Anemia of Prematurity - Portal Neonatal

to the lumbar and sacral elements. The neural plate is formed at stage 8 (days 17-19), the neural
fold occurs at stage 9 (days 19-21), and the fusion of the neural folds occurs at stage 10 (days 22-
23). Any disruption at stages 8-10 (ie, when the neural plate begins its first fold and fuses to form
the neural tube) can cause craniorachischisis, the most severe form of NTD.
Stage 11 (days 23-26) is when the closure of the rostral neuropore occurs. Failure at this point
results in anencephaly (see Images 6-7). Myelomeningocele is a result of disruption of stage 12
(days 26-30), closure of the caudal neuropore. Beyond day 26, a disruption is unlikely to be able to
cause an NTD such as myelomeningocele (see Image 1).
Studies on mice embryos have provided some unifying theories for explaining the associated
anomalies seen with neural tube defects. Associated defects include hydrocephalus and hindbrain
malformations such as Chiari II malformation. McLone and Naidich, in 1992, proposed a unifying
theory of neural tube defects that explains both the hindbrain anomalies and the spinal cord
anomalies. According to these investigators, the initial event is a failure of the neural folds to
completely close, leaving a dorsal defect or myeloschisis. This permits the CSF to leak from the
ventricles through the central canal and into the amniotic fluid and creates a collapse of the
primitive ventricular system.
Failure of the primitive ventricular system to increase in size and volume leads to both downward
and upward herniation of the small cerebellum. In addition, the posterior fossa does not develop to
its full size, and the neuroblasts do not migrate outward at a normal rate from the ventricles into the
cortex. Therefore, the entire panoply of defects occurs from an initial inciting event.
The precise genes (overexpressed or underexpressed) in this event have not been identified. The
sonic hedgehog (Shh) gene has been identified in defects that cause hydrocephalus secondary to
holoprosencephaly. This gene is believed to induce growth of the neural plate and helps close the
neural tube by exerting a strong influence on the ventral and medial structure of the
prosencephalon. The precise relationship of the Shh gene with neural tube defects is yet to be
defined. Below is a table with the suspected embryologic event and result.
Days of
Gestation
Table 1. Human Central Nervous System Malformations
0-18 Formation of three germ layer
and neural plate
18 Formation of neural plate and
groove form
Event Resultant Malformation
Death or unclear effect
Anterior midline defects
22-23 Appearance of optic vessels Hydrocephalus (18-60 d)
24-26 Close anterior neuropore Anencephaly
26-28 Close posterior neuropore Cranium bifidum, spina bifida cystica,
spina bifida occulta
32 Vascular circulation Microcephaly (30-130 d), migration
anomalies
33-35 Splitting of prosencephalon to
make paired telencephalon
Holoprosencephaly
70-100 Formation of corpus callosum Agenesis of the corpus callosum