Materiały źródłowe

• #1 Spina Bifida: A Review of the Genetics, Pathophysiology and Emerging Cellular Therapies

  https://www.mdpi.com/2221-3759/10/2/22

  Spina bifida (SB) is the most common congenital defect of the central nervous system. […] An intricate relationship between environmental, genetic, and maternal factors has been implicated in the etiology and pathogenesis of this congenital malformation. […] There exist two proposed mechanisms for NTDs. First, the neural tube fails to close due to abnormalities in cellular behavior (inefficient proliferation, disorganized cellular death, and poor collective cell movement). Second, the closed neural tube reopens, possibly due to a breakdown in critical cell–cell adhesion junctions. […] Aberrations in neural tube closure during primary neurulation can lead to a host of NTDs, including SB. […] The primary injury in SB is due to the disorder in primary neurulation. […] The „two-hit” hypothesis of injury for the destruction and damage to the spinal cord as the prevailing theory on how the exposed cord eventually succumbs to neurological disability.

• #2 Etiology and Pathophysiology of the Spina Bifida

  https://openresearchlibrary.org/chapter/a045c8c2-5333-45e5-b3a4-1e63caffab2e

  Genetic, nutritional and environmental factors play a role in the etiology and pathogenesis of the spina bifida. […] The spina bifida is a congenital anomaly that results in an abnormal formation of the spine and the spinal cord.

• #3 Spina Bifida – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559265/

  Spina bifida is a congenital condition resulting from the incomplete closure of the neural tube during fetal development, leading to varying degrees of spinal cord and nerve damage. […] The process of neuralization occurs in 2 phases: primary and secondary neuralization. Primary neuralization refers to the closure of the neural tube, forming the brain and spinal cord. Secondary neuralization involves the formation of the caudal structures of the neural tube, which form the sacral and coccygeal portions. These caudal structures develop around day 26 of gestation, and failure to close results in varying degrees of spinal dysraphisms. […] Defects in neural tube development are thought to be multifactorial, including environmental and genetic influences. The most common environmental cause is folate deficiency, with most cases deemed folic acid-sensitive.

• #4 Spina Bifida: Pathogenesis, Mechanisms, and Genes in Mice and Humans

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5327787/

  The process of neurulation in mammals and some other vertebrates is considered discontinuous because it occurs simultaneously at multiple sites along the neuraxis. There are three points of de novo neural tube fusion in the mouse, which is the most studied mammalian model. Closure 1 occurs adjacent to somite 3 in embryos with 6-7 somites and progresses rostrally and caudally, closure 2 occurs at the midbrain-forebrain boundary at around the 10-somite stage and progresses caudally, and closure 3 occurs at the rostral end of the forebrain, soon after closure 2. […] Failure of closure 1 leads to craniorachischisis; failure of closures 2 and/or 3 causes exencephaly and/or anencephaly, respectively, while failure of neurulation to progress from the site of closure 1 caudally along the spinal axis leads to spina bifida aperta.

• #5 Spina Bifida: A Review of the Genetics, Pathophysiology and Emerging Cellular Therapies

  https://www.mdpi.com/2221-3759/10/2/22

  Spina bifida (SB) is the most common congenital defect of the central nervous system. […] An intricate relationship between environmental, genetic, and maternal factors has been implicated in the etiology and pathogenesis of this congenital malformation. […] There exist two proposed mechanisms for NTDs. First, the neural tube fails to close due to abnormalities in cellular behavior (inefficient proliferation, disorganized cellular death, and poor collective cell movement). Second, the closed neural tube reopens, possibly due to a breakdown in critical cell–cell adhesion junctions. […] Aberrations in neural tube closure during primary neurulation can lead to a host of NTDs, including SB. […] The primary injury in SB is due to the disorder in primary neurulation. […] The „two-hit” hypothesis of injury for the destruction and damage to the spinal cord as the prevailing theory on how the exposed cord eventually succumbs to neurological disability.

