隐球菌脑膜炎62例临床分析

Clinical Analysis of 62 Patients with Cryptococcal Meningitis

目的分析隐球菌脑膜炎患者的临床特点及诊疗策略,进一步提高该病的临床诊治水平。方法回顾性总结并分析2000年1月至2016年12月间北京协和医院感染内科隐球菌性脑膜炎住院患者的临床资料(包括发病年龄、性别、基础疾病、鸟类接触史等流行病学特点)、临床表现、实验室检查、头颅影像学检查、治疗方案及预后。结果共62例患者入选本研究,其中男41例,女21例,中位年龄39岁(16~68岁);有基础疾病者37例(59.7%,37/62),有鸽子等流行病学接触史者23例(37.1%,23/62);入院前误诊为结核性脑膜炎或病毒性脑膜炎者分别为20例(32.3%,20/62)和9例(14.5%,9/62);头痛为最常见临床症状(98.4%,61/62),其次为发热(82.3%,51/62);19例(30.6%,19/62)伴眼部症状,13例(21.0%,13/62)出现中枢神经系统以外器官受累。55例(88.7%,55/62)患者出现颅内压增高,其中34例(61.8%,34/55)颅内压大于330 mm H2O(1 mm H2O=0.0098 k Pa)。脑脊液常规检查示白细胞中位计数[71×106/L(0~408×106/L)],55例(88.7%,55/62)患者表现为以单核细胞为主的脑脊液细胞学异常;62例患者均行脑脊液墨汁染色检测,其中53例(85.5%,53/62)阳性;55例患者接受脑脊液隐球菌抗原检测,其中51例(92.7%,51/55)阳性;57例患者接受脑脊液培养检测,其中28例(49.1%,28/57)阳性。25例患者因出现药物难以控制的颅内高压行侧脑室引流术。治疗方案分4种,包括氟康唑单药治疗(4例)、两性霉素B+5-氟胞嘧啶联合治疗(7例)、两性霉素B+氟康唑联合治疗(16例)、两性霉素B+5-氟胞嘧啶+氟康唑联合治疗(35例),两性霉素B中位疗程19.6周(2~42周),平均用量4139 mg;治愈10例,好转44例,无效6例,死亡2例,总有效率为87.1%(54/62)。结论隐球菌脑膜炎可发生于免疫功能正常人群,临床误诊率高。脑脊液隐球菌抗原乳胶凝集试验及墨汁染色是早期诊断的敏感指标,并可用于疗效评估。两性霉素B、5-氟胞嘧啶和氟康唑联合治疗是治疗隐球菌脑膜炎的有效方法,早期行侧脑室引流术缓解颅内高压是提高治疗成功率的关键。

Objective The aim was to study the clinical characteristics and therapeutic strategies of cryptococcal meningitis and provide further evidence for clinical diagnosis and therapy. Methods Data of the inpatients with cryptococcal meningitis who were admitted in the Department of Infectious Diseases,Peking Union Medical College Hospital from January 2000 to December 2016,including clinical data（ age,gender,comorbidi-ty,history of avian contact）,clinical manifestations,laboratory examination,CT and magnetic resonance imaging findings,therapy,and prognosis,were analyzed retrospectively. Results The age of the 62 enrolled inpatients ranged from 16 to 68 years（ median 39）. 41 patients were male and 21 were female. There were 37 patients（ 59. 7%,37/62） with comorbidity and 23 patients（ 37. 1%,23/62） had contacted with pigeons or poultries.The number of cases misdiagnosed with tubercular meningitis or virus meningitis was 20（ 32. 3%,20/62） and 9（ 14. 5%,9/62）,respectively. The main clinical symptoms included headache（ 98. 4%,61/62） and fever（ 82. 3%,51/62）; 19（ 30. 6%,19/62） patients had blurred vision; 13（ 21. 0%,13/62） had organ involvement beyond the central nervous system. The intracranial pressure increased in 55 patients（ 88. 7%,55/62） and34（ 61. 8%,34/55） had an opening pressure of more than 330 mm H2 O. The white blood cell count of cerebrospinal fluid had a median of 71×106 cells/L（ range 0-408×106 cells/L）,dominated by mononuclear cells in 55 patients（ 88. 7%,55/62）. Fifty-three（ 85. 5%） of the 62 cases were positive of cryptococcus by India ink stain of cerebrospinal fluid; latex coagulate test was performed in 55 cases with 51（ 92. 7%,51/55） positive; cerebrospinal fluid culture was positive in 28 cases（ 49. 1%,28/57）. Twenty-five patients with a dilated ventricle received brain ventricular drainage. Only 4 cases used fluconazole monotherapy; 7 patients received intravenous amphotericin B（ Am B） and flucytosine combined therapy; 16 patients took Am B and fluconazole combined therapy;35 patients received Am B,flucytosine,and fluconazole combined therapy. The average dosage of Am B was 4139 mg; the median treatment duration was 19. 6 weeks（ range 2-42 weeks）. In general,10 of the 62 cases were cured,44 improved,6 no response,and 2 died; the total effective rate was 87. 1%（ 54/62）. Conclusions Cryptococcal meningitis might occur in immunocompetent patients with a high misdiagnosis rate. India ink stain and cryptococcal antigen test of cerebrospinal fluid are useful assays for early diagnosis of cryptococcal meningitis and therapeutic effect evaluation. We recommend the combination of amphotericin B with flucytosine and fluconazole as the standard therapy for cryptococcal meningitis. Early ventricular drainage is the key point to improve the treatment success for cryptococcal meningitis.