[Clinical features and influencing factors of long-term prognosis in patients with tuberculous meningitis].

Objective: To investigate the clinical features and influencing factors of long-term prognosis of tuberculous meningitis(TBM), and to provide a recommendation for treatment and early intervention of TBM. Methods: Clinical data of TBM patients were retrospectively collected at Peking Union Medical College Hospital from January 2014 to December 2021. Patients who were followed-up more than one year were divided into two groups according to modified Rankin Scale (mRS). Risk factors associated with long-term prognosis were analyze by conditional logistic stepwise regression. Results: A total of 60 subjects were enrolled including 33 (55%) males and 27 (45%) females with age 15-79 (44.5±19.8) years. There were 30 cases (50%) complicated with encephalitis, 21 cases (35%) with miliary tuberculosis. The diagnosis was microbiologically confirmed in 22 patients (36.7%), including 5 cases (22.7%, 5/22) by acid-fast staining, 8 cases (36.4%, 8/22) by Mycobacterium tuberculosis (MTB) culture, and 20 cases (90.9%, 20/22) by molecular biology. The median follow-up period was 52(43, 66 ) months in 55 cases surviving more than one year. Among them, 40 cases (72.7%) were in favorable group (mRS 0-2) and 15 cases (27.3%) were in unfavorable group (mRS 3-6) with poor prognosis. The mortality rate was 20% (11/55). Elderly (OR=1.06, P=0.048 ) , hyponatremia(OR=0.81,P=0.020), high protein level in cerebrospinal fluid (CSF) (OR=3.32,P=0.033), cerebral infarction(OR=10.50,P=0.040) and hydrocephalus(OR=8.51,P=0.049) were associated with poor prognosis in TBM patients. Conclusions: The mortality rate is high in patients with TBM. Molecular biology tests improves the sensitivity and shorten the diagnosis time of TBM. Elderly, hyponatremia, high protein level in CSF, cerebral infarction and hydrocephalus are independent risk factors of long-term survival in TBM patients.

Prognostic factors of adult tuberculous meningitis in intensive care unit: a single-center retrospective study in East China.

BACKGROUND: Tuberculous meningitis (TBM) is the most lethal form of tuberculosis worldwide. Data on critically ill TBM patients in the intensive care unit (ICU) of China are lacking. We tried to identify prognostic factors of adult TBM patients admitted to ICU in China. METHODS: We conducted a retrospective study on adult TBM in ICU between January 2008 and April 2018. Factors associated with unfavorable outcomes at 28 days were identified by logistic regression. Factors associated with 1-year mortality were studied by Cox proportional hazards modeling. RESULTS: Eighty adult patients diagnosed with TBM (age 38.5 (18-79) years, 45 (56 %) males) were included in the study. An unfavorable outcome was observed in 39 (49 %) patients and were independently associated with Acute Physiology and Chronic Health Evaluation (APACHE) II > 23 (adjusted odds ratio (aOR) 5.57, 95 % confidence interval (CI) 1.55-19.97), Sequential Organ Failure Assessment (SOFA) > 8 (aOR 9.74, 95 % CI 1.46-64.88), and mechanical ventilation (aOR 18.33, 95 % CI 3.15-106.80). Multivariate Cox regression analysis identified two factors associated with 1-year mortality: APACHE II > 23 (adjusted hazard ratio (aHR) 4.83; 95 % CI 2.21-10.55), and mechanical ventilation (aHR 9.71; 95 % CI 2.31-40.87). CONCLUSIONS: For the most severe adult TBM patients of Medical Research Council (MRC) stage III, common clinical factors aren't effective enough to predict outcomes. Our study demonstrates that the widely used APACHE II and SOFA scores on admission can be used to predict short-term outcomes, while APACHE II could also be used to predict long-term outcomes of adult patients with TBM in ICU.

Risk factors for poor outcome in childhood tuberculous meningitis.

