Microcephaly

Susan I. Blaser, MD, FRCPC

DIFFERENTIAL DIAGNOSIS

Common

Secondary/Acquired from
- Hypoxic Ischemic Encephalopathy
- TORCH Infections
- Nonaccidental Trauma
- Meningitis
- Fetal Alcohol Syndrome

Less Common

Primary/Genetic with
- Gyral Simplification
- Cortical Dysplasia
- Midline Anomaly
- Cerebellar Hypoplasia
- Hypomyelination

Rare but Important

Microlissencephaly
Pseudo-TORCH
- Aicardi-Goutières
Progeroid Syndromes
- Cockayne

ESSENTIAL INFORMATION

Key Differential Diagnosis Issues

Was head circumference ever normal?
Decreased cranio-facial ratio on sagittal view helpful, tape measure best
Do not disregard nonaccidental trauma as cause of small head

Helpful Clues for Common Diagnoses

Hypoxic Ischemic Encephalopathy
- Perinatal or birth asphyxia (asphyxia neonatorium)
- Patterns helpful, even if no history
- Profound: Atrophy, gliosis
  - Posterior putamen
  - Lateral thalami
  - Rolandic cortex
- Prolonged progressive
  - Typical watershed encephalomalacia
- Mixed
  - Features of both, ± calcified thalami
TORCH Infections
- Cytomegalovirus (CMV) (common) and rubella (rare, today) most likely to have microcephaly
- Toxo, CMV, HIV, and rubella may have intracranial Ca++, which may help in determining underlying etiology
  - CMV: Parenchymal or periventricular Ca++
  - HIV: Basal ganglia and subcortical calcifications
  - Toxo: Parenchymal or periventricular Ca++
  - Rubella and HSV cause lobar brain destruction/encephalomalacia
  - CMV may also have cortical dysplasia, periventricular Ca++, hypomyelination
Nonaccidental Trauma
- History is crucial
  - Majority of abuse in children < 1 year old
  - Most common in children 2-6 months old
  - After trauma: Subarachnoid and subdural hemorrhages are common
  - Subdural hemorrhage over convexity, interhemispheric, overlying tentorium
  - Caution in attempting to determine age of subdural hemorrhage
- BUT look for evidence of trauma/fractures on ALL available films
- Brain imaging of microcephaly
  - Global atrophy or hemiatrophy
  - Hemosiderin
Meningitis
- Early infancy: Group B strep most damaging
  - Hypothalamus
  - Chiasm
  - Inferior basal ganglia
  - Diffuse cortex, often asymmetric
Fetal Alcohol Syndrome
- Microcephaly
  - By tape measure
  - Or MR volumetrics
  - Anomalies may occur, but not specific
- Diffusion tensor imaging (DTI) reported to show abnormal connectivity

Helpful Clues for Less Common Diagnoses

Gyral Simplification
- Small, grossly normal brain
- Looks like “small but perfect” brain
- Corpus callosum may appear thick, lack isthmus
Cortical Dysplasia
- Any severe, diffuse dysplasia
  - Lissencephaly
  - Pachygyria
Midline Anomaly
- Holoprosencephaly
  - Most severe are smallest
- Agenesis of corpus callosum
  - Assess corpus callosum presence, size, shape
  - Is there isthmus?
Cerebellar Hypoplasia
- In multiple syndromes
  - Olivopontocerebellar degeneration
  - Spinocerebellar ataxia
  - Carbohydrate deficient glycoprotein syndrome type 1a
- May be clue to rare disorders
  - Microlissencephaly
  - TUBA1A mutations: Lissencephaly PLUS cerebellar hypoplasia
- Assess degree of deficiency
  - Fastigial recess, primary fissure
  - Degree of vermian lobulation
  - Tegmento-vermian angle (is the inferior 4th ventricle open?)
Hypomyelination
- May be a clue to rare disorders
  - Early onset West syndrome with cerebral hypomyelination and reduced white matter
  - 3-phosphoglycerate dehydrogenase deficiency
  - Progressive encephalopathy, edema, hypsarrhythmia, optic atrophy (PEHO)

Helpful Clues for Rare Diagnoses

Microlissencephaly
- Z-shaped brainstem
- Callosal agenesis
- Surface often totally smooth
- Very small brain
Pseudo-TORCH
- Aicardi-Goutières
- CMV-like: Ca++
- Hypomyelinaton
- Atrophy
- Autosomal recessive, important to diagnose
- Elevated CSF α-interferon
- Early onset: TREX1 mutation
- Late onset: RNASEH2B mutation
Progeroid Syndromes
- Cockayne
  - Cachectic dwarfism with mental retardation
  - Disorder of DNA repair: Several mutations known, but lack phenotype-genotype correlation
  - Facies & neuroimaging progressive
  - Basal ganglia/dentate Ca++
  - Demyelination
  - Atrophy