Tuberculous meningitis associated with urinary tract tuberculosis

The association of tuberculous meningitis (TBM) and urinary tract tuberculosis is very rare. Two cases of this condition are reported. Both presented with subacute to chronic meningitis with lymphocytic pleocytosis, elevation of protein content and depression of glucose level of cerebrospinal fluid. Pyuria and hematuria were detected and Ziehl-Neelsen's stain was positive for acid fast bacilli (AFB). Urographic abnormalities were compatible with urinary tract tuberculosis. AFB smear of urine is the simplest method to detect urinary tract tuberculosis.     

结核性脑膜炎100例临床分析

目的探讨成人结核性脑膜炎的临床特点、脑脊液改变、影像学特点、诊治方法及其转归。方法回顾性分析1982年1月至2003年12月间在北京协和医院确诊或临床诊断为结核性脑膜炎的100例住院患者的临床资料。结果100例结核性脑膜炎患者中,男性49例,女性51例;年龄（31±11）岁。70％为慢性病程（11．1±9．2）周。13例确诊病例,脑脊液结核杆菌培养阳性,或开颅脑活检病理证实为结核性肉芽肿或粟粒样结核;87例为临床诊断病例。临床表现以发热（97％）,头痛（92％）、意识障碍（71％）和脑膜刺激征多见（77％）,44例伴颅神经损害,以动眼神经和外展神经受损为主。35例X线胸片有活动性肺结核表现,肺外活动性结核12例,陈旧性肺结核18例。腰穿示颅内压增高者占86％,脑脊液呈非化脓性改变,白细胞增高以淋巴细胞为主,蛋白质明显增高,葡萄糖显著下降。52例患者头颅影像学有异常发现,脑室扩张、交通性脑积水和脑梗死最常见。全部病例均接受抗结核治疗,9例行侧脑室外引流术。81例患者病情好转,4例因合并开放性肺结核转结核病院治疗,8例自动出院,死亡7例。结论慢性脑膜炎若伴发肺结核或肺外结核者应高度疑诊结核性,鉴别诊断和诊断性抗结核治疗有效有助诊断。脑脊液涂片和（或）培养抗酸杆菌／结核分枝杆菌阳性,以及脑活检为诊断的金标准。早期诊断、早期治疗是改善本病预后的关键。     

结核性脑膜炎患者脑脊液中腺苷脱氨酶和结核抗体水平研究

目的探讨结核性脑膜炎(TBM)的早期诊断方法。方法采用氨的偶联酶测定法和酶联免疫吸附实验(ELISA)检测3组病例(结脑组51例,病脑组30例,非脑膜炎组20例)脑脊液(CSF)中腺苷脱氨酶(ADA)的活性水平和脑脊液结核抗体(PPD-IgG)的阳性率。结果研究发现结脑组脑脊液中腺苷脱氨酶活性水平明显升高,与病脑组和非脑膜炎组比较有显著性差异(p<0.01)。而病脑组与非脑膜炎组比较无显著性差异(p>0.05);结核性脑膜炎早期脑脊液中结核抗体的阳性率为80.4%(其中2周内PPD-IgG阳性率为80.4%,1周内为23.5%,其他为3.9%),在随后的临床跟踪检测中为100%。结论说明共同检测脑脊液中腺苷脱氨酶的活性明显升高和结核抗体阳性可以作为结脑早期诊断的重要依据。     

Detection of antibody to Mycobacterium tuberculosis protein antigens in the cerebrospinal fluid of patients with tuberculous meningitis

Antibodies against Mycobacterium tuberculosis antigens were detected by enzyme-linked immunosorbent assay in cerebrospinal fluid (CSF) samples obtained from 442 patients with tuberculous meningitis (TBM) and 102 control patients. Antibodies were found in the CSF of 87% of patients with clinical (culture-negative) TBM, 72% of patients with culture-positive TBM, and 65% of patients with autopsy-proven TBM. That anti-M. tuberculosis antibodies were detected in the CSF of patients with clinically diagnosed cases more frequently than in patients with culture-positive cases suggests that the detection of antibodies in CSF tends to decrease as bacillary load increases. Of the patients with clinical TBM who were coinfected with human immunodeficiency virus (HIV), 70% exhibited anti-M. tuberculosis antibody in CSF, which suggests that antibody responses in this group were substantially weaker than those in HIV-negative patients with clinical TBM. Some groups showed a stronger response to certain antigens, which suggests that antigen recognition patterns may be specific for the stage of disease.     

