Ellis W G, Sobel R A, Nielsen S L
J Infect Dis. 1982 Aug;146(2):125-37. doi: 10.1093/infdis/146.2.125.
Clinical and autopsy studies of 14 patients treated with amphotericin B methyl ester (AME) for focal, disseminated, and nervous system mycotic infections revealed a high incidence of progressive neurologic dysfunction (dementia, akinesia, mutism, hyperreflexia, and tremor) and diffuse white matter degeneration. All of seven patients who received greater than 9.8 g of AME intravenously developed severe neurologic and neuropathologic changes. Two of three patients given 5-7.2 g of AME developed less severe neurologic symptoms; all three had mild diffuse white matter gliosis. Four patients given less than 1.5 g of AME had no bran abnormalities except those related to coccidioidal meningitis. Thirty-one control patients who died on untreated or amphotericin B-treated coccidioidal meningitis showed no diffuse white matter abnormalities. These findings indicate that prolonged administration of AME and/or other contaminating polyenes injures human white matter. Long-term animal studies, with particular attention to nervous system histology, must precede human use of other polyene derivatives.
对14例接受两性霉素B甲酯（AME）治疗局灶性、播散性和神经系统真菌感染患者的临床及尸检研究显示，进行性神经功能障碍（痴呆、运动不能、缄默症、反射亢进和震颤）及弥漫性白质变性的发生率很高。所有7例静脉内接受超过9.8g AME的患者均出现了严重的神经和神经病理学改变。3例接受5 - 7.2g AME的患者中有2例出现了不太严重的神经症状；所有3例均有轻度弥漫性白质胶质增生。4例接受少于1.5g AME的患者除了与球孢子菌性脑膜炎相关的异常外没有脑部异常。31例死于未经治疗或接受两性霉素B治疗的球孢子菌性脑膜炎的对照患者未显示弥漫性白质异常。这些发现表明，长期给予AME和/或其他污染性多烯会损伤人类白质。在人类使用其他多烯衍生物之前，必须先进行长期动物研究，尤其要关注神经系统组织学。
