Predictors of Resolution of Meningitis Symptoms in Tuberculous Meningitis: A Clinical, Magnetic Resonance Imaging, and Biomarker Study.

In tuberculous meningitis (TBM), the meningeal symptoms and their resolution after treatment may be dependent on clinical-radiological severity, cerebrospinal fluid (CSF), and proinflammatory cytokines, and these findings may be associated with outcome. There is a paucity of studies on the resolution of meningitis symptoms in TBM. We report on associations of clinical, magnetic resonance imaging (MRI), laboratory, and proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin 6 (IL-6)] findings with the resolution of meningitis symptoms (RMS), and the impact of RMS duration on the outcome in TBM. Seventy-one patients with TBM were included, and their clinical, laboratory, and MRI findings at baseline were recorded. mRNA profiling of TNF-α and IL-6 was done by reverse transcriptase polymerase chain reaction. The day of RMS (fever, headache, and vomiting) after treatment was noted. Predictors of long duration of RMS (>3 weeks) were evaluated by univariate followed by multivariate analysis. The impact of RMS on 6-month mortality and outcome was analyzed. Patients' median age was 25 years, and 45 (63.4%) were males. After antitubercular treatment, meningeal symptoms resolved in 35 (50.70%) by 21 days and in 90% of patients by 49 days. Longer time of RMS was associated with TBM stage, pretreatment duration, seizure, and hydrocephalus but not with TNF-α and IL-6. Seven (9.8%) patients died at 6 months, and duration of RMS predicted death (hazard ratio = 25.55, 95% CI: 1.108-589.40; P = 0.04).

Prevalence, incidence, and case fatality of tuberculous meningitis in adults living with HIV: a systematic review and meta-analysis.

BACKGROUND: Tuberculous meningitis (TBM) emerges as a grave complication of tuberculosis in people living with HIV (PLWH). The diagnosis and treatment of TBM pose significant challenges, leading to elevated mortality rates. To comprehensively grasp the epidemiological landscape of TBM in PLWH, a systematic review and meta-analysis were meticulously undertaken. METHODS: We performed a comprehensive search in PubMed, Embase, and Web of Science from database inception to September 19th, 2023, with no limitations on the publication type. The search terms were HIV/AIDS terms (AIDS OR HIV OR PLWH) and TBM-related terms (tuberculous meningitis OR TBM). Studies included in this meta-analysis evaluated the incidence of TBM among PLWH, or we were able to calculate the incidence of TBM among PLWH from the research. RESULTS: The analysis revealed that the prevalence of TBM among PLWH was 13.6% (95% CI: 6.6-25.9%), with an incidence rate of 1.5 cases per 1000 persons per year. The case fatality rate was found to be 38.1% (95% CI: 24.3-54.1%). No significant publication bias was observed. Meta-regression analysis identified the proportion of females and finance situation as factors influencing the outcomes. CONCLUSIONS: Our study highlights TBM as a prevalent opportunistic infection that targets the central nervous system in PLWH. The elevated case fatality rate is especially prominent among PLWH in impoverished regions, underscores the pressing necessity for enhanced management strategies for PLWH suffering from TBM. TRIAL REGISTRATION: PROSPERO; No: CRD42022338586.

Dynamic PET reveals compartmentalized brain and lung tissue antibiotic exposures of tuberculosis drugs.

Tuberculosis (TB) remains a leading cause of death, but antibiotic treatments for tuberculous meningitis, the deadliest form of TB, are based on those developed for pulmonary TB and not optimized for brain penetration. Here, we perform first-in-human dynamic 18F-pretomanid positron emission tomography (PET) in eight human subjects to visualize 18F-pretomanid biodistribution as concentration-time exposures in multiple compartments (NCT05609552), demonstrating preferential brain versus lung tissue partitioning. Preferential, antibiotic-specific partitioning into brain or lung tissues of several antibiotics, active against multidrug resistant (MDR) Mycobacterium tuberculosis strains, are confirmed in experimentally-infected mice and rabbits, using dynamic PET with chemically identical antibiotic radioanalogs, and postmortem mass spectrometry measurements. PET-facilitated pharmacokinetic modeling predicts human dosing necessary to attain therapeutic brain exposures. These data are used to design optimized, pretomanid-based regimens which are evaluated at human equipotent dosing in a mouse model of TB meningitis, demonstrating excellent bactericidal activity without an increase in intracerebral inflammation or brain injury. Importantly, several antibiotic regimens demonstrate discordant activities in brain and lung tissues in the same animal, correlating with tissue antibiotic exposures. These data provide a mechanistic basis for the compartmentalized activities of antibiotic regimens, with important implications for developing treatments for meningitis and other infections in compartments with unique antibiotic penetration.

