Intracranial calcification in children - clues to etiology

 

This was a 5 month old baby boy who presented with developmental delay and seizures. He was born term with no perinatal asphyxia but weighed just 1.5 Kg at birth. His MRI brain at 5 months had right frontal pachygyria, cerebellar hypoplasia, white matter asymmetric hyperintentsities on FLAIR/T2 and CT Brian showed periventricular  and basal ganglia calcification.

Our first possibility of course was congenital CMV infection. But he was already 5 months old, his urine PCR for CMV was negative. And the big question was - Can the pattern of calcification alone predict etiology?

I sat down to understand this further. There were some useful tips I learnt. 

You need to ask some questions:

1. Is it calcification? Make sure you are not looking at haemorrhage, iron or manganese which can look similar.

Generally CT will pick up calcification much better than MRI brain. However SWI images are probably as good as CT. SWI wins over CT because it can differentiate bleeds form calcium. This happens in the phase images of SWI not the routine magnitude images. In corrected phase images calcium appears bright and blood appears dark. https://doi.org/10.1007/s13244-011-0086-3

2. Is it metastatic calcification as seen in hypo/hyperparathyroidism or dystrophic calcification ( seen in a range of brain injuries)?

Metastatic calcification due to disorders in parathyroid metabolism will have a symmetric basal ganglia, thalamic calcification with sometimes deep gyral calcification.

3. What is the pattern of calcification?

Is it dot like, linear, conglomerate masses, rock like, blush or gyrinform band like? For eg congenital CMV patients will often have nodular mass like calcification in the periventricular region but dot like pattern in the basal ganglia. Most intra-axial tumours have nodular, clumped mass like lesions. A cyst with an eccentric dot of calcification is likely to be neurocysticerscosis and a central dot of calcification is seen in tuberculomas. The gyriform calcification of Sturge Webers is unmistakable. https://dx.doi.org/10.3941%2Fjrcr.v13i8.3633

4. Where is the calcification?

Characteristic locations sometimes help to nail the etiology. Calcification in the pineal gland and choroid plexus is often physiological. Cerebellar calcification is a clue to SLE, neurosarcoidosis and neurofibromatosis. True periventricular calcification is common in congenital CMV. Krabbes disease has a peculiar internal capsule and corona radiata calcification. Subependymal calcified nodules are typical of tuberous sclerosis.

5. Are there associated brain malformations? 

Presence of cysts along with calcification is seen in congenital CMV, RNASET2 disease, COATS plus disease and COL4A mutations ( porencephaly). https://doi.org/10.1111/dmcn.12359

While cortical malformations like polymcrogyria are common with congenital CMV, it is unknown with its closest mimic Aicardi Gautiere Syndrome. True periventricular calcification is also uncommon in AGS.

My patient was finally found to have chorioretinitis typical of CMV and so we deferred further genetic testing!