{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:09:24Z","timestamp":1792087764088,"version":"4.4.0"},"reference-count":44,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:sec id=\"ab-noi240081-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>\n                      Typical cysteine-altering\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      (\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      <jats:sup>cys<\/jats:sup>\n                      ) variants are highly prevalent (approximately 1 in 300 individuals) and are associated with a broad spectrum of small vessel disease (SVD), ranging from early-onset stroke and dementia (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [CADASIL]) to nonpenetrance. A staging system that captures the full\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      -SVD severity spectrum is needed and currently lacking.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi240081-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To design a simple disease severity staging system that captures the broad clinicoradiological\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      -SVD severity spectrum.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi240081-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>\n                      A cohort study was performed in which the\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      -SVD severity staging system was developed using a discovery cohort (2019-2020) and validated in independent international CADASIL cohorts (1999-2023) and the UK Biobank. Clinical and imaging data were collected from participants originating from 23 international CADASIL cohorts and from the UK Biobank. Eligibility criteria were presence of a\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      <jats:sup>cys<\/jats:sup>\n                      variant, availability of brain magnetic resonance imaging, and modified Rankin Scale score. The discovery cohort consisted of 195\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      <jats:sup>cys<\/jats:sup>\n                      -positive cases from families with CADASIL; the validation set included 1713\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      <jats:sup>cys<\/jats:sup>\n                      -positive cases from 15 countries. The UK Biobank cohort consisted of 101\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      <jats:sup>cys<\/jats:sup>\n                      -positive individuals. Data from 2-year (2019-2023) and 18-year (1999-2017) follow-up studies were also analyzed. Data analysis was performed from July 2023 to August 2024.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi240081-7\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>\n                      Percentage of cases following the sequence of events of the\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      -SVD stages, and the association between the stages and ischemic stroke, intracerebral hemorrhage, global cognition, processing speed, brain volume, brain microstructural damage, and serum neurofilament light chain (NfL) level.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi240081-8\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      -SVD staging system encompasses 9 disease stages or substages, ranging from stage 0 (premanifest stage) to stage 4B (end stage). Of all 1908 cases, which included 195 in the discovery cohort (mean [SD] age, 52.4 [12.2] years) and 1713 in the validation cohorts (mean [SD] age, 53.1 [13.0] years), 1789 (94%) followed the sequence of events defined by the\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      -SVD staging system. The\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      -SVD stages were associated with neuroimaging outcomes in the\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      <jats:sup>cys<\/jats:sup>\n                      -positive cases in the CADASIL cohorts and in the UK Biobank and with cognitive outcomes and serum NfL level in cases from the CADASIL cohorts. The\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      -SVD staging system captured disease progression and was associated with 18-year survival.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi240081-9\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      -SVD staging system captures the full disease spectrum, from asymptomatic individuals with a\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      <jats:sup>cys<\/jats:sup>\n                      variant to patients with end-stage disease. The\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      -SVD staging system is a simple but effective tool for uniform disease staging in the clinic and in research.