Boogerd W, vd Sande J J, Moffie D
Neurological Department of the Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis), Amsterdam.
J Neurol Neurosurg Psychiatry. 1988 Oct;51(10):1277-83. doi: 10.1136/jnnp.51.10.1277.
Nine out of 14 patients treated with intraventricular methotrexate (MTX) for meningeal carcinomatosis from breast carcinoma and surviving more than 4 months developed disseminated necrotising leukoencephalopathy (DNL). All four patients who had received both intraventricular MTX and whole brain radiotherapy developed DNL. Five of the six patients who experienced an acute febrile reaction with mild encephalopathic signs following intraventricular administration of MTX developed DNL after a mean time of 5 months and a low mean dose of 44 mg MTX. DNL was also noted in two patients without a previous febrile reaction or whole brain radiotherapy, following prolonged intraventricular MTX therapy after a mean time of 19.5 months and a mean dose of 147 mg MTX. These findings confirm the hazards of (1) high cumulative doses of intrathecal MTX and (2) combined intrathecal chemotherapy and whole brain radiotherapy. This study also suggests a possible relationship between an early and transient febrile reaction during intraventricular administration of MTX and the development of DNL.
14名因乳腺癌脑膜癌病接受脑室内甲氨蝶呤（MTX）治疗且存活超过4个月的患者中，有9人发生了播散性坏死性白质脑病（DNL）。所有接受脑室内MTX和全脑放疗的4名患者均发生了DNL。6名在脑室内给予MTX后出现急性发热反应并伴有轻度脑病体征的患者中，有5人在平均5个月的时间和平均44 mg MTX的低剂量后发生了DNL。在2名既往无发热反应或全脑放疗的患者中，在平均19.5个月的时间和平均147 mg MTX的剂量后，经过长时间的脑室内MTX治疗也发现了DNL。这些发现证实了（1）鞘内MTX高累积剂量和（2）鞘内化疗与全脑放疗联合应用的危害。本研究还提示脑室内给予MTX期间早期短暂发热反应与DNL发生之间可能存在关联。
