Leukoencephalopathy with calcifications and cysts

Dr Henry Knipe ◉ ◈ and Dr Dylan Kurda et al.

Leukoencephalopathy with calcifications and cysts, also known as Labrune syndrome, is a rare condition that consists of a triad of leukoencephalopathy, cerebral calcifications and oedematous cysts.

Leukoencephalopathy with calcifications and cysts is an extremely rare condition, with only a small number of cases reported in the literature ^2,5. Clinical onset occurs from early infancy to late adulthood, with most cases being diagnosed in children to young adults. A modest predilection for females appears to be present (F:M 3:2) ⁵.

Clinical presentation

Leukoencephalopathy with calcifications and cysts can present with a variety of symptoms depending on cyst location and degree of intracranial hypertension. Symptoms include headaches, slowing of cognitive performance, seizures, visual disturbance and a combination of extrapyramidal, cerebellar, and pyramidal features ^1,5.

Pathology

The underlying pathophysiology is thought to be a diffuse cerebral microangiopathy resulting in initially microcystic, followed by macrocystic, parenchymal degeneration ¹.

Histological features include tumour-like vascular hyperplasia, calcification, Renshaw cell proliferation, Rosenthal fibres and glial proliferation ⁵. A variety of other histological features are also encountered including demyelination, necrosis, iron deposition and haemorrhage ^5,6.

Genetics

Leukoencephalopathy with calcifications and cysts has been associated with mutations in the SNORD118 gene ⁴.

Radiographic features

CT

CT is the modality of choice for demonstrating calcifications, where progressive calcifications in the basal ganglia and cerebellar nuclei, as well as the subcortical white matter, are invariably seen ⁵.

MRI

MRI is the modality of choice for demonstrating the leukoencephalopathy and cysts ^3,5.

cysts
- location:
  - supratentorial white matter: centrum semiovale most common
  - cerebellum
  - brainstem
  - basal ganglia
- T1: hypointense, but brighter than CSF ³
- T2: hyperintense, but brighter than CSF, with FLAIR suppression evident - hyperintensity if presumably due to the absence of flow-induced signal loss ³
- DWI: may show increased diffusion signal
- T1 C+ (Gd)
  - ring enhancement of the cyst wall may be evident
  - probably reflecting disruption of the blood-brain barrier ^1,3,5
leukoencephalopathy
- T2/FLAIR: diffuse hyperintensity in the white matter, especially prominent around cysts (due to vasogenic oedema), with relative sparing of the subcortical U-fibres and corpus callosum ³
calcifications
- T1: often hypointense, but can be variable ³
- T2/FLAIR: hypointense ³
- SWI: hypointense with blooming artefact ³

MR spectroscopy of the cysts may demonstrate a lactate peak and no evidence of the normal metabolites of the brain ³.

Treatment and prognosis

Disease progression is variable in the cases reported in the literature. To date, no specific treatment is available although medical management of epilepsy, oedema and raised intracranial pressure is often required ⁵. Surgical pressure management is also sometimes needed ⁵.