Susan I. Blaser, MD, FRCPC



  • 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-Goutieres

  • Progeroid Syndromes

    • Cockayne


Key Differential Diagnosis Issues

  • Was head circumference ever normal?

  • Decreased cranio-facial ratio on sagittal view helpful, tape measure best

Helpful Clues for Common Diagnoses

  • Hypoxic Ischemic Encephalopathy

    • 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

    • Agents most frequently causing microcephaly

      • Cytomegalovirus (CMV) most common by far

      • Rubella (now rare)

    • Look for cortical dysplasia, periventricular Ca++, hypomyelination (typically associated with CMV)

  • Nonaccidental Trauma

    • History is crucial

    • BUT look for evidence of trauma/fractures on ALL available films

    • Brain imaging

      • Global atrophy or hemiatrophy

      • Hemosiderin

  • Meningitis

    • Early infancy: Group B strep the 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, agenesis CC

    • Assess corpus callosum presence, size, shape

      • Is there an isthmus?

    • Holoprosencephaly

      • Most severe are the smallest

  • Cerebellar Hypoplasia

    • 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-Goutieres

      • Autosomal recessive, important to diagnose

      • Elevated CSF alpha-interferon

      • Early onset: TREX1 mutation

      • Late onset: RNASEH2B mutation

      • Imaging CMV-like

      • Ca++

      • Hypomyelination

      • Atrophy

  • Progeroid Syndromes

    • Cockayne

      • Cachectic dwarfism with mental retardation

      • Disorder of DNA repair

      • Several mutations known

      • Lack phenotype-genotype correlation

      • Facies & neuroimaging progressive

      • Basal ganglia/dentate Ca++

      • Demyelination

      • Atrophy


1. Gul A et al: Novel protein-truncating mutations in the aspm gene in families with autosomal recessive primary microcephaly. J Neurogenet. 21(3):153-63, 2007

2. Hassan MJ et al: Previously described sequence variant in CDK5RAP2 gene in a pakistani family with autosomal recessive primary microcephaly. BMC Med Genet. 2007

3. Kure-Kageyama H et al: A patient with simplified gyral pattern followed by progressive brain atrophy. Brain Dev. 29(6):383-6, 2007

4. Ornoy A et al: Fetal effects of primary and secondary cytomegalovirus infection in pregnancy. Reprod Toxicol. 21(4):399-409, 2006

5. Tang BL: Molecular genetic determinants of human brain size. Biochem Biophys Res Commun. 345(3):911-6, 2006

6. Sztriha L et al: Extreme microcephaly with agyria-pachygyria, partial agenesis of the corpus callosum, and pontocerebellar dysplasia. J Child Neurol. 20(2):170-2, 2005

7. Abdel-Salam GM et al: Aicardi-Goutieres syndrome: clinical and neuroradiological findings of 10 new cases. Acta Paediatr. 93(7):929-36, 2004

8. de Vries LS et al: The spectrum of cranial ultrasound and magnetic resonance imaging abnormalities in congenital cytomegalovirus infection. Neuropediatrics. 35(2):113-9, 2004

9. Riley EP et al: Teratogenic effects of alcohol: a decade of brain imaging. Am J Med Genet C Semin Med Genet. 127(1):35-41, 2004

Image Gallery

Coronal FLAIR MR shows cystic encephalomalacia image in the border zone distribution in this 3 year old with a history of peripartum prolonged partial asphyxia.

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Aug 7, 2016 | Posted by in NEUROLOGY | Comments Off on Microcephaly

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