Tuberculous Meningitis Patients Research Articles

Tuberculostearic acid, a potential parameter for scoring system construction for tuberculous meningitis diagnosis.

This study aimed to validate the value of tuberculostearic acid (TBSA) whether it could implicate the existence of Mycobacterium tuberculosis (Mtb) and assist for the clinical diagnosis of tuberculous meningitis (TBM). The patient's cerebrospinal fluid (CSF) specimen was collected through the lumbar puncture and detected for TBSA with gas chromatography/mass spectrometry. At the same time, gold standard tests, i.e., CSF direct culture, CSF smear microscopy, or nucleic acid amplification tests, for Mtb were routinely performed. Furthermore, we evaluated all patients by the Lancet consensus scoring system, which classifies suspected patients to "Definite (depend on gold standard results only)," "Probable (>10 pts without imaging or >12 pts with imaging information)," "Possible (6-9 pts without imaging or 6-11 pts with imaging)," and "Not (<6 pts or with alternative diagnoses)" TBM. In total, 140 patients were admitted for our study included 27 confirmed TBM patients and 50 TBSA-positive patients. Sensitivity (0.7407, confidence interval [CI] 95%: 0.5372-0.8889) and specificity (0.7345, CI 95%: 0.6432-0.8132) were calculated. The Lancet consensus scoring system was also applied to evaluate the possibility of TBM in suspected patients, finding that TBSA-positive patients showed a similar grouping distribution as the definite TBM patients. Our study implicates that the prospective utilization of TBSA is worth combining into a scoring system for characterizing the features of Mtb, showing a great potential of TBM diagnosis by TBSA in future.

Predictors of Infarction in Tuberculous Meningitis in Indian Patients

BackgroundStroke is a devastating complication of tuberculous meningitis (TBM) and is an important determinant of its outcome. We propose a model which would help to predict development of infarction or cerebrovascular events in patients of TBM. MethodsA prospective study with n=129 patients of TBM were evaluated for predictors and outcomes of stroke. A diagnostic grid was formulated with clinical, laboratory and radiology as parameters to predict the vascular outcomes. All patients were followed up for mortality and disability on the basis of modified rankin score (mRS). MRI & CSF cytokines TNF–alpha, IFN- gamma & IL-6,8, 10 were measured at baseline and 3 months. The diagnosis of TBM included definite, probable & possible types and stage I & II with early and late onset of symptoms respectively. ResultsThe mortality was 16.2% and 19.4% of all patients developed stroke. The mean GCS, barthel index and mRS at admission was 57.03± 9.5,10.2±2.3 & 3.3±0.03 respectively mild to moderate infection and functional limitation. Barthel index (BI) happened to be a strong predictor [F=32.6, p=0.001, t=15.5, βeta coefficient =0.002] followed by biomarker TNF-α [F=18.9, p=0.02, t= -2.07, βeta coefficient=-0.04]. N=25 patients developed stroke with TNF-α, IL-6, IFN -γ showing statistically significant increase in all the stroke affected TBM (95% CI; 4.5 to 1.2; p=0.003). At 3 months, it was observed that mRS was statistically significant between stage I & II (95% CI; 5.4 to 2.1; p=0.04). ConclusionsOur data revealed that 19.4% patients developed vascular events during the hospital stay or follow up. We recruited late onset TBM as compared to early onset. BI, TNF-α, IL6 are most potent predictors of stroke post TBM.

Clinical analysis of 103 cases of tuberculous meningitis complicated with hyponatremia in adults.

