Genetic and imaging features of CADASIL patients with acute ischemic stroke

Abstract Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is caused by mutations in the NOTCH3 gene, is associated with early-onset strokes. However, the specific genetic and imaging characteristics associated with acute ischemic stroke (AIS...

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Main Authors: Jae Young Park, Jeong Yun Song, Jun Young Chang, Dong-Wha Kang, Sun U. Kwon, Chong Hyun Suh, Hyunjin Kim, Jae-Sung Lim, Satoshi Saito, Sang Hee Ha, Bum Joon Kim
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-00220-1
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author Jae Young Park
Jeong Yun Song
Jun Young Chang
Dong-Wha Kang
Sun U. Kwon
Chong Hyun Suh
Hyunjin Kim
Jae-Sung Lim
Satoshi Saito
Sang Hee Ha
Bum Joon Kim
author_facet Jae Young Park
Jeong Yun Song
Jun Young Chang
Dong-Wha Kang
Sun U. Kwon
Chong Hyun Suh
Hyunjin Kim
Jae-Sung Lim
Satoshi Saito
Sang Hee Ha
Bum Joon Kim
author_sort Jae Young Park
collection DOAJ
description Abstract Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is caused by mutations in the NOTCH3 gene, is associated with early-onset strokes. However, the specific genetic and imaging characteristics associated with acute ischemic stroke (AIS) in patients with CADASIL remain unclear. We reviewed CADASIL patients with NOTCH3 mutations, dividing them into two groups based on the presence of clinically relevant AIS lesions on diffusion-weighted imaging, observed at any time, regardless of the timing of CADASIL diagnosis. Clinical, imaging, and genetic features were compared between these groups. Genetic variations were categorized by exon location: specifically, exon 3 including Arg75Pro, and exon 11 including Arg544Cys, were examined in detail. Factors associated with AIS in CADASIL patients were analyzed. A total of 141 patients were included, of whom 70 (49.6%) were diagnosed with AIS. While there were no significant differences in vascular risk factors between the two groups, patients with AIS had a higher prevalence and greater number of lacunes (p < 0.001) and exhibited more severe white matter changes (p = 0.007). CADASIL patients with AIS had a higher rate of exon 3 variant and a lower rate of exon 11 variant compared to those without AIS. Multivariable analysis revealed that exon 11 variants were associated with a reduced risk (aOR = 0.270, 95% CI 0.099–0.733; p = 0.010). CADASIL who experienced AIS had unique genetic and imaging characteristics when compared to those who did not experience AIS.
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spelling doaj-art-dde55880ca31456ebe56f4cbe0cf9d322025-08-20T03:53:58ZengNature PortfolioScientific Reports2045-23222025-05-011511910.1038/s41598-025-00220-1Genetic and imaging features of CADASIL patients with acute ischemic strokeJae Young Park0Jeong Yun Song1Jun Young Chang2Dong-Wha Kang3Sun U. Kwon4Chong Hyun Suh5Hyunjin Kim6Jae-Sung Lim7Satoshi Saito8Sang Hee Ha9Bum Joon Kim10Departments of Neurology Asan Medical Center, University of Ulsan College of MedicineDepartments of Neurology Asan Medical Center, University of Ulsan College of MedicineDepartments of Neurology Asan Medical Center, University of Ulsan College of MedicineDepartments of Neurology Asan Medical Center, University of Ulsan College of MedicineDepartments of Neurology Asan Medical Center, University of Ulsan College of MedicineDepartment of Neurology and Radiology Asan Medical Center, University of Ulsan College of MedicineDepartments of Neurology Asan Medical Center, University of Ulsan College of MedicineDepartments of Neurology Asan Medical Center, University of Ulsan College of MedicineDepartment of Neurology, National Cerebral and Cardiovascular CenterDepartement of Neurology, Gil Medical Center, Gachon UniversityDepartments of Neurology Asan Medical Center, University of Ulsan College of MedicineAbstract Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is caused by mutations in the NOTCH3 gene, is associated with early-onset strokes. However, the specific genetic and imaging characteristics associated with acute ischemic stroke (AIS) in patients with CADASIL remain unclear. We reviewed CADASIL patients with NOTCH3 mutations, dividing them into two groups based on the presence of clinically relevant AIS lesions on diffusion-weighted imaging, observed at any time, regardless of the timing of CADASIL diagnosis. Clinical, imaging, and genetic features were compared between these groups. Genetic variations were categorized by exon location: specifically, exon 3 including Arg75Pro, and exon 11 including Arg544Cys, were examined in detail. Factors associated with AIS in CADASIL patients were analyzed. A total of 141 patients were included, of whom 70 (49.6%) were diagnosed with AIS. While there were no significant differences in vascular risk factors between the two groups, patients with AIS had a higher prevalence and greater number of lacunes (p < 0.001) and exhibited more severe white matter changes (p = 0.007). CADASIL patients with AIS had a higher rate of exon 3 variant and a lower rate of exon 11 variant compared to those without AIS. Multivariable analysis revealed that exon 11 variants were associated with a reduced risk (aOR = 0.270, 95% CI 0.099–0.733; p = 0.010). CADASIL who experienced AIS had unique genetic and imaging characteristics when compared to those who did not experience AIS.https://doi.org/10.1038/s41598-025-00220-1
spellingShingle Jae Young Park
Jeong Yun Song
Jun Young Chang
Dong-Wha Kang
Sun U. Kwon
Chong Hyun Suh
Hyunjin Kim
Jae-Sung Lim
Satoshi Saito
Sang Hee Ha
Bum Joon Kim
Genetic and imaging features of CADASIL patients with acute ischemic stroke
Scientific Reports
title Genetic and imaging features of CADASIL patients with acute ischemic stroke
title_full Genetic and imaging features of CADASIL patients with acute ischemic stroke
title_fullStr Genetic and imaging features of CADASIL patients with acute ischemic stroke
title_full_unstemmed Genetic and imaging features of CADASIL patients with acute ischemic stroke
title_short Genetic and imaging features of CADASIL patients with acute ischemic stroke
title_sort genetic and imaging features of cadasil patients with acute ischemic stroke
url https://doi.org/10.1038/s41598-025-00220-1
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