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Annual Review of Neuroscience 2014Neural tube defects (NTDs), including spina bifida and anencephaly, are severe birth defects of the central nervous system that originate during embryonic development... (Review)
Review
Neural tube defects (NTDs), including spina bifida and anencephaly, are severe birth defects of the central nervous system that originate during embryonic development when the neural tube fails to close completely. Human NTDs are multifactorial, with contributions from both genetic and environmental factors. The genetic basis is not yet well understood, but several nongenetic risk factors have been identified as have possibilities for prevention by maternal folic acid supplementation. Mechanisms underlying neural tube closure and NTDs may be informed by experimental models, which have revealed numerous genes whose abnormal function causes NTDs and have provided details of critical cellular and morphological events whose regulation is essential for closure. Such models also provide an opportunity to investigate potential risk factors and to develop novel preventive therapies.
Topics: Animals; Folic Acid; Genetic Predisposition to Disease; Humans; Neural Tube Defects; Neurulation; Risk Factors
PubMed: 25032496
DOI: 10.1146/annurev-neuro-062012-170354 -
Birth Defects Research Nov 2019Neural tube defects (NTDs) are the second most common congenital malformations in humans affecting the development of the central nervous system. Although NTD... (Review)
Review
Neural tube defects (NTDs) are the second most common congenital malformations in humans affecting the development of the central nervous system. Although NTD pathogenesis has not yet been fully elucidated, many risk factors, both genetic and environmental, have been extensively reported. Classically divided in two main sub-groups (open and closed defects) NTDs present extremely variable prognosis mainly depending on the site of the lesion. Herein, we review the literature on the histological and pathological features, epidemiology, prenatal diagnosis, and prognosis, based on the type of defect, with the aim of providing important information based on NTDs classification for clinicians and scientists.
Topics: Anencephaly; Female; Humans; Neural Tube Defects; Pregnancy; Prenatal Diagnosis; Risk Factors
PubMed: 30421543
DOI: 10.1002/bdr2.1380 -
Cell May 2023Neural tube (NT) defects arise from abnormal neurulation and result in the most common birth defects worldwide. Yet, mechanisms of primate neurulation remain largely...
Neural tube (NT) defects arise from abnormal neurulation and result in the most common birth defects worldwide. Yet, mechanisms of primate neurulation remain largely unknown due to prohibitions on human embryo research and limitations of available model systems. Here, we establish a three-dimensional (3D) prolonged in vitro culture (pIVC) system supporting cynomolgus monkey embryo development from 7 to 25 days post-fertilization. Through single-cell multi-omics analyses, we demonstrate that pIVC embryos form three germ layers, including primordial germ cells, and establish proper DNA methylation and chromatin accessibility through advanced gastrulation stages. In addition, pIVC embryo immunofluorescence confirms neural crest formation, NT closure, and neural progenitor regionalization. Finally, we demonstrate that the transcriptional profiles and morphogenetics of pIVC embryos resemble key features of similarly staged in vivo cynomolgus and human embryos. This work therefore describes a system to study non-human primate embryogenesis through advanced gastrulation and early neurulation.
Topics: Animals; Humans; Blastocyst; Embryo, Mammalian; Embryonic Development; Macaca fascicularis; Neural Tube Defects; Neurulation; Tissue Culture Techniques
PubMed: 37172562
DOI: 10.1016/j.cell.2023.04.019 -
Trends in Neurosciences Jul 2020Neural tube defects (NTDs) represent a failure of the neural plate to complete the developmental transition to a neural tube. NTDs are the most common birth anomaly of... (Review)
Review
Neural tube defects (NTDs) represent a failure of the neural plate to complete the developmental transition to a neural tube. NTDs are the most common birth anomaly of the CNS. Following mandatory folic acid fortification of dietary grains, a dramatic reduction in the incidence of NTDs was observed in areas where the policy was implemented, yet the genetic drivers of NTDs in humans, and the mechanisms by which folic acid prevents disease, remain disputed. Here, we discuss current understanding of human NTD genetics, recent advances regarding potential mechanisms by which folic acid might modify risk through effects on the epigenome and transcriptome, and new approaches to study refined phenotypes for a greater appreciation of the developmental and genetic causes of NTDs.
