Macrocephaly
Alexander J. Towbin, MD
DIFFERENTIAL DIAGNOSIS
Common
Benign Extracranial Collections of Infancy
Hydrocephalus
Child Abuse
Less Common
Neurofibromatosis Type 1
Vein of Galen Aneurysmal Malformation
Rare but Important
Tay-Sachs Disease
Alexander Disease
Canavan Disease
Krabbe Disease
Leigh Syndrome
ESSENTIAL INFORMATION
Key Differential Diagnosis Issues
Measurement of head circumference is part of typical well child check
Macrocrania is defined as head circumference > 95th percentile
Determinants of head circumference: Brain size, cerebral spinal fluid volume, and subdural spaces
Helpful Clues for Common Diagnoses
Benign Extracranial Collections of Infancy
a.k.a. benign hydrocephalus of infancy or external hydrocephalus
Characterized by excess cerebral spinal fluid (CSF) in subarachnoid space and macrocephaly
Excess fluid is more abundant overlying frontal lobes
Often family history of macrocephaly
Normal long-term development and no additional risk for hydrocephalus
Extraaxial collection resolves by age 2
Hydrocephalus
Incidence has declined along with decrease of open neural tube defects
2 main types: Communicating and noncommunicating
Communicating: Overproduction or underresorption of CSF
Obstructive: Intraventricular hemorrhage, aqueductal stenosis, and migrational abnormalities
Present with enlarging head, crossing percentiles
May have signs of ↑ intracranial pressure
Often treated with shunting
Child Abuse
Cranial trauma is most common cause of death in abuse
Most common cause of head trauma in children < 2 years
Mechanism of injury: Shaking and impact
Evaluation includes skeletal survey and head CT
Findings: Skull fracture, subdural hematomas of different ages, and brain edema
Helpful Clues for Less Common Diagnoses
Neurofibromatosis Type 1
Autosomal dominant disorder
Affects 1:3,000
Characteristic features: Café-au-lait macules, benign neurofibromas, plexiform neurofibromas, and iris hamartomas
Neurologic findings: Optic pathway gliomas, seizures, headache, hydrocephalus, and macrocephaly
Risk for central nervous system tumors: Astrocytomas, optic pathway gliomas
Vein of Galen Aneurysmal Malformation
Account for 1% of all intracranial vascular malformations
30% of vascular intracranial malformations in children
Ectatic vascular structure is median prosencephalic vein, not vein of Galen
Occurs due to direct communication between arterial network and median prosencephalic vein
After birth, increase in blood flow through malformation
Up to 80% of left ventricular output may supply brain
Leads to increased cardiac output and heart failure
Usually associated with other intracranial venous anomalies
Helpful Clues for Rare Diagnoses
Tay-Sachs Disease
Autosomal recessive disorder
More common in Ashkenazi Jews
Cause: Deficiency of β-hexosaminidase
Characterized by progressive weakness and loss of motor skills beginning at 2-6 months of age
Findings: ↑ startle response, hypotonia, hyperreflexia, and cherry red macule
Progressive neurodegeneration with macrocephaly
Macrocephaly due to accumulation of GM2 ganglioside
Alexander Disease
Demyelinating disorder characterized by Rosenthal fibers
Usually sporadic disorder
Types: Infantile, juvenile, and adult
Infantile form is most common
Characterized by macrocephaly, psychomotor retardation, muscle weakness, pyramidal tract signs, seizures
Average age of onset: 6 months
Juvenile form characterized by progressive paresis, bulbar signs, and brisk reflexes
Average age of onset: 9 years
Adult form: Intermittent neurologic disorders similar to multiple sclerosis
MR: Frontal lobe demyelination and cysts, ventriculomegaly, and poor gray-white differentiation
Canavan Disease
Autosomal recessive disorder
More common in Ashkenazi Jews
Cause: Inborn error of metabolism, deficiency of aspartoacylase enzyme
Leads to increased N-acetyl L-aspartate
Characterized by spongy degeneration of brain
Findings: Poor head control, macrocephaly, mental retardation, optic atrophy, and seizures
Krabbe Disease
Autosomal recessive disorder
Characterized by severe myelin loss
Cause: Deficiency of lysosomal enzyme galactosylceramidase
2 types: Early infantile or late onset
Most common: Early infantile (90%)
Leigh Syndrome
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