Multimodal imaging analyses in patients with genetic and sporadic forms of small vessel disease

Ko Woon Kim,Yong Bum Kim,Won Tae Yoon,Jong Min Lee,Young Chul Youn,Yeo Jin Kim,Gyeong-Moon Kim,Chin-Sang Chung,Cindy W Yoon,Young Eun Kim ,Marco Duering,Hee Jin Kim,Hyemin Jang,Yeshin Kim,Byoung‐Soo Shin ,Jin San Lee,Hyuk-Min Kwon ,Seungjoo Kim ,Hanna Cho,Duk L Na,Yong Suk Jang ,Chang‐Seok Ki ,Oh Young Bang,Sang Won Seo

doi:10.1038/s41598-018-36580-0

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is thought to be a pure genetic form of subcortical vascular cognitive impairment (SVCI). The aim of this study was to compare white matter integrity and cortical thickness between typical CADASIL, a genetic form, and two sporadic forms of SVCI (with NOTCH3 and without NOTCH3 variants). We enrolled typical CADASIL patients (N = 11) and SVCI patients [with NOTCH3 variants (N = 15), without NOTCH3 variants (N = 101)]. To adjust the age difference, which reflects the known difference in clinical and radiologic courses between typical CADASIL patients and SVCI patients, we constructed a W-score of measurement for diffusion tensor image and cortical thickness. Typical CADASIL patients showed more frequent white matter hyperintensities in the bilateral posterior temporal region compared to SVCI patients (p < 0.001, uncorrected). We found that SVCI patients, regardless of the presence of NOTCH3 variants, showed significantly greater microstructural alterations (W-score, p < 0.05, FWE-corrected) and cortical thinning (W-score, p < 0.05, FDR-corrected) than typical CADASIL patients. In this study, typical CADASIL and SVCI showed distinct anatomic vulnerabilities in the cortical and subcortical structures. However, there was no difference between SVCI with NOTCH3 variants and SVCI without NOTCH3 variants.

Highlights

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is thought to be a pure genetic form of subcortical vascular cognitive impairment (SVCI)
Typical CADASIL patients showed more frequent white matter hyperintensities in the bilateral posterior temporal region compared to SVCI patients (p < 0.001, uncorrected)
We found that SVCI patients, regardless of the presence of NOTCH3 variants, showed significantly greater microstructural alterations (W-score, p < 0.05, FWE-corrected) and cortical thinning (W-score, p < 0.05, false discovery rate (FDR)-corrected) than typical CADASIL patients

Summary

Introduction

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is thought to be a pure genetic form of subcortical vascular cognitive impairment (SVCI). The aim of this study was to compare white matter integrity and cortical thickness between typical CADASIL, a genetic form, and two sporadic forms of SVCI (with NOTCH3 and without NOTCH3 variants). Mutant NOTCH3 receptors have been proposed to induce the deposition of granular osmiophilic material (GOM) in vascular smooth muscle cells in the small arterioles This leads to ischemia in the white matter, Research Design and Evaluation, Seoul, Korea. Previous neuroimaging studies have shown that patients with typical CADASIL and SVCI exhibit white matter microstructural changes[16,17,18] and cortical thinning compared to healthy controls[19,20,21]. Our studies showed that SVCI patients exhibited cortical thinning in the frontal, perisylvian, basal temporal, and posterior cingulate regions compared with healthy controls[18,20,21]. CADASIL and SVCI have not been directly and comprehensively compared

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