Role of Oxidative Stress in Tuberculous Meningitis: a Clinico-Radiological Correlation.

Central nervous system infection may be associated with oxidative stress and may influence clinical severity and outcome. We report oxidative stress markers in the patients with tuberculous meningitis (TBM) and correlate these with clinico-radiological severity and outcome. Fifty-six patients with TBM diagnosed on the basis of clinical, cerebrospinal fluid (CSF), and magnetic resonance (MRI) were included. Plasma glutathione (GSH), total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured in the patients and 55 matched healthy controls. Hospital death was noted. Disabilities at 3 and 6 months were categorized using the modified Rankin Scale (mRS) as poor (mRS > 2) or good (mRS ≤ 2). The patients had lower levels of GSH (1.49 ± 0.49 vs 2.57 ± 0.39 mg/dL, p Ë‚ 0.001) and TAC (0.25 ± 0.17 vs 2.20 ± 0.31 mmol Trolox Eq/L, p Ë‚ 0.001), and higher level of MDA (6.61 ± 1.72 vs 3.09 ± 0.38 nmol/mL, p < 0.001) compared to controls. Total antioxidant capacity correlated with cranial nerve palsy and CSF pleocytosis. Patients with tuberculoma had lower GSH compared to those without. Six patients died in the hospital, and they had lower GSH (p < 0.01) and TAC (p = 0.02) levels compared to those who survived. Thirty-one and 36 patients had a good outcome at 3 and 6 months respectively. The patients with good outcome had higher GSH level.

Hypothalamic and pituitary dysfunction is common in tubercular meningitis: A prospective study from a tertiary care center in Northern India.

INTRODUCTION: Current literature is poor with respect to well conducted prospective studies of hypothalamic pituitary axis (HPA) dysfunction in tubercular meningitis (TBM). As hormonal deficiencies are associated with poor clinical outcome in various neurological and non-neurological disorders, we prospectively evaluated the hypothalamic pituitary axis (HPA) dysfunction in TBM. PATIENTS AND METHODS: Present study included newly diagnosed drug naive TBM patients (n = 63) at a tertiary care centre in Northern India. All patients underwent detailed clinical, radiological evaluation (Gadolinium enhanced magnetic resonance imaging of brain) and HPA hormonal profiles (electrochemiluminescence assay) both at initial presentation and at six month follow up. All the data was recorded on a predesigned proforma. RESULTS: 77.8% patients had definite and 22.2% had highly probable TBM. 84.2% of patients had pituitary hormonal abnormalities at presentation. These included hyperprolactinemia (49.2%), secondary adrenal deficiency (42.9%), secondary hypogonadism (38.1%) and central hypothyroidism (9.5%). At follow up, 42.1% patients had HPA abnormalities [hyperprolactinemia (13.2%), secondary hypogonadism (15.8%), secondary adrenal deficiency (10.5%) and central hypothyroidism (10.5%)]. On multivariate logistic regression analysis, secondary hypocortisolism (Odd ratio: 4.042; 95% CI = 1.074-15.22; P = .039) was associated with poor outcome in TBM. CONCLUSION: Abnormalities of HPA are common in TBM. Patients with TBM should be evaluated for dysfunction of HPA and treated accordingly.

Progress on Diagnosis of Tuberculous Meningitis.

Central nervous system (CNS) disease caused by Mycobacterium tuberculosis (MTB) is highly devastating. Tuberculous meningitis (TBM) is the most common form of CNS tuberculosis (TB). Rapid, sensitive, and affordable diagnostic tests are not available. Ziehl-Neelsen (ZN) stain has a very low sensitivity in cases of TBM, the sensitivity rates is of about 10-20%.The detection rate can be improved by taking large volume CSF samples (>6 ml) and prolonged slide examination (30 min). Culture of MTB from the CSF is slow and insufficiently sensitive. The sensitivity is different, which varies from 36% to 81.8%. The microscopic observation drug susceptibility (MODS) assay was recommended by the World Health Organization in 2011. The sensitivity is 65%, which is more sensitive and faster than CSF smear. Commercial PCR assays were found to be insensitive at detecting MTB in CSF samples. Many research provided the value of ADA on the TBM diagnosis. Interferon-gamma release assays (IGRAs) are not recommended for diagnosis of active TB disease. Imaging is essential in diagnosis and showing complications of CNS TB. Thwaites criteria and the Lancet consensus scoring system (LCSS) were developed to improve the diagnosis of TBM. Clinicians will continue to make judgment based on clinical examination, inflammatory CSF examinations, imaging studies, and scoring systems.