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaneurol.2024.4487","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T03:30:28Z","timestamp":1732851028000},"page":"49","source":"Crossref","is-referenced-by-count":27,"title":["Disease Severity Staging System for\n                    <i>NOTCH3<\/i>\n                    -Associated Small Vessel Disease, Including CADASIL"],"prefix":"10.1001","volume":"82","author":[{"given":"Gido","family":"Gravesteijn","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie W.","family":"Rutten","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minne N.","family":"Cerfontaine","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remco J.","family":"Hack","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chu","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan"},{"name":"Department of Neurology, Brain Research Center, and Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy A.","family":"Jolly","sequence":"additional","affiliation":[{"name":"Stroke Research Group, Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Guey","sequence":"additional","affiliation":[{"name":"Centre NeuroVasculaire Translationnel and Centre de R\u00e9f\u00e9rence des Maladies Vasculaires Rares du Cerveau et de L\u2019Oeil, Lariboisi\u00e8re Hospital and Universit\u00e9 Paris-Cit\u00e9, Paris, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit 1141 NeuroDiderot, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Lun","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brain Research Center, and Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-young","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kopczak","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research, University Hospital of Ludwig-Maximilians-University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Rifino","sequence":"additional","affiliation":[{"name":"Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam J.","family":"Neilson","sequence":"additional","affiliation":[{"name":"Centre for Stroke & Brain Imaging, University of Glasgow, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Poggesi","sequence":"additional","affiliation":[{"name":"Stroke Unit, Careggi University Hospital, Florence, Italy"},{"name":"Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Manjurul Islam","family":"Shourav","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Jacksonville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Ishiyama","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Dom\u00ednguez Mayoral","sequence":"additional","affiliation":[{"name":"Unidad de Enfermedades Neurovasculares Infrecuentes, Hospital Virgen Macarena, Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital SARAH Kubitschek, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Mui\u00f1o","sequence":"additional","affiliation":[{"name":"Stroke Pharmacogenomics and Genetics Group, Institut de Recerca Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Andersen","sequence":"additional","affiliation":[{"name":"Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden"},{"name":"Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"De Stefano","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Santo","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital of Coimbra, Unidade Local de Sa\u00fade de Coimbra, Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nontapat","family":"Sukhonpanich","sequence":"additional","affiliation":[{"name":"Stroke Research Group, Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom"},{"name":"Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Mele","sequence":"additional","affiliation":[{"name":"Neurology and Stroke Unit, Luigi Sacco University Hospital, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Seok","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Medicine, Jeju National University, Jeju, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar","family":"Rodr\u00edguez-Girondo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiaan J. J.","family":"Vonk","sequence":"additional","affiliation":[{"name":"Software developer in personal capacity, Weesp, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Brodtmann","sequence":"additional","affiliation":[{"name":"School of Translational Medicine, Monash University, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"B\u00f6rjesson-Hanson","sequence":"additional","affiliation":[{"name":"Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden"},{"name":"Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Pantoni","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center, Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israel","family":"Fern\u00e1ndez-Cadenas","sequence":"additional","affiliation":[{"name":"Stroke Pharmacogenomics and Genetics Group, Institut de Recerca Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Rita","family":"Silva","sequence":"additional","affiliation":[{"name":"Center for Research in Neuropsychology and Cognitive Behavioral Interventions, University of Coimbra, Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vin\u00edcus V. A.","family":"Montanaro","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital SARAH Kubitschek, Bras\u00edlia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh N.","family":"Kalaria","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Lopergolo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Ihara","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F.","family":"Meschia","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Jacksonville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith W.","family":"Muir","sequence":"additional","affiliation":[{"name":"School of Cardiovascular & Metabolic Health, University of