Yi Youbin, Kang Hyung Jin, Shin Hee Young, Kim Keewon
Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
J Child Neurol. 2015 Feb;30(2):246-9. doi: 10.1177/0883073814527157. Epub 2014 Mar 20.
Intrathecal chemotherapy including methotrexate is well documented for neurotoxicity of diverse clinical manifestation. Acute or chronic leukoencephalopathy is the most common type of methotrexate-induced neurotoxicity, and subacute myelopathy is rare. Although its pathogenesis is not fully understood, it is postulated that direct damage of methotrexate to the central nervous system plays a major part and elevated levels of homocysteine and its excitatory amino acid neurotransmitter metabolites (homocysteic acid and cysteine sulfinic acid) could mediate, in part, MTX-associated neurotoxicity. On the while, subacute combined degeneration is a progressive degeneration of the dorsal and lateral columns of the spinal cord, mostly due to vitamin B12 deficiency. The authors report a case of a 15-year-old boy with Burkitt leukemia who developed progressive myelopathy after intrathecal triple therapy (methotrexate, cytarabine, and hydrocortisone) whose clinical and radiologic features were compatible with subacute combined degeneration. The pathogenic mechanism could be explained by biochemical alteration by methotrexate and a possible treatment strategy was discussed.
鞘内化疗（包括甲氨蝶呤）导致的神经毒性具有多种临床表现，这已得到充分记录。急性或慢性白质脑病是甲氨蝶呤诱导的神经毒性最常见的类型，亚急性脊髓病则较为罕见。尽管其发病机制尚未完全明确，但据推测，甲氨蝶呤对中枢神经系统的直接损害起主要作用，而高半胱氨酸及其兴奋性氨基酸神经递质代谢产物（高半胱氨酸和半胱亚磺酸）水平升高可能部分介导了与甲氨蝶呤相关的神经毒性。同时，亚急性联合变性是脊髓背侧和外侧柱的进行性变性，主要由维生素B12缺乏引起。作者报告了一例15岁患伯基特白血病的男孩，在接受鞘内三联疗法（甲氨蝶呤、阿糖胞苷和氢化可的松）后出现进行性脊髓病，其临床和放射学特征与亚急性联合变性相符。其致病机制可用甲氨蝶呤引起的生化改变来解释，并讨论了可能的治疗策略。
