Macrocephaly

Susan I. Blaser, MD, FRCPC

DIFFERENTIAL DIAGNOSIS

Common

Benign Familial Macrocrania
Hydrocephalus and Obstructed CSF Spaces
- Intraventricular Hemorrhage
- Aqueductal Stenosis
- Arachnoid Cyst
- Enlarged Subarachnoid Spaces
- Villous Hypertrophy of the Choroid Plexus
- Subdural Hematoma, Chronic

Less Common

Dandy-Walker Continuum
Neoplasm
- Glioblastoma Multiforme
- Teratoma
Neurocutaneous Disorders
- Neurofibromatosis Type 1
- Tuberous Sclerosis Complex
Hemimegalencephaly
Megalencephaly Syndromes

Rare but Important

Hydranencephaly
Inborn Errors of Metabolism
- Glutaric Aciduria Type 1
- MLC1
- Mucopolysaccharidosis
- Alexander Disease
- Canavan Disease
Achondroplasia
Fibrous Dysplasia

ESSENTIAL INFORMATION

Key Differential Diagnosis Issues

Macrocephaly = head circumference > 2 standard deviations above mean for age-matched controls
Macrocephaly = macrocrania
Megalencephaly = subtype of macrocrania
Imaging infants/children with macrocephaly
- Hydrocephalus or white matter abnormality found? Use contrast!
Glutaric aciduria type 1 = child abuse mimic

Helpful Clues for Common Diagnoses

Benign Familial Macrocrania
- Family history important
Intraventricular Hemorrhage
- Hemosiderin not always apparent on follow-up images
Aqueductal Stenosis
- Look for associated hemosiderin, vascular anomalies
Arachnoid Cyst
- Steady-state acquisition sequence to identify cyst wall
Enlarged Subarachnoid Spaces
- Look for traversing veins
- Natural history: Resolution by 12-18 months
Villous Hypertrophy of the Choroid Plexus
- Likely on a spectrum, including choroid plexus papilloma
- Bilateral choroid plexus lesions typical
Subdural Hematoma, Chronic
- MR identifies hemorrhagic components

Helpful Clues for Less Common Diagnoses

Dandy-Walker Continuum
- Classic Dandy-Walker & Blake pouch cyst: Vermian angulation, large bony posterior fossa
- Classic Dandy-Walker
  - Incompletely lobulated vermis, deficient fastigial recess/primary fissure
- Blake pouch cyst
  - Intact vermis, fastigial recess, and primary fissure
Neoplasm
- Large, bulky neonatal tumors
- Glioblastoma Multiforme
  - Enhancement, necrosis, hemorrhage
- Teratoma
  - Fat, calcium, enhancing soft tissue
Neurofibromatosis Type 1
- Look for foci of abnormal signal intensity (FASI), optic nerve gliomas, café-au-lait spots
- Macrocrania predominantly derived from bulky white matter
Tuberous Sclerosis Complex
- Cutaneous markers (ash-leaf spots) may be occult in 1st year of life
- Look for Ca++ subependymal nodules, radial lines
Hemimegalencephaly
- Look for cutaneous markers & stigmata of overgrowth syndromes
  - Hypomelanosis of Ito
  - Proteus syndrome
  - Linear sebaceous nevus syndrome
Megalencephaly Syndromes
- Clues in name
  - Megalencephaly, polymicrogyria syndrome
  - Megalencephaly with dilated Virchow-Robin spaces
  - Cerebral gigantism (Soto syndrome)
  - Macrocrania-cutis marmorata telangiectatica congenita

Helpful Clues for Rare Diagnoses

Hydranencephaly
- Distinguish from maximal hydrocephalus
- MR shows cortex, falx
Glutaric Aciduria Type 1
- Bilateral temporal lobe hypoplasia & large sylvian fissures
- Resembles bilateral middle cranial fossa arachnoid cysts
- Crisis: Caudate, putamen, globus pallidus swelling, & ↑ signal
MLC1
- Diffusely ↑ white matter signal
- Temporal pole & frontoparietal cysts
- Macrocrania differentiates from CMV (common microcephaly)
Mucopolysaccharidosis
- Dilated perivascular spaces
Alexander Disease
- Enhancement is the key to diagnosis!
- Infant: Frontal swelling & ↑ signal & enhancement
- Juvenile: Brainstem foci of ↑ signal & enhancement
Canavan Disease
- MRS key: ↑ ↑ NAA
Achondroplasia
- Small skull base
  - Jugular foramina coarctation: CSF drainage impaired
  - Foramen magnum coarctation: Cervicomedullary compression
Fibrous Dysplasia
- Focal or diffuse (leontiasis ossea) may ↑ head circumference
- Classic radiograph/CT: Ground-glass
- MR (T2): Black velvet appearance

SELECTED REFERENCES

1. Colombani M et al: A new case of megalencephaly and perisylvian polymicrogyria with post-axial polydactyly and hydrocephalus: MPPH syndrome. Eur J Med Genet. 49(6):466-71, 2006

2. Groeschel S et al: Magnetic resonance imaging and proton magnetic resonance spectroscopy of megalencephaly and dilated Virchow-Robin spaces. Pediatr Neurol. 34(1):35-40, 2006

3. D’Ambrosio AL et al: Villous hypertrophy versus choroid plexus papilloma: a case report demonstrating a diagnostic role for the proliferation index. Pediatr Neurosurg. 39(2):91-6, 2003

4. Medina LS et al: Children with macrocrania: clinical and imaging predictors of disorders requiring surgery. AJNR Am J Neuroradiol. 22(3):564-70, 2001

5. Wilms G et al: CT and MR in infants with pericerebral collections and macrocephaly: benign enlargement of the subarachnoid spaces versus subdural collections. AJNR Am J Neuroradiol. 14(4):855-60, 1993

Image Gallery

Sagittal T1WI MR shows a normal-appearing corpus callosum and callosal isthmus

, gyral pattern, myelin maturation, and midline structures in this child with benign familial macrocrania.

Anteroposterior radiograph shows massive macrocrania in a child with untreated hydrocephalus.

(Left) Axial NECT shows massive tri-ventricular hydrocephalus. The choroid plexus dangles in the fluid

, and the massa intermedia

is stretched thin. (Right) Axial T2WI MR in a 27 week gestational age (corrected) premature infant shows an age-appropriate immature sulcal pattern. There is a small focus of ependymal hemosiderin

in the right trigone, a small clot

in the left.

(Left) Axial T2* GRE MR in an infant born prematurely with shunted hydrocephalus shows evidence of hemosiderin and volume loss in left caudothalamic groove