Congenital CNS Anomalies

Neural Tube Defects - Open & Shut Cases

• Neural tube closure failure (3rd-4th week gestation). Folic acid prevents.
• Open NTDs: Exposed neural tissue; no skin cover. ↑ Alpha-fetoprotein (AFP).
  • Anencephaly: Absent cranial vault & cerebral hemispheres. "Frog-eye" sign.
  • Myelomeningocele: Protrusion of meninges & spinal cord. Associated with Chiari II malformation.
  • Encephalocele: Herniation of cranial contents through skull defect.
• Closed NTDs: Skin-covered defect; neural tissue not exposed. Normal AFP.
  • Spina Bifida Occulta: Vertebral arch defect, often tuft of hair or dimple.
  • Lipomyelomeningocele: Lipoma attached to tethered spinal cord.
  • Diastematomyelia: Sagittally split spinal cord.

⭐ Lemon sign (frontal bone scalloping) and Banana sign (cerebellar effacement) on fetal US are strong indicators of open spina bifida, often seen with Chiari II malformation (herniation of cerebellum & brainstem).

Forebrain Cleavage Disorders - Midline Mayhem

• Holoprosencephaly (HPE) Spectrum: Failure of prosencephalon (forebrain) cleavage.

  • Alobar: Most severe. Monoventricle, fused thalami & basal ganglia, absent falx/corpus callosum. Facial: cyclopia, proboscis.

  • Semilobar: Partial separation. Rudimentary occipital/temporal horns. Incomplete falx.

  • Lobar: Least severe. Near-complete separation. Absent septum pellucidum, fused fornices.

  • Middle Interhemispheric Variant (MIHV) / Syntelencephaly: Non-separation of posterior frontal/parietal lobes.

• Septo-optic Dysplasia (SOD) / de Morsier Syndrome: Triad (often incomplete):
  • Optic nerve hypoplasia.
  • Pituitary hypoplasia (→ endocrinopathy).
  • Absent septum pellucidum (in ~50%).
• Agenesis of Corpus Callosum (ACC):
  • Complete or partial. Associated with Probst bundles, colpocephaly (dilated occipital horns), high-riding 3rd ventricle.
  • 📌 "Racing car" sign on axial MRI.

⭐ Holoprosencephaly is strongly associated with Trisomy 13 (Patau syndrome) and mutations in the Sonic Hedgehog (SHH) gene pathway.

Neuronal Migration Disorders - Brainy Wanderings

📌 Mnemonic: Little Hippos Play Soccer (Lissencephaly, Heterotopia, Polymicrogyria, Schizencephaly)

• Lissencephaly (Agyria-Pachygyria): Smooth brain; absent (agyria) or few, broad (pachygyria) gyri.
  • Type 1 (Classic): "Hourglass"/"Figure-8" MRI. LIS1/DCX genes.
  • Type 2 (Cobblestone): Pebbly surface. Walker-Warburg, Fukuyama.
• Heterotopia: Ectopic neuronal clusters due to arrested migration.
  • Subependymal: Nodules along ventricles. Most common. FLNA gene (X-linked).
  • Subcortical (Band/Double Cortex): Layer of gray matter. DCX gene (X-linked). )
• Polymicrogyria: Many small, disorganized gyri. Bilateral perisylvian common. CMV, ischemia.
• Schizencephaly: Gray matter-lined clefts (pial to ventricle). Open/closed lip. EMX2 gene.

⭐ Band heterotopia ("double cortex") is characteristically seen in females and is X-linked, often due to DCX gene mutations.

Posterior Fossa Malformations - Cerebellar Conundrums

• Key anomalies: Dandy-Walker Malformation (DWM), Chiari Malformations, Joubert Syndrome, Rhombencephalosynapsis.
• Dandy-Walker Malformation (DWM):
  • Cystic 4th ventricle dilation
  • Inferior vermian hypoplasia
  • Enlarged posterior fossa, ↑torcular
  • Hydrocephalus common (~80%)
• Chiari Malformations:
  • Type I: Tonsillar ectopia >5mm (adults) / >6mm (kids) below foramen magnum. Syringomyelia common.
  • Type II (Arnold-Chiari): Inferior vermis & tonsil herniation, myelomeningocele, tectal beaking, hydrocephalus.
  • Type III: Occipital/cervical encephalocele + cerebellum. Rare.
• Joubert Syndrome:
  • "Molar tooth sign" (MRI): thickened Superior Cerebellar Peduncles, deep interpeduncular fossa.
  • Vermian hypoplasia.
• Rhombencephalosynapsis:
  • Vermian agenesis, fused cerebellar hemispheres & dentate nuclei.

⭐ Chiari II malformation is almost universally associated with myelomeningocele.

High‑Yield Points - ⚡ Biggest Takeaways

• Chiari II malformation: Associated with myelomeningocele; features tonsillar herniation, tectal beaking, and often hydrocephalus.
• Dandy-Walker malformation: Characterized by cystic 4th ventricle dilation, vermian agenesis/hypoplasia, and enlarged posterior fossa with torcular-lambdoid inversion.
• Holoprosencephaly: Results from failed forebrain cleavage (alobar most severe); associated with midline facial defects (e.g., cyclopia).
• Agenesis of Corpus Callosum: Presents with "racing car" sign (parallel lateral ventricles), colpocephaly, Probst bundles, and high-riding 3rd ventricle.
• Lissencephaly ("smooth brain"): Shows agyria/pachygyria and a classic "hourglass" or "figure-of-8" axial appearance.
• Schizencephaly: Defined by gray matter-lined clefts extending from pial surface to ventricle; can be open-lip or closed-lip.
• Neural Tube Defects (e.g., anencephaly, myelomeningocele): Associated with ↑ maternal serum alpha-fetoprotein (AFP) levels during pregnancy.