新型隐球菌脑膜炎53例临床分析

目的总结分析新型隐球菌性脑膜炎的临床特征。方法分析53例新型隐球菌脑膜炎患者的临床表现、实验室检查、治疗及转归。结果新型隐球菌脑膜炎的临床表现以颅内压增高、脑膜刺激征为主。有基础性疾病者30例(占56．6%)。发病前有鸽子、禽类接触史者30例。脑脊液压力升高51例,其中49例超过200 mmH_2O。30例患者应用两性霉素B与氟康唑联合治疗。53例患者治愈4例,好转27例,死亡5例,自动出院17例。结论新型隐球菌性脑膜炎的主要临床表现是进行性颅内压增高。对进行性颅内压增高、脑膜刺激征阳性的患者反复进行脑脊液墨汁染色查新型隐球菌,有助于减少该病的误诊和误治。两性霉素B联合氟康唑静滴治疗隐球菌脑膜炎仍然安全、有效。     

艾滋病并发新生隐球菌性脑膜炎20例临床分析

目的:总结艾滋病并发新生隐球菌性脑膜炎(隐脑)的临床特点。方法:对20例艾滋病并发隐脑患者的临床资料进行数理分析。结果与结论:该组病例入院前后均曾误诊,以结核性脑膜炎为主(70%)。均有发热,不同程度头痛、呕吐及体重下降等临床表现。脑膜刺激征阳性14例(70%),眼底视乳头水肿11例(55%),淋巴结肿大10例(50%),四肢无力或抽搐8例(40%)。腰椎穿刺检查均示颅内压明显增高,脑脊液蛋白均增高,糖和氯化物以下降为主(分别为70%和75%)。首次墨汁染色涂片镜检新生隐球菌阳性高达90%(18/20)。该组抗真菌治疗以联合使用两性霉素B、氟康唑为主,抗病毒治疗以司他夫定、拉米夫定、奈韦拉平等药物为主。经综合治疗后9例好转,死亡11例(55%),其中死于脑疝或MODS4例,放弃抢救自动出院7例死亡。艾滋病并发隐脑预后不良,应引起临床医师的高度重视。     

获得性免疫缺陷综合征合并新型隐球菌脑膜炎临床分析

目的总结分析新型隐球菌性脑膜炎的临床特点,提高对获得性免疫缺陷综合征(AIDS)合并隐球菌性脑膜炎的认识。方法分析总结住院的72例患者的临床特点,在给予高效抗反转录病毒治疗的同时,给予抗真菌治疗。结果 AIDS合并隐球菌性脑膜炎的临床表现以颅内压增高(81.9%),脑膜刺激征为主(84.7%),全部合并有概率性感染(100%),免疫功能低表现为CD4+<50 cell/μL(83.3%)。结论 AIDS合并隐球菌性脑膜炎病情重、预后差、病死率高(37.5%),反复实验室病原学检查结果是诊断新型隐球菌性脑膜炎的主要依据。两性霉素B联合氟胞嘧啶治疗新型隐球菌性脑膜炎仍是安全、有效的。     

艾滋病并发新型隐球菌脑膜炎28例临床分析

目的分析艾滋病合并新型隐球菌脑膜炎的临床特点以及影响预后的因素。方法回顾性分析2013年1月至2016年12月首都医科大学附属北京地坛医院收治的28例艾滋病合并新型隐球菌性脑膜炎患者的病原学检查、实验室检查、诊断、治疗等相关临床资料,根据患者治疗方案分为两组,氟康唑方案治疗组和两性霉素B方案治疗组,并对根据患者的预后对上述资料进行分析。结果 28例患者均以头痛症状入院,18例(64.3%)伴发热,13例(46.4%)伴脑膜刺激征;26例(92.9%)患者的CD4~+T淋巴细胞100/μl;28例患者均在脑脊液中检出隐球菌。9例(32.1%)患者头颅CT或MRI检查提示异常,包括脑实质损伤3例、脑积水3例、颅内占位3例。通过Log-Rank单因素分析显示,是否使用两性霉素B、两性霉素B剂量750 mg、两性霉素B剂量1 500 mg、CD4~+T淋巴细胞20/μl、颅内压272mm H_2O与1年归因病死率减少显著相关。结论艾滋病合并新型隐球菌脑膜炎患者多以头痛为主诉,伴发热及颅内压增高等表现多见;应用两性霉素B、CD4计数、颅内压测定可作为判断艾滋病合并新型隐球菌脑膜炎患者预后的重要指标,早诊断、早治疗可降低病死率。     

