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

Lombardia GENS-group, A. Bersano, G. Bedini, H.S. Markus, P. Vitali, E. Colli-Tibaldi, F. Taroni, C. Gellera, S. Baratta, L. Mosca, P. Carrera, M. Ferrari, C. Cereda, G. Grieco, S. Lanfranconi, F. Mazucchelli, D. Zarcone, M.L. De Lodovici, G. Bono, G.B. BoncoraglioE.A. Parati, M.V. Calloni, P. Perrone, B.M. Bordo, C. Motto, E. Agostoni, A. Pezzini, Alessandro Padovani, G. Micieli, A. Cavallini, Graziella Molini, Francesco Sasanelli, M. Sessa, G. Comi, Nicoletta Checcarelli, Massimo Camerlingo, M. Corato, S. Marcheselli, Laura Fusi, Giampiero Grampa, Davide Uccellini, S. Beretta, Carlo Ferrarese, Barbara Incorvaia, Carlo Sebastiano Tadeo, Laura Adobbati, V. Silani, Giuseppe Faragò, Nadia Trobia, Caspar Grond-Ginsbach, Livia Candelise, M.T. Bassi

Research output: Contribution to journalArticlepeer-review


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. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
Original languageEnglish
Pages (from-to)2934-2943
Number of pages10
JournalJournal of Neurology
Issue number12
Publication statusPublished - 2018


  • Diagnosis
  • Monogenic disorders
  • Neuroimaging
  • NOTCH3 gene
  • Stroke genetics
  • genomic DNA
  • Notch3 receptor
  • NOTCH3 protein, human
  • adult
  • aged
  • Article
  • brain atrophy
  • brain hemorrhage
  • cerebrovascular accident
  • clinical feature
  • dementia
  • demography
  • diagnostic accuracy
  • diagnostic test accuracy study
  • external capsule
  • family history
  • female
  • gene mutation
  • genetic association
  • genetic screening
  • gliosis
  • human
  • lacunar stroke
  • major clinical study
  • male
  • middle aged
  • neuroimaging
  • neuroradiology
  • nuclear magnetic resonance imaging
  • predictive value
  • priority journal
  • sensitivity and specificity
  • stroke patient
  • temporal lobe
  • thalamus
  • transient ischemic attack
  • white matter
  • white matter lesion
  • atrophy
  • brain
  • diagnostic imaging
  • genetics
  • pathophysiology
  • prospective study
  • Adult
  • Aged
  • Atrophy
  • Brain
  • Cerebral Hemorrhage
  • Female
  • Humans
  • Ischemic Attack, Transient
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Prospective Studies
  • Receptor, Notch3
  • Stroke, Lacunar
  • White Matter


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