Diagnostic and therapeutic approach to chronic meningitis in Brazil: a narrative review / Abordagem diagnóstica e terapêutica da meningite crônica no Brasil: uma revisão narrativa

Abstract Background Chronic meningitis (CM) is characterized by neurological symptoms associated with the evidence of cerebrospinal fluid pleocytosis lasting > 4 weeks. Studies on the management of CM in Brazil are scarce. Objective To critically review the literature on CM and propose a rational approach in the Brazilian scenario. Methods Narrative literature review discussing the epidemiology, clinical evaluation, basic and advanced diagnostic testing, and empirical and targeted therapy for the most relevant causes of CM. The present review was contextualized with the local experience of the authors. In addition, we propose an algorithm for the management of CM in Brazil. Results In Brazil, tuberculosis and cryptococcosis are endemic and should always be considered in CM patients. In addition to these diseases, neurosyphilis and other endemic conditions should be included in the differential diagnosis, including neurocysticercosis, Baggio-Yoshinari syndrome, and endemic mycosis. After infectious etiologies, meningeal carcinomatosis and autoimmune diseases should be considered. Unbiased and targeted methods should be used based on availability and clinical and epidemiological data. Conclusion We propose a rational approach to CM in Brazil, considering the epidemiological scenario, systematizing the etiological investigation, and evaluating the timely use of empirical therapies.

Resumo Antecedentes A meningite crônica (MC) é caracterizada por sintomas neurológicos associados à evidência de pleiocitose do líquido cefalorraquidiano por > 4 semanas. Os estudos sobre o manejo da MC no Brasil são escassos. Objetivo Rever criticamente a literatura sobre MC e propor uma abordagem racional no cenário brasileiro. Métodos Revisão da literatura narrativa discutindo a epidemiologia, avaliação clínica, testes diagnósticos básicos e avançados, além da terapia empírica e direcionada para as causas mais relevantes do MC. A presente revisão foi contextualizada com a experiência local dos autores. Além disso, propomos um algoritmo para o manejo da MC no Brasil. Resultados No Brasil, a tuberculose e a criptococose são endêmicas e devem ser sempre consideradas em pacientes com MC. Além destas doenças, a neurossífilis e outras condições endêmicas devem ser incluídas no diagnóstico diferencial, incluindo: neurocisticercose, síndrome de Baggio-Yoshinari e micoses endêmicas. Após etiologias infecciosas, devem ser consideradas a carcinomatose meningeal e doenças autoimunes sistêmicas. Métodos diagnósticos devem ser utilizados com base na disponibilidade, nos dados clínicos e nos dados epidemiológicos. Conclusão Propomos uma abordagem racional para a MC no Brasil, considerando o cenário epidemiológico, sistematizando a investigação etiológica e avaliando o uso oportuno de terapias empíricas.

Tuberculosis miliar y meningitis multidrogorresistente (MDR) en paciente pediátrico: Reporte de un caso / Complicated multidrug-resistant tuberculosis (MDR) in a pediatric patient: Case report

Objetivo: Presentar el caso de un paciente pediátrico con cuadro inicial de tuberculosis (TB) ganglionar con abandono de tratamiento en 2 ocasiones que evolucionó a la forma miliar y meningitis tuberculosa multidrogorresistente. Reporte del caso: Varón de 4 años con diagnóstico inicial de tuberculosis ganglionar, que abandonó el esquema sensible de tratamiento en dos ocasiones. Tres meses después, se evidenció compromiso bilateral sugestivo de TB miliar y durante la hospitalización desarrolló tuberculosis meníngea e hidrocefalia. Por el antecedente de abandono de tratamiento, se solicitó un estudio de sensibilidad en aspirado gástrico, identificándose como multidrogorresistente; pasando al esquema EZLfxKmEtoCs y manejo de complicaciones, consiguiendo mejoría. Conclusiones: El abandono de tratamiento es una de las principales causas de resistencia a fármacos antituberculosos y de complicaciones. Es necesario reforzar la detección temprana y tratamiento efectivo de esta infección en niños, poniéndose énfasis el seguimiento de casos para evitar abandonos de tratamiento y las complicaciones consecuentes.

