{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:12:41Z","timestamp":1768263161669,"version":"3.49.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Fluids Barriers CNS"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Fetal spina bifida aperta (SBA) is characterized by a spinal meningomyelocele (MMC) and associated with cerebral pathology, such as hydrocephalus and Chiari II malformation. In various animal models, it has been suggested that a loss of ventricular lining (neuroepithelial\/ependymal denudation) may trigger cerebral pathology. In fetuses with MMC, little is known about neuroepithelial\/ependymal denudation and the initiating pathological events.<\/jats:p>\n            <jats:p>The objective of this study was to investigate whether neuroepithelial\/ependymal denudation occurs in human fetuses and neonates with MMC, and if so, whether it is associated with the onset of hydrocephalus.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Seven fetuses and 1 neonate (16\u201340 week gestational age, GA) with MMC and 6 fetuses with normal cerebral development (22\u201341 week GA) were included in the study. Identification of fetal MMC and clinical surveillance of fetal head circumference and ventricular width was performed by ultrasound (US). After birth, MMC was confirmed by histology. We characterized hydrocephalus by increased head circumference in association with ventriculomegaly. The median time interval between fetal cerebral ultrasound and fixing tissue for histology was four days.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>At 16 weeks GA, we observed neuroepithelial\/ependymal denudation in the aqueduct and telencephalon together with sub-cortical heterotopias in absence of hydrocephalus and\/or Chiari II malformation. At 21\u201334 weeks GA, we observed concurrence of aqueductal neuroepithelial\/ependymal denudation and progenitor cell loss with the Chiari II malformation, whereas hydrocephalus was absent. At 37\u201340 weeks GA, neuroepithelial\/ependymal denudation coincided with Chiari II malformation and hydrocephalus. Sub-arachnoidal fibrosis at the convexity was absent in all fetuses but present in the neonate.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>In fetal SBA, neuroepithelial\/ependymal denudation in the telencephalon and the aqueduct can occur before Chiari II malformation and\/or hydrocephalus. Since denuded areas cannot re-establish cell function, neuro-developmental consequences could induce permanent cerebral pathology.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1743-8454-5-4","type":"journal-article","created":{"date-parts":[[2008,3,4]],"date-time":"2008-03-04T07:13:38Z","timestamp":1204614818000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Pathogenesis of cerebral malformations in human fetuses with meningomyelocele"],"prefix":"10.1186","volume":"5","author":[{"given":"Olga A","family":"de Wit","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilfred FA","family":"den Dunnen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krystyne M","family":"Sollie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa Iris","family":"Mu\u00f1oz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda C","family":"Meiners","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oebele F","family":"Brouwer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esteban M","family":"Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah A","family":"Sival","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2008,3,1]]},"reference":[{"key":"285_CR1","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1227\/00006123-198605000-00008","volume":"18","author":"JN Gilbert","year":"1986","unstructured":"Gilbert JN, Jones KL, Rorke LB, Chernoff GF, James HE: Central nervous system anomalies associated with meningomyelocele, hydrocephalus, and the Arnold-Chiari malformation: reappraisal of theories regarding the pathogenesis of posterior neural tube closure defects. 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