Tuberculous meningitis (TBM) is a common infection of the central nervous system. TBM with hyponatremia is very common. If hyponatremia is not treated properly, it might affect the outcome of TBM patients. We included 226 patients diagnosed with TBM who were admitted from August 2010 to August 2015 and retrospectively analyzed the clinical data of patients with and without hyponatremia. In total, 45.6% (103/226) patients had hyponatremia and 54.4% (123/226) patients did not have hyponatremia. Serum sodium and severity of TBM were independent prediction factors of poor outcomes in TBM. The prognosis of patients with hyponatremia was worse than that of patients without hyponatremia. The mortality was 3.9% (4/103) in the hyponatremia group, while 0% (0/123) in the non-hyponatremia group. The degree of hyponatremia was related to imaging, cerebrospinal fluid (CSF) cell count and protein, severity of TBM, time to correct hyponatremia, and prognosis. We analyzed the causes of hyponatremia and found syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was the most common cause (77.7%, 80/103), followed by cerebral salt wasting (CSW) (17.5%, 18/103). Comparing SIADH and CSW, there was a significant difference in mean blood pressure, albumin, and hematocrit, and no significant difference in demographic characteristics, imaging, CSF cell count and protein, severity, occurrence and correction time of hyponatremia, or prognosis. TBM with hyponatremia was dominated by moderate hyponatremia, which often manifested as SIADH. The more severe hyponatremia was, the longer the correction time of hyponatremia, which will affect the prognosis of TBM patients.

Safety and efficacy of high-dose rifampicin in the management of tuberculosis meningitis: Systematic review and meta-analysis.

Mycobacterium tuberculosis (TB) practically affects any part of the body, but when the brain is involved, the consequences are devastating. Tuberculous meningitis (TBM) is the most severe form of drug-susceptible TB, with an estimation of more than 100,000 new cases occurring every year and a high mortality rate globally. The treatment strategy is based on pulmonary TB (PTB) management regimens which consider rifampicin as the backbone. Optimal treatment regimens for PTB may not be the most effective option for TBM due to difference in TB drug penetration across the blood-cerebrospinal fluid barrier, hence the need for other treatment options. This study aims to review the efficacy and safety of higher doses of rifampicin (>10 mg/kg) compared to 10 mg/kg rifampicin as part of standard therapy for the treatment of TBM. A systematic review and meta-analysis was conducted to assess the efficacy and safety of high-dose rifampicin for TBM. A search was done on PubMed, Google Scholar, and Cochrane library databases without publication date limit to identify studies providing data on the use of high-dose rifampicin for the treatment of TBM. Titles and abstracts were screened for relevance by three reviewers. Two reviewers used a predefined checklist on the inclusion criteria to assess full text for their eligibility in the review. A heterogeneity test was conducted to assess the variations among study outcomes. The risk ratio (RR) with a 95% confidence interval (CI) was calculated as a measure of intervention effect. The study is registered on PROSPERO and the registration number is CRD42020212737. Five Phase 2 trials with a total of 1028 participants were included in this meta-analysis. All the five trials were used to analyze safety data, which found that there was no significant increase in the risk of Grade 3-5 adverse events in high-dose rifampicin (RR = 1.05; 95% CI = 0.95-1.18). Only four of them were included for the analysis of efficacy. The findings indicated that exposure to high-dose rifampicin is not associated with a reduced risk of mortality (RR = 0.95; 95% CI = 0.78-1.16). It can be concluded from this meta-analysis that there is no significant relation of high-dose rifampicin with adverse events and the reduction of mortality in TBM patients. Whether in future optimized TBM treatment regimen will include high-dose rifampicin or not should be determined by a large-scale clinical trial.

Tuberculous Meningitis: Impact of Timing of Treatment Initiation on Mortality.

We conducted a retrospective cross-sectional study of adult hospitalized patients with confirmed tuberculous meningitis to determine the impact of the timing of treatment initiation on mortality. The mortality of tuberculous meningitis patients was high and was associated with delay in initiation of treatment, older age, HIV infection, and higher disease severity at admission.

