Neural Tube Defects

DEFINITION

Neural Tube Defects (NTDs) are a group of congenital malformations resulting from the failure of the neural tube to close during the 3rd and 4th weeks of gestational age (days 21 to 28 post-conception).

CLASSIFICATION (TYPES)

NTDs are broadly classified based on the involvement of overlying skin and the site of the defect.

1. Open Neural Tube Defects (ONTDs)

The defect is not covered by skin; neural tissue is exposed.

• Anencephaly: Failure of the anterior neuropore to close; absence of a major portion of the brain, skull, and scalp.
• Encephalocele: Herniation of brain and meninges through a cranial defect (most common in the occipital region).
• Myelomeningocele: Most common form; herniation of both spinal cord and meninges through a vertebral defect.
• Myeloschisis: The most severe form of spina bifida where the spinal cord is exposed as a flattened mass of nervous tissue.

2. Closed Neural Tube Defects (Slight/Occult)

The defect is covered by skin.

• Spina Bifida Occulta: Failure of fusion of vertebral arches without protrusion of spinal cord or meninges. Often marked by a tuft of hair, nevus, or dimple.
• Meningocele: Herniation of meninges only; spinal cord remains in the canal.
• Lipomyelomeningocele: A lipoma attached to the spinal cord.
• Tethered Cord Syndrome: Abnormal attachment of the spinal cord to surrounding tissues, limiting its movement.

EMBRYOGENESIS

The development of the nervous system occurs in two main phases:

1. Primary Neurulation (Days 18-28)

Failure at this stage leads to Open NTDs.

• The neural plate folds to form the neural groove.
• Closure begins at the level of the future neck and proceeds cranially and caudally like a zipper.
• Anterior Neuropore closes on Day 25 (failure results in Anencephaly).
• Posterior Neuropore closes on Day 27-28 (failure results in Myelomeningocele).

2. Secondary Neurulation (Days 28-48)

Failure at this stage leads to Closed NTDs.

• Involves the formation of the lower sacral and coccygeal segments.
• A mesenchymal cell mass (caudal cell mass) canalizes to join the primary neural tube.

Pathogenesis Factors

• Genetic: MTHFR (Methylenetetrahydrofolate reductase) gene polymorphisms.
• Environmental: Maternal diabetes, obesity, hyperthermia, and teratogens (Valproate, Carbamazepine).

PREVENTION

Prevention is primarily focused on peri-conceptional Folic Acid supplementation.

1. Primary Prevention (Folic Acid)

• Low Risk (General Population): 400 mcg (0.4 mg) daily starting at least 1 month prior to conception through the first trimester.
• High Risk (Previous child with NTD, Maternal Diabetes, Anticonvulsants): 4 mg (4000 mcg) daily starting 3 months prior to conception.

2. Secondary Prevention (Prenatal Screening)

• Maternal Serum Alpha-Fetoprotein (MSAFP): Elevated in 80-90% of Open NTDs (performed at 15-20 weeks).
• Targeted Ultrasound: "Lemon sign" (scalloping of frontal bones) and "Banana sign" (curved cerebellum) indicate Chiari II malformation associated with myelomeningocele.
• Amniocentesis: Elevated Acetylcholinesterase in amniotic fluid is diagnostic of ONTD.

MANAGEMENT

Management is multidisciplinary, involving Neonatologists, Neurosurgeons, Urologists, and Physiotherapists.

1. Immediate Neonatal Care

• Positioning: Prone or lateral position to avoid pressure on the sac.
• Moist Dressings: Cover the defect with sterile, non-adherent saline-soaked gauze to prevent desiccation and infection.
• Antibiotics: Broad-spectrum IV antibiotics to prevent meningitis.

2. Surgical Management

• Primary Closure: Definitive surgical repair of the defect within 24 to 48 hours of birth.
• Ventriculoperitoneal (VP) Shunt: Required in 80-90% of cases due to associated Hydrocephalus or Chiari II malformation.
• Fetal Surgery: In-utero repair (MOMS trial) reduces the need for shunting and improves motor outcomes but carries maternal risks.

3. Long-term Multidisciplinary Care

• Urological: Intermittent catheterization (CIC) and Anticholinergics to manage neurogenic bladder and prevent renal scarring.
• Orthopedic: Management of clubfoot (TEV), hip dysplasia, and scoliosis.
• Bowel Management: High-fiber diet and suppositories for neurogenic bowel.
• Psychosocial: Assessment for learning disabilities and support for family.