Cytokines do play a role in pathogenesis of tuberculous meningitis: A prospective study from a tertiary care center in India.

BACKGROUND: Though animal studies have suggested a role for proinflammatory cytokines in pathogenesis their exact role in pathogenesis of human meningeal tuberculosis continues to be controversial with different studies yielding contradictory results. AIM AND OBJECTIVES: To study the levels of proinflammatory cytokines in serum and cerebrospinal fluid (CSF) of patients with tubercular meningitis (TBM) and to determine whether these correlate with disease severity. PATIENTS AND METHODS: Present study included 146 patients with TBM (90- Definite TBM; 56- Probable TBM), diagnosed according to criteria laid by Ahuja et al. which were modified to include CSF nucleic acid based tests. Serum (n=146) and CSF (n=140) levels of various proinflammatory cytokines (IL-1ß, IL-2, IL-6, TNF-α and IFNγ) were compared between TBM patients and healthy volunteers (n=99). These levels were correlated with various clinical, radiological and CSF parameters of TBM patients. RESULTS: Proinflammatory cytokines include cytokines which promote systemic inflammation. In current study, the serum and CSF levels of various cytokines (IL-2, IL-4, IL-6, IL-1ß, IFN-γ and TNF-α) were significantly elevated in TBM patients compared to controls. A significant correlation was found between a) Higher stage of TBM and various cytokines (except for serum IL-6 and CSF IFN-γ); b) High CSF TNF-α, IL-4 and IL-1ß with severity of hydrocephalus; c) High CSF IL1ß and IFN-γ with presence of exudates on MRI; d) Serum and CSF levels of all cytokines with poor outcome as determined by death or as defined by S and E ADL (Schwab and England activities of daily living) score or by GOS (Glasgow outcome scale) (except for interferon gamma); and e) Serum and CSF IL-4 and IL1ß with presence of infarcts on MRI brain. CONCLUSION: Proinflammatory cytokines play an important role in the pathogenesis of TBM and contribute significantly towards severity of disease.

Biomarkers of Cerebral Injury and Inflammation in Pediatric Tuberculous Meningitis.

Background: Tuberculous meningitis (TBM) leads to death or disability in half the affected individuals. Tools to assess severity and predict outcome are lacking. Neurospecific biomarkers could serve as markers of the severity and evolution of brain injury, but have not been widely explored in TBM. We examined biomarkers of neurological injury (neuromarkers) and inflammation in pediatric TBM and their association with outcome. Methods: Blood and cerebrospinal fluid (CSF) of children with TBM and hydrocephalus taken on admission and over 3 weeks were analyzed for the neuromarkers S100B, neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP), in addition to multiple inflammatory markers. Results were compared with 2 control groups: patients with (1) a fatty filum (abnormal filum terminale of the spinal cord); and (2) pulmonary tuberculosis (PTB). Imaging was conducted on admission and at 3 weeks. Outcome was assessed at 6 months. Results: Data were collected from 44 patients with TBM (cases; median age, 3.3 [min-max 0.3-13.1] years), 11 fatty filum controls (median age, 2.8 [min-max 0.8-8] years) and 9 PTB controls (median age, 3.7 [min-max 1.3-11.8] years). Seven cases (16%) died and 16 (36%) had disabilities. Neuromarkers and inflammatory markers were elevated in CSF on admission and for up to 3 weeks, but not in serum. Initial and highest concentrations in week 1 of S100B and NSE were associated with poor outcome, as were highest concentration overall and an increasing profile over time in S100B, NSE, and GFAP. Combined neuromarker concentrations increased over time in patients who died, whereas inflammatory markers decreased. Cerebral infarcts were associated with highest overall neuromarker concentrations and an increasing profile over time. Tuberculomas were associated with elevated interleukin (IL) 12p40, interferon-inducible protein 10, and monocyte chemoattractant protein 1 concentrations, whereas infarcts were associated with elevated tumor necrosis factor α, macrophage inflammatory protein 1α, IL-6, and IL-8. Conclusions: CSF neuromarkers are promising biomarkers of injury severity and are predictive of mortality. An increasing trend suggested ongoing brain injury, even though markers of inflammation declined with treatment. These findings could offer novel insight into the pathophysiology of TBM.

