Cerebrospinal Fluid Adenosine Deaminase Research Articles

Study of cerebrospinal fluid adenosine deaminase activity for differential diagnosis of tuberculous and non-tuberculous meningitis

Background: Diagnosing a case of tuberculous meningitis (TBM) has always been challenging. Numerous previous studies have demonstrated that cerebrospinal fluid-Adenosine deaminase (CSF-ADA) estimation is useful in the diagnosis of TBM and can differentiate TBM from other types of meningitis. Aims and Objectives: The current study aims to look for a simple, rapid, cost-effective, and specific test to differentiate tubercular etiology from other causes of meningitis. Materials and Methods: A total of 80 patients admitted to the hospital with signs and symptoms of meningitis were selected and divided into two groups: Group 1 (Cases): 40 patients of TBM, Group 2 (Control): 40 patients of pyogenic and viral meningitis. The CSF ADA was estimated by enzymatic method, CSF Protein by turbidimetric method, and CSF Glucose by Glucose oxidase (GOD) and Peroxidase (POD) method. Results: CSF ADA levels (mean ± SD) in the TBM and non-TBM groups were 10.874+7.72 IU/L and 2.44+1.757 IU/L, respectively (highly significant, P<0.001). With the CSF ADA cut off as >6 IU/L, the sensitivity of the test was 95%, and the specificity of 92.5%. On comparison of the values of CSF ADA in the two groups, the t value is −6.75, and the difference in these two values was found to be highly significant (P<0.01). Conclusion: ADA estimation in CSF is a simple, inexpensive, rapid, and specific method for making a diagnosis of tuberculous etiology in TBM. As a screening test, the determination of ADA activity in CSF can help the physician diagnose TBM early and reduce irreversible brain damage and neurologic sequelae by early administration of anti-tuberculous medications.

Diagnostic Accuracy of Cerebrospinal Fluid (CSF) Adenosine Deaminase (ADA) for Tuberculous Meningitis (TBM) in Adults: A Systematic Review and Meta-Analysis.

Tuberculous meningitis is the most serious complication of tuberculosis. Early diagnosis is crucial to start relevant treatment to prevent death and disability. Electronic databases PubMed, Google Scholar, and Cochrane Library were used to find relevant articles from January 1980 to June 2022. The random-effect model in terms of pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence interval was adopted to derive the diagnostic efficacy of cerebrospinal fluid (CSF) adenosine deaminase (ADA) for the diagnosis of tuberculous meningitis (TBM) in adult patients. A total of 22 studies (20 prospective and two retrospective data) have been included in this meta-analysis, having 1927 participants. We perceived acceptable pooled sensitivity, specificity, summary receiver operating characteristics (SROCs), and diagnostic odds ratio (DOR) of 0.85 (95% CI: 0.77-0.90), 0.90 (95% CI: 0.85-0.93), 0.94 (95% CI: 0.91-0.96) and 48 (95% CI: 26-86), respectively, for CSF-ADA for differentiating TBM from non-TBM in adult patients. To ascertain the certainty of evidence for CSF-ADA as a diagnostic marker for TBM, Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) analysis was used. CSF-ADA is an auspicious diagnostic test with a high degree of specificity and acceptable sensitivity for the diagnosis of tuberculous meningitis, however, with very low certainty of evidence.

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

(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. 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. 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%. 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.

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 ≥12years 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.

Correlation between cerebrospinal fluid abnormalities before ventriculoperitoneal shunt and postoperative intracranial infection in adult patients with hydrocephalus: A clinical study.

