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.

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.

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.

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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.

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.

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.

Surgical treatment for recurrent thoracic ventral intradural arachnoid cyst secondary to tuberculous meningitis: a case report.

INTRODUCTION: Spinal intradural arachnoid cysts (SIACs) are rare spinal entities that are categorized as primary or secondary pathologies. Secondary cysts can arise from various traumatic or inflammatory causes including subarachnoid hemorrhage, intrathecal injection or surgery, and infectious meningitis/arachnoiditis. Only a few cases of SIAC secondary to tuberculous meningitis have been previously reported, without details of the surgical treatment. CASE PRESENTATION: A 27-year-old woman diagnosed with tuberculous meningitis developed myelopathy caused by thoracic ventral SIAC and intradural abscess. The patient underwent abscess evacuation and cyst fenestration; however, cyst recurrence occurred. The 2nd surgery consisted of cyst resection via a posterolateral approach with expansive duraplasty and spinal arthrodesis. Re-recurrence occurred, and at the 3rd surgery, cyst-subarachnoid bypass was performed. One year after the 3rd surgery, the myelopathic symptoms recovered, and MR images demonstrated a decreased cyst size. DISCUSSION: Here, we report a rare case of recurrent thoracic SIAC secondary to tuberculous meningitis and arachnoiditis. Simple fenestration is associated with a high risk of recurrence in this pathology. Ventrally located thoracic cysts can be approached with posterolateral approach with pedicles resected followed by instrumented arthrodesis. Even in cases involving gross total resection of the cyst wall, there is a risk of recurrence. In such cases, cyst-subarachnoid bypass with a large-diameter tube can be effective.

An 11-month-old boy with tuberculous meningitis presenting as progressive limb weakness, fever, developmental retardation, and loss of consciousness: a case report.

BACKGROUND: Tuberculous meningitis (TBM) accounts for about 1% of all tuberculosis cases and about 5% of extrapulmonary tuberculosis cases. However, it poses major importance because approximately half of those affected die or become severely disabled. Herein, the successful treatment of an 11-month-old boy with progressive limb weakness, fever, developmental retardation, and loss of consciousness due to tuberculosis, was reported. CASE PRESENTATION: An 11-month-old (Iranian Turk) boy was referred to Loghman Hakim hospital for progressive limb weakness and loss of previously attained developmental milestones for the past 2 months. He also had persistent fever and loss of consciousness for about 14 to 21 days. Before being referred to our center, the patient had been diagnosed with hydrocephalus at another center due to possible acute bacterial meningitis based on a CT scan and MRI imaging. On physical examination, anterior fontanel bulging and neck stiffness were observed on the admission. His body temperature and heart rate were 38.1 C and 86 beats per minute (bpm), respectively. He had left 6 cranial nerve palsy and spastic quadriparesis with a power of grade 3/5. Other systemic examinations were normal. Endoscopic third ventriculostomy (ETV) (and leptomeningeal biopsy) revealed diffuse thickening of the floor and lateral walls of the 3rd ventricle and also a cobblestone appearance in the form of multiple white patchy lesions was detected on the floor of the 3rd ventricle. CSF analysis and polymerase chain reaction confirmed the TB meningitis. During hospitalization, a temporary EVD (external ventricular drain) was initially inserted. Eventually, defervescence was denoted 5-6 days after initiation of anti-TB medications, and a permanent ventriculoperitoneal shunt was inserted due to hydrocephalus. Gradually his truncal and limb tone and motor function improved, as did his emotional responses to his parents and ability to eat. The patient can walk without help in the 15th month following the operation and resolved hydrocephalus demonstrated on follow-up imaging. CONCLUSION: Over half of treated TB meningitis patients die or suffer severe neurological sequelae, mainly due to late diagnosis. Hence, early diagnosis and prompt initiation of TB treatment offer the best chance of a good neurological outcome.

Migration of the anal distal end due to ventriculoperitoneal shunt placement: an atypical case report of a 9-month-old infant with tuberculous meningitis and review of the literature.