Topics: Folic Acid; Humans; Neural Tube Defects
PubMed: 32423763
DOI: 10.1016/j.tins.2020.04.009 -
The Lancet. Neurology Aug 2013Neural tube defects are severe congenital malformations affecting around one in every 1000 pregnancies. An innovation in clinical management has come from the finding... (Review)
Review
Neural tube defects are severe congenital malformations affecting around one in every 1000 pregnancies. An innovation in clinical management has come from the finding that closure of open spina bifida lesions in utero can diminish neurological dysfunction in children. Primary prevention with folic acid has been enhanced through introduction of mandatory food fortification in some countries, although not yet in the UK. Genetic predisposition accounts for most of the risk of neural tube defects, and genes that regulate folate one-carbon metabolism and planar cell polarity have been strongly implicated. The sequence of human neural tube closure events remains controversial, but studies of mouse models of neural tube defects show that anencephaly, open spina bifida, and craniorachischisis result from failure of primary neurulation, whereas skin-covered spinal dysraphism results from defective secondary neurulation. Other malformations, such as encephalocele, are likely to be postneurulation disorders.
Topics: Animals; Databases, Factual; Disease Models, Animal; Folic Acid; Genetic Predisposition to Disease; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Mutation; Neural Tube Defects
PubMed: 23790957
DOI: 10.1016/S1474-4422(13)70110-8 -
World Neurosurgery Dec 2016Neurenteric cysts are rare central nervous system lesions derived from an endodermal origin. There is no consensus concerning pathogenesis because of the paucity of...
BACKGROUND
Neurenteric cysts are rare central nervous system lesions derived from an endodermal origin. There is no consensus concerning pathogenesis because of the paucity of occurrences. We report an immunohistochemical study of 10 cases with neurenteric cysts and postulate its pathogenesis.
METHODS
Ten patients underwent surgical treatment for neurenteric cysts from 1995 to 2015. We retrospectively reviewed clinical, radiologic, operative, and pathologic findings for these patients. Immunohistochemical stains were completed in all cases to distinguish cell type and origin.
RESULTS
Three cell types were identified: pseudostratified-ciliated, goblet-columnar, and simple cuboidal cells. All cases were positive for cytokeratin 7, and negative for cytokeratin 20, caudal-type homeobox 2, mucin 2, thyroid transcription factor 1, human chorionic gonadotropin, placental alkaline phosphatase, and cluster of differentiation 31. Four of them had positive staining for mucin 5AC, with expression only in goblet-columnar cells. According to the immunohistochemical results, the cells resembled the respiratory tract (pseudostratified-ciliated), stomach (goblet-columnar), and respiratory bronchioles (simple cuboidal). Seventy-five percent of cases with recurrence had a goblet-columnar component, emphasizing the importance of total resection of the cyst and complete pathologic examination.
CONCLUSIONS
We postulate that the cystic tumor was derived from multipotent endodermal cells that migrated and traveled along the neuroectoderm, with incomplete differentiation into various cell types as a result of an unsuitable microenvironment. Because the neurenteric canal was only the channel of migration rather than a component of the cysts, the term neuroendodermal cysts is more precise in presenting the embryopathogenesis.
