不同剂量异烟肼对结核性脑膜炎患者的影响

目的:探析结核性脑膜炎应用不同剂量异烟肼治疗对患者预后及临床症状的改善效果。方法:将2016年4月～2018年1月收治的100例结核性脑膜炎患者随机分为对照组和观察组各50例。两组患者均采取常规四联疗法,对照组在此基础上给予地塞米松2.5 mg与异烟肼0.05 g鞘内注射,观察组给予地塞米松5.0 mg与异烟肼0.10 g鞘内注射。比较两组临床疗效、脑脊液炎症指标水平及不良反应发生情况。结果:观察组治疗总有效率高于对照组(P0.05);治疗后观察组脑脊液白细胞计数、蛋白含量低于对照组,葡萄糖水平高于对照组(P0.05);两组患者用药不良反应比较无明显差异(P0.05)。结论:高剂量异烟肼鞘内注射治疗可有效提高结核性脑膜炎患者的临床疗效,改善脑脊液炎症状态,且具有一定的安全性。     

结核分枝杆菌异烟肼耐药基因突变与其他抗结核药物耐药的相关性

目的 探讨不同抗结核药物对结核分枝杆菌异烟肼耐药相关基因突变的影响，以进一步准确理解结核分枝杆菌异烟肼耐药的分子机制。方法 在广州地区分枝杆菌菌株库中选择异烟肼、利福平、乙胺丁醇、链霉素、阿米卡星、克拉霉素、左氧氟沙星、莫西沙星、利福布丁、丙硫异烟胺和对氨基水杨酸等11种抗结核药物的药敏性试验临床测定结果明确的结核分枝杆菌分离株进行katG、mabA-inhA、oxy RahpC、kasA和ndh基因测序，以结核分枝杆菌H37Rv标准序列为参照进行基因突变分析，应用卡方检验对比分析H^-(R/F/O)^-与H^-(R/F/O)⁺、H⁺R^-与H⁺R⁺、H⁺F^-与H⁺F⁺和H⁺O^-与H⁺O⁺几大菌群之间5种基因突变发生总频率的差异(其中R、H、F、O...     

结核性脑膜炎脑脊液检测标志物研究进展

结核(Tuberculosis,TB)是最古老、最具破坏性的传染病之一,全球近三分之一的人感染了结核分枝杆菌(Mycobacterium tuberculosis,Mtb)。结核性脑膜炎是肺外结核的最严重形式,导致高致残率和致死率,约占全部结核病的1%。结核性脑膜炎(tuberculous meningitis,TBM)的早期诊断和治疗对预后至关重要。目前关于TBM实验室检查主要有脑脊液抗酸杆菌(acid‐fast bacillus,AFB)涂片、细菌培养、PCR技术及新型的抗原抗体检测等,本文对TBM脑脊液检测标志物研究进展做一综述。     

肺结核与结核性脑膜炎病例中结核分枝杆菌耐利福平相关基因突变分布分析

目的分析结核性脑膜炎与肺结核病例中,导致结核分枝杆菌利福平耐药的rpoB基因突变分布规律及差异。方法对包含利福平耐药决定区81bp的102株结核分枝杆菌临床分离株的PCR产物进行测序分析。结果 102株利福平耐药的结核分枝杆菌的rpoB基因测序发现,63株导致肺结核的结核分枝杆菌的rpoB基因突变常见位点为:531(53.97%),526(20.63%),516(6.45%)。39株导致结核性脑脑膜炎的rpoB基因突变最常见位点为:531(61.54%),526(20.51%),533(7.69%)。结论导致结核性脑膜炎与导致肺结核的结核分枝杆菌耐利福平rpoB基因的最常见两个突变位点(531和526)无显著差异。其中531位密码子的Ser-Leu突变率占明显优势。     

结核性脑膜炎76例死亡分析

我院近10年共收治结核性脑膜炎(简称结脑)363例,其中死亡76例,根据临床资料分析如下。 1 临床资料 男35例,女41例。年龄6月～73岁,其中14～50岁60例。急性起病3例,亚急性起病73例。临床有结核中毒症状者61例(占80.3％),有头痛、呕吐、发热、脑膜刺激征50例(占65.8％),截瘫3例,偏瘫9例,抽搐13例,精神异常9例,意识障碍58例。76例均有脑脊液典型改变,墨汁染色均阴性。有脑外结核31例(占40.8％),42例作脑脊液免疫学检查,结果IgG140.42～180.53mg/L,IgA25.45～31.35mg/L,IgM15.38～19.88mg/L。42例作脑脊液涂片找抗酸杆菌2例阳性。25例作脑脊液直接荧光抗体检查阳性20例。曾误诊为散发性脑炎9例,化脑5例,蛛网膜下腔出血2例,感染性腹泻3例。死于脑疝30例,全身衰竭26例,呼吸循环衰竭20例。     