To identify the relationship between preoperative cerebrospinal fluid (CSF) leukocyte, chloride, glucose, aspartate aminotransferase, lactate dehydrogenase, adenosine deaminase, lactic acid and protein levels and ventriculoperitoneal shunt infection. Records of 671 consecutive adult patients who underwent ventriculoperitoneal shunt surgery for the treatment of hydrocephalus at Zhujiang Hospital affiliated with Southern Medical University from January 2011 to March 2022 were reviewed. The patients were divided into infection and non-infection groups based on the presence of postoperative infection. For all patients, we analyzed age; sex; primary disease; preoperative CSF leukocyte, chloride, glucose, aspartate aminotransferase, lactate dehydrogenase, adenosine deaminase, lactic acid and protein levels; postoperative temperature; and postoperative infection. A total of 397 patients were included, 28 (7.05%) of whom had an infection within 6 months of the operation and the remaining had no infection. There was no significant difference in age, sex, primary disease, leukocyte, chloride ion, aspartate aminotransferase, lactate dehydrogenase, adenosine deaminase and protein levels in CSF between infection group and non-infection group (p > 0.05). The postoperative infection rate of patients with CSF glucose < 2.8 mmol/L (x 2 = 11.650, p = 0.001) and CSF lactic acid >2.8 mmol/L (x 2 = 12.455, p < 0.001) was higher than that of patients with CSF glucose level ≥2.8 mmol/L and CSF lactic acid level in the range of (1-2.8) mmol/L, respectively, with statistical difference. Compared with the non-infection group, the level of CSF glucose (t = 4.113, p < 0.001) was significantly lower, and the level of CSF lactic acid (t = 6.651, p < 0.001) was significantly higher in the infection group. Multivariate logistic regression analysis showed that preoperative cerebrospinal fluid glucose < 2.8 mmol/L (OR = 3.911, 95% CI: 1.653~9.253, p = 0.002) and cerebrospinal fluid lactate >2.8 mmol/L (OR = 4.712, 95% CI: 1.892~11.734, p = 0.001) are risk factors for infection after ventriculoperitoneal shunt. ROC analysis revealed that the area under the curve (AUC) for CSF glucose and lactic acid level were 0.602 (95% CI: 0.492-0.713) and 0.818 (95% CI: 0.738-0.898), respectively. The infection group had higher rates of fever and body temperature on postoperative day 3-7 (p < 0.05). For adult hydrocephalus patients without clinical manifestations of intracranial infection but only with simple abnormality of cerebrospinal fluid, when the content of glucose in cerebrospinal fluid is < 2.8 mmol/L, and the content of lactic acid is >2.8 mmol/L, it is recommended to perform ventriculoperitoneal shunt after further improvement of cerebrospinal fluid indicators, otherwise, hasty operation will increase the postoperative infection rate. The postoperative fever rate of ventriculoperitoneal shunt surgery is high and the body temperature drops rapidly. If there is still fever after day 3 after surgery, whether there is intracranial infection should be considered.

High cerebrospinal fluid lactate concentration at 48 h of hospital admission predicts poor outcomes in patients with tuberculous meningitis: A multicenter retrospective cohort study.

ObjectiveThis study aimed to analyze the cerebrospinal fluid (CSF) parameters affecting the outcomes of patients with tuberculous meningitis (TBM).MethodsThis is a multi-center, retrospective, cohort study involving 81 patients who were diagnosed with TBM and treated in Haihe Clinical College of Tianjin Medical University, Tianjin Medical University General Hospital, and General Hospital of Air Force PLA from January 2016 to December 2019. Baseline data, Glasgow Coma Scale (GCS) score, and clinical presentations of all patients were collected at admission. CSF samples were collected at 48 h, 1, 2, and 3 weeks after admission. CSF lactate, adenosine deaminase, chloride, protein, glucose levels and intracranial pressure were measured. After a follow-up of 16.14 ± 3.03 months, all patients were assessed using the modified Rankin Scale (mRS) and divided into good (mRS scores of 0–2 points) and poor outcome groups (mRS scores of 3–6 points). The differences in patients' baseline data, GCS score, clinical presentations, and levels of CSF parameters detected at 48 h, 1, 2, and 3 weeks after admission between two groups were compared. Statistically significant variables were added to the binary logistic regression model to identify the factors impacting the outcomes of patients with TBM. Receiver operating characteristic (ROC) curve was used to assess the predictive ability of the model.ResultsThe CSF lactate level exhibited a decreasing trend within 3 weeks of admission in the two groups. For the within-group comparison, statistically significant differences in the lactate level was found in both groups between four different time points. A binary logistic regression model revealed that CSF lactate level at 48 h after admission, age, and GSC score on admission were independently associated with the outcomes of patients with TBM. ROC curve analysis showed that the area under the ROC curve (AUC) was 0.786 for the CSF lactate level (48 h), 0.814 for GCS score, and 0.764 for age.ConclusionHigh CSF lactate level at 48 h after admission is one of the important factors for poor outcomes in patients with TBM.

Factors Predictive of Varicella Zoster Virus Encephalitis/Meningitis: A Single-Center, Retrospective Study.

