{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:20:46Z","timestamp":1790742046402,"version":"4.1.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>\n              Intracerebral hemorrhage (ICH) is increasingly recognized in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, especially in Asian patients with the\n              <jats:italic toggle=\"yes\">NOTCH3<\/jats:italic>\n              R544C variant. The associations between ICH,\n              <jats:italic toggle=\"yes\">NOTCH3<\/jats:italic>\n              variants, and hypertension remain unclear.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>We enrolled patients from 2 independent cohorts with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in France (recruited since 2003) and Taiwan (recruited since 2019) and performed a cross-sectional retrospective analysis. Clinical history and evaluation were collected using standardized questionnaires and scales, while neuroimaging features were assessed with the CADA-MRIT inventory tool. Patients with and without a history of ICH were compared. Logistic regression and mediation analyses were conducted to identify factors associated with ICH.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Of 552 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (440 from France and 112 from Taiwan), 34 (6.2%) had a history of ICH. Patients with ICH were older (62.9\u00b111.4 versus 53.4\u00b112.3 years), had a higher proportion of the\n              <jats:italic toggle=\"yes\">NOTCH3<\/jats:italic>\n              R544C variant (79.4% versus 15.3%), and had hypertension (85.3% versus 24.9%). Analysis of magnetic resonance imaging data showed that they had more cerebral microbleeds, worse cerebral atrophy, and higher number of dilated perivascular spaces in basal ganglia. Hypertension (odds ratio, 7.90 [95% CI, 2.83\u201322.08]) and\n              <jats:italic toggle=\"yes\">NOTCH3<\/jats:italic>\n              R544C variant (odds ratio, 9.91 [95% CI, 3.84\u201325.57]) were each independently associated with ICH, while no multiplicative interaction was detected between these 2 factors (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              <jats:sub>interaction<\/jats:sub>\n              =0.81). Having both\n              <jats:italic toggle=\"yes\">NOTCH3<\/jats:italic>\n              R544C variant and hypertension carried an additive effect on the risk of ICH (36.9% if both present, 8.8% if having\n              <jats:italic toggle=\"yes\">NOTCH3<\/jats:italic>\n              R544C variant without hypertension, 5.4% if having hypertension without\n              <jats:italic toggle=\"yes\">NOTCH3<\/jats:italic>\n              R544C variant, and 0.6% if both absent;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              <jats:sub>trend<\/jats:sub>\n              &lt;0.001). Finally, in the mediation analysis, 49.9% of the effects of the\n              <jats:italic toggle=\"yes\">NOTCH3<\/jats:italic>\n              R544C variant on the occurrence of ICH would be explained by the effects of hypertension.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>\n              Both the\n              <jats:italic toggle=\"yes\">NOTCH3<\/jats:italic>\n              R544C variant and hypertension appear to be independent risk factors for ICH in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, with a potential additive effect. However, due to the study\u2019s cross-sectional design and population-specific factors, causality cannot be established. Prospective studies are thus needed to validate these findings and clarify underlying mechanisms.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.124.050484","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T05:00:15Z","timestamp":1745470815000},"page":"2159-2166","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Intracerebral Hemorrhage in Patients With CADASIL: Additive Impact of the\n            <i>NOTCH3<\/i>\n            R544C Variant and Hypertension?"],"prefix":"10.1161","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1258-8775","authenticated-orcid":true,"given":"Chih-Hao","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurology, National Taiwan University Hospital, Neurology, Taipei (C.-H.C., Y.-W.C., S.-C.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3054-6333","authenticated-orcid":true,"given":"Yu-Wen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Taiwan University Hospital, Neurology, Taipei (C.-H.C., Y.-W.C., S.-C.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China (R.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2866-4330","authenticated-orcid":true,"given":"Sophie","family":"Tezenas Du Montcel","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Paris Brain Institute, Inria, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), France (S.T.D.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6096-3595","authenticated-orcid":true,"given":"St\u00e9phanie","family":"Guey","sequence":"additional","affiliation":[{"name":"Lariboisi\u00e8re Hospital, AP-HP, Universit\u00e9 Paris Cit\u00e9 and INSERM U1161, Federation Hospitalo-Universitaire (FHU) NeuroVasc, France (S.G., D.H., H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6197-6275","authenticated-orcid":true,"given":"Dominique","family":"Herv\u00e9","sequence":"additional","affiliation":[{"name":"Lariboisi\u00e8re Hospital, AP-HP, Universit\u00e9 Paris Cit\u00e9 and INSERM U1161, Federation Hospitalo-Universitaire (FHU) NeuroVasc, France (S.G., D.H., H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3731-5973","authenticated-orcid":true,"given":"Sung-Chun","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Taiwan University Hospital, Neurology, Taipei (C.-H.C., Y.-W.C., S.-C.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8436-6074","authenticated-orcid":true,"given":"Hugues","family":"Chabriat","sequence":"additional","affiliation":[{"name":"Lariboisi\u00e8re Hospital, AP-HP, Universit\u00e9 Paris Cit\u00e9 and INSERM U1161, Federation Hospitalo-Universitaire (FHU) NeuroVasc, France (S.G., D.H., 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