Tuberculous Meningitis Genetic predisposition: Understanding cellular interactions, molecular mechanisms and genetic dimensions.

Tuberculous meningitis, a severe form of tuberculosis caused by Mycobacterium tuberculosis (BK), remains a major public health challenge worldwide. In addition to the complex mechanisms of the innate and adaptive immune response against Mycobacterium tuberculosis, there is a crucial genetic dimension to consider. Individuals with specific genetic variations may have altered immune responses that make them more susceptible to this form of tuberculosis. Genetic mutations in genes encoding surface receptors, adaptor proteins, kinases, transcription factors, nucleic receptors and other molecules involved in cellular interactions and molecular mechanisms have been associated with susceptibility to TB. Understanding the molecular mechanisms of immune interactions in host response to Mycobacterium tuberculosis is crucial to understanding the genetic dimension in susceptibility to tuberculosis, particularly its dreaded form of tuberculous meningitis. The aim of this update is to explore in details the key interactions between the main players in innate and adaptive immunity during infection with Mycobacterium tuberculosis, with particular emphasis on the genetic factors associated with susceptibility to tuberculosis, especially its dreaded form of tuberculous meningitis.

Clinical, Laboratory and Radiological Correlates of Xpert MTB/RIF Assay Study in Cerebrospinal Fluid in CNS Tuberculosis.

BACKGROUND: Cerebrospinal fluid (CSF) Xpert MTB/RIF assay is an initial test for the diagnosis of tuberculous meningitis (TBM). Nevertheless, it is not very clear which of the factors govern CSF-Gene Xpert/MTB positivity. OBJECTIVE: Hence, we aimed to assess the relationship, if any, between the clinical, laboratory and radiological parameters of the central nervous system (CNS) tuberculosis patients and the Gene Xpert study in CSF in such patients. METHODS AND MATERIAL: First, we studied 200 patients with CNS tuberculosis according to the case definition, and subsequently, we performed a Gene Xpert study on the CSF of these patients. Then, we correlated the clinical, radiological, and CSF criteria with the Gene Xpert positivity using the univariate binary logistic regression method via SPSS 20 (P-value <0.05). RESULTS: Seventy-five (37.5%) patients (57.3% females) of median 24 years of age, were CSF-Gene Xpert/MTB-positive and 125 (62.5%) patients were negative. The mean duration of illness (P = 0.017), weight loss or failure to thrive (P < 0.001), loss of consciousness or seizure (P = 0.001), signs of meningeal irritation (P = 0.027), stage III of TBM (P < 0.001), evidence of dissemination (P = 0.003), basal exudates (P = 0.004), hydrocephalus (P = 0.018), CSF lymphocytic predominance (P < 0.001), and reduced CSF glucose (P = 0.011) correlated significantly with positive the Gene Xpert/MTB results. Also, Gene Xpert had a sensitivity of 80% and a specificity of 74.84% against culture Xpert. CONCLUSIONS: Xpert MTB/RIF might be more useful in the later stages of the disease and those with more severe disease.

The value of nanopore sequencing as a diagnostic tool in tuberculous meningitis: A protocol of systematic review and meta-analysis.

