STEPTRACKERNERVOUS SYSTEM | PATHOLOGY + EMBRYOLOGY | HIGH-YIELD REVIEW

Developmental CNS Anomalies

When the neural tube doesn't close, the forebrain doesn't split, or the hindbrain is crowded into the foramen magnum.

FOCUS ON
Neural tube defects: neuropores fail to close by week 4; ↑ AFP and acetylcholinesterase in amniotic fluid; prevent with folate; risk with valproate, diabetes. Chiari II: lumbosacral myelomeningocele + hydrocephalus. Chiari I: tonsils low, adults, syrinx. Dandy-Walker: no vermis, big 4th ventricle. Holoprosencephaly: SHH, trisomy 13, cyclopia.
ANOMALY
MECHANISM
FEATURES
CLUE
Neural tube defects — overview
Failure of neuropore closure (week 4); ↓ folate, maternal diabetes, obesity, valproate, carbamazepine
Open defects leak fetal proteins
↑ AFP (maternal serum, amniotic fluid), ↑ amniotic AChE · folate 0.4 mg/day (4 mg if prior NTD)
Anencephaly
Anterior neuropore fails to close
No forebrain or calvarium; incompatible with life; polyhydramnios (no swallowing)
Very high AFP
Spina bifida occulta
Vertebral arch fails to close; no herniation
Lumbosacral tuft of hair or dimple; usually asymptomatic; dura intact
Normal AFP
Meningocele
Meninges herniate through a bony defect
Cystic sac; cord in normal position; few deficits
↑ AFP
Myelomeningocele
Meninges + spinal cord/roots herniate
Leg paralysis, bladder/bowel dysfunction, sensory loss below the level
With Chiari II and hydrocephalus · latex allergy
Encephalocele
Brain tissue herniates through a skull defect (often occipital)
Sac at the back of the head
Meckel-Gruber syndrome
Chiari I malformation
Cerebellar tonsils extend below the foramen magnum (small posterior fossa)
Adolescents/adults: occipital headache worse with cough/Valsalva, cerebellar signs
Associated syringomyelia
Chiari II malformation
Cerebellar vermis and tonsils + medulla herniate; tectal beaking
Infants: noncommunicating hydrocephalus (aqueductal stenosis), stridor, dysphagia
Lumbosacral myelomeningocele
Dandy-Walker malformation
Agenesis/hypoplasia of the cerebellar vermis; cystic enlargement of the 4th ventricle filling an enlarged posterior fossa
Hydrocephalus, macrocephaly, ataxia, developmental delay
Big posterior fossa (vs small in Chiari)
Holoprosencephaly
Prosencephalon fails to split into hemispheres (weeks 5–6); SHH mutations
Single ventricle, fused hemispheres; cleft lip/palate, single central incisor; severe: cyclopia, proboscis
Trisomy 13, fetal alcohol, maternal diabetes
Lissencephaly
Failed neuronal migration (LIS1)
Smooth brain without gyri; seizures, severe intellectual disability
"Smooth brain"

Mechanism — from neural tube to brain

Neural plateEctoderm (notochord → SHH)
→
Neural tubeCloses day 21–28
→
Anterior neuropore openAnencephaly
Posterior neuropore openSpina bifida
ProsencephalonTelencephalon + diencephalon
MesencephalonMidbrain, aqueduct
RhombencephalonPons, cerebellum, medulla

Neural tube → CNS neurons and glia; neural crest → PNS, adrenal medulla, melanocytes.

Posterior fossa malformations

FEATURE
CHIARI I
CHIARI II
DANDY-WALKER
What moves
Tonsils down
Vermis + tonsils + medulla
Vermis absent
Posterior fossa
Small
Small
Enlarged, cystic
Age
Adult/teen
Infant
Infant
Associated
Syringomyelia
Myelomeningocele, hydrocephalus
Hydrocephalus

How it's tested

COMMON CONFUSIONSpina bifida occulta has normal AFP (closed, skin-covered); meningocele and myelomeningocele raise AFP. A hair tuft at the low back means occulta.
THE TRAPFolate must be started before conception — the neural tube closes by week 4, often before a woman knows she's pregnant.
YOUR APPROACHOpen or closed defect (AFP) → level (cranial, spinal) → contents (meninges, cord, brain) → associated malformation (Chiari II, hydrocephalus) → risk factor (folate, valproate, diabetes, trisomy).

If you see… think…

↑ maternal AFP and ↑ amniotic acetylcholinesterase → open neural tube defect
Epileptic mother on valproate, fetal spinal defect → neural tube defect
Lumbosacral hair tuft, normal neuro exam → spina bifida occulta
Newborn with lumbar sac containing cord, leg paralysis, hydrocephalus → myelomeningocele + Chiari II
Absent skull and forebrain, polyhydramnios → anencephaly
Teen with cough headache and cape-like sensory loss → Chiari I + syringomyelia
Absent cerebellar vermis and huge 4th ventricle → Dandy-Walker
Single central incisor, cleft lip, fused hemispheres → holoprosencephaly
Holoprosencephaly + polydactyly + cutis aplasia → trisomy 13
Smooth brain with no gyri → lissencephaly