Congenital and Hereditary Diseases of the Spinal Cord.

Congenital anomalies of the spinal cord can pose a diagnostic dilemma to the radiologist. Several classification systems of these anomalies exist. Antenatal ultrasound and fetal magnetic resonance imaging is playing an increasingly important role in the early diagnosis and management of patients. Understanding the underlying anatomy as well as embryology of these disorders can be valuable in correctly identifying the type of spinal cord dysraphic defect. Hereditary spinal cord diseases are rare but can be devastating. When the onset is in adulthood, delay in diagnosis is common. Although the spine findings are nonspecific, some imaging features combined with brain imaging findings can be distinctive. Sometimes, the radiologist may be the first to raise the possibility of these disorders.

Efectos del tratamiento con vitamina E en el tubo neural y médula espinal en embriones y fetos de ratones Mus musculus expuestos al uso de ácido valproico / Effects of treatment with vitamin E in the neural tube and spinal cord Mus musculus mouse embryos exposed to the use of valproic acid

El ácido valproico (VPA) es el principal anticonvulsivante utilizado contra la epilepsia durante la gestación. Sin embargo, en etapas iniciales del embarazo actúa como teratógeno y ocasiona malformaciones como fisura labio-palatina, alteraciones en el desarrollo genital y espina bífida, siendo esta última la más frecuente. Esto se produce debido al aumento de especies reactivas de oxígeno, pudiendo contrarrestarse administrando vitamina E. El objetivo fue determinar si la vitamina E disminuye el daño en tubo neural y médula espinal de embriones y fetos de ratonas expuestas a VPA. Se conformaron 8 grupos de animales. A los 8 días post-fecundación se les administró a los grupos 1 y 5 suero fisiológico 0,3 mL; grupos 2 y 6 VPA 600 mg/Kg; grupos 3 y 7 VPA 600 mg/Kg y vitamina E 200 UI/Kg; grupos 4 y 8 vitamina E 200 UI/kg. A los 12 días post-fecundación, se sacrificaron los grupos 1, 2, 3 y 4, y a los 17 días los restantes grupos. Los embriones fueron procesados y teñidos con cresil violeta, observándose cortes histológicos a nivel cervical, torácico y lumbar. Los grupos tratados con vitamina E presentaron menor cantidad de neuroblastos y motoneuronas, pero de tamaño mayor en comparación al grupo tratado con VPA (p<0,05), siendo similares a los grupos controles. Al comparar el tubo neural y médula espinal en los distintos niveles (cervical, torácico y lumbar), no hubo diferencias estadísticamente significativas. La administración prenatal de vitamina E disminuye los defectos en tubo neural y médula espinal de embriones de 12 y 17 días de gestación sometidos a VPA.

Valproic Acid (VPA) is the main anticonvulsant used for epilepsy throughout the gestation period. However, when used at early stages of pregnancy, it acts as a tetarogenic agent, causing congenital malformations such as cleft-lip and/or cleft palate, abnormal genital development and spina bifida, being the latter the most frequent. This is the result of the increase of reactive oxygen species, which can be countered with the supplementation of vitamin E. The aim was determine if vitamin E minimizes the damage to the neural tube and spinal cord of mice embryos and fetuses previously exposed to VPA. Eight groups of mice were constituted. Eight days post fertilization, groups 1 and 5 were administered 0,3 ml of saline solution; groups 2 and 6 600mg/Kg of VPA, groups 3 and 7 600mg/Kg of VPA and 200UI/Kg of Vitamin E; groups 4 and 8 200 UI/Kg of Vitamin E. 12 days after fertilization, groups 1, 2, 3 and 4 were euthanized, whereas in the case of the remaining groups, the same process was performed 17 days after fertilization. The embryos were stained with cresyl violet, thus enabling the observation of histological sections at cervical, thoracic and lumbar levels. Groups supplied with vitamin E presented a lower amount of neuroblasts and motoneurons. However, these elements were bigger in size compared to the group treated with VPA (p<0,05), being these results similar to those obtained with the control groups. When comparing the neural tube and spinal cord at different levels (cervical, thoracic and lumbar), no statistically significant differences were found. It was determined that prenatal administration of vitamin E lessens the damage to the neural tube and spinal cord of mice embryos of 12 and 17 days of gestation previously exposed to VPA.

Peripheral nervous system defects in a mouse model for peroxisomal biogenesis disorders.

Peroxisome biogenesis disorders (PBD) are autosomal recessive disorders in humans characterized by skeletal, eye and brain abnormalities. Despite the fact that neurological deficits, including peripheral nervous system (PNS) defects, can be observed at birth in some PBD patients including those with PEX10 mutations, the embryological basis of the PNS defects is unclear. Using a forward genetic screen, we identified a mouse model for Pex10 deficiency that exhibits neurological abnormalities during fetal development. Homozygous Pex10 mutant mouse embryos display biochemical abnormalities related to a PBD deficiency. During late embryogenesis, Pex10 homozygous mutant mice experience progressive loss of movement and at birth they become cyanotic and die shortly thereafter. Homozygous Pex10 mutant fetuses display decreased integrity of axons and synapses, over-extension of axons in the diaphragm and decreased Schwann cell numbers. Our neuropathological, molecular and electrophysiological studies provide new insights into the embryological basis of the PNS deficits in a PBD model. Our findings identify PEX10 function, and likely other PEX proteins, as an essential component of the spinal locomotor circuit.