新生隐球菌性脑膜炎25例临床分析

目的分析新生隐球菌性脑膜炎的临床特点,提高临床医师对本病的诊疗水平。方法回顾性分析我中心感染科确诊的新生隐球菌性脑膜炎25例住院患者临床资料。结果25例患者中,男17例,女8例,以青壮年居多。21例合并有基础疾病,包括艾滋病、淋巴瘤、干燥综合征、重症肌无力。所有患者均有发热、颅高压症状。17例(68%)出现意识障碍;5例(20%)出现抽搐;9例(36%)出现视力下降或视物模糊,6例(24%)出现听力下降。脑膜刺激征阳性14例(56%),病理征阳性12例(48%)。脑脊液检查提示蛋白增高,白细胞计数均在100×106/L以下,糖和氯化物降低。脑脊液压力明显增高。23例患者脑脊液涂片墨汁染色找到隐球菌。16例治愈或好转出院,死亡9例。结论隐球菌性脑膜炎是病情危重的中枢神经系统感染性疾病。脑脊液涂片墨汁染色找到隐球菌可明确诊断。早期诊断,及时抗真菌治疗是提高隐脑救治成功率的关键。     

30例HIV阴性患者隐球菌性脑膜炎的临床分析

目的探讨非HIV感染患者隐球菌性脑膜炎的临床特征,以提高该病的诊治水平。方法回顾性分析同济医院收治的30例诊断为隐球菌性脑膜炎患者的临床资料。结果 30例患者均有头痛症状(100%),22例患者有发热症状(73.3%);脑脊液葡萄糖(1.827±1.042 mmol/L)降低尤为显著;脑脊液IgG(128.51±62.42 mg/L)、IgA(15.17±11.51mg/L)和IgM(7.56±10.12mg/L)升高明显。所有患者均有不同程度的颅内压增高表现。脑脊液涂片墨汁染色阳性24例(80%),脑脊液培养出新型隐球菌23例(76.7%),隐球菌荚膜多糖抗原检测阳性者30例(100%)。培养出的隐球菌对两性霉素B、5-氟胞嘧啶和氟康唑的敏感率分别为95.6%、91.3%和100%。20例患者首诊使用两性霉素B联合5-氟胞嘧啶治疗,症状均有不同程度缓解。结论隐球菌性脑膜炎早期诊断和早期治疗很重要;新型隐球菌对两性霉素B及三唑类抗真菌药的敏感性较高,两性霉素B联合5-氟胞嘧啶仍是治疗隐球菌感染的首选方案,早期控制感染及降低颅内高压是治疗的关键。     

艾滋病合并隐球菌性脑膜炎70例临床分析

目的探讨艾滋病(AIDS)合并隐球菌性脑膜炎(CM)患者脑脊液检测指标的变化特点。方法回顾性分析2014年1月至2016年10月北京地坛医院收治的AIDS合并CM患者70例,分别采用真菌培养法、墨汁染色法、隐球菌抗原乳胶凝集法检测隐球菌。结果患者脑脊液外观均为无色透明,不浑浊,常规检测结果无明显变化,其中白细胞计数为(27.6±31.9)个/微升,血糖水平为(2.74±0.67)mmol/L,蛋白水平为(69.8±53.9)mg/L。外周血中CD4+T细胞计数为(29.9±25.3)个/微升,其中54例50个/微升,15例为50~100个/微升,1例为105个/微升。隐球菌抗原乳胶凝集法的阳性检出率为100.0%(70/70),真菌培养法的阳性检出率为57.1%(40/70),墨汁染色法的阳性检出率为80.0%(56/70)。对真菌培养阳性的40株隐球菌进行药敏试验,氟胞嘧啶、二性霉素B、伊曲康唑、伏立康唑敏感37株,中介3株。临床采用单一或联合的抗真菌药对70例AIDS合并CM患者进行治疗,好转48例,未愈15例,死亡7例,病死率为10%。结论采用墨汁染色法、真菌培养法及隐球菌抗原乳胶凝集法进行联合检测,有助于AIDS合并CM患者的早诊断,可大大提高CM治愈好转率。     