Adequacy of Rifampin Absorption after Jejunostomy Tube Administration.

It is not always possible to administer antituberculosis pharmacotherapy orally for reasons that may be a direct consequence of tuberculosis itself. To our knowledge, no published literature is available regarding antituberculosis drug absorption via feeding tube. We present the case of a patient with tuberculosis meningitis who required medication administration via percutaneous endoscopic jejunostomy (PEJ) tube. Blood samples were collected during the continuation phase of antituberculosis therapy, immediately before dose administration, and then at 1, 2, 4, and 6 hours after dose administration for quantification of serum rifampin concentrations. Assaying these concentrations by high-pressure liquid chromatography demonstrated a peak serum rifampin level (C(max)) of 18 µg/ml and total rifampin exposure (area under the curve from 0-6 hours [AUC(0-6)]) of 50.1 µg/ml. These are high compared with rifampin C(max) and AUC(0-6) values reported in patients after oral rifampin administration; C(max) tends to range between 4.0-10.5 µg/ml and AUC(0-6) 7.0-52.9 µg/ml after oral administration of 600 mg at steady state. Based on our patient's results, therefore, rifampin administered by PEJ tube appears to be well absorbed, with preservation of adequate C(max) and AUC values. It is worth noting that this was in the context of drug administration in the fasted state. In the absence of any published evidence of adequate absorption via jejunal feeding tube in the nonfasted state, it would seem prudent to ensure that patients are fasted when rifampin is administered via PEJ tube, just as patients are when oral rifampin is administered. This report represents the first documented evidence, to our knowledge, of adequate rifampin absorption when administered via PEJ tube and provides important reassurance for health care providers, patients, and families facing similar clinical scenarios.

Detection of Delta-like 1 ligand for the diagnosis of tuberculous meningitis: An effective and rapid diagnostic method.

OBJECTIVE: To investigate the diagnostic value of Delta-like 1 ligand (DLL1) in cerebrospinal fluid (CSF) and serum, in tuberculous meningitis (TBM). METHODS: Patients with a definite diagnosis of central nervous system infection (TBM, viral meningitis/encephalitis or bacterial meningitis) were prospectively enrolled alongside patients with intracranial metastatic tumour and patients with no diagnosis (who served as controls). DLL1 content in CSF and serum was measured quantitatively by enzyme-linked immunosorbent assay; analyses were blinded. RESULTS: A total of 173 patients were enrolled: 62 with TBM; 38 with viral meningitis/encephalitis; 26 with bacterial meningitis; 17 with intracranial metastatic tumour; 30 with no diagnosis. CSF DLL1 content was highest for TBM; there were no differences in CSF DLL1 between the other groups. Serum DLL1 content was highest for the TBM and intracranial metastatic tumour groups, with significant differences between the TBM group and the viral meningitis/encephalitis, bacterial meningitis and nondiagnosed groups. There were no differences in serum DLL1 between the viral meningitis/encephalitis, bacterial meningitis and nondiagnosed groups, or between the TBM group and the tumour group. CONCLUSION: As a new biomarker, DLL1 may be of great clinical importance in the diagnosis of TBM.

Adenosine deaminase activity in cerebrospinal fluid and serum for the diagnosis of tuberculous meningitis.