CLINICAL SPECTRUM AND OUTCOME OF PATIENTS WITH TUBERCULOUS MENINGITIS AT A TERTIARY CARE HOSPITAL OF PAKISTAN

Objective: To assess the clinical profile and outcome of patients admitted with the diagnosis of tuberculous meningitis (TBM) at neurology unit of a tertiary care teaching hospital of Pakistan.&#x0D; Study Design: Cross-sectional study.&#x0D; Place and Duration of Study: Neurology department, Pak Emirates Military Hospital Rawalpindi, from Dec 2018 to Jun 2019.&#x0D; Methodology: This study was conducted on 69 patients of tuberculous meningitis admitted. Demographic profile included age, gender, and the symptoms with which the patient presented. Neurological complications were also documented among the target population. Outcomes included recovery, shifting to intensive care unit and death.&#x0D; Results: A total of 69 patients admitted in neurology ward diagnosed and managed as tuberculous meningitis in the study duration time. Male to female ratio was 1.4:1. Mean age of patients diagnosed with tuberculous meningitis in our study was 34.23 ± 3.915 years. Most of the patients presented with the fever followed by headache. Out of 69 patients, 41 (59.4%) recovered, 22 (31.9%) were shifted to the intensive care unit and 6 (8.7%) died. Seizures were the commonest neurological complication faced by the patients followed by cranial nerve palsies.&#x0D; Conclusion: Fever and headache were common symptoms with which patients of tuberculous meningitis presented in our study population. Most of the patients recovered in the ward but a high percentage required intensive care unit admission as well. Seizures and cranial nerve palsies were commonly experienced complication by patients included in our study.

Clinical features and management strategies of Meningitis in adult patients: A hospital based study from Kuwait

Introduction: High mortality rate of meningitis has been reported in Kuwait, however, limited data is available describing this disease in adult patients. With this background, we conducted a prospective study on patients admitted with meningitis, with an objective to describe the risk factors, clinical presentation, disease course and outcome; focus given on diagnostic problems and consequent management difficulties.&#x0D; Methods: Our team diagnosed, managed and documented hospital records of patients (n=44) admitted with suspected meningitis at a referral hospital during 2010-12. Detailed information was collected regarding clinical presentation, CSF analysis, treatment, hospital course and outcome as per Glasgow Outcome Scale (GOS). Results: Bacterial, viral, and tuberculosis (TB) meningitis were seen in 22.8%, 52.3%, and 15.9% of patients. Clinical features of our cohort were consistent with available literature. Positive identification of organism by culture, gram stain, or antigen test was possible in only 6 patients i.e. Streptococcus pneumonae-(n=3), Streptococcus agalactiae-(n=2), Neisseria meningitides-(n=1). CSF polymerase chain reaction was detected positive for Enterovirus RNA, and Herpes simplex virus DNA for one patient each. Empirical antimicrobial treatment directed against common causative organisms was the mainstay of management of bacterial meningitis. Viral meningitis was managed symptomatically. TB meningitis patients were administered anti-tubercular treatment. As per GOS, 38(85.4%) patients recovered with no neurological deficit. Six patients recovered with mild to moderate deficit. Conclusion: Low positive culture rates and inability to identify pathogens have been a diagnostic challenge faced by our team. Strong clinical suspicion, early empiric antibiotic and dexamethasone therapy perhaps contributed to very good recovery in our study.&#x0D; Keywords: Meningitis, Kuwait, Clinical Suspicion, Antibiotic, Dexamethasone

Direct economic burden of patients with tuberculous meningitis in western China.

To estimate the direct economic burden of tuberculous meningitis (TBM) in China for the first time. Patients who were first diagnosed with TBM from December 2015 to December 2018 in Western China Hospital were enrolled. We retrospectively collected data on demographic and clinical features, resource utilization, costs, and long-term outcomes. The patients were followed up for 15-53months. We performed a cost-of-illness study and analyzed the cost contributors with a generalized linear model. In total, the cases of 154 TBM patients (95 males, 59 females, aged 14-82years) were reviewed. The average total direct cost per person was USD (United States dollars) 9,484 (range 1,822-67,285), with a mean direct medical cost of USD 8,901 (range 1,189-67,049). The average inpatient cost and drug cost after discharge were USD 6,837 (range 845-52,921) and USD 1,967 (range 0-60,423), respectively. The mean direct nonmedical cost was USD 583 (range 33-3,817), which accounted for 6.2% of the total direct cost. The average length of stay (LOS) in hospital was 25.0days (range 6-152). A total of 117 of the patients (76.0%) had good outcomes (mRS=0-2). There was no significant difference in the costs, LOS, or outcomes between rural and urban patients. Contributors to total direct cost were definite TBM, fever, coma, seizures, multidrug resistance, hydrocephalus, and poor long-term outcome. Although the accessibility of medical resources in remote and rural regions has significantly improved in China, the cost of TBM imposes a catastrophic burden on patients.