Rapid diagnosis of Mycobacterium tuberculosis meningitis by enumeration of cerebrospinal fluid antigen-specific T-cells.

SETTING: Hospital in-patients with suspected tuberculous meningitis (TBM), predominantly in India. OBJECTIVE: To determine whether interferon-gamma (IFN-gamma) secreting Mycobacterium tuberculosis antigen-specific T-cells are present in the cerebrospinal fluid (CSF) of patients with TBM and to evaluate the feasibility of CSF enzyme-linked immunospot (ELISpot) for the diagnosis of active TBM. DESIGN: Prospective blinded hospital-based study. RESULTS: The overnight ELISpot assay detected M. tuberculosis antigen-specific IFN-gamma secreting T-cells in CSF from nine of 10 prospectively recruited patients with TBM, and zero of seven control patients with meningitis of other aetiology. This corresponds to a diagnostic sensitivity of 90% (95%CI 56-100) and specificity of 100% (95%CI 59-100). CONCLUSION: This pilot study demonstrates proof-of-principle for a new T-cell-based diagnostic test for TBM which is rapid, sensitive and specific.     

不典型表现的结核性脑膜炎62例临床分析

目的　总结不典表现的结核性脑膜炎 (结脑)的诊断与治疗。方法 回顾性分析 62例不典型结脑患者的临床资料。结果 本组病例在临床上没有典型的结脑症状，表现意识障碍 17例(27.4%)、头晕、低热 47例 (75.8%)、乏力、精神萎靡 13例 (21.0%)；肢体麻木 21例 (33.9%)、瘫痪5例 (8.1%)、颅神经损害 18例 (29.0%)和尿潴留 10例；(16.1%)、癫痫样发作 4例 (6.5%)。胸部影像学检查阳性 37例 (59.7%)、头颅CT阳性 13例 (21%)。脑脊液检查 :糖降低 30例 (48.4%)、氯化物降低 32例 (51.6%)、蛋白升高 36例 (58.1%)、腺苷酸脱氨酶 (ADA)阳性 58例 (93.5%)、结核抗体 (PPD IgG)阳性 48例 (77.4%)、涂片抗酸杆菌阳性 2例 (3.2%)。 61例经抗结核治疗痊愈，1例死亡。结论 不典型结脑临床表现缺乏特异性，脑脊液改变不典型，但脑脊液中结核抗体阳性对于诊断中枢神经系统结核病有参考意义，且腺苷酸脱氨酶是一个敏感及特异性强的指标，实验实及影像学检查对确诊该病有重要意义。规范抗结核治疗配合鞘内注射效果佳。     

Efficiency of polymerase chain reaction for the diagnosis of tuberculous meningitis

The early diagnosis of tuberculous meningitis (TBM) is very important. In this study, the efficiency of the polymerase chain reaction (PCR), one of the most reliable and sensitive DNA-based assays, was compared with conventional methods (acid-fast microscopy and culture) for the detection of M. tuberculosis in cerebrospinal fluid(CSF) specimens from patients suspected of TBM. Of the 29 CSF specimens from highly-probable TBM patients (based on clinical features), 25 were positive by PCR (86.2%), whereas only one of 29 was acid-fast microscopy (AFM) positive (3.4%), and 5 out of 29 were culture-positive (17.2%). No positive results were found by AFM, culture or PCR in the non-tuberculous control group. The results of this study indicate that the application of PCR should be extremely useful in the diagnosis of TBM.     