OBJECTIVE: To evaluate the usefulness of serum and CSF adenosine deaminase (ADA) activity for the diagnosis of tuberculous meningitis (TBM) from other meningitis. METHODS: We studied CSF and serum ADA activity for 83 cases of TBM, 148 of bacterial meningitis (BM), and 262 of viral or aseptic meningitis. RESULTS: The mean ADA activities (IU/L) in CSF and serum were higher in TBM (11.80 ± 2.50, 30.28 ± 7.30) than in other types of meningitis (8.52 ± 3.60, 17.90 ± 9.20 in BM; 5.26 ± 1.90, 8.56 ± 5.9 in viral or aseptic meningitis). When we accepted a serum ADA activity cut-off value of 15 IU/L for the differential diagnosis of TBM and non-TBM with ROC analysis, the sensitivity was 84% and specificity was 82%. Combining CSF (≥ 10) and serum (≥ 15) ADA activity significantly increased overall specificity from 92% to 97% for the diagnosis of TBM. CONCLUSIONS: The determination of CSF and serum ADA activity is a simple and reliable test for differentiating TBM from other types of meningitis.

Vascular endothelial growth factor in tuberculous meningitis.

Vascular endothelial growth factor (VEGF) is linked to brain edema and infarction, but there is paucity of studies correlating VEGF level with magnetic resonance imaging (MRI) changes in tuberculous meningitis (TBM). The aim of this study was to measure serum VEGF level in TBM and correlate it with clinical, laboratory, and MRI findings. Forty patients with TBM underwent cranial evaluation, cranial MRI, and MR angiography (MRA). Presence of exudates, hydrocephalous, infarction, tuberculoma, and MRA abnormalities was noted. Serum VEGF level was measured by enzyme-linked immunosorbent assay and compared in patients and controls. The VEGF level was also correlated with clinical, MRI, and MRA findings. The median age of the patients was 26.5 years. There was a trend towards higher serum VEGF level in TBM patients (100.7 ± 110.6 pg/ml) compared to the controls (60.6 ± 20.3 pg/ml). There was also a trend towards higher VEGF level in patients with shorter duration of illness (127.5 ± 152.4 pg/ml vs 76.5 ± 40.9 pg/ml), MRI evidence of infarction (131.4 ± 150.7 pg/ml vs. 73.0 ± 41.4 pg/ml), and paradoxical response (122.3 ± 157.6 pg/ml vs. 88.8 ± 50.8 pg/ml). Five patients died, and death was not related to VEGF level. It can be concluded that serum VEGF level in TBM patients is insignificantly higher in those with shorter duration of illness and infarction.

Neurological complications of miliary tuberculosis.

INTRODUCTION: The symptomatic central nervous system involvement is often seen in patients with miliary tuberculosis. MATERIALS AND METHODS: In this study, we evaluated 60 consecutive miliary tuberculosis patients, who presented with some neurological manifestations. Evaluation included neurological examination, a battery of blood tests, HIV serology, sputum examination, cerebrospinal fluid (CSF) examination along with imaging of the brain and spinal cord. The patients were followed up after completion of 6 months of antituberculous treatment. RESULTS: Patients ranged between 14 and 53 years in age. Three patients tested HIV positive. Forty-eight (80%) patients had tuberculous meningitis. In 12 (20%) patients, the CSF examination was normal. In 27 patients with tuberculous meningitis, neuroimaging revealed intracerebral tuberculoma. Fourteen patients showed multiple tuberculomas, while 7 had a solitary tuberculoma. In six patients, the tuberculomas were small and numerous. In two patients, neuroimaging revealed a spinal tuberculoma. For three patients with tuberculous brain masses, the CSF was normal. Nine (15%) patients presented with myelopathy. Three patients exhibited Pott's paraplegia. Three patients had transverse myelitis (with normal neuroimaging). In three patients, the spinal MRI revealed an intramedullary tuberculoma. On follow-up, 15 (25%) patients expired. Thirty-one (52%) patients showed significant improvement. Eight patients (13%) showed nil or partial recovery. Six of the patients with no improvement developed vision loss. Six (10%) patients were lost to follow up. CONCLUSION: A variety of neurological complications were noted in military tuberculosis patients, tuberculous meningitis and cerebral tuberculomas being the most frequent complications. However, a majority of patients improved following antituberculous treatment.

