CADASIL with Multiorgan Involvement: a Complete Autopsy Examination Report

Histopathological features of degeneration of the medial smooth muscle cells (SMCs) accompanied by deposition of periodic acid Schiff (PAS)-positive, electron dense granular osmiophilic material (GOM) in the small arteries and arterioles have been predominantly reported in autopsied brains and skin biopsies.2 Skin involvement in CADASIL is well known and a documented means of making the diagnosis other than genetic testing. Genetic testing consisted of bi-directional sequencing and polymerase chain reaction testing of the Notch3 gene exons 2 through 24, containing all 34 epidermal growth factor-like repeats of the Notch3 receptor protein. Figure 2 (a) Hematoxylin and eosin stained vessel showing no obvious vascular abnormalities; (b) Periodic acid-Schiff (PAS) staining showing PAS-positive, granular, osmiophilic material within the small and medium sized vessels; (c) Electron microscopic examination showing electron-dense, osmiophilic, granular deposits within the vessel walls; (d) Notch3 antibody highlighting the osmiophilic, PAS-positive granular material within the blood vessel wall. The Notch3 gene has been mapped on chromosome 19p13.1.3 Disease-causing mutations of the Notch3 gene are characterized by a loss or gain of cysteine residues located within the 23 exons (exons 2-24) that encode for the 34 epidermal growth factor (EGF)-like repeat domains of the Notch3 receptor.