Neural tube defects
Neural tube formation and neural tube defects: spina bifida, anencephaly
How the neural tube forms and closes by day 28, and the defects when it fails: anencephaly, spina bifida and tethered cord, with AFP and folic acid. Each defect is explained from where and when closure failed.
Neurulation
- The notochord induces the overlying ectoderm to thicken into the neural plate (about day 18, week 3).
- The edges rise as neural folds with a neural groove between them. The folds meet in the midline first in the future cervical region (about day 22) and the tube zips up towards both ends.
- The open ends are the neuropores: the anterior (cranial) neuropore closes at about day 25, the posterior (caudal) neuropore at about day 27–28. So the whole tube is closed by the end of week 4, often before a woman knows she is pregnant.
- Neural crest cells leave the crests of the folds as they meet.
- Below the level of the caudal neuropore (lower sacral and coccygeal cord), the cord forms by secondary neurulation from the tail bud, a solid mass that cavitates; defects here give closed (skin-covered) lesions.
- The surrounding sclerotome mesenchyme forms the vertebral arches and paraxial mesoderm forms the dura; incomplete fusion of the vertebral arches is what "spina bifida" means.
From tube to brain and cord
| Primary vesicle | Secondary vesicle | Adult derivative | Cavity |
|---|---|---|---|
| Prosencephalon | Telencephalon | Cerebral hemispheres | Lateral ventricles |
| Prosencephalon | Diencephalon | Thalamus, hypothalamus, posterior pituitary, retina | Third ventricle |
| Mesencephalon | Mesencephalon | Midbrain | Cerebral aqueduct |
| Rhombencephalon | Metencephalon | Pons, cerebellum | Upper fourth ventricle |
| Rhombencephalon | Myelencephalon | Medulla | Lower fourth ventricle |
- In the wall of the tube, the dorsal alar plate forms sensory neurones and the ventral basal plate forms motor neurones, separated by the sulcus limitans.
- The cord initially fills the vertebral canal; because the column grows faster, the conus ends at about L3 at birth and L1–L2 in adults.
Neural tube defects
| Defect | What failed | Features |
|---|---|---|
| Anencephaly | Anterior neuropore | Absent forebrain and skull vault; polyhydramnios because the fetus cannot swallow amniotic fluid; incompatible with life; very high AFP |
| Encephalocele | Skull defect | Brain and meninges herniate, usually occipital |
| Spina bifida occulta | Vertebral arches only | Commonest overall, usually L5/S1; skin intact with a tuft of hair, dimple, naevus or lipoma; usually symptomless; normal AFP |
| Meningocele | Arches plus dura | Sac of meninges and CSF only; cord in place; usually little deficit |
| Myelomeningocele | Arches, meninges and cord | Commonest open defect; cord in the sac; paralysis, sensory loss, neurogenic bladder and bowel; Chiari II and hydrocephalus |
| Rachischisis (myeloschisis) | Neural folds never closed | Flat open neural plate |
- Chiari II malformation: cerebellar vermis and medulla pushed down through the foramen magnum, blocking CSF flow, so hydrocephalus is common. Chiari I (tonsils only) presents in adults with headache and syringomyelia.
- Tethered cord syndrome: a low-lying conus (for example at L4) held by a thick filum, lipoma or old repair is stretched during growth spurts, bending or lifting. It gives back pain, leg weakness or numbness, foot deformity and bladder symptoms. A hairy patch or dimple with symptoms is not harmless occulta and needs MRI.
- Latex allergy: children with spina bifida have repeated early exposure to latex (catheters, surgery) and a high rate of latex sensitisation. Theatre must be latex-free; anaphylaxis can start when gloves touch mucosa or peritoneum.
Screening and diagnosis
- Maternal serum AFP is raised in open defects (best measured at 15–20 weeks, typically 16). AFP leaks from exposed neural tissue into amniotic fluid and then maternal blood.
- Amniotic fluid AFP and acetylcholinesterase confirm an open defect.
- Ultrasound is now the best diagnostic test: anencephaly is visible from the first trimester; at the 18–20 week scan spina bifida shows the lemon sign (scalloped frontal bones) and banana sign (cerebellum dragged down).
