This article narrates the thrilling story of how the pathogenetic understanding of myelomeningocele was fundamentally revised during the last decades and how these new insights, in particular the "two-hit hypothesis," have prepared the terrain for human fetal surgery. Formerly, the devastating cluster of neurologic and neurogenic problems was mainly attributed to the primary malformation, that is, failure of neurulation. At present, there is solid evidence that in early gestation the nonneurulated spinal cord functions well, but suffers from progressive traumatic and degenerative damage in later gestation because it is openly exposed to the amniotic cavity. There is no doubt that the secondary, in utero acquired spinal cord destruction is mainly responsible for the disastrous and irreversible peripheral neurologic deficit present at birth, and there is no doubt either that timely prenatal protective coverage can potentially arrest these deleterious dynamics and preserve neurologic function. Also, tethering of the cord within and constant outflow of cerebrospinal fluid from the lesion are seen as the driving forces behind the Chiari II malformation and consequent ventriculomegaly. Untethering and watertight sealing of the lesion reverses hindbrain herniation and lowers the risk for a relevant hydrocephalus. This article then details how human fetal surgery started in the late 1990s and follows the evolution from the pioneer case studies via the first case series providing encouraging results to the ground breaking Management of Myelomeningocele Study Trial, published in The New England Journal of Medicine in February 2011 by Adzick et al, that has, for the first time, generated unequivocal evidence that patients with prenatal repair do significantly better than those with postnatal care only. Finally, this review looks at several other critical issues, including the hitherto immature endoscopic approach to fetal repair, some future directions of research and clinical practice, and also utters a plea for concentration of these equally rare and complex cases to a few truly qualified centers worldwide. The conclusion derived from all data existing today is that maternal-fetal surgery, although not a cure and not free of risks, represents a novel standard of care for select mothers and their fetuses suffering from one of the most ruinous nonlethal congenital malformations.
Georg Thieme Verlag KG Stuttgart · New York.