隐球菌脑膜炎146例临床分析

Clinical analysis of 146 patients with cryptococcal meningitis

目的分析新型隐球菌脑膜炎(隐脑)患者的临床特征、预后及其影响因素。方法收集我院2000年1月至2006年12月收治的146例隐脑患者的临床资料,对患者的诊断与误诊、实验室和病原学检查、治疗与预后等进行回顾性统计分析。结果146例患者中合并其他疾病者78例,占53.4%。首诊误诊106例,占72.6%%。87例患者脑脊液墨汁染色发现隐球菌,占59.6%,63例隐球菌培养阳性,占43.2%,134例乳胶凝集试验(LAT)抗原阳性,占91.7%。两性霉素B(AmpB)或其脂质体和氟胞嘧啶(5-FC)联合治疗者98例,其中62例在疾病早期联合氟康唑治疗,单用氟康唑13例,脑室扩大植入Ommaya储液囊经侧脑室引流者53例,囊内或鞘内注射AmpB者53例。AmpB平均用量3.06 g,疗程12周至20个月。治愈104例,占71.2%;好转27例,占18.5%;死亡15例,占10.3%;复发34例,占23.3%。结论隐脑误诊率高;各种原因所致的免疫缺陷是引发隐脑的主要危险因素;脑脊液LAT是诊断最敏感的指标;尽早明确诊断、联合AmpB与5-FC抗真菌治疗、积极控制颅内压是降低病死率、改善预后的关键。

Objectives To investigate the clinical features, prognosis and risk factors of patients with cryptococcal meningitis. Methods Totally 146 patients with cryptococcal meningitis who were hospitalized in Huashan Hospital from January 2000 to December 2006 were enrolled in this study. The clinical data including diagnosis and misdiagnosis, experimental and etiology tests, treatments and prognosis from all the patients were analyzed retrospectively. Results Among the 146 patients enrolled in the study, 78 patients（53.4 % ）had concomitant diseases. The misdiagnosis rate of all patients was 72.6% （106/146）. The positive rate of cerebrospinal fluid（CSF） India ink smear was 59.6%（87/106）, while 43. 2% （63/146） cases of cryptococcus neoformans culture in CSF was positive. The positive rate of Latex agglutination test（LAT） was 91.7 % （134/146） in CSF among all patients. The treatments were as follows：combination of Amphotericin B（AmpB） or its lipid formulations with flucytosine（5-FC） （ 98 cases）, including combination with Fluconazole initally （62 cases）, single therapy of Fluconazole（13 cases）. Ommaya implanted for lateral cerebral ventricle drainage（53 cases） and AmpB intrathecal injection（53 cases）. The average dose of AmpB is 3.06 g. The course of treatment lasted from 12 weeks to 20 months. There were 104 patients（71.2%） cured, 27（18.5%） improved, 15 （10.3%） died and 34 （23. 3%） relapsed. Conclusions High misdiagnosis rate is common in patients with cryptococcal meningitis. Immunodeficiency is the major risk factor for cryptococcal meningitis. CSF LAT is the most sensitive diagnostic test. Early diagnosis, combination of AmpB with 5-FC antifungal therapy and control of acute intracranial hypertension are the keys to improve prognosis of cryptococcal meningitis.