Objetive:To describe a pediatric case with initial diagnosis of lymph node tuberculosis (TB) that became multidrug resistant miliar and meningeal tuberculosis (TB-MDR) due to treatment dropout twice. Case report: a 4-year-old boy with initial diagnosis of lymphnode tuberculosis who had two episodes of dropout from the sensitive scheme treatment. Three months later, there was evidence of bilateral involvement suggestive of miliary TB. During hospitalization, he developed meningeal tuberculosis and hydrocephalus. Due to the history of treatment dropout, a sensitivity of gastric aspirate study was requested, identifying it as multidrug-resistant TB. He started the EZLfxKmEtoCs treatment scheme and complications management, achieving improvement. Conclusions: Treatment dropout is one of the main causes of drug resistance in tuberculosis and its complications. It is necessary to reinforce the early detection and effective treatment of this infection in children, focusing on the follow-up of cases to avoid treatment dropout and the consequent complications.

Clinical features and influencing factors of long-term prognosis in patients with tuberculous meningitis / 中华内科杂志

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.

Clinical characteristics and prognosis of central nervous system tuberculosis in adults / 中华传染病杂志

Objective:To investigate the clinical characteristics of central nervous system tuberculosis in adults and the possible factors affecting the mortality and disability of the patients.Methods:The clinical data of patients diagnosed as "tuberculous meningitis" "tuberculous meningoencephalitis" "tuberculous cerebrospinal meningitis" or "tuberculous brain ubscess" in Huashan Hospital, Fudan University and Jing′an Branch, Huashan Hospital, Fudan University in Shanghai from January 1, 2010 to December 31, 2017 were collected, and a retrospective cohort was established. The clinical characteristics were analyzed, Medical Research Council (MRC) grade system was used to assess the severity of meningitis, and the modified Rankin Scale was used to assess the impairment of self-care. Survival rate and disability rate of the cohort were analyzed. Binary logistic regression was used for multivariate analysis. Kaplan-Meier survival curve was used for survival analysis.Results:A total of 161 patients with central nervous system tuberculosis were enrolled. Among the 161 patients, 55 cases (34.2%) were confirmed, 72 cases (44.7%) were highly suspected and 34 cases (21.1%) were suspected diagnosis. There were 56 cases (34.8%) with MRC grade Ⅰ, 76 cases (47.2%) with MRC grade Ⅱ and 29 cases (18.0%) patients with MRC grade Ⅲ before treatment. Up to January 1, 2019, ten (6.2%) patients died, 32 (19.9%) patients lost to follow-up, 119 (73.9%) patients survived. The five-year survival rate was 92.83%. There were 72 patients with no impact on life, 34 patients with moderate impact and 13 patients with severe impact. The disability rate was 39.5% (47/119). Binary logistic regression analysis showed that increasing age (odds ratio ( OR)=1.06, 95%confidence interval ( CI) 1.00 to 1.13, P=0.032) and deterioration of MRC grade during anti-tuberculosis treatment ( OR=89.00, 95% CI4.46 to 1 779.00, P=0.003) were independent risk factors for death. When severe disability and death were used as adverse outcomes, logistic regression analysis showed increasing age ( OR=1.07, 95% CI 1.01 to 1.13, P=0.035) and deterioration of MRC grade during anti-tuberculosis treatment ( OR=77.17, 95% CI4.45 to 1 337.00, P=0.003) were still independent risk factors for adverse outcomes. Conclusions:The mortality of central nervous system tuberculosis in adults in this cohort is relatively low, but the disability rate is still high. Increasing age and deterioration of MRC grade during anti-tuberculosis treatment are independent risk factors for death and disability.

Tuberculosis infantil en Chile: ¿de dónde provienen los casos? / Childhood tuberculosis in Chile: where do the cases come from?

La tuberculosis es la principal causa de muerte por un agente infeccioso a nivel mundial y se estima que un 6% de los casos nuevos corresponde a tuberculosis infantil. La presencia de tuberculosis en niños es una señal de la existencia de transmisión del agente en la comunidad. Esta investigación busca describir las características epidemiológicas de la tuberculosis infantil en Chile entre 2011 y 2020. METODOLOGÍA: estudio descriptivo de los casos de tuberculosis infantil registrados en Chile entre los años 2011 y 2020. RESULTADOS: se registraron 544 casos de tuberculosis en menores de 15 años en el período analizado, con una tasa de incidencia anual entre 1,1 y 2,2 casos por 100.000. Se observa un importante aumento de casos en los últimos tres años, especialmente en el grupo de menores de 5 años. 63,2% corresponden a tuberculosis pulmonar, y de ellos 62,3% fueron confirmados por bacteriología. La mayoría de los casos no presenta comorbilidades que impliquen inmunosupresión y la incidencia de meningitis tuberculosa en menores de 5 años es baja. La proporción de contactos es de 29% y la de extranjeros de 17%, ambas variables en aumento en los últimos años. CONCLUSIÓN: La tuberculosis en niños sigue siendo un problema de salud poco frecuente en Chile. Sin embargo, su aumento en los últimos años debe alertar sobre un incremento de la transmisión comunitaria de la enfermedad, por lo que se debe reforzar la detección oportuna de casos contagiantes, la investigación de contactos y el tratamiento preventivo.

