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

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

Xpert MTB/RIF ultra for the diagnosis of tuberculous meningitis: A diagnostic accuracy study from India.

SETTING: Studies evaluating Xpert MTB/RIF Ultra assay (Xpert Ultra) for diagnosing tuberculous meningitis (TBM) are scarce and have reported contrasting results in comparison to Xpert MTB/RIF assay (Xpert). OBJECTIVE: To evaluate the performance of Xpert Ultra in diagnosing TBM and compare it with Xpert and multiplex polymerase chain reaction (MPCR). DESIGN: Xpert Ultra was performed on 244 cerebrospinal fluid (CSF) samples: 56 definite TBM, 148 probable TBM and 40 non-TBM controls. 105/244 CSF samples were also subjected to Xpert and MPCR (IS6110, MPB64, protein B). RESULTS: The overall sensitivity of Xpert Ultra in diagnosing TBM from 244 CSF samples was 72.05% (96.42% - definite TBM, 62.83% - probable TBM) with a specificity of 100%. 18 (12.24%) cases [8 definite TBM, 10 probable TBM] were reported rifampicin resistant (RifR) by Xpert Ultra and confirmed by rpoB sequencing. 60 (40.81%) cases [9 definite TBM, 51 probable TBM] were reported rifampicin indeterminate (RifI) by Xpert Ultra (all trace category), out of which 45 [8 definite, 37 probable) were rifampicin susceptible (RifS) and 5 probable cases were RifR on rpoB sequencing. Out of 105 CSF samples subjected to all three techniques, TBM was diagnosed in 70.66%, 28% and 88% by Xpert Ultra, Xpert and MPCR, respectively. CONCLUSION: Xpert Ultra detected TBM with higher sensitivity than Xpert. Among trace category, constituting 40% of TBM cases, rpoB gene sequencing confirmed 5 RifR cases.

18FDG-PET is sensitive tool for detection of extracranial tuberculous foci in central nervous system tuberculosis - Preliminary observations from a tertiary care center in northern India.

PURPOSE: To study the role of 18FDG- PET (Flourodeoxyglucose positron emission tomography) in a) determining the extent of cranial and extra-cranial disease and b) diagnosis as well as prognosis of CNS TB (central nervous system tuberculosis) including TBM (tuberculous meningitis). PATIENTS AND METHODS: This prospective observational study (n = 70) was carried out at a tertiary care institute in Northern India from 1.1.2017 to 30.6.2018. Diagnosis of TBM was made according to modified Ahuja's criteria. All patients were evaluated in detail and treated as per standard guidelines. All patients underwent 18FDG-PET scanning of brain and whole body at baseline. RESULTS: Mean age was 35.2 ±â€¯14.8 years. There were 37 men. Majority of patients (n = 47; 67.1%) were below 40 years of age. 43 (61.4%) patients were in stage II TBM. The mean duration of illness was 77 ±â€¯101.9 days. Majority of patients presented with fever (94.3%), headache (90%) and vomiting (84.3%). MRI was abnormal at baseline in 67 (95.7%) of patients, most common abnormalities being meningeal enhancement (68.6%) and tuberculomas (57.1%). PET was abnormal in 66 (95.7%) of patients. All these patients had either lung lesions (n = 62, 88.6%) or lymphadenopathy (n = 61; 87.1%). 18FDG-PET revealed evidence of brain lesions in 52 (74.3%) patients. It revealed vertebral involvement in 19 (27.1%) and genitourinary lesions in 9 (12.9%) patients. PET evidence of lymphadenopathy correlated significantly (p = .04) with good outcome in CNS TB. Conclusion 18FDG-PET does seem to have a promising role in initial evaluation of patients with CNS TB.