BACKGROUND: Ventriculoperitoneal shunt (VPS) represents one of the most classic and widely used treatments for hydrocephalus in pediatric patients. Migration and externalization of the distal end of the catheter through the rectum are extremely rare complications of intestinal perforation with devastating consequences such as meningitis or peritonitis due to enteric bacteria that are significantly life-threatening. Besides, one of the biggest topics with that is that it can happen without producing symptoms, like the patient we present in this case report, which further masks the condition and puts the patient's life more at risk. CASE PRESENTATION: We present a case of a 9-month-old infant patient, with a history of prematurity, tuberculous meningitis (TBM), and hydrocephalus, who came to ED with a functional VPS and the distal end of the catheter protruding outside the rectum for 7 days, without presenting neurological or intestinal symptoms accompanying. One of the parameters that guided the diagnosis and made us suspicious of asymptomatic intestinal perforation (IP) was the background of TMB. The patient was immediately transferred to the OR where both ends of the shunt were removed: in the first instance, the shunt tube was disconnected through the abdomen, thus withdrawing through the anus, and subsequently, the proximal end of the catheter was exteriorized. In turn, the intestinal fistula was successfully repaired laparoscopically, and prophylactic antibiotic treatment was early administered. On the 6th postop day, a shunt was internalized, and a child was discharged on postop day 15 without complications with alarm guidelines. CONCLUSIONS: The authors of this article strongly suggest that (1) anal extrusion of catheters is an uncommon complication but real: for this reason, its development should be considered in all patients with VPS, especially in infants. (2) The patients are often asymptomatic since false tracts can form around the catheter protecting it from spillage, and thus can be removed without complications. (3) Special care should be taken in patients with conditions that increase the risk of developing IP, such as TMB.

Chronic meningitis in adults: a comparison between neurotuberculosis and neurobrucellosis.

BACKGROUND: In regions endemic for tuberculosis and brucellosis, distinguishing between tuberculous meningitis (TBM) and brucella meningitis (BM) poses a substantial challenge. This study investigates the clinical and paraclinical characteristics of patients with TBM and BM. METHODS: Adult patients diagnosed with either TBM or BM who were admitted to two referral hospitals between March 2015 and October 2022, were included, and the characteristics of the patients were analyzed. RESULTS: Seventy patients formed the study group, 28 with TBM and 42 with BM, were included. TBM patients had a 2.06-fold (95% CI: 1.26 to 3.37, P-value: 0.003) higher risk of altered consciousness and a 4.80-fold (95% CI: 1.98 to 11.61, P-value: < 0.001) higher risk of extra-neural involvement as compared to BM patients. Cerebrospinal fluid (CSF) analysis revealed a significantly higher percentage of polymorphonuclear leukocytes (PMN) in TBM compared to BM (Standardized mean difference: 0.69, 95% CI: 0.18 to 1.20, P-value: 0.008). Neuroimaging findings indicated higher risks of hydrocephalus (P-value: 0.002), infarction (P-value: 0.029), and meningeal enhancement (P-value: 0.012) in TBM compared to BM. Moreover, TBM patients had a 67% (95% CI: 21% to 131%, P-value:0.002) longer median length of hospital stay and a significantly higher risk of unfavorable outcomes (Risk ratio: 6.96, 95% CI: 2.65 to 18.26, p < 0.001). CONCLUSIONS: Our study emphasizes that TBM patients displayed increased frequencies of altered consciousness, PMN dominance in CSF, extra-neural involvement, hydrocephalus, meningeal enhancement, and brain infarction. The findings emphasize the diagnostic difficulties and underscore the importance of cautious differentiation between these two conditions to guide appropriate treatment strategies.

Dancing Out of Step: A Case of Tuberculous Meningitis Presenting as Childhood Chorea.

Background: Acute to subacute pediatric movement disorders require prompt diagnosis to identify potentially treatable diseases. Case Report: We present a 6-year-old male with a three-week history of generalized chorea transitioning to predominantly right-sided hemichorea and then to left hemiplegia. Discussion: We review the mechanisms in tuberculous meningitis underlying his movement abnormalities.

Acute ischemic stroke in tuberculous meningitis.

