On the Diagnosis of CADASIL

Article type: Research Article

Authors: Ampuero, Israel^{a; *} | Alegre-Abarrategui, Javier^{a; b} | Rodal, Izaskun^a | España, Antonio^a | Ros, Raquel^a | Sendón, José Luis Lopez^b | Galloway, Eva García^c | Cervelló, Ángeles^d | Belén Caminero, Ana^e | Zabala, Antxon^f | Erro, Elena^g | Jarauta, Fernando^g | Morlán, Lorenzo^h | López-Valdés, Eva^h | Aladro, Yolanda^h | Seijo, Manuelⁱ | Rivas, Guillermo García^b | Muñoz, David G.^a | de Yébenes, Justo García^{a; b}

Affiliations: [a] Banco de Tejidos para Investigaciones Neurológicas (BTIN), Facultad de Medicina, Universidad Commplutense de Madrid, Madrid, Spain | [b] Servicio de Neurología, Hospital Ramón y Cajal, Madrid, Spain | [c] Servicio de Genética, Hospital Ramón y Cajal, Madrid, Spain | [d] Hospital General de Valencia, Valencia, Spain | [e] Hospital Nuestra Señora de Sonsoles, Ávila, Spain | [f] Clínica Puerta de Hierro, Madrid, Spain | [g] Hospital de Navarra, Pamplona, Spain | [h] Hospital de Getafe, Madrid, Spain | [i] Complexo Hospitalario de Pontevedra, Pontevedra, Spain

Correspondence: [*] Corresponding author: Israel Ampuero, Banco de Tejidos para Investigaciones Neurológicas, Facultad de Medicina, Universidad Commplutense de Madrid, Avda Complutense, s/n. Madrid 28040, Spain. Tel.: +34 91 3941326; Fax: +34 91 3941329; E-mail: fuinvesn@med.ucm.es.

Abstract: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic arteriopathy related to Notch3 mutations, is difficult to diagnosis. The goal of this study was to determine the value of clinical, immunohistochemical, and molecular techniques for the diagnosis of CADASIL. Clinical features and the immunohistochemical and molecular findings in 200 subjects with suspected CADASIL in whom 93 biopsies and 190 molecular studies are reported. Eighteen pathogenic mutations of the Notch3 gene, six of them previously unreported, were detected in 67 patients. The clinical features did not permit differentiation between CADASIL and CADASIL-like syndromes. The sensitivity and specificity of the skin biopsies was 97.7% and 56.5%, respectively, but increased to 100% and 81.5%, respectively, in cases with proven family history. In conclusion, a clinical diagnosis of CADASIL is difficult to determine and confirmatory techniques should be used judiciously.

Keywords: CADASIL, familial stroke with dementia, Notch3, NOTCH3 immunostaining

DOI: 10.3233/JAD-2009-1112

Journal: Journal of Alzheimer's Disease, vol. 17, no. 4, pp. 787-794, 2009