Tuberculosis is the leading cause of death from a single infectious agent worldwide and it is estimated that 6% of new cases are children. Childhood tuberculosis reflects ongoing transmission within communities. This study aims to describe the epidemiological characteristics of childhood tuberculosis in Chile between 2011 and 2020. METHODOLOGY: descriptive study of the cases of tuberculosis under 15 years-old registered in Chile from 2011 to 2020. RESULTS: 544 cases were registered in the period analyzed, with an annual incidence rate between 1.1 and 2.2 cases per 100,000. A significant increase in cases is observed in the last three years, especially in the group under 5 years-old. 63.2% correspond to pulmonary tuberculosis, and among them 62.3% are confirmed by bacteriology. Most of the cases do not have comorbidities and the incidence of tuberculous meningitis in children under 5 years is low. Contacts are 29% of the cases and foreigners are 17%, both percentages are increasing in the last years. CONCLUSION: Childhood tuberculosis remains a low frequency health problem in Chile. However, its increase in recent years implies an increase in the community transmission. Active case finding, contact tracing and preventive treatment should be reinforced.

Hallazgos de tuberculosis extrapulmonar en imágenes de resonancia magnética en una paciente pediátrica / MRI findings on extrapulmonary tuberculosis in a pediatric patient

Resumen | La tuberculosis pulmonar es la más común en niños y su forma extrapulmonar corresponde aproximadamente a 30 a 40 % de los casos. Se presenta el caso de una niña indígena con tuberculosis diseminada: pulmonar, cerebral, medular y musculoesquelética, con importantes secuelas en el neurodesarrollo. Este caso ilustra el espectro de la tuberculosis extrapulmonar pediátrica en países endémicos en desarrollo. Además, evidencia la gravedad de las complicaciones neurológicas causantes de grave discapacidad y resalta el valor de las imágenes radiológicas para orientar la sospecha diagnóstica de compromiso extrapulmonar.

Abstract | Pulmonary tuberculosis is the most common in children and its extrapulmonary manifestations are present in 30% to 40% of cases. We present the case of an indigenous girl with disseminated tuberculosis: pulmonary, brain, medullary, and musculoskeletal with substantial neurodevelopmental sequelae. This case exemplifies the spectrum of pediatric extrapulmonary tuberculosis in endemic developing countries. Furthermore, it shows the severity of highly disabling neurological complications and stresses the importance of radiological imaging in guiding diagnostic suspicion of extrapulmonary involvement.

Research progress in treatment of tuberculous meningitis / 中华临床感染病杂志

Tuberculous meningitis is the most common and serious type of central nervous system tuberculosis, with high mortality and disability rate, which has attracted extensive attention of global public health. The high mortality rate and disability rate of tuberculosis meningitis may be related to its lack of specific clinical and imaging characteristics, insufficient attention from clinicians, lack of early sensitive and specific diagnostic testing techniques, delay in treatment, and restricted penetration of anti-TB drugs into the blood-brain barrier or/and MDR-TB, etc. This article reviews the disease burden of TBM, chemotherapy drugs and regimens, anti-inflammatory agents, aspirin, interventional and surgical treatment to provide reference for clinical management of this disease.

Diagnostic characteristics of Xpert MTB/RIF assay for the diagnosis of tuberculous meningitis and rifampicin resistance in Southern Brazil / Características diagnósticas do Xpert MTB/RIF para o diagnóstico de meningite tuberculosa e resistência à rifampicina no Sul do Brasil

ABSTRACT Background: The timely diagnosis of tuberculous meningitis (TBM) is challenging. Molecular diagnostic tools are necessary for TBM, particularly in low- and middle-income countries. Objectives: We aimed to calculate the diagnostics characteristics of Xpert MTB/RIF for the detection of Mycobacterium tuberculosis in the cerebrospinal fluid (CSF) and the frequency of rifampicin (RIF)-resistance in the CSF samples. Methods: A total of 313 consecutive CSF samples were studied and categorized into TBM definite, probable, possible, or not TBM cases based on the clinical, laboratory, and imaging data. Results: For the definite TBM cases (n=7), the sensitivity, specificity, efficiency, and positive likelihood ratio were 100, 97, 97, and 38%, respectively. However, for the TBM definite associated with the probable cases (n=24), the sensitivity decreased to 46%. All CSF samples that were Xpert MTB/RIF-positive were RIF susceptible. Conclusion: Xpert MTB/RIF showed high discriminating value among the microbiology-proven TBM cases, although the values for the probable and possible TBM cases were reduced. Xpert MTB/RIF contributes significantly to the diagnosis of TBM, mainly when coupled with the conventional microbiological tests and clinical algorithms.

