Complete fusion of the neural tube usually occurs between days 18 and 26 after ovulation. Neural tube defects are malformations of the neuroectoderm and are associated with abnormalities of surrounding mesodermal structures. Neural tube defects can be classified as:

• Open: frequently involve the entire central nervous system; neural tissue is exposed with associated leakage of cerebrospinal fluid.
• Closed: localised and confined to the spine with the brain rarely affected; neural tissue is not exposed although the skin covering the defect may be dysplastic.

Cranial neural tube defects¹

• Anencephaly
• Encephalocele (meningocele or meningomyelocele)
• Congenital dermal sinus

Spinal neural tube defects¹

• Spina bifida
• Spina bifida occulta
• Myelomeningocele
• Meningocele
• Congenital dermal sinus
• Caudal agenesis

Epidemiology

• Incidence has declined significantly in the last 30 years and now occurs in approximately 0.8/1000 total births.²
• Anencephaly and spina bifida account for up to 95% of all neural tube defects with equal prevalence.

Risk factors

• Family history: one type of malformation puts other family members at risk of all types of defect.
• May occur as part of a number of different syndromes and chromosomal disorders.
• Diet low in folic acid.
• Therapy with sodium valproate and folic acid antagonists, e.g. some anti-epileptics, trimethoprim
• Dysraphism is used to describe situations where there is continuity between the posterior neuroectoderm and cutaneous ectoderm.

Presentation and management

See also separate articles Neonatal Examination and Paediatric Examination.

Cranial dysraphism

• Anencephaly:
  • Cranial vault is absent.
  • Most cases are now terminated following prenatal diagnosis.
  • In live born babies, initial neurological examination may appear normal if brainstem structures are relatively intact and there may be seizures despite lack of cerebral hemispheres.
  • Infants usually die within hours or days.
• Cephaloceles:
  • Brain matter herniates through a defect in skull. A cranial meningocele contains only meninges, encephalocele contains brain tissue; a ventriculocele contains part of the ventricle within the herniated part of the brain.
  • These are rarer than anencephaly or spina bifida, with an incidence of 1-3/10,000 live births.
  • Associated with other brain abnormalities, e.g. agenesis of corpus callosum or abnormal gyration and may be part of a recognised syndrome.
  • Posterior cephaloceles are most common in western countries with most being occipital encephaloceles of variable size occurring above or below the tentorium. If below, then they are associated with severe cerebellar defects, e.g. Chiari III malformation.
  • Depending on size, site and associated abnormalities, there may be visual, sensorimotor disturbance, intellectual impairment and seizures.
  • In some parts of Asia, anterior cephaloceles are more common and may protrude into the nose, ethmoid or orbit. They often include olfactory tissue and frontal lobe tissue.

Spinal dysraphism

Spina bifida includes spina bifida occulta and spina bifida cystica, which may be either a meningocele without neural tissue or a myelomeningocele where the spinal cord forms part of the cyst wall.

• Meningocele:
  • Protrusion of the meninges outside the spinal canal accounts for 5% of cases of spina bifida cystica.
  • No associated hydrocephalus, and neural examination is often normal.
• Myelomeningocele:
  • Occurs in 80-90% of spina bifida cystica cases.
  • 80% are lumbosacral consisting of a sac covered with a thin membrane that may leak CSF.
  • Level of lesion is best assessed by determining the upper limit of sensory loss but at all levels there is disturbance of bladder and bowel control.
  • Higher lesions are associated with bladder outlet obstruction with consequent dilatation of the upper urinary tract, and chronic pyelonephritis.
  • Hydrocephalus occurs in approximately 90% of cases at birth even with normal head circumference.
  • Usually associated with Chiari II malformation but it may also be due to aqueduct stenosis or have no clear cause.
  • Usually detected by ultrasound.
  • If there are signs of progressive ventricular dilatation or rising intracranial pressure, there is usually need for insertion of a ventriculoperitoneal shunt.
• Chiari II malformation:
  • Occurs in approximately 70% of cases of myelomeningocele.
  • Consists of downward protrusion of the medulla below the foramen magnum to overlap the spinal cord.
  • This causes the medulla to be kinked and the cerebellar vermis to be indented, fourth ventricle elongated and midbrain distorted.
  • Problems include palsies and central apnoea.
  • Treatment by closure of the defect remains controversial and is not always performed.
• Spina bifida occulta:
  • Defect of the posterior arch of one or more lumbar or sacral vertebrae (often L5 and S1).
  • Often found incidentally on X-ray in children admitted to hospital; may be considered as a normal variant.
  • However, if examination reveals a naevus, hairy patch, dimple, sinus or subcutaneous mass, then MRI scan of the spinal cord is recommended even if there are no associated problems with sphincter or limb control.
  • It can cause asymmetrical lower motor neurone weakness associated with wasting, deformity and diminished reflexes.
  • There may also be progressive gait disturbance with spasticity and impaired bladder control.
• Dorsal dermal sinuses:
  • Often found in the occipital and lumbosacral areas and can connect the skin surface to the dura or to an intradural dermoid cyst.
  • If open, it can produce recurrent meningitis so should be explored and removed if possible, before infection occurs.
• Lipomyelomeningocele:
  • Seen as a bulge in the lumbosacral region normally lateral to the midline.
  • This is a lipoma or lipofibroma attached to the spinal cord which is low-lying.
  • They are often associated with meningocele.
• Diastematomyelia:
  • Sagittal cleft dividing the spinal cord into two halves, each surrounded by its pia mater.
  • The cord may be transfixed by a bony or cartilaginous spur.
  • Usually occurs in the low thoracic or lumbar regions.
  • Overlying skin abnormality is present in 75% of cases and X-rays show abnormalities in most cases, including abnormal segmentation of vertebrae, spina bifida and scoliosis.
  • Neurosurgery is normally indicated if abnormality involves cord or nerve roots with the objective of freeing spinal cord from abnormal attachment to allow for normal growth and prevent further damage.