BACKGROUND: Rapid diagnosis of tuberculous meningitis (TBM) remains very difficult. Nanopore sequencing is gaining ground in the field of rapid tuberculosis (TB) diagnostics. The purpose of this study was to complete a protocol to guide the conduct of a systematic review and meta-analysis evaluating the accuracy of nanopore sequencing for the rapid diagnosis of TBM. METHODS: In accordance with the Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) guidelines, we completed this protocol, which was also registered on the PROSPERO platform. We will search the EMBASE, PubMed, the Cochrane Library, Wanfang database, and China National Knowledge Infrastructure databases for literature that evaluated the accuracy of nanopore sequencing for rapid diagnosis of TBM and screen them according to the inclusion and exclusion criteria, and qualified literature will be extracted with relevant data for further analysis. Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) will be used for evaluating the methodological quality of included studies. Stata (V 15.0; Stata Corp., College Station, TX, the USA) with midas module will be used to perform relevant meta-analysis. Heterogeneity between studies will be assessed by I2 statistics. When significant heterogeneity exists between studies, we will conduct meta-regression analyses, subgroup analyses and sensitivity analyses to further explore the sources of heterogeneity. CONCLUSION: We completed this study protocol, and this systematic review and meta-analysis will be the first systematic evaluation of the role of nanopore sequencing in the rapid diagnosis of TBM, which will allow clinicians to have a better understanding of the test. TRIAL REGISTRATION: Systematic review registration PROSPERO Registration number: CRD42024549837.

Predicting cerebral infarction in tuberculous meningitis and its prognostic significance.

Aim: Tuberculous meningitis (TBM) often causes cerebral infarction, but its predictive factors are not well understood. Methods: Patients aged ≥13 years admitted with TBM were enrolled prospectively. Cerebral infarction was diagnosed using magnetic resonance imaging. Results: Of 186 patients, 80 (43%) had infarction. Most infarctions were multiple and located in the cortical areas, basal ganglia and subcortical regions. Independent predictors of infarction at admission included high blood pressure, short illness duration, low Glasgow coma scale and hydrocephalus. Neuroimaging inflammation signs, cerebrospinal fluid analysis abnormalities and pre-existing cardiovascular risks did not predict infarction. In-hospital mortality was higher in TBM with infarction, particularly in those with advanced TBM (stage 3). Conclusion: Baseline parameters of raised intracranial pressure predict cerebral infarction in TBM.

[Box: see text].

Rifabutin central nervous system concentrations in a rabbit model of tuberculous meningitis.

Tuberculous meningitis (TBM) has a high mortality, possibly due to suboptimal therapy. Drug exposure data of antituberculosis agents in the central nervous system (CNS) are required to develop more effective regimens. Rifabutin is a rifamycin equivalently potent to rifampin in human pulmonary tuberculosis. Here, we show that human-equivalent doses of rifabutin achieved potentially therapeutic exposure in relevant CNS tissues in a rabbit model of TBM, supporting further evaluation in clinical trials.

Computer-aided prognosis of tuberculous meningitis combining imaging and non-imaging data.

Tuberculous meningitis (TBM) is the most lethal form of tuberculosis. Clinical features, such as coma, can predict death, but they are insufficient for the accurate prognosis of other outcomes, especially when impacted by co-morbidities such as HIV infection. Brain magnetic resonance imaging (MRI) characterises the extent and severity of disease and may enable more accurate prediction of complications and poor outcomes. We analysed clinical and brain MRI data from a prospective longitudinal study of 216 adults with TBM; 73 (34%) were HIV-positive, a factor highly correlated with mortality. We implemented an end-to-end framework to model clinical and imaging features to predict disease progression. Our model used state-of-the-art machine learning models for automatic imaging feature encoding, and time-series models for forecasting, to predict TBM progression. The proposed approach is designed to be robust to missing data via a novel tailored model optimisation framework. Our model achieved a 60% balanced accuracy in predicting the prognosis of TBM patients over the six different classes. HIV status did not alter the performance of the models. Furthermore, our approach identified brain morphological lesions caused by TBM in both HIV and non-HIV-infected, associating lesions to the disease staging with an overall accuracy of 96%. These results suggest that the lesions caused by TBM are analogous in both populations, regardless of the severity of the disease. Lastly, our models correctly identified changes in disease symptomatology and severity in 80% of the cases. Our approach is the first attempt at predicting the prognosis of TBM by combining imaging and clinical data, via a machine learning model. The approach has the potential to accurately predict disease progression and enable timely clinical intervention.

