Jose L Encinas1, Miguel Ángel García-Cabezas2, James Barkovich3, César G Fontecha4, Jose L Peiró5, Garriboli M Carmen Soto6, Victor Borrell7, Isabel Reillo7, Manuel López-Santamaría6, Juan A Tovar6, Diana L Farmer8. 1. Department of Pediatric Surgery, Hospital Universitario "La Paz," Madrid, Spain. Electronic address: encinas.j@tiscali.it. 2. Department of Pathology, Hospital Universitario "La Paz," Madrid, Spain. 3. Section of Neuroradiology, Department of Radiology, UCSF, San Francisco, CA. 4. Pediatric Orthopedic Unit, Department of Orthopedic Surgery, Hospital Universitario "Vall D'Hebron," Barcelona, Spain. 5. Fetal and Neonatal Surgery Unit, Pediatric Surgery Service, Hospital Universitario "Vall D'Hebron," Barcelona, Spain. 6. Department of Pediatric Surgery, Hospital Universitario "La Paz," Madrid, Spain. 7. Instituto de Neurociencias CSIC-UMH, Sant Joan d'Alacant, Alicante, Spain. 8. Pediatric Surgery Department and Fetal Treatment Laboratory, UCSF, San Francisco, CA.
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 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.
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 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.
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