• #6 Contemporary Urological Management of Spina Bifida – The Journal of Pediatric Research

  https://jpedres.org/articles/contemporary-urological-management-of-spina-bifida/doi/jpr.33154

  Spina bifida is a neural tube defect causing the exposure of spinal cord starting from antenatal period. This exposure ends up with the spinal cord injury both antenatally and postnatally. […] Spinal cord injury is the primary cause of neuropathic dysfunction in spina bifida. In the antenatal period, according to the two hit hypothesis, the first hit comes from the defective vertebral development whereas the second hit comes either from the irritative effect of amniotic fluid or mechanical trauma directly to the spinal cord related with fetal movements. […] Neuropathic bladder dysfunction is the main urological problem in spina bifida. Normal urinary function is defined as safe and continent storage and complete voluntary emptying. Thus, voiding cycle is divided into storage and emptying phases. Both of these phases are controlled by the nervous system.

• #7 Validation of the Fetal Lamb Model of Spina Bifida | Scientific Reports

  https://www.nature.com/articles/s41598-019-45819-3

  Spina bifida is the most frequent congenital anomaly of the central nervous system accounting for 4.9/10,000 live births in Europe and 3.17/10,000 in the United States. The pathogenesis of this condition is explained by two consecutive hits. This malformation arises when the neural tube fails to close by the 6th week of gestation. This exposes the neural elements continuously to direct trauma and neurotoxic agents in the amniotic fluid during gestation, leading to progressive changes. Over the lesion there is leakage of cerebrospinal fluid (CSF), leading to a suction gradient, in turn causing hindbrain herniation and smaller posterior fossa and cerebellum (both referred to as Chiari II malformation) and/or ventriculomegaly. This progressive prenatal deterioration paved the way for fetal surgery. We show that the myelotomy model best phenocopies the anatomy, etiopathophysiology and symptomatology of non-cystic SB. This encompasses hindbrain herniation, ventriculomegaly, posterior fossa anomalies, loss of brain neurons; lumbar CSF leakage, hindlimb somatosensory-motor deficit with absence of motor and somatosensory evoked potentials due to loss of spinal cord neurons, astroglial cells and myelin; urinary incontinence. In conclusion, surgical induction of SBA including myelotomy resulted in a complete and homogeneous phenotype of a non-cystic lumbar L1L6 SBA. […] The non-myelotomy model does not mimic a SBA but a heterogeneous in utero lumbar spinal cord injury.

• #8 (PDF) Spina Bifida: Pathogenesis, Mechanisms, and Genes in Mice and Humans

  https://www.academia.edu/34444772/Spina_Bifida_Pathogenesis_Mechanisms_and_Genes_in_Mice_and_Humans

  Spina bida is among the phenotypes of the larger condition known as neural tube defects (NTDs). […] Our understanding of spina bida is currently limited to the observations we make in mouse models, which reect complete or targeted knockouts of genes, which perturb the whole gene(s) without taking into account the issue of haploinsuciency, which is most prominent in the human spina bida condition. […] The mouse is a powerful tool to study spina bi da because it is a mammal like humans and its embryology is similar to humans and therefore it is an indispensable tool to mechanistically study the structural changes involved in spinal neural tube closure. […] The pathogenesis of this condition is explained by two consecutive hits. This malformation arises when the neural tube fails to close by the 6th week of gestation.

• #9 Spina Bifida: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/311113-overview

  During prenatal development, neuroectoderm thickens into the neural plate, which then folds into a neural groove by the time somites appear. The groove deepens to become the neural tube, and dorsal fusion begins centrally, extending cephalad and caudally, with the cephalad pole fusing at the 25th day. […] Some studies suggest that an increased amount of neural crest material in the defect prevents neural tube closure. Another hypothesis is that an already closed tube ruptures; increased permeability of the rhombic groove leads to greater CSF secretion and increased luminal pressure, with the tube then expanding and essentially splitting the neural element at its weakest areas (ie, the cephalic and caudal ends). […] Research by McLone and Knepper supports the latter hypothesis and details the implications of this defect on the entire CNS.