- Raised AFP also occurs with wrong dates, multiple pregnancy, abdominal wall defects and fetal death.
Risk factors
| Factor | Mechanism or note |
|---|---|
| Folate deficiency | Poor intake of green vegetables and fruit; the main preventable cause |
| Folate antagonists | Valproate (highest risk), carbamazepine, methotrexate, trimethoprim |
| Vitamin B12 deficiency | Low B12 is an independent risk factor beyond folate |
| Maternal diabetes and obesity | Poor glycaemic control at conception |
| Previous affected pregnancy | Recurrence risk about 2–5% |
| Maternal hyperthermia | Fever or sauna in early pregnancy |
Prevention
- Folic acid 400 micrograms daily from before conception until 12 weeks, because closure is complete by day 28.
- 5 mg daily for women at high risk: previous NTD pregnancy, either partner with an NTD, antiepileptic drugs, diabetes, BMI 30 or more, coeliac disease or malabsorption, sickle cell disease or thalassaemia.
- Food fortification with folate lowers population rates.
Other CNS anomalies
- Hydrocephalus: commonest congenital cause is aqueduct stenosis.
- Dandy–Walker malformation: cystic fourth ventricle, absent cerebellar vermis.
- Holoprosencephaly: forebrain fails to divide (trisomy 13, maternal diabetes, sonic hedgehog defects); cyclopia in severe forms.
Remember The tube closes by day 28: folic acid must start before conception.
Exam trap Spina bifida occulta has a normal AFP because the defect is skin-covered.
Exam trap A meningocele contains meninges only; a myelomeningocele contains cord too and carries the deficits and Chiari II.
How FCPS asks about this
- Timing of neuropore closure: anterior about day 25, posterior about day 27–28 (end of week 4).
- Failure of the anterior neuropore: anencephaly, with polyhydramnios from impaired fetal swallowing.
- Lumbosacral swelling of meninges without neural tissue: meningocele.
- Tumour marker and best test for open NTD: raised AFP at about 16 weeks; ultrasound for diagnosis.
- Vitamin deficiencies linked to NTD: folate, also B12; 5 mg folic acid after an affected pregnancy.
- Hairy patch with back pain and bladder urgency, conus at L4: tethered cord syndrome.
- Theatre precaution in spina bifida: latex-free environment.
Test yourself on this topic
5 of the 14 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A baby had a lumbar myelomeningocele closed at birth. Over the next weeks the head circumference rises across centiles and the fontanelle bulges. Which associated malformation best explains this?
Answer: Chiari II malformation
Almost all children with open myelomeningocele have a Chiari II malformation: the cerebellar vermis, fourth ventricle and medulla are pulled down through the foramen magnum. This blocks CSF outflow from the fourth ventricle, so most develop hydrocephalus, often after the back is closed, and many need a ventriculoperitoneal shunt. Head circumference is measured regularly after repair for this reason.
Myelomeningocele and the brain
- Chiari II in almost all
- Hindbrain pulled through foramen magnum
- Blocks CSF: hydrocephalus
- Often needs a VP shunt
Remember Back lesion, watch the head.
Exam trap Hydrocephalus often appears after the back is repaired, not at birth.
Why the other options are wrong
- Dandy-Walker cyst Cystic fourth ventricle, not linked to myelomeningocele.
- Holoprosencephaly Failure of forebrain division, small head.
- Craniosynostosis Fused sutures limit head growth.
- Arachnoid cyst Usually an incidental finding.
A woman on sodium valproate for epilepsy plans pregnancy. What folic acid dose is advised before conception and in early pregnancy?
Answer: 5 mg daily
All women planning pregnancy should take 400 micrograms of folic acid daily from before conception to 12 weeks. Higher-risk women take 5 mg daily: previous neural tube defect, either partner or family history of NTD, antiepileptic drugs, diabetes, obesity (BMI 30 or more), coeliac disease or sickle cell disease. Valproate should be switched where possible because it is highly teratogenic.
Folic acid in pregnancy
- Standard: 400 micrograms
- High risk: 5 mg daily
- High risk: previous NTD, antiepileptics, diabetes, obesity
- Start before conception, to 12 weeks
Remember High risk gets the big 5 mg dose.
