ABSTRACT
THEORETICAL BACKGROUND The rationale for fetal repair of the back lesion in spina bifida was outlined by Heffez and associates in 1990 in a paper titled “The paralysis associated with myelomeningocele: Clinical and experimental data implicating a preventable spinal cord injury” (1). They exposed the spinal cord of fetal rats to amniotic fluid and found that the rats were born with severe weakness of the hind limbs and tail. Histology of the affected spinal cords showed necrosis and erosion of the neural tissue, which they thought looked similar to that seen in the myelomeningoceles of children with spina bifida. The authors thought that the paralysis in these children was due not only to the myelodysplasia but also to intrauterine injury, a hypothesis which they called the “two hit” theory. They went further to suggest that “. . . intrauterine protection of the exposed spinal cord might prevent some or all of the paralysis.” Fetal surgery for the repair of the back lesion in spina bifida in human fetuses was proposed by Joe Brunner and his colleagues at Vanderbilt Medical Center, Nashville, in the 1990s (2). As a preliminary they created a model of spina bifida in sheep and showed that it was possible to endoscopically cover the exposed spinal cord with skin grafts. The rationale for the procedure was based on the hypothesis proposed by Meuli and associates who agreed with Heffez’s contention that “. . . the neurologic deficit associated with open spina bifida is not directly caused by the primary defect but rather is due to chronic mechanical and chemical trauma since the unprotected neural tissue is exposed to the intrauterine environment” (3). In support of this proposition, Meuli showed that the spinal cord of normal midterm fetal sheep exposed to the amniotic fluid in the cavity of the uterus was progressively destroyed during pregnancy unless it was covered by a skin graft, in which case its form and function were largely preserved. While the fetal rat and sheep models clearly did not closely resemblance the spinal cord malformed by a myelomeningocele, it was thought the findings were relevant if it was accepted that early in fetal developmental significant neurological function was present in the human spinal cord deformed by a myelomeningocele and that this function was lost by exposure to the amniotic fluid.