• #10 Spina Bifida General Principles | The Bone School

  http://www.boneschool.com/paediatrics/spine/spinal-dysraphism/spina-bifida-general-principles

  Early problem 26th gestational day (24-28) […] Two theories […] A. Failure of neural tube to close […] B. Initially closed tube which reopens due increased intraluminal pressure […] The latter theory is favoured explains other defects such as diastematomyelia etc.

• #11 Spina Bifida: Pathogenesis, Mechanisms, and Genes in Mice and Humans

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5327787/

  Spina bifida aperta (SBA), sometimes referred to as spina bifida cystica, is usually visible at birth as an exposed neural tissue with or without a protruding sac at the site of the lesion. SBA may be referred to as either myeloschisis or myelomeningocele. Myelomeningocele is when the spinal cord protrudes from the spinal canal into a fluid-filled sac resulting from incomplete closure of the primary neural tube. Myeloschisis is when the incomplete closure of the primary neural plate results in a cleft spinal cord with the edges flush with the defect. The extent and severity of the neurological deficits depend on the location of the lesion along the neuraxis. […] Myelomeningocele (MMC) is usually associated with a type II Chiari hindbrain malformation, ventriculomegaly, and hydrocephalus. Chiari type II malformation is the downward displacement of the cerebellar vermis into the cervical vertebral canal. It is often symptomatic and is diagnosed prenatally with ultrafast fetal magnetic resonance imaging (MRI). This malformation causes elongation of the brain stem and obliteration of the fourth ventricle, leading to obstruction of cerebrospinal fluid circulation and development of hydrocephalus in 90% of patients.

• #12 Spina Bifida: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/311113-overview

  Neural tube defects are the result of a teratogenic process that causes failed closure and abnormal differentiation of the embryonic neural tube. Neural tube defects occur between the 17th and 30th day of gestation, at a time when the mother may not be aware that she is pregnant and the fetus is estimated to be about the size of a grain of rice. […] Myelomeningocele results from failed closure of the caudal end of the neural tube, resulting in an open lesion or sac that contains dysplastic spinal cord, nerve roots, meninges, vertebral bodies, and skin. The anatomic level of the myelomeningocele sac roughly correlates with the patient’s neurologic, motor, and sensory deficits. […] Myelomeningocele is associated with abnormal development of the cranial neural tube, which results in several characteristic CNS anomalies. The Chiari type II malformation is characterized by cerebellar hypoplasia and varying degrees of caudal displacement of the lower brainstem into the upper cervical canal through the foramen magnum. This deformity impedes the flow and absorption of cerebrospinal fluid (CSF) and causes hydrocephalus, which occurs in more than 90% of infants with myelomeningocele.

• #13 Hydrocephalus in spina bifida

  http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S0256-95742014000400032

  Hydrocephalus is one of the most common complications of spinal dysraphism. […] The underlying developmental abnormalities and the exact pathogenesis of hydrocephalus remain subject to debate. Children with this condition nearly always have a Chiari II malformation, which is characterised by an abnormal posterior fossa and herniation of the cerebellar vermis across the foramen magnum. […] The exact causal relationship between the Chiari II malformation and hydrocephalus has only recently begun to be well understood. […] Recent data show a decrease in the rate of Chiari II malformation and subsequent hydrocephalus in patients in whom the spinal defect is repaired in utero. […] The open system of cerebrospinal fluid (CSF) circulation resulting from open spinal dysraphism (with fluid production in the ventricular system and passage down and out through the spinal defect) is thought to play a central role in hindbrain descent and subsequent hydrocephalus. […] Several mechanisms for the development of hydrocephalus have been proposed, but in reality some of these probably co-exist in different patients.

