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Brain : a Journal of Neurology Aug 2023Neural tube defects are the most severe congenital malformations that result from failure of neural tube closure during early embryonic development, and the underlying...
Neural tube defects are the most severe congenital malformations that result from failure of neural tube closure during early embryonic development, and the underlying molecular mechanisms remain elusive. Retinoic acid, an active derivative of vitamin A, is critical for neural system development, and retinoic acid receptor (RAR) signalling malfunctions have been observed in human neural tube defects. However, retinoic acid-retinoic acid receptor signalling regulation and mechanisms in neural tube defects are not fully understood. The mRNA expression of RARs and retinoid X receptors in the different human neural tube defect phenotypes, including 11 pairs of anencephaly foetuses, 10 pairs of hydrocephalus foetuses and nine pairs of encephalocele foetuses, was investigated by NanoString nCounter technology. Immunoprecipitation-mass spectrometry was performed to screen the potential interacting targets of retinoic acid receptor γ. The interactions between proteins were confirmed by co-immunoprecipitation and immunofluorescence laser confocal microscopy. Luciferase and chromatin immunoprecipitation with quantitative real-time polymerase chain reaction assays were used to clarify the underlying mechanism. Moreover, a neural tube defect animal model, constructed using excess retinoic acid, was used for further analysis with established molecular biology technologies. We report that level of retinoic acid receptor γ (RARγ) mRNA was significantly upregulated in the brain tissues of human foetuses with anencephaly. To further understand the actions of retinoic acid receptor γ in neural tube defects, methylenetetrahydrofolate dehydrogenase 1 was identified as a specific retinoic acid receptor γ target from IP-MS screening. Additionally, methylenetetrahydrofolate dehydrogenase 1 negatively regulated retinoic acid receptor γ transcription factor activity. Furthermore, low expression of methylenetetrahydrofolate dehydrogenase 1 and activation of retinoic acid receptor signalling were further determined in human anencephaly and a retinoic acid-induced neural tube defect mouse model. This study reveals that methylenetetrahydrofolate dehydrogenase 1, the rate-determining enzyme in the one-carbon cycle, might be a specific regulator of retinoic acid receptors; these findings provide new insights into the functional linkage between nuclear folate metabolism and retinoic acid receptor signalling in neural tube defect pathology.
Topics: Mice; Pregnancy; Animals; Female; Humans; Anencephaly; Methylenetetrahydrofolate Dehydrogenase (NADP); Receptors, Retinoic Acid; Tretinoin; Neural Tube Defects; RNA, Messenger; Minor Histocompatibility Antigens
PubMed: 36928982
DOI: 10.1093/brain/awad084 -
Ecotoxicology and Environmental Safety Apr 2023Metallic elements play a pivotal role in maternal and fetal health. Metals can cross the placental barrier and be absorbed by fetuses, where they may affect closure of... (Review)
Review
Metallic elements play a pivotal role in maternal and fetal health. Metals can cross the placental barrier and be absorbed by fetuses, where they may affect closure of the neural tube during embryonic development. Neural tube defects (NTDs), which result from aberrant closure of the neural tube three to four weeks post-conception, have a multifactorial and complex etiology that combines genetic variants and environmental exposure. Recent advances in population-level association studies have investigated the link between maternal environmental exposure and NTDs, particularly the influence of metals on the incidence of NTDs. Herein, we present a broad and qualitative review of current literature on the association between maternal and prenatal metal exposure via the maternal peripheral blood, amniotic fluid, placenta, umbilical cord, and maternal hair, and the risk of developing NTDs. Specifically, we identify the various aggravating or attenuating effects of metallic exposure on the risk of NTD formation. This review provides novel insights into the association between environmental metals and NTDs and has important applications for NTD prevention and mitigating environmental exposure to metals.
