Cystic leukoencephalopathy without megalencephaly

Cystic leukoencephalopathy without megalencephaly, is an autosomal recessive inherited condition that manifests in the early childhood with moderate to severe psychomotor retardation and spasticity.

On imaging, it is characterized by bilateral anterior subcortical temporal lobe cysts and extensive multifocal white matter hyperintensities in a normal sized brain. 

Terminology 

The condition is also referred in the literature as leukoencephalopathy with bilateral anterior temporal lobe cysts and non-progressive leukoencephalopathy with bilateral anterior temporal cysts. However, those terms may cause confusion with the main differential diagnosis on imaging, which is megalencephalic leukoencephalopathy with subcortical cysts.

Clinical presentation

This is a non-progressive condition that manifests in the early childhood with psychomotor retardation and spasticity. Other commonly related symptoms are: seizures, spasticity, athetoid hand movements, dystonia, nystagmus, and hearing loss. Normocephaly or microcephaly on physical examination ². 

A variability in clinical phenotype has been observed, with patients having a normal cognitive function ³.

Pathology

The pathological basis of the defect remains to be defined. Genetic analyzes have shown that loss-of-function mutations in the gene RNASET2, encoding the RNASET2 glycoprotein, leads to cystic leukoencephalopathy without megalencephaly ⁴.

Radiographic features

MRI 

Typical MRI features in brain include bilateral anterior subcortical temporal lobe cystic lesions, with multifocal white matter hyperintensities, pericystic abnormal myelination and symmetric lesions in the periventricular regions, including the occipital lobes ^5-6.

History and etymology

It was first described by Olivier et al. in 1998 ¹.

Differential diagnosis

The differential diagnosis of cystic lesions of the temporal lobe are:

• with microcephaly:

  • congenital CMV infection

• normocephaly: 

  • congenital muscular dystrophy merosin negative

  • Aicardi-Goutieres syndrome

• with megalencephaly: 

  • megalencephalic leukoencephalopathy with subcortical cysts (also known as Van der Knaap disease).

Other differential diagnoses to include:

• leukoencephalopathy with vanishing white matter 

• leukodystrophies