• #14 Spina Bifida – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559265/

  The genomic landscape pertaining to spina bifida is diverse (omnigenic model). Some genetic factors have also been correlated with poor neuralization, including several chromosomal syndromes and genetic polymorphism. Research has implicated polymorphism of the gene encoding the MTHFR enzyme, which is involved in folate metabolism, as a likely genetic risk factor.

• #15 Oral clefts may stem from a shared genetic cause as neural tube defects – Children’s National

  https://innovationdistrict.childrensnational.org/oral-clefts-may-stem-from-a-shared-genetic-cause-as-neural-tube-defects/

  Research by an international team that includes Childrens National faculty, published online Jan. 25, 2019 in Human Molecular Genetics, suggests that genetic mutations that cause cleft lip and palate also may contribute to neural tube defects, such as spina bifida. […] According to the National Institutes of Health, spina bifida, which affects the spinal cord, is the most common neural tube defect in the U.S., affecting up to 2,000 infants each year. […] There is strong evidence that genetic factors are a leading cause of such structural birth defects, but in most cases, the cause is unknown. Our teams study is the first published research to demonstrate that DNA variants in the gene IRF6 can cause spina bifida, Schutte says. […] Whats more, the research team identified a mechanism to explain how altering IRF6 leads to neural tube defects. This mechanism links IRF6 function to two other genes known as transcription Factor AP2A (TFAP2A) and Grainyhead Like 3 (GRHL3) that are also known to be required for the development of the neural tube, lip and palate.

• #16 Oral clefts may stem from a shared genetic cause as neural tube defects – Children’s National

  https://innovationdistrict.childrensnational.org/oral-clefts-may-stem-from-a-shared-genetic-cause-as-neural-tube-defects/

  The team found that Tfap2a, Irf6 and Grhl3 are components of a gene regulatory network required for neurulation, a folding process that results in the neural tube bending and then fusing to become the basis of the embryos nervous system, from brain to spinal cord. […] Interferon Regulatory Factor 6 functions best when there is neither too much expression nor too little. Overexpression of Irf6 suppresses Transcription Factor Activation Protein 2A and Grainyhead Like 3, causing exencephaly, a neural tube defect characterized by the brain being located outside of the skull. Counterintuitively, experimental models that had too little Irf6 also ended up with reduced levels of Tfap2a and Grhl3 that led to a structural birth defect, but at the opposite end of the neural tube. […] To test whether the experimental model findings held true in humans, they sequenced samples from people who had spina bifida and anencephaly the rare birth defect that Kousa spotted in the experimental models and found IRF6 function was conserved in people. […] If we can identify the genetic pathway, we might also be able to modify it to prevent a birth defect.

• #17 Spina bifida – Wikipedia

  https://en.wikipedia.org/wiki/Spina_bifida

  Spina bifida is believed to be due to a combination of genetic and environmental factors. […] Research has shown the lack of folic acid (folate) is a contributing factor in the pathogenesis of neural tube defects, including spina bifida. […] Spina bifida occurs when local regions of the neural tube fail to fuse or there is failure in formation of the vertebral neural arches. […] Maternal diabetes, anti-seizure medication use, obesity are known risk factors for the development of spina bifida. […] Extensive evidence from mouse strains with spina bifida indicates that there is sometimes a genetic basis for the condition. […] It is unknown how or why folic acid has this effect.

• #18 (PDF) Spina Bifida: Pathogenesis, Mechanisms, and Genes in Mice and Humans

  https://www.academia.edu/34444772/Spina_Bifida_Pathogenesis_Mechanisms_and_Genes_in_Mice_and_Humans

  To better understand the pathogenesis of this abnormality, we conducted a microarray study using Mouse Whole Genome Bioarrays which have $36,000 gene targets, to compare gene expression profiles between two mouse models; CXL-Splotch and FKBP8 Gt(neo) which express a similar spina bifida phenotype. […] These results indicate that there are multiple pathways and gene networks perturbed in mouse embryos with shared phenotypes.

