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Prenatal surgery for myelomeningocele: review of the literature and future directions

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Abstract

Open spina bifida or myelomeningocele (MMC) is one of the most common serious congenital malformations. Historically, this condition has been treated with closure of the MMC defect shortly after birth. The goal of postnatal closure is to cover the exposed spinal cord and prevent infection. However, postnatal surgery does not reverse or prevent the neurologic injury seen in MMC, reverse hindbrain herniation, or prevent hydrocephalus. The neurologic defects result from primary incomplete neurulation and secondary chronic prenatal damage to the exposed neural elements through mechanical and chemical trauma. In a hope to reduce the numerous surgical procedures, medical complications, and lifelong disabilities associated with MMC, the proposal of prenatal closure was put forth more than two decades ago. After promising results in animal models and some clinical series, a randomized controlled trial, the Management of Myelomeningocele Study (MOMS), was conducted. The MOMS trial demonstrated that closure during the prenatal period could be performed relatively safely and can result in significant benefit to the child. Specifically, prenatal closure results in improved motor function, reduced hindbrain herniation, and reduced need for a cerebral spinal fluid diversion. Long-term outcomes of the patients in the MOMS trial continues in the MOMS 2 study as these children grow. Additionally, investigations are underway on modifications to the open fetal MMC closure techniques.

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References

  1. Bauman JA, Schwartz DM, Welch WC, Sutton LN (2011) Congenital anomalies of the spinal cord. In: Herkowitz HN, Garfin SR, Eismont FJ, Bell GR, Balderston RA (eds) Rothman-Simeone the spine, 6th edn. Saunders, Philadelphia, pp 573–607

    Chapter  Google Scholar 

  2. Kancherla V, Druschel CM, Oakley GP Jr (2014) Population-based study to determine mortality in spina bifida: New York state congenital malformations registry, 1983 to 2006. Birth Defects Res Part A Clin Mol Teratol 100:563–575

    Article  CAS  PubMed  Google Scholar 

  3. Shin M, Kucik JE, Siffel C, Lu C, Shaw GM, Canfield MA, Correa A (2012) Improved survival among children with spina bifida in the United States. J Pediatr 161:1132–1137

    Article  PubMed  PubMed Central  Google Scholar 

  4. Meuli M, Meuli-Simmen C, Hutchins GM, Seller MJ, Harrison MR, Adzick NS (1997) The spinal cord lesion in human fetuses with myelomeningocele: implications for fetal surgery. J Pediatr Surg 32:448–452

    Article  CAS  PubMed  Google Scholar 

  5. Adzick NS (2010) Fetal myelomeningocele: natural history, pathophysiology, and in-utero intervention. Semin Fetal Neonatal Med 15:9–14

    Article  PubMed  Google Scholar 

  6. Meuli M, Meuli-Simmen C, Hutchins GM, Yingling CD, Hoffman KM, Harrison MR, Adzick NS (1995) In utero surgery rescues neurological function at birth in sheep with spina bifida. Nat Med 1:342–347

    Article  CAS  PubMed  Google Scholar 

  7. Adzick NS, Sutton LN, Crombleholme TM, Flake AW (1998) Successful fetal surgery for spina bifida. Lancet 352:1675–1676

    Article  CAS  PubMed  Google Scholar 

  8. Tulipan N, Hernanz-Schulman M, Bruner JP (1998) Reduced hindbrain herniation after intrauterine myelomeningocele repair: a report of four cases. Pediatr Neurosurg 29:274–278

    Article  CAS  PubMed  Google Scholar 

  9. Sutton LN, Adzick NS, Bilaniuk LT, Johnson MP, Crombleholme TM, Flake AW (1999) Improvement in hindbrain herniation demonstrated by serial fetal magnetic resonance imaging following fetal surgery for myelomeningocele. JAMA 282:1826–1831

    Article  CAS  PubMed  Google Scholar 

  10. Bruner JP, Tulipan N, Paschall RL, Boehm FH, Walsh WF, Silva SR, Hernanz-Schulman M, Lowe LH, Reed GW (1999) Fetal surgery for myelomeningocele and the incidence of shunt-dependent hydrocephalus. JAMA 282:1819–1825

    Article  CAS  PubMed  Google Scholar 

  11. Adzick NS, Thom EA, Spong CY, Brock JW 3rd, Burrows PK, Johnson MP, Howell LJ, Farrell JA, Dabrowiak ME, Sutton LN, Gupta N, Tulipan NB, D’Alton ME, Farmer DL, Investigators M (2011) A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med 364:993–1004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tulipan N, Wellons JC 3rd, Thom EA, Gupta N, Sutton LN, Burrows PK, Farmer D, Walsh W, Johnson MP, Rand L, Tolivaisa S, D’Alton ME, Adzick NS, Investigators M (2015) Prenatal surgery for myelomeningocele and the need for cerebrospinal fluid shunt placement. J Neurosurg Pediatr 16:613–620