Investigations

• MRI is the study of choice for imaging neural tissue and for identifying contents of the defect in the newborn.
• CT scan allows direct visualisation of the bony defect and anatomy.
• Ultrasound is used antenatally for screening.

Prenatal screening

See also separate article Prenatal Diagnosis.

• Alpha-fetoprotein in maternal serum: best detected at 16-18 weeks pregnancy but may not detect closed defects and is less sensitive in women taking valproate.
• Ultrasound: recommended for all at-risk women (positive serum alpha-fetoprotein, previously affected child).³ Can detect anencephaly from the 12th week and spina bifida from 16-20 weeks (may occasionally be missed, especially in the L5-S2 region).
• Amniocentesis: only used when unable to obtain adequate ultrasound images; used to measure alpha-fetoprotein and neuronal acetylcholinesterase.

Management

• Affected children will require treatment from a multidisciplinary team to address any associated physical, developmental, hearing, visual and learning difficulties that may occur in association with the neural tube defect.
• The newborn with an open neural tube defect should be kept warm and the defect covered with a sterile saline dressing.
• The baby should be positioned in the prone position to prevent pressure on the defect.
• Open neural tube defects should be closed promptly.
• Hydrocephalus: ventriculoperitoneal shunt placed at the time of myelomeningocele closure.
• Symptomatic Chiari malformations: suboccipital craniotomy and decompression of the posterior fossa and tonsils.
• Syrinx (a fluid-filled cavity within the spinal cord or brainstem): laminectomy and placement of a syringosubarachnoid stent to divert the CSF out of the central canal.

Complications

• Infections
• Associated motor and sensory problems, particularly lower limb
• Associated learning disability, developmental delay and hearing impairment
• Bladder and bowel dysfunction

Prognosis

Depends on the nature of the defect and associated malformations.

Prevention

• Periconceptional folate supplementation has a strong protective effect against neural tube defects.⁴ Supplementation must begin before conception for it to be effective.⁵
• To prevent a first occurrence, women who are planning to become pregnant should take 400 micrograms of folic acid daily before conception and during the first 12 weeks of pregnancy.⁶ To prevent recurrence, 5 mg folic acid daily should be taken.
• Food fortification with the addition of folate to grain products is considered the most effective method of ensuring adequate intake of folic acid in pregnant women.³

Document references

1. Jallo GI; Neural Tube Defects, eMedicine, Dec 2008
2. Kramer MS; The epidemiology of adverse pregnancy outcomes: an overview. J Nutr. 2003 May;133(5 Suppl 2):1592S-1596S. [abstract]
3. Birnbacher R, Messerschmidt AM, Pollak AP; Diagnosis and prevention of neural tube defects. Curr Opin Urol. 2002 Nov;12(6):461-4. [abstract]
4. Lumley J, Watson L, Watson M, et al; Periconceptional supplementation with folate and/or multivitamins for preventing Cochrane Database Syst Rev. 2001;(3):CD001056. [abstract]
5. Busby A, Abramsky L, Dolk H, et al; Preventing neural tube defects in Europe: population based study. BMJ. 2005 Mar 12;330(7491):574-5.
6. Rosenberg KD, Gelow JM, Sandoval AP; Pregnancy intendedness and the use of periconceptional folic acid. Pediatrics. 2003 May;111(5 Part 2):1142-5. [abstract]

Internet and further reading

• Association for Spina Bifida and Hydrocephalus; Resources and help for parents of children with the condition
• Surgical Tutor; Neural tube defects

Acknowledgements