Tuberculous meningitis (TBM) remains a serious disease for children and its risk factors of poor outcome remain unclear. Therefore, a retrospective study was conducted aiming to investigate the risk factors associated with poor outcome of childhood TBM. Between January 2006 and December 2019, consecutive children patients (≤ 15 years old) who had a diagnosis of TBM were included for the analysis. The demographic, clinical, laboratory, and radiographic data were collected from the electronic medical records retrospectively. Poor outcome was defined as death or transfer to a higher-level hospital. Patients were then divided into good and poor outcome groups. Subsequently, risk factors for poor outcome were estimated using univariate and multivariate logistic regression analysis. A total of 149 children with TBM was enrolled, twenty-two patients suffered poor outcome, including 16 transfers to a higher-level hospital and 6 deaths, and the remaining 127 patients were classified as good outcome group. Further multivariate analysis revealed that coma (age- and sex-adjusted OR = 6.425, 95% CI: 1.743, 23.676; P < 0.01) and cerebrospinal fluid (CSF) protein (> 1188.3 mg/L; age- and sex-adjusted OR = 4.680, 95% CI: 1.469, 14.902; P < 0.01) were associated with the poor outcome of childhood TBM. Childhood TBM remains to have a high mortality rate in China. High CSF protein and coma were identified as risk factors for poor outcome of childhood TBM. Hence, more attention is required to be paid to suspected patients with such characteristics, thus facilitating access to optimum treatment.

Forty years of Tuberculous meningitis: The new face of an old enemy.

BACKGROUND: Tuberculous meningitis (TBM) occurs in 1-5% of cases of tuberculosis. Without early treatment, mortality and permanent disability rates are high. METHODS: A retrospective study performed at a tertiary hospital in Madrid (Spain) to describe clinical, diagnostic, and therapeutic aspects of TBM and analyze epidemiological trends over forty years, divided into two intervals (1979-1998 and 1999-2018). RESULTS: Overall, TBM was diagnosed in 65 patients (1.8% of new tuberculosis diagnoses), 48 in the first period and 17 in the second one. Median age at diagnosis increased from 38.5 to 77 years (p = 0.003). The proportion of non-HIV immunosuppressed patients increased (from 2.1% to 29.4%, p < 0.001), while the percentage of patients with a history of drug-abuse decreased (from 33.3% to 5.9%, p = 0.027). The median time between the onset of neurological symptoms and lumbar puncture increased from seven to 15 days (p = 0.040). The time between the onset of symptoms and the initiation of tuberculostatic treatment also increased from eleven to 18 days (p = 0.555). Results from image, biochemical, and microbiological tests showed no differences between both periods. A decreasing trend was observed in survival rates at 1-week (from 97.9% to 64.7%, p < 0.001), 1-month (from 91.7% to 58.8%, p = 0.002) and 1-year (from 85.4% to 47.1%, p = 0.002) after TBM diagnosis. CONCLUSIONS: The profile of patients diagnosed with TBM has changed from a young HIV-infected patient with a history of drug addiction to an elderly patient with non-HIV immunosuppression. Diagnosis and start of treatment both experienced a noticeable delay in the second period, which could help explain the increase in mortality observed across the two periods.

Inclusion of Mechanical Ventilation in Severity Staging of Tuberculous Meningitis Improves Outcome Prediction.

Patients with tuberculous meningitis (TBM) in any stage of the British Medical Research Council (BMRC) scale, if requiring mechanical ventilation (MV), are likely to have a poor outcome. We report the usefulness of BMRC, BMRC-MV, and BMRC-hydrocephalus (BMRC-HC) staging, and Haydarpasa Meningitis Severity Index (HAMSI) scoring in predicting the outcome of TBM. One hundred ninety-seven TBM patients were analyzed from a prospectively maintained TBM registry. The severity of meningitis was categorized using BMRC (stages I-III), BMRC-MV (I-IV [MV patients were grouped as stage IV]), and BMRC-HC (I-IV [BMRC stage III patients with hydrocephalus were grouped as stage IV]). Haydarpasa Meningitis Severity Index scoring was categorized as < 6 and ≥ 6. The outcome was defined at 6 months using the modified Rankin Scale (mRS) as death, poor (mRS score > 2), or good (mRS score ≤ 2). Forty-nine (25%) patients died. BMRC-mechanical ventilation stage IV had the highest predictive value for defining death, with a sensitivity of 88% and a specificity of 86%. About 81.7% of surviving patients had a good outcome at 6 months. BMRC-mechanical ventilation stages I-III had the highest predictive value for defining good outcome, with a sensitivity of 93% and a specificity of 61%. In TBM, BMRC-MV staging has the best predictive value for defining death and disability.

