The role of clinical and neuroimaging features in the diagnosis of CADASIL

• DOI: 10.1007/s00415-018-9072-8
• Publication Date: 2018-10-11T04:31:24Z
• Authors: Anna Bersano; Gloria Bedini; Hugh Stephen Markus; Paolo Vitali; Enrico Colli-Tibaldi; Franco Taroni; Cinzia Gellera; Silvia Baratta; Lorena Mosca; Paola Carrera; Maurizio Ferrari; Cristina Cereda; Gaetano Grieco; Silvia Lanfranconi; Franca Mazucchelli; Davide Zarcone; Maria Luisa De Lo...; Giorgio Bono; Giorgio Battista ...; Eugenio Agostino ...; Maria Vittoria Ca...; Patrizia Perrone; Bianca Maria Bordo; Cristina Motto; Elio Agostoni; Alessandro Pezzini; Alessandro Padovani; Giuseppe Micieli; Anna Cavallini; Graziella Molini; Francesco Sasanelli; Maria Sessa; Giancarlo Comi; Nicoletta Checcar...; Massimo Carmerlingo; Manuel Corato; Simona Marcheselli; Laura Fusi; Giampiero Grampa; Davide Uccellini; Simone Beretta; Carlo Ferrarese; Barbara Incorvaia; Carlo Sebastiano ...; Laura Adobbati; Vincenzo Silani; Giuseppe Faragò; Nadia Trobia; Caspar Grond-Gins...; Livia Candelise
• Keywords: 0301 basic medicine; Adult; Male; Monogenic disorder; 610; CADASIL; Neuroimaging; 03 medical and health sciences; 0302 clinical medicine; Diagnosis; Humans; Prospective Studies; Receptor, Notch3; Aged; Cerebral Hemorrhage; Stroke genetics; Monogenic disorders; CADASIL; diagnosis; monogenic disorders; neuroimaging; NOTCH3 gene; stroke genetics; neurology; neurology (clinical); Brain; Middle Aged; Magnetic Resonance Imaging; White Matter; 3. Good health; Ischemic Attack, Transient; Stroke, Lacunar; Female; Atrophy; CADASIL; Diagnosis; Monogenic disorders; Neuroimaging; NOTCH3 gene; Stroke genetics; Adult; Aged; Atrophy; Brain; CADASIL; Cerebral Hemorrhage; Female; Humans; Ischemic Attack, Transient; Magnetic Resonance Imaging; Male; Middle Aged; Prospective Studies; Receptor, Notch3; Stroke, Lacunar; White Matter; Neuroimaging; Neurology; Neurology (clinical); NOTCH3 gene; Diagnosi

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial cerebral small vessel disease, caused by NOTCH3 gene mutations. The aim of our study was to identify clinical and neuroradiological features which would be useful in identifying which patients presenting with lacunar stroke and TIA are likely to have CADASIL. METHODS: Patients with lacunar stroke or TIA were included in the present study. For each patient, demographic and clinical data were collected. MRI images were centrally analysed for the presence of lacunar infarcts, microbleeds, temporal lobe involvement, global atrophy and white matter hyperintensities. RESULTS: 128 patients (mean age 56.3 ± 12.4 years) were included. A NOTCH3 mutation was found in 12.5% of them. A family history of stroke, the presence of dementia and external capsule lesions on MRI were the only features significantly associated with the diagnosis of CADASIL. Although thalamic, temporal pole gliosis and severe white matter hyperintensities were less specific for CADASIL diagnosis, the combination of a number of these factors together with familial history for stroke result in a higher positive predictive value and specificity. CONCLUSIONS: A careful familial history collection and neuroradiological assessment can identify patients in whom NOTCH3 genetic testing has a higher yield.