Myelomeningocele: Characterization of a surgically induced sheep model and its central nervous system similarities and differences to the human disease

Objective: The purpose of this study was to determine how closely the surgically induced sheep myelomeningocele (MMC) model resembles the central nervous system derangements seen in human disease, and identify which aspects of MMC are the result of the early neuronal developmental defect, and which are secondary to the cerebrospinal fluid (CSF) drainage. Study design: An MMC-like lesion was created surgically in 16 fetal sheep at 75 days' gestation: 5 died in utero, 7 underwent no fetal repair, 4 were repaired (2-layer closure or biological glue) at 100 days' gestation. MMC sheep were delivered at term and allowed to survive up to 17 days for analysis of behavioral status and feeding behavior. Animals not repaired in utero were repaired at birth. All lambs were sacrificed and analyzed for hindbrain herniation, hydrocephalus, and other CNS derangements. Results: Hindbrain herniation was observed in 43% of animals not repaired in utero, and in 1 lamb repaired with Bioglue. No animal developed hydrocephalus or other CNS derangements. Conclusion: Although this sheep MMC-like model reproduces the CSF leak, but not the developmental defect seen in humans, it suggests CSF leak contributes to hindbrain herniation seen in humans. This model may be useful to develop new minimally invasive techniques to halt CSF leak in utero.