Neurotuberculosis: A Clinical Review.

In September 2018, the United Nations General Assembly held the first ever meeting to discuss the global epidemic of tuberculosis (TB) and adopted a political declaration titled "United to end tuberculosis: an urgent global response to a global epidemic." The timing of the meeting was prescient but overdue since Mycobacterium tuberculosis surpassed the human immunodeficiency virus as the world's leading infectious killer in 2014. Infection of the central nervous system by Mycobacterium tuberculosis, herein referred to as neurotuberculosis, is the most feared and dangerous form of tuberculosis, requiring a high level of suspicion and clinical experience for prompt diagnosis and treatment. Neurologists, infectious disease specialists, orthopedic surgeons, neurosurgeons, and hospitalists in all countries need to recognize the spectrum of neurotuberculosis and be able to integrate clinical information, laboratory data, and radiological findings to make a diagnosis with or without microbiological confirmation.

Tuberculous meningitis: Challenges in diagnosis and management.

Tuberculous meningitis (TBM) is the most lethal and disabling form of tuberculosis. In 2017, approximately 10 million people developed TB worldwide, of whom more than 100,000 new cases of TBM are estimated to occur per year. In patients who are co-infected with HIV-1, TBM has a mortality approaching 50%. Diagnosis of TBM is often delayed by the insensitive and lengthy culture technique required for disease confirmation. GeneXpert represents the most significant advance in TBM diagnostics over the past decade, but it lacks sensitivity and cannot be used to rule out the diagnosis. Higher volume of cerebrospinal fluid (CSF) seems to be interesting to improve the diagnosis performances. New rapid and accurate diagnostic tools are necessary. Better advances have been made concerning the anti-tuberculosis chemotherapy of TBM, with the publication of clinical trials and pharmacokinetic studies exploring the use of higher rifampicin doses and fluoroquinolones. The rise of drug-resistant TBM is another challenge for management because TBM caused by multidrug resistant organisms results in death or severe disability in almost all sufferers.

Matrix Metalloproteinases in Pulmonary and Central Nervous System Tuberculosis-A Review.

Tuberculosis (TB) remains the single biggest infectious cause of death globally, claiming almost two million lives and causing disease in over 10 million individuals annually. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes with various physiological roles implicated as key factors contributing to the spread of TB. They are involved in the breakdown of lung extracellular matrix and the consequent release of Mycobacterium tuberculosis bacilli into the airways. Evidence demonstrates that MMPs also play a role in central nervous system (CNS) tuberculosis, as they contribute to the breakdown of the blood brain barrier and are associated with poor outcome in adults with tuberculous meningitis (TBM). However, in pediatric TBM, data indicate that MMPs may play a role in both pathology and recovery of the developing brain. MMPs also have a significant role in HIV-TB-associated immune reconstitution inflammatory syndrome in the lungs and the brain, and their modulation offers potential novel therapeutic avenues. This is a review of recent research on MMPs in pulmonary and CNS TB in adults and children and in the context of co-infection with HIV. We summarize different methods of MMP investigation and discuss the translational implications of MMP inhibition to reduce immunopathology.

Tuberculoid Granuloma in the Brainstem: Case Report

Meningitis or meningoencephalitis are the most common presentations of Koch bacilli infection on the central nervous system (CNS), especially in immunosuppressed patients, in whom the bacilli normally reaches the meninges and the cerebral parenchyma.. A least common pathological presentation is the tumoral growth pattern disease known as tuberculoma. This pathological entity is more common in the cerebral hemispheres and is rarely located in the brainstem. The present case report describes a case of a 55-year-old patient under regular antiretroviral therapy who was hospitalized with signs of brainstem and cerebellar disturbances. Computed tomography (CT) and magnetic resonance imaging (MRI) of the brain showed an exophytic lesion in the dorsal region of the pons. The patient underwent total resection of the lesion and the histopathologic analysis was consistent with a tuberculoma.

Characteristics of miliary tuberculosis in pregnant women after in vitro fertilisation and embryo transfer.