RESUMO Introdução: O diagnóstico da meningite tuberculosa (TBM) é desafiador. Ferramentas de diagnóstico molecular são necessárias para esse diagnóstico, particularmente em países de baixa e média renda. Objetivos: Calcular as características diagnósticas do Xpert MTB/RIF para a detecção de Mycobacterium tuberculosis no líquido cefalorraquidiano (LCR) e a frequência de resistência à rifampicina (RIF) nas amostras do LCR. Métodos: Um total de 313 amostras consecutivas de LCR foram estudadas e categorizadas em casos de TBM definida, provável, possível ou não TBM, com base nos dados clínicos, laboratoriais e de imagem. Resultados: Para os casos definidos de TBM (n=7), sensibilidade, especificidade, eficiência e razão de verossimilhança positiva foram de 100, 97, 97 e 38%, respectivamente. No entanto, para os casos de TBM definidos associados aos prováveis (n=24), a sensibilidade diminuiu para 46%. Todas as amostras de LCR que foram positivas para Xpert MTB/RIF foram suscetíveis a RIF. Conclusão: O Xpert MTB/RIF mostrou alto valor discriminante entre os casos TBM comprovados por microbiologia, porém o valor nos casos prováveis e possíveis de TBM foram reduzidos. O Xpert MTB/RIF contribui significativamente para o diagnóstico de TBM, principalmente quando associado aos testes microbiológicos convencionais e algoritmos clínicos.

Dynamic changes of cerebrospinal fluid cytology in the course of tuberculous meningitis and its diagnostic value / 中国医师杂志

Objective To investigate the dynamic changes of cerebrospinal fluid (CSF) cytology in the course of tuberculous meningitis (TBM) and its diagnostic value.Methods 37 children with TBM who were treated in the department during January 2008 to December 2016 were selected as the observation group.Another 40 children with non-TBM (including viral encephalitis and suppurative encephalitis) were selected as the control group at the same time.The CSF samples were collected for routine,biochemical and CSF cytological examinations.The detection of mycobacterium tuberculosis antigen pure protein derivative (PPD) positive cell rate (monocyte) was performed,and the value of CSF cytology in the diagnosis of TBM was summarized.Results (1) The lumbar puncture pressure,white blood cell count,lymphocyte count and protein quantification in the observation group were higher than those in subgroups of the control group,while the glucose and chloride levels were lower than those in the subgroups (P ＜ 0.05).(2) The cytological examination of CSF in the observation group mainly was mixed cell reaction,accounting for 83.78％,followed by lymphocyte reaction (10.81％).Viral meningitis mainly manifested as lymphocyte reaction,accounting for 82.14％,while suppurative meningitis mainly manifested as polymorphonnclear response,accounting for 75.00％.(3) The positive rate of PPD antigen in the observation group was 81.08％,which was significantly higher than that in children with viral meningitis,suppurative meningitis (P ＜ 0.05).(4) The accuracy rate of protein level ＞0.45 g/L in the diagnosis of TBM was 89.19％,and the accuracy rate of CSF cytological mixed cell response was 83.78％.(5) The white blood cell count,the proportion of monocytes and the proportion of neutrophils were the highest in children with tuberculous meningitis less than 2 weeks,compared with those in children with 3-4 weeks and ＞4 weeks (P ＜0.05).The above-mentioned cytological indexes were decreased while the proportion of lymphocytes was increased in children with TBM whose course of disease was 3-4 weeks.The white cell count,proportions of monocytes,lymphocytes and proportion of neutrophils in children whose course of disease was longer than 4 weeks were lower than those in children whose course of disease was 3-4 weeks (P ＜ 0.05).Conclusions The white blood cell count,proportion of monocyte and proportion of neutrophils were relatively higher in the first 2 weeks of TBM,and maintained for 2 weeks.2 weeks later,levels of above-mentioned cells decreased except for lymphocytes while the proportion of lymphocytes increased continuously and then decreased gradually 4 weeks later.The diagnostic accuracy rate of CSF cytological mixed reaction to TBM was relatively higher,and the consistency with tuberculosis antigen PPD examination was high,which could be used as a choice for early diagnosis of TBM.