艾滋病合并新型隐球菌脑膜脑炎的MRI表现

目的探讨艾滋病合并新型隐球菌脑膜脑炎的MRI表现。材料与方法回顾性分析14例AIDS合并新型隐球菌脑膜脑炎患者的MRI资料。结果 14例患者的MRI中有13例呈阳性表现(92.86%),其中胶状假囊及以胶状假囊引起的血管周围间隙扩大6例(42.29%);脑膜炎4例(28.57%);结节性肉芽肿(即隐球菌瘤)3例(21.43%);局灶性脑水肿2例(14.29%);脑积水1例(7.14%);脑萎缩1例(7.14%)。结论艾滋病合并新型隐球菌脑炎的MRI表现呈多样化,主要表现为脑膜炎型、脑膜脑炎型及脑炎型,其中胶状假囊和胶状假囊引起的血管周围间隙扩大是其特征性表现。     

艾滋病并发新生隐球菌脑膜炎21例的观察与护理

目的探讨艾滋病患者(AIDS)并发新生隐球菌脑膜炎的临床观察及护理方法。方法分析总结21例AIDS并发新生隐球菌脑膜炎的临床特点、护理经验。结果新生隐球菌脑膜炎症状好转,血CD4淋巴细胞上升,17例病情好转出院,3例自动出院,1例死亡。结论 AIDS并发新生隐球菌脑膜炎病情复杂,但只要提高对该病的认识,通过有效的治疗及积极地护理,可改变患者预后及提高生命质量。     

隐球菌性脑膜炎患者中Th17细胞相关细胞因子的高表达及其临床意义

目的研究Th17细胞相关细胞因子IL-17A、IL-17F、IL-22在隐球菌性脑膜炎患者发病机制中的作用。方法收集了2011年2月至2013年2月期间来院就诊的免疫功能正常的隐球菌患者22例以及同期来院体检的健康个体20例,收集外周抗凝血,分离了外周血单个核细胞,采用RT-PCR以及ELISA检测了隐球菌性脑膜炎患者和健康对照者外周血单个核细胞(PBMC)中Th17相关细胞因子1L-17A、IL-17F以及IL-22的mRNA表达以及血浆中各蛋白水平的表达。并分析其与脑脊液蛋白浓度、颅内压、脑脊液隐球菌抗原滴度、脑脊液葡萄糖浓度的关系。结果隐球菌性脑膜炎患者外周血单个核细胞中IL-17A、IL-22的mRNA水平以及血浆中IL-17A、IL-22水平较健康对照组显著增高(P0.01),且与隐球菌性脑膜炎患者的预后因子脑脊液蛋白浓度、颅内压、脑脊液隐球菌抗原滴度、脑脊液葡萄糖浓度相关。结论 Th17细胞相关细胞因子IL-17A、IL-22可能参与了隐球菌性脑膜炎的发病机制,可能是潜在的评价隐球菌性脑膜炎病情的指标。     

Use of cerebrospinal fluid shunt for the management of elevated intracranial pressure in a patient with active AIDS-related cryptococcal meningitis.

Persistently elevated intracranial pressure (ICP) is one of the most accurate predictors of a poor prognosis in patients with AIDS-related cryptococcal meningitis. We present a severe case of persistent cryptococcal meningitis in a patient with advanced AIDS, complicated by elevation of ICP. A ventriculoperitoneal shunt was placed that successfully lowered the ICP and alleviated the associated symptoms. The elevated ICP secondary to AIDS-related cryptococcal meningitis should be treated aggressively. Despite the risk of shunt complications, cerebrospinal fluid shunts can be considered in these patients if they do not respond to other treatment.     

