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. 2025 May 16;15(1):17113.
doi: 10.1038/s41598-025-00220-1.

Genetic and imaging features of CADASIL patients with acute ischemic stroke

Jae Young Park  1 , Jeong Yun Song  1 , Jun Young Chang  1 , Dong-Wha Kang  1 , Sun U Kwon  1 , Chong Hyun Suh  2 , Hyunjin Kim  1 , Jae-Sung Lim  1 , Satoshi Saito  3 , Sang Hee Ha #  4 , Bum Joon Kim #  5
Affiliations

Genetic and imaging features of CADASIL patients with acute ischemic stroke

Jae Young Park et al. Sci Rep. .

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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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This study protocol was reviewed and approved by from the Institutional Review Board of Asan medical center, approval number (2023 − 0381).

Figures

Fig. 1
Fig. 1
illustrates the distribution of (A) NOTCH 3 exon mutations and (B) EGFR mutations in patients with and without acute ischemic stroke among CADASIL patients. Orange bars represent patients who experienced acute ischemic stroke, while gray bars represent patients without acute ischemic stroke.
Fig. 2
Fig. 2
Kaplan-Meier analysis of stroke-free survival in CADASIL patients based on exon variants. This figure shows the probability of remaining stroke-free over time, stratified by genotype. The blue line represents patients with an Exon 11 NOTCH3 variant, while the green line represents patients with other variants.
See this image and copyright information in PMC

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