Diagnostic value of T cells spot test of tuberculosis infection on blood and cerebrospinal fluid for tuberculous meningitis / 中华传染病杂志

Objective To evaluate the diagnostic value of T cells spot test of tuberculosis infection (T-SPOT .TB) on blood and cerebrospinal fluid for tuberculous meningitis (TBM ).Methods One hundred and fifteen adult patients with suspected tuberculous meningitis were retrospectively enrolled from March 2013 to March 2017 in Huashan Hospital affiliated to Fudan University .Among them ,30 were diagnosed with TBM (7 definite ,19 highly probable and 4 possible) ,37 with other infectious meningitis and 29 with non-infectious meningitis .The diagnostic sensitivity ,specificity ,positive predictive values (PPV) and negative predictive values (NPV) of T-SPOT .TB on peripheral mononuclear cells (PBMC) and cerebrospinal fluid mononuclear cells (CSF-MC ) were analyzed using Fisher exact test , and the diagnostic performance was evaluated by using receiver operating characteristic (ROC ) curve and area under the curve (AUC).Results When including the 30 TBM cases and 66 non-TBM cases into analysis , the sensitivities and specificities , PPV and NPV of PBMC and CSF-MC for diagnosing TBM were as follows :93 .1% and 66 .7%,77% and 87 .7%,65 .9% and 71 .4%,95 .9% and 85 .1%,respectively . When including the 30 TBM and 37 other infectious meningitis into analysis , the sensitivities and specificities ,PPV and NPV of the PBMC and CSF-MC for diagnosing TBM were as follows :93 .1% and 66.7%,68 .6% and 86 .5%,71.1% and 80 .0%,92 .3% and 76 .2%,respectively .By ROC curve analysis ,the AUC of blood and CSF were 0 .882 (95% CI :0 .795－0 .969) and 0 .814 (95% CI :0 .704－0 .925) ,respectively .Using a cut-off value of 32 spot forming cells (SFC) per million CSF-MC for T-SPOT .TB on CSF-MC showed a sensitivity of 66 .7%,a specificity of 91 .9%,PPV of 87 .0% and NPV of 77 .3% .The positive likelihood ratio and negative likelihood ratio were 8 .22 and 0 .363 respectively . Conclusions T-SPOT .TB on CSF-MC has a role in diagnosing TBM .And 32 SFC per million CSF-MC might be the optimal cut-off value to differentiate TBM and non-TBM .

Research on the relationship between the gene polymorphism of leukotriene A4 hydrolase and the severity of tuberculous meningitis / 中华神经科杂志

Objective To investigate the relationship between rs17525495 locus polymorphism of leukotriene A4 hydrolase (LTA4H) gene and the severity of tuberculous meningitis (TBM). Methods A total of 184 TBM patients from Department of Neurology, the Second Hospital of Hebei Medical University from January 2014 to October 2016 were selected as research subjects. According to the British Medical Research Council criteria, the severity of TBM patients was divided into three stages. The single nucleotide polymorphism rs17525495 of LTA4H gene was sequenced, and the general case data, clinical manifestations and results of lumbar puncture were analyzed. Results There were 91 cases (49.5％) of CC genotypes of rs17525495 locus in LTA4H gene of 184 cases, 75 cases (40.8％) of CT genotypes and 18 cases (9.8％) of TT genotypes. The frequency of allele C was 69.8％ and T was 30.2％. Patients with different genotypes were compared for their severity, clinical manifestations and lumbar puncture results. Among CC patients, the proportion of stage Ⅰ patients(54.9％, 50/91)was higher than that of stage Ⅱ(22.0％, 20/91)and Ⅲ(23.1％, 21/91). Among TT patients, the proportion of patients with stage Ⅱ(8/18)and Ⅲ(8/18)was higher than patients with stageⅠ(2/18)(χ2=15.898,P=0.003). The incidence of headache, fever, nausea and vomiting, neck stiffness, epilepsy and disturbance of consciousness was statistically analyzed. Compared with CC and CT patients, the incidence of fever(TT:13/18,CC:42/91,CT:50/75,χ2=8.932,P=0.011)and neck stiffness(TT:12/18,CC:38/91,CT:46/75,χ2=7.993,P=0.018)was higher in TT patients. Headache, nausea and vomiting, disturbance of consciousness, and the incidence of epilepsy showed no statistically significant difference. And there was no statistically significant difference in lumbar puncture pressure, chloride, protein and glucose between different genotypes. Conclusion TBM patients with mild illness frequently prompt LTA4H gene rs17525495 locus for the CC type;while patients with severe disease prompt TT type.

