Neural tube defects

Neural tube defects (NTDs) are one of the most common congenital central nervous system (CNS) malformations. They develop between the 3^rd and 4^th week of pregnancy and are often caused by folic acid deficiency. The deficiency results in improper closure of the neural plate in the embryo, mainly at the caudal or cranial ends. The formation of defects at the caudal end is more common and is known as spina bifida. Spina bifida may occur without any apparent clinical features (spina bifida occulta), or manifest with protrusion of the meninges, and potentially also the spinal cord (myelomeningocele), through a gap in the vertebrae. Myelomeningoceles predominantly cause symptoms of sensory and motor function loss, such as bladder dysfunction and paraplegia. NTDs at the cranial end can cause cranial fissure malformations; the most severe manifestation of this, anencephaly, is incompatible with life. The diagnosis of NTDs is often established during pregnancy via ultrasound and detection of elevated alpha-fetoprotein levels in the amniotic fluid. Treatment involves prophylactic administration of antibiotics and swift surgical closure of the defect to avoid CNS infections. Supplementation with folic acid is an important preventative measure and should ideally be initiated 4 weeks prior to conception.

• Maternal folic acid deficiency during pregnancy; disorders or drug intake affecting folate metabolism
• Concomitant chromosomal aberrations (e.g., trisomy 13 and 18); genetic mutations in the folate and homocysteine metabolism pathways
• Associated maternal conditions: diabetes mellitus, obesity, fever/hyperthermia during first trimester

References:^[3]

Spina bifida

• Definition
  • Spina bifida occulta: failure of one or more vertebrae to close completely; the spinal cord, spinal meninges, and overlying skin remain intact
  • Spina bifida cystica; : failure of one or more vertebrae to close completely; the meninges (meningocele) and potentially the spinal cord (myelomeningocele) may protrude through the gap
• Location: primarily in the lower lumbar to sacral region
• Symptoms
  • Spina bifida occulta: usually asymptomatic; possibly visible dimple, collection of fat, or patch of hair on the skin above the defect
  • Spina bifida cystica
    • Symptoms of spinal cord dysfunction
      • Varying degrees of motor loss, possible flaccid paralysis
      • Sensory deficits
      • Bladder and bowel dysfunction
    • Further symptoms
      • Developmental delays, cognitive impairment, progressive neurological symptoms
      • Skeletal malformations (esp. of the spine and lower extremities), joint contractures, back pain
      • Hydrocephalus

Cranial defects

• Definition: cranial cleft formation with involvement of the skull and brain
  • Acrania: absent skull bones
  • Anencephaly: variable presentations of diminished cranium and forebrain, as well as cerebellum
  • Encephalocele: protrusion of the brain via an opening in the skull
  • Cranial meningocele: protrusion of meninges through parietal foramina or abnormal bony openings of the skull
• Location: variable
• Symptoms: malformations and neurological deficits that vary in severity; in severe cases always lethal

The most common NTDs are myelomeningocele, anencephaly, and encephalocele.

Congenital dermal sinus

• Definition: : mainly lumbar or lumbosacral fistulae; extend from the surface of the skin to the spinal canal and frequently end in a dermoid or epidermoid cyst

References:^[3][4][5]

• Prenatal screening
  • Elevated levels of alpha-fetoprotein (AFP) in amniotic fluid at 13–15 weeks' gestation
  • Fetal ultrasonography at 20 weeks' gestation
• CT scans and cranial ultrasonography (in infants) to monitor possible hydrocephalus
• MRI for assessment of spinal cord malformations

References:^[3]

• Folic acid supplementation
  • 400–800 μg/day at least 4 weeks prior to a planned pregnancy
  • Intake should continue through the first trimester.
  • Women who have had a child with an NTD or have one themselves should take 4 mg/day starting 4 weeks prior to trying to conceive.

References:^[3][8]