pleural effusion (9 cases) and transudative pleural effusion (8 cases). The mean ADA activity was 64.67 IU/L +/- 21.68 in group I and 6.99 +/- 3.69 in Group II. Increased mean pleural fluid ADA activity in tuberculous pleural effusion was highly significant (p < 0.001) when compared with pleural effusion of non-tuberculous etiology. Based on lowest value of ADA activity found in tuberculous pleural effusion (30 IU/L), the test has a sensitivity and specificity of 1.     

Efficacy of adenosine deaminase in the diagnosis of pleural effusions

Adenosine deaminase (ADA) activity was studied in 53 patients with pleural effusions. Patients with tuberculous pleural effusion (36) had significantly higher ADA activity (77.68 IU/L; P less than 0.001) in comparison to malignant (14.47 IU/L) and parapneumonic (28.65 IU/L) effusions. When tested with a reference limit of over 50.75 IU/L, the specificity of ADA activity was found to be 94.1 per cent. With a sensitivity of 100 per cent, low cost and easy performance pleural fluid ADA activity is proposed as a routine investigation for etiological diagnosis in pleural effusion.     

新型隐球菌性脑膜炎与结核性脑膜炎的临床鉴别

目的 探讨新型隐球菌性脑膜炎与结核性脑膜炎的鉴别要点。 方法 回顾分析19例隐球菌性脑膜炎及50例结核性脑膜炎患者的临床表现、脑脊液改变和头颅CT或MRI特点。 结果 隐球菌性脑膜炎延误诊断时间为（2.3±1.7）个月,合并颅外结核病26.3%,合并慢性基础病36.8%,颅神经损害发生率5.3%,颅内压（320.0±57.7）mmH₂O,脑脊液葡萄糖含量（1.2±0.8）mmol/L, PCR-TB阳性率0,抗结核抗体阳性率10.5%,红细胞沉降率（42.1±31.2）mm/1h、头颅CT或MRI检查阳性发现率57.9%等方面与结核性脑膜炎存在差异。而2者在临床症状、脑脊液白细胞数、蛋白、氯化物、腺苷脱氨酶含量和头颅CT或MRI表现等方面差异无统计学意义。 结论 隐球菌性脑膜炎临床表现不典型,与结脑不易鉴别,容易误诊。但提高对隐球菌性脑膜炎的认识,并行多项指标检测有利于早期诊断。     

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.     

结核性与癌性胸腔积液的实验室检测比较研究

目的比较研究实验室检测腺苷脱氨酶(ADA)、乳酸脱氢酶(LDH)、癌胚抗原(CEA)、蛋白(TP)、葡萄糖(GLU)等多项指标对结核性与癌性胸腔积液的鉴别诊断价值。方法对151例明确诊断为结核性或癌性胸腔积液分别测定胸水ADA、LDH、CEA、TP、GLU和血清TP,并进行统计分析。结果结核性胸腔积液中ADA、LDH、TP含量都明显高于癌性胸腔积液,其中胸水ADA以28U/L作为诊断结核性胸水的临界值则其敏感性和特异性均极高,结核性胸水中GLU含量则低于癌性胸水,癌性胸水CEA的阳性率高达76.0%,而结核性胸水CEA均阴性。结论联合检测胸水ADA、LDH、CEA、TP和GLU可以作为结核性与癌性胸腔积液的诊断和鉴别诊断依据,其中ADA28U/L可以考虑作为结核性胸腔积液的单独诊断依据。     

结核性脑膜炎患者脑脊液中腺苷脱氨酶和结核抗体水平研究

目的探讨结核性脑膜炎(TBM)的早期诊断方法。方法采用氨的偶联酶测定法和酶联免疫吸附实验(ELISA)检测3组病例(结脑组51例,病脑组30例,非脑膜炎组20例)脑脊液(CSF)中腺苷脱氨酶(ADA)的活性水平和脑脊液结核抗体(PPD-IgG)的阳性率。结果研究发现结脑组脑脊液中腺苷脱氨酶活性水平明显升高,与病脑组和非脑膜炎组比较有显著性差异(p<0.01)。而病脑组与非脑膜炎组比较无显著性差异(p>0.05);结核性脑膜炎早期脑脊液中结核抗体的阳性率为80.4%(其中2周内PPD-IgG阳性率为80.4%,1周内为23.5%,其他为3.9%),在随后的临床跟踪检测中为100%。结论说明共同检测脑脊液中腺苷脱氨酶的活性明显升高和结核抗体阳性可以作为结脑早期诊断的重要依据。     

Discrimination of exudative pleural effusions based on multiple biological parameters.