Clinical characteristics and prognosis of human immunodeficiency virus infected patients with tuberculous meningitis / 中华传染病杂志

Objective To investigate the impact of human immunodeficiency virus(HIV) infection on clinical characteristics and short term outcome of tuberculous meningitis (TBM).Methods One hundred and fifty-one cases of TBM patients were retrospectively collected from Chongqing Public Health Medical Center between January 2015 and December 2015.Among them,61 were infected with HIV (HIV/TBM group) and 90 were without HIV infection (TBM group).Clinical manifestations,whether complicated by pulmonary tuberculosis,cerebrospinal fluid parameters and CD4+ T lymphocyte counts and their clinical outcomes were compared.Chi square test,t test and non-parameter test were used.Results The incidences of fever,headache,vomiting and meningeal irritation sign in HIV/TBM group were 80.3％ (49),90.2％ (55),47.5％ (29) and 8.2％ (5),respectively,and those in TBM group were 88.9％ (80),88.9％ (80),47.8％ (43) and 17.8％ (16),all of which showed no significant differences (x2=2.141,0.062,0.001 and 2.787,respectively,all P＞0.05).HIV-infected patients had higher percentage of altered consciousness (34.4 ％ vs 16.7 ％,x2 =6.316,P＜0.05),whereas patients without HIV infection had higher percentages of night sweating and pulmonary tuberculosis than those with HIV infection (60.0％ vs31.1％,x2=12.120;97.8％ vs73.8％,x2=19.958,both P＜0.05).The mean value of cerebrospinal pressures in patients with HIV infection was 218.4 mmH2O (1 mmH2O =0.009 8 kPa),which was significantly lower than that of patients without HIV infection (263.6 mmH2O)(t=-2.240,P＜0.05).The median CD4+ T cell counts in HIV/TBM group was 62 (1-540) cells/μL,while that in TBM group was 291 (16 1 689) cells/μL,with significant difference (Z=-7.994,P＜0.01).There was no statistical difference in CSF parameters,imaging findings and in-hospital mortality between two groups (all P＞0.05).Conclusions HIV infected TBM patients are more likely to have altered consciousness,and less likely to have high CSF pressure and pulmonary tuberculosis.Patients with HIV/TBM eoinfection have comparable CSF parameters,head imaging findings and short-term outcomes compared with TBM patients without HIV infection.

Xinjiang region the clinical characteristics and prognosis of tuberculous meningitis factor analysis / 中国医师杂志

Objective To describe the Xinjiang region of tuberculous meningitis (TBM) (age ＞ 18 years of age) in patients with the clinical features,analysis of factors influencing the prognosis.Methods A retrospective of cases included in the data collection,describe the clinical characteristics,using the single factor and multiple factors Logistic regression analysis of factors influencing the prognosis.Results A total of 200 cases of TBM patients had the following characteristics:120 cases of male,female 80 cases;age 18 -75 (37.35 ±+ 14.24) years old;the course of the disease 3-270 (36.86 +43.86)days;and 179 cases of survival,21 cases of death,with a mortality of l0.5％.Single factor analysis showed that hydrocephalus,encephaledema,clinical staging,erythrocyte sedimentation rate,cerebro-spinal fluid (CSF)-protein had statistically significant difference between survival group and death group,respectively (P ＜ 0.05).The multi-factor Logistic regression analysis showed that encephaledema and erythrocyte sedimentation rate were independent factors to affect the prognosis of TBM (P ＜ 0.05).Conclusions Encephaledema and erythrocyte sedimentation rate are independent risk factors of poor prognosis in patients with TBM,early identify predictors,formulate corresponding clinical countermeasures,and can improve the prognosis of patients with tuberculous meningitis.