头颅MR增强扫描在急性血行播散性肺结核患者中筛查结核性脑膜炎的价值

目的 探讨头颅MR增强扫描在急性血行播散性肺结核患者中筛查结核性脑膜炎的价值。方法 搜集北京胸科医院2012年1月至2018年5月住院的415例急性血行播散性肺结核患者的临床资料,筛选出进行了头颅MR增强扫描及脑脊液常规及生化检查的患者235例,男∶女=1.12∶1(124/111),年龄15~87岁,平均年龄(36±18)岁,15~35岁年龄组患者占62.1%(146/235)。采用SPSS 22.0软件进行统计分析,计数资料组间比较采用卡方检验。当总数>40,且1<理论频数<5时采用校正卡方检验。配对计数资料的比较采用配对卡方检验,以P<0.05为差异有统计学意义。结果 235例急性血行播散性肺结核患者,头颅MR增强扫描发现的异常率(89.8%,211/235)较脑脊液常规及生化(63.0%,148/235)高,差异有统计学意义(McNemar检验,P=0.000)。按照结核性脑膜炎诊断标准,“确诊”及“很可能”结核性脑膜炎219例中,头颅MR增强扫描发现的异常率(96.3%,211/219)较脑脊液常规及生化检查(67.6%,148/219)高,且差异有统计学意义(McNemar检验,P=0.000)。有中枢神经系统症状的143例患者中,头颅MR增强扫描发现的异常率(95.8%,137/143)较脑脊液常规及生化发现的异常率(88.1%,126/143)高,差异有统计学意义(McNemar检验,P=0.035)。无中枢神经系统症状的76例患者中,头颅MR增强扫描发现的异常率(97.4%,74/76)较脑脊液常规及生化高(28.9%,22/76),差异有统计学意义(McNemar检验,P=0.000)。有中枢神经系统症状与无中枢神经系统症状患者的头颅MR增强扫描发现的异常率[95.8%(137/143)与97.4%(74/76)]比较,差异无统计学意义(校正χ ²检验,P=0.834);有中枢神经系统症状较无中枢神经系统症状患者脑脊液常规及生化检查发现的异常率[88.1%(126/143)与28.9%(22/76)]高,差异有统计学意义(χ ²=79.286,P=0.000)。 结论 头颅MR增强扫描在急性血行播散性肺结核患者中对颅内病变的发现率高;特别是对于无神经系统症状的结核性脑膜炎患者,脑脊液常规及生化检查发现的异常率偏低,而头颅MR增强扫描发现的异常率仍>95%。     

Neoplastic meningitis with eosinophilic pleocytosis in Hodgkin's disease: a case with cerebellar dysfunction and a review of the literature

A 31-year-old man had Hodgkin's disease (stage IIA, nodular sclerosis) in apparent remission after radiotherapy. Nine months after the diagnosis of Hodgkin's disease, he developed neoplastic meningitis with eosinophilic pleocytosis and neurologic findings suggestive of peri-fourth ventricle infiltration. Morphologic and surface marker analysis of cerebrospinal fluid cells showed large numbers of T-lymphocytes and Reed-Sternberg variant cells positive for CD15, the Lex hapten expressed on myeloid cells and on a variety of malignant cells. Therapy with intrathecal methotrexate, oral dexamethasone, and cranial irradiation resulted in prompt resolution of his cerebrospinal fluid abnormalities and neurologic deficits. Ten months after the diagnosis of eosinophilic meningitis, systemic relapse of Hodgkin's disease occurred in right iliac and inguinal lymph nodes. The diagnosis, pathogenesis, and therapy of this unusual complication of Hodgkin's disease are reviewed.     

