title: Maldevelopment of the cerebral cortex in the surgically induced model of myelomeningocele: implications for fetal neurosurgery.
abstract: OBJECTIVE
  The purpose of this study is to describe the malformations of cortical development detected in a model of cerebrospinal fluid (CSF) leakage and the influence of surgical closure technique on developmental outcome.
  
  
  METHODS
  Using a surgically induced model of myelomeningocele (MMC) in sheep, we studied the effects of different repair methods upon the development of hydrocephalus, the presence of the Arnold-Chiari II (AC-II) hindbrain malformation, and cerebral cortex developmental anomalies using gross and histologic (hematoxylin and eosin and Nissl staining) study techniques.
  
  
  RESULTS
  A malformed cerebral cortex, including 2 anomalous cortical folding patterns, and lower brain weights were observed in the untreated animals. Hydrocephalus and AC-II malformations were also found in this group. These malformations were mostly prevented with prenatal 2-layer closure.
  
  
  CONCLUSIONS
  Cerebral cortical malformations and hydrocephalus, in addition to the AC-II hindbrain malformation, are disorders caused by fetal CSF leakage. These malformations were prevented with the technique of MMC closure currently used in humans. Both observations magnify the importance of the second hit associated with chronic CSF leakage, in addition to the primary defect causing the MMC, in the development of the malformation complex.
authors.affiliation: Department of Pediatric Surgery, Hospital Universitario "La Paz," Madrid, Spain. Electronic address: encinas.j@tiscali.it.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Encinas
authors.affiliation: Department of Pathology, Hospital Universitario "La Paz," Madrid, Spain.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: García-Cabezas
authors.affiliation: Section of Neuroradiology, Department of Radiology, UCSF, San Francisco, CA.
authors.forename: James
authors.initials: J
authors.lastname: Barkovich
authors.affiliation: Pediatric Orthopedic Unit, Department of Orthopedic Surgery, Hospital Universitario "Vall D'Hebron," Barcelona, Spain.
authors.forename: César G
authors.initials: CG
authors.lastname: Fontecha
authors.affiliation: Fetal and Neonatal Surgery Unit, Pediatric Surgery Service, Hospital Universitario "Vall D'Hebron," Barcelona, Spain.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Peiró
authors.affiliation: Department of Pediatric Surgery, Hospital Universitario "La Paz," Madrid, Spain.
authors.forename: Garriboli M Carmen
authors.initials: GMC
authors.lastname: Soto
authors.affiliation: Instituto de Neurociencias CSIC-UMH, Sant Joan d'Alacant, Alicante, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Borrell
authors.affiliation: Instituto de Neurociencias CSIC-UMH, Sant Joan d'Alacant, Alicante, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Reillo
authors.affiliation: Department of Pediatric Surgery, Hospital Universitario "La Paz," Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: López-Santamaría
authors.affiliation: Department of Pediatric Surgery, Hospital Universitario "La Paz," Madrid, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Tovar
authors.affiliation: Pediatric Surgery Department and Fetal Treatment Laboratory, UCSF, San Francisco, CA.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Farmer
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000196:embryology / Q000601:surgery; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000473:pathology / Q000601:surgery; D008591:Meningomyelocele / Q000196:embryology / Q000601:surgery*; D019635:Neurosurgical Procedures / Q000379:methods*; D011247:Pregnancy; D011270:Pregnancy, Animal; D012756:Sheep / Q000196:embryology