Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in a Chinese pedigree: A case report using brain magnetic resonance imaging and biospy

Abstract

The present study enrolled a Chinese family that comprised 34 members and spanned three generations. Eight members were diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and disease diagnoses corresponded with autosomal incomplete dominance inheritance. The primary clinical manifestations included paralysis, dysarthria, and mild cognitive deficits. Magnetic resonance imaging revealed diffuse leukoencephalopathy with involvement of bilateral anterior temporal lobes, in particular the pons. In addition, multiple cerebral infarction was identified in the proband. Sural nerve biopsy findings of the proband revealed granular osmophilic material deposits in the extracellular matrix, which were adjacent to smooth muscle cells of dermal arterioles. Screening exons 2-4 for NOTCH 3 mutations by direct sequencing did not reveal any abnormalities.

Keywords: NOTCH 3; cerebral autosomal dominant arteriopathy; dysarthria; granular osmophilic material; leukoencephalopathy; paresis; subcortical infarcts.

Figure 1

Pedigree chart of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy family from three generations with eight affected members.

Figure 2

Brain magnetic resonance images from the 41-year-old proband. On T2-weighted images, there are symmetric hyperintense signals in white matter from both temporal lobes (C), as well as an abnormal high signal in the brain stem and genu of callosum (A, B, D). Diffuse hyperintense signal is seen in the subcortical and deep white matter on fluid-attenuated inversion recovery sequence. The red arrows point to multiple brain lesions. R: Right.

Figure 3

Sural nerve biopsy findings of the proband at 41 years of age. Granular osmophilic material deposits are visible in the extracellular matrix adjacent to smooth muscle cells of dermal arterioles (A, × 25 000) and within smooth muscle cells of dermal arterioles (B, × 30 000). Black deposits are marked by arrows.