Spina Bifida is a congenital anomaly in which the spinal column is bifid due to failed closure of the neural tube during embryonic neural development. The most severe form of spina bifida is myelomeningocele, also known as open spina bifida. In this condition, a placode resting in a meningeal sac is formed on the back of the newborn baby and the vertebrae remain incomplete dorsally and lack neural arches at the lesion. Patients with this condition may have impairment of both sensory and motor function below the level of the lesion. The deficits may result in lower-limb weakness, urinary and fecal incontinence, hindbrain herniation, hydrocephalus, etc. This neurological dysfunction is considered a two-hit process: failed closure of neural tube and interrupted axonal connection and function in the utero as a result of amniotic fluid toxicity.
Various forms of Spina bifida are spina bifida occulta (closed asymptomatic neural tube defect in which some of the vertebrae are not completely closed at the lesion), Meningocele (protrusion of CSF-filled meningeal sac through the defect in the spine), Myelomeningocele (open spinal cord with meningeal cyst). The genetic contribution is thought to be between 60-70 %, however, only a handful of causative genes have been identified thus far using mouse models. Potential non-genetic maternal factors include low folate intake, alcohol consumption, low vit B12, zinc, vit C intake, smoking, pregestational obesity, diabetes mellitus, etc. Furthermore, exposure to various environmental factors such as pollutants and personal toxicants may contribute to this defect.
On day 22, primary neurulation initiates, and the neural tube zips bi-directionally down the spine and into the hindbrain. Neural tube defects can result from the failure of any part of this neurulation sequence. The most severe neural tube defect is craniorachischisis, in which neural tube closure failed to be initiated on day 22. Among various forms of spina bifida, myelomeningocele is associated with brain malformation as well as various neurocognitive difficulties. Approximately half or one-third of individuals with myelomeningocele have corpus callosum hypogenesis and a greater reduction in posterior white matter integrity in association with tectal beaking, reduced IQ, and dexterity of the fingers. This corpus callosum anomaly results in reduced communication between two hemispheres and difficulties in integrating sensory information via reading, language, or social interaction. These cognitive difficulties can be observed as early as six months of age and affect individuals throughout their lives.
This condition is generally diagnosed during pregnancy via ultrasonography and biochemical tests such as α-fetoprotein measurement in amniotic fluid, maternal obesity screening, etc. The management includes prenatal fetal surgery or postnatal surgery within 48 hours of birth. The child’s back is surgically closed to minimize the risk of meningitis or other information. A premature birth is significantly common after prenatal surgery. Almost all individuals with thoracic lesions require a ventriculoperitoneal shunt whereas, 70% with sacral lesions and 85% with lumbar lesions need this intervention. In severe cases with hindbrain herniation, posterior fossa decompression surgery is suggested. Significantly less hindbrain herniation is observed to occur in the fetal surgery group.
Spina bifida has a pervasive impact on the psychological, neurocognitive, and social functioning of affected individuals. During late childhood, they may have lower self-esteem or high depressive symptoms than unaffected individuals. There are a few areas that may promote primary prevention and improve the lives of individuals with spina bifida. Efforts are made to unravel the cause by the application of high-throughput genomic and epi-genomic technologies such as exosome sequencing. Moreover, exogenous folic acid may enhance embryonic cell proliferation by stimulating purine and pyrimidine synthesis. Further research is going on the effect of folate or other supplementation depending on the specific subgroups of human spina bifida. To date, some preclinical studies are done on stem cell transplantation with mesenchymal stem cells, neural stem cells, and skin-derived induced pluripotent stem cells. However, several domains, such as psychological intervention, family-based intervention, in the life of the individual with spina bifida need further research. Progress towards such interventions could considerably improve the lives of individuals with spina bifida.
Reference:
Copp, A. J., Adzick, N. S., Chitty, L. S., Fletcher, J. M., Holmbeck, G. N., & Shaw, G. M. (2015). Spina bifida. Nature reviews. Disease primers, 1, 15007. https://doi.org/10.1038/nrdp.2015.7
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