Intradural neurenteric cyst--two case reports of surgical treatment.

Intradural neurenteric cysts are rare congenital lesions and arise from incomplete separation of the developing notochord and foregut in the embryo. Neurenteric cysts are often seen in conjunction with other forms of occult spinal dysraphism. The cases of a 48-year-old male with pain in the right shoulder and numbness in both hands and a 7-year-old girl with subacute muscle weakness of the lower extremities are presented. Both patients underwent surgery. One lesion was completely excised, while the other could be only partially removed because of negative monitoring potential during the operation. Histological examination, showing pseudostratified ciliated columnar epithelium, confirmed the diagnosis of neurenteric cyst. The symptoms in both patients nearly disappeared after surgery. Recurrence of cyst was observed in the girl, though without neurological symptoms. In conclusion, two cases of intradural extramedullary cysts are reported. Clinical presentations, intraoperative findings, and histological features are discussed with a review of the literature.

Prenatal diagnosis of mediastinal neurentric cyst with an intraspinal component.

Mediastinal neurenteric cysts are the least common types of the bronchopulmonary foregut malformations, and their antenatal diagnosis is rare. We report a case of mediastinal neurenteric cyst diagnosed on antenatal ultrasonography at 28 weeks' gestation. A small intraspinal component and vertebral segmentation anomalies were also noted. The diagnosis was confirmed on postnatal magnetic resonance imaging and at the time of operation.

Supratentorial neurenteric cysts-A fascinating entity of uncertain embryopathogenesis.

The histopathological, immunologic, and ultrastructural findings of neurenteric cysts support an endodermal derivation. These developmental cystic lesions are generally located in the posterior mediastinum, abdomen, and pelvis and may also contain some mesodermal and neuroectodermal elements. In contrast, neurenteric cysts of the central nervous system are very infrequent and occur most commonly in the spinal canal. Intraspinal neurenteric cysts are usually encountered in the cervicothoracic region with an intradural, extramedullary location and are commonly associated with congenital defects of the overlying skin and/or vertebral bodies. Intracranial neurenteric cysts are very uncommon and typically located in the posterior fossa. Several hypotheses have been postulated to explain the origin of intracranial neurenteric cysts. However, the embryologic basis of these fascinating lesions remains incompletely understood. Supratentorial neurenteric cysts are distinctly rare often represent a diagnostic challenge on preoperative neuroimaging. In fact, only 22 cases of supratentorial neurenteric cysts have been reported in the literature including our own patient with a laterally based convexity extraaxial cyst presenting with seizures. In this report, we review the clinical, radiographic, and histological findings of supratentorial neurenteric cysts. We discuss the differential diagnoses and surgical considerations in the management of these intriguing lesions. We also provide an extensive review of normal human embryogenesis and discuss putative mechanisms of embryopathogenesis of supratentorial neurenteric cysts.

The effects of amniotic fluid on the histopathologic changes of exposed spinal cord in fetal sheep.

BACKGROUND: Experimental studies have shown that in myelomeningocele, the primary malformation is neural tissue damage resulting from exposure of neural tissue to amniotic fluid. In this study, the effects of amniotic fluid on histopathologic changes of exposed spinal cord in fetal sheep were evaluated. METHODS: In an experimental trial, 10 fetal sheep in two groups containing five subjects (group A) and five shams (group B) were studied. In the sheep at 90 - 100 days of gestation (term: 145 - 150 days) the lumbar skin was incised, paraspinal soft tissues were excised, laminectomy was performed at L2 - L4, and dura matter was opened. In group A, the dura matter was not dorsally closed and thus the spinal cord was left exposed to amniotic fluid, and in group B the skin was immediately closed. The lambs were delivered near term by cesarean section and were assessed clinically and morphologically. RESULTS: In group A, all lambs (n=5) had a complete or incomplete flaccid sensorimotor paraplegia and suffered from urine incontinence. Four lambs in this group were stool incontinent. In group B (n=4), only one lamb had paraparesis (P=0.048) and all lambs were urine and stool continent. In group A, all lambs had hypoplastic longitudinal muscles of the rectum but well- developed circular muscles. The anal sphincter muscles did not develop normally. In group B, all lambs had well-developed longitudinal and circular muscles and anal sphincter muscles developed normally (P=0.048). Histopathologic examination of the spinal cords showed edema, focal calcification, fibrosis, and capillary cell proliferation in group A, but in group B such changes were not seen. The number of ganglion cells was significantly higher in group B compared with group A (P<0.0005). CONCLUSION: Exposure of spinal cord to amniotic fluid causes structural neural tissue damage that can be prevented by fetal surgery through repairs of myelomeningocele.

Tethering of the spinal cord in mouse fetuses and neonates with spina bifida.

