-
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 -
Annual Review of Nutrition Aug 2022For three decades, the US Public Health Service has recommended that all persons capable of becoming pregnant consume 400 μg/day of folic acid (FA) to prevent neural... (Review)
Review
For three decades, the US Public Health Service has recommended that all persons capable of becoming pregnant consume 400 μg/day of folic acid (FA) to prevent neural tube defects (NTDs). The neural tube forms by 28 days after conception. Fortification can be an effective NTD prevention strategy in populations with limited access to folic acid foods and/or supplements. This review describes the status of mandatory FA fortification among countries that fortify ( = 71) and the research describing the impact of those programs on NTD rates (up to 78% reduction), blood folate concentrations [red blood cell folate concentrations increased ∼1.47-fold (95% CI, 1.27, 1.70) following fortification], and other health outcomes. Across settings, high-quality studies such as those with randomized exposures (e.g., randomized controlled trials, Mendelian randomization studies) are needed to elucidate interactions of FA with vitamin B as well as expanded biomarker testing.
Topics: Dietary Supplements; Female; Folic Acid; Food, Fortified; Humans; Neural Tube Defects; Pregnancy; Vitamin B 12
PubMed: 35995050
DOI: 10.1146/annurev-nutr-043020-091647 -
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 -
Nature Nov 2021Understanding human organ formation is a scientific challenge with far-reaching medical implications. Three-dimensional stem-cell cultures have provided insights into...
Understanding human organ formation is a scientific challenge with far-reaching medical implications. Three-dimensional stem-cell cultures have provided insights into human cell differentiation. However, current approaches use scaffold-free stem-cell aggregates, which develop non-reproducible tissue shapes and variable cell-fate patterns. This limits their capacity to recapitulate organ formation. Here we present a chip-based culture system that enables self-organization of micropatterned stem cells into precise three-dimensional cell-fate patterns and organ shapes. We use this system to recreate neural tube folding from human stem cells in a dish. Upon neural induction, neural ectoderm folds into a millimetre-long neural tube covered with non-neural ectoderm. Folding occurs at 90% fidelity, and anatomically resembles the developing human neural tube. We find that neural and non-neural ectoderm are necessary and sufficient for folding morphogenesis. We identify two mechanisms drive folding: (1) apical contraction of neural ectoderm, and (2) basal adhesion mediated via extracellular matrix synthesis by non-neural ectoderm. Targeting these two mechanisms using drugs leads to morphological defects similar to neural tube defects. Finally, we show that neural tissue width determines neural tube shape, suggesting that morphology along the anterior-posterior axis depends on neural ectoderm geometry in addition to molecular gradients. Our approach provides a new route to the study of human organ morphogenesis in health and disease.
Topics: Ectoderm; Humans; Models, Biological; Morphogenesis; Neural Plate; Neural Tube; Neural Tube Defects; Organ Culture Techniques; Regeneration; Stem Cells
PubMed: 34707290
DOI: 10.1038/s41586-021-04026-9 -
The Pan African Medical Journal 2023
Topics: Humans; Neural Tube Defects
PubMed: 37013212
DOI: 10.11604/pamj.2023.44.24.35962 -
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 -
Saudi Medical Journal Dec 2014
Topics: Humans; Neural Tube Defects
PubMed: 25551105
DOI: No ID Found -
Journal of Pediatric Rehabilitation... 2020While the neuropsychological profile for individuals with Spina Bifida (SB) can vary, often certain patterns of strengths and weaknesses are evident across the lifespan.... (Review)
Review
While the neuropsychological profile for individuals with Spina Bifida (SB) can vary, often certain patterns of strengths and weaknesses are evident across the lifespan. Understanding variability related to neural structure, genetics, ethnicity, and the environment is key to understanding individual differences in outcomes and can be vital in planning interventions and tracking progress. This article outlines the SB Guideline for the Neuropsychological Care of People with Spina Bifida from the 2018 Spina Bifida Association's Fourth Edition of the Guidelines for the Care of People with Spina Bifida and acknowledges that further research in SB neurocognitive profiles is warranted.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Nervous System Diseases; Practice Guidelines as Topic; Spinal Dysraphism; Young Adult
PubMed: 33285647
DOI: 10.3233/PRM-200761 -
PloS One 2016Folate-sensitive neural tube defects (NTDs) are an important, preventable cause of morbidity and mortality worldwide. There is a need to describe the current global... (Review)
Review
BACKGROUND
Folate-sensitive neural tube defects (NTDs) are an important, preventable cause of morbidity and mortality worldwide. There is a need to describe the current global burden of NTDs and identify gaps in available NTD data.
METHODS AND FINDINGS
We conducted a systematic review and searched multiple databases for NTD prevalence estimates and abstracted data from peer-reviewed literature, birth defects surveillance registries, and reports published between January 1990 and July 2014 that had greater than 5,000 births and were not solely based on mortality data. We classified countries according to World Health Organization (WHO) regions and World Bank income classifications. The initial search yielded 11,614 results; after systematic review we identified 160 full text manuscripts and reports that met the inclusion criteria. Data came from 75 countries. Coverage by WHO region varied in completeness (i.e., % of countries reporting) as follows: African (17%), Eastern Mediterranean (57%), European (49%), Americas (43%), South-East Asian (36%), and Western Pacific (33%). The reported NTD prevalence ranges and medians for each region were: African (5.2-75.4; 11.7 per 10,000 births), Eastern Mediterranean (2.1-124.1; 21.9 per 10,000 births), European (1.3-35.9; 9.0 per 10,000 births), Americas (3.3-27.9; 11.5 per 10,000 births), South-East Asian (1.9-66.2; 15.8 per 10,000 births), and Western Pacific (0.3-199.4; 6.9 per 10,000 births). The presence of a registry or surveillance system for NTDs increased with country income level: low income (0%), lower-middle income (25%), upper-middle income (70%), and high income (91%).
CONCLUSIONS
Many WHO member states (120/194) did not have any data on NTD prevalence. Where data are collected, prevalence estimates vary widely. These findings highlight the need for greater NTD surveillance efforts, especially in lower-income countries. NTDs are an important public health problem that can be prevented with folic acid supplementation and fortification of staple foods.
Topics: Global Health; Humans; Neural Tube Defects; Prevalence
PubMed: 27064786
DOI: 10.1371/journal.pone.0151586