Maldevelopment of the cerebral cortex in the surgically induced model of myelomeningocele: implications for fetal neurosurgery ☆,☆☆ Jose L. Encinas a, ⁎ , Miguel Ángel García-Cabezas b , James Barkovich c , César G. Fontecha d , Jose L. Peiró e , Garriboli M. Carmen Soto a , Victor Borrell f , Isabel Reillo f , Manuel López-Santamaría a , Juan A. Tovar a , Diana L. Farmer g a Department of Pediatric Surgery, Hospital Universitario “La Paz,” Madrid, Spain b Department of Pathology, Hospital Universitario “La Paz,” Madrid, Spain c Section of Neuroradiology, Department of Radiology, UCSF, San Francisco, CA d Pediatric Orthopedic Unit, Department of Orthopedic Surgery, Hospital Universitario “Vall D'Hebron,” Barcelona, Spain e Fetal and Neonatal Surgery Unit, Pediatric Surgery Service, Hospital Universitario “Vall D'Hebron,” Barcelona, Spain f Instituto de Neurociencias CSIC-UMH, Sant Joan d'Alacant, Alicante, Spain g Pediatric Surgery Department and Fetal Treatment Laboratory, UCSF, San Francisco, CA Received 25 July 2010; revised 10 November 2010; accepted 10 November 2010 Key words: Myelomeningocele; Brain; Folding; Sheep; Cortex; Fetal surgery Abstract Purpose: 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 ☆ JLE is a research fellow of Fondo de Investigación Sanitaria (Programa Rio Hortega) Spanish Health Institute Carlos III (grant RD08/0072: Maternal, Child Health, and Development Network). ☆☆ This study was supported by Fondo de Investigación Sanitaria (07/0827) and Fundación Mutua Madrileña 2007 and 2009 to JLE. This study was also funded in part by grants from MICINN (SAF2009-07367) and from The International Human Frontier Science Program Organization (CDA0027/2007) to VB. IR is a recipient of an FPU fellowship from the Spanish Ministry of Science and Innovation (MICINN). ⁎ Corresponding author. Department of Pediatric Surgery, La Paz University Hospital, Paseo de la Castellana 261, 28230, Madrid, Spain. Tel.: +34 917277019. UCSF, Fetal Treatment Laboratory, 531 Parnassus Ave, San Francisco, CA. Tel.: +011415-4760449. E-mail address: encinas.j@tiscali.it (J.L. Encinas). www.elsevier.com/locate/jpedsurg 0022-3468/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2010.11.028 Journal of Pediatric Surgery (2011) 46, 713–722