Hook C C, Kimmel D W, Kvols L K, Scheithauer B W, Forsyth P A, Rubin J, Moertel C G, Rodriguez M
Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905.
Ann Neurol. 1992 Mar;31(3):262-7. doi: 10.1002/ana.410310306.
A cerebral demyelinating disease developed in 3 patients during adjuvant therapy with 5-fluorouracil and levamisole for adenocarcinoma of the colon. None of the patients had evidence of metastatic disease or prior neurological disease. The duration of chemotherapy before onset of neurological symptoms ranged from 15 to 19 weeks. The total dose of 5-fluorouracil was 9.7 to 15.7 gm. The total dose of levamisole was 2.7 to 3.75 gm. Two patients presented with a subacute (2-3 weeks) progressive decline in mental status and ataxia. The third patient had two unexplained episodes of loss of consciousness. In each, magnetic resonance imaging with gadolinium demonstrated prominent multifocal enhancing white matter lesions. Cerebral biopsy was performed stereotaxically in 2 patients. The morphological features were those of active demyelinating disease. The myelin loss was associated with numerous dispersed as well as vasocentric macrophages, sparing of axons, and perivascular lymphocytic inflammation. Electron microscopy confirmed the light microscopic findings. All 3 patients improved after cessation of chemotherapy and a short course of corticosteroid therapy. Our patients represent the first reported examples of an inflammatory leukoencephalopathy associated with the administration of 5-fluorouracil and levamisole. This syndrome may represent the pathological basis for 5-fluorouracil neurotoxicity, although we cannot completely exclude the role of levamisole.
3例结肠癌患者在接受5-氟尿嘧啶和左旋咪唑辅助治疗期间发生了脑脱髓鞘疾病。所有患者均无转移性疾病证据或既往神经疾病史。神经症状出现前的化疗持续时间为15至19周。5-氟尿嘧啶的总剂量为9.7至15.7克。左旋咪唑的总剂量为2.7至3.75克。2例患者表现为亚急性（2 - 3周）精神状态进行性下降和共济失调。第3例患者有两次不明原因的意识丧失发作。每例患者经钆增强磁共振成像均显示明显的多灶性强化白质病变。2例患者接受了立体定向脑活检。形态学特征为活动性脱髓鞘疾病。髓鞘丢失与大量散在以及血管周围的巨噬细胞、轴突保留和血管周围淋巴细胞炎症有关。电子显微镜检查证实了光镜检查结果。所有3例患者在停止化疗和短期皮质类固醇治疗后均有改善。我们的患者是首例报道的与5-氟尿嘧啶和左旋咪唑给药相关的炎症性白质脑病病例。尽管我们不能完全排除左旋咪唑的作用，但该综合征可能代表了5-氟尿嘧啶神经毒性的病理基础。