    Article  PubMed  PubMed Central  Google Scholar 

  13. Moldenhauer JS, Soni S, Rintoul NE, Spinner SS, Khalek N, Martinez-Poyer J, Flake AW, Hedrick HL, Peranteau WH, Rendon N, Koh J, Howell LJ, Heuer GG, Sutton LN, Johnson MP, Adzick NS (2015) Fetal myelomeningocele repair: the post-MOMS experience at the Children’s Hospital of Philadelphia. Fetal Diagn Ther 37:235–240

    Article  PubMed  Google Scholar 

  14. Riva-Cambrin J, Kestle JR, Holubkov R, Butler J, Kulkarni AV, Drake J, Whitehead WE, Wellons JC 3rd, Shannon CN, Tamber MS, Limbrick DD Jr, Rozzelle C, Browd SR, Simon TD, Hydrocephalus Clinical Research N (2016) Risk factors for shunt malfunction in pediatric hydrocephalus: a multicenter prospective cohort study. J Neurosurg Pediatr 17:382–390

    Article  PubMed  Google Scholar 

  15. Warf BC (2011) Hydrocephalus associated with neural tube defects: characteristics, management, and outcome in sub-Saharan Africa. Childs Nerv Syst 27:1589–1594

    Article  PubMed  Google Scholar 

  16. Warf BC, Mugamba J, Kulkarni AV (2010) Endoscopic third ventriculostomy in the treatment of childhood hydrocephalus in Uganda: report of a scoring system that predicts success. J Neurosurg Pediatr 5:143–148

    Article  PubMed  Google Scholar 

  17. Kulkarni AV, Drake JM, Mallucci CL, Sgouros S, Roth J, Constantini S, Canadian Pediatric Neurosurgery Study G (2009) Endoscopic third ventriculostomy in the treatment of childhood hydrocephalus. J Pediatr 155(254–259):e251

    Google Scholar 

  18. Dias MS, McLone DG (1993) Hydrocephalus in the child with dysraphism. Neurosurg Clin N Am 4:715–726

    CAS  PubMed  Google Scholar 

  19. McLone DG, Knepper PA (1989) The cause of Chiari II malformation: a unified theory. Pediatr Neurosci 15:1–12

    Article  CAS  PubMed  Google Scholar 

  20. Charney EB, Rorke LB, Sutton LN, Schut L (1987) Management of Chiari II complications in infants with myelomeningocele. J Pediatr 111:364–371

    Article  CAS  PubMed  Google Scholar 

  21. McLone DG, Dias MS (2003) The Chiari II malformation: cause and impact. Childs Nerv Syst 19:540–550

    Article  PubMed  Google Scholar 

  22. Rintoul NE, Sutton LN, Hubbard AM, Cohen B, Melchionni J, Pasquariello PS, Adzick NS (2002) A new look at myelomeningoceles: functional level, vertebral level, shunting, and the implications for fetal intervention. Pediatrics 109:409–413

    Article  PubMed  Google Scholar 

  23. Brock JW 3rd, Carr MC, Adzick NS, Burrows PK, Thomas JC, Thom EA, Howell LJ, Farrell JA, Dabrowiak ME, Farmer DL, Cheng EY, Kropp BP, Caldamone AA, Bulas DI, Tolivaisa S, Baskin LS, Investigators M (2015) Bladder function after fetal surgery for myelomeningocele. Pediatrics 136:e906–e913

    Article  PubMed  PubMed Central  Google Scholar 

  24. Danzer E, Adzick NS (2011) Fetal surgery for myelomeningocele: patient selection, perioperative management and outcomes. Fetal Diagn Ther 30:163–173

    Article  PubMed  Google Scholar 

  25. Heuer GG, Adzick NS, Sutton LN (2015) Fetal myelomeningocele closure: technical considerations. Fetal Diagn Ther 37:166–171

    Article  PubMed  Google Scholar 

  26. Cohen AR, Couto J, Cummings JJ, Johnson A, Joseph G, Kaufman BA, Litman RS, Menard MK, Moldenhauer JS, Pringle KC, Schwartz MZ, Walker WO Jr, Warf BC, Wax JR, Force MMCM-FMT (2014) Position statement on fetal myelomeningocele repair. AJOG 210:107–111

