Kubo M, Azuma E, Arai S, Komada Y, Ito M, Sakurai M
Department of Pediatrics, Mie University School of Medicine, Japan.
Pediatr Hematol Oncol. 1992 Apr-Jun;9(2):157-65. doi: 10.3109/08880019209018331.
An episode of transient encephalopathy after the first course of intravenous high-dose methotrexate (HD-MTX; 1000 mg/m2) was observed in a 4-year-old girl with acute lymphoblastic leukemia. The neurological abnormalities took place 5 days after HD-MTX therapy. She experienced complex partial seizure and left hemiparesis, which resolved spontaneously in 5 days. Cranial computed tomographic scan and magnetic resonance imaging showed multiple low-density lesions in bilateral hemispheres. It is well appreciated that neurotoxicity from MTX follows prolonged exposures, often accompanying or following radiation therapy. To our knowledge, however, there have been no reports that such neurological complications developed following a single exposure of HD-MTX in patients with ALL. Follow-up electroencephalograms showed that she had periodic lateralized epileptiform discharges (PLEDS), suggesting functional deafferentation of cortical neurons following HD-MTX. Moreover, the serum and CSF MTX levels following a second low-dose course and her clinical course suggested that she had presumably central nervous system leukemia at the time of HD-MTX therapy, which might have been related to neurological complications. The pathogenesis of MTX-induced neurotoxicity is discussed.
在一名4岁急性淋巴细胞白血病女童中，观察到在首次静脉注射大剂量甲氨蝶呤（HD-MTX；1000 mg/m²）疗程后出现了一过性脑病发作。神经学异常在HD-MTX治疗5天后发生。她经历了复杂部分性癫痫发作和左侧偏瘫，并在5天内自发缓解。头颅计算机断层扫描和磁共振成像显示双侧半球有多个低密度病变。众所周知，甲氨蝶呤的神经毒性发生在长时间暴露后，常伴随放疗或在放疗后出现。然而，据我们所知，尚无关于急性淋巴细胞白血病患者单次暴露于HD-MTX后出现此类神经并发症的报道。随访脑电图显示她有周期性一侧性癫痫样放电（PLEDS），提示HD-MTX后皮质神经元功能性传入阻滞。此外，第二次低剂量疗程后的血清和脑脊液甲氨蝶呤水平以及她的临床病程提示，在HD-MTX治疗时她可能患有中枢神经系统白血病，这可能与神经并发症有关。本文讨论了甲氨蝶呤诱导神经毒性的发病机制。