Tuberculous meningitis in the elderly.

Although the elderly population remains at high risk for tuberculosis, studies addressing tuberculous meningitis (TBM) in this age group are scarce. The present study aimed to evaluate the spectrum and outcome of geriatric TBM and document differences between older and young patients. A prospective cohort study was conducted in the adult TBM patients admitted at PGIMER, Chandigarh (India). Consecutive older patients aged 60 years and above were enrolled from January 2019 to December 2020, and young adults aged 18-59 years were enrolled from July 2019 to December 2019. Fifty-five older patients with a mean age of 66.6 years and 73 young patients with a mean age of 35.1 years were enrolled. At admission, older patients were more likely to have altered mental status (96.4% vs. 78.1%, P = 0.003) and advanced disease with British medical research council staging 2 or 3 (98.2% vs. 89.0%, P = 0.043); however, headache (38.2% vs. 67.1%, P = 0.001), vomiting (18.2% vs. 35.6%, P = 0.030) and fever (80.0% vs. 91.8%, P = 0.052) were less common. Cerebrospinal fluid (CSF) abnormalities were less marked in older patients, with a significant difference in median total cells (70 vs. 110/µl, P = 0.013). Hydrocephalous and infarct were common neuroimaging abnormalities in both groups; however, tuberculomas were significantly less in the elderly (15.1% vs. 35.2%, P = 0.012). Older patients had a significantly low survival rate (56.4% vs. 76.7%, P = 0.021). Significant differences in clinical, CSF and radiological characteristics exist between elderly and young TBM patients, with survival remains dismal in the elderly.

A decade of drug-resistant tuberculous meningitis: A wake-up call for patient-centric therapy

On analyzing the drug susceptibility profile of 151 clinical isolates collected from patients of tuberculous meningitis (TBM) over 10 years, we reflect on few lessons learnt from the trend of susceptibility profile – drug resistance was not uncommon, fluoroquinolone resistance was observed even among otherwise susceptible isolates and hetero-resistance was observed against rifampicin, isoniazid and also fluoroquinolones. In the midst of widening gap between incidence of drug resistant TBM and availability of effective drugs, our data suggests that universal testing for drug resistance, careful choice of drugs having optimal penetration and individualized therapy should form important pillars of TBM management.

The association between serum sodium level and tuberculous meningitis compared with viral and bacterial meningitis

We evaluated the association between hyponatremia and tuberculous meningitis (TBM) with the aim of providing additional information for differential diagnosis from other types of infectious meningitis, especially viral meningitis (VM). Cross-sectional and longitudinal data involving 5026 participants older than 18 years were analyzed in the total population and a propensity-matched population. The initial and lowest sodium levels and longitudinal changes in TBM, bacterial meningitis (BM), and VM patients were compared. Participants in the TBM group were enrolled when they were diagnosed as possible, probable, or definite TBM according to the Marais’ criteria. The initial serum sodium level was significantly lower in TBM patients than in BM and VM patients (136.9 ± 5.9 vs. 138.3 ± 4.7 mmol/L, p < 0.001 for TBM vs. BM, and 139.0 ± 3.1, p < 0.001 for TBM vs. VM), and it decreased significantly more steeply to lower levels in both the TBM and BM patients compared with VM patients. The lowest serum sodium level was in the order of TBM < BM < VM patients, and the change was statistically significant in all subgroups (131.8 ± 6.4, 133.1 ± 5.1, 137.4 ± 3.7, respectively, p < 0.001). Participants with lower serum sodium level were more likely to have a diagnosis of TBM rather than VM, and this association was more pronounced for the lowest sodium level than the initial sodium level [OR 4.6 (95% CI 2.4–8.8, p < 0.001)]. These findings indicate that baseline and longitudinal evaluation of serum sodium level can provide information for differential diagnosis of TBM from BM or VM.