Background: The underlying mechanism for stroke in patients with tuberculous meningitis (TBM) remains unclear. This study aimed to investigate the predictors of acute ischemic stroke (AIS) in TBM and whether AIS mediates the relationship between inflammation markers and functional disability. Methods: TBM patients admitted to five hospitals between January 2011 and December 2021 were consecutively observed. Generalized linear mixed model and subgroup analyses were performed to investigate predictors of AIS in patients with and without vascular risk factors (VAFs). Mediation analyses were performed to explore the potential causal chain in which AIS may mediate the relationship between neuroimaging markers of inflammation and 90-day functional outcomes. Results: A total of 1,353 patients with TBM were included. The percentage rate of AIS within 30 days after admission was 20.4 (95% CI, 18.2-22.6). A multivariate analysis suggested that age ≥35 years (OR = 1.49; 95% CI, 1.06-2.09; P = 0.019), hypertension (OR = 3.56; 95% CI, 2.42-5.24; P < 0.001), diabetes (OR = 1.78; 95% CI, 1.11-2.86; P = 0.016), smoking (OR = 2.88; 95% CI, 1.68-4.95; P < 0.001), definite TBM (OR = 0.19; 95% CI, 0.06-0.42; P < 0.001), disease severity (OR = 2.11; 95% CI, 1.50-2.90; P = 0.056), meningeal enhancement (OR = 1.66; 95% CI, 1.19-2.31; P = 0.002), and hydrocephalus (OR = 2.98; 95% CI, 1.98-4.49; P < 0.001) were associated with AIS. Subgroup analyses indicated that disease severity (P for interaction = 0.003), tuberculoma (P for interaction = 0.008), and meningeal enhancement (P for interaction < 0.001) were significantly different in patients with and without VAFs. Mediation analyses revealed that the proportion of the association between neuroimaging markers of inflammation and functional disability mediated by AIS was 16.98% (95% CI, 7.82-35.12) for meningeal enhancement and 3.39% (95% CI, 1.22-6.91) for hydrocephalus. Conclusion: Neuroimaging markers of inflammation were predictors of AIS in TBM patients. AIS mediates < 20% of the association between inflammation and the functional outcome at 90 days. More attention should be paid to clinical therapies targeting inflammation and hydrocephalus to directly improve functional outcomes.

Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome in initiating ART among HIV-Infected patients in China-risk factors and management.

BACKGROUND: China is a country burdened with a high incidence of both tuberculosis (TB) and HIV, Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an important early complication in TB and HIV co-infected patients, but data from China are limited. Additionally, as an integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) regimen becomes the first-line treatment, concerns have arisen regarding the potential increase in the incidence of paradoxical TB-IRIS. Nevertheless, the existing data are inconclusive and contradictory. METHODS: We conducted a retrospective study at Chongqing Public Health Clinical Center from January 2018 to December 2021. We collected demographic and clinical data of HIV/TB co-infected patients who initiated ART. We described the patient characteristics, identified predictors for TB-IRIS, and determined clinical outcomes. The Statistical Package for Social Science (SPSS 25) was used to analyse the data. Continuous variables were compared using Student's t-test or rank sum test. Counting data were compared using the chi-square test or Fisher's exact test. The variables with statistical significance in the univariate analysis were added to the binary logistic regression. A p-value less than 0.05 was considered statistically significant. RESULTS: A total of 384 patients co-infected with naive HIV and pulmonary TB (PTB) who were given ATT and ART combination were included. 72 patients (18.8%) developed paradoxical TB-IRIS with a median of 15 (12, 21) days after initiating ART. Baseline age ≤ 40years, CD4 + T-cell counts ≤ 50cells/µL, HIV viral load ≥ 500,000 copies/mL were found to be significantly associated with development of paradoxical TB-IRIS. Mortality rates were similar in the TB-IRIS (n = 5, 6.9%) group and non-TB-IRIS (n = 13, 4.2%) group. Interestingly, CD4+ T-cell counts recovery post-ART was significant higher in the TB-IRIS group when compared to the non-TB-IRIS group at the end of 24 weeks (P = 0.004), as well as at 48 weeks (P = 0.015). In addition, we consider that INSTI- based ART regimen do not increased the risk of Paradoxical TB-IRIS. CONCLUSION: Paradoxical TB-IRIS, while often leading to clinical deterioration and hospitalization, is generally manageable. It appears to have a positive impact on the recovery of CD4 + T-cell counts over time. Importantly, our data suggest that INSTI-based ART regimens do not elevate the risk of TB-IRIS. Thus, paradoxical TB-IRIS should not be considered an impediment to initiating ART in adults with advanced immunodeficiency, except in the case of tuberculous meningitis (TBM).

Occurrence and determinants of seizures and their impact on tuberculous meningitis: a prospective evaluation.

