{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:21:33Z","timestamp":1787962893858,"version":"build-2784847793"},"reference-count":55,"publisher":"BMJ","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Pract Neurol"],"accepted":{"date-parts":[[2026,4,16]]},"abstract":"<jats:p>\n                    CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) is a hereditary small vessel disease caused by pathogenic\n                    <jats:italic>NOTCH3<\/jats:italic>\n                    variants, predominantly affecting cysteine residues in epidermal growth factor-like repeats. Clinically, patients present with migraine with aura, subcortical ischaemic strokes, mood disturbances, apathy and progressive cognitive decline, with disability accumulating over decades. Neuroimaging typically shows symmetrical white matter hyperintensities, lacunar infarcts and cerebral microbleeds. Its diagnosis relies on genetic testing, with skin biopsy reserved for uncertain cases. Management remains supportive and symptom-directed, emphasising vascular risk-factor control, stroke prevention, migraine management and cognitive and multidisciplinary care. Emerging therapeutic strategies targeting\n                    <jats:italic>NOTCH3<\/jats:italic>\n                    include exon skipping, gene silencing, immunotherapy, growth factors and peptides, with preclinical studies showing restoration of mural cell function, reduced protein aggregation and improved vascular and cognitive outcomes. We need further research to translate these approaches into safe and effective disease-modifying therapies for patients.\n                  <\/jats:p>","DOI":"10.1136\/pn-2025-004718","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T17:20:31Z","timestamp":1778001631000},"page":"pn-2025-004718","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["CADASIL: a practical review for the neurologist"],"prefix":"10.1136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6121-3497","authenticated-orcid":false,"given":"Miranda","family":"Wan","sequence":"first","affiliation":[{"name":"University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6269-1543","authenticated-orcid":false,"given":"Michael D","family":"Hill","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"2026050510202847000_pn-2025-004718v1.1","first-page":"961","article-title":"Enc\u00e9phalopathie sous-corticale progressive (Binswanger) \u00e0 \u00e9volution rapide chez deux soeurs","volume":"24","author":"Bogaert","year":"1955","journal-title":"Med Hellen"},{"key":"2026050510202847000_pn-2025-004718v1.2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00691704"},{"key":"2026050510202847000_pn-2025-004718v1.3","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1016\/S0140-6736(77)92576-4","article-title":"Chronic familial vascular encephalopathy","volume":"1","author":"Stevens","year":"1977","journal-title":"Lancet"},{"key":"2026050510202847000_pn-2025-004718v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/ng0393-256"},{"key":"2026050510202847000_pn-2025-004718v1.5","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.22.10.1297"},{"key":"2026050510202847000_pn-2025-004718v1.6","doi-asserted-by":"crossref","first-page":"149754","DOI":"10.1016\/j.brainres.2025.149754","article-title":"The role of NOTCH3 in CADASIL pathogenesis: insights into novel therapies","volume":"1863","author":"Felix-Ilemhenbhio","year":"2025","journal-title":"Brain Res"},{"key":"2026050510202847000_pn-2025-004718v1.7","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12266"},{"key":"2026050510202847000_pn-2025-004718v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70127-9"},{"key":"2026050510202847000_pn-2025-004718v1.9","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/383707a0","article-title":"Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia","volume":"383","author":"Joutel","year":"1996","journal-title":"Nature New Biol"},{"key":"2026050510202847000_pn-2025-004718v1.10","doi-asserted-by":"crossref","DOI":"10.1212\/NXG.0000000000000434","article-title":"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy revisited: Genotype-phenotype correlations of all published cases","volume":"6","author":"Xiromerisiou","year":"2020","journal-title":"Neurol Genet"},{"key":"2026050510202847000_pn-2025-004718v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"2026050510202847000_pn-2025-004718v1.12","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22981"},{"key":"2026050510202847000_pn-2025-004718v1.13","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41392-022-00934-y","article-title":"Notch signaling pathway: architecture, disease, and therapeutics","volume":"7","author":"Zhou","year":"2022","journal-title":"Sig Transduct Target Ther"},{"key":"2026050510202847000_pn-2025-004718v1.14","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01285-09"},{"key":"2026050510202847000_pn-2025-004718v1.15","article-title":"Most common NOTCH3 mutations causing CADASIL or CADASIL-like cerebral small vessel disease: A systematic review","volume":"6","author":"Boston","year":"2024","journal-title":"Cereb Circ Cogn Behav"},{"key":"2026050510202847000_pn-2025-004718v1.16","doi-asserted-by":"crossref","first-page":"e452","DOI":"10.1161\/STR.0000000000000444","article-title":"Management of Inherited CNS Small