Feasibility and usefulness of tele-follow-up in the patients with tuberculous meningitis.

BackgroundTuberculous meningitis (TBM) is the most severe form of tuberculosis and these patients need close follow-up because of a high frequency of complications. The coronavirus disease 2019 pandemic and lockdown resulted in an interruption in physical follow-up. In this situation, tele-follow-up may be helpful. We report the feasibility and usefulness of a telephonic follow-up in patients with TBM.MethodsPatients with TBM managed by us from January 2017 to March 2020 were included from the TBM registry. Their presenting symptoms, and clinical and investigation findings were noted. We contacted these patients telephonically and their clinical status was obtained using a questionnaire. Based on the telephonic information, outcomes were categorized as death, poor or good. Patients with the new medical problems were advised as to relevant investigations and the reports were obtained through WhatsApp for prescribing treatment.ResultsThe telephone numbers of 103 of 144 (71.5%) patients were viable. Twenty-seven (26.2%) patients died, 15 (19.7%) had a poor outcome and 61 (80.2%) had a good outcome. Twenty-five (32.9%) patients had new medical problems: 18 TBM related and 7 TBM unrelated. The medical problems of 23 patients could be managed telephonically and only 3 (4%) patients needed a physical visit. Sixty-five (85.5%) patients happily answered the questionnaire and willing responders needed a treatment modification more frequently than the reluctant responders (p=0.008). Patients on active antitubercular treatment needed treatment modification more frequently (80% vs 21.3%).ConclusionsTele-follow-up is feasible in 96% of TBM patients and is beneficial, cost effective and overcomes the barrier of distance.

Improving host-directed therapy for tuberculous meningitis by linking clinical and multi-omics data

There is a clear need to improve host-directed therapy for tuberculous meningitis (TBM), the most severe and deadly manifestation of tuberculosis. Corticosteroids represent the only host-directed therapy of proven benefit in TBM, yet their effect is modest, the mechanism by which they reduce mortality is unknown, and there is evidence for heterogeneity in their effect. Novel therapeutic approaches are therefore urgently needed. Cellular metabolism is critical for the function of immune cells; through unbiased metabolomics we recently found that high concentrations of cerebrospinal fluid (CSF) tryptophan are associated with increased mortality in Indonesian TBM patients, and that CSF tryptophan concentrations are under strong genetic regulation. Many questions remain. How exactly is tryptophan metabolism altered during TBM? How does it correlate with inflammation, immunopathology, and response to corticosteroids? How is tryptophan metabolism genetically regulated? What is the effect of HIV co-infection on tryptophan metabolism before and during TBM treatment?The ULTIMATE project addresses these questions by integrating data and specimens from large patient studies and clinical trials evaluating the effects of corticosteroids in Vietnam and Indonesia. Through its powerful and unbiased approach, ULTIMATE aims to identify which TBM patients benefit from corticosteroids and if novel therapeutic targets, such as the tryptophan pathway, could be targeted.

Contrast-Enhanced Fluid Attenuated Recovery (FLAIR) Sequence of Magnetic Resonance Imaging for Tuberculous Meningitis in Paediatric Population