Analysis of risk factors for long-term mortality in patients with stage II and III tuberculous meningitis.

OBJECTIVE: To investigate risk factors associated with long-term mortality in patients with stage II and III tuberculous meningitis (TBM). METHODS: This retrospective analysis examined patients who were first diagnosed with stage II and III TBM at West China Hospital of Sichuan University between January 1, 2018 and October 1, 2019. Patients were followed via telephone and categorized into survival and mortality groups based on 4-year outcomes. Multivariate logistic regression identified independent risk factors for long-term mortality in stage II and III TBM. RESULTS: In total, 178 patients were included, comprising 108 (60.7%) males and 36 (20.2%) non-survivors. Mean age was 36 ± 17 years. Compared to survivors, non-survivors demonstrated significantly higher age, heart rate, diastolic blood pressure, blood glucose, rates of headache, neurological deficits, cognitive dysfunction, impaired consciousness, hydrocephalus, and basal meningeal inflammation. This group also exhibited significantly lower Glasgow Coma Scale (GCS) scores, blood potassium, albumin, and cerebrospinal fluid chloride. Multivariate analysis revealed age (OR 1.042; 95% CI 1.015-1.070; P = 0.002), GCS score (OR 0.693; 95% CI 0.589-0.814; P < 0.001), neurological deficits (OR 5.204; 95% CI 2.056-13.174; P < 0.001), and hydrocephalus (OR 2.680; 95% CI 1.081-6.643; P = 0.033) as independent mortality risk factors. The ROC curve area under age was 0.613 (95% CI 0.506-0.720; P = 0.036) and 0.721 (95% CI 0.615-0.826; P < 0.001) under GCS score. CONCLUSION: Advanced age, reduced GCS scores, neurological deficits, and hydrocephalus were identified as independent risk factors for mortality in stage II and III TBM patients.

[Efficacy and safety of first-line anti-tuberculosis drugs combined with Linezolid for the treatment of pediatric tuberculous meningitis in real-word practice].

Objective: To evaluate the efficacy and safety of first-line anti-tuberculosis (TB) drugs combined with linezolid in treatment of children with tuberculous meningitis (TBM). Methods: A retrospective cohort study design was performed. Eight-nine Children diagnosed as TBM during January 1st 2016 and December 31st 2023 in Department of Infectious Disease, Children's Hospital of Chongqing Medical University were enrolled in the study. According to different treatment regimens, children were divided into a group of first-line anti-tuberculous drugs (isoniazid, rifampicin, pyrazinamide, ethambutol (HRZE)) and a group of HRZE and linezolid combination (HRZEL). The efficacy and safety of the 2 regimens were compared and the relationship between linezolid drug concentration and adverse reactions were analyzed. Comparisons between groups were performed using χ2 test and Mann-Whitney U test. Results: The 89 children with TBM included 53 males and 36 females with an onset age of 4.6 (1.4, 9.6) years. There were 27 cases in the HZREL group and 62 cases in the HRZE group. Before treatment, positive rate of interferon-gamma release assays (IGRA) in HRZEL group was lower than that in HRZE group (64% (16/25) vs.92% (55/60), χ2=9.82, P<0.05), but protein level of cerebrospinal fluid (CSF) was higher than that in HRZE group (1.2 (1.0, 2.0) vs.0.8 (0.4,1.4) g/L, Z=0.32, P<0.05). By the end of the intensive phase, there were no significant differences of rates of CSF improvement and etiology negativity between HRZEL group and HRZE group (both P>0.05).The 44 TBM children with high CSF protein (>1 g/L) included 25 males and 19 females with an onset age of 6.7 (3.0, 11.8) years. There were 21 cases in the HZREL group and 23 cases in the HRZE group accordingly. Before treatment, there were no significant differences of positive rate of IGRA test and CSF protein level between the 2 groups (62% (13/21) vs. 87% (20/23), 1.7 (1.1, 2.2) vs. 1.5 (1.2, 1.9) g/L, χ2=3.67, Z=0.23, both P>0.05). There were no significant differences in CSF indicators, etiology negativity or imaging remission between the two groups by the end of intensive phase (all P>0.05). Higher frequencies of granulocytopenia, gastrointestinal symptoms as well as withdrawal or change of drugs were found in HRZEL group when compared to those in HRZE group (44% (12/27) vs. 19% (12/62), 7% (2/27) vs. 0, 33% (9/27) vs. 3% (2/62), χ2=6.01, 4.70, 15.74, all P<0.05). Conclusions: The efficacy of HRZEL regimen is similar to conventional HRZE regimen in children with TBM, but with higher adverse effect. Prudentially evaluating the pros and cons of linezolid in the usage of drug-susceptible TB and carefully monitoring of linezolid associated adverse effects is suggested.