Correlation between culture of Mycobacterium tuberculosis and IgG antibody to Mycobacterium tuberculosis antigen-5 in the cerebrospinal fluid of patients with tuberculous meningitis

A retrospective study was made of the correlation between culture of Mycobacterium tuberculosis and detection of IgG antibody to M. tuberculosis antigen-5 in cerebrospinal fluid (CSF) by means of an enzyme linked immunosorbent assay (ELISA). Mycobacterium tuberculosis was cultured from the CSF in 14 of 70 patients with a clinical diagnosis of tuberculous meningitis (TBM). IgG antibody to M. tuberculosis antigen-5 was demonstrated in significant titres (80-640) in all 14 culture-positive patients. Thus, positive correlation was observed between culture of M. tuberculosis and detection of IgG antibody in the CSF. As a result of this observation, the CSF from 56 culture-negative patients with a clinical diagnosis TBM was specifically investigated for the detection of IgG antibody to M. tuberculosis antigen-5 and the findings were correlated with those of culture-positive patients. The assay was positive in 34 of 56 patients, the antibody titre ranging between 80 and 640. In the CSF of 70 patients with non-tuberculous neurological diseases, the assay was negative at a dilution of 1 in 80. Thus, detection of IgG antibody to M. tuberculosis antigen-5 by indirect ELISA carried 100% specificity and 60.7% sensitivity for a tuberculous aetiology in culture-negative patients with TBM. The results of this study suggest that indirect ELISA for IgG antibody to M. tuberculosis antigen-5 in CSF holds definite promise in diagnosis of TBM, particularly when repeated cultures of CSF are negative for M. tuberculosis.     

Diagnostic utility of cerebrospinal fluid studies in patients with clinically suspected tuberculous meningitis.

OBJECTIVE: To compare yields of cerebrospinal fluid (CSF) studies in the diagnosis of tuberculosis meningitis (TBM). DESIGN: Prospective laboratory study, Kenyatta National Hospital, Kenya. STUDY POPULATION: Consecutive patients with 1) headache, neck stiffness and altered consciousness for more than 14 days, 2) above features plus evidence of tuberculosis elsewhere in the body, and 3) on standard antimeningitic drugs for one week without response, were included. Those with contraindications to lumbar puncture, confirmed causes of meningitis (except TB) and on anti-tuberculosis treatment were excluded. METHODS: CSF cell counts, glucose and protein were assayed. CSF was stained on ZN, cultured on LJ and BACTEC and subjected to PCR and LCR for Mycobacterium tuberculosis DNA sequences. Positive tests for M. tuberculosis were classified as definite and the rest as probable TBM. RESULTS: Fifty-eight patients with a mean age of 33.0 years were recruited. Mean CSF cell count was 71/microl and CSF lymphocyte count up 67%. Mean CFS protein and glucose were 2.10 g/l and 2.05 mmol/l, respectively. BACTEC was positive in 20 cases, LJ 12, LCR eight, and PCR and ZN one each. Twenty-six patients had definite and 32 probable TBM. Patients with definite TBM had significantly higher CSF protein, lower CSF glucose, higher CSF cell count and lower CSF lymphocytes. CONCLUSION: TBM can be confirmed in half of clinically suspected cases. More sensitive tests for confirmation of TBM are required.     

Detection and its clinical significance of IgM antibody in cerebrospinal fluid in patients with tuberculous meningitis

Specific antibody for IgM in cerebrospinal fluid (CSF) of 45 patients with tuberculous meningitis (TBM), 33 patients with non-TBM and 51 control patients was determined by enzyme-linked immunosorbent assay, and compared with specific antibody for IgG. The sensitivity and specificity was 71.1% and 98.8% for IgM antibody, and 88.9% and 96.4% for IgG antibody respectively, but the positive rate of IgM antibody at early stage of TBM was higher than that of IgG antibody. There was a highly significant positive correlation between positive rates of the two types of antibody and contents of protein in CSF. The sensitivity and specificity was 97.8% and 98.8% respectively in detecting both the IgM and IgG antibodies in CSF simultaneously, which can be used as a supplementary method for the diagnosis of TBM.     

TB PCR in the early diagnosis of tuberculous meningitis: evaluation of the Roche semi-automated COBAS Amplicor MTB test with reference to the manual Amplicor MTB PCR test. .