OBJECTIVE: To analyse the clinical characteristics of miliary tuberculosis (TB) in pregnant women after in vitro fertilisation and embryo transfer (IVF-ET). METHODS: Six pregnant women with miliary TB after IVF-ET between October 2010 and July 2015 were retrospectively analysed. RESULTS: The patients were aged between 29 and 39 years. Fever, cough and dyspnoea were the main symptoms, and started during the first and second trimesters of pregnancy. Erythrocyte sedimentation rate and C-reactive protein were increased. White blood cell count was normal or slightly increased. Tuberculin purified protein derivative and acid-fast smear of sputum tests were negative. T-SPOT®.TB was performed in two cases and the results were positive. Chest computed tomography showed typical miliary nodules. One patient had tuberculous meningitis. Although all patients were cured, the foetuses died. CONCLUSIONS: The principal symptoms of miliary TB in pregnant women after IVF-ET were fever and dyspnoea. Physicians should consider the occurrence of miliary TB, particularly in the case of fever of long duration, respiratory symptoms and no response to antibiotic treatment.

Paradoxical reaction in HIV-negative tuberculous meningitis patients with spinal involvement.

OBJECTIVE: The aim of this study was to investigate the occurrence of paradoxical reaction (PR) in HIV-negative tuberculous meningitis (TBM) patients with spinal involvement, as well as its possible risk factors. METHODS: Fifty TBM patients with spinal involvement were studied retrospectively and divided into a PR group and a non-PR group according to the presence of PR. Their demographic, clinical, radiological, and laboratory data, and status at follow-up were collected and compared. RESULTS: PR developed in 26 patients (52%), with the median time to the development of PR being 30days (range 15-330 days) after the initiation of tuberculosis therapy. At initial diagnosis, age, documented acid-fast bacilli (AFB), and the cerebrospinal fluid protein level were found to differ significantly between the two groups. After multivariate analysis, age, documented AFB, and vertebral involvement were significantly associated with the development of PR. CONCLUSIONS: PR was common in TBM patients with spinal involvement. Age, documented AFB, and musculoskeletal involvement may be predictors of PR development.

Seizures in tuberculous meningitis.

OBJECTIVE: We report the frequency of seizure, its possible mechanisms and effect of seizure on the outcome of tuberculous meningitis (TBM). METHODS: Seventy-nine patients with TBM admitted during 2014-2017 were evaluated. The seizures were categorized as per International League Against Epilepsy as well as into early (within 1 month of meningitis) and late (>1 month) seizure. The possible association of seizures was recorded and the outcome was assessed using modified Rankin Scale (mRS ≤ 2 as good, and mRS > 2 as poor). RESULTS: The median age was 27 (18-76) years and 43 (54.4%) of whom were females. Tuberculous meningitis was definite in 31 (39.2%) and highly probable in the remaining. Seizures occurred in 27 (34.2%): early onset in 8 (29.6%) and late in 19 (70.4%) patients. The seizures were focal in 11(13.9%), focal to bilateral in 9 (11.4%), generalised tonic clonic in 7 (8.9%) and status epilepticus in 6 (7.6%) patients. Early seizures were associated with meningeal irritation and late seizures with tuberculoma, infarction and hyponatremia (P = 0.01). Seizure did not affect the mortality but were associated with worse six months outcome (P = 0.03). CONCLUSION: Seizures occurred in 34% patients with TBM and were associated with poor outcome at six months.

Cost-effectiveness of home-based vs. in-hospital treatment of paediatric tuberculous meningitis.

SETTING: Cape Town, South Africa, 2014. OBJECTIVE: To assess the societal costs and cost-effectiveness of home-based vs. in-hospital treatment of paediatric tuberculous meningitis. DESIGN: This was an economic evaluation from a societal perspective using probabilistic analysis. Health care, informal care, lost productivity costs and costs in other sectors, health-related quality of life (HRQoL) and family impact were assessed during interviews with care givers, children, medical staff and management. RESULTS: Societal costs for home-based treatment were USD3857, and USD28 043 for in-hospital treatment. Home-based vs. in-hospital treatment HRQoL scores were 90.9% vs. 84.5%, while family impact scores were 94.8% vs. 73.1%. The point estimate of the incremental cost-effectiveness ratio indicated that improving HRQoL and family impact by 1% was associated with a saving of respectively USD3726 and USD1140 for home-based vs. in-hospital treatment. The probability that home-based treatment was less expensive and more effective than in-hospital treatment was 96.3% for HRQoL and 100% for family impact. CONCLUSION: Societal costs of home-based treatment were lower than for in-hospital treatment. Children treated at home had a better HRQoL and family impact scores. Home-based treatment was a cost-effective alternative to in-hospital treatment of drug-susceptible tuberculous meningitis.

