Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL)

Abstract

This study was performed on a family of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) subjects. Neuropathological alterations of small arteries consisting in thickening, reduplication and fragmentation of the internal elastic lamella, and granular periodic acid-Schiff-positive material deposited in the arterial media were demonstrated in 1 autopsy case by histochemistry and electron microscopy. This material reacted with a monoclonal antibody anti-elastin (aE), as demonstrated by immunohistochemistry and immunoelectron microscopy. Significant increases of aE-immunoreactivity and elastin mRNA expression were found in cultured skin fibroblasts from 5 family members genetically affected by CADASIL, but not genetically and clinically healthy members. These results suggest that alterations of the elastic apparatus are associated with CADASIL genotype and related to the clinical expression of the disease.

Deep White Matter Hyperintensities, Decreased Serum Low-Density Lipoprotein, and Dilative Large Arteriopathy

“…16 Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which involves severe DWMHs, includes pathological alterations in the median and internal elastic lamella. 17 In addition, Fabry disease often accompanies SVDs, 18,19 and intracranial arterial dolichoectasia and dilative arteriopathy have been associated with Fabry disease. 20,21 Recent pathological findings in the brain in Fabry disease have demonstrated medial involvement, including smooth muscle cells together with the intima and adventitia.…”

Review: Molecular genetics and pathology of hereditary small vessel diseases of the brain

“…The severe arteriopathy is accompanied by the presence of granular osmiophilic material (GOM) in the arterial walls of both the brain and systemic organs [74], but the degenerative changes appear to be most severe in cerebral WM (Figure 1). Loss of arterial VSMCs is followed by fibrosis of the tunica media in small and medium‐sized penetrating arteries [11]; arteriosclerotic changes are concomitant with stenosis, especially at the arteriolar level, through intimal thickening and wall expansion with extracellular matrix components such as collagens, laminin and fibronectin [28,75] and compounded by altered protein–carbohydrate interactions [76–78]. These arterial changes likely reduce cerebral blood flow [40] and blood volume in affected WM with effects on the haemodynamic reserve by decreasing the vasodilatory response.…”

Thrombophilic risk factors and unusual clinical features in three Italian CADASIL patients

“…The mechanism leading from the Notch3 gene mutation to the clinical expression of the disease is unknown but it is hypothesized that the alterations of the small vessels seen in CADASIL patients play a key role in the pathogenesis of the disease (Ruchoux et al. , 1995; Caronti et al. , 1998).…”