结核性脑膜炎30例临床与CT分析

报告３０例结核性脑膜炎患者的临床和ＣＴ表现，结果提示对早期结脑要有高度的警惕性，ＣＴ对结脑有诊断价值；并体会到ＣＴ对结脑，特别是晚期结脑的治疗有一定的指导意义。     

鞘内注射异烟肼加地塞米松同时等量生理盐水置换治疗结核性脑膜炎临床疗效观察

目的 观察脑脊液置换联合鞘内注射给药治疗结核性脑膜炎的临床疗效.方法 对我院2004年8月至2006年12月期间收治的60例成年结核性脑膜炎患者随机分为治疗组与观察组各30例,分别采用鞘内注射INH加地塞米松同时等量生理盐水置换和四联抗痨方法治疗.结果 治疗组比观察组临床症状消失和脑脊液恢复正常时间明显缩短,疗效差异有显著性.结论 治疗结核性脑膜炎时采取加鞘内注射INH及地塞米松同时等量生理盐水置换治疗是一种比较经济实用和安全有效的方法.     

结核性脑膜炎的CT与临床分析

作者报告56例结核性脑膜炎(TBM)的临床和CT改变，CT对TBM的检出率为83．9％。病损类型将其分为8类：(1)脑积水；(2)脑底部增生性脑膜炎；(3)脑结核瘤；(4)血管炎所致的脑梗塞；(5)脑萎缩；(6)并出血；(7)栗粒型脑结核；(8)正常。根据CT改变，就诊断和治疗等有关问题做了讨论。CT检查可为TBM病人的病损类型、病变部位、累及范围、病理形态提供准确的定位及定性诊断依据。对临床型、病期判定、指导治疗方案及预后估价有重要意义。     

Enzyme-linked immunosorbent assay to detect Mycobacterium tuberculosis antigen 5 and antimycobacterial antibody in cerebrospinal fluid of patients with tuberculous meningitis

Inhibition ELISA and indirect ELISA was standardised to detect Mycobacterium tuberculosis antigen 5 and antimycobacterial antibody in cerebrospinal fluid (CSF) specimens of 75 patients with tuberculous meningitis, (TBM) and 75 patients with non-tuberculous neurological diseases (control group). In both ELISAs, no false-negative results were observed in 15 culture proven patients with TBM. Detection of M. tuberculosis antigen 5 is more sensitive than detection of antimycobacterial antibody. However, both ELISAs showed 100% specificity for tuberculous aetiology in culture-negative patients with TBM. ELISA should be considered as one of the approaches in the laboratory diagnosis of TBM, particularly when standard bacteriological methods are unable to demonstrate M. tuberculosis in CSF specimens of patients with TBM.     

脑脊液单核细胞内结核抗原检测在结核性脑膜炎早期诊断中的价值

目的探讨脑脊液单核细胞内结核抗原检测在结核性脑膜炎临床诊断中的价值。方法脑脊液样本120例,其中结核性脑膜炎组60例,对照组60例,采用免疫组化法检测脑脊液中单核细胞内的结核抗原,同时进行脑脊液细胞学检查。结果与对照组比较,结脑组中性粒细胞、淋巴样细胞(包括转移淋巴)、激活单核细胞明显升高,差异均有统计学意义(χ2分别=22.76、17.05、4.04、11.76,P均<0.05)。结核性脑膜炎患者脑脊液中单核细胞内存在结核菌素抗原,60例结核性脑膜炎患者中首次检查48例阳性,敏感性为80.00%;对照组有1例阳性,特异性为98.33%,结核性脑膜炎组和对照组多次检测结果敏感性和特异性均较高,差异均有统计学意义(χ2分别=76.19、71.55、35.28,P均<0.05)。结论检测脑脊液中单核细胞内结核抗原可以做为结核性脑膜炎早期诊断的一种重要手段。     

