Congenital malformations of the central nervous system

1. Neural Tube Defects (NTDs)

Overview

• Most frequent group of CNS malformations.
• Neurulation: ectoderm thickens → neural plate → folding + closure → neural tube.
• Failure of closure or reopening → several malformations.

Etiology

• Folic acid deficiency in early pregnancy (most important modifiable cause).
• Genetic defects.
• Maternal serum α-fetoprotein (AFP) elevated → screening test.
• Maternal DM, valproate.

2. Defects of Posterior Neuropore Closure

A) Spina Bifida Occulta

• Occulta = hidden.
• Small gap in spine (failure of vertebral arch fusion).
• Usually asymptomatic.
• May have overlying tuft of hair, dimple, lipoma.

B) Meningocele

• Sac of fluid (cyst-like) in spine.
• Spinal cord NOT in sac (only meninges).

C) Myelomeningocele

• Most serious type (open spina bifida).
• Cyst-like structure containing spinal cord + nerves protrudes through defect.
• Causes motor + sensory disabilities → poor ability to walk + impaired bladder/bowel control.
• Associated with Arnold-Chiari II malformation.

3. Defects of Anterior Neuropore Closure

A) Anencephaly

• Absence of brain + top of skull.
• Malformation of anterior end of neural tube.
• Incompatible with life (stillborn or dies shortly after birth).
• Maternal ↑↑ AFP + polyhydramnios.

B) Encephalocele

• Diverticulum of malformed CNS tissue extending through a defect in the cranium.
• Often occipital.

4. Forebrain Malformations

A) Megalencephaly + Microencephaly

• Brain volume abnormally large (megalencephaly) or small (microencephaly).
• Microencephaly usually associated with microcephaly (small head).
• Causes: chromosomal abnormalities, fetal alcohol syndrome, HIV, intrauterine infections.
• Pathology: ↓ number of neurons destined for cerebral cortex.

B) Lissencephaly + Pachygyria

• Lissencephaly (agyria) = absence of normal gyration → smooth-surfaced brain.
• Pachygyria = more patchy involvement.
• Cortex abnormally thickened and usually only 4-layered (normal = 6).

C) Polymicrogyria

• ↑ Number of irregularly formed gyri → bumpy or cobblestone-like surface.
• Focal or widespread.

D) Holoprosencephaly

• Disruption of normal midline patterning.
• Mild: absence of olfactory bulbs.
• Severe: brain not divided into hemispheres (single ventricle).
• Associated with trisomy 13, fetal alcohol syndrome.
• Facial midline defects: cleft lip/palate, cyclopia.

5. Posterior Fossa Malformations

Most common: misplaced or absent cerebellum. Typically associated with hydrocephalus.

A) Chiari Type I

• Low-lying cerebellar tonsils extend through foramen magnum.
• → Obstruction of CSF flow + compression of medulla.
• May be associated with syringomyelia.
• Often diagnosed in adults; headaches, gait issues.

B) Chiari Type II (Arnold-Chiari Malformation)

• Small posterior fossa + misshapen midline cerebellum with downward extension of vermis into foramen magnum.
• Hydrocephalus + tectum deformation typically present.
• Strongly associated with myelomeningocele.

C) Dandy-Walker Malformation

• Enlarged posterior fossa + hypoplastic/absent cerebellar vermis.
• Cystically dilated 4th ventricle.
• Associated with hydrocephalus.

6. Perinatal Brain Damage

Causes

• Prematurity:
  • Intraparenchymal hemorrhage from germinal matrix.
  • Intraventricular hemorrhage.
  • Periventricular leukomalacia (necrosis of white matter near ventricles).
• Intrauterine infections → TORCH (Toxoplasma, Other [syphilis], Rubella, CMV, Herpes/HIV).

Clinical Features

• Cerebral palsy (Little’s disease):
  • Non-progressive motor deficits, not present at birth.
  • Spasticity, dystonia, ataxia, athetosis, paresis.

7. Spinal Cord Malformations

• Hydromyelia: expansion of ependymal-lined central canal of spinal cord.
• Syringomyelia: fluid-filled cleft-like cavity in inner spinal cord (often C-T region).
  • Classically presents with cape-like loss of pain + temperature sensation (spinothalamic decussation affected) with preserved touch/proprioception.
• Both: destroy adjacent gray + white matter → reactive gliosis.
• Associated with Chiari I.

8. Summary Table

Malformation	Defect	Key features
Spina bifida occulta	Posterior NT closure	Hidden, asymptomatic, tuft of hair
Meningocele	Posterior NT closure	Meninges in sac; cord intact
Myelomeningocele	Posterior NT closure	Cord + nerves in sac; disabilities
Anencephaly	Anterior NT closure	No brain/skull; fatal; ↑↑ AFP
Encephalocele	Anterior NT closure	CNS tissue herniates through cranial defect (occipital)
Holoprosencephaly	Midline forebrain split fails	Trisomy 13, FAS, cyclopia, cleft lip
Lissencephaly	Cortical migration	Smooth brain, 4-layer cortex
Chiari I	Tonsils through foramen magnum	Adult headache; syringomyelia
Chiari II (Arnold-Chiari)	Small post fossa, vermis through FM	Myelomeningocele + hydrocephalus
Dandy-Walker	Vermis hypoplasia	Enlarged post fossa + cystic 4th ventricle
Syringomyelia	Spinal cord cyst	Cape-like ↓ pain/temp sensation; Chiari I
Cerebral palsy	Perinatal injury	Non-progressive motor deficits; prematurity + TORCH

💡 High-yield: Folic acid deficiency = #1 modifiable cause of NTDs; ↑ maternal serum AFP. Spina bifida: occulta (hidden) → meningocele (meninges only) → myelomeningocele (cord + nerves; ↑ AFP). Anencephaly = no brain/skull, fatal. Holoprosencephaly = midline fails, trisomy 13, cyclopia, FAS. Lissencephaly = smooth brain. Chiari I = adult; tonsils through FM; syringomyelia (cape-like ↓ pain/temp). Chiari II (Arnold-Chiari) = myelomeningocele + hydrocephalus. Dandy-Walker = absent vermis + cystic 4th ventricle. Cerebral palsy = non-progressive motor deficit from prematurity/TORCH.