Pleural effusion is a common complication of various diseases. Conventional methods are not always capable of establishing the cause of pleural effusion, so alternative tests are needed. The aim of this study was to explore means of discriminating between different pleural effusion groups, malignant, parapneumonic and tuberculous, based on the combined function of seven biological markers. Adenosine deaminase (ADA), interferon-gamma, C-reactive protein (CRP), carcinoembryonic antigen, interleukin-6, tumour necrosis factor-alpha and vascular endothelial growth factor concentration levels were measured in pleural fluid from 45 patients with malignant, 15 with parapneumonic and 12 with tuberculous pleural effusion. Receiver operating characteristic curve analysis, multinomial logit modelling and canonical variate analysis were applied to discriminate the pleural effusion groups. The three groups could be discriminated successfully using the measured markers. The most important parameters for discrimination were ADA and CRP concentration levels. An individual with an ADA concentration level of >45 U.L(-1) and a CRP concentration of <4 mg.dL(-1) was more likely to belong to the tuberculous pleural effusion group, whereas one with an ADA concentration level of <40 U.L(-1) and a CRP concentration of >6 mg.dL(-1) was more likely to belong to the parapneumonic pleural effusion group, and one with a CRP concentration of <4 mg.dL(-1) to the malignant pleural effusion group. The combination of adenosine deaminase and C-reactive protein levels might be sufficient for discriminating between the three different groups of exudative pleural effusion: malignant, tuberculous and parapneumonic.     

Ascites Adenosine Deaminase Activity is Decreased in Tuberculous Ascites with Low Protein Content

The value of adenosine deaminase activity (ADA) in ascitic fluid was examined in 12 patients with confirmed peritoneal tuberculosis and compared with that of 96 patients with ascites of other different etiologies as an age-matched control group, to determine the diagnostic value of the ADA activity in tuberculous ascites. The mean adenosine deaminase activity (ADA) value in ascitic fluid of the tuberculous peritonitis group was 47.9 +/- 21.9 IU/L and in the control group 9.6 +/- 5 U/L (mean +/- SD); p less than 0.01. A different method than that usually reported in tuberculous peritonitis was used for ascites ADA estimation. The best sensitivity and specificity was obtained when greater than 32 U/L was used as a cutoff point. The ascites ADA activity correlated with the ascites total protein concentration in the tuberculosis group (r = 0.842). Our findings confirm other results and support the ADA activity determination in ascitic fluid as a useful noninvasive screening test in the diagnosis of peritoneal tuberculosis in endemic areas or in high risk patients. However, false-negative results may occur in those patients in which ascites total protein concentration is low.     

Evaluation of usefulness of pleural fluid adenosine deaminase in diagnosing tuberculous pleural effusion from empyema

ObjectiveTo evaluate the utility of adenosine deaminase activity in the pleural fluid for the diagnosis of tuberculous pleural effusion from empyema of non-tubercular origin.MethodA retrospective analysis of data was performed on patients who were diagnosed to have tuberculous pleural effusion and empyema of non tubercular origin. Among 46 patients at Kasturba Hospital, Manipal University, Manipal, Karnataka, India, from November 2012 to February 2013 who underwent pleural fluid adenosine deaminase estimation, 25 patients with tuberculous pleural effusion and 21 patients with empyema were diagnosed respectively. Adenosine deaminase in pleural fluid is estimated using colorimetric, Galanti and Guisti method.ResultsPleural fluid Adenosine Deaminase levels among tuberculous pleural effusion(109.38±53.83), empyema (141.20±71.69) with P=0.27.ConclusionPleural fluid adenosine deaminase alone cannot be used as a marker for the diagnosis of tuberculous pleural effusion.     

The influence of HIV infection on clinical presentation, response to treatment, and outcome in adults with Tuberculous meningitis

BACKGROUND: Tuberculous meningitis occurs more commonly in human immunodeficiency virus (HIV)-infected individuals than in HIV-uninfected individuals, but whether HIV infection alters the presentation and outcome of tuberculous meningitis is unknown. METHODS: We performed a prospective comparison of the presenting clinical features and response to treatment in 528 adults treated consecutively for tuberculous meningitis (96 were infected with HIV and 432 were uninfected with HIV) in 2 tertiary-care referral hospitals in Ho Chi Minh City, Vietnam. Logistic regression was used to model variables associated independently with HIV infection, 9-month survival, and the likelihood of having a relapse or an adverse drug event. Kaplan-Meier estimates were used to compare survival rates and times to fever clearance, coma clearance, relapse, and adverse events. RESULTS: HIV infection did not alter the neurological presentation of tuberculous meningitis, although additional extrapulmonary tuberculosis was more likely to occur in HIV-infected patients. The 9-month survival rate was significantly decreased in HIV-infected patients (relative risk of death from any cause, 2.91 [95% confidence interval, 2.14-3.96]; P < .001), although the times to fever clearance and coma clearance and the number or timing of relapses or adverse drug events were not significantly different between the groups. CONCLUSIONS: HIV infection does not alter the neurological features of tuberculous meningitis but significantly reduces the survival rate.     

