Periventricular Calcification

Susan I. Blaser, MD, FRCPC

DIFFERENTIAL DIAGNOSIS

Common

TORCH, General
- CMV, Congenital
- Toxoplasmosis, Congenital
- Herpes Encephalitis, Congenital
- HIV, Congenital
- Rubella, Congenital
Tuberous Sclerosis Complex

Less Common

Neurocysticercosis
Tuberculosis
Ventriculitis (Chronic)
Germinal Matrix Hemorrhage

Rare but Important

Radiation and Chemotherapy
Pseudo-TORCH
- Aicardi-Goutières Syndrome
- Coats-Plus Syndrome

ESSENTIAL INFORMATION

Key Differential Diagnosis Issues

Look for associations
- Brain destruction
- Malformations
- Other loci of calcification
- History

Helpful Clues for Common Diagnoses

TORCH, General
- Classic acronym for congenital infections
  - Caused by transplacental transmission of pathogens
  - TOxoplasmosis, Rubella, Cytomegalovirus, Herpes
  - All cause parenchymal Ca++
  - Most can cause lenticulostriate mineralization, vasculopathy
  - Some (CMV) cause migrational defects
  - Some (syphilis, herpes) cause meningitis, meningoencephalitis
  - Some (e.g., CMV) cause germinolytic cysts
  - Others (e.g., rubella, HSV) cause striking lobar destruction/encephalomalacia
- Congenital HIV, syphilis also considered part of TORCH
- Consider congenital HIV if bilateral symmetric basal ganglia C++ identified in child > 2 months old!
- If congenital infection is diagnostic consideration, obtain NECT to detect Ca++
CMV, Congenital
- Most common cause of intrauterine infection in USA
- Timing of infection predicts pattern of damage
- Hypomyelination
- Cortical gyral anomalies
- Microcephaly
- Symmetric periventricular Ca++ in 30-70%
Toxoplasmosis, Congenital
- Periventricular & scattered Ca++
- Hydrocephalus (colpocephaly-like)
Herpes Encephalitis, Congenital
- Calcification pattern varies in HSV2
  - Asymmetric periventricular
  - Scattered periventricular and deep gray
  - Subcortical white matter & cortex
  - Calcification pronounced in foci of hemorrhagic ischemia
  - Like rubella, rare cause of “stone brain”
- Brain atrophy or cystic encephalomalacia
  - Focal or diffuse
HIV, Congenital
- Vertical HIV infection
- Basal ganglia Ca++, atrophy
- Consider congenital HIV if bilateral symmetric basal ganglia C++ identified in child > 2 months old!
Rubella, Congenital
- Periventricular and scattered
- Scattered or hazy basal ganglia Ca++
- Rare “stone brain”
  - Extensive gyral calcification & gliosis
- Micro-infarcts
Tuberous Sclerosis Complex
- Look for cutaneous markers of TS
- Subependymal nodules
  - Variable-sized periventricular calcifications
- Cortical tubers also calcify

Helpful Clues for Less Common Diagnoses

Neurocysticercosis
- Best clue: Dot inside cyst
- Usually convexity subarachnoid space
- Also gray-white junction, intraventricular
- Nodular calcified (healed) stage
  - Shrinks to small Ca++ puncta or nodule
Tuberculosis
- Best diagnostic clue: Basal meningitis and pulmonary TB
- Acute
  - Typically basal meningitis
  - ± Localized CNS tuberculoma
- Chronic
  - Residual pachymeningeal
  - ± Localized Ca++
- “Target sign”
  - Calcification surrounded by enhancing rim (not specific)
Ventriculitis (Chronic)
- Areas of prior hemorrhagic infarction prone to dystrophic calcification
Germinal Matrix Hemorrhage
- Occasional ependymal, germinal matrix calcific foci

Helpful Clues for Rare Diagnoses

Radiation and Chemotherapy
- History!
- Mineralizing microangiopathy
Pseudo-TORCH
- Aicardi-Goutières Syndrome
  - “Mendelian mimic of congenital infection”
  - Multifocal punctate calcifications
  - Variable locations including periventricular white matter, basal ganglia, dentate nuclei
  - Elevated CSF interferon (IFN-α)
  - TREX1 mutations in some
- Coats-Plus Syndrome
  - a.k.a., cerebroretinal microangiopathy with calcifications and cysts (CRMCC)
  - Ocular coats: Retinal telangiectasia & exudate
  - CNS small blood vessel calcification
  - Extensive thalamic and gyral calcification
  - Defects of bone marrow & integument
  - Growth failure

SELECTED REFERENCES

1. Briggs TA et al: Cerebroretinal microangiopathy with calcifications and cysts (CRMCC). Am J Med Genet A. 146A(2):182-90, 2008

2. Crow YJ et al: Aicardi-Goutières syndrome: an important Mendelian mimic of congenital infection. Dev Med Child Neurol. 50(6):410-6, 2008

3. Rice G et al: Clinical and molecular phenotype of Aicardi-Goutieres syndrome. Am J Hum Genet. 81(4):713-25, 2007

4. Linnankivi T et al: Cerebroretinal microangiopathy with calcifications and cysts. Neurology. 67(8):1437-43, 2006

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

6. Malinger G et al: Fetal cytomegalovirus infection of the brain: the spectrum of sonographic findings. AJNR Am J Neuroradiol. 24(1):28-32, 2003

7. Numazaki K et al: Intracranial calcification with congenital rubella syndrome in a mother with serologic immunity. J Child Neurol. 18(4):296-7, 2003

8. Tanaka F et al: Association of osteopontin with ischemic axonal death in periventricular leukomalacia. Acta Neuropathol. 100(1):69-74, 2000

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