T细胞斑点试验在结核性脑膜炎诊断中的应用价值

目的分析结核感染T细胞斑点试验(T-SPOT.TB)在结核性脑膜炎诊断中的应用价值。方法以2017年1月-2019年12月安徽省胸科医院收治的93例脑膜炎患者为研究对象,其中确诊或临床诊断为结核性脑膜炎62例,非结核性脑膜炎31例。所有入组患者治疗前均检测外周血T-SPOT.TB,脑脊液腺苷脱氨酶(ADA)、结核分枝杆菌DNA(TBDNA)、抗酸杆菌(AFB)涂片,对试验结果进行分析。结果外周血T-SPOT.TB检测诊断结核性脑膜炎的灵敏度为82.3%(51/62),特异度为80.7%(25/31),灵敏度明显高于脑脊液ADA(61.3%,38/62)、脑脊液TB-DNA(27.4%,17/62)、脑脊液AFB涂片(16.1%,10/62),差异均有显著统计学意义(P<0.01)。采用受试者工作特征(ROC)曲线及其曲线下面积(AUC)来分析不同试验方法的诊断价值,外周血T-SPOT.TB、脑脊液ADA、脑脊液TB-DNA和脑脊液AFB涂片的AUC值分别为0.815、0.661、0.637、0.581。外周血T-SPOT.TB在结核性脑膜炎中的诊断效能最高。结论外周血T-SPOT.TB在结核性脑膜炎的诊断中,可作为可靠的辅助参考指标之一。     

结核性脑膜炎患者脑脊液中腺苷脱氨酶的动态观察

目的　动态观察结核性脑膜炎患者脑脊液中腺苷脱氨酶的变化 ,以期对结核性脑膜炎的早期诊断和预后判断提供依据。方法　采用比色法动态检测 4 3例结核性脑膜炎患者脑脊液中腺苷脱氨酶活力的变化 ,并以 2 2例病毒性脑膜炎患者作为对照组。结果　 4 3例结核性脑膜炎患者酶活性较对照组明显升高 ,差异有统计学意义 (P <0 .0 5 ) ,治疗后 2周内结核性脑膜炎患者腺苷脱氨酶活力较其他时间明显增高 ,此后腺苷脱氨酶活力随治疗时间的延长呈进行性下降趋势。另外 8例有不同程度的神经系统并发症结核性脑膜炎患者呈现持续高水平。结论　检测脑脊液中腺苷脱氨酶是早期诊断结核性脑膜炎的一个简单而可靠的方法 ;动态观察腺苷脱氨酶还能对疾病的预后判断提供依据。     

结核性脑膜炎高热病人的亚低温护理探讨

[目的]探讨结核性脑膜炎高热病人的亚低温护理方法。[方法]以整体护理为指导,按照PDCA程序,在降温方法、症状监测与护理、并发症的防护、基础护理等方面进行规范和指引。[结果]亚低温治疗期病人无冻伤、压疮、肺部感染、泌尿系感染、电解质紊乱、胃出血、心律失常等并发症发生。[结论]亚低温降温护理能保证亚低温治疗的顺利进行,有效降低晚期结核性脑膜炎高热病人体温。     

脑脊液与外周血T-SPOT.TB检测在结核性脑膜炎诊断中的临床应用价值

目的探讨脑脊液与外周血结核感染T细胞斑点试验(T-SPOT.TB)在结核性脑膜炎(TBM)诊断中的临床价值。方法选取2015年9月至2016年9月该院收治的35例TBM患者和40例非TBM患者分别作为观察组和对照组,采用TSPOT.TB检测脑脊液和外周血单个核细胞中结核分枝杆菌效应T细胞。结果观察组脑脊液、外周血T-SPOT.TB检测的阳性率(97.14%、80.00%)明显高于对照组(2.50%、0.00%),差异有统计学意义(P0.05);脑脊液T-SPOT.TB检测的灵敏度、阴性预测值(97.14%、97.50%)明显高于外周血(80.00%、85.11%),差异有统计学意义(P0.05);脑脊液T-SPOT.TB检测的特异度、阳性预测值(97.50%、97.14%)和外周血(100.00%、100.00%)比较,差异无统计学意义(P0.05)。结论脑脊液和外周血T-SPOT.TB检测可对TBM提供早期诊断依据,且脑脊液T-SPOT.TB检测灵敏性较高,具有重要的临床应用价值。     

Normal cerebrospinal fluid protein and associated clinical characteristics in children with tuberculous meningitis