Background: Tuberculous meningitis is a well known consequence of tuberculosis, related with top mortality and morbidity in emergent nations. Prompt recognition can play a noteworthy part in rewarding and treating patients of tuberculous meningitis. Aim: To Ascertain the accuracy of contrast FLAIR MRI for diagnosis of tuberculous meningitis in children considering CSF culture as benchmark. Setting: Radiology Department of AKUH. Study Design: Cross-sectional study. Place and Duration: This study was conducted at Department of Radiology, Aga Khan University Hospital, Karachi From January 2015 to December 2016 Sample Selection: A total of 148 paediatric patients with clinical impression of tuberculous meningitis for 6 months were incorporated in study. FLAIR images were carried out from skull base to vertex in coronal plane from nasion to occipital protuberance with interval of 1.5 mm and 5 mm sections were taken. Data Analysis: Percentage were calculated for presentation of variables including FLAIR imaging findings, CSF Culture results and gender. Sensitivity, specificity, accuracy, positive and negative predictive values of FLAIR calculated and presented in percentages. Chi square test was applied taking P &lt;0.05 as significant. Results: 148 patients of which 67 were males (45.3%) and 81 were females (54.7%). Contrast enhanced FLAIR MRI test correctly identified 78.68 % of healthy individuals and labeled 76.68 % of the diseased correctly. Final stat showed 43 % of the people were correctly identified as true positive, 94 % of the people who were found negative were disease free in reality. The conclusive certainty for the imaging was found to be 78.37%. Conclusion: MRI Contrast FLAIR imaging is a justifiable tool which can assist in before time identification of tuberculous infection of brain and primary start of antituberculous medications without waiting for CSF results which require up to weeks. Keywords: Magnetic resonance imaging, Fluid attenuated inversion recovery, tuberculous meningitis.

Phenotype of Peripheral NK Cells in Latent, Active, and Meningeal Tuberculosis.

The mechanisms underlying the immunopathology of tuberculous meningitis (TBM), the most severe clinical form of extrapulmonary tuberculosis (TB), are not understood. It is currently believed that the spread of Mycobacterium tuberculosis (Mtb) from the lung is an early event that occurs before the establishment of adaptive immunity. Hence, several innate immune mechanisms may participate in the containment of Mtb infection and prevent extrapulmonary disease manifestations. Natural killer (NK) cells participate in defensive processes that distinguish latent TB infection (LTBI) from active pulmonary TB (PTB). However, their role in TBM is unknown. Here, we performed a cross-sectional analysis of circulating NK cellCID="C008" value="s" phenotype in a prospective cohort of TBM patients (n = 10) using flow cytometry. Also, we addressed the responses of memory-like NK cell subpopulations to the contact with Mtb antigens in vitro. Finally, we determined plasma levels of soluble NKG2D receptor ligands in our cohort of TBM patients by enzyme-linked immunosorbent assay (ELISA). Our comparative groups consisted of individuals with LTBI (n = 11) and PTB (n = 27) patients. We found that NK cells from TBM patients showed lower absolute frequencies, higher CD69 expression, and poor expansion of the CD45RO+ memory-like subpopulation upon Mtb exposure in vitro compared to LTBI individuals. In addition, a reduction in the frequency of CD56brightCD16− NK cells characterized TBM patients but not LTBI or PTB subjects. Our study expands on earlier reports about the role of NK cells in TBM showing a reduced frequency of cytokine-producing cells compared to LTBI and PTB.

Tuberculosis associated immune reconstitution inflammatory syndrome in patients infected with HIV: the current state of the problem

Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an enhanced inflammatory immune response to Mycobacterium tuberculosis antigens due to immune system recovery in HIV-infected patients within 6 months of antiretroviral therapy (ART).&#x0D; Objective — to assess the incidence of TB-IRIS in patients with tuberculous meningitis. Evaluation of mortality caused by TB-IRIS.&#x0D; Materials and methods. A retrospective analysis of 60 cases of confirmed tuberculous meningitis in patients who were treated in anti-tuberculosis institutions in Kiev and Kiev region in 2017—2019 was carried out. The medical records of the patients were studied.Results and discussion. Co-infection with HIV-TB among patients was confirmed in 57 (95 %) cases. In 21 patients (36.8 %; CI 24.7—50.0 %) with HIV-TB co-infection, a link was established between the appointment of ART and the development of tuberculous meningitis. 19 (90.5 %) of them had risk factors at the time of ART. Fifteen (71.4 %) patients had other localizations of tuberculosis besides tuberculosis of the central nervous system (pulmonary tuberculosis, tuberculosis of intrathoracic lymph nodes, tuberculosis of peripheral lymph nodes, tuberculosis of the genitourinary system). The mean CD4+-lymphocyte count before ART was (61.6 ± 16.9) cells/µL (p ≤ 0.05). All patients were prescribed standard antimycobacterial therapy and ART. 9 (42.8 %) patients were cured. One (4.7 %) developed severe disability: peripheral tetraparesis and severe cerebrosthenia. 11 patients died, mortality was 52.4 % (CI 30.2—74.1 %).&#x0D; Conclusions. TB-IRIS is the cause of tuberculous meningitis in HIV-infected patients in 36.8 % of cases; (CI 24.7—50.0 %). Tuberculous meningitis always complicates the prognosis with TB-IRIS, while the mortality rate is 52.4 % (CI 30.2—74.1 %).

