Myelomeningocele (MMC), seen in 0.5-1 per 1000 live births, is almost always associated with hindbrain herniation or Chiari II malformation, and represents one of the most debilitating birth defects in humans. Hindbrain herniation results in impaired brainstem and cranial nerve function. Abnormal cerebral spinal fluid flow results in syrinx formation and hydrocephalus. Therefore, patients present with respiratory depression, apneic spells, lower cranial nerve palsies, and quadriparesis. Hydrocephalus develops in 83-90% of patients and almost always requires shunting. Shunt malfunction and infection represent the most common late mortality in MMC patients. We propose to prevent hindbrain herniation and hydrocephalus formation in sheep via in utero repair of surgically created MMC. Fetal lambs will undergo MMC creation at mid-gestation and half will be repaired in utero at 2/3 of gestation. At birth, lambs with in utero MMC repair should be free of hindbrain herniation and not develop hydrocephalus, in comparison with lambs without in utero MMC repair. If this holds true, in utero repair in humans may prevent the devastating consequences of hindbrain herniation and hydrocephalus. Furthermore, we will characterize in lambs gross pathological and axonal pathfinding anomalies usually seen in the human disease.
| von Koch, Cornelia S; Compagnone, Nathalie; Hirose, Shinjiro et al. (2005) Myelomeningocele: characterization of a surgically induced sheep model and its central nervous system similarities and differences to the human disease. Am J Obstet Gynecol 193:1456-62 |