艾滋病合并新型隐球菌脑膜炎患者的护理

目的总结艾滋病合并新型隐球菌脑膜炎患者的护理体会。方法回顾性分析2007年1月～2009年12月本院收治的13例艾滋病合并新型隐球菌脑膜炎患者的临床资料,并总结护理要点。结果 13例患者住院时间4～137d,中位住院时间78.6d;经对症治疗和护理后,11例病情好转出院,2例病情未愈主动要求出院,转外院继续治疗。结论艾滋病合并新型隐球菌脑膜炎患者病程较长,治疗难度大,护士应配合做好心理护理,加强基础护理,保证患者的营养摄入,以提高患者的治疗效果,促进患者康复。     

The clinical laboratory evaluation of cryptococcal infections in the acquired immunodeficiency syndrome

The medical and laboratory records were reviewed in 37 acquired immunodeficiency syndrome (AIDS) patients with cryptococcal infections. In 24 patients with the presentation of cryptococcal meningitis, the initial cerebrospinal fluid (CSF) culture was positive. The initial India ink mount demonstrated organisms in 79% of culture positive CSF specimens. After therapy the subsequent India ink mounts demonstrated 84% sensitivity and 53% specificity with respect to culture outcome. Cultures of blood, bronchoalveolar lavage fluid, and brain were more likely to be positive than cultures from other sites. The initial blood cultures were positive in eight of eight patients at presentation of cryptococcal meningitis. When the initial CSF titer was greater than 1:2, the corresponding CSF culture was always positive. A negative culture during therapy did not necessarily indicate eradication of infection. The initial cerebrospinal fluid and serum cryptococcal antigen titers varied significantly and could not be correlated with survival. In three instances when the CSF cryptococcal antigen titers and cultures were negative, a positive serum cryptococcal antigen greater than 1:8 suggested disseminated infection.     

The spectrum of meningitis in a population with high prevalence of HIV disease

We studied the spectrum of meningitis and impact of HIV infection retrospectively (8 months) and prospectively (5 months) in 284 adult patients with meningitis hospitalized in Soweto, South Africa. Tuberculous meningitis (TBM) was the most common cause of meningitis (25.4%) followed by acute bacterial meningitis (ABM; 22.5%), acute viral meningitis (14.1%) and cryptococcal meningitis (13%). The in-hospital mortality was &gt;40% in TBM, ABM, cryptococcal meningitis, the neurosurgery and the parameningeal/parenchymal groups. At least 37.3% of all patients were HIV-seropositive (only 67% of patients were tested). In at least 27% of the study group the meningitis was an AIDS-defining illness (TBM, cryptococcal meningitis). Only 56.2% of patients with ABM has positive cultures (CSF or blood), of which <it>Streptococcus pneumoniae</it> was by far the most frequently found organism (35.8%). The spectrum of meningitis in HIV-affected communities in Africa can be expected to change towards a predominance of TBM and cryptococcal meningitis.      

Role of quantitative CSF microscopy to predict culture status and outcome in HIV-associated cryptococcal meningitis in a Brazilian cohort