SETTING: Cecilia Makiwane Hospital, Mdantsane, Eastern Cape, Republic of South Africa. OBJECTIVE: To assess the role of the semi-automated Roche COBAS AMPLICOR(TM)Mycobacterium tuberculosis PCR test in the diagnosis of tuberculous meningitis (TBM). DESIGN: Eighty-three specimens of cerebrospinal fluid (CSF) were collected prospectively from 69 patients with suspected TBM. The COBAS AMPLICOR TB PCR test was compared with the manual AMPLICOR(TM)TB PCR test, clinical and cerebrospinal fluid (CSF) findings, direct ZN smear and radiometric TB culture. RESULTS: CSF from 7/40 (17.5%) patients treated for TBM were positive by TB COBAS AMPLICOR(TM). The sensitivity of the test was not significantly different (p=0.375) from the manual TB AMPLICOR(TM)PCR test. The comparative sensitivities of the TB COBAS AMPLICOR(TM)PCR and the manual AMPLICOR PCR for detecting cases of definite and probable TBM from CSF collected within 9 days of commencing antituberculosis treatment were 40% and 60% respectively. All 29 patients not treated for TBM were negative by COBAS AMPLICOR(TM), giving a specificity of 100%. CONCLUSION: The COBAS AMPLICOR(TM)TB PCR test is a rapid and highly specific diagnostic test for TBM. However, there was a non-significant trend favouring slightly greater sensitivity using the manual AMPLICOR(TM)TB PCR test.     

Rapid molecular diagnosis of tuberculous meningitis using the Gen-probe Amplified Mycobacterium Tuberculosis direct test in a large Canadian public health laboratory.

OBJECTIVE: A 5-year retrospective study of the performance of the Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (MTD) for detecting Mycobacterium tuberculosis complex in cerebrospinal fluid (CSF). Patient data from culture-confirmed cases of tuberculous meningitis (TBM) were also analysed. RESULTS: In total, 311 CSF specimens were tested by the MTD, of which 17 were positive. When compared with culture (gold standard), the sensitivity and specificity of the MTD test were 93.8% and 99.3%, respectively. The positive and negative predictive values for TBM were 88.2%, and 99.7%. Clinical and epidemiological information was requested for all culture-positive TBM patients. These data were used to assess the mortality rate (55.6%) and to determine common factors that could be applied as selection criteria for the appropriate testing of CSF by MTD. CONCLUSION: The study found the MTD test to be a rapid, sensitive and specific test for TBM. A history of immigration from an area endemic for tuberculosis (TB), a history of TB, symptoms of neurological deficits and the results of CSF analyses could be used to appropriately select CSF for MTD testing in order to provide a critical early diagnosis of TBM.     

结核性脑膜炎患者行脑脊液实验室检测方法的现状与进展

结核性脑膜炎(tuberculous meningitis,TBM)是最常见的肺外结核之一,约占全部结核病患者的1%;但死亡率可达26.8%,死亡多发生在患病最初的6个月,早期诊断及治疗是改善TBM预后的重要因素。临床上对TBM的诊断是通过临床表现、脑脊液检测、头颅影像学检查及是否并发颅外结核等综合分析后作出的。脑脊液检测是诊断TBM的重要指标,通过检测脑脊液中的结核分枝杆菌及其特异性的标志物,可以为TBM的诊断提供重要帮助。     

脑脊液检测在结核性脑膜炎早期诊断中的研究进展

结核性脑膜炎(tuberculous meningitis,TBM)是肺外结核中最严重的临床表现类型,具有较高的病死率及致残率,故早期、快速诊断及鉴别诊断TBM对疾病的治疗和预后至关重要。笔者通过综述近年来脑脊液(cerebrospinal fluid,CSF)检测在TBM早期诊断及与化脓性脑膜炎、病毒性脑膜炎(viral meningitis,VM)和新型隐球菌性脑膜炎(cryptococcul neoformans meningitis,CNM)的鉴别诊断方法,旨在为TBM的早期诊断与鉴别诊断提供一定的诊疗思路。     

