RESUMEN
BACKGROUND: 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.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. METHODS: Seven fetuses and 1 neonate (16-40 week gestational age, GA) with MMC and 6 fetuses with normal cerebral development (22-41 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. RESULTS: 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 21-34 weeks GA, we observed concurrence of aqueductal neuroepithelial/ependymal denudation and progenitor cell loss with the Chiari II malformation, whereas hydrocephalus was absent. At 37-40 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. CONCLUSION: 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.
RESUMEN
OBJECTIVE: In neonates with spina bifida aperta (SBA), leg movements innervated by spinal segments located caudal to the meningomyelocele are transiently present. This study in neonates with SBA aimed to determine whether the presence of leg movements indicates functional integrity of neuronal innervation and whether these leg movements disappear as a result of dysfunction of upper motor neurons (axons originating cranial to the meningomyelocele) and/or of lower motor neurons (located caudal to the meningomyelocele). METHODS: Leg movements were investigated in neonates with SBA at postnatal day 1 (n = 18) and day 7 (n = 10). Upper and lower motor neuron dysfunction was assessed by neurologic examination (n = 18; disinhibition or inhibition of reflexes, respectively) and by electromyography (n = 12; absence or presence of denervation potentials, respectively). RESULTS: Movements, related to spinal segments caudal to the meningomyelocele, were present in all neonates at postnatal day 1. At day 1, leg movements were associated with signs of both upper (10 of 18) and lower (17 of 18) motor neuron dysfunction caudal to the meningomyelocele. In 7 of 10 neonates restudied after the first postnatal week, leg movements had disappeared. The absence of leg movements coincided with loss of relevant reflexes, which had been present at day 1, indicating progression of lower motor neuron dysfunction. CONCLUSIONS: We conclude that the presence of neonatal leg movements does not indicate integrity of functional lower motor neuron innervation by spinal segments caudal to the meningomyelocele. Present observations could explain why fetal surgery at the level of the meningomyelocele does not prevent loss of leg movements.