OBJECTIVE: To assess the incidence of seizures and the factors contributing to poor outcomes in patients with tuberculous meningitis (TBM). METHODS: In this prospective observational study, 129 patients with TBM were enrolled at the Department of Neurology, King George's Medical University, Uttar Pradesh, India, from April 2021 to April 2023. Detailed clinical history, neurological examinations, baseline laboratory tests, contrast-enhanced Magnetic resonance imaging (MRI) and electroencephalography (EEG) were obtained for all patients. Patients received anti-tuberculous therapy and, if necessary, anti-epileptic treatment. Patients were followed for 6 months, with outcomes evaluated using the Modified Rankin Scale (MRS). RESULTS: Of the 129 patients, 48 (37.2%) reported seizures. Advanced TBM stage (p = 0.040, OR = 2.50 95% CI:1.02-6.07), cortical involvement (p = .0.013, OR = 2.58 95% CI:1.20-5.51) and spike-wave discharges in the EEG (p = 0.001) were significantly associated with seizure occurrence. After multivariate analysis, only cortical involvement (p = 0.031, OR = 2.34, 95% CI:1.08-5.08) emerged as independent predictor of for seizures. Focal to bilateral seizures (p = 0.008, OR = 9.41, 95% CI: 1.76-74.04), status epilepticus (p = 0.002, OR = 8.00, 95% CI: 1.86-34.32), and rifampicin resistance (p = 0.022, OR = 9.25, 95% CI: 1.43-59.50) were significantly associated with poor outcomes at the 6-month mark. CONCLUSION: Seizures were significantly associated with advanced stage of the disease, cortical involvement on neuro-imaging and epileptiform pattern on EEG. Additionally, focal to bilateral seizures and status epilepticus adversely affected the outcome.

Mortality and sequelae of tuberculous meningitis in a high-resource setting: A cohort study, 1990-2017.

INTRODUCTION: Tuberculous meningitis (TBM), the most serious form of tuberculosis, results in high mortality and long-term disability in low-resource countries. We investigated temporal trends in mortality and sequelae in a high-resource low-incidence country. METHODS: We performed a retrospective cohort study of all adult patients with TBM at two third-level teaching hospitals in Barcelona (Spain), between January 1990 and December 2017, assessing temporal trends in mortality and sequelae after 12 months over four consecutive 7-year time windows. Rates observed across the four periods were adjusted for covariates. RESULTS: Of the 135 cases included, all but one started tuberculosis (TB) treatment and 120 (89.6%) received rifampicin, isoniazid, and pyrazinamide, with or without ethambutol. The probability of being alive at month 12 was 81.8%, with no differences among the four periods: in comparison with the 1990-1996 period, the adjusted hazard ratios and 95% confidence intervals (CI) were 2.55 (0.71-9.25), 0.70 (0.13-3.85), and 1.29 (0.28-5.91) for the 1997-2003, 2004-2010, and 2011-2017 periods respectively. Sequelae were present in 28.3% at month 12, with no differences across the four periods in the adjusted analysis: in comparison with the 1990-1996 period, the odds ratios and 95% CIs were 0.80 (0.09-7.22); 1.94 (0.21-17.96), and 2.42 (0.25-23.07) for the 1997-2003, 2004-2010, and 2011-2017 periods respectively. CONCLUSION: This study shows that TBM still causes high mortality and disability even in a high-resource low-incidence TB setting and without improvement over time.

Prolonged paradoxical reaction requiring over 5 years of corticosteroid administration in a patient with severe tuberculous meningitis.

Tuberculous meningitis (TBM) is a rare disease in low-incidence countries like Japan, where general physicians have fewer experience with TBM. Despite its proper treatment and early improvement of the condition, TBM often causes paradoxical reactions (PRs), which can lead to severe complications such as stroke. As PRs in the brain are difficult to detect without regular neuroimaging surveillance and have a later onset than in other organs, delayed treatment can be fatal. We report a case of a 54-year-old, human immunodeficiency virus (HIV)-negative man who presented with TBM and miliary tuberculosis (TB) in an unconscious state. Standard anti-tuberculous therapy with adjunctive systemic high-dose dexamethasone brought rapid clinical and microbiological improvement, which allowed the dexamethasone to be tapered. However, he developed cerebral infarction with left hemiplegia due to a TBM-related PR five months after admission. Therefore, the initial high-dose dexamethasone was again added to the anti-tuberculous drugs, achieving the significant effects on the PR-related lesions. Anti-tuberculous drugs had been administered for 3 years and the dexamethasone was carefully tapered. Nevertheless, enlargement of PR-related lesions in the brain recurred 5 years later. Accordingly, the dose of corticosteroid was again increased, resulting in resolving the lesions. It is important to note that severe TBM may cause prolonged PRs, which require a long-term neuroimaging follow-up and anti-inflammatory drugs for the successful management of the TBM-related PR.