    Article  Google Scholar 

  27. Midrio P, Silberstein HJ, Bilaniuk LT, Adzick NS, Sutton LN (2002) Prenatal diagnosis of terminal myelocystocele in the fetal surgery era: case report. Neurosurgery 50:1152–1154 discussion 1154-1155

    PubMed  Google Scholar 

  28. Husler MR, Danzer E, Johnson MP, Bebbington M, Sutton L, Adzick NS, Wilson RD (2009) Prenatal diagnosis and postnatal outcome of fetal spinal defects without Arnold-Chiari II malformation. Prenat Diagn 29:1050–1057

    Article  PubMed  Google Scholar 

  29. Mangels KJ, Tulipan N, Tsao LY, Alarcon J, Bruner JP (2000) Fetal MRI in the evaluation of intrauterine myelomeningocele. Pediatr Neurosurg 32:124–131

    Article  CAS  PubMed  Google Scholar 

  30. Chao TT, Dashe JS, Adams RC, Keefover-Hicks A, McIntire DD, Twickler DM (2011) Fetal spine findings on MRI and associated outcomes in children with open neural tube defects. AJR Am J Roentgenol 197:W956–W961

    Article  PubMed  Google Scholar 

  31. Gupta N, Farrell JA, Rand L, Cauldwell CB, Farmer D (2012) Open fetal surgery for myelomeningocele. J Neurosurg Pediatr 9:265–273

    Article  PubMed  Google Scholar 

  32. Yang EY, Adzick NS (1998) Fetoscopy. Semin Laparosc Surg 5:31–39

    CAS  PubMed  Google Scholar 

  33. Bruner JP, Richards WO, Tulipan NB, Arney TL (1999) Endoscopic coverage of fetal myelomeningocele in utero. AJOG 180:153–158

    Article  CAS  Google Scholar 

  34. Verbeek RJ, Heep A, Maurits NM, Cremer R, Hoving EW, Brouwer OF, van der Hoeven JH, Sival DA (2012) Fetal endoscopic myelomeningocele closure preserves segmental neurological function. Dev Med Child Neurol 54:15–22

    Article  PubMed  Google Scholar 

  35. Pedreira DA, Zanon N, Nishikuni K, de Sa Moreira RA, Acacio GL, Chmait RH, Kontopoulos EV, Quintero RA (2016) Endoscopic surgery for the antenatal treatment of myelomeningocele: the CECAM trial. AJOG 214:111 e111

    Article  Google Scholar 

  36. Degenhardt J, Schurg R, Winarno A, Oehmke F, Khaleeva A, Kawecki A, Enzensberger C, Tinneberg HR, Faas D, Ehrhardt H, Axt-Fliedner R, Kohl T (2014) Percutaneous minimal-access fetoscopic surgery for spina bifida aperta. Part II: maternal management and outcome. Ultrasound Obstet Gynecol 44:525–531

    Article  CAS  PubMed  Google Scholar 

  37. Eggink AJ, Roelofs LA, Feitz WF, Wijnen RM, Mullaart RA, Grotenhuis JA, van Kuppevelt TH, Lammens MM, Crevels AJ, Hanssen A, van den Berg PP (2005) In utero repair of an experimental neural tube defect in a chronic sheep model using biomatrices. Fetal Diagn Ther 20:335–340

    Article  CAS  PubMed  Google Scholar 

  38. Watanabe M, Jo J, Radu A, Kaneko M, Tabata Y, Flake AW (2010) A tissue engineering approach for prenatal closure of myelomeningocele with gelatin sponges incorporating basic fibroblast growth factor. Tissue Eng A 16:1645–1655

    Article  CAS  Google Scholar 

  39. Watanabe M, Li H, Roybal J, Santore M, Radu A, Jo J, Kaneko M, Tabata Y, Flake A (2011) A tissue engineering approach for prenatal closure of myelomeningocele: comparison of gelatin sponge and microsphere scaffolds and bioactive protein coatings. Tissue Eng A 17:1099–1110

    Article  CAS  Google Scholar 

  40. Fontecha CG, Peiro JL, Sevilla JJ, Aguirre M, Soldado F, Fresno L, Fonseca C, Chacaltana A, Martinez V (2011) Fetoscopic coverage of experimental myelomeningocele in sheep using a patch with surgical sealant. Eur J Obstet Gynecol Reprod Biol 156:171–176

    Article  PubMed  Google Scholar 

  41. Adzick NS (2013) Fetal surgery for spina bifida: past, present, future. Semin Pediatr Surg 22:10–17

    Article  PubMed  Google Scholar 

  42. Flake A (2014) Percutaneous minimal-access fetoscopic surgery for myelomeningocele—not so minimal! Ultrasound Obstet Gynecol 44:499–500