Topics: Humans; Female; Pregnancy; Prenatal Exposure Delayed Effects; Placenta; Neural Tube Defects; Neural Tube; Fetus
PubMed: 36948008
DOI: 10.1016/j.ecoenv.2023.114815 -
The Science of the Total Environment Feb 2024Exposure to pesticides during pregnancy has been associated with several serious congenital malformations, such as neural tube defects, therefore, is a cause for concern... (Review)
Review
Exposure to pesticides during pregnancy has been associated with several serious congenital malformations, such as neural tube defects, therefore, is a cause for concern in terms of human health. This review aims to gather information related to maternal exposure during pregnancy and the risk of triggering neural tube defects in the offspring. The search strategy for the studies followed the PRISMA guidelines. We conducted a systematic search in the Science Direct, PubMed, Cochrane Library, Embase, Scopus, and Web of Science databases for all epidemiological studies that sought to associate exposure to pesticides during embryonic development with the risk of neural tube defects (NTDs). The keywords used were "pesticide", "herbicide", "congenital" and "neural". Of the 229 articles, 8 eligible ones (7 case-control and 1 cross-sectional) evaluated pesticide exposure in pregnancy. Different methods were used, including analysis of biological samples and questionnaires. The pesticides studied included insecticides, herbicides, fungicides, and nematicides. Insecticides were the most studied, with variations in concentrations between tissues and studies. Distinct levels of pesticides have been detected in maternal serum, placenta, and umbilical cord. Models were statistically adjusted for confounding factors, such as smoking and dietary supplement intakes. Concentrations were measured in different exposure windows (periconception and prenatal), related to NTDs such as anencephaly and spina bifida. Different data collection techniques, types of biological samples, and exposure windows were used, which made comparison difficult. The main pesticides studied included DDT, DDE, HCH, and endosulfan. Maternal serum showed the highest concentrations of pesticides, but detection in placental tissue and umbilical cord confirms embryonic exposure. Confounding variables were adjusted for in the analysis of the articles, but they may still contribute to the risk of NTDs. All the studies analyzed pesticide exposure and the relationship with NTDs. However, a more standardized survey would be ideal for better comparisons.
Topics: Female; Humans; Pregnancy; Pesticides; Insecticides; Cross-Sectional Studies; Placenta; Neural Tube Defects; Herbicides; Risk Factors
PubMed: 38104833
DOI: 10.1016/j.scitotenv.2023.169317 -
Journal of Medicine and Life 2021Spina bifida is a disorder characterized by failure of the neural tube to form during embryological development. The early signs in the head and spine may be detected on...
Spina bifida is a disorder characterized by failure of the neural tube to form during embryological development. The early signs in the head and spine may be detected on ultrasound from 11 weeks of gestation. Diabetes is a well-known teratogen factor that increases the chances of birth defects, such as neural tube defects. We report a 12 weeks case of spina bifida in type 1 diabetes.
Topics: Diabetes Mellitus; Female; Humans; Neural Tube Defects; Pregnancy; Spinal Dysraphism; Ultrasonography
PubMed: 35126760
DOI: 10.25122/jml-2021-0249 -
Journal of Neurosurgery. Pediatrics Jul 2023The two main objectives of this study were to explore the rate of spinal dysraphism within bladder and cloacal exstrophy and to analyze the relationship between spinal...
OBJECTIVE
The two main objectives of this study were to explore the rate of spinal dysraphism within bladder and cloacal exstrophy and to analyze the relationship between spinal dysraphism surgery, including timing of spinal dysraphism surgery, with urological and neurological outcomes.
METHODS
A prospectively maintained IRB-approved database of pediatric exstrophy patients treated from 1982 to 2021 was retrospectively reviewed for patients with spinal dysraphism. Spinal dysraphism was categorized into the following 7 subtypes: lipoma-based closed defect, myelomeningocele, meningocele, diastematomyelia, myelocystocele, low-lying conus with tethered cord/fatty filum, and sacral bony defect. Other factors assessed included patient demographic characteristics, type of spinal dysraphism procedure, reoperation, complication, presence of other neurological problems (e.g., hydrocephalus, Chiari malformation), neurological status, and urological function.