Vascular endothelial growth factor as a marker of disease activity in neurotuberculosis.

Vascular endothelial growth factor (VEGF) is a potent angiogenesis mediator. Scant reports are available defining the role of VEGF in active and inactive tubercular meningitis (TBM) with no studies on brain tuberculoma. We quantified VEGF levels by enzyme linked immunoassay (ELISA) in cerebrospinal fluid (CSF) and serum in 20 cases each with active and inactive TBM as well as 22 cases of intraparenchymal tuberculoma. VEGF expression and microvessel angiogenesis quantification was done in 7 cases where tuberculomas were excised. Significantly increased VEGF levels in CSF were found in active TBM cases (106.0+/-50.0 pg/ml) compared to inactive TBM cases (14.7+/-10.0 pg/ml) (p<0.001). Mean serum VEGF levels in active TBM, inactive TBM and tuberculoma were 694.93+/-820.66 pg/ml, 499.61+/-238.33 pg/ml and 541.0+/-389.0 pg/ml, respectively. Immunohistochemical staining of excised tuberculoma demonstrated high expression of VEGF in granulomatous areas with intense positivity in inflammatory mononuclear cells, Langhan's giant cells as well as reactive astrocytes and fibrocytes. A strong positive correlation was observed between microvessel density and VEGF expression. Serial decrease in serum VEGF levels was observed with increasing duration of therapy in tuberculoma. We conclude that increased CSF and serum VEGF levels are a measure of activity of the disease in neurotuberculosis and its gradual decrease over a period of time is probably an indicator of therapeutic response.

Pretreatment intracerebral and peripheral blood immune responses in Vietnamese adults with tuberculous meningitis: diagnostic value and relationship to disease severity and outcome.

Tuberculous meningitis (TBM) is the most devastating form of tuberculosis. Both intracerebral and peripheral blood immune responses may be relevant to pathogenesis, diagnosis, and outcome. In this study, the relationship between pretreatment host response, disease phenotype, and outcome in Vietnamese adults with TBM was examined. Before treatment, peripheral blood IFN-gamma ELISPOT responses to the Mycobacterium tuberculosis Ags ESAT-6, CFP-10, and purified protein derivative (PPD) were a poor diagnostic predictor of TBM. Cerebrospinal fluid IL-6 concentrations at presentation were independently associated with severe disease presentation, suggesting an immunological correlate of neurological damage before treatment. Surprisingly however, elevated cerebrospinal fluid inflammatory cytokines were not associated with death or disability in HIV-negative TBM patients at presentation. HIV coinfection attenuated multiple cerebrospinal fluid inflammatory indices. Low cerebrospinal fluid IFN-gamma concentrations were independently associated with death in HIV-positive TBM patients, implying that IFN-gamma contributes to immunity and survival. Collectively, these results reveal the effect of HIV coinfection on the pathogenesis of TBM and suggest that intracerebral immune responses, at least in HIV-negative cases, may not be as intimately associated with disease outcome as previously thought.

Expression of vascular endothelial growth factor in tuberculous meningitis.

The pathogenesis of tuberculous meningitis is still unclear. Recently, vascular endothelial growth factor (VEGF) was found to be associated with inflammatory diseases and we found the increased serum level of VEGF in pulmonary tuberculosis. We hypothesized that VEGF might be associated with the pathogenesis of tuberculous meningitis and measured serum and cerebrospinal fluid (CSF) levels of VEGF in 28 patients with tuberculous meningitis and 31 non-tuberculous infectious meningitis patients (13 bacterial meningitis patients, eight fungal meningitis patients and 10 patients with viral meningitis) before therapy. We examined the CSF VEGF levels 3 months after in 12 tuberculous meningitis patients. The serum and CSF levels of VEGF were significantly higher in tuberculous meningitis than in other meningitis. The decrease in titer of CSF VEGF paralleled the clinical improvement of tuberculous meningitis. Immunohistochemical staining of autopsied brains demonstrated the presence of VEGF in the inflammatory mononuclear cells of the dense fibroconnective tissue both in the subarachnoid space and surrounding the vasculitis lesion. We found the expression of VEGF in tuberculous meningitis and think that VEGF reflects its activity.