• #19 Spina Bifida | Lurie Children’s

  https://www.luriechildrens.org/en/specialties-conditions/spina-bifida/

  Open spina bifida, or myelomeningocele, is a birth defect that occurs when the bones in a babys spinal column do not properly close. […] The exact cause of spina bifida is unknown, but many environmental and genetic factors are thought to play a role. […] Although the precise mechanism of action is unknown, folate has been shown to decrease the incidence of open spina bifida in several population studies. […] During in utero development, open spina bifida allows escape of spinal fluid where the spinal cord is exposed. […] This egress of spinal fluid may lead to abnormalities in the development of the brain and spinal cord, known as the Chiari II malformation. […] A pediatric neurosurgeon will monitor the infant with open spina bifida for progressive enlargement of the ventricles, or hydrocephalus.

• #20 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Spina-Bifida-Pathophysiology.aspx

  Spina bifida is characterized by an opening of the spine, which originates from the formation of the neural tube in the first month of development of the embryo. […] The period of time directly after the closure, from the 26th to the 30th day, is the crucial moment for the formation of the neural tube and disruptions in the process can cause defects such as spina bifida. […] Therefore, genetic susceptibility is thought to play a role in the pathophysiology of spina bifida but environmental factors are also important. […] Although the mechanism of action remains unknown, there is considerable research to support folic acid supplementation for the prevention of spina bifida.

• #21 Spina Bifida: Pathogenesis, Mechanisms, and Genes in Mice and Humans

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5327787/

  Spina bifida occulta (SBO) is the second major form of NTDs, where the site of the lesion is not left exposed. Spina bifida occulta encompasses lipomyelomeningocele, lipomeningocele, and spinal dorsal dermal sinus tract ranging phenotypically from dysplastic skin, tuft of hair, and vestigial tail as well as other forms of spinal dysraphism, which lack a pathogenic representation when the vertebrae develop abnormally leading to absence of the neural arches. In symptomatic cases, tethering of the spinal cord within the vertebral canal can result in pain, weakness, and incontinence in otherwise normal, healthy children or adults. […] The etiology of spina bifida is heterogeneous. Most nonsyndromic spina bifida is thought to be of multifactorial origin with influence of both genetic and environmental factors. Among the environmental factors associated with increased risk of spina bifida are increased pregnancy weight, maternal smoking, drug intake specifically of antiepileptic drugs, and maternal illnesses such as diabetes and hyperthermia.

• #22 Spina bifida – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/spina-bifida/symptoms-causes/syc-20377860

  Spina bifida is more common among Hispanic people and white people. Also, female babies are affected more often than male babies. […] Too little folate in the pregnant person’s body. Folate, the natural form of vitamin B-9, is important to the development of a healthy baby. Folic acid is the synthetic form that’s found in supplements and fortified foods. If folate levels are too low, it’s known as a deficiency. Folate deficiency increases the risk of spina bifida and other conditions that affect the neural tube. […] Having diabetes that is not well controlled before becoming pregnant increases the risk of having a baby with spina bifida. […] Obesity at the time of pregnancy also is associated with an increased risk of spina bifida. […] Some evidence suggests that increased body temperature in the early weeks of pregnancy may increase the risk of spina bifida. A high core body temperature can be caused by a fever or by using a sauna or hot tub.