Topics: Adult; Aged; Alkaline Phosphatase; CDX2 Transcription Factor; Central Nervous System Diseases; Child; Chorionic Gonadotropin; Cysts; Diagnosis, Differential; Endoderm; Female; GPI-Linked Proteins; Humans; Immunohistochemistry; Infant; Isoenzymes; Keratin-20; Keratin-7; Male; Middle Aged; Mucin 5AC; Mucin-2; Neural Tube Defects; Nuclear Proteins; Platelet Endothelial Cell Adhesion Molecule-1; Recurrence; Retrospective Studies; Thyroid Nuclear Factor 1; Transcription Factors; Young Adult
PubMed: 27586176
DOI: 10.1016/j.wneu.2016.08.089 -
Biomedical Papers of the Medical... Sep 2021Enteric cysts are very rare conditions, occurring mainly in the posterior mediastinum and posterior neck. Their pathomorphology corresponds with that of intraspinal...
INTRODUCTION
Enteric cysts are very rare conditions, occurring mainly in the posterior mediastinum and posterior neck. Their pathomorphology corresponds with that of intraspinal neurenteric cysts. Both formations are derivatives of the posterior foregut. However, their embryopathogenesis has not been elucidated satisfactorily as yet. For those associated with vertebral anomalies, the split notochord theory has been widely accepted. However, this is be hardly conceivable for cases free of these anomalies.
CASE REPORT
Here, a patient with concurrent separated enteric and neurenteric cysts and cervical spine dysmorphism is presented.
DISCUSSION
The review of the relevant literature revealed sporadic analogical cases in which a transvertebral communication between the two cysts was present or absent. The latter was associated with a minimal abnormality of the vertebral body.
CONCLUSION
The authors suggest that normal vertebrae may be formed in patients with enteric cysts, which would make the notochord-split theory plausible also for those free of spinal malformations.
Topics: Cervical Vertebrae; Cysts; Hernia, Diaphragmatic; Humans; Magnetic Resonance Imaging; Neural Tube Defects
PubMed: 32686772
DOI: 10.5507/bp.2020.030 -
World Journal of Gastroenterology Jun 2008Neurenteric cysts are extremely rare congenital anomalies, often presenting in the first 5 years of life, and are caused by an incomplete separation of the notochord...
Neurenteric cysts are extremely rare congenital anomalies, often presenting in the first 5 years of life, and are caused by an incomplete separation of the notochord from the foregut during the third week of embryogenesis. They are frequently accompanied with spinal or gastrointestinal abnormalities, but the latter may be absent in adults. Although usually located in the thorax, neurenteric cysts may be found along the entire spine. We present a 24-year-old woman admitted for epigastric pain, nausea, vomiting, low grade fever and leucocytosis. She underwent cystgastrostomy for a loculated cyst of the distal pancreas at the age of 4 years, which recurred when she was at the age of 11 years. Ultrasound and computer tomograghy (CT) scan revealed a 16 cm multiply 15 cm cystic mass in the body and tail of pancreas, with a 6-7 mm thickened wall. Laboratory data and chest X-ray were normal and spinal radiographs did not show any structural abnormalities. The patient underwent a complete cyst excision, and after an uneventful recovery, remained symptom-free without recurrence during the 5-year follow-up. The cyst was found to contain 1200 mL of pale viscous fluid. It was covered by a primitive single-layered cuboidal epithelium, along with specialized antral glandular parenchyma and hypoplastic primitive gastric mucosa. Focal glandular groups resembling those of the body of the stomach were also seen. In addition, ciliary respiratory epithelium, foci of squamous metaplasia and mucinous glands were present. The wall of the cyst contained a muscular layer, neuroglial tissue with plexogenic nerve fascicles, Paccini corpuscle-like structures, hyperplastic neuroganglionar elements and occasional psammomatous bodies, as well as fibroblast-like areas of surrounding stroma. Cartilagenous tissue was not found in any part of the cyst. Immunohistochemistry confirmed the presence of neurogenic elements marked by S-100, GFAP, NF and NSE. The gastric epithelium showed mostly CK7 and EMA immunoexpression, and the respiratory epithelium revealed a CK8 and CK18 immunoprofile without CK 10/13 positive elements, though neither CEA or AFP positive cells were found. To our knowledge, this is the first reported case of an abdominally located neurenteric cyst with no associated spinal anomalies.