Diagnosis of tuberculous meningitis by detection of antigen and antibodies in CSF and sera.

OBJECTIVE: To evaluate diagnostic potential of three immunological tests, namely, detection of H37Rv antigen of M. Tuberculosis in CSF, detection of antibodies (IgG) against H37Rv in CSF and detection of antibodies (IgG) against H37Rv in serum for diagnosis of tuberculous meningitis in children. SUBJECTS: 50 children diagnosed as patients of tuberculous meningitis were included as cases and 48 children with CNS diseases of nontubercular etiology [pyogenic meningitis (n = 31), encephalitis (n = 10), seizure disorder of unknown etiology (n = 5), brain tumor (n = 2)] served as controls. METHODS: H37Rv antigen of M. tuberculosis was detected in CSF by Dot ELISA, and antibodies (IgG) against H37Rv in CSF and serum were detected by Plate ELISA. RESULTS: Detection of H37Rv antigen in CSF was the most sensitive (90%) and specific (95.83%) with positive and negative predictive values of 95.74% and 90.19%, respectively, followed by detection of antibodies in CSF (sensitivity-74%, specificity-89.58%, positive predictive value-88.10%, negative predictive value-76.78%). Detection of antibodies in serum had low sensitivity (50%), specificity (91.67%), positive predictive value (86.21%) and negative predictive value (63.76%). CONCLUSIONS: Detection of antigen in CSF is a rapid, sensitive and specific test for diagnosis of tuberculous meningitis in children. Detection of antibody in CSF may be useful in some cases but needs further evaluation. Detection of antibody in serum does not appear to be useful for diagnosis of tuberculous meningitis.

Multiple intracranial tuberculomas with atypical response to tuberculostatic chemotherapy: literature review and a case report.

Approximately 34 cases of intracranial tuberculomas with paradoxical response to antituberculous chemotherapy have been documented worldwide. In most of the previously reported cases an associated tuberculous meningitis was reported. The majority of these patients were children or young adults, who had inoperable intracranial tuberculomas located in high risk regions that developed a few weeks or months after the start of an appropriate chemotherapy. Fifty-three percent of the patients recovered completely, 37% improved with mild neurological defects and 10% died. It is interesting that these intracranial tuberculomas developed or enlarged at a stage when systemic tuberculosis was being treated successfully. A recent experience with these potentially curable tumors of the central nervous system is reported. The literature is reviewed, and diagnostic and therapeutic considerations are discussed. The possible immunological mechanisms of this phenomenon are analyzed. In conclusion, patients who are suspected to have a CNS-tuberculosis should receive a prolonged (12-30 months) course of effective antituberculous therapy. The evidence of new intracranial tuberculomas or the expansion of older existing lesions does not indicate the need to change the antituberculous drug program. In such cases systemic dexamethasone as adjuvant therapy for 4 to 8 weeks is worthwhile and effective. Surgical intervention may be necessary in situations with acute complications of CNS tuberculosis, such as shunting procedures for the treatment of hydrocephalus. When the diagnosis is not ensured and there is no response to therapy within 8 weeks, a stereotactic biopsy on a suspected tuberculoma could be performed. If the largest lesion is not located in high risk deep regions of the brain, it could be totally removed surgically. With this combined management, a satisfactory outcome can be obtained in the majority of cases.

Multiple intracranial tuberculomas with atypical response to tuberculostatic chemotherapy: literature review and a case report.