• #23 Identification of MicroRNA Profiles in Fetal Spina Bifida: The Role in Pathomechanism and Diagnostic Significance

  https://www.mdpi.com/1422-0067/25/5/2896

  Distinct miRNA expression patterns may reflect anomalies related to fetal congenital malformations such as spinal bifida (SB). […] The pathogenesis of SB is still unknown. […] Our results highlight the SB-specific miRNA signature and the differentially expressed miRNAs that may be involved in SB pathogenesis. […] Our study revealed the dysregulation of several miRNAs in amniotic fluid from fetuses with SB. […] Based on the role of miRNAs, it can be concluded that miRNA dysregulation results from the SB pathomechanism, rather than the dysregulated miRNAs actively participating in SB development. […] Our results suggest the involvement of miRISC in modulating repressive activity in SB; however, the detailed impact of miRISC in SB pathogenesis is yet to be determined. […] The potentially disturbed function of genes indicated by DE miRNAs suggests involvement in the processes of neurogenesis, responses to oxidative stress, lipid metabolism, and the transport and distribution of folic acid, which confirms the complex pathogenesis of developmental defects in SB.

• #24

  https://neuroscirn.org/ojs/index.php/nrnotes/article/view/132

  The occurrence of neuroinflammation after the failure of neural tube closure, resulting in spina bifida aperta, is well established but whether or not neuroinflammation contributes to damage to the neuroepithelium prior to and during closure is not known. […] Evidence suggests that early neuroinflammation is detrimental, whereas the later chronic phase of neuroinflammation may have useful roles. […] The role of neuroinflammation in neural tube defects is complex. […] The current understanding remains that the chronic damage to the developing spinal cord is likely due to the chemical and mechanical damage of the exposed neural tissue owing to the aggressive intrauterine environment, described as the two-hit mechanism. […] Astrogliosis in the exposed spinal cord has been described in animal models of spina bifida after the failure of closure during embryonic life.

• #25 Etiology and Pathophysiology of the Spina Bifida | IntechOpen

  https://www.intechopen.com/chapters/76268

  The devastating role of secondary insult to the exposed nervous tissue underlines the presence of dorsal and ventral parts of the spinal cord with developed nerve roots and ganglia, what is evidence of preexisting appropriate early embryogenic development. […] The spina bifida is associated with another brain malformations and development of the hydrocephalus. […] Insufficient distribution of the embryonic ventricular system can be considered to be the cause of Chiari II malformation in children with myelomeningocele. […] The reduction in cerebellar volume in children with meningomyelocele represents a reconfiguration involving anterior lobe enlargement and posterior lobe reduction. […] The spina bifida involves congenital problems that result in abnormal bone formation in the spine and spinal cord. Closed spinal dysraphism is the mildest form of the neural tube defects which involves a hidden vertebral defect and minimal neural involvement. Open spinal dysraphism refers to a defect in which neural tissues communicate with the external environment such as meningocele and myelomeningocele. The incidence of neural tube defects has different rates among different ethnicity, geography, gender, and also countries. Various nutritional, maternal and environmental factors play a role in the etiology and pathogenesis of the spina bifida. However, the impact of these factors is ambiguous and further research is needed in this area.

• #26 Spina Bifida: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/311113-overview

  The neurologic damage generally results in a neurogenic bowel and bladder, which leads to incontinence. With a lack of neural input, a contracted bladder causes hydronephrosis, along with infections and renal failure, which may be the prime determinant of longevity in patients with spina bifida. […] Normal intelligence can be expected with aggressive shunting for hydrocephalus, although seizure activity secondary to the neural tube defect may be noted. In addition, subtle defects in coordination may be associated with the cerebellar deficiency from the Arnold-Chiari malformation, which is a malformation of the cerebellum, with elongation of the cerebellar tonsils and with the cerebellum drawn into the fourth ventricle. […] Myelomeningocele often occurs along with multiple system congenital anomalies. Commonly associated anomalies are facial clefts, heart malformations, and genitourinary tract anomalies. Urinary tract anomalies, such as solitary kidney or malformed ureters, may contribute to increased morbidity in the presence of neurogenic bladder dysfunction.

