Pathophysiology of Myelomeningocele
Myelomeningocele results from a localized failure of primary neurulation during the fourth week of embryonic development, followed by progressive secondary injury to the exposed neural tissue throughout gestation. 1
Primary Embryological Defect
The fundamental defect is failure of neural tube closure during the fourth week of embryonic development (approximately 28 days post-conception), representing a failure of primary neurulation. 1, 2
This initial failure results in incomplete closure of both the neural tube and the overlying vertebral arches, leaving the spinal cord exposed on the skin surface as a placode. 2
The placode is always present on the skin surface and may be flat or elevated on a dome-shaped sac filled with cerebrospinal fluid; if the thin tissue tears, CSF escapes and the malformation appears flat. 2
Two-Hit Hypothesis of Injury
The pathological progression involves two distinct phases of injury:
Primary Defect (First Hit)
- Failure of neural tube and vertebral arch closure occurs at early gestational ages (fourth week). 3, 1
Secondary Progressive Injury (Second Hit)
After the initial failure of closure, the exposed neural tissue undergoes continued mechanical and chemical injury throughout the remainder of fetal development. 3, 4
The exposed spinal cord suffers progressive damage from direct trauma, amniotic fluid exposure, and impaired spinal cord and vertebral growth during gestation. 3, 5
This secondary injury mechanism made myelomeningocele a candidate for in-utero surgical repair, as early closure could theoretically interrupt the progressive pathological process. 3, 4
Associated Malformations
The neural tube defect triggers a cascade of secondary structural abnormalities:
Chiari type II malformation occurs in 98% of cases, representing hindbrain herniation through the foramen magnum. 2
Hydrocephalus develops in approximately 70% of patients. 2
Syringomyelia affects 40-80% of patients. 2
Spinal cord tethering occurs in virtually all cases. 2
Neurologic Impairment Determinants
The severity of neurologic impairment correlates directly with the anatomic level and size of the defect—larger lesions and more cranial locations produce greater neurologic deficits. 2
Initial ambulatory status depends on the anatomic level of the neural tube defect. 2
Preventable Risk Factors
Folic acid deficiency during the periconceptional period is a major preventable risk factor; supplementation with 400 μg (0.4 mg) daily throughout reproductive years reduces NTD incidence by 40-80%. 2
The mechanism involves folic acid's role in DNA synthesis and cell division during the critical period of neural tube closure (first 28 days post-conception, often before pregnancy recognition). 2