64例不典型结核性脑膜炎临床诊断和治疗分析

目的探讨不典型结核性脑膜炎（结脑）的临床分类、诊断和治疗方法.方法回顾性总结分析68例不典型结脑临床特点、诊断依据,采用3HS（E）RZ/9HRZ化疗方案,并用地塞米松、降颅压治疗.结果68例不典型结脑分为脑脊液改变不典型、脑脊液和临床表现均不典型两类;治疗结果67例存活,死亡1例,无明显后遗症.随访2年以上者64例.结论不典型结脑诊断参考：（1）活动性肺结核表现;（2）不典型脑脊液改变或/和不典型结脑临床表现;（3）抗结核试验治疗有效;（4）除外非结脑疾病;（5）脑脊液PPD抗体阳性、腺苷脱氨酶（ADA）增高;（6）CT或MR符合结脑影像;（7）病理显示结核样改变或脑脊液检出抗酸杆菌;具备1～6项中3项或第7项可诊断.采用HS（E）RZ四联12个月化疗,安全、有效.     

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。     

联检脑脊液中LAM-IgG和TB-DNA在诊断结核性脑膜炎中的应用

目的　了解脑脊液 (CSF)中阿拉伯糖甘露糖脂IgG抗体 (LAM-IgG)和TB-DNA指标对结脑的诊断价值。方法 以CSF为标本,用酶联免疫吸附试验 (ELISA)检测LAM-IgG,用聚合酶链反应(PCR)检测TB-DNA。结果 102份结脑病人CSF标本,LAM-IgG阳性率51.0% (52102),TB-DNA阳性率81.4% (83102),LAM-IgG阳性及 或TB-DNA阳性共93例 (91.2%)。40份非结核性的中枢神经系统疾病病例的CSF标本,均未检出LAM-IgG和TB-DNA.结论 LAM-IgG和TB-DNA均是诊断结脑的较好的指标,两者联检可进一步提高检测敏感性。     

误诊结核性脑膜炎38例临床分析

目的　提高对结核性脑膜炎鉴别诊断水平。方法 1985年1月至2000年10月住院结核性脑膜炎342例中对非结核性脑膜炎患者误诊为结核性脑膜炎的38例进行回顾分析。结果 总误诊率11.1% (38342)。误诊疾病病毒性脑膜炎19例占误诊病例50.0%,新型隐球菌脑膜炎7例占18.4%,脑囊虫病3例占8.0%,红斑狼疮脑病、急性播散性脑脊髓炎各2例,各占5.3%,脑脓肿、松果体旁囊肿、脑室膜瘤、脑胶质瘤、非特异性大脑导水管狭窄各1例,均占2.6%。误诊时间最短2d,最长360d,平均37d。结论 ①结核病专科医师应熟悉其他脑部疾病临床表现,提高结核性脑膜炎的诊断与鉴别水平。②对临床经过和脑脊液 (CSF)表现不典型、抗结核治疗效果不良的结核性脑膜炎患者,应提高警惕,需进一步排除隐球菌性脑膜炎及脑囊虫病等其他脑部疾患。③对起病急、进展快、早期出现意识障碍、截瘫、括约肌功能障碍,而CSF改变轻微者,应考虑急性播散性脑脊髓炎的可能。④脑部CT(增强)或核磁共振检查对结核性脑膜炎诊断、鉴别诊断有重要作用。     

SARS的X线表现

目的　提高对SARS的影像学认识和诊断。方法 回顾性分析52例明确诊断SARS病例的X线表现。结果 主要X射线改变:(1)肺纹理粗重、僵硬呈枯枝状改变;(2)肺野透亮度减低,肺内密度普遍增高呈;(3)肺纹理粗重,沿肺纹理走行可见片状、斑片状灶;(4)肺间质密度增高,其内可见网状改变、小结节灶及浸润灶;(5)肺段、叶实变。结论 SARS影像表现多种多样,变化快,影像学显著改变与临床体征轻微不相符。通过对SARS的X线改变的认识,有助于SARS的早期诊断,早期治疗与隔离。     

