Chapter 38: Neural Tube Defects

I. Intensive care

Neural tube defects (NTDs)

1. Definition

   Broad spectrum of anomalies caused by failure or incomplete closure of neural tube

   1. “Open”: Defect in primary neural tube closure

      1. Anencephaly

         • Lethal condition

         • Restricted to cranial end

         • Absence of the cranial vault and absent or markedly diminished cerebral and cerebellar hemispheres

         • Holocrania if foramen magnum involved

         • Merocrania if the foramen magnum is not involved

      2. Spina bifida aperta or “myelomeningocele”

         • Defect involves spinal portion of neural tube

         • Characterized by level of spinal involvement

      3. Craniorachischisis

         • Lethal condition

         • Involves both cranium and spine

   2. “Closed”: Skin covered lesions that involve defects in both primary and secondary neural tube closure. Closed spinal lesions are also called spina bifida occulta

      1. Encephalocele

      2. Meningocele

      3. Lipomyelomeningocele

      4. Split cord malformations

      5. Sacral agenesis

      6. Terminal myelocystocele

      7. Other occult spinal dysraphisms

2. Incidence and prevalence

   1. NTD is the second most common type of birth defect after congenital heart defects and remain a leading cause of death and disability in children.

   2. Frequency varies with geographic and anatomic locations.

   3. In the United States, incidence of 10 per 10,000 live births in American Whites; lower rates in Black Americans and Asian-Americans, and higher rates in Hispanic-Americans.

   4. Because only a proportion of affected conceptuses survive to a stage where an NTD is likely to be recognized and some of the recognized affected fetuses are electively terminated or are stillborn, the true prevalence of these conditions is unknown, since only live-born infants are counted.

   5. In general, prevalence of spina bifida is higher than anencephaly.

   6. Prevalence of NTD is higher in females than males.

3. Pathophysiology

   1. These lesions result from the combined effects of genetic and environmental influences.

   2. Formation of the neural tube gives rise to the brain and spinal cord in three phases.

      1. Gastrulation: Forms the three embryonic germ layers (ectoderm, mesoderm, and endoderm). Split cord malformations may occur during this phase.

      2. Neurulation

         • Primary neurulation

           • Neural plate folds into neural tube forming the brain and majority of spinal cord.

           • Occurs during third to fourth weeks of gestation.

           • Defects give rise to anencephaly, myelomeningocele, meningocele, lipomeningocele.

         • Secondary neurulation

           • Occurs in fourth week of gestation.

           • Process of differentiation and canalization forms caudal end of spinal cord—the conus and filum terminale.

           • Defects give rise to occult spinal dysraphism including tethered cord malformations.

      3. Post-neurulation rapid growth and differentiation, which is when encephaloceles are thought to occur.

   3. There is active research concerning whether the architecture of the fetal myelomeningocele placode is normal. This is important since fetal surgery for repair is predicated on belief that it is preventing secondary injury caused by the intrauterine environment.

4. Risk factors

   1. Family history increases risk from 1-2/1000 live births to 3% to 8% in children of affected individuals, and to 5% in subsequent children if one is affected. If two children are affected the risk rises to 12%. Increased risk has also been noted in second- and third-degree relatives.

   2. Affected parent-child pairs are rare; most affected relatives are second or third degree.

   3. NTDs are associated with other known genetic ...