The Spectrum of Intracranial Arteriopathies and Ischemic Strokes in Pediatric Tubercular Meningitis: A Tricentric Study From Eastern India.

INTRODUCTION: Addressing the need to uniformly classify arteriopathies among patients with arterial ischemic stroke (AIS) due to tubercular meningitis (TBM), we used the Childhood AIS Standardised Classification and Diagnostic Evaluation (CASCADE) criteria. METHODS: This tri-centric prospective study included children aged 0.5-12 years with TBM and AIS. Magnetic resonance angiographies (MRAs) were done during admission and repeated 3 and 12 months after discharge. Arteriopathies were classified according to the primary CASCADE criteria. We used the modified Pediatric Alberta Stroke Programme Early Computed Tomography Score as an ordinal measure of infarct volume. The severity of arteriopathies was graded using the focal cerebral arteriopathy severity score (FCASS). The final outcomes were measured at the 12-month follow-up visit using the Pediatric Stroke Outcome Measure (PSOM). RESULTS: Out of 55 patients, 64% had MRA-evidenced arteriopathies and 84% had multiple infarcts. The middle cerebral (46%) and internal carotid arteries (22%) were most commonly affected. The basal ganglia (70%) and the cerebral cortex (61%) were most commonly infarcted. CASCADE categories included 3b (40%), 1d (38%), 2b (16%), 2c (5%), progressive (32%), and stable (44%) arteriopathies. Younger age, hypertrophic pachymeningitis, cortical infarcts, recurrent strokes, progressive arteriopathies, EEG abnormalities, and mortality were significantly higher among patients with MRA-proven arteriopathies. Patients with progressive arteriopathies had a significantly higher prevalence of hypertrophic pachymeningitis, cortical infarcts, and recurrent strokes. FCASS correlated positively with outcomes measured by the Pediatric Stroke Outcome Measure and modified Pediatric Alberta Stroke Programme Early Computed Tomography Score. CONCLUSION: The CASCADE classification clarified the arteriopathy patterns, enabling us to correlate them with the characteristics of the infarcts. FCASS is useful to grade the arteriopathy severity and progression in TBM.

Miliary meningeal tuberculosis - an unusual imaging presentation for an early definitive diagnosis.

PURPOSE: Tuberculous meningitis (TBM) causes significant morbidity and mortality in young children. Early treatment can be initiated with magnetic resonance (MR) imaging diagnosis. We present MR-detectable miliary meningeal TB in two patients. CASE 1: A 9-year-old girl developed fevers, cough, lethargy, and seizures. Brain MRI demonstrated multiple, small, T2-dark, rim-enhancing lesions, associated with cranial nerve and leptomeningeal enhancement. CSF showed pleocytosis, low glucose, and high protein. Chest CT showed mediastinal lymphadenopathy, multiple small interstitial lung nodules, and a splenic hypo enhancing lesion. Serial bronchoalveolar lavage studies were Xpert MTB/RIF and acid-fast negative. Endobronchial US-guided biopsy of a subcarinal lymph node was positive for Xpert MTB PCR. She was started on a 4-drug treatment for TBM and dexamethasone. Contact tracing revealed a remote positive contact with pulmonary tuberculosis. CASE 2: A 17-year-old female with Crohn's disease on adalimumab developed refractory ear infections despite multiple courses of antibiotics. She underwent myringotomy, with negative aerobic ear fluid culture. Brain MRI, obtained due to persistent otorrhea, showed multiple, small, round, T2-dark lesions. CSF studies were normal. CT chest, abdomen, and pelvis to assess for disseminated disease showed left upper lobe tree-in-bud nodules, hypoattenuating splenic lesions and a left obturator internus abscess with adjacent osteomyelitis. She underwent CT-guided aspiration of the obturator muscle collection, bronchoscopy with bronchoalveolar lavage, biopsy of two preexisting chronic skin lesions, and ear fluid aspiration. QuantiFERON Gold was positive. Ear fluid was Xpert MTB/RIF assay and acid-fast stain positive. Cultures from the ear fluid, skin tissue, muscle tissue, and alveolar lavage showed growth of acid-fast bacilli. She was started on 4-drug therapy and prednisone. CONCLUSION: Our cases highlight that TBM in many cases remains a diagnostic dilemma - both our patients presented in a prolonged atypical manner. The term miliary TB not only refers to a pattern of interstitial nodules on chest radiographs but also indicates the hematogenous spread of the disease and concurrent pulmonary and extrapulmonary involvement with high risk of TB meningitis. We promote the use of the term miliary meningeal TB - in both cases, the neuroimaging diagnosis of TB preceded both chest imaging and laboratory confirmation of the disease. Miliary meningeal nodules on MRI may have characteristic T2 low signal and may be more conspicuous in children and immunocompromised individuals where background basal meningeal enhancement is less prominent.