    Article  CAS  PubMed  Google Scholar 

  43. Wilson RD, Johnson MP, Crombleholme TM, Flake AW, Hedrick HL, King M, Howell LJ, Adzick NS (2003) Chorioamniotic membrane separation following open fetal surgery: pregnancy outcome. Fetal Diagn Ther 18:314–320

    Article  PubMed  Google Scholar 

  44. Soni S, Moldenhauer JS, Spinner SS, Rendon N, Khalek N, Martinez-Poyer J, Johnson MP, Adzick NS (2016) Chorioamniotic membrane separation and preterm premature rupture of membranes complicating in utero myelomeningocele repair. AJOG 214:e1–e7

    Article  Google Scholar 

  45. Danzer E, Thomas NH, Thomas A, Friedman KB, Gerdes M, Koh J, Adzick NS, Johnson MP (2016) Long-term neurofunctional outcome, executive functioning, and behavioral adaptive skills following fetal myelomeningocele surgery. AJOG 214(269):e261–e268

    Google Scholar 

  46. Danzer E, Adzick NS, Rintoul NE, Zarnow DM, Schwartz ES, Melchionni J, Ernst LM, Flake AW, Sutton LN, Johnson MP (2008) Intradural inclusion cysts following in utero closure of myelomeningocele: clinical implications and follow-up findings. J Neurosurg Pediatr 2:406–413

    Article  PubMed  Google Scholar 

  47. Mazzola CA, Albright AL, Sutton LN, Tuite GF, Hamilton RL, Pollack IF (2002) Dermoid inclusion cysts and early spinal cord tethering after fetal surgery for myelomeningocele. N Engl J Med 347:256–259

    Article  PubMed  Google Scholar 

  48. Iwasaki M, Yoshida Y, Shirane R, Yoshimoto T (2000) Spinal dermoid cyst secondary to myelomeningocele repair: a case report. No Shinkei Geka - Neurol Surg 28:155–160

    CAS  Google Scholar 

  49. Kirsch WM, Hodges FJ 3rd (1966) An intramedullary epidermal inclusion cyst of the thoracic cord associated with a previously repaired meningocele. Case report. J Neurosurg 24:1018–1020

    Article  CAS  PubMed  Google Scholar 

  50. Scott RM, Wolpert SM, Bartoshesky LE, Zimbler S, Klauber GT (1986) Dermoid tumors occurring at the site of previous myelomeningocele repair. J Neurosurg 65:779–783

    Article  CAS  PubMed  Google Scholar 

  51. Martinez-Lage JF, Masegosa J, Sola J, Poza M (1983) Epidermoid cyst occurring within a lumbosacral myelomeningocele. Case report. J Neurosurg 59:1095–1097

    Article  CAS  PubMed  Google Scholar 

  52. Storrs BB (1994) Are dermoid and epidermoid tumors preventable complications of myelomeningocele repair? Pediatr Neurosurg 20:160–162

    Article  CAS  PubMed  Google Scholar 

  53. Chadduck WM, Roloson GJ (1993) Dermoid in the filum terminale of a newborn with myelomeningocele. Pediatr Neurosurg 19:81–83

    Article  CAS  PubMed  Google Scholar 

  54. Thawani JP, Nayak NR, Pisapia JM, Tahiri Y, Gebbia J, Adzick NS, Sutton LN, Taylor JA, Heuer GG (2015) Myofascial closure of intradural inclusion cysts following in utero myelomeningocele repair. Pediatr Neurosurg 50:286–290

    Article  PubMed  Google Scholar 

  55. Jackson EM, Schwartz DM, Sestokas AK, Zarnow DM, Adzick NS, Johnson MP, Heuer GG, Sutton LN (2014) Intraoperative neurophysiological monitoring in patients undergoing tethered cord surgery after fetal myelomeningocele repair. J Neurosurg Pediatric 13:355–361

    Article  Google Scholar 

  56. Wilson RD, Lemerand K, Johnson MP, Flake AW, Bebbington M, Hedrick HL, Adzick NS (2010) Reproductive outcomes in subsequent pregnancies after a pregnancy complicated by open maternal-fetal surgery (1996-2007). AJOG 203(209):e201–e206

    Google Scholar 

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Heuer, G.G., Moldenhauer, J.S. & Scott Adzick, N. Prenatal surgery for myelomeningocele: review of the literature and future directions. Childs Nerv Syst 33, 1149–1155 (2017). https://doi.org/10.1007/s00381-017-3440-z

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