急性布鲁氏菌病并发中枢神经损害患者临床特征分析

目的 分析布鲁氏菌病中枢神经损害脑脊液特征,探讨其临床诊断价值。方法 选择2007年至2014年黑龙江省农垦总局总医院住院治疗的急性布鲁氏菌病并发中枢神经损害患者20例作为观察对象。临床诊断:并发脑膜炎8例、脑膜脑炎3例、脊髓炎7例和脑脓肿2例。调查其住院病例资料,观察脑脊液常规检查各项指标,分析和评估脑脊液改变特点。结果 脑脊液异常改变,颅内压增高13例,白细胞计数增多18例(90.00%),蛋白增高19例(95.00%),葡萄糖和氯化物降低16例(80.00 %)。结论 布鲁氏菌病并发中枢神经损害患者脑脊液多发生异常改变,颅内压升高,白细胞计数增多,葡萄糖和氯化物降低为特征,诊断需要与结核性脑膜炎相鉴别。     

支气管结核248例临床分析

目的　探索气管、支气管结核的临床特征及诊断治疗手段。方法 分析248例1993～2000年住院气管支气管结核病例资料临床表现、影像学、纤支镜检查,治疗结果。结果 248例患者中15～34年龄组青年女性明显高于其它组占69.2% (72/104)。左侧支气管病变多于右侧。影像学、纤支镜、实验室检查确诊234例,肺切除术后病理确诊14例。全组病例均予规范抗结核化疗,其中并用雾化治疗72例。经纤支镜支气管腔内给药26例有效率84.6%。外科治疗47例。结论 纤支镜检查是诊断气管支气管结核最重要的方法。在实施规范抗结核化疗同时并用雾化及经纤支镜支气管内给药治疗,是改善临床症状,减轻或消除支气管狭窄的有效方法。对不可逆结核性支气管狭窄、肺不张及严重肺功能损毁患者应及时外科治疗。     

成年局限性肺下叶结核的临床表现与诊断

目的　探讨成人局限性肺下叶结核的临床特点,提高诊断水平。方法 分析42例成人中不同年龄组肺下叶结核表现,探索其临床特点。结果 多数患者临床表现不典型,多被并存病掩盖;X线表现在原发肺部疾病基础上呈现多数小片状或斑片状渗出影。多形性混合灶及空洞很少见。结论 成人局限性肺下叶结核临床症状、X线表现均不典型,常为并存病所掩盖,极易漏诊或误诊。痰菌及纤支镜检查有助于早期诊断。     

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。     

重组人白细胞介素-Ⅱ辅助治疗复治肺结核临床观察

目的　研究和评价重组人白细胞介素-Ⅱ(IL-2)辅助治疗肺结核的临床效果。方法 选痰菌阳性复治肺结核43例,观察组22例,采用2HL₂AK(E)Z(TH)V+IL-2/1HL₂(TH)V+IL-2/5HL₂V方案化疗;对照组21例,采用2HL₂AK(E)Z(TH)V/1HL₂(TH)V/5HL₂V方案化疗。结果 完成疗程可评价疗效者40例,其中观察组20例,对照组20例,观察组痰菌阴转、病灶吸收、空洞的缩小和闭合以及免疫检测结果均优于对照组。无严重不良反应发生。结论 重组人IL—2有辅助治疗肺结核的作用,可加速结核菌阴转速度,促进病灶吸收,提高机体免疫力,是安全可靠的生物制剂。     

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。     

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.     

结核性脑膜炎评分系统对儿童结核性脑膜炎的诊断价值

目的 评价结核性脑膜炎(TBM)评分系统对儿童TBM与病毒性脑炎进行鉴别的价值。方法 回顾性分析2010年1月1日至2017年12月31日天津市儿童医院呼吸科收住院的确诊及临床诊断TBM的患儿102例(TBM组),以及同期病毒性脑炎患儿125例(病毒性脑炎组)。TBM评分系统采用包括临床表现、脑脊液检测结果、影像学表现、肺结核或肺外结核的其他表现进行综合评分来诊断TBM(分值越高,越支持TBM诊断;评分≥12分可以临床诊断TBM)。采用病例对照研究的方法,比较该评分系统诊断TBM的敏感度及特异度;同时比较该评分系统与结核菌素皮肤试验(TST)、γ干扰素释放试验(IGRA)及脑脊液病原学检测敏感度的差异。结果 TBM组患儿中,16例(15.69%,16/102)脑脊液病原学检测阳性,确诊为TBM患儿;其余86例(84.31%,86/102)TBM患儿经评分系统评估,分值为(13.25±2.22)分,明显高于病毒性脑炎组患儿的评分[(3.79±2.48)分],差异有统计学意义(t=29.97,P<0.001)。86例患儿中,76例患儿TBM评分≥12分,判断为临床诊断TBM患儿;TBM诊断的敏感度为90.20%(92/102),特异度为100.00%(102/102)。脑脊液病原学检查中,抗酸杆菌染色的敏感度为15.69%(16/102),结核分枝杆菌培养的敏感度为10.78%(11/102),DNA检测的敏感度为16.47%(14/85),均明显低于TBM评分系统(χ ²值分别为113.65、128.66、100.64,P值均<0.001)。免疫学检查方法中,TST的敏感度为50.00%(51/102),特异度为99.20%(124/125);IGRA的敏感度为72.55%(74/102),特异度为99.20%(124/125);敏感度均明显低于TBM评分系统(χ ²值分别为39.31、10.48,P值均<0.001)。 结论 TBM评分系统对TBM诊断价值较好,其敏感度明显高于脑脊液抗酸染色、脑脊液结核分枝杆菌培养、脑脊液DNA检测、TST及IGRA等检测方法。     