Vessel Diseases: The CADASIL Example: A Scientific Statement From the American Heart Association","volume":"54","author":"Meschia","year":"2023","journal-title":"Stroke"},{"key":"2026050510202847000_pn-2025-004718v1.17","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2024.105297","article-title":"Clinical and neuroradiological spectrum of biallelic variants in NOTCH3","volume":"107","author":"Iruzubieta","year":"2024","journal-title":"EBioMedicine"},{"key":"2026050510202847000_pn-2025-004718v1.18","doi-asserted-by":"crossref","DOI":"10.1007\/s11940-017-0468-z","article-title":"CADASIL: Treatment and Management Options","volume":"19","author":"Bersano","year":"2017","journal-title":"Curr Treat Options Neurol"},{"key":"2026050510202847000_pn-2025-004718v1.19","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0136501","article-title":"Characterization of CADASIL among the Han Chinese in Taiwan: Distinct Genotypic and Phenotypic Profiles","volume":"10","author":"Liao","year":"2015","journal-title":"PLoS One"},{"key":"2026050510202847000_pn-2025-004718v1.20","doi-asserted-by":"crossref","first-page":"17113","DOI":"10.1038\/s41598-025-00220-1","article-title":"Genetic and imaging features of CADASIL patients with acute ischemic stroke","volume":"15","author":"Park","year":"2025","journal-title":"Sci Rep"},{"key":"2026050510202847000_pn-2025-004718v1.21","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199709000-00001"},{"key":"2026050510202847000_pn-2025-004718v1.22","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/S0140-6736(95)91557-5","article-title":"Clinical spectrum of CADASIL: a study of 7 families","volume":"346","author":"Chabriat","year":"1995","journal-title":"The Lancet"},{"key":"2026050510202847000_pn-2025-004718v1.23","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000210193","article-title":"Determining Clinical Disease Progression in Symptomatic Patients With CADASIL","volume":"104","author":"Kaisaridi","year":"2025","journal-title":"Neurology (ECronicon)"},{"key":"2026050510202847000_pn-2025-004718v1.24","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-023-12177-0"},{"key":"2026050510202847000_pn-2025-004718v1.25","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.120.016233","article-title":"Cerebral Microbleed Burdens in Specific Brain Regions Are Associated With Disease Severity of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy","volume":"9","author":"Chung","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"2026050510202847000_pn-2025-004718v1.26","doi-asserted-by":"publisher","DOI":"10.1161\/hs0102.100885"},{"key":"2026050510202847000_pn-2025-004718v1.27","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1017\/cjn.2023.54","article-title":"Acute Fatal Leukoencephalopathic Presentation of CADASIL","volume":"51","author":"Huddar","year":"2024","journal-title":"Can J Neurol Sci"},{"key":"2026050510202847000_pn-2025-004718v1.28","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.118.023661"},{"key":"2026050510202847000_pn-2025-004718v1.29","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1111\/ene.14183","article-title":"Monogenic cerebral small\u2010vessel diseases: diagnosis and therapy. Consensus recommendations of the European Academy of Neurology","volume":"27","author":"Mancuso","year":"2020","journal-title":"Euro J of Neurology"},{"key":"2026050510202847000_pn-2025-004718v1.30","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1212\/WNL.56.5.628","article-title":"MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL","volume":"56","author":"O\u2019Sullivan","year":"2001","journal-title":"Neurology (ECronicon)"},{"key":"2026050510202847000_pn-2025-004718v1.31","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1002\/acn3.70054","article-title":"Occurrence, Risk Factors, and Prognosis of Acute Cerebral Microinfarcts in CADASIL","volume":"12","author":"Men","year":"2025","journal-title":"Ann Clin Transl Neurol"},{"key":"2026050510202847000_pn-2025-004718v1.32","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.112.665927"},{"key":"2026050510202847000_pn-2025-004718v1.33","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2023.1219324","article-title":"Adult-onset leukodystrophies: a practical guide, recent treatment updates, and future directions","volume":"14","author":"Muthusamy","year":"2023","journal-title":"Front Neurol"},{"key":"2026050510202847000_pn-2025-004718v1.34","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1177\/0333102420941814","article-title":"The potential danger of blocking CGRP for treating migraine in CADASIL patients","volume":"40","author":"de Boer","year":"2020","journal-title":"Cephalalgia"},{"key":"2026050510202847000_pn-2025-004718v1.35","doi-asserted-by":"crossref","DOI":"10.3390\/jcm13071870","article-title":"Long-Term Treatment with the Calcitonin Gene-Related Peptide Receptor Antagonist Erenumab in CADASIL: Two Case Reports","volume":"13","author":"Albanese","year":"2024","journal-title":"J Clin Med"},{"key":"2026050510202847000_pn-2025-004718v1.36","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1111\/head.14942","article-title":"Genetic migraine disorders and the response to calcitonin gene-related peptide antagonist