• Clinical science

Neural tube defects

Abstract

Neural tube defects (NTDs) are one of the most common congenital central nervous system (CNS) malformations. They develop between the 3rd and 4th 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.

Definition

Epidemiology

  • NTDs occur between the 22nd and 28th day post-conception ; the neural tube in the embryo closes during this time.
  • Incidence: 1–2 cases per 1000 births

References:[1][2]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

References:[3]

Subtypes and variants

Spina bifida

Cranial defects

  • Definition: cranial cleft formation with involvement of the skull and brain
  • 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
  • Etiology: incomplete or lack of separation of the neural ectoderm from the dermal ectoderm
  • Clinical findings
    • Changes in the skin (retraction, visible ostium, hypertrichosis, vascular nevi)
    • Infections (meningitis, abscess)
    • Neurological symptoms due to lesions in the spinal canal
  • Treatment: neurosurgical exploration and potential resection of the dermoid or epidermoid cysts

References:[3][4][5]

Diagnostics

  • 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]

Differential diagnoses

Tethered cord syndrome

  • Definition: abnormal stretching of the spinal cord caused by adhesions or obstructions that tether the cord to the base of the spinal canal
  • Etiology
  • Symptoms
  • Diagnosis: MRI shows abnormally low position of the conus medullaris.
  • Treatment: removal of structure tethering the spinal cord (e.g., adhesiolysis, resection of lipomas) → prevents progressive deterioration, corrects existing conditions (e.g., urinary retention)

References:[6]

The differential diagnoses listed here are not exhaustive.

Treatment

References:[3][7]

Prevention

  • 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]