BackgroundThe outcomes of varicella zoster virus (VZV) encephalitis/meningitis vary from complete recovery to severe complications. This study aimed to investigate the predictive factors of encephalitis and meningitis caused by VZV reactivation.Material/MethodsVZV encephalitis/meningitis patients (n=39) who were treated between January 2019 and December 2021 were included. Patients were followed up for 3 months after discharge and divided into a favorable outcome group (FO, n=18; 46.2%) and an unfavorable outcome group (UO, n=21; 53.8%) according to whether it affects quality of life. The clinical data were retrospectively analyzed and compared between groups.ResultsAs compared to the FO group, patients in the UO group were more likely to have higher body temperature (>38°C) at admission, longer interval from onset of CNS symptoms to initial of antiviral therapy, higher white blood cells (WBC) and adenosine deaminase (ADA) in the cerebrospinal fluid (CSF) and higher CRP in the blood (P<0.05 or P<0.01). Univariate logistic regression analysis showed CSF ADA (OR=1.279, 95% CI: 0.996~1.642) and interval from onset of CNS symptoms to initial of antiviral therapy (OR=1.299, 95% CI: 1.011~1.669) were independent risk factors for unfavorable outcomes (P<0.05). The sensitivity and specificity of combined CSF ADA and time interval from onset of CNS symptoms to initial of antiviral therapy were 78.8% and 95.2%, respectively, in predicting outcomes.ConclusionsHigher CSF ADA and longer interval from onset of CNS symptoms to initial of antiviral therapy predict an unfavorable outcome, and the combination of both factors can achieve better performance.

Stroke in Tuberculous Meningitis and Its correlation with Magnetic Resonance Angiography Manifestations.

Objective The primary objective of the study was to assess the location of cerebral infarction and look for corresponding magnetic resonance angiography (MRA) changes in patients with tuberculous meningitis (TBM). We also evaluated the predictors of ischemic stroke in TBM and the impact of these infarctions on patient's outcome. Methods This was a single-center prospective study between September 2018 and September 2020. Demographic and laboratory parameters were noted. Cranial magnetic resonance imaging and MRA were performed at the time of admission to the hospital. Results Among 120 patients with TBM, 46 had stroke. Nineteen (15.8%) patients died, of which 12 (10%) suffered from stroke. The most common site of infarction was the basal ganglia (54.3%). The commonest site of MRA abnormalities was the middle cerebral artery (39.1%). British Medical Research Council (BMRC) stage 3, cerebrospinal fluid (CSF) sugar, CSF adenosine deaminase (ADA) level, basal exudates, hydrocephalus, and hyponatremia were found to be predictors of stroke in TBM, while BMRC stage 3, CSF cell count, CSF ADA level, and anemia were found to be significantly associated with mortality in TBM patients with stroke. Conclusion The basal ganglia were the most common site of ischemic stroke in TBM, and middle cerebral artery was the most often involved intracranial blood vessel. BMRC stage 3 was significantly associated with both stroke and mortality in TBM patients with stroke.

Value of CSF-Cl, CSF-GS, CSF-MALB, and CSF-ADA in Differential Diagnosis of Secondary Hydrocephalus.

Objectives To investigate the value of cerebrospinal fluid chloride (CSF-Cl), cerebrospinal fluid glucose (CSF-GS), cerebrospinal fluid microalbumin (CSF-MALB), and cerebrospinal fluid adenosine deaminase (CSF-ADA) in the differential diagnosis of secondary hydrocephalus. Methods 103 patients with secondary hydrocephalus treated in our hospital from January 2018 to April 2022 were selected. According to different types, it is divided into the hemorrhagic hydrocephalus group and tumor hydrocephalus group. By detecting the levels of inflammatory factors such as CSF-Cl, CSF-GS, CSF-MALB, and CSF-ADA in the two groups, we can analyze the value of these inflammatory factors in the differential diagnosis of secondary hydrocephalus. Results The level of CSF-MALB in the hemorrhagic hydrocephalus group was significantly higher than that in the tumor hydrocephalus group, and the difference between the two groups was statistically significant (P < 0.05). There was no significant difference in the levels of CSF-Cl, CSF-GS, and CSF-ADA between the two groups (P > 0.05). The area under ROC curve (AUC) of CSF-Cl, CSF-GS, CSF-MALB, and CSF-ADA in the differential diagnosis of secondary hydrocephalus was 0.438, 0.553, 0.750, and 0.542, respectively, sensitivity was 15.1%, 45.3%, 79.2%, and 18.9%, respectively, and specificity was 96.0%, 80.0%, 80.0%, and 94.0%, respectively. Conclusions The inflammatory reaction of hemorrhagic hydrocephalus was significantly greater than that of tumor hydrocephalus. Moreover, CSF-MALB is closely related to the pathogenesis of hemorrhagic hydrocephalus. At the same time, CSF-MALB can be used as a good index for rapid differential diagnosis of secondary hydrocephalus.

