Meuli Martin, Moehrlen Ueli
Department of Pediatric Surgery, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland,
Pediatr Surg Int. 2014 Jul;30(7):689-97. doi: 10.1007/s00383-014-3524-8. Epub 2014 Jun 8.
Formerly, the disastrous cluster of neurologic deficits and associated neurogenic problems in patients with myelomeningocele (MMC) was generally thought to solely result from the primary malformation, i.e., failure of neurulation. Today, however, there is no doubt that a dimensional additional pathogenic mechanism exists. Most likely, it contributes much more to loss of neurologic function than non-neurulation does. Today, there is a large body of compelling experimental and clinical evidence confirming that the exposed part of the non-neurulated spinal cord is progressively destroyed during gestation, particularly so in the third trimester. These considerations gave rise to the two-hit-pathogenesis of MMC with non-neurulation being the first and consecutive in utero acquired neural tissue destruction being the second hit. This novel pathophysiologic understanding has obviously triggered the question whether the serious and irreversible functional loss caused by the second hit could not be prevented or, at least, significantly alleviated by timely protecting the exposed spinal cord segments, i.e., by early in utero repair of the MMC lesion. Based on this intriguing hypothesis and the above-mentioned data, human fetal surgery for MMC was born in the late nineties of the last century and has made its way to become a novel standard of care, particularly after the so-called "MOMS Trial". This trial, published in the New England Journal of Medicine, has indisputably shown that overall, open prenatal repair is distinctly better than postnatal care alone. Finally, a number of important other topics deserve being mentioned, including the necessity to work on the up till now immature endoscopic fetal repair technique and the need for concentration of these extremely challenging cases to a small number of really qualified fetal surgery centers worldwide. In conclusion, despite the fact that in utero repair of MMC is not a complete cure and not free of risk for both mother and fetus, current data clearly demonstrate that open fetal-maternal surgery is to be recommended as novel standard of care when pregnancy is to be continued and when respective criteria for the intervention before birth are met. Undoubtedly, it is imperative to inform expecting mothers about the option of prenatal surgery once their fetus is diagnosed with open spina bifida.
以前，脊髓脊膜膨出（MMC）患者出现的灾难性神经功能缺损及相关神经源性问题通常被认为完全是由原发性畸形，即神经胚形成失败所致。然而如今，毫无疑问还存在一种额外的致病机制。很可能，它对神经功能丧失的影响比神经胚形成失败更大。如今，有大量令人信服的实验和临床证据证实，在妊娠期，未形成神经的脊髓暴露部分会逐渐遭到破坏，在妊娠晚期尤其如此。这些因素引发了MMC的双打击发病机制，其中神经胚形成失败是第一次打击，而随后在子宫内获得性神经组织破坏则是第二次打击。这种新的病理生理学认识显然引发了一个问题：第二次打击所导致的严重且不可逆转的功能丧失，能否通过及时保护暴露的脊髓节段，即通过子宫内早期修复MMC病变来预防，或者至少显著减轻。基于这一引人入胜的假设和上述数据，针对MMC的人类胎儿手术于上世纪九十年代末诞生，并逐渐成为一种新的标准治疗方法，尤其是在所谓的“MOMS试验”之后。该试验发表在《新英格兰医学杂志》上，无可争议地表明，总体而言，开放性产前修复明显优于单纯的产后护理。最后，还有一些其他重要话题值得一提，包括改进至今仍不成熟的内镜胎儿修复技术的必要性，以及将这些极具挑战性的病例集中到全球少数真正合格的胎儿手术中心的需求。总之，尽管子宫内修复MMC并非完全治愈方法，且对母亲和胎儿都存在风险，但目前的数据清楚地表明，当决定继续妊娠且满足出生前干预的相应标准时，开放性胎儿 - 母体手术应被推荐为新的标准治疗方法。毫无疑问，一旦孕妇的胎儿被诊断为开放性脊柱裂，就必须告知她们产前手术这一选择。
