Search

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., Competing Interests: None

Purpose: Tubercular meningitis (TBM) has the propensity to cause secondary vasculitis through various mechanisms leading to development of cerebrovascular complications. These vascular involvements can be detected by vessel wall imaging (VWI). In this study, we aimed to study detailed findings of vessel wall imaging in cases of tubercular meningitis., Methods: All consecutive patients of suspected tubercular meningitis in whom diagnosis of TBM could be made according to diagnostic criteria given by Ahuja et al. were included in the study. High-resolution MR VWI and time of flight (TOF) magnetic resonance angiography (MRA) were done along with routine MRI sequences. Arteries up to second-order branches were studied, and statistical analyses were done with respect to stage of tubercular meningitis, infarctions and TOF MRA findings., Results: Out of all 101 cases of TBM, infarctions were found in 49 cases (48.5%), and vessel wall enhancement was seen in 67 cases (66.3%). With increasing severity of disease, more severe vascular involvement was seen on VWI. There was significant association between enhancement of individual arteries and infarctions in their territories. VWI had better sensitivity than the MRA, while MRA had better specificity than VWI for detection of vascular complications., Conclusion: Tubercular vasculitis can be detected by VWI in the form of nodular or smooth segmental enhancement of vessel wall with or without stenosis. Incorporation of VWI in routine MR imaging can play a greater role in early detection and management of cerebrovascular complications which can help to improve prognosis of the disease., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

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 ± 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 ± 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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

It has been approximately five decades since Dastur et al., published their seminal work on pathology of tuberculous meningitis (TBM). Though most of their findings find relevance in today's era, there is an important difference; these findings can now be replicated during life using modern day technology. In this article, we review the seminal words of Professor Dastur and colleagues, analyse their findings, interpret how these revolutionized our understanding of TBM and highlight their relevance in today's era. We also discuss challenges in the management of TBM, which we continue to face today and the various options required to overcome these challenges., Competing Interests: Authors declare that they do not have any conflict of interest. They do not have any source of funding

Objectives: The predictors of poor outcome in tuberculous meningitis (TBM) remain to be delineated. We determined role of various clinical, radiological and cerebrospinal fluid (CSF) parameters in prediction of outcome in TBM., Patients and Methods: Current study was a prospective observational study including 209 patients of TBM. All patients underwent detailed evaluation including Gadolinium enhanced Magnetic resonance imaging (GdMRI) of brain as well as tests to detect evidence of tuberculosis elsewhere in body. They also underwent GdMRI at three and nine month follow up. All patients received treatment as per standard guidelines., Results: Mean age was 30.4±13.8years. 139 (66.5%) patients had definite TBM while 70 (34.5%) had highly probable TBM. 53 (25.4%) patients died. On univariate analysis, longer duration of illness, altered sensorium, stage III TBM, hydrocephalus and exudates correlated with poor outcome. On multivariate analysis presence of hydrocephalus (p=0.003; OR=3.2; 95% CI=1.5-6.7) and stage III TBM (p<0.0001; OR=8.7; 95% CI=3.7-20.2) correlated with higher risk of mortality. In addition, there was significant positive association between presence of hydrocephalus (p=0.05; OR=2.2; 95% CI=0.97-5.1), stage III TBM (p<0.0001; OR=28; 95% CI=4.9-158) and presence of altered sensorium (p=0.05; OR=22; 95% CI=0.99-4.8) with either death or survival with severe disability., Conclusions: It is possible to prognosticate TBM using a combination of clinical and radiological. The duration of illness (65.9±92days) before diagnosis of TBM continues to be unacceptably long and this stresses on need to educate primary care physicians about TBM. Future studies where intensity and duration of treatment is guided by these cues may help in sorting out some of the most difficult questions in TBM, namely duration of antitubercular therapy as well as dose and duration of steroid therapy etc., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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-1β, 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-1β, 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-1β with severity of hydrocephalus; c) High CSF IL1β 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 IL1β 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., (Copyright © 2017 Elsevier B.V. All rights reserved.)