Chiari malformation and tuberculous meningitis: aetiology and management.

This is the first reported case of a Chiari 1 malformation in association with tuberculous (TB) meningitis. We present a case of a 23-year-old woman with a 2-week history nocturnal fever, vertigo, headache and projectile vomiting. She had nystagmus, scanning speech, bilateral papilloedema and ataxia. Cranial imaging showed a 10 mm tonsillar herniation. Posterior fossa decompression was done. Because the patient's gamut of symptoms was highly suspicious for a central nervous system infection, a lumbar tap was done which revealed TB meningitis. Four years later, after anti-TB medications and rehabilitation, all her symptoms except gait instability resolved.

Human immunodeficiency virus in patients with tuberculous meningitis: systematic review and meta-analysis.

INTRODUCTION: Human immunodeficiency virus (HIV)-infected individuals are at increased risk for all forms of extrapulmonary tuberculosis (TB), including tuberculous meningitis (TBM). This study aimed to investigate the frequency of HIV in patients with TBM. METHODS: PubMed, Embase, Web of Science and Cochrane Library were searched for articles including relevant data. Stata version 14.0 (StataCorp, College Station, Texas, USA) was used to analyse the data. RESULTS: Twenty studies were identified. The pooled frequency of HIV among adult patients with TBM was 38.0% (95% CI: 21.0-57.0; I2 = 97%). In children (under the age of 15 years), 6.0% (95% CI: 1.0-13.0; I2 = 0.0%) had HIV infection. In patients with bacterial meningitis other than TBM, 36.0% (95% CI: 19.0-53.0; I2 = 100%) were HIV-infected. CONCLUSIONS: A relatively high frequency of HIV in patients with TBM was indicated by our study. Establishment of diagnostic criteria and effective treatment strategies for TBM/HIV co-infection are recommended for better management of patients with TBM+HIV.

Other central nervous system infections: cytomegalovirus, Mycobacterium tuberculosis, and Treponema pallidum.

Human immunodeficiency virus (HIV)-infected individuals are particularly susceptible to several central nervous system infections: human cytomegalovirus, which may cause encephalitis, ventriculitis, polyradiculitis, or polyradiculomyelitis; Mycobacterium tuberculosis, which can cause meningitis or space-occupying lesions; and Treponema pallidum subspecies pallidum (T. pallidum), which affects the meninges, cerebrospinal fluid, cranial nerves, and vasculature in early neurosyphilis, and additionally the brain and spinal cord parenchyma in late neurosyphilis. Central nervous system cytomegalovirus infection is seen in HIV-infected individuals with very advanced immunosuppression. Its prognosis is poor and optimal therapy has not been determined. Tuberculous meningitis has a high mortality in those also infected with HIV, especially in the developing world, and better therapies are urgently needed. As the rates of syphilis increase in the developed world, neurosyphilis and in particular ocular syphilis are increasingly reported. The likelihood of all three of these central nervous system infections is decreased in individuals who receive potent antiretroviral therapy.

Clinical presentations and outcomes of the children with tuberculous meningitis: An experience at a tertiary care hospital.

OBJECTIVE: To determine the clinical presentations and outcomes of the children suffering from tuberculous meningitis. METHODS: This prospective, descriptive study was conducted at the Children's Hospital and the Institute of Child Health, Multan, Pakistan, from February to December 2015. The Pakistan Paediatric Association scoring chart for tuberculosis was used as a tool for the probable diagnosis. The clinical symptoms with their durations were noted. Clinical stages of tuberculous meningitis, cerebrospinal fluid analysis and computerised tomography brain findings were noted for each patient. The outcomes in the form of death or neurological disabilities at the time of hospital discharge were noted. SPSS 19 was used for data analysis. RESULTS: Of the 40 participants, 25(62.5%) were males and 15(37.5%) were females. The mean age of the patients was 4.24±3.32 years. Besides, 26(65%) patients were less than 5 years of age. All the patients (100%) were categorised as stage 3 tuberculous meningitis. The history of prolonged duration of fever 39(97.55%) and altered level of sensorium 40(100%) were the most common clinical presentations. Moreover, 2(5%) patients died during this study. All the 38(95%) survivors had neurological disabilities. There were motor deficits in 37(97.4%) patients, altered level of sensorium in 35(92%), cranial nerve palsies in 9(23.5%), epilepsy in 29(76.3%) and hydrocephalus in 32(84%) patients. CONCLUSIONS: The children were the most vulnerable group for the worst form of tuberculous meningitis and had a grave outcome.