treatment","volume":"65","author":"Kuczynski","year":"2025","journal-title":"Headache"},{"key":"2026050510202847000_pn-2025-004718v1.37","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.124.048515"},{"key":"2026050510202847000_pn-2025-004718v1.38","doi-asserted-by":"crossref","first-page":"2831","DOI":"10.1007\/s10072-023-06773-1","article-title":"Antiplatelet use and CADASIL: a retrospective observational analysis","volume":"44","author":"Muppa","year":"2023","journal-title":"Neurol Sci"},{"key":"2026050510202847000_pn-2025-004718v1.39","doi-asserted-by":"crossref","unstructured":"Reyes-Soffer G , Ginsberg HN , Berglund L , et al . Lipoprotein(a): A Genetically Determined, Causal, and Prevalent Risk Factor for Atherosclerotic Cardiovascular Disease: A Scientific Statement From the American Heart Association. ATVB 2022;42. doi:10.1161\/ATV.0000000000000147","DOI":"10.1161\/ATV.0000000000000147"},{"key":"2026050510202847000_pn-2025-004718v1.40","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1055\/s-0039-1687907","article-title":"Vascular Disease and Dementia: Lipoprotein(a) as a Neglected Link","volume":"45","author":"Lippi","year":"2019","journal-title":"Semin Thromb Hemost"},{"key":"2026050510202847000_pn-2025-004718v1.41","unstructured":"Davis LL , Koschinsky M , Lamendola C , et al . Lp(a): a toolkit for health care professionals. American Heart Asociation; 2023.1\u201324."},{"key":"2026050510202847000_pn-2025-004718v1.42","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/S0140-6736(24)01308-4","article-title":"Lipoprotein(a) and cardiovascular disease","volume":"404","author":"Nordestgaard","year":"2024","journal-title":"The Lancet"},{"key":"2026050510202847000_pn-2025-004718v1.43","doi-asserted-by":"crossref","DOI":"10.31083\/j.rcm2511393","article-title":"Lipoprotein (a): Underrecognized Risk with a Promising Future","volume":"25","author":"Manzato","year":"2024","journal-title":"Rev Cardiovasc Med"},{"key":"2026050510202847000_pn-2025-004718v1.44","doi-asserted-by":"crossref","DOI":"10.1016\/j.jlr.2024.100524","article-title":"PCSK9 vaccines: a promising new strategy for the treatment of hypercholesterolemia?","volume":"65","author":"Chackerian","year":"2024","journal-title":"J Lipid Res"},{"key":"2026050510202847000_pn-2025-004718v1.45","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2023.1144584","article-title":"The role of homocysteine levels as a risk factor of ischemic stroke events: a systematic review and meta-analysis","volume":"14","author":"Pinzon","year":"2023","journal-title":"Front Neurol"},{"key":"2026050510202847000_pn-2025-004718v1.46","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70046-2"},{"key":"2026050510202847000_pn-2025-004718v1.47","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.010696"},{"key":"2026050510202847000_pn-2025-004718v1.48","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2024-334823"},{"key":"2026050510202847000_pn-2025-004718v1.49","unstructured":"Hack R , Rutten J , Lesnik Oberstein S . CADASIL. In: Adam MP , Bick S , Mirzaa GM , et al , eds. GeneReviews. Seattle (WA): University of Washington, 2000: 1993\u20132025."},{"key":"2026050510202847000_pn-2025-004718v1.50","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1111\/ane.12784","article-title":"Pregnancy in CADASIL","volume":"136","author":"Donnini","year":"2017","journal-title":"Acta Neurol Scand"},{"key":"2026050510202847000_pn-2025-004718v1.51","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1212\/01.WNL.0000158655.71323.8A","article-title":"Neurologic symptoms are common during gestation and puerperium in CADASIL","volume":"64","author":"Roine","year":"2005","journal-title":"Neurology (ECronicon)"},{"key":"2026050510202847000_pn-2025-004718v1.52","unstructured":"An Act to Prohibit and Prevent Genetic Discrimination. 2017."},{"key":"2026050510202847000_pn-2025-004718v1.53","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2023.15894","article-title":"Evaluation and Management of Deficiency of Adenosine Deaminase 2: An International Consensus Statement","volume":"6","author":"Lee","year":"2023","journal-title":"JAMA Netw Open"},{"key":"2026050510202847000_pn-2025-004718v1.54","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1111\/ene.15708","article-title":"Ischaemic cerebral small vessel disease caused by adenosine deaminase 2 deficiency syndrome","volume":"30","author":"Giossi","year":"2023","journal-title":"Euro J of Neurology"},{"key":"2026050510202847000_pn-2025-004718v1.55","doi-asserted-by":"crossref","DOI":"10.1002\/ajmg.c.32099","article-title":"Multiorgan manifestations of COL4A1 and COL4A2 variants and proposal for a clinical management protocol","volume":"196","author":"Gasparini","year":"2024","journal-title":"American J of Med Genetics Pt C"}],"container-title":["Practical Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/pn-2025-004718","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T17:20:44Z","timestamp":1778001644000},"score":1,"resource":{"primary":{"URL":"https:\/\/pn.bmj.com\/lookup\/doi\/10.1136\/pn-2025-004718"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,5]]},"references-count":55,"alternative-id":["10.1136\/pn-2025-004718"],"URL":"https:\/\/doi.org\/10.1136\/pn-2025-004718","relation":{},"ISSN":["1474-7758","1474-7766"],"issn-type":[{"value":"1474-7758","type":"print"},{"value":"1474-7766","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,5]]}}}