Analysis on misdiagnosis of tuberculous meningitis in the elderly / 中华老年医学杂志

Objective To explore the clinical characteristics of elderly patients with tuberculous meningitis (TBM) and analyze the causes of misdiagnosis.Methods The clinical data of patients aged 60 years and over with TBM in Beijing Chest Hospital Affiliated to Capital Medical University from January 2011 to January 2017 were retrospectively analyzed.The clinical characteristics of the elderly patients with TBM were analyzed and compared between misdiagnosis and non-misdiagnosis groups.Results Among 60 elderly patients with TBM,32 cases (53.3%) were misdiagnosed before hospitalization.Among 32 misdiagnosed cases,11 (34.4%) were misdiagnosed as pulmonary infection,6 (18.8%) as infectious diseases with unspecified site,4(12.5%) as upper respiratory tract infections and 3 (9.4%) as cerebral vascular diseases,and so on.The onset time of TBM,fever prevalence and CSF glucose levels were 42.5 (20.3,60.0) d,96.9% (31 cases),1.5(1.1,2.3)mmol/L in misdiagnosis group respectively,and 15.0 (10.0,20.0) d,75.0%(21 cases),2.3(1.4,3.2)mmol/L in non-misdiagnosis group respectively,which was statistically significantly different between the two groups (all P 0.05).Conclusions Elderly patients with TBM have atypical clinical manifestations,many comorbidities,and less specific imaging,and especially,the cerebrospinal fluid pathogen sensitivity is low,which may result in higher misdiagnosis rate.

Surgical Management of Syringomyelia Associated with Spinal Adhesive Arachnoiditis, a Late Complication of Tuberculous Meningitis: A Case Report / 대한신경손상학회지

Syringomyelia associated with tuberculous meningitis is an extremely rare condition. Only a few studies have reported clinical experience with syringomyelia as a late complication of tuberculous meningitis. Twenty-six years after a tuberculous meningitis episode, a 44-year-old man presented with progressively worsening spastic paresis of the lower limbs and impaired urinary function for 2 years. Radiological examination revealed syringomyelia extending from the level of C2 to T9 and arachnoiditis with atrophy of the spinal cord between C2 and T3. We performed laminectomy from C7 to T1, dissected the arachnoid adhesion and placed a syringo-pleural shunt via keyhole myelotomy. One year after the operation, his neurological condition improved. The postoperative control magnetic resonance imaging revealed the correctly located shunt and significantly diminished syringomyelia cavities. We aim to discuss the mechanism of syrinx formation following tuberculous meningitis and to share our surgical therapeutic experience with this rare disease entity.

Tuberculous Meningitis-Mimicking Varicella-Zoster Meningitis / 감염과화학요법

BACKGROUND: Varicella-zoster virus (VZV) is one of the most common etiologies of aseptic meningitis. The severest manifestation of VZV meningitis is occasionally confused with tuberculous meningitis (TBM). Thus, we investigated the clinical manifestations of VZV meningitis as compared with those of TBM. MATERIALS AND METHODS: All adult patients who were diagnosed with VZV meningitis or TBM were enrolled at a tertiary hospital in Seoul, South Korea, during an 8-year period. The clinical characteristics and cerebrospinal fluid (CSF) profile of patients were analyzed. RESULTS: Seventy-nine patients with VZV meningitis and 24 patients with TBM were enrolled in this study. Of the 79 patients with VZV meningitis, 63 (80%) did not received empirical anti-tuberculous therapy (Group 1) and the remaining 16 (20%) received empirical anti-tuberculous therapy (Group 2), compared with 24 patients with TBM (Group 3). Altered mental status, intensive care unit (ICU) admission, neurologic sequelae, CSF protein levels, and CSF adenosine deaminase levels revealed a trend of being higher in Group 3 than Group 2, which was higher than Group 1. However, the CSF/serum glucose ratio was significantly lower in Group 3 than in Group 1 or Group 2. CONCLUSION: About one fifth of VZV meningitis cases presented as severe manifestations, mimicking TBM. The CSF/serum glucose ratio might be useful to differentiate VZV meningitis from TBM until definite diagnostic tests are available. Physicians should keep in mind that a differential diagnosis between severe VZV meningitis and TBM is needed.

The comparison of the efficacy of different anti -tuberculosis schemes in the treatment of tuberculous meningitis / 中国基层医药

Objective To evaluate the clinical efficacy and safety of modified anti -tuberculosis scheme in the treatment of tuberculous meningitis.Methods 60 cases with tuberculous meningitis were randomly divided into two groups.We enrolled 30 patients in each group.The traditional anti -tuberculosis group used traditional anti -tuberculosis scheme with isoniazid,rifampicin,pyrazinamide,streptomycin,and the modified anti -tuberculosis group was given isoniazid,rifampicin,pyrazinamide,levofloxacin,the treatment course of tuberculous meningitis was 12 months.The efficacy and safety through clinical manifestations and laboratory examinations,the dynamic changes of cerebrospinal fluid were evaluated by statistical methods.Results The total effective rate of the modified anti -tuberculosis group was significantly higher than the traditional anti -tuberculosis group(86.6% vs.63.3%,χ2 =4.36,P 0.05).Conclusion Levofloxacin combined with other first -line anti -tuberculosis drugs,glucocorticoids,dehydration and other comprehensive measures improved brain function for the treatment of tuberculous meningitis is recommended.

