-
Current Research in Translational... Nov 2020Myelomeningocele (MMC) is a spinal cord congenital defect that leads to paraplegia, bladder incontinence and bowel dysfunction. A randomized human trial demonstrated...
Myelomeningocele (MMC) is a spinal cord congenital defect that leads to paraplegia, bladder incontinence and bowel dysfunction. A randomized human trial demonstrated that in utero surgical repair of the MMC defect improves lower limb motor function. However, functional recovery remains incomplete. Stem cell therapy has recently generated great interest in the field of prenatal repair of MMC. In this systematic review we attempt to provide an overview of the current application of stem cells in different animal models of MMC. Publications were retrieved from PubMed and Cochrane Library databases. This process yielded twenty-two studies for inclusion in this review, experimenting five different types of stem cells: human embryonic stem cells, neural stem cells, induced pluripotent stem cells, human amniotic fluid stem cells, and mesenchymal stem cells (MSCs). Rodents and ovine were the two major species used for animal model studies. The source, the aims, and the main results were analyzed. Stem cell therapy appears to be a promising candidate for prenatal repair of MMC, especially MSCs. Further explorations in ovine and rodent models, reporting clinical and functional results, are necessary before an application in humans.
Topics: Amniotic Fluid; Animals; Cell- and Tissue-Based Therapy; Humans; Meningomyelocele; Mesenchymal Stem Cells; Sheep; Spinal Cord; Stem Cell Transplantation
PubMed: 32624428
DOI: 10.1016/j.retram.2020.04.004 -
Journal of Human Genetics Jul 2024Spondylocostal dysostosis (SCDO) encompasses a group of skeletal disorders characterized by multiple segmentation defects in the vertebrae and ribs. SCDO has a complex...
Spondylocostal dysostosis (SCDO) encompasses a group of skeletal disorders characterized by multiple segmentation defects in the vertebrae and ribs. SCDO has a complex genetic etiology. This study aimed to analyze and identify pathogenic variants in a fetus with SCDO. Copy number variant sequencing and whole exome sequencing were performed on a Chinese fetus with SCDO, followed by bioinformatics analyses, in vitro functional assays and a systematic review on the reported SCDO cases with LFNG pathogenic variants. Ultrasound examinations in utero exhibited that the fetus had vertebral malformation, scoliosis and tethered cord, but rib malformation was not evident. We found a novel homozygous variant (c.1078 C > T, p.R360C) within the last exon of LFNG. The variant was predicted to cause loss of function of LFNG by in silico prediction tools, which was confirmed by an in vitro assay of LFNG enzyme activity. The systematic review listed a total of 20 variants of LFNG in SCDO. The mutational spectrum spans across all exons of LFNG except the last one. This study reported the first Chinese case of LFNG-related SCDO, revealing the prenatal phenotypes and expanding the mutational spectrum of the disorder.
Topics: Humans; Female; Exome Sequencing; Fetus; Pregnancy; Abnormalities, Multiple; Mutation; Meningomyelocele; DNA Copy Number Variations; Asian People; East Asian People; Hernia, Diaphragmatic
PubMed: 38565611
DOI: 10.1038/s10038-024-01248-3 -
The Journal of Maternal-fetal &... May 2020To summarize current evidence on the use of tocolytic medications perioperatively for open prenatal repair of fetal myelomeningocele including tocolytic agent options,...
To summarize current evidence on the use of tocolytic medications perioperatively for open prenatal repair of fetal myelomeningocele including tocolytic agent options, regimens, efficiency, and potential risks. A search of Medline, Embase, and SCOPUS databases was conducted from inception to March 2017. Studies that described their tocolytic protocol, gestational age at delivery, perinatal outcomes were included. Studies that did not exclusively assessed fetal myelomeningocele or did not adequately endorse obstetric and neonatal outcomes were excluded. Neither sample size nor language was a basis for exclusion. Out of 570 studies retrieved on initial search, 462 were excluded for irrelevance. Of the 61 remaining titles, 17 were animal studies, 17 were reviews, 12 studied a spectrum of anomalies, three specified fetoscopy, four did not report neonatal outcomes, and one article was retracted. Two studies were added to the pool when the literature search was updated. Nine articles were eventually included; three case reports, six cohort studies with a total of 205 cases. Fetuses were managed at gestational ages between 19 and 30 weeks. Although tocolytic regimens were variable, indomethacin was commonly utilized as a preoperative tocolytic. Magnesium sulfate was usually initiated intraoperatively and was resumed postoperatively for a variable duration (18-48 hours) with or without subcutaneous terbutaline. Gestational age at delivery ranged from 30-37 weeks with an average of 33-35 weeks. Pulmonary edema was reported in two studies to be 2.2-5.5%. Perinatal outcomes were overall favorable. Preoperative indomethacin and postoperative course of magnesium sulfate seem to be a favorable tocolytic option in women with open prenatal myelomeningocele repair. Risks are generally minimal. However, adequate information on the duration of postoperative tocolysis seems to be inadequate.