OBJECT: Tethering of the spinal cord is a well-known complication in humans with spina bifida aperta or occulta. Its pathogenesis consists of a pathological fixation of the spinal cord resulting in traction on the neural tissue which, in turn, leads to ischemia and progressive neurological deterioration. Although well established in humans, this phenomenon has not been described in animal models of spina bifida. METHODS: A fetal mouse model with naturally occurring, genetically determined spina bifida was produced by generating double mutants between the curly tail and loop-tail mutant strains. Microdissection, labeling with 1,1'-dioctadecyl-3,3,3,',3'-tetramethylindocarbocyanine perchlorate, immunohistochemistry for neurofilaments, H & E staining of histological sections, and whole-mount skeletal preparations were performed and comparisons made among mutant and normal fetuses. Normal fetuses exhibited the onset of progressive physiological ascent of the spinal cord from embryonic Day 15.5. Spinal cord ascent resulted, by embryonic Day 18.5, in spinal nerve roots that pass caudolaterally from the spinal cord toward the periphery. In contrast, fetuses with spina bifida exhibited spinal cord tethering that resulted, at embryonic Day 18.5, in nerve roots that run in a craniolateral direction from the spinal cord. The region of closed spinal cord immediately cranial to the spina bifida lesion exhibited marked narrowing, late in gestation, suggesting that a potentially damaging stretch force is applied to the spinal cord by the tethered spina bifida lesion. CONCLUSIONS: This mouse model provides an opportunity to study the onset and early sequelae of spinal cord tethering in spina bifida.

Neuro-osteology.

Neuro-osteology stresses the biological connection during development between nerve and hard tissues. It is a perspective that has developed since associations were first described between pre-natal peripheral nerve tissue and initial osseous bone formation in the craniofacial skeleton (Kjaer, 1990a). In this review, the normal connection between the central nervous system and the axial skeleton and between the peripheral nervous system and jaw formation are first discussed. The early central nervous system (the neural tube) and the axial skeleton from the lumbosacral region to the sella turcica forms a unit, since both types of tissue are developmentally dependent upon the notochord. In different neurological disorders, the axial skeleton, including the pituitary gland, is malformed in different ways along the original course of the notochord. Anterior to the pituitary gland/sella turcica region, the craniofacial skeleton develops from prechordal cartilage, invading mesoderm and neural crest cells. Also, abnormal development in the craniofacial region, such as tooth agenesis, is analyzed neuro-osteologically. Results from pre-natal investigations provide information on the post-natal diagnosis of children with congenital developmental disorders in the central nervous system. Examples of these are myelomeningocele and holoprosencephaly. Three steps are important in clinical neuro-osteology: (1) clinical definition of the region of an osseous or dental malformation, (2) embryological determination of the origin of that region and recollection of which neurological structure has developed from the same region, and (3) clinical diagnosis of this neurological structure. If neurological malformation is the first symptom, step 2 results in the determination of the osseous region involved, which in step 3 is analyzed clinically. The relevance of future neuro-osteological diagnostics is emphasized.

[A case of cervical intramedullary neurenteric cyst].

A case of cervical intramedullary neurenteric cyst was reported. A 12-year-old girl was admitted with severe pain over the nape and shoulders, and weakness of all extremities. At the age of 4 years, she had suffered from the nape pain and paraparesis which, however, cleared later spontaneously. Neurological examination revealed evidences of presumptive cervical intramedullary lesion, and myelography showed a complete block at the third cervical level accordingly. Surgical exploration through C3-C5 laminectomy disclosed an intramedullary cyst situated within the right half of the cord. The cyst was removed except for its upper and lower apices. Excellent clinical results followed the operation. The cyst was composed of collagen fibers with an inner epithelial lining, which consisted of single or pseudostratified layer of columnar, cuboidal or squamous cells. Cells were ciliated at some parts. The base of the epithelial cells rested upon the basement membrane. Nuclei were positioned near the base of the cells, to present a row. The cytoplasm in the majority of cells contained abundant mucin positive to PAS staining. Pathological diagnosis of neurenteric cyst was made on the basis of these histological findings. Usually intraspinal neurenteric cyst is located in the subarachnoid space and ventrally to the spinal cord. Neurenteric cyst appears histologically similar to ependymal cyst, though, in the latter the epithelial cells seldom contain mucin, and only in scanty amount, if any present. Embryogenesis during the third week of embryonic life was discussed in relation to the development of neurenteric cyst.

Comparative prenatal development of the spinal cord in normal and dysraphic dogs: embryonic stage.

The prenatal development of the canine spinal cord was examined by light microscopy in 8 normal embryos and compared with the development of the spinal cord in 10 embryos obtained by mating severely dysraphic Weimaraner dogs. Dysraphic lesions were found in 80% of the embryos examined from dysraphic matings. The primary lesion was aberrantly positioned mantle cells ventrad to the central canal in the floor plate area. In 30% of the embryos of this group, there was a division of the terminal neural tube. The dysraphic embryos had significantly shorter gray matter and spinal cord transverse diameters. This confirmed the observation that the mantle cells in the dysraphic specimens were less differentiated, being more compact and appearing more basophilic when hematoxylin and eosin stains were used.