Abstract
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.
Keywords
fetal surgery - myelomeningocele - spina bifida - prenatal diagnosis