Topics: Female; Fetoscopy; Gestational Age; Humans; Indomethacin; Meningomyelocele; Obstetric Labor, Premature; Pregnancy; Tocolytic Agents
PubMed: 30526147
DOI: 10.1080/14767058.2018.1528222 -
Disability and Health Journal Apr 2020We combined literature review and consensus-building methodologies to develop health care guidelines for people with Spina Bifida across the life span.
BACKGROUND
We combined literature review and consensus-building methodologies to develop health care guidelines for people with Spina Bifida across the life span.
OBJECTIVE
The present paper describes the methodology used to update and expand this fourth edition of the Guidelines for the Care of People with Spina Bifida ("Guidelines"). This process was a fundamental initiative within the Spina Bifida Collaborative Care Network.
METHODS
Working groups were formed consisting of international, multidisciplinary teams of clinical and research experts. A systematic review of multiple databases was conducted. The consensus building methodology, One-Text Procedure, was followed to draft and revise documents. Each section of the Guidelines was presented by working group chairs at a face-to-face meeting using the Nominal Group Technique (NGT).
RESULTS
The Level 1 review resulted in 2449 abstracts being reviewed, and the Level 2 review resulted in 874 full text articles being archived for working groups. After working groups added and eliminated articles, a total of 803 manuscripts were included in the bibliography of the Guidelines. The final version of the Guidelines was then released in 2018.
CONCLUSIONS
Evidenced based-research and consensus methodologies were used to develop the fourth edition of the Guidelines. It is hoped that this document will guide not only health care providers, but also patients and families, so that people with Spina Bifida can have the best and most scientifically-based care and treatments throughout ever-longer and higher-quality lives.
Topics: Consensus; Delivery of Health Care; Disabled Persons; Evidence-Based Medicine; Female; Health Services for Persons with Disabilities; Humans; Practice Guidelines as Topic; Quality of Life; Spinal Dysraphism; Systematic Reviews as Topic
PubMed: 31248776
DOI: 10.1016/j.dhjo.2019.06.005 -
BJOG : An International Journal of... Jan 2021Abnormal intracranial findings are often detected at mid-trimester ultrasound (US) in fetuses with myelomeningocele (MMC). It is unclear whether these findings...
BACKGROUND
Abnormal intracranial findings are often detected at mid-trimester ultrasound (US) in fetuses with myelomeningocele (MMC). It is unclear whether these findings constitute a spectrum of the disease or are an independent finding, which should contraindicate fetal surgery.
OBJECTIVE
To ascertain the spectrum and frequency of US-detected cranial findings in fetuses with MMC.
SEARCH STRATEGY
MEDLINE, Embase, Web of Science and CENTRAL were searched from January 2000 to June 2020.
SELECTION CRITERIA
Study reporting incidence of cranial US findings in consecutive cases of second-trimester fetuses with MMC.
DATA COLLECTION AND ANALYSIS
Publication quality was assessed by Newcastle-Ottawa Scale (NOS) and modified NOS. Meta-analysis could not be performed as a result of high clinical diversity and study heterogeneity.
MAIN RESULTS
Fourteen cranial US findings were reported in 15 studies. Findings in classic Chiari II malformation (CIIM) spectrum included posterior fossa funnelling (96%), small transcerebellar diameter (82-96%), 'banana' sign (50-100%), beaked tectum (65%) and 'lemon' sign (53-100%). Additional cranial findings were small biparietal diameter (BPD) and head circumference (HC) (<5th centile; 53 and 71%, respectively), ventriculomegaly (45-89%), abnormal pointed shape of the occipital horn (77-78%), thinning of the posterior cerebrum, perinodular heterotopia (11%), abnormal gyration (3%), corpus callosum disorders (60%) and midline interhemispheric cyst (42%).
CONCLUSIONS
We identified 14 cranial findings by second-trimester US in fetuses with MMC. The relatively high incidence of these findings and their unclear prognostic significance might not contraindicate fetal surgery in the case of normal fetal genetic testing. Some cranial findings may independently affect postnatal outcome, however. Long-term detailed follow-up is required to investigate this.
TWEETABLE ABSTRACT
A high rate of cranial abnormalities found on second-trimester ultrasound in fetuses with myelomeningocele.
Topics: Female; Fetal Diseases; Humans; Meningomyelocele; Pregnancy; Pregnancy Trimester, Second; Skull; Ultrasonography, Prenatal
PubMed: 32926566
DOI: 10.1111/1471-0528.16496