Spina bifida: paralyzing fluid in the womb?

Spina bifida: Paralyzing fluid in the womb?

Amniotic fluid would seem a safe haven for the developing fetus. But scientists report evidence that within this fluid may float substances that, while safe for the skin, sabotage the spinal cord. If verified, the new findings could explain the paralysis and bladder dysfunction associated with the most serious form of spina bifida, the researchers say.

No current treatment can reverse the damage suffered by those born with myelomeningocele, the most common birth defect in North America and the most severe form of spina bifida. In this congenital neural-tube defect, some as-yet-unidentified initial assault causes abnormal development of the spinal cord and the overlying bone and skin, leaving the cord in an exterior position and exposed to the amniotic fluid, explains Dan S. Heffez, a pediatric neurosurgeon at Johns Hopkins University School of Medicine in Baltimore. It is this secondary exposure to the amniotic fluid that causes much of the spinal cord injury borne by human infants with myelomeningocele, the new research suggests.

Heffez and co-worker John Aryanpur removed and operated on about 50 fetuses from 20 pregnant rats, removing the bone and skin over the cord. In half the fetal rats -- their control group -- they closed the skin. All fetuses were replaced in the mothers' wombs. At birth, all of the 14 live-born experimental rats had paralyzed hind limbs and deformed spines, but none of the six live-born control pups with healed wounds displayed these abnormalities, Heffez reported last week at the Johns Hopkins Centennial Science Writers Seminar.

Using a light microscope, the researchers found extensive tissue damage at the surface of the spinal cords of the open-wound rats, while the spinal cords of the closed-wound controls appeared normal. The pathology looks "extremely similar" to that of human children with myelomeningocele, Heffez says. In addition, the microscope revealed scarred and distended kidneys in eight of 14 experimental rat pups. Heffez says this is exactly what would be expected in human infants with myelomeningocele, whose malfunctioning bladders cause urine to back up, harming the kidney, Heffez says.

While the new results are compelling, not all experiments support Heffez's "two hit" theory for the cause of myelomeningocele. Neurosurgeon David G. McLone of Children's Memorial Hospital in Chicago says his mice with genetic myelomeningocele do not show any destruction of nervous tissue, adding that he is unaware of the evidence Heffez cites of such nerve damage in humans.

The Hopkins scientists are trying to see whether they can prevent the damage by surgically intervening in a second procedure to cover the exposed spinal cord after one day' exposure to amniotic fluid. So far, they have successfully closed the wounds of two such rats, which appeared normal at birth. Two control pups, whose wounds were not closed, showed severe neurological deficits, Heffez says.

"If [the Hopkins researchers] are right, then it's an important finding because it indicates that [myelomeningocele] is a progressive disease [and so] we should be doing something to interrupt [its progression] while the fetus is still in the uterus," McLone says. What will turn out to be the best "interruption" remains unclear. To minimize or prevent spina bifida's symptoms, Heffez suggests, physicians may someday modify human amniotic fluid, induce premature delivery -- if problems associated with premature birth can be overcome--or even perform fetal surgery.