Colombo North Teaching Hospital, Ragama, Sri Lanka.
Department of Paediatrics, Faculty of Medicine, University of Kelaniya, Thalagolla Road, Ragama, 11010, Sri Lanka.
J Med Case Rep. 2024 Sep 28;18(1):475. doi: 10.1186/s13256-024-04824-5.
Methotrexate is an essential medicine used to treat childhood malignancies including acute lymphoblastic leukemia. Neurotoxicity manifesting as leukoencephalopathy is an important adverse effect of methotrexate. Methotrexate-induced leukoencephalopathy classically demonstrates sub-acute-onset neurological manifestations that include learning disability, progressive dementia, drowsiness, seizures, ataxia, and hemiparesis. These are rare in children and are generally reported following intrathecal or intravenous use of methotrexate. In contrast, acute onset neurotoxicity with oral use of methotrexate is very rare. We report a 10-year-old boy presenting with acute onset limb weakness and neurological signs due to methotrexate-induced leukoencephalopathy following oral methotrexate.
A 10-year-old Sri Lankan boy presented with fever and headache for 5 days and difficulty in walking for 2 days. He was unable to stand unaided on admission, and his parents complained of repetitive, involuntary extension movements involving the right upper limb. He is a child diagnosed with acute lymphoblastic leukemia who was on treatment for a relapse with daily oral dexamethasone and mercaptopurine, weekly oral methotrexate and folinic acid, and once every two weeks intrathecal vincristine. On examination, he had dystonic movements of the right upper limb and hypotonia and reduced muscle power (grade 3/5) of the left upper and lower limbs proximally and distally. The muscle power of the right side was grade 4 (out of 5). Tendon reflexes were diminished in all four limbs, and the plantar response was flexor bilaterally. The child had dysmetria and intension tremors on both sides. T2-weighted magnetic resonance imaging of the brain revealed symmetrical high signal intensities with diffusion restriction involving bilateral putamen, subcortical areas, and deep white matter, suggesting treatment-related neurotoxicity due to methotrexate-induced leukoencephalopathy. Oral methotrexate was discontinued. He showed gradual improvement in limb weakness and other neurological signs following treatment with intravenous folinic acid, aminophylline, dexamethasone, and oral dextromethorphan.
This case report describes a patient with rapidly progressing methotrexate-induced leukoencephalopathy following oral methotrexate. It highlights that the risk of neurotoxicity persists even with the oral use of methotrexate; therefore, the prescribers should be vigilant of this uncommon side effect.
甲氨蝶呤是一种重要的药物，用于治疗包括急性淋巴细胞白血病在内的儿童恶性肿瘤。其神经毒性表现为脑白质病，是甲氨蝶呤的重要不良反应。甲氨蝶呤引起的脑白质病典型表现为亚急性发作的神经症状，包括学习障碍、进行性痴呆、嗜睡、癫痫、共济失调和偏瘫。这些在儿童中较为少见，通常在鞘内或静脉内使用甲氨蝶呤后发生。相比之下，口服甲氨蝶呤引起的急性发作神经毒性非常罕见。我们报告了一例 10 岁男孩，因口服甲氨蝶呤引起的甲氨蝶呤诱导的脑白质病，出现急性发作的肢体无力和神经体征。
一名 10 岁的斯里兰卡男孩因发热和头痛 5 天，行走困难 2 天就诊。入院时他无法独立站立，父母抱怨他出现重复的、无意识的右上肢伸展运动。他是一名急性淋巴细胞白血病患儿，正在接受复发治疗，每日口服地塞米松和巯嘌呤，每周口服甲氨蝶呤和亚叶酸，每两周鞘内注射长春新碱。检查时，他的右上臂出现张力障碍，四肢肌肉张力低下，近端和远端的左上、下肢肌力（3/5 级）下降。右侧肌力为 4 级（5 级）。四肢腱反射减弱，双侧跖反射为屈性。患儿两侧均有辨距不良和意向性震颤。脑 T2 加权磁共振成像显示双侧壳核、皮质下区和深部白质对称性高信号，弥散受限，提示甲氨蝶呤诱导的脑白质病所致与治疗相关的神经毒性。停用口服甲氨蝶呤。给予静脉亚叶酸、氨茶碱、地塞米松和口服右美沙芬治疗后，患儿肢体无力和其他神经体征逐渐改善。
本病例报告描述了一例口服甲氨蝶呤后迅速进展的甲氨蝶呤诱导的脑白质病患者。这表明即使口服甲氨蝶呤也存在神经毒性风险，因此，医生应警惕这种不常见的副作用。