Cerebrospinal fluid analysis is associated with enhancement on MRI in bacterial and tuberculous meningitis: A retrospective observational study

ObjectiveAlong with cerebrospinal fluid (CSF) analysis, enhancement on contrast-enhanced MRI is useful to diagnose meningitis. However, the conditions for its appearance have not been clarified. This study aimed to investigate the association between CSF parameters and enhancement on contrast-enhanced head or spinal MRI in patients with bacterial meningitis (BM) or tuberculous meningitis (TM). MethodsA total of 12 patients with BM and 23 patients with TM who underwent both CSF analysis and contrast-enhanced MRI were included. The correlation between CSF analysis and MRI findings has been examined using receiver operating characteristic (ROC) analysis. ResultsContrast enhancement was found in 7 and 10 patients with BM and TM, respectively. Both CSF analysis and MRI were useful to distinct between BM and TM, and the enhancement implied the severity of them. In patients with BM, higher CSF protein and lower CSF glucose were associated with enhancement on MRI, while not only CSF protein and glucose but also leukocyte and lymphocyte counts were associated with it in TM. CSF adenosine deaminase (ADA) did not show discriminant ability of the MRI findings. ConclusionsCSF analysis is associated with enhancement on contrast-enhanced MRI both in BM and TM. Our findings indicate the importance of CSF analysis in assessing the need to perform contrast-enhanced MRI, which may be useful in diagnosis, distinction, and estimation of prognosis in those patients.

Epidemiology of patients with central nervous system infections, mainly neurosurgical patients: a retrospective study from 2012 to 2019 in a teaching hospital in China

BackgroundCentral nervous system (CNS) infections are relatively rare but are associated with high mortality worldwide. Empirical antimicrobial therapy is crucial for the survival of patients with CNS infections, and should be based on the knowledge of the pathogen distribution and antibiotic sensitivities. The aim of this study was to investigate the features of pathogens in patients with CNS infections in North China and evaluate the risk factors for mortality and multi-drug-resistant (MDR) bacterial infections.MethodsA retrospective study was conducted with patients with positive cerebrospinal fluid (CSF) cultures in a teaching hospital from January 2012 to December 2019. The following data were collected: demographic characteristics, laboratory data, causative organisms and antimicrobial sensitivity results. Data were analyzed with SPSS 16.0. Univariate analysis and binary logistic regression analyses were performed to identify the risk factors for mortality and MDR bacterial infections.ResultsA total of 72 patients were diagnosed with CNS infections, and 86 isolates were identified. The proportions of Gram-positive bacteria, Gram-negative bacteria and fungi were 59.3, 30.2 and 10.5%, respectively. The predominant Gram-positive bacteria was Coagulase-negative Staphylococci. Acinetobacter baumannii, Escherichia coli and Klebsiella spp. were the predominant Gram-negative bacteria. Compared to 2012–2015 years, the proportion of Gram-negative bacteria increased markedly during 2016–2019 years. Coagulase-negative Staphylococci, Streptococcus pneumoniae and Enterococcus faecium had 100% sensitivity to vancomycin, teicoplanin and linezolid. Acinetobacter baumannii and Klebsiella pneumoniae were 100% sensitive to tigecycline. Escherichia coli had 100% sensitivity to amikacin, meropenem and imipenem. The overall mortality rate in the 72 patients was 30.6%. In multivariate analysis, age > 50 years, pulmonary infections and CSF glucose level < the normal value were associated with poor outcomes. CSF adenosine deaminase level > the normal value and the presence of external ventricular drainage/lumbar cistern drainage were associated with MDR bacterial infections.ConclusionsThe mortality rate due to CNS infections reached 30.6% in our study. The proportion of Gram-negative bacteria has increased markedly in recent years. We should give particular attention to patients with risk factors for mortality and MDR bacterial infections mentioned above.

