CADASIL patient with extracellular calcium deposits

Area of Science:

• Neurology
• Pathology
• Genetics

Background:

• Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare genetic disorder.
• It affects small blood vessels in the brain and body, leading to stroke and cognitive decline.

Observation:

• A 57-year-old male patient diagnosed with CADASIL underwent skin-muscle biopsy.
• Ultrastructural analysis revealed typical CADASIL features like granular osmiophilic material (GOM) and vascular smooth muscle cell (VSMC) degeneration.
• Notably, abundant laminar calcium deposits were found in the basement membrane of microvessels and surrounding skeletal muscle fibers, a finding not previously described in CADASIL.

Findings:

• Degeneration of pericytes and endothelial cells led to mural cell loss and thickened basement membranes.
• Skeletal muscle arterioles showed VSMC vacuolization, nuclear abnormalities, and hyaline/calcium deposits.
• The extensive laminar calcifications represent a novel histopathological observation in CADASIL.

Implications:

• These findings expand the histopathological spectrum of CADASIL.
• Understanding these vascular changes may offer new insights into disease mechanisms and potential therapeutic targets.
• The study highlights the importance of detailed ultrastructural analysis in diagnosing and characterizing genetic angiopathies.