[Extramedullary intradural tuberculosis: a case report and review of the literature]. / Tuberculoma intradural extramedular: descripcion de un caso clinico y revision de la bibliografia.

INTRODUCTION: Central nervous system tuberculosis is a common chronic infection in developing countries, being the most frequent forms: tuberculous meningitis and intracranial tuberculosis. Extramedullary intradural tuberculosis is a rare entity with few cases described in the world literature, and is usually associated with a history of tuberculous meningitis or during antituberculosis treatment. CASE REPORT: A 17 years-old male patient, without history of tuberculosis, with subacute onset and progressive course of compressive myelopathy. Spinal magnetic resonance imaging revealed an intradural extramedullary mass lesion between the C4 and T8 spinal levels. Surgical resection of tuberculoma was realized, followed by chemotherapy. The histopathological study confirmed the diagnostic. CONCLUSIONS: Tuberculosis of the central nervous system is an entity of high incidence in developing countries, and intradural extramedullary tuberculoma should be included in the differential diagnosis of expansive spinal cord injuries, especially if the patient is young and there is a history of pulmonary tuberculosis or tuberculous meningitis. It is also important to take it into account as part of a paradoxical reaction after the initiation of specific treatment. Although surgical resection improves compressive medullary symptoms, medical therapy remains the mainstay in the treatment of tuberculomas.

TITLE: Tuberculoma intradural extramedular: descripcion de un caso clinico y revision de la bibliografia.Introduccion. La tuberculosis del sistema nervioso central es una infeccion cronica comun en paises en vias de desarrollo, y la meningitis tuberculosa y los tuberculomas intracraneales son las formas mas frecuentes. El tuberculoma intradural extramedular es una entidad poco frecuente, con pocos casos descritos en la bibliografia mundial, y por lo general se asocia a un antecedente de meningitis tuberculosa o durante el tratamiento antituberculoso. Caso clinico. Varon de 17 años, sin antecedente de tuberculosis, con cuadro clinico de una mielopatia compresiva de aparicion subaguda y curso progresivo, cuya neuroimagen evidencio una lesion extensa intradural extramedular. Se le realizo cura quirurgica mas laminectomia descompresiva en D4-D8 seguido de quimioterapia. El estudio histopatologico confirmo el diagnostico. Conclusiones. La tuberculosis del sistema nervioso central es una entidad de alta incidencia en nuestro medio, y el tuberculoma intradural extramedular deberia incluirse en el diagnostico diferencial de lesiones expansivas de la medula espinal, mas aun si el paciente es joven y existe el antecedente de tuberculosis pulmonar o meningitis tuberculosa. Asimismo, es importante tenerla en cuenta como parte de una reaccion paradojica despues del inicio del tratamiento especifico. Aunque la reseccion quirurgica mejora los sintomas compresivos medulares, la terapia medica continua siendo el pilar en el tratamiento de los tuberculomas.

Tuberculous tales: an East London experience.

Tuberculous meningitis presents a diagnostic and therapeutic challenge, and considering its long history and increasing global incidence, the evidence base for its treatment is relatively scanty. Many UK neurologists will have little first-hand experience of this deadly condition, and if faced with a patient with possible tuberculous meningitis will find decision making less than straightforward. In parts of East London (UK) the rates of tuberculosis and tuberculous meningitis are among the highest in Western Europe, and so the neurologists and respiratory physicians at the Royal London Hospital have encountered many such patients over the years. We have found experience to be a valuable teacher and so would like to share five cases that illustrate the complexities of diagnosis and management of the disease, and complications of its treatment.