NEURAL TUBE DEFECTS EMBRYOLOGY

EMBRYOLOGY
The human embryo passes through 23 stages after conception, each occupying approximately 2-3 days. Two different processes form the central nervous system. The first is primary neurulation, which refers to the formation of the neural structures into a tube, thereby forming the brain and 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. 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.

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.