Exam trap The neural tube closes by day 28, often before pregnancy is known, so start early.
Why the other options are wrong
- 400 micrograms daily Standard dose for low-risk women.
- 50 micrograms daily Too low.
- 1 mg weekly Not a recognised regimen.
- Folic acid is not needed She is at high risk; folic acid is essential.
A 20-week scan shows anencephaly with polyhydramnios. Which of the following explains the excess fluid?
Answer: Impaired fetal swallowing
Amniotic fluid volume is balanced between fetal urine production and fetal swallowing with absorption in the gut. In anencephaly, failure of the anterior neuropore to close leaves the forebrain undeveloped, and the brainstem centres that coordinate swallowing are often abnormal. The fetus swallows little, so fluid accumulates. The same mechanism explains polyhydramnios in oesophageal and duodenal atresia.
Anencephaly
- Anterior neuropore fails to close
- Raised AFP
- Polyhydramnios: poor swallowing
- Not compatible with life
Remember No swallowing, too much fluid.
Exam trap Folic acid before conception reduces neural tube defects; 5 mg is given after an affected pregnancy.
Why the other options are wrong
- Excess fetal urine output Urine output is not the main change.
- Leakage of CSF into amniotic fluid Exposed tissue may leak, but this is not the main cause.
- Placental overgrowth Not a feature of anencephaly.
- Maternal diabetes Not indicated; the anomaly explains it.
A child has a lipoma of the filum terminale with a low-lying conus, but the skin over the back is closed. The lowest part of the spinal cord and the filum form by a different process from the rest of the cord. What is that process?
Answer: Secondary neurulation from the caudal eminence
Most of the neural tube forms by primary neurulation: the neural plate folds and closes, ending when the posterior neuropore closes at about day 28. Below about the second sacral level, the cord, conus and filum form by secondary neurulation, in which a solid mass of cells in the tail bud (caudal eminence) cavitates to form a tube that joins the rest. Errors here produce skin-covered (closed) defects such as filar lipoma and tethered cord, rather than open spina bifida.
Two ways to build the tube
- Primary: plate folds and closes
- Secondary: caudal eminence cavitates
- Secondary forms conus and filum
- Errors: closed defects, tethered cord
Remember Skin-covered low-cord defects point to secondary neurulation.
Exam trap Skin-covered defects are not explained by failed neuropore closure.
Why the other options are wrong
- Folding of the neural plate (primary neurulation) Forms the brain and cord down to about S2; failures give open defects.
- Fusion of the posterior neuropore on day 28 Ends primary neurulation; failure causes open lumbosacral defects.
- Migration of neural crest into the sacral region Neural crest forms ganglia and Schwann cells, not the cord.
- Segmentation of the sacral somites Somites form vertebrae and muscle, not neural tissue.
An adult has a tuft of hair over the L5 spine, with no neurological deficit. What is the most likely underlying abnormality?
Answer: Spina bifida occulta
Spina bifida occulta is failure of the vertebral arches to fuse (usually L5/S1) with intact meninges and cord; it is often asymptomatic, marked by a hair tuft, dimple, naevus or lipoma. Meningocele: meninges herniate in a CSF-filled sac. Myelomeningocele: cord and meninges protrude (neurological deficit, hydrocephalus, Arnold–Chiari II). Folic acid reduces neural tube defects; AFP is raised in open defects.
Neural tube defects
- Occulta: hair tuft, no sac, usually normal
- Meningocele: meninges only
- Myelomeningocele: cord + meninges, deficit; folic acid prevents
Remember Hairy patch on the back: hidden spina bifida.
Why the other options are wrong
- Meningocele Visible sac.
- Myelomeningocele Neurological deficit.
- Anencephaly Absent forebrain and skull vault.
- Sacrococcygeal teratoma Mass at the coccyx.
Where this sits in the CPSP syllabus
- Paper 1: General and systemic embryology, Neural tube and its defects
- Surgery & Allied, Paper 2: Embryology for surgery, Neural tube and its defects
- Medicine & Allied, Paper 2: Embryology: heart, brain and kidney development, Neural tube and its defects
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