Topics: Abdomen; Adult; Female; Humans; Immunohistochemistry; Neural Tube Defects; Pancreatic Cyst; Recurrence; Tomography, X-Ray Computed
PubMed: 18595146
DOI: 10.3748/wjg.14.3759 -
Spinal Cord Series and Cases Mar 2022Intradural cysts of the spine are arachnoid cysts, neuroenteric cysts, and ependymal cysts. The usual finding in case of a neurenteric cyst is a ventrally located...
BACKGROUND
Intradural cysts of the spine are arachnoid cysts, neuroenteric cysts, and ependymal cysts. The usual finding in case of a neurenteric cyst is a ventrally located non-contrast-enhancing lesion that is isointense on T1-weighted sequence and hyperintense on T2-weighted imaging. An arachnoid cyst is hypointense in T1-weighted image and hyperintense in T2-weighted image, mimicking cerebrospinal fluid(CSF), and the location is dorsal to the cord. But a neurenteric cyst can mimic an arachnoid cyst in appearance.
CASE
A 48-yr old autorikshaw driver presented with weakness of fingers and lower limbs. All sensations were decreased below xiphisternum(T6). The gait was spastic. Magnetic Resonance Imaging(MRI) showed an extramedullary intradural cyst at C7-T1 level. It was hypointense on T1-weighted image and hyperintense on T2-weighted image. There was no enhancement with contrast. C7/T1 Laminectomy was done. On gentle retraction of the cord, a whitish cyst was seen. Some clear fluid was aspirated and cyst was excised en toto. Myelopathy improved over two weeks. Histopathological examination showed a cyst wall composed of fibrocollagenous tissue, and lined by pseudostratified epithelium containing many goblet cells and having focal ciliation. The findings were consistent with neurenteric cyst. Follow-up MRI after five years showed no recurrence.
CONCLUSION
To our knowledge, the peculiarities of the case are that the radiological features mimicked arachnoid cyst in having the intensity of CSF. But the ventral location was suggestive of a neurenteric cyst. Total excision could be done through the posterior approach after decompressing the cyst by aspiration.
Topics: Arachnoid Cysts; Cervical Vertebrae; Humans; Laminectomy; Neural Tube Defects; Spinal Cord Diseases
PubMed: 35288542
DOI: 10.1038/s41394-022-00500-2 -
The Pan African Medical Journal 2017Diastematomyelia is a rare spinal dysraphism in which the spinal cord and its content are split. Two types of diastematomyelia have been described. We report the case of...
Diastematomyelia is a rare spinal dysraphism in which the spinal cord and its content are split. Two types of diastematomyelia have been described. We report the case of a 12 year old male patient presenting with reduced lower limb muscle strength without associated sphincteric disorders. The patient underwent axial, sagittal and coronal T1 and T2-weighted MRI sequence of the spine. MRI showed a bifid appearance of the bone marrow of thoracolumbar vertebrae in two hemi-cords without bone spur separating the two hemi-marrows, compatible with type 1 diastematomyelia. It was associated with low tethered spinal cord with syringomyelic cavity involving the left hemi-marrow and with biloculated fibrotic lesion at the level of the right hemi-marrow compatible with a neuroenteric cyst. MRI also showed incomplete closure of the posterior arch of D12 vertebra which communicated with a subcutaneous pocket in relation to a dermal sinus. Diastematomyelia is a rare abnormality of the spine which can be associated with other malformations. Therapeutic strategy essentially depends on the progression of the clinical signs (neurological) and of associated malformations.
Topics: Child; Humans; Magnetic Resonance Imaging; Male; Neural Tube Defects; Spinal Cord; Spinal Dysraphism
PubMed: 29721147
DOI: 10.11604/pamj.2017.28.317.14500