Spinal Cord Injury in Myelomeningocele: Prospects for Therapy

Frontiers in Cellular Neuroscience, 2020 · DOI: 10.3389/fncel.2020.00201 · Published: June 30, 2020

Simple Explanation

Myelomeningocele (MMC) is a congenital defect where the spinal cord doesn't fully close during development, leading to the cord's exposure and progressive injury. This exposure to the intrauterine environment causes further damage, exacerbating neurological deficits beyond the initial malformation. Current research focuses on prenatal surgical repair and tissue engineering to protect the spinal cord and improve neurological outcomes, but a better understanding of the injury mechanisms is needed.

Study Duration

Not specified

Participants

Human specimens, mouse genetic models, fetal rats, lambs

Evidence Level

Review article

Key Findings

1
The neurological deficits in MMC are not solely due to the initial defect but are worsened by in utero spinal cord injury.
2
Amniotic fluid toxicity and mechanical trauma to the exposed spinal cord contribute to prenatal spinal cord damage in MMC.
3
Prenatal surgical repair of MMC defects can improve functional outcomes compared to postnatal repair, but it carries maternal and fetal risks.

Research Summary

This review discusses the pathological development of MMC, focusing on in utero injury to the exposed spinal cord and the need for understanding the causative factors and pathophysiological alterations associated with the injury. The 'two-hit hypothesis' explains the pathogenesis of spinal cord injury in MMC: the initial failure of neural tube closure and subsequent exposure to the intrauterine environment. Future research should focus on developing targeted prenatal therapies based on a better understanding of the pathophysiological mechanisms underlying spinal cord injury in MMC to improve neurological outcomes.

Practical Implications

Prenatal Intervention Strategies

Further research into the mechanisms of spinal cord injury in MMC can lead to the development of targeted prenatal therapies to minimize neurological deficits.

Improved Surgical Techniques

Continued optimization of minimally invasive fetoscopic surgery and closure techniques can reduce maternal and fetal risks associated with open repair.

Biomarker Development

Identifying biomarkers that can detect the presence and progression of fetal spinal cord injury in MMC could aid in the timing of prenatal intervention.

Study Limitations

1
Etiology of MMC remains poorly understood
2
Factors that trigger and/or contribute to the progression of the injury are not fully understood
3
Cellular and molecular mechanisms underlying the formation of astrocytosis as well as other pathophysiological derangements that parallel the injury have not yet been entirely defined.

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