Comparative analysis between tuberculous meningitis and other forms of extrapulmonary tuberculosis.

Tuberculosis is a multisystem disease that may affect any organ or tissue. Tuberculous meningitis (TBM) is the most severe form of tuberculosis and commonly affects the brain. We aimed to study the epidemiological, clinical, therapeutic and evolutionary features of TBM among adults and to compare them with other forms of extrapulmonary tuberculosis. We conducted a retrospective study including all patients hospitalized for extrapulmonary tuberculosis in the infectious disease department in Sfax, Tunisia between 1993 and 2018. We specified the particularities of TBM cases, and we compared them with other extrapulmonary tuberculosis cases. We encountered 78 patients diagnosed with TBM, among 519 patients with extrapulmonary tuberculosis (15%). The median age was 36 years (23-50) years. There were 44 females (56.4%). In comparison with other forms of extrapulmonary tuberculosis, fever [odds ratio (OR)=4.4; p<0.001], asthenia (OR=3.4; p<0.001) and anorexia (OR=2.3; p=0.001) were significantly more frequent in TBM patients. Adverse effects of antitubercular therapy were more frequent among TBM patients (OR=3.1; p<0.001). The mean duration of antitubercular therapy was 15 (12-20) months. Recovery occurred in 66 cases (84.6%), complications in 44 cases (56.4%) and death in 7 cases (9%). Comparison of the disease evolution showed that complications (OR=7.4; p<0.001) and mortality rates (OR=10.7; p<0.001) were significantly more frequent in TBM patients, while recovery was significantly more frequent in other sites of extrapulmonary tuberculosis patients (OR=0.5; p=0.02). In our country, TBM remains a disabling disease. Despite antitubercular therapy, the prognosis was more severe with the occurrence of not only complications but also a high mortality rate in comparison with other forms of extrapulmonary tuberculosis. When clinical and laboratory features suggest the diagnosis of TBM, clinicians should look for tuberculosis elsewhere in the body.

Frequency of Hyponatremia in Patients of Tuberculosis Bacterial Meningitis in a Tertiary Care Hospital.