Characteristics and biomarkers of patients with central nervous system infection admitted to a referral hospital in Northern Vietnam

BackgroundLaboratory facilities for etiological diagnosis of central nervous system (CNS) infection are limited in developing countries; therefore, patients are treated empirically, and the epidemiology of the pathogens is not well-known. Tubercular meningitis is one of the common causes of meningitis, which has high morbidity and mortality, but lacks sensitive diagnostic assays. The objectives of this study were to determine the causes of meningitis in adult patients by using molecular assays, to assess the risk factors associated with them, and to explore whether biomarkers can differentiate tubercular meningitis from bacterial meningitis.MethodsWe conducted a cross-sectional study in the Department of Infectious Diseases, Bach Mai Hospital, Hanoi, Vietnam, from June 2012 to May 2014. All patients who were ≥ 16 years old and who had meningoencephalitis suggested by abnormal cerebrospinal fluid (CSF) findings (CSF total cell >5/mm3 or CSF protein ≥40 mg/dL) were included in the study. In addition to culture, CSF samples were tested for common bacterial and viral pathogens by polymerase chain reaction (PCR) and for biomarkers: C-reactive protein and adenosine deaminase (ADA).ResultsTotal number of patients admitted to the department was 7506; among them, 679 were suspected to have CNS infection, and they underwent lumbar puncture. Five hundred eighty-three patients had abnormal CSF findings (meningoencephalitis); median age was 45 (IQR 31–58), 62.6% were male, and 60.9% were tested for HIV infection. Among 408 CSF samples tested by PCR, out of them, 358 were also tested by culture; an etiology was identified in 27.5% (n=112). S. suis (8.8%), N. meningitis (3.2%), and S. pneumoniae (2.7%) were common bacterial and HSV (2.2%), Echovirus 6 (0.7%), and Echovirus 30 (0.7%) were common viral pathogens detected. M. tuberculosis was found in 3.2%. Mixed pathogens were detected in 1.8% of the CSF samples. Rural residence (aOR 4.1, 95% CI 1.2–14.4) and raised CSF ADA (≥10 IU/L) (aOR 25.5, 95% CI 3.1–212) were associated with bacterial meningitis when compared with viral meningitis; similarly, raised CSF ADA (≥10 IU/L) (aOR 42.2, 95% CI 2.0–882) was associated with tubercular meningitis.ConclusionsAddition of molecular method to the conventional culture had enhanced the identification of etiologies of CNS infection. Raised CSF ADA (≥10 IU/L) was strongly associated with bacterial and tubercular meningitis. This biomarker might be helpful to diagnose tubercular meningitis once bacterial meningitis is ruled out by other methods.

English

BACKGROUND Acute infections of the nervous system are generally widespread and cause significant problems in the field medicine and therefore early detection, right decision making, and early initiation of therapy can be lifesaving. Meningitis is the inflammation of the membranes that cover the brain and spinal cord. It is a general clinical problem during infancy and childhood. Delay in differentiating between bacterial, tubercular &amp; viral meningitis and institution of its treatment may have irreparable consequences that lead to significant morbidity &amp; mortality. The present study was conducted to find out the utility of cerebrospinal fluid-adenosine deaminase (CSF-ADA) for the early diagnosis &amp; differentiation of tubercular &amp; viral meningitis in adults. METHODS 50 meningitis patients who met the inclusion criteria were selected. Investigations including complete haemogram, liver function test (LFT), renal function test (RFT), random blood sugar (RBS), serum electrolytes, human immunodeficiency virus (HIV) test, chest x-ray and computed tomography (CT) brain (plain) were done. CSF cytology, biochemistry, gram stain, acid-fast bacteria (AFB) stain &amp; culture were done. These cases were further divided in to two groups based on clinical and CSF laboratory findings as group I: tubercular meningitis, group II: viral meningitis. An estimation of CSF-ADA was done in all patients. RESULTS The mean age of the 50 patients studied was 37.76 + 15.58 years, with the maximum number of patients suffering from tubercular meningitis. The incidence of meningitis was more in males. CSF-adenosine deaminase activity was found to be higher in tubercular meningitis, the mean value was 17.67 ± 8.13 IU / L. CONCLUSIONS Assessment of CSF-ADA will be helpful for early diagnosis and differentiation of tubercular and viral meningitis. This is needed when gold standard investigations for meningitis like smear and / or culture for acid fast bacilli are not available or negative or are time consuming. KEY WORDS CSF-Cerebrospinal Fluid, ADA-Adenosine Deaminase, AFB-Acid Fast Bacilli.