• #27 Open spina bifida: In utero treatment and delivery considerations – UpToDate

  https://www.uptodate.com/contents/open-spina-bifida-in-utero-treatment-and-delivery-considerations

  Open spina bifida is the focus of this topic. The spinal defect results from incomplete closure of the caudal portion of the neural tube between 22 and 28 embryological days (ie, five to six weeks of gestation). […] The defect usually involves the lumbar or sacral spine and can vary considerably in size. Postnatal clinical manifestations correlate with the spinal level and size of the defect, and usually include lower limb paralysis and bowel and bladder dysfunction. Open spina bifida is usually associated with a Chiari II malformation (Arnold-Chiari malformation), which includes a constellation of CNS anomalies such as hindbrain herniation, brainstem abnormalities, low-lying venous sinuses, a small posterior fossa, and some degree of hydrocephalus. […] The Chiari II malformation has deleterious effects on motor, cranial nerve, and cognitive functions.

• #28 Spina Bifida | Lurie Children’s

  https://www.luriechildrens.org/en/specialties-conditions/spina-bifida/

  Prenatal closure of the open myelomeningocele has been shown to decrease the need for permanent CSF diversion at 12 months in a fetus with ventricles less than 15 mm as well as improved lower extremity strength when assessed at 30 months. […] Prenatal surgery, however, carries significant risks for the mother and unborn child and must be carefully considered for each pregnancy.

• #29 Spina Bifida (Myelomeningocele) | Texas Children’s

  https://www.texaschildrens.org/health/spina-bifida

  Spina bifida is a birth defect that occurs when the spine doesn’t close properly during fetal development. It is a type of neural tube defect (NTD), abnormalities that affect the brain, spinal cord, or spine of a developing fetus. […] The exact cause of neural tube defects remains unknown. They occur during the first month of pregnancy. […] Suspected risk factors include genetic issues, insufficient folic acid and other nutritional deficiencies in the mother, and environmental factors. […] To improve outcomes at birth, a landmark study was conducted on the fetal repair of myelomeningocele. This clinical trial, known as the Management of Myelomeningocele Study (MOMS), showed that surgery performed on the fetus to repair the defect leads to decreased rates of hydrocephalus, reducing or preventing the need for a shunt, and improved leg function compared to standard after-birth repair.

• #30 Spina bifida causes, symptoms and treatment | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/spina-bifida

  Spina bifida occurs in 1 per 2,000 live births in the United States and is the most common central nervous system birth defect. […] The most common and serious form of spina bifida is called myelomeningocele (myelomeningocele) (MMC), in which part of the spinal cord and surrounding nerves push through the open bones (vertebrae) in the spine and protrude from the fetus back. […] Continuous bathing of the fragile developing spinal cord in amniotic fluid over the course of gestation is thought to result in progressive neurologic injury. […] Myelomeningocele has genetic and micronutrient causes. […] Because spinal cord damage is progressive during gestation, prenatal repair of myelomeningocele may prevent further damage. […] Experts at Childrens Hospital of Philadelphia (CHOP) co-led the landmark Management of Myelomeningocele Study (MOMS), which compared outcomes after open prenatal and postnatal repair of myelomeningocele. Results demonstrated that prenatal repair can offer significantly better results than traditional postnatal repair. […] Fetal surgery for myelomeningocele (MMC), the most severe form of spina bifida, is offered as a standard of care at CHOP.

• #31 Spina Bifida (Myelomeningocele) | Texas Children’s

  https://www.texaschildrens.org/health/spina-bifida

  Fetoscopic fetal surgery to repair spina bifida can lead to longer gestation, improved outcomes, lower rates of hydrocephalus, decreased need for shunts and improved leg function compared to after-birth repair. […] This minimally invasive approach offers benefits over both open fetal surgery and surgical repair after birth.