Interpretation of mycobacterial antibodies in the cerebrospinal fluid of adults with tuberculous meningitis

Objective Microbiological identification of Mycobacterium tuberculosis is insensitive and slow, and clinical distinction of tuberculous meningitis (TBM) from other subacute or chronic meningoenchephalitides (SACM) is difficult. Successful use of highly specific M. tuberculosis serological assays on cerebrospinal fluid has been reported, but their performance for diagnosis in a tuberculosis endemic country where they would be of most value is unclear. We sought to determine the biological basis for the uncertainty in interpretation of antibody detection in the CSF of TBM patients. Methods We identified prospectively 46 adults with SACM and explored the concordance between TBM diagnosis and detection of highly specific M. tuberculosis antibodies in CSF. The source of antibodies in CSF was explored by evaluating the correlation between antibody titres in CSF with those in serum, or with the albumin quotient. Intrathecal IgG synthesis was assessed by the IgG index. Results Positive antibody titres were more frequent among TBM patients (76%), but were also present in individuals with other SACM (59%). A positive correlation between antibody titres in CSF with those in serum, or with the albumin quotient, supported the leakage of antibodies from plasma to CSF through an increased blood–brain barrier permeability. Intrathecal IgG synthesis was only detected in 35% of the TBM cases. Conclusion Plasma antibodies likely synthesized in response to previous tuberculosis infections were a major source of mycobacterial antibodies in CSF due to leakage through an impaired blood–brain barrier. Interpretation of mycobacterial antibodies in CSF of adults for TBM, however specific, must take into account the contribution of antibodies from plasma, and hence, has questionable use for diagnosis.     

Penicillinase ELISA for detection of tubercular antigen in tuberculosis.

Stick sandwich enzyme linked immunosorbent assay (ELISA) using rabbit anti PPD-RT 23 immunoglobulins and enzyme penicillinase has been explored for detection of tubercular antigen in sera and CSF samples of pulmonary tuberculosis and tubercular meningitis (TBM) respectively. The analysis of sera showed 73.3% of pulmonary tuberculosis cases, 16.2% of healthy controls and 44.4% of Hansen's disease positive for tubercular antigen. The accuracies of positive and negative predictive values were 69% and 82% respectively. The analysis of CSF samples showed the presence of tubercular antigen in 76.4% of TBM, 16.6% of pyogenic meningitis cases, 19.4% of neurological diseases other than meningitis and 16.1% non-neurological disease controls. The accuracies of positive and negative predictive values were 48% and 94% respectively. Hence this simple test using economical and indigenous reagents can be applied for the diagnosis of pulmonary and extra-pulmonary tuberculosis.     

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。     

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.     

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.     

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.     

脑脊液标志物在结核性脑膜炎诊断中的研究进展

结核性脑膜炎(tuberculous meningitis, TBM)患者早期的临床表现和影像学变化均不具有特异性,且缺乏有效的实验室诊断方法,致使其诊断异常困难。早期诊断TBM对于患者的及时治疗和改善预后至关重要。脑脊液(cerebrospinal fluid, CSF)中存在多种生物标志物,对TBM早期诊断具有一定的潜在价值。本文主要针对CSF中宿主诊断生物标志物用于TBM诊断的研究进展及挑战进行综述和讨论。