颅内真菌性肉芽肿三例诊断与治疗

Diagnosis and treatment of 3 patients of intracranial fungal granulomas

目的分析颅内真菌性肉芽肿（ICFG）的临床表现、影像学特点、治疗方法及其预后，提高对ICFG的认识。方法回顾性分析3例手术后经病理证实ICFG患者的临床资料，并复习相关文献。结果3例ICFG成人患者，其中有颅脑外伤史1例，糖尿病及长期与鸟类接触史1例；均以头痛、呕吐起病，伴低热、颅高压以及局灶性神经体征，临床表现、影像学资料以及实验室检查缺乏特征性表现；颅内肉芽肿多发，且位置深在，累及重要结构，术中难以将病灶全部切除。3例患者手术明确病理诊断后即使用二性霉素B（AMB）和氟康唑治疗，由于AMB不易透过血脑屏障，同时还需鞘内给药。其中2例患者在3个月内完成AMB和氟康唑总量治疗后分别继续接受氟康唑（200mg／d）口服治疗3及6个月，另一例在治疗1个月后因自觉症状好转拒绝继续治疗，自动出院。3例分别随访3、24、48个月，其中2例抗真菌药物足量治疗者治愈，另一例于3个月后复发，再次入院使用AMB和氟康唑治疗无效死亡。结论ICFG临床表现缺乏特异性，早期诊断困难。手术目的为明确诊断、减少占位效应以及改善抗真菌药物的疗效；无论术中肉芽肿全切与否，术后足量全程使用AMB和氟康唑是治愈ICFG的重要手段。

Objective To examine clinical features, neuroimaging presentation and treatment of intracranial fungal granulomas （ICFG） in order to improve the accuracy rates of diagnosis and cure. Methods Three pathologically proven cases with ICFG were retrospectively analyzed. Cases of ICFG reported in literature were also summarized. Results Among the 3 patients with ICFG, 1 patient had a history of head trauma and craniotomy and 1 had a history of type 2 diabetes mellitus and a long history of exposure to doves. In all 3 patients, the symptoms started with headache and vomiting, accompanied by lowgrade fever, convulsion, and cranial nerve deficits. Intracranial mass lesion was revealed on brain computed tomography （CT） scan and （or） magnetic resonance imaging （MRI） with or without intravenous contrast. CT scan showed low-density lesions and granulations with ring and homogenous enhancement, indicating fungal abscesses. MRI in all 3 cases showed one or multiple circumscribed intracranial space-occupying lesion, with ring, heterogeneous contrast enhancement and perilesional edema. The treatments were initiated with craniotomy and surgical resection of granulations followed by intravenous injection of amphotericin B （AMB） combined with fluconazole. The daily administration of AMB was increased gradually from 0. 25-- 1.50 mg/kg and the total dosage of 2--4 g should be achieved within 3 months. The combination therapy with fluconazole （400 mg/d ） was also given by intravenous injection. To increase penetration into cerebrospinal fluid, intrathecal injection of AMB had also been given at the maximum dosage of 1 mg every time, twice a week. Two patients were administered fluconazole （200 mg/d） orally for 3, 6 months consecutively after completing the combination therapy of AMB with fluconazole, while the other patient refused continuous antifungal treatment 1 month postoperatively. All 3 patients were followed up for a period between 3, 24, 48 months. The 2 patients that completed full antifungal treatment were cured without recurrence. The other patient had improved transiently after operation but died after 3 months. Conclusions Because no distinct clinical and neuroimaging features are presented in ICFG, it is difficuh to diagnose preoperatively. Indications for surgery include diagnosis, relief mass effect and increase efficiency of drug treatment. Use of appropriate and completed antifungal treatment decreases mortality. The treatment requires continued and long-term administration of antifungal medication to prevent relapses, whether granulomas are totally removed or not.