Glasgow, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Bersano","sequence":"additional","affiliation":[{"name":"Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Pescini","sequence":"additional","affiliation":[{"name":"Stroke Unit, Careggi University Hospital, Florence, Italy"},{"name":"Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Duering","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research, University Hospital of Ludwig-Maximilians-University Munich, Munich, Germany"},{"name":"Medical Image Analysis Center and Translational Imaging in Neurology, Department of Biomedical Engineering, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay Chol","family":"Choi","sequence":"additional","affiliation":[{"name":"College of Medicine, Jeju National University, Jeju, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunjin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh S.","family":"Markus","sequence":"additional","affiliation":[{"name":"Stroke Research Group, Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugues","family":"Chabriat","sequence":"additional","affiliation":[{"name":"Centre NeuroVasculaire Translationnel and Centre de R\u00e9f\u00e9rence des Maladies Vasculaires Rares du Cerveau et de L\u2019Oeil, Lariboisi\u00e8re Hospital and Universit\u00e9 Paris-Cit\u00e9, Paris, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit 1141 NeuroDiderot, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan"},{"name":"Department of Neurology, Brain Research Center, and Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan"},{"name":"Center for Intelligent Drug Systems and Smart Bio-Devices, National Yang Ming Chiao Tung University, Hsinchu, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia A. J.","family":"Lesnik Oberstein","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"7","key":"noi240081r1","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1016\/S1474-4422(19)30079-1","article-title":"Small vessel disease: mechanisms and clinical implications.","volume":"18","author":"Wardlaw","year":"2019","journal-title":"Lancet Neurol"},{"issue":"13","key":"noi240081r2","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1212\/WNL.0b013e31824d586c","article-title":"The minimum prevalence of CADASIL in northeast England.","volume":"78","author":"Narayan","year":"2012","journal-title":"Neurology"},{"issue":"11","key":"noi240081r3","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1002\/acn3.344","article-title":"Archetypal NOTCH3 mutations frequent in public exome: implications for CADASIL.","volume":"3","author":"Rutten","year":"2016","journal-title":"Ann Clin Transl Neurol"},{"issue":"6","key":"noi240081r4","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000639","article-title":"Pathogenic NOTCH3 variants are frequent among the Korean general population.","volume":"7","author":"Kang","year":"2021","journal-title":"Neurol Genet"},{"issue":"1","key":"noi240081r5","doi-asserted-by":"publisher","first-page":"e87","DOI":"10.1212\/WNL.0000000000008700","article-title":"NOTCH3 cysteine-altering variant is an important risk factor for stroke in the Taiwanese population.","volume":"94","author":"Lee","year":"2020","journal-title":"Neurology"},{"issue":"12","key":"noi240081r6","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1001\/jamaneurol.2022.3832","article-title":"Association of vascular risk factors and genetic factors with penetrance of variants causing monogenic stroke.","volume":"79","author":"Cho","year":"2022","journal-title":"JAMA Neurol"},{"issue":"12","key":"noi240081r7","doi-asserted-by":"publisher","first-page":"3562","DOI":"10.1161\/STROKEAHA.120.030343","article-title":"Cysteine-altering NOTCH3 variants are a risk factor for stroke in the elderly population.","volume":"51","author":"Hack","year":"2020","journal-title":"Stroke"},{"issue":"7","key":"noi240081r8","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1136\/jnnp-2020-325838","article-title":"NOTCH3 variants are more common than expected in the general population and associated with stroke and vascular dementia: an analysis of 200 000 participants.","volume":"92","author":"Cho","year":"2021","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"13","key":"noi240081r9","doi-asserted-by":"publisher","first-page":"e1835","DOI":"10.1212\/WNL.0000000000010525","article-title":"Broad phenotype of cysteine-altering NOTCH3 variants in UK Biobank: CADASIL to nonpenetrance.","volume":"95","author":"Rutten","year":"2020","journal-title":"Neurology"},{"issue":"6","key":"noi240081r10","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.1161\/STROKEAHA.121.036307","article-title":"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy family members with a pathogenic NOTCH3 variant can have a normal brain magnetic resonance imaging and skin biopsy beyond age 50 years.","volume":"53","author":"Hack","year":"2022","journal-title":"Stroke"},{"issue":"1-2","key":"noi240081r11","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.jns.2007.10.017","article-title":"A pathogenic mutation on exon 21 of the NOTCH3 gene causing CADASIL in an octogenarian paucisymptomatic patient.","volume":"267","author":"Pescini","year":"2008","journal-title":"J Neurol