Using cerebrospinal fluid nanopore sequencing assay to diagnose tuberculous meningitis: a retrospective cohort study in China.

OBJECTIVE: This study aimed to evaluate the efficiency of nanopore sequencing for the early diagnosis of tuberculous meningitis (TBM) using cerebrospinal fluid and compared it with acid-fast bacilli (AFB) smear, mycobacterial growth indicator tube culture and Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF). DESIGN: Single-centre retrospective study. SETTING: The Tuberculosis Diagnosis and Treatment Center of Zhejiang Chinese and Western Medicine Integrated Hospital. PARTICIPANTS: We enrolled 64 adult patients with presumptive TBM admitted to our hospital from August 2021 to August 2023. METHODS: We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of AFB smear, culture, Xpert MTB/RIF and nanopore sequencing to evaluate their diagnostic efficacy compared with a composite reference standard for TBM. RESULTS: Among these 64 patients, all tested negative for TBM by AFB smear. The sensitivity, specificity, PPV and NPV were 11.11%, 100%, 100% and 32.2% for culture, 13.33%, 100%, 100% and 2.76% for Xpert MTB/RIF, and 77.78%, 100%, 100% and 65.52% for nanopore sequencing, respectively. CONCLUSION: The diagnostic accuracy of the nanopore sequencing test was significantly higher than that of conventional testing methods used to detect TBM.

Granulomatous amoebic encephalitis due to Acanthamoeba spp complicating multidrug-resistant tuberculous meningitis in an immunocompetent individual.

Granulomatous amoebic encephalitis due to Acanthamoeba spp is a rare, near-fatal central nervous system infection. It is often seen in immunocompromised individuals. Here we describe a survivor of this infection who was co-infected with multidrug-resistant tuberculosis. He presented to us with features of meningitis and a history of chronic cough. The chest X-ray was classical for pulmonary tuberculosis. Neuroimaging was suggestive of encephalitis; herpes simplex virus PCR was negative. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis. Wet mounts revealed trophozoites of Acanthamoeba Currently, he is being treated with oral bedaquiline, levofloxacin, linezolid, clofazimine, cycloserine and pyridoxine for tuberculosis. He received intravenous amikacin and oral cotrimoxazole and fluconazole for Acanthamoeba infection for 1 month. The resolution was confirmed by repeating the CSF wet mount, culture and neuroimaging. He was then discharged with oral rifampicin, cotrimoxazole and fluconazole. He is currently under our close follow-up.

Efficacy and safety of intrathecal dexamethasone combined with isoniazid in the treatment of tuberculous meningitis: a meta-analysis.

