Diagnostic value of ultrastructural skin biopsy studies in CADASIL

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) primarily affects vascular smooth muscle cells (VSMCs).1 The arterioles of the brain are the main target.1 Severe destruction of VSMCs leads to hypotonic cerebral arterioles and hemodynamic damage, responsible for MRI changes and clinical symptoms. The pathologic hallmark of the disease is extracellular deposition of granular osmiophilic material (GOM) in the tunica media, close to the basal membrane of the VSMCs. The nature of GOM is unclear, though it is thought to be derived from degenerating VSMCs. Although clinical symptoms are restricted to the CNS, extracerebral vessels may also be implicated in the pathologic process.1–4 This suggests that GOM in dermal arterioles could be used as a diagnostic marker.4 Though specific, this diagnostic procedure has a variable sensitivity ranging from 45% to 90%.1–4 In this work, we made a comparison between molecular genetic and ultrastructural skin biopsy studies in a series of