This retrospective study aimed to evaluate the clinical, laboratory, and quantitative cerebrospinal fluid (CSF) cryptococcal cell counts for associations with in-hospital outcomes of HIV-infected patients with cryptococcal meningitis. Ninety-eight HIV-infected adult patients with CSF culture-proven cryptococcal meningitis were admitted between January 2006 and June 2008 at a referral center in Sao Paulo, Brazil. Cryptococcal meningitis was the first AIDS-defining illness in 69%, of whom 97% (95/98) had known prior HIV infection. The median CD4+ T-cell count was 39 cells/μL (interquartile range 17-87 cells/μL). Prior antiretroviral therapy was reported in 50%. Failure to sterilize the CSF by 7-14 days was associated with baseline fungal burden of ≥ 10 yeasts/μL by quantitative CSF microscopy (odds ratio [OR] = 15.3, 95% confidence interval [CI] 4.1-56.7; P < 0.001) and positive blood cultures (OR = 11.5, 95% CI 1.2-109; P = 0.034). At 7-14 days, ≥ 10 yeasts/μL CSF was associated with positive CSF cultures in 98% versus 36% with <10 yeasts/μL CSF (P < 0.001). In-hospital mortality was 30% and was associated with symptoms duration for >14 days, altered mental status (P < 0.001), CSF white blood cell counts <5 cells/μL (P = 0.027), intracranial hypertension (P = 0.011), viral loads >50,000 copies/mL (P = 0.036), ≥ 10 yeasts/μL CSF at 7-14 days (P = 0.038), and intracranial pressure >50 cmH(2)0 at 7-14 days (P = 0.007). In conclusion, most patients were aware of their HIV status. Fungal burden of ≥ 10 yeasts/μL by quantitative CSF microscopy predicted current CSF culture status and may be useful to customize the induction therapy. High uncontrolled intracranial pressure was associated with mortality.     

Cerebrospinal fluid beta 2-microglobulin in AIDS related central nervous system involvement

We measured cerebrospinal fluid (CSF) and serum beta 2-microglobulin (beta 2-M) in Acquired Immunodeficiency Syndrome (AIDS) patients with or without clinical evidence of central nervous system (CNS) involvement. The CSF beta 2-M level was significantly higher than the serum level in AIDS patients with neurological symptoms, but not in AIDS without neurological symptoms, suggesting an increased shedding of this protein in CSF, as a result of rapid cellular turnover within CNS. CSF beta 2-M level increases both in Human Immunodeficiency Virus type 1 (HIV-1) related and in opportunistic CNS syndromes, confirming that beta 2-M is a non specific marker of CNS involvement in AIDS. Nevertheless, the highest CSF beta 2-M values were observed in patients with severe dementia and autoptic diagnosis of multifocal giant cells encephalitis (MGCE) without other opportunistic diseases. This observation could have important implications for monitoring AIDS dementia complex in AIDS patients. Finally, 5 out of 7 (71%) AIDS patients with cryptococcal meningitis showed a decline in CSF beta 2-M level well related to the decrease of cryptococcal antigen (Crypto-Ag) titres and the clinical remission. This data suggests that CSF beta 2-M determination could be used as a useful test in monitoring efficacy of therapy of CNS pathologies in AIDS patients.     

隐球菌荚膜抗原胶体金免疫层析法在非HIV患者隐球菌脑膜炎诊断中的价值

目的探讨隐球菌荚膜抗原胶体金免疫层析法在非HIV患者隐球菌脑膜炎中的诊断价值。方法回顾性分析2013-2018年复旦大学附属华山医院3627例疑似中枢神经系统感染的住院患者的临床资料,收集符合隐球菌脑膜炎初诊的患者214例,分析各检验结果对隐球菌脑膜炎的诊断价值。结果隐球菌脑膜炎患者多数表现为脑脊液糖和氯化物水平显著下降,蛋白含量增高,白细胞增多且以单核细胞为主,脑脊液真菌镜检和培养的阳性率分别为75.23%和78.04%,脑脊液隐球菌胶体金免疫层析法检测阳性率高达100%。隐球菌脑膜炎患者随治疗时间的推移,脑脊液和血的隐球菌荚膜抗原滴度逐渐下降。结论胶体金免疫层析法适用于非HIV患者隐球菌脑膜炎的快速诊断,灵敏度高、特异性强,对隐球菌肺炎的患者能提前筛查是否有中枢神经系统感染,对荚膜抗原的动态监测有助于隐球菌病治疗疗效的观察。     