BACKGROUND: The treatment regimen for tuberculous meningitis (TBM) remains unclear and requires optimization. There are some reports on successful adjunct intrathecal dexamethasone and isoniazid (IDI) treatment strategies for TBM, however, there is equivocal evidence on their efficacy and safety. METHODS: A comprehensive search of English and Chinese databases was conducted from inception to February 2024. A meta-analysis was performed on randomized controlled trials (RCTs) estimating the effects of adjunct IDI on conventional anti-TB (C anti-TB) treatments or C anti-TB alone. Efficacy, adverse reaction rate, cerebrospinal fluid (CSF) leukocytes, and CSF protein were used as primary outcome indicators. CSF glucose, CSF chlorides, CSF pressure, recovery time for laboratory indicators and recovery time for clinical symptoms were used as secondary outcome indicators. RESULTS: A total of 17 studies involving 1360 (IDI group vs. C anti-TB group: 392 vs. 372; higher-dose IDI group vs. lower-dose IDI group: 319 vs. 277) patients were included in our analysis. Efficacy was significantly higher (RR 1.3, 95% CI 1.2-1.4, P < 0.001) and adverse reaction rate was significantly lower in the IDI groups (RR 0.59, 95% CI 0.37-0.92, P = 0.021). Furthermore, CSF leukocytes (WMD - 29.33, 95% CI [- 40.64 to-18.02], P < 0.001) and CSF protein (WMD - 0.79, 95%CI [-0.96 to-0.61], P < 0.001) were significantly lower in the IDI groups. Recovery time indicators were all shorter in the IDI groups, fever (SMD - 2.45, 95% CI [-3.55 to-1.35], P < 0.001), coma (SMD-3.75, 95% CI [-4.33 to-3.17], P < 0.001), and headache (SMD  - 3.06, 95% CI [- 4.05 to-2.07], P < 0.001), respectively. Higher-dose IDI was more effective than lower-dose IDI (RR 1.23, 95% CI 1.14-1.33, P < 0.001), with no significant difference in adverse reaction rate between the two (RR 0.82, 95%CI 0.43-1.56, P = 0.544). CONCLUSION: Adjunct IDI with C anti-TB can enhance therapeutic outcomes and reduce adverse reaction rate in adult TBM patients, with higher-dose IDI showing superior efficacy. These findings highlight the potential of IDI as an adjunctive therapy in TBM management. However, more high-quality RCTs from more regions should be conducted to support our results. TRIAL REGISTRATION: Retrospectively registered in PROSPERO  https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023388860 .

Risk Factors for Stroke in Children with Tuberculous Meningitis: A Prospective Observational Study.

OBJECTIVE: The purpose of the study is to establish the prevalence of stroke as well as the clinical and radiological correlates of stroke in children with tuberculous meningitis (TBM). METHODS AND MATERIALS: A prospective observational study was conducted at the Pediatric Department, King George's Medical University (KGMU), Lucknow, Uttar Pradesh, India. Using a computed tomography (CT) scan/brain magnetic resonance imaging (MRI), patients were divided into stroke and non-stroke groups. Demographic characteristics, clinical presentations, cerebrospinal fluid examination, basal meningeal enhancement, hydrocephalus, tuberculoma, and clinical outcome were compared between the two groups. RESULTS: Seventy-eight TBM patients, aged between 6 months and 14 years, were included. Out of 78 enrolled patients, 3 (3.8%) had definite TBM, 73 (91%) had probable TBM, and 4 (5.1%) had possible TBM (LCS). As per the Medical Research Council (MRC) staging, 13% had Stage 1 TBM, 26% had stage 2, and 61% had stage 3 TBM. Out of 78 patients with chest X-ray findings, 42 (53%) had findings suggestive of tuberculosis (TB), which included 33 (42%) with hilar lymphadenopathy and 9 (11%) with a miliary pattern. On neuroimaging, hydrocephalous was seen in 62.8% of cases, basal meningeal enhancement in 64.1%, tuberculoma in 6.4% of cases, and infarction in 53.8% of cases. There was no statistically significant association found between the staging of TBM and the presence of infarction as the majority of cases involved were in stage 3 of the disease (61.5%). TBM patients with stroke had poor clinical outcomes. CONCLUSION: Age, altered sensorium, focal neurological deficits, vomiting, and basal meningeal enhancement can predict the occurrence of stroke in young adults with TBM.