Marques-Dias Maria Joaquina, Gonzalez Claudette H, Rosemberg Sergio
Department of Neurology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Birth Defects Res A Clin Mol Teratol. 2003 Dec;67(12):1002-7. doi: 10.1002/bdra.10144.
Misoprostol exposure in the first trimester of pregnancy has been related to congenital malformations, particularly the Möbius sequence and terminal transverse limb defects.
Neuropathological findings of three patients with Möbius sequence related to misoprostol are reported. No previous pathological studies have shown these abnormalities to be associated with misoprostol exposure in utero. The brain stem was cut serially, from the rostral mesencephalum to the caudal aspect of the medulla, and all fragments were stained with hematoxylin-eosin and cresyl violet. Old ischemic-anoxic foci of gliosis, with necrosis and calcification, dorsally situated, were present from the pons to the medulla, involving some cranial nerve nuclei (especially the IV, VII, and XII) that were partially or completely depopulated of neural cells.
The findings suggest a circulatory mechanism to the Möbius sequence, with vascular disruption involving the territory of the subclavian artery, occurring in a critical period of embryonic life between six to eight weeks postconception. These cases add further evidence of the role of misoprostol as a teratogen.
孕期头三个月接触米索前列醇与先天性畸形有关,尤其是默比厄斯序列征和肢体末端横向缺损。
报告了三例与米索前列醇相关的默比厄斯序列征患者的神经病理学发现。以往尚无病理研究表明这些异常与子宫内接触米索前列醇有关。将脑干从脑桥上段至延髓尾端连续切片,所有切片均用苏木精-伊红和甲酚紫染色。从脑桥到延髓背侧存在陈旧性缺血缺氧性胶质增生灶,伴有坏死和钙化,累及一些脑神经核(尤其是动眼神经核、面神经核和舌下神经核),这些神经核的神经细胞部分或完全缺失。
这些发现提示默比厄斯序列征存在一种循环机制,即血管破坏累及锁骨下动脉供血区域,发生在受孕后6至8周的胚胎关键期。这些病例进一步证明了米索前列醇作为致畸剂的作用。