RESULTS
Analysis revealed that 114/1401 patients had coexisting spinal dysraphism. Of these 114, sufficient records including type of dysraphism were available for 54. Spinal dysraphism was most common within cloacal exstrophy (83.3% [45/54 patients]), followed by cloacal exstrophy variants (9.3% [5/54]), classic bladder exstrophy (3.7% [2/54]), and classic bladder exstrophy variants (3.7% [2/54]). Within spinal dysraphism, lipoma-based closed defects (63.0% [34/54]) and low-lying conus with tethered cord/fatty filum (11.1% [6/54]) were most common. Hydrocephalus and Chiari malformation occurred in 24.1% (13/54) and 11.1% (6/54) of patients. All 13 patients with hydrocephalus underwent shunt placement. Among those who underwent neurosurgical intervention, the complication rate for spinal dysraphism was 14.6% (7/48). Motor function data were available for 41 patients and revealed that motor function declined for 2/41 (4.8%) patients and improved for 6/41 (14.6%) after neurosurgery. There was no statistical difference in lower-extremity motor outcome related to timing of neurosurgery and exstrophy closure.
CONCLUSIONS
The authors have reported the surgical management and outcomes of patients with exstrophy and coexisting spinal dysraphism (n = 54). In 54 patients, spinal dysraphism was most common in the subset of patients with cloacal exstrophy (83.3%). Lipoma-based closed defects (63.0%) and low-lying conus with tethered cord/fatty filum (11.1%) were the most common, and the rates of hydrocephalus and Chiari malformation were 24.1% and 11.1%, respectively. There was no difference in lower-extremity motor outcome related to timing of neurosurgery and exstrophy closure.
Topics: Humans; Child; Bladder Exstrophy; Retrospective Studies; Spinal Dysraphism; Neural Tube Defects; Meningomyelocele; Arnold-Chiari Malformation; Hydrocephalus; Digestive System Abnormalities; Lipoma
PubMed: 37119103
DOI: 10.3171/2023.3.PEDS22447 -
Child's Nervous System : ChNS :... Nov 2017The management of concomitant scoliosis and tethered cord syndrome in the non-spina bifida pediatric population is challenging. In the present study, we evaluate the... (Review)
Review
BACKGROUND
The management of concomitant scoliosis and tethered cord syndrome in the non-spina bifida pediatric population is challenging. In the present study, we evaluate the efficacy of different treatment modalities and propose a treatment plan for the management of affected patients.
METHODS
A systematic literature review was conducted by querying the MEDLINE, PubMed, Cochrane, EMBASE, Scopus, and Web of Science databases for papers published between January 1996 and June 2016 and reporting on concomitant scoliosis and tethered cord. We excluded animal studies, non-English papers as well as papers reporting on patients with multiple concomitant intraspinal anomalies such as spina bifida.
RESULTS
Out of 1993 articles, only 13 met our inclusion criteria. These 13 articles described six main management approaches: Observation, cord untethering only, cord untethering followed by deformity correction, simultaneous cord untethering and deformity correction, and deformity correction without untethering. Selection of the best approach is a function of the patient's symptomatology and Cobb angle.
CONCLUSION
We propose treatment plan for the management of patients with concomitant tethered cord syndrome and spinal deformity. Asymptomatic patients can be followed conservatively and managed as scoliosis patients with no need for untethering. Surgical management in a staged fashion seems appropriate in symptomatic patients with a Cobb angle less than 35°. In these patients, deformity can improve following untethering, thus sparing the patient the risks of surgical correction of scoliosis. Staged or non-staged cord untethering and curve correction seem to be adequate in symptomatic patients with Cobb angle >35° as these patients are likely to require both untethering and deformity correction.
Topics: Child; Female; Humans; Male; Neural Tube Defects; Scoliosis
PubMed: 28695338
DOI: 10.1007/s00381-017-3504-0 -
Clinical Genetics Apr 2022Neural tube defects (NTDs) are the most severe birth defects and the main cause of newborn death; posing a great challenge to the affected children, families, and... (Review)
Review
Neural tube defects (NTDs) are the most severe birth defects and the main cause of newborn death; posing a great challenge to the affected children, families, and societies. Presently, the clinical diagnosis of NTDs mainly relies on ultrasound images combined with certain indices, such as alpha-fetoprotein levels in the maternal serum and amniotic fluid. Recently, the discovery of additional biomarkers in maternal tissue has presented new possibilities for prenatal diagnosis. Over the past 20 years, "omics" techniques have provided the premise for the study of biomarkers. This review summarizes recent advances in candidate biomarkers for the prenatal diagnosis of fetal NTDs based on omics techniques using maternal biological specimens of different origins, including amniotic fluid, blood, and urine, which may provide a foundation for the early prenatal diagnosis of NTDs.