艾滋病合并结核性脑膜炎32例临床分析

目的 探讨艾滋病合并结核性脑膜炎(TBM)的临床特征、诊断和治疗,提高艾滋病合并TBM的认识。 方法 回顾性总结1999年1月-2009年12月收治的32例艾滋病合并TBM的临床资料。 结果发热30例、头痛29例、意识障碍18例、抽搐12例,脑膜刺激征25例,咳嗽27例,咳痰25例。不同程度存在艾滋病相关表现。常合并肺结核（75%）及其他肺外结核（12.5%）。所有病例CD4＜200/mm³。脑脊液压力升高,白细胞升高,蛋白质升高,糖降低,氯化物降低,ADA 升高。结论 艾滋病合并TBM临床表现复杂,无特异性,病情重,致残率高,死亡率高。治疗上抗结核治疗+激素,适时联合HARRT治疗可降低病死率,提高生活质量,延长生命。     

宏基因组二代测序技术检测脑脊液在结核性脑膜炎诊断中的应用价值的Meta分析

目的 评价宏基因组二代测序技术检测脑脊液在结核性脑膜炎诊断中的应用价值。方法 通过计算机检索PubMed、Embase、Cochrane Library、中国知网、万方、维普等数据库。中文检索词:宏基因组二代测序、二代测序、结核、结核性脑膜炎;英文检索词:metagenomic next-generation sequencing、mNGS、next-generation sequencing、tuberculosis、tuberculous meningitis、tuberculosis meningitis。收集从建库至2021年4月30日发表的宏基因组二代测序技术应用于脑脊液检测诊断结核性脑膜炎的相关文献,由2名研究者独立进行文献检索、筛选、数据提取,质量评价。以MetaDisc 1.4 软件进行Meta分析。结果 检索出628篇文献,依据纳入和排除标准最终纳入7篇文献,包含477例患者,其中结核性脑膜炎患者231例。Meta分析结果显示,宏基因组二代测序技术检测脑脊液诊断结核性脑膜炎的汇总敏感度为62.0%(95%CI: 55.0%~68.0%)、汇总特异度为97.0%(95%CI: 94.0%~99.0%)、汇总阳性似然比为10.57(95%CI:4.84~23.11)、汇总阴性似然比为0.41(95%CI:0.27~0.60)、汇总诊断OR值为21.39(95%CI:10.18~44.95)、汇总受试者工作特征曲线下面积为0.956。结论 宏基因组应用于脑脊液检测对结核性脑膜炎具有较高的诊断价值,可作为快速诊断结核性脑膜炎的有效方法。     

20例成人耐药结核性脑膜炎临床观察

目的分析成人耐药结核性脑膜炎(结脑)的临床特点。方法对2008年1月—2008年12月住院的20例成人耐药结脑病例进行回顾性分析。结果20例脑脊液结核分枝杆菌培养阳性中,耐单药者10例,多耐药者6例,耐多药(MDR)者4例。耐药结脑病情危重,合并意识障碍者10例(50%),合并高颅压者18例(90%),脑脊液常规生化及细胞学符合典型结脑特点,脑膜脑炎8例(40%),脑脊髓膜炎4例(20%)。抗结核并辅助激素和脱水药物治疗好转19例,死亡1例。结论耐药结脑经早期抗结核并辅助治疗,疗效满意。     

Serial lactate determinations in tuberculous meningitis

Lactate levels in the cerebrospinal fluid (CSF) were determined in 21 patients with culture-proved tuberculous meningitis (TBM). All patients showed uniformly high lactate level (greater than or equal to 3.9 mmol/l). Neither the clinical stage of TBM nor the prognosis was related to the CSF lactate concentration. Repeated CSF studies demonstrated persistently high lactate levels in the early stage of illness despite adequate antituberculous therapy.