Sci"},{"issue":"3","key":"noi240081r12","doi-asserted-by":"publisher","first-page":"352","DOI":"10.5853\/jos.2022.01578","article-title":"Elderly CADASIL patients with intact neurological status.","volume":"24","author":"Zhang","year":"2022","journal-title":"J Stroke"},{"issue":"2","key":"noi240081r13","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1161\/STROKEAHA.116.015750","article-title":"Predictors and clinical impact of incident lacunes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.","volume":"48","author":"Ling","year":"2017","journal-title":"Stroke"},{"issue":"1","key":"noi240081r14","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1177\/17474930231191991","article-title":"Modifiable vascular risk factors contribute to stroke in 1080 NOTCH3 R544C carriers in Taiwan Biobank.","volume":"19","author":"Lin","year":"2024","journal-title":"Int J Stroke"},{"issue":"10","key":"noi240081r15","doi-asserted-by":"publisher","first-page":"3133","DOI":"10.1161\/STROKEAHA.122.039325","article-title":"Effect of NOTCH3 EGFr group, sex, and cardiovascular risk factors on CADASIL clinical and neuroimaging outcomes.","volume":"53","author":"Hack","year":"2022","journal-title":"Stroke"},{"issue":"10","key":"noi240081r16","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209310","article-title":"Association of NOTCH3 variant risk category with 2-year clinical and radiologic small vessel disease progression in patients with CADASIL.","volume":"102","author":"Cerfontaine","year":"2024","journal-title":"Neurology"},{"issue":"7","key":"noi240081r17","doi-asserted-by":"publisher","first-page":"2913","DOI":"10.1093\/brain\/awac486","article-title":"Three-tiered EGFr domain risk stratification for individualized NOTCH3-small vessel disease prediction.","volume":"146","author":"Hack","year":"2023","journal-title":"Brain"},{"issue":"3","key":"noi240081r18","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1148\/radiol.2293021354","article-title":"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: MR imaging findings at different ages\u20143rd-6th decades.","volume":"229","author":"van den Boom","year":"2003","journal-title":"Radiology"},{"issue":"7","key":"noi240081r19","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/S1474-4422(09)70127-9","article-title":"Cadasil.","volume":"8","author":"Chabriat","year":"2009","journal-title":"Lancet Neurol"},{"issue":"11","key":"noi240081r20","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1176\/appi.ajp.162.11.2078","article-title":"The pattern of cognitive performance in CADASIL: a monogenic condition leading to subcortical ischemic vascular dementia.","volume":"162","author":"Peters","year":"2005","journal-title":"Am J Psychiatry"},{"issue":"17","key":"noi240081r21","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1212\/WNL.0000000000003252","article-title":"Prediction of 3-year clinical course in CADASIL.","volume":"87","author":"Jouvent","year":"2016","journal-title":"Neurology"},{"issue":"2","key":"noi240081r22","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1212\/01.wnl.0000265221.05610.70","article-title":"Lacunar lesions are independently associated with disability and cognitive impairment in CADASIL.","volume":"69","author":"Viswanathan","year":"2007","journal-title":"Neurology"},{"issue":"9298","key":"noi240081r23","doi-asserted-by":"publisher","first-page":"2049","DOI":"10.1016\/S0140-6736(01)07142-2","article-title":"Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis.","volume":"358","author":"Joutel","year":"2001","journal-title":"Lancet"},{"issue":"17","key":"noi240081r24","doi-asserted-by":"publisher","first-page":"1430","DOI":"10.1212\/01.wnl.0000264018.46335.c8","article-title":"Diagnostic value of ultrastructural skin biopsy studies in CADASIL.","volume":"68","author":"Malandrini","year":"2007","journal-title":"Neurology"},{"issue":"2","key":"noi240081r25","doi-asserted-by":"publisher","first-page":"351","DOI":"10.2214\/ajr.149.2.351","article-title":"MR signal abnormalities at 1.5 T in Alzheimer\u2019s dementia and normal aging.","volume":"149","author":"Fazekas","year":"1987","journal-title":"AJR Am J Roentgenol"},{"issue":"7","key":"noi240081r26","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1016\/S1474-4422(23)00131-X","article-title":"Neuroimaging standards for research into small vessel disease-advances since 2013.","volume":"22","author":"Duering","year":"2023","journal-title":"Lancet Neurol"},{"issue":"5","key":"noi240081r27","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1586\/14737159.2014.922880","article-title":"Interpretation of NOTCH3 mutations in the diagnosis of CADASIL.","volume":"14","author":"Rutten","year":"2014","journal-title":"Expert Rev Mol Diagn"},{"issue":"9","key":"noi240081r28","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.3390\/ijms18091964","article-title":"Systematic review of cysteine-sparing NOTCH3 missense mutations in patients with clinical suspicion of CADASIL.","volume":"18","author":"Mui\u00f1o","year":"2017","journal-title":"Int J Mol Sci"},{"issue":"10","key":"noi240081r29","doi-asserted-by":"publisher","first-page":"2482","DOI":"10.1161\/STROKEAHA.116.013761","article-title":"Brief screening of vascular cognitive impairment in patients with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy without dementia.","volume":"47","author":"Brookes","year":"2016","journal-title":"Stroke"},{"issue":"1","key":"noi240081r30","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1161\/STROKEAHA.115.010696","article-title":"Predictors of clinical worsening in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: prospective cohort study.","volume":"47","author":"Chabriat","year":"2016","journal-title":"Stroke"},{"issue":"4","key":"noi240081r31","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1002\/ana.24758","article-title":"A novel imaging marker for small vessel disease based on skeletonization of white matter tracts and diffusion histograms.","volume":"80","author":"Baykara","year":"2016","journal-title":"Ann Neurol"},{"issue":"1","key":"noi240081r32","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1002\/acn3.678","article-title":"Serum neurofilament light correlates with CADASIL disease severity and survival.","volume":"6","author":"Gravesteijn","year":"2018","journal-title":"Ann Clin Transl Neurol"},{"issue":"2","key":"noi240081r33","doi-asserted-by":"publisher","first-page":"228","DOI":"10.5853\/jos.2017.02565","article-title":"Serum neurofilament light chain levels are related to small vessel disease burden.","volume":"20","author":"Duering","year":"2018","journal-title":"J Stroke"},{"key":"noi240081r34","doi-asserted-by":"publisher","DOI":"10.1016\/j.cccb.2023.100170","article-title":"Novel grading system for CADASIL severity: a multicenter cross-sectional study.","volume":"5","author":"Anisetti","year":"2023","journal-title":"Cereb Circ Cogn Behav"},{"issue":"3","key":"noi240081r35","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1161\/STROKEAHA.120.030664","article-title":"Intracerebral hemorrhage in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: prevalence, clinical and neuroimaging features and risk factors.","volume":"52","author":"Liao","year":"2021","journal-title":"Stroke"},{"issue":"12","key":"noi240081r36","doi-asserted-by":"publisher","first-page":"3918","DOI":"10.1161\/STROKEAHA.120.032265","article-title":"Rare NOTCH3 variants in a Chinese population-based cohort and its relationship with cerebral small vessel disease.","volume":"52","author":"Liu","year":"2021","journal-title":"Stroke"},{"issue":"10","key":"noi240081r37","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1212\/01.wnl.0000344166.03470.f8","article-title":"Apathy: a major symptom in CADASIL.","volume":"72","author":"Reyes","year":"2009","journal-title":"Neurology"},{"issue":"6","key":"noi240081r39","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1002\/ana.26916","article-title":"Pro-hemorrhagic cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy associated with NOTCH3 p.R75P mutation with low vascular NOTCH3 aggregation property.","volume":"95","author":"Ishiyama","year":"2024","journal-title":"Ann Neurol"},{"issue":"12","key":"noi240081r40","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.025629","article-title":"Systematic review of cerebral phenotypes associated with monogenic cerebral small-vessel disease.","volume":"11","author":"Whittaker","year":"2022","journal-title":"J Am Heart Assoc"},{"issue":"10","key":"noi240081r41","doi-asserted-by":"publisher","DOI":"10.1172\/JCI172841","article-title":"Pathophysiology of cerebral small vessel disease: a journey through recent discoveries.","volume":"134","author":"Dupr\u00e9","year":"2024","journal-title":"J Clin Invest"},{"issue":"4","key":"noi240081r42","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1161\/01.STR.0000157596.13234.95","article-title":"Reliability of the modified Rankin Scale across multiple raters: benefits of a structured interview.","volume":"36","author":"Wilson","year":"2005","journal-title":"Stroke"},{"issue":"2-3","key":"noi240081r43","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/S0925-4927(99)00036-0","article-title":"Reliability and validity of ratings of signal hyperintensities on MRI by visual inspection and computerised measurement.","volume":"92","author":"Sachdev","year":"1999","journal-title":"Psychiatry Res"},{"issue":"2","key":"noi240081r44","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1161\/01.STR.0000049766.26453.E9","article-title":"Visual rating of age-related white matter changes on magnetic resonance imaging: scale comparison, interrater agreement, and correlations with quantitative measurements.","volume":"34","author":"Kapeller","year":"2003","journal-title":"Stroke"},{"key":"noi240081r38","unstructured":"Leids Universitair Medisch Centrum. NOTCH3-SVD staging system. Accessed November 12, 2024. https:\/\/www.lumc.nl\/notch3-svd-staging-system"}],"container-title":["JAMA Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/articlepdf\/2827600\/jamaneurology_gravesteijn_2024_oi_240081_1735932276.97202.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T11:02:00Z","timestamp":1736766120000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/fullarticle\/2827600"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,1]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaneurol.2024.4487","relation":{},"ISSN":["2168-6149"],"issn-type":[{"value":"2168-6149","type":"print"}],"subject":[],"published":{"date-parts":[[2025,1,1]]}}}