Topics: Amniotic Fluid; Biomarkers; Child; Female; Humans; Infant, Newborn; Neural Tube Defects; Pregnancy; Prenatal Diagnosis
PubMed: 34761376
DOI: 10.1111/cge.14087 -
Spinal Cord Sep 2014To evaluate computed tomography (CT) and magnetic resonance imaging (MRI) features in patients with diastematomyelia and to investigate clinical characteristics of this...
OBJECTIVE
To evaluate computed tomography (CT) and magnetic resonance imaging (MRI) features in patients with diastematomyelia and to investigate clinical characteristics of this lesion.
STUDY DESIGN
A retrospectively study.
SETTING
The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University.
METHODS
A total of 82 diastematomyelia cases were retrospectively studied. All the patients underwent neurological examinations as well as MRI and CT of the spine. A self-established neurological functional grading system was used, and posterior tibial nerve somatosensory cortical-evoked potential (PTNSCEP) was measured to assess the neurological status of the patients. Imaging features of symmetry of splitting, presence of septum, location of lesion and number of split segments were studied. The neurological functional grading, PTNSCEP, and imaging findings were then analyzed and compared, and the difference was considered to be significant if P-value was lower than 0.05.
RESULTS
Neurological functional grading and latency of PTNSCEP were significantly different but related in terms of symmetry of splitting, presence of septum and location of lesion. Although no significant differences were present in the number of split segments, the severity of the neurological functional grading and PTNSCEP impairment were not related to the number of split segments.
CONCLUSION
The imaging features in diastematomyelia are characteristic and relate well with the clinical manifestations according to neurological functional grading and PTNSCEP measurement, except the number of split segments.
Topics: Adolescent; Adult; Child; Child, Preschool; Disability Evaluation; Evoked Potentials, Somatosensory; Humans; Magnetic Resonance Imaging; Middle Aged; Neural Tube Defects; Retrospective Studies; Severity of Illness Index; Tomography, X-Ray Computed
PubMed: 24796446
DOI: 10.1038/sc.2014.68 -
Spine Apr 2016Tethered cord syndrome (TCS) occurs as a constellation of neurologic signs and symptoms resulting from longitudinal traction on the spinal cord between fixed points....
Tethered cord syndrome (TCS) occurs as a constellation of neurologic signs and symptoms resulting from longitudinal traction on the spinal cord between fixed points. This condition involves a tug-of-war between ascent and inhibition of ascent of intrathecal nervous tissue within the vertebral canal during growth. Causes include thickened filum terminale, myelomeningocele, split cord malformation, and previous intradural surgery. Patients report low back, lower extremity, and perineal pain; lower extremity sensory and motor deficits; urinary and bowel incontinence; and sexual dysfunction. When not treated early or adequately, TCS can lead to neurologic devastation.
Topics: Humans; Neural Tube Defects; Osteotomy; Spinal Cord; Spinal Cord Injuries
PubMed: 27015066
DOI: 10.1097/BRS.0000000000001433 -
Journal of Clinical Neuroscience :... Jun 2017The filum terminale has oven been overlooked in the literature probably due to its small size and historical lack of research on its true morphology. However, this... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The filum terminale has oven been overlooked in the literature probably due to its small size and historical lack of research on its true morphology. However, this structure's roll in the tethered cord syndrome has become more apparent. Therefore, the current comprehensive review seemed timely.
METHODS
Using standard search engines, the history, embryology, anatomy, pathology and surgery of the filum terminale were reviewed.
CONCLUSIONS
It is only recently that the true anatomy and pathological involvement of the filum terminale in the tethered cord syndrome have been elucidated.
Topics: Cauda Equina; Humans; Neural Tube Defects; Peripheral Nervous System Diseases
PubMed: 28087185
DOI: 10.1016/j.jocn.2016.12.020