Methotrexate neurotoxicity--Resolution and evolution of MRI changes within 48 hours

Figure 1 First cranial MRI scan

Diffusion-weighted imaging shows restricted diffusion in the left centrum semiovale (A). This correlated with decreased apparent diffusion coefficient signal in the same area (B).

Figure 2 Cranial MRI scan 44 hours later

Diffusion-weighted imaging shows resolution of prior left-sided changes and evolution of a new area of restricted diffusion in the right centrum semiovale (A). Again, this correlated with decreased apparent diffusion coefficient signal (B).

     A 13-year-old girl presented with acute-onset right hemiparesis involving the face, arm, and leg equally. She was receiving weekly intrathecal methotrexate (last dose 6 days prior) for recently diagnosed acute lymphocytic leukemia. Brain MRI (figure 1) showed diffusion restriction in the left centrum semiovale with reduced apparent diffusion coefficient. Her hemiparesis resolved within 24 hours, but 2 hours later she developed 12-hour left hemiparesis involving face, upper limb, and dysarthria. Follow-up neurologic examination was normal. Repeat MRI (figure 2) 44 hours after the original MRI showed acute right centrum semiovale changes. The changes that were previously seen on the left side had resolved. As before, all changes noted were localized completely in white matter, nonvascular territory. This was consistent with methotrexate neurotoxicity,1,2 possibly secondary to homocysteine accumulation causing direct endothelial injury.3 The patient resumed intrathecal methotrexate 1 month later as part of her ongoing chemotherapeutic regimen without further incidents.

      女性，13岁，以急性起病的右侧偏身无力就诊。患者有急性淋巴细胞性白血病，目前正在接受鞘内注射甲氨蝶呤治疗，每周一次，上一剂量于6天前使用。头颅MRI示左侧半卵圆区异常信号，DWI呈高信号，ADC呈低信号（图1）。

     患者的右侧轻偏瘫在24小时后缓解，但2小时后，患者又出现持续12小时的左侧偏瘫伴构音障碍。随后神经科查体示完全正常。

        44小时后复查头颅MRI（图2）提示提示右侧急性半卵圆区病变，之前在左侧半卵圆区的异常信号消失。

      患者所有病灶均位于白质，不符合血管分布，考虑与甲氨蝶呤的神经毒性有关，可能继发于同型半胱氨酸堆积直接损害血管内皮有关。患者继续甲氨蝶呤治疗，此后未再出现类似的现象。

                                     Neurology. 2013 Sep 3;81(10):e73-4

评论：

    尽管临床错综复杂，但有果就有因，有时我们可以用“减法”推出可能病因，然后再进行相关检查或查资料印证。

    正如此例病人，病人为急性淋巴细胞性白血病，本来没有神经科啥事，但在引入一个新元素（鞘内注射甲氨蝶呤）后出现了一过性神经功能缺损，从因果论的角度做一个减法，即神经系统新症状-原来的急性淋巴细胞白血病=鞘内注射甲氨蝶呤，由此应该高度怀疑和新元素（鞘内注射甲氨蝶呤）有关，最后经求助文献得以确诊。

    由此可见，在神经科临床上，假设推理后检查证实或文献求助是常用的手段。

后记：

    随着药物治疗的广泛应用，药物导致的损害在临床日益增多，不仅仅是抗癌药物的损害，很多化学药物都可以引起各个系统的损害和复杂的相应的影像表现，而这些影像表现往往没有特异性，所以在临床工作中遇到无法解释的异常影像时，应该考虑到药物性损害的可能。