Factors associated with in-hospital mortality in HIV-infected children treated for tuberculous meningitis hydrocephalus.

PURPOSE: The study aimed to investigate factors associated with in-hospital mortality in children diagnosed with tuberculous meningitis (TBM) hydrocephalus and HIV co-infection undergoing cerebrospinal fluid diversion procedures and their complications. METHODS: Data were collected retrospectively and prospectively between 2007 and 2022. Data collected included demographics, clinical characteristics, antiretroviral therapy (ART) status, biochemistry results, CD4 count, radiology findings, CSF diversion procedures (and complications), length of hospital stay (LOHS), and in-hospital mortality. RESULTS: Thirty-one children were included, with a mean age of 6.7 ± 5.3 years and 67.7% males. Median admission Glasgow Coma Scale (GCS) was 11 (IQR 9-15). Hypertonia (64.5%) and seizures (51.6%) were frequently observed clinical characteristics. Sixty-one percent of children were on ART. Cerebral infarcts and extra-meningeal TB were diagnosed in 64.5% and 19.3% of cases, respectively. The median CD4 count was 151 (IQR 70-732) cells/µL. Surgical procedures included ventriculoperitoneal shunt (VPS) in 26 cases and endoscopic third ventriculostomy (ETV) in five children. VPS complication rate was 27%. No complications were reported for ETV. Median LOHS was 7 days (IQR 4-21). Eleven children (35.5%) died during admission. Factors associated with mortality included GCS (p = 0.032), infarcts (p = 0.004), extra-meningeal TB (p = 0.003), VPS infection (p = 0.018), low CD4 count (p = 0.009), and hyponatremia (p = 0.002). No statistically significant factors were associated with VPS complications. CONCLUSION: TBM hydrocephalus in HIV-infected children carries a high mortality. Clinicians in high-prevalence settings should have a high suspicion index and institute early treatment.

Tuberculous Meningitis or Neurosarcoidosis-a Diagnostic Quandary. From the National Multiple Sclerosis Society Case Conference Proceedings

Distinguishing granulomatous diseases remains diagnostically challenging. Clinical phenotypes and neuroimaging findings resemble many infectious and noninfectious disorders. We describe a Hispanic/Latino man diagnosed with tuberculous meningitis who deteriorated neurologically after treatments. Additional workup revealed a pathology more consistent with neurosarcoidosis. Care access delays and social circumstances likely complicated his diagnosis.

Stroke in Tuberculous Meningitis.

A 17-year-old male presented with a 20-day history of vomiting, abdominal pain, weight loss, headache and fever progressing to dysarthria, somnolence, urinary incontinence, slurred speech, weakness, and inability to walk. Neurological examination revealed diminished visual acuity and diplopia. A head computed tomography (CT) showed acute hydrocephalus (Figure 1). Cerebrospinal fluid (CSF) analysis revealed pleocytosis (lymphocyte predominant), hypoglycorrhachia (8 mg/dL), and hyperproteinorrachia (156 mg/dL). The brain magnetic resonance imaging (MRI) revealed leptomeningitis, basal ganglia infarcts and basal meningeal enhancement highly suggestive of tuberculous meningitis (TBM) (Figure 2). We calculated a positive Thwaites score (-5) for TBM. The patient responded well to antituberculous treatment and dexamethasone. At 2 year follow-up the patient remains symptom-free. Stroke is a frequent complication of TBM and might contribute to long-term disability. Brain imaging findings, such as basal meningeal enhancement and basal exudates, hydrocephalus, and infarctions (TBM triad) are useful tools to rapidly identify probable TBM(3,4). Brain infarcts in TBM are located mostly in the arterial territory of distal branching arterires(5). Other less frequent imaging findings are tuberculomas and vasospasm. Key message: Hydrocephalus, basal meningeal enhancement, and basal ganglia infarcts should raise suspicion of tuberculosis, especially in endemic regions.