BackgroundAlthough abnormal cerebrospinal fluid (CSF) protein can be used to predict the outcome of tuberculous meningitis (TBM) and diagnose TBM, normal CSF protein remains a concern in patients with TBM. This retrospective study aimed to assess the clinical characteristics associated with normal CSF protein, to resolve the dilemma of CSF protein in the management of childhood TBM.MethodsBetween January 2006 and December 2019, consecutive child patients (≤15 years old, a diagnosis of TBM, and tested for CSF protein) were included for analysis. CSF protein was tested on a chemistry analyzer using the pyrogallol red-molybdate method. Abnormal CSF protein was defined as >450 mg/L. Patient characteristics were collected from the electronic medical records. Then, characteristics associated with normal CSF protein were estimated in the study, using univariate and multivariate logistic regression analysis.ResultsA total of 125 children who met the criteria were enrolled during the study period. Twenty-nine patients had a normal CSF protein and 96 had an abnormal CSF protein. Multivariate analysis (Hosmer–Lemeshow goodness-of-fit test: χ²=2.486, df = 8, p = .962) revealed that vomiting (age- and sex-adjusted OR = 0.253, 95% CI: 0.091, 0.701; p = .008) and serum glucose (>5.08 mmol/L; age- and sex-adjusted OR = 0.119, 95% CI: 0.032, 0.443; p = .002) were associated with the normal CSF protein in childhood TBM.ConclusionIn suspected childhood TBM, patients without vomiting or having low serum glucose are easy to present with normal CSF protein. Hence, when interpreting the level of CSF protein in children with such characteristics, a careful clinical assessment is required.

KEY MESSAGES

• In suspected childhood tuberculous meningitis, patients without vomiting or having low serum glucose are easy to present with normal CSF protein. Hence, when interpreting the level of CSF protein in children with such characteristics, a careful clinical assessment is required.

     

Drug-resistant tuberculous meningitis

Drug-resistant tuberculosis, including drug-resistant tuberculous meningitis, is an emerging health problem in many countries. An association with Beijing strains and drug resistance-related mutations, such as mutations in katG and rpoB genes, has been found. The pathology, clinical features and neuroimaging characteristics of drug-resistant tuberculous meningitis are similar to drug-responsive tuberculous meningitis. Detection of mycobacteria in cerebrospinal fluid (CSF) by conventional methods (smear examination or culture) is often difficult. Nucleic acid amplification assays are better methods owing to their rapidity and high sensitivity. The Xpert^® MTB/RIF assay (Cepheid, CA, USA) is a fully-automated test that has also been found to be effective for CSF samples. Treatment of multidrug-resistant tuberculous meningitis depends on the drug susceptibility pattern of the isolate and/or the previous treatment history of the patient. Second-line drugs with good penetration of the CSF should be preferred. Isoniazid monoresistant disease requires addition of another drug with better CSF penetration. Drug-resistant tuberculous meningitis is associated with a high mortality. HIV infected patients with drug-resistant tuberculous meningitis have severe clinical manifestations with exceptionally high mortality. Prevention of tuberculosis is the key to reduce drug-resistant tuberculous meningitis.     

Diagnostic scoring system for tuberculous meningitis among adult patients with non-suppurative and non-bacterial meningitis

Tuberculous meningitis (TBM) is the most severe form of extra-pulmonary tuberculosis. The definite diagnosis of this disease is difficult and can result in delayed treatment. Conventional culture yields low sensitivity while high-sensitivity diagnostic techniques are costly and unpractical. Adenosine deaminase (ADA) is used to diagnose several settings of extra-pulmonary tuberculosis but it is limited in TBM especially among HIV-infected patients. We retrospectively reviewed the data of patients with non-suppurative meningitis and compared the patient data with TBM and other causes including carcinomatous, lymphomatous, lymphocytic and fungal meningitis. We found that HIV infection, diabetes mellitus, duration of symptoms <14 days, radiologic findings of hydrocephalus, and CSF ADA level >10 IU were associated with TBM. The scoring system based on these parameters and their coefficients in the final model achieved an area under the receiver operating characteristic curve of 0.95,625. The indices were HIV infection = 5, diabetes mellitus = 3, duration of symptoms <14 days = 5, hydrocephalus = 4, and ADA in CSF >10 IU = 5. Based on the assumed costs of the patients with false negative and false positive, an appropriate cut off value of 10 was selected and the sensitivity was 92% and specificity was 89%.