Diagnostic Importance of Cerebrospinal Fluid Adenosine Deaminase Levels in Tuberculous Meningitis

Introduction: Estimation of Cerebrospinal Fluid (CSF) Adenosine Deaminase (ADA) is used for early diagnosis of Tuberculous Meningitis (TBM) and has got importance in differentiating TBM from bacterial and viral types of meningitis. Hence, estimation of ADA in CSF can be carried out in all clinically suspected meningitis patients, especially in developing countries like India with high prevalence of Tuberculosis (TB). Aim: To evaluate CSF ADA as a diagnostic test for TBM. Materials and Methods: The prospective study was done on 80 cases admitted with meningitis in Government General Hospital Kakinada, Andhra Pradesh, India, in a period of eight months during August 2018 to March 2019. In all the subjects the concentrations of CSF ADA, Glucose, Total proteins, Calcium, and Phosphorus were assayed. Results: The results shows that the mean values of CSF ADA in TBM were significantly increased (15.13±12.2) when compared with other types of meningitis due to stimulation of T-cells by Mycobacterium antigens. Mean values of CSF glucose were significantly decreased in bacterial and TBM. Mean values of CSF total proteins were increased in all three types. Conclusion: Therefore, this study suggests the need for routine measurement of CSF ADA in the diagnosis of TBM and thus helps in early detection of TBM which warrants timely intervention leading to lowered morbidity and mortality.

Machine-Learning-Based Approach to Differential Diagnosis in Tuberculous and Viral Meningitis.

BackgroundTuberculous meningitis (TBM) is the most severe form of tuberculosis, but differentiating between the diagnosis of TBM and viral meningitis (VM) is difficult. Thus, we have developed machine-learning modules for differentiating TBM from VM.Material and MethodsFor the training data, confirmed or probable TBM and confirmed VM cases were retrospectively collected from five teaching hospitals in Korea between January 2000 - July 2018. Various machine-learning algorithms were used for training. The machine-learning algorithms were tested by the leave-one-out cross-validation. Four residents and two infectious disease specialists were tested using the summarized medical information.ResultsThe training study comprised data from 60 patients with confirmed or probable TBM and 143 patients with confirmed VM. Older age, longer symptom duration before the visit, lower serum sodium, lower cerebrospinal fluid (CSF) glucose, higher CSF protein, and CSF adenosine deaminase were found in the TBM patients. Among the various machine-learning algorithms, the area under the curve (AUC) of the receiver operating characteristics of artificial neural network (ANN) with ImperativeImputer for matrix completion (0.85; 95% confidence interval 0.79 - 0.89) was found to be the highest. The AUC of the ANN model was statistically higher than those of all the residents (range 0.67 - 0.72, P <0.001) and an infectious disease specialist (AUC 0.76; P = 0.03).ConclusionThe machine-learning techniques may play a role in differentiating between TBM and VM. Specifically, the ANN model seems to have better diagnostic performance than the non-expert clinician.

Adenosine deaminase and lactate dehydrogenase levels in serum and cerebrospinal fluid of patients with tuberculous meningitis

Meningitis is an active inflammatory condition of CNS. However prompt and precise aetiological diagnosis remains a challenge. Often a thorough CSF examination may not give a precise diagnosis.There is considerable urgency in establishing correct diagnosis in patients with tuberculous meningitis because specific therapy is most effective when initiated early in course of illness, delay may cause irreversible brain damage.Diagnosis often rests on circumstantial evidence such as history, typical CSF findings and other evidence for presence of tuberculosis such as acid fast bacilli in sputum, positive tuberculosis test and suspicious Chest x-ray. Under present study the role of enzymes such as adenosine deaminase and lactate dehydrogenase has been evaluated in diagnosis of tuberculous meningitis. Result of the study suggest that adenosine deaminase level in CSF and serum may be a useful parameter along with other routine estimations. The enzyme activity is high in disease such as tuberculosis where cellular mediated immunity is stimulated.Estimation of lactate dehydrogenase levels may not be a specific parameter for tuberculous meningitis this requires further studies in patients of meningitis with different aetiological diagnosis.