BKV-DNA and JCV-DNA in CSF of Patients with Suspected Meningitis or Encephalitis

Abstract. Background: Few studies have looked for the polyoma viruses JC or BK virus in the central nervous system (CNS) of patients without neurological symptoms or with neurological symptoms other than progressive multifocal leukoencephalopathy (PML). PCR-microplate hybridization method was employed for the detection of BKV-DNA or JCV-DNA in cerebrospinal fluid (CSF) specimens from patients with suspected meningitis or encephalitis. Materials and Methods: A total of 181 CSF specimens from 151 patients with suspected meningitis or encephalitis was examined for BKV or JCV using PCR-microplate hybridization method. None of the patients had (clinically diagnosed) PML. A control group consisting of 20 CSF specimens from normal subject was also included. Results: BKV DNA was found in five out of 131 (3.8%) and JCV DNA in two out of 131 (1.5%) of the patients with suspected meningitis or encephalitis by PCR ELISA. BKV or JCV DNA was not detected in CSF samples of any of 19 HIVpositive patients. BKV and JCV DNAs were detected respectively in two CSF samples in which Mycobacterium tuberculosis (TB) PCR was also positive. Another patient who was positive for JCV PCR died with a diagnosis of cerebral lymphoma. Among the BK virus infected patients there was a patient with a previous history of hemolytic uremia and acute renal failure. Neither BKV nor JCV DNA was found in any of the 20 CSF samples from normal patients undergoing lumbar puncture for myelography as a part of an investigation of lower back pain. Conclusion: These results suggest that BK virus may be associated with neurological diseases either in immunocompetent or immunocompromised patients. Detection of BKV and JCV DNA in the CSF of the patients suspected to have either meningitis or encephalitis suggests that these viruses may have an etiological role. Thus, diagnostic tests for BK and JC viruses should be included in the investigative program for meningitis or encephalitis patients.     

Attenuated cerebrospinal fluid leukocyte count and sepsis in adults with pneumococcal meningitis: a prospective cohort study

Background  

A low cerebrospinal fluid (CSF) white-blood cell count (WBC) has been identified as an independent risk factor for adverse outcome in adults with bacterial meningitis. Whereas a low CSF WBC indicates the presence of sepsis with early meningitis in patients with meningococcal infections, the relation between CSF WBC and outcome in patients with pneumococcal meningitis is not understood.     

血管内皮细胞生长因子C与腺苷脱氨酶联合检测在胸腔积液鉴别诊断中的意义

目的 了解血管内皮细胞生长因子C(VEGF-C)及腺苷脱氨酶(ADA)在不同原因胸腔积液中的表达,并探讨通过比值构建联合诊断对胸腔积液鉴别诊断的作用.方法 选择143例临床确诊的胸腔积液患者(恶性胸腔积液40例,结核性胸膜炎45例,其他类型58例),采用双抗夹心ELISA法检测胸水VEGF-C,采用速率法检测胸水ADA,计算VEGF-C/ADA比值,比较不同类型胸腔积液患者中上述诊断指标的变化,并计算它们的敏感度、特异度和准确度.结果 恶性胸腔积液中VEGF-C浓度高于结核性胸腔积液及类肺炎性等其他类型胸腔积液,(286.32±102.65)ng/L vs(133.46±39.83)ng/L,(140.14±44.62)ng/L,P<0.05.结核性胸腔积液中ADA浓度高于恶性胸腔积液及其他类型胸腔积液,(78.6±36.3)IU/L vs(23.4±11.2)IU/L,(26.1±10.5)IU/L,P<0.05.VEGF-C/ADA≥8对恶性胸腔积液诊断的敏感度为87.5%,特异度为81.4%;VEGF-C/ADA≤3对结核性胸腔积液诊断的敏感度为84.4%,特异度为86.4%.结论 VEGF-C与ADA浓度比值对胸腔积液的鉴别诊断具有较好的临床价值.