系统性红斑狼疮合并隐球菌性脑膜炎临床分析

目的：探讨系统性红斑狼疮（SLE）合并隐球菌性脑膜炎的临床特点、诊断厦治疗，以提高对本病的认识和诊治水平。方法：时8例SLE合并隐球菌性脑膜炎（隐脑）病例的临床表现、脑脊液（cSF）特点和诊治经过进行回顾性分析。结果：SLE正患者出现隐脑时，病情隐匿，临床厦CSF系列生化检查呈非特异性，确诊所需时间2～16周，误诊率达50％，及时并重复进行CSF隐球菌乳胶凝集试验、涂片镜检厦培养是诊断的关键，以两性霉素B为主的抗真菌治疗效果较好，有效率100％。结论：SLE合并隐脑患者如能早期诊断并给予有效抗隐球菌治疗可显著改善预后。     

Parenteral and oral fluconazole for acute cryptococcal meningitis in AIDS: experience with thirteen patients.

OBJECTIVE: Cryptococcus neoformans infections of the central nervous system affect up to ten percent of AIDS patients. Standard therapy with amphotericin B with or without 5-flucytosine has a high rate of failure, relapse, and toxicity. Fluconazole is a new triazole antifungal agent available in both oral and intravenous forms that has shown efficacy in the primary and maintenance treatment of cryptococcal meningitis in AIDS patients. In this open, noncomparative trial, we evaluated the safety and efficacy of intravenous fluconazole followed by oral fluconazole in the treatment of acute cryptococcal meningitis in AIDS patients. METHODS: Thirteen AIDS patients with acute cryptococcal meningitis, or relapse after successful primary therapy, received 400 mg of intravenous fluconazole daily for 12-16 days followed by oral fluconazole 400 mg/d for the duration of primary therapy. If cerebrospinal fluid (CSF) cultures converted to negative within 32 weeks of treatment, the fluconazole dose was decreased to 200 mg/d as maintenance therapy. RESULTS: Fluconazole therapy was successful in six patients (46 percent) and unsuccessful in seven (54 percent). Of the seven patients considered unsuccessful, one demonstrated clinical improvement but remained CSF-culture positive, five were clinical failure and were switched to amphotericin B therapy, and one died after two weeks secondary to cryptococcal meningitis. No patient experienced any adverse reactions necessitating discontinuation of therapy. CONCLUSIONS: In this small group of patients, moderate doses of parenteral and oral fluconazole for acute cryptococcal meningitis in AIDS patients demonstrated failure rates similar to those reported in other studies with fluconazole and with amphotericin B. As there was no difference in initial Karnofsky scores or the severity of disease in treatment successes versus failures, it is difficult to determine who might respond to fluconazole as initial therapy or who should be treated initially with another agent. Further studies and clinical experience are needed.     

病原治疗前脑脊液隐球菌负荷量在新生隐球菌性脑膜炎临床转归中的意义

目的:探讨新生隐球菌性脑膜炎患者病原治疗前脑脊液隐球菌负荷量与治疗效果及临床转归的关系.方法:收集52例新生隐球菌性脑膜炎患者的临床资料,以治疗前脑脊液隐球菌计数与临床转归关系的特异度及灵敏度之和的最大值所对应的脑脊液隐球菌计数2 125个/ml为分界点,分为脑脊液隐球菌计数＜2 125个/ml(低量)组31例和脑脊液隐球菌计数≥2 125个/ml(高量)组21例,比较抗真菌治疗后两组患者的阴转率和临床疗效.结果:抗真菌治疗后低量组的脑脊液隐球菌阴转率为52％,高量组的脑脊液隐球菌阴转率为14％,两组比较差异有统计学意义(P＜0.01);低量组治愈率48％,好转率23％,总有效率71％:高量组治愈率14％,好转率14％,总有效率29％,两组的治愈率及总有效率比较差异均有统计学意义(P＜0.01).结论:在新生隐球菌性脑膜炎患者中,病原治疗前脑脊液隐球菌计数＜2 125个/ml者相比于≥2125个/ml者,抗真菌治疗后脑脊液隐球菌阴转率高,临床转归好,脑脊液隐球菌负荷量是评估治疗效果和临床转归的一个实用、便捷的参数.