The evaluation of Xpert MTB/RIF for the diagnosis of tuberculous meningitis / 中华检验医学杂志

Objective To evaluate the diagnostic performance of Xpert MTB/RIF for the diagnosis of tuberculous meningitis (TBM).Methods This was a prospective, single center clinical trial.A total of 116 consecutive patients with suspected meningitis who were admitted to Xijing Hospital from October 2013 to June 2015 were recruited.Mycobacterium tuberculosis ( MTB) and rifampicin ( RIF) resistance mutations in 1 ml cerebrospinal fluid ( CSF) were detected with Xpert MTB/RIF and the remaining sample was tested by Ziehl-Neelsen staining , MGIT960 liquid culture and other laboratory tests .And the enrolled patients were grouped according to the 2010 South African expert consensus .The diagnostic performance of Xpert MTB/RIF was evaluated by comparing against clinical score >5 points and MGIT960 liquid culture as reference standards respectively .The comparison was performed using a χ2 test or Fisher′s exact test for categorical variables and a nonparametric rank sum test for continuous variables .Results Among the enrolled 116 subjects, 23 subjects were diagnosed as definite-TBM by MGIT960 liquid culture, 16 subjects were classified as probable TBM , 27 subjects were classified as possible TBM , and 50 subjects were classified as non-TBM.When clinical score >5 points was used as a reference standard , the sensitivity of Xpert MTB/RIF (39.4%) was comparable with that of MGIT960 liquid culture (34.8%) (χ2 =0.292, P=0.589), and significantly better than that of Ziehl-Neelsen staining (9.9%) (χ2 =16.500, 12.771, P<0.001). No significant differences were found among the specificities of Xpert MTB /RIF, MGIT960 liquid culture and Ziehl-Neelsen staining ( 98.0%, 100.0% vs 98.0%, χ2 =1.014, P=0.602 ) .When tested against MGIT960 liquid culture as a reference standard , the sensitivity of Xpert MTB/RIF was 91.3%. Conclusions Xpert MTB/RIF is a rapid and specific method to detect MTB and RIF resistance in CSF .It exhibits a good rule in value for the diagnosis of TBM and a comparable sensitivity with MGIT 960 liquid culture, thus it can be used as the initial method for the diagnosis of tuberculous meningitis .

Hypopituitarism Presenting as Osteoporotic Fracture after Cured Tuberculous Meningitis

Tuberculous meningitis is a well-known cause of hypothalamic pituitary dysfunction. However, deficiencies of anterior pituitary hormones may only become evident years after recovery because symptoms are of insidious-onset and nonspecific. Pituitary hormones are essential for normal growth and sexual development in childhood, and for maintenance of healthy body composition. In addition, pituitary hormones and vitamin D are important for cardiovascular and bone health. Although evidence of the relationship between hypovitaminosis D and hypopituitarism is limited, some studies suggested that the incidence of vitamin D deficiency increased in hypopituitarism. We describe herein an unusual case of hypopituitarism and severe hypovitaminosis D presenting as osteoporotic fracture after cured tuberculous meningitis.

Study of miR-125b, miR-29a and miR-155-5p as biomarkers of tuberculous meningitis / 天津医药

Objective To investigate the expression levels of microRNA(miR)-125b, miR-29a and miR-155-5p in ce?rebrospinal fluid (CSF) and plasma from the patients with tuberculous meningitis and their clinic significance. Methods Cerebrospinal fluid and plasma samples were collected from 20 patients with tuberculous meningitis (tuberculous meningitis group) and 20 patients suffered from primary headache (control group). The total RNAs were extracted.The levels of miR-125b, miR-29a and miR-155-5p were determined by real-time quantitative PCR (q-PCR). Results Levels of miR-29a and miR-125b in both CSF and plasma of patients in tuberculous meningitis group were significantly higher than those in pa?tients from control group with statistical significance (P<0.01). Mean time, the level of miR-155-5p in plasma but not in CSF of patients in tuberculous meningitis group was higher than those in control group with statistical significance ( P<0.01). Conclusion Expression of miR-125b, miR-29a and miR-155-5p may participate in regulating the occurrence and development of tuberculous meningitis. And miR-125b and miR-29a may be used as potential biomarkers for diagnosing tu?berculous meningitis.