IntroductionTuberculous meningitis (TBM) brings significant morbidity and mortality worldwide. Hyponatremia has long been documented as a potentially grave metabolic result of TBM. The syndrome of inappropriate antidiuretic hormone (SIADH) secretion has been supposed to be accountable for the majority of cases of hyponatremia in TBM. Cerebral salt wasting syndrome (CSWS) is being progressively reported as a basis of hyponatremia in some of these cases. Differentiating CSWS from SIADH can be challenging but is vital because treatment of these two conditions is profoundly different.ObjectiveThe rationale of our study is to determine the frequency of hyponatremia and etiology in patients presenting with TBM in a tertiary care hospital in order to establish the local perspective as there is paucity of local data.MethodsA total of 160 hospitalized patients at a tertiary care hospital in Pakistan who fulfilled the inclusion criteria were enrolled in this study after informed consent. The study was conducted for six months at the department of neurology, Jinnah Postgraduate Medical Centre (JPMC), Karachi, Pakistan. Brief history was taken and demographic information was entered in the performa by researchers. The data was collected and analyzed on Statistical Package for Social Sciences (SPSS) version 18.0 (IBM Corp., Armonk NY, USA). Demographic data were presented as simple descriptive statistics giving mean and standard deviation for age, height, weight, GCS (Glasgow Coma Scale), serum sodium and duration of symptoms. Frequencies and percentages were calculated for categorical variables like gender, hypertension, smoking status, T2DM (Type 2 Diabetes Mellitus), BMRC (British Medical Research Council Contemporary Clinical Criteria for TBM) stage, hyponatremia, SIADH and CSWS. Effect modifiers were controlled through stratification of age, gender, hypertension, smoking status, T2DM, BMRC stage and duration of symptoms to see the effect of these on the outcome variable (hyponatremia). Quantitative data were presented as simple descriptive statistics giving mean and standard deviation and qualitative variables were presented as frequency and percentages. Post stratification chi-square test was applied with a p-value of ≤0.05 taken as significant.ResultsIn our study, out of 160 patients with TBM, 40% (64) had hyponatremia. Moreover, 14.4% and 25.6% had SIADH and CSWS, respectively with 60% (96) of patients were male and 40% (64) were female. Mean age of patients in our study was 46.78±2.81 years. Whereas, mean duration of symptoms, serum sodium, GCS, height and weight in our study was 1.2±0.78 weeks, 128.65±7.52 mmol/L and 11.21±3.14%, 158±7.28 cm and 78.7±9.87 kg, respectively.ConclusionThis study concluded that the frequency of hyponatremia among patients of TBM was significant, consistent with previous studies. Privation of proper assessment and management can lead to grave and permanent neurological consequences, as well as death. Healthcare providers should be aware of the implication of sodium deregulation among patients of TBM and differentiate between the numerous therapeutic preferences in order to advocate safe and effective treatment.

Is cerebral salt wasting related to sympathetic dysregulation in tuberculous meningitis?

BackgroundCerebral Salt wasting (CSW) is common in Tuberculous Meningitis (TBM) and is suggested to be due to sympathetic dysregulation of renal blood supply but has not been proven. ObjectiveTo evaluate plasma Catecholamines in TBM patients with CSW and correlate with the markers of stress. Materials and methodsThe diagnosis of TBM was based on clinical, CSF and MRI criteria. Catecholamines level was measured by LC–MS on admission, at the time of hyponatremia and on correction of hyponatremia. Catecholamine levels were correlated with clinical and laboratory markers of stress, hyponatremia and severity of CSW using pre-defined criteria. ResultsThere were 24 patients with TBM (12 with CSW) and 12 controls. The median age of patients was 31 (18−75) years and 12 (50 %) were females. TBM patients with CSW had significantly higher levels of catecholamines compared to controls (p < 0.001). TBM patients with CSW had higher levels of norepinephrine than those without CSW (p = 0.034). Sequential studies revealed that dopamine and epinephrine increased at the time of hyponatremia and declined on its correction. Severity of TBM was related to dopamine (p = 0.04) and severity of CSW was related to epinephrine (p = 0.016). ConclusionCSW in TBM seems to be related to catecholamine dysregulation.

Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in a clinical practice setting of China

A comparative performance evaluation of the novel Xpert MTB/RIF Ultra (Xpert Ultra) and MTB/RIF Xpert (Xpert) for tuberculous meningitis (TBM) diagnosis was performed. The cerebrospinal fluids of suspected TBM patients were collected consecutively and subjected to smear microscopy, culture, Xpert, and Xpert Ultra. In total, 160 patients were recruited. Xpert Ultra produced a higher sensitivity (45%, 34 of 76) than Xpert (28%, 21 of 76; P = 0.001) and culture (18%, 14 of 76; P < 0.001), respectively. Inclusion of Xpert Ultra outcomes increased the percentage of definite TBM case from 36% (27 of 76) to 51% (39 of 76). Both Xpert Ultra and Xpert accurately identified the one rifampicin (RIF)-resistant and the 5 RIF-sensitive cases defined by phenotypic drug sensitivity test. The specificities of all of the culture, Xpert and Xpert Ultra were 100% (45 of 45). Xpert Ultra outperformed both Xpert and culture for TBM diagnosis, which may speed up the appropriate treatment of patients in clinical practice.