Approximately 34 cases of intracranial tuberculomas with paradoxical response to antituberculous chemotherapy have been documented worldwide. In most of the previously reported cases of this entity an associated tuberculous meningitis has been reported. The majority of these patients were children or young adults, who had inoperably located intracranial tuberculomas in high risk regions developing a few weeks or months after the start of appropriate chemotherapy. 53% of them recovered completely, 37% improved with mild neurological deficits and 10% died. It is interesting that these intracranial tuberculomas developed or enlarged at a stage when systemic tuberculosis was being treated successfully. We report our recent experience with these potentially curable tumours of the central nervous system. The literature is reviewed and diagnostic and therapeutic considerations are discussed. The possible immunological mechanisms of this phenomenon are analysed. In conclusion, patients, who are suspected to be suffering from CNS-tuberculosis should receive a prolonged (12-30 months) course of effective antituberculous therapy. Evidence of new intracranial tuberculomas or the expansion of older existing lesions require no change in the antituberculous drug programme. In such cases systemic dexamethasone as adjuvant therapy for 4 to 8 weeks is worthwhile and effective. Surgical intervention may be necessary in situations with acute complications of CNS tuberculosis such as shunting procedures for the treatment of hydrocephalus. When the diagnosis is not firm and there is no response to therapy within 8 weeks, a stereotactic biopsy of a suspected tuberculoma should be performed. If the largest lesion is not located in high risk deep regions of the brain, it should be total removed surgically. With this combined management, a satisfactory outcome can be obtained in the majority of cases.

Detection of metabolites by frequency-pulsed electron capture gas-liquid chromatography in serum and cerebrospinal fluid of a patient with Nocardia infection.

Serum (SR) and cerebrospinal fluid (CSF) from a patient suspected of having tuberculous meningitis were submitted to our laboratory for analysis by frequency-pulsed electron capture gas-liquid chromatography (FPEC GLC). The samples were tested for the presence of carboxylic acids, alcohols, hydroxy acids, and amines by methods described previously (C. C. Alley, J. B. Brooks, and D. S. Kellogg, Jr., J. Clin. Microbiol. 9:97-102, 1977; J. B. Brooks, C. C. Alley, and J. A. Liddle, Anal. Chem. 46:1930-1934, 1974; J. B. Brooks, D. S. Kellogg, Jr., M. E. Shepherd, and C. C. Alley, J. Clin. Microbiol. 11:45-51, 1980; J. B. Brooks, D. S. Kellogg, Jr., M. E. Shepherd, and C. C. Alley, J. Clin. Microbiol. 11:52-58, 1980). The results were different from previous FPEC GLC profiles of SR and CSF from patients with known tuberculous meningitis. Both the SR and CSF contained several unidentified compounds that were not previously detected in tuberculous meningitis or any of our other studies of body fluids. Nocardia brasiliensis was later isolated from the patient. Detection of these metabolites by FPEC GLC could prove to be useful for rapid diagnosis of Nocardia disease, and their identification will provide a better understanding of metabolites produced by Nocardia sp. in vivo.

The simultaneous determination of cerebrospinal fluid and plasma adenosine deaminase activity as a diagnostic aid in tuberculous meningitis.

The simultaneous determination of cerebrospinal fluid (CSF) and plasma adenosine deaminase (ADA) activity was evaluated as a diagnostic aid in tuberculous meningitis (TBM). CSF and plasma ADA activity were determined in four groups of patients: (i) a 'no meningitis' group of 174 children investigated for possible meningitis, but found to be uninfected; (ii) an aseptic meningitis group of 40 children; (iii) a bacterial meningitis group of 31 children; and (iv) a TBM group of 27 patients (24 children and 3 adults). CSF ADA alone was determined in a further 23 children with aseptic meningitis, 19 with bacterial meningitis and 13 children and 7 adults with TBM. Both the CSF/plasma ADA ratio and the absolute CSF ADA activity were raised in TBM (mean values 0,24 and 12,61 U/I respectively) and bacterial meningitis (mean values 0,59 and 15,43 U/I respectively), but not in the aseptic meningitis group (mean values 0,06 and 2,00 U/I) or the 'no meningitis' group (mean values 0,04 and 1,51 U/I). Both values will distinguish TBM from aseptic meningitis, but do not appear to hold any marked advantages over conventional CSF criteria in the diagnosis of TBM.