Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) – literature review apropos an autopsy case

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a non-atherosclerotic, non-amyloid cerebral angiopathy involving small arteries and arterioles. This entity presents vascular changes in the form of smooth muscle degeneration with swollen myocytes and PAS-positive granular deposits, together with vascular fibrosis and hyalinization. In parallel, diffuse white matter destruction with infarcts, tissue rarefaction, spongiosis, lacunes and demyelination are characteristic. Ultrastructurally, vascular granular osmiophilic material (GOM) is pathognomonic for this hereditary disease caused by NOTCH3 mutation.

We diagnosed CADASIL in the autopsy examination of a 53-year-old woman with a 9-year history of a progressive neurological disease with complex motor and cognitive deficits, accompanied by non-specific diffuse white matter changes on neuroimaging. Despite several multicentre hospitalizations, the precise diagnosis was not established until the post-mortem examination of the brain was made.

CADASIL is a rare entity, but it should be considered by a pathologist in a differential diagnosis of vascular diseases of the brain, especially in cases with atypical clinical presentation and familial history. The prompt diagnosis depends on the quality of the brain autopsy and proper sampling. The post mortem examination, where “Morituri vivos docent”, is still significant.