Cerebrospinal fluid adenosine deaminase level as a diagnostic marker in adult tuberculous meningitis: a study conducted in a tertiary care hospital of Eastern India

Background: Tubercular meningitis is one of the highly prevalent form of meningitis in the world and is a significant cause of morbidity and mortality in developing countries like India. Lack of early and timely diagnosis and subsequent initiation of treatment makes the fatality rate even higher. Cerebrospinal fluid (CSF) analysis is most important aspect of lab diagnosis in tuberculous meningitis (TBM) worldwide. The objective of this study was to study the cerebrospinal fluid CSF adenosine deaminase (ADA) levels in TBM and non-TBM meningitis cases and to determine its diagnostic significance as a biochemical marker of TBM infection.Methods: The study population comprised three different patient groups. TBM (n=36), pyogenic meningitis (n=17) and aseptic meningitis group (n=12). Total 75 subjects were enrolled consecutively in the study and CSF specimens were collected from them. ADA and other cytological and biochemical estimation were carried out using standard protocol.Results: ADA level in TBM in compare to non-TBM was more and mean ADA level of TBM, AM and PM are 26.423±3.8, 2.602±0.5 and 6.29±0.3 respectively. There are highly significant differences between the TBM and non-TBM groups and also in compare with individual groups.Conclusions: CSF ADA levels are elevated in the TBM cases as compared to the non-TBM - meningitis cases. Results are statistically significant. It is a simple and inexpensive diagnostic adjunctive test in the rapid and early diagnosis of TBM.

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

AimsTuberculous 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...

Adenosine deaminase, an aid in the diagnosis of tubercular meningitis – hospital based study

Introduction: Tubercular meningitis (TBM) is the most prevalent and most grave form of extrapulmonary tuberculosis. It is associated with high mortality rate. The confounding factor for this is the delay in diagnosing the disease and initiation of treatment. The present study aims to look for the diagnostic utility of ADA estimations in Tubercular meningitis patients. Materials and Methods: For this study the patients with the signs and symptoms of meningitis and attending our hospital within a st ipulated period of one year approximately, were taken as subjects. As per the accepted criteria, the patients were segregated into two broad groups: tubercular meningitis cases and nontubercular meningitis cases. CSF specimens were collected and ADA levels were estimated on semiautoanalyser in the laboratory. Results: Out of 31 patients of tubercular meningitis, 27 showed ADA levels above 10 U/L while 2 showed lower values. On the other hand 32 cases of non- tubercular meningitis showed ADA levels below 10 U/L and 4 showed higher values, thereby supporting the fact that ADA evaluation in CSF is of substantial value in diagnosing TBM. It also illustrious that if CSF ADA value of 10 U/L is taken as bench mark then the sensitivity for diagnosing TBM is 93.10% and specificity is 88.87% which is fairly good. Conclusion: Therefore, just by evaluating CSF ADA levels we can diagnose the TBM cases with respectably good sensitivity and high specificity and consuming least time and resources. Therefore, ADA estimation is a valuable adjunct to routine investigations in diagnosis of TBM. Keywords: Tubercular Meningitis (TBM), Cerebrospinal fluid (CSF), Adenosine Deaminase (ADA).

Clinical study of meningitis in children and role of adenosine deaminase in differentiating tubercular from non-tubercular meningitis

Background: In diseases where cell mediated immunity plays an important role like in tuberculosis, CSF (Cerebrospinal fluid) adenosine deaminase (ADA) activity is increased. Hence, this testing is done especially among children with suspected tubercular meningitis. The objective of this was to study role of Adenosine Deaminase in differentiating tubercular from non-tubercular meningitis.Methods: This was a hospital based cross sectional study was carried out among 50 children of proven meningitis for a period of two years. CSF ADA levels were done for all cases. They were divided into tubercular meningitis and non-tubercular meningitis group and compared.Results: Incidence of tuberculous meningitis (TBM) was found high in the age group 5-8 years. Male:female ratio was 2.3:1. Fever was present in all cases followed by vomiting and neck rigidity. CSF AFB was positive in 3 cases (6%). Neuroimaging was done in all cases in which 3 patients had basal exudate in which 2 patients had TBM and 1 patient was Non-TBM. 3 patients had hydrocephalus in MRI in which 2 had TBM diagnosed and 1 had non-TBM. As per ADA levels, 10 were diagnosed as TBM out of which 8 patients had ADA level ≥10 IU/L and 2 had ADA level &lt;10 IU/L which was missed by ADA and later confirmed by other modalities.Conclusions: It was concluded that if ADA level in CSF is ≥10IU/l the diagnosis of TBM should be considered.