The fetal spinal cord does not regenerate after in utero transection in a large mammalian model

C Meuli-Simmen  1 , M Meuli, G M Hutchins, C D Yingling, G B Timmel, M R Harrison, N S Adzick

Regeneration and functional recovery after spinal cord transection do not occur in mammalian animals and humans postnatally. The goal of this study was to test whether in utero transection of the fetal spinal cord is succeeded by anatomic healing and functional recovery.

Journal: Neurosurgery (Volume 39, Issue 3, Pages 555-560)

Date: 01/09/1996

1 Fetal Treatment Center, University of California San Francisco, USA.

Acquired spinal cord injury in human fetuses with myelomeningocele

G M Hutchins  1 , M Meuli, C Meuli-Simmen, M A Jordan, D S Heffez, K J Blakemore

Experimental studies have shown that there is a potential to attempt in utero repair of myelomeningocele in human fetuses. To provide a better understanding of the pathology of these lesions we prospectively studied eight stillborn human fetuses with myelomeningocele autopsied at The Johns Hopkins Hospital. The intact vertebral column with surrounding structures was removed, processed as a single block, and prepared as serial histologic sections. Study of the slides showed in all cases that in the center of the myelomeningocele the vertebral arch was open, the arrangement of meninges was such that the dura mater was open and in continuity with the deep layers of the dermis, and the pia mater was open and in continuity with a layer consisting of the superficial dermis and the epidermis. These meningeal relationships created an abnormally configured arachnoid space containing cerebrospinal fluid ventral to the spinal cord, which rested on the open pia mater and was exposed on the dorsal aspect of the sac. At the level of the myelomeningocele the naked cord had undergone varying degrees of injury up to complete loss of neural tissue. Where ventral remnants of the cord remained it was evident that a large degree of normal development of the cord had occurred. In most instances it appeared that the injury or destruction of the dorsal spinal cord was recent and consistent with occurrence during delivery. The results of this study support the concept that in utero surgery could preserve and protect the exposed spinal cord in a myelomeningocele of a human fetus and thus could reduce the severity of the neurologic deficit at birth.

Journal: Pediatric pathology & laboratory medicine: Journal of the Society for Pediatric Pathology, affiliated with the International Paediatric Pathology association (Sep-Oct 1996;16(5):701-12)

Date: 01/09/1996

1 Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.

Experimental fetal transesophageal and intracardiac echocardiography utilizing intravascular ultrasound technology

T Kohl  1 , Z Szabo, K J VanderWall, S J Hutchinson, E J Stelnicki, M Meuli, M R Harrison, N H Silverman, T M Chou

Fetal transesophageal and intracardiac echocardiography by utilizing ultrasound technology permits accurate definition of cardiac anatomy in fetal sheep. Because fetal transesophageal echocardiography is less invasive than intracardiac echocardiography, it has the potential to serve as a monitoring tool for currently developed open and fetoscopic fetal cardiac interventions.

Journal: The American Journal of Cardiology (Volume 77, Issue 10, Pages 899-903)

Date: 01/04/1996

1 Division of Pediatric Cardiology, University of California, San Francisco 94143, USA.

Percutaneous access to the uterus for fetal surgery

K J VanderWall  1 , M Meuli, Z Szabo, S W Bruch, T Kohl, W Y Hoffman, N S Adzick, M R Harrison

In utero repair of selected life-threatening malformations in the human fetus is now a clinical reality, yet fetal surgery continues to pose significant risks to both the mother and the unborn child. Preterm labor is a major problem directly related to the large uterine incision required for fetal exposure. Using technology developed for laparoscopic surgery, we have devised instruments and techniques to perform fetal endoscopic surgery. We now report a percutaneous technique for direct endoscopic access to the uterus. Minimally invasive fetoscopic surgery may expand the indications for fetal surgery by decreasing fetal risks, facilitating intervention earlier in gestation, and reducing preterm labor. This technique was developed in 4 fetal lambs who underwent endoscopic intervention at 105-110 days gestation (term = 145 days). Under ultrasound guidance, a 20-gauge spinal needle was advanced through the maternal abdomen, uterus, and directly into the amniotic cavity. Warmed saline was infused through the needle to expand the amniotic cavity. Next, a 5-mm balloon-tipped trocar was placed percutaneously with ultrasound guidance into the amniotic cavity. A 5-mm laparoscope was introduced and under endoamniotic vision two more 5-mm trocars were percutaneously placed. In all four sheep a 5-mm trocar was placed percutaneously into the gravid uterus. The most difficult step was puncturing through the amniotic membranes, but the sharp tip of the trocar facilitated getting into the amniotic cavity. Excellent visualization of the fetus was obtained with minimal uterine trauma. We have developed a fetoscopic technique in sheep for percutaneous placement of trocars into the uterus using ultrasound guidance. This approach allowed excellent visualization of the fetus with significantly less uterine trauma than open fetal surgery and is an essential prerequisite for future fetal endoscopic interventions.

Journal: Journal of Laparoendoscopic Surgery (1996 Mar;6 Suppl 1:S65-7.)

Date: 01/03/1996

1 Fetal Treatment Center, Department of Surgery, University of California, San Francisco, USA.

In utero repair of experimental myelomeningocele saves neurological function at birth

M Meuli  1 , C Meuli-Simmen, C D Yingling, G M Hutchins, G B Timmel, M R Harrison, N S Adzick

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.

Journal: Journal of Pediatric Surgery (Volume 31, Issue 3, Pages 397-402)

Date: 01/03/1996

1 Department of Anesthesia, University of California, San Francisco, USA.