In utero repair of experimental myelomeningocele saves neurological function at birth

Martin Meuli, Claudia Meuli-Simmen, Charles D. Yingling, Grover M. Hutchins, Gregory Timmel, Michael R. Harrison, N. Scott Adzick

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

In a previous series of fetal sheep experiments, the authors demonstrated that midgestational exposure of the normal spinal cord to the amniotic space leads to a myelomeningocele (MMC) at birth that closely resembles human MMC phenotypes in terms of morphology and functional deficit. The present study tested whether delayed in utero repair of such evolving experimental MMC lesions spares neurological function. In 12 sheep fetuses, a spina bifida-type lesion with exposure of the lumbar spinal cord was created at 75 days' gestation (full term, 150 days). Four weeks later, the developing MMC lesions were repaired in utero for seven fetuses (five fetuses died before this time). Of those that had repair, three were delivered near term by cesarean section, and four died in utero or were aborted. All survivors had healed skin wounds and near-normal neurological function. Despite mild paraparesis, they were able to stand, walk, and perform demanding motor tests. Sensory function of the hindlimbs was present clinically and confirmed electrophysiologically. No signs of incontinence were detected. Histologically, the exposed and then covered spinal cord showed significant deformation, but the anatomic hallmarks as well as the cytoarchitecture of the spinal cord essentially were preserved. These findings show that timely in utero repair of developing experimental MMC stops the otherwise ongoing process of spinal cord destruction and 'rescues' neurological function by the time of birth. Because there is evidence that a similar secondary damage to the exposed neural tissue also occurs in human MMC, we propose that in utero repair of selected human fetuses might reduce the neurological disaster commonly encountered after birth.

Original languageEnglish (US)
Pages (from-to)397-402
Number of pages6
JournalJournal of Pediatric Surgery
Volume31
Issue number3
DOIs
StatePublished - Mar 1996
Externally publishedYes

Fingerprint

Meningomyelocele
Spinal Cord
Parturition
Fetus
Sheep
Paraparesis
Spinal Dysraphism
Disasters
Hindlimb
Cesarean Section
Phenotype
Pregnancy
Skin
Wounds and Injuries

ASJC Scopus subject areas

  • Surgery

Cite this

Meuli, M., Meuli-Simmen, C., Yingling, C. D., Hutchins, G. M., Timmel, G., Harrison, M. R., & Adzick, N. S. (1996). In utero repair of experimental myelomeningocele saves neurological function at birth. Journal of Pediatric Surgery, 31(3), 397-402. https://doi.org/10.1016/S0022-3468(96)90746-0

In utero repair of experimental myelomeningocele saves neurological function at birth. / Meuli, Martin; Meuli-Simmen, Claudia; Yingling, Charles D.; Hutchins, Grover M.; Timmel, Gregory; Harrison, Michael R.; Adzick, N. Scott.

In: Journal of Pediatric Surgery, Vol. 31, No. 3, 03.1996, p. 397-402.

Research output: Contribution to journalArticle

Meuli, M, Meuli-Simmen, C, Yingling, CD, Hutchins, GM, Timmel, G, Harrison, MR & Adzick, NS 1996, 'In utero repair of experimental myelomeningocele saves neurological function at birth', Journal of Pediatric Surgery, vol. 31, no. 3, pp. 397-402. https://doi.org/10.1016/S0022-3468(96)90746-0
Meuli, Martin ; Meuli-Simmen, Claudia ; Yingling, Charles D. ; Hutchins, Grover M. ; Timmel, Gregory ; Harrison, Michael R. ; Adzick, N. Scott. / In utero repair of experimental myelomeningocele saves neurological function at birth. In: Journal of Pediatric Surgery. 1996 ; Vol. 31, No. 3. pp. 397-402.
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