• #32 Spina Bifida – almostadoctor

  https://almostadoctor.co.uk/encyclopedia/spina-bifida

  Spina Bidifa is a neural tube defect that results from a defect in the closure of the neural tube (which goes to form the spinal column) during embryological development. […] The exact mechanism is not known, but low folate levels during pregnancy are known to increase the risk of the foetus developing the condition. […] Risk factors: Low maternal folate, particularly significant between days 17 and 30 of pregnancy this is a time when many mothers are not yet aware that they are pregnant and thus pre-pregnancy planning and supplementation are an important factor in prevention. […] In severe cases, then fetal surgery before 26 weeks gestation may be considered. This can prevent herniation of the brain and Chiari II malformation, and reduce the need for ventriculoperitoneal shunt after birth.

• #33 Identification of MicroRNA Profiles in Fetal Spina Bifida: The Role in Pathomechanism and Diagnostic Significance

  https://www.mdpi.com/1422-0067/25/5/2896

  Our analysis demonstrates the usefulness of evaluating miRNA expression patterns in the prenatal diagnosis of spinal bifida (SB). Additionally, a screening panel comprising miR-205-5p + miR-362-5p and miR-320e may be introduced as a potential tool for the maternal serum prenatal screening of SB. Furthermore, characterizing the regulatory network of DE miRNAs and target genes in amniotic fluid is important for investigating the pathways that contribute to a better understanding of SB pathogenesis.

• #34 A-Z of medical terms | RCOG

  https://www.rcog.org.uk/for-the-public/a-z-of-medical-terms/

  Spina bifida A condition which affects the unborn baby in the early stages of pregnancy. Spina bifida causes damage to the spinal cord and nerves. […] Folic acid A B vitamin which reduces the risk of a baby being born with a spinal defect such as spina bifida. Ideally, a woman should take folic acid (400 micrograms) 3 months before conceiving. All women should take it for the first 12 weeks of pregnancy. A higher dosage (5 mg) is recommended if you are overweight, on epilepsy treatment, are diabetic or are having twin/triplets. […] Neural tube defects Abnormalities of the skull or back bone of a developing baby that happen during the first 12 weeks of your pregnancy and which will affect your baby from birth. Taking folic acid before becoming pregnant and for the first 3 months of pregnancy can help to prevent neural tube defects.

• #35 Spina Bifida – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/congenital-neurologic-anomalies/spina-bifida

  Spina bifida is defective closure of the vertebral column. […] Although the cause is often unknown, low folate levels during pregnancy increase risk. […] Causes of spina bifida seem multifactorial. Folate deficiency is a significant factor, and there seems to be a genetic component. […] Other risk factors include maternal use of certain medications (eg, valproate) and maternal diabetes. […] Spina bifida involves defective closure of the vertebral column, sometimes with a protruding sac containing meninges (meningocele), spinal cord (myelocele), or both (myelomeningocele). […] Chiari II type malformation, often causing hydrocephalus, is common. […] Folate deficiency is a significant risk factor, but other factors include maternal use of certain medications (eg, valproate), maternal diabetes, and possibly a genetic component. […] Repair the spinal lesion, place a shunt for symptomatic hydrocephalus, and treat orthopedic and urologic abnormalities as needed. […] Reduce risk by giving folate supplementation beginning before conception.

• #36

  https://link.springer.com/article/10.1007/s004290100169

  This paper reviews 50 years of progress towards understanding the aetiology and pathogenesis of neural tube defects (NTD) in the curly tail (ct) mutant mouse. […] The failure of closure of the spinal neural tube, which leads to spina bifida in this mouse, has been traced back to a tissue-specific defect of cell proliferation in the tail bud of the E9.5 embryo. […] Neurulation movements are opposed, leading to delayed neuropore closure and spina bifida, or tail defects. […] In addition to the principal ct gene, which maps to distal Chromosome 4, the curly tail phenotype is influenced by several modifier genes and by environmental factors. […] NTD in curly tail are resistant to folic acid, as is thought to be the case in 30% of human NTD, whereas they can be prevented by myo-inositol. […] These and other features of NTD in this system bear striking similarities to the situation in humans, making curly tail a model for understanding a sub-type folic acid-resistant human NTD.

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