Anna Bersano1, Gloria Bedini2, Hugh Stephen Markus3, Paolo Vitali4, Enrico Colli-Tibaldi4, Franco Taroni5, Cinzia Gellera5, Silvia Baratta5, Lorena Mosca6, Paola Carrera7, Maurizio Ferrari7, Cristina Cereda8, Gaetano Grieco8, Silvia Lanfranconi9, Franca Mazucchelli10, Davide Zarcone10, Maria Luisa De Lodovici11, Giorgio Bono11, Giorgio Battista Boncoraglio12, Eugenio Agostino Parati12, Maria Vittoria Calloni13, Patrizia Perrone13, Bianca Maria Bordo14, Cristina Motto15, Elio Agostoni15, Alessandro Pezzini16, Alessandro Padovani16, Giuseppe Micieli17, Anna Cavallini17, Graziella Molini18, Francesco Sasanelli18, Maria Sessa19, Giancarlo Comi19, Nicoletta Checcarelli20, Massimo Carmerlingo21, Manuel Corato22, Simona Marcheselli22, Laura Fusi23, Giampiero Grampa23, Davide Uccellini24, Simone Beretta25, Carlo Ferrarese25, Barbara Incorvaia26, Carlo Sebastiano Tadeo26, Laura Adobbati27, Vincenzo Silani27, Giuseppe Faragò28, Nadia Trobia12, Caspar Grond-Ginsbach29, Livia Candelise9. 1. Cerebrovascular Unit, Neurological Institute "C. Besta" IRCCS Foundation, Via Celoria 11, 20133, Milan, Italy. anna.bersano@gmail.com. 2. Laboratory of Cellular Neurobiology, Neurological Institute "C. Besta" IRCCS Foundation, Milan, Italy. 3. Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. 4. Neuroradiology, IRCCS Foundation C, Mondino Neurological Institute, Pavia, Italy. 5. Clinical Pathology and Medical Genetic Laboratory, Neurological Institute "C. Besta" IRCCS Foundation, Milan, Italy. 6. Laboratorio di Genetica, Azienda Ospedaliera Niguarda Ca' Granda, Milan, Italy. 7. Unit of Genomics for Human Disease Diagnosis and Laboratory of Clinical Molecular Biology, IRCCS Ospedale San Raffaele, Milan, Italy. 8. Genomic and Post-Genomic Center, IRCCS C. Mondino National Neurological Institute, Pavia, Italy. 9. Neurology Unit, Department of Neuroscience and Sensory Organs, Maggiore Policlinico Hospital Foundation IRCCS Ca' Granda, Milan, Italy. 10. Stroke Unit, S. Antonio Abate Hospital, Gallarate, Italy. 11. Stroke Unit, Circolo Hospital and Macchi Foundation, Varese Hospital, Varese, Italy. 12. Cerebrovascular Unit, Neurological Institute "C. Besta" IRCCS Foundation, Via Celoria 11, 20133, Milan, Italy. 13. Stroke Unit, Legnano and Cuggiono Hospital, Legnano, Italy. 14. Neurological Unit and Stroke Unit, Ospedale di Desio, Desio, Italy. 15. Stroke Unit, Azienda Ospedaliera Niguarda Ca Granda, Milan, Italy. 16. Department of Clinical and Experimental Sciences, Neurology Clinic, University of Brescia, Brescia, Italy. 17. Neurology and Stroke Unit, Department of Urgency, IRCCS Foundation C. Mondino Neurological Institute, Pavia, Italy. 18. AO Melegnano-Ospedale di Vizzolo Predabissi, Melegnano, Italy. 19. Stroke Unit, San Raffaele Hospital, Milan, Italy. 20. Stroke Unit, Valduce Hospital, Como, Italy. 21. UO Neurologia Policlinico San Marco, Zingonia, Italy. 22. Istituto Clinico Humanitas, Rozzano, Italy. 23. Stroke Unit, Ospedale di Circolo, Saronno, Italy. 24. Tradate Hospital, Tradate, Italy. 25. Stroke Unit, Azienda Ospedaliera San Gerardo, Milan Bicocca University, Monza, Italy. 26. Stroke Unit, Istituto Clinico Città Studi, Milan, Italy. 27. Stroke Unit, Istituto Auxologico, Milan, Italy. 28. Neuroradiological Unit, Neurological Institute "C. Besta" IRCCS Foundation, Milan, Italy. 29. Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
Abstract
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.
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.
Authors: Anna Bersano; Hugh Stephen Markus; Silvana Quaglini; Eloisa Arbustini; Silvia Lanfranconi; Giuseppe Micieli; Giorgio B Boncoraglio; Franco Taroni; Cinzia Gellera; Silvia Baratta; Silvana Penco; Lorena Mosca; Maurizia Grasso; Paola Carrera; Maurizio Ferrari; Cristina Cereda; Gaetano Grieco; Stefania Corti; Dario Ronchi; Maria Teresa Bassi; Laura Obici; Eugenio A Parati; Alessando Pezzini; Maria Luisa De Lodovici; Elena P Verrengia; Giorgio Bono; Francesca Mazucchelli; Davide Zarcone; Maria Vittoria Calloni; Patrizia Perrone; Bianca Maria Bordo; Antonio Colombo; Alessandro Padovani; Anna Cavallini; Simone Beretta; Carlo Ferrarese; Cristina Motto; Elio Agostoni; Graziella Molini; Francesco Sasanelli; Manuel Corato; Simona Marcheselli; Maria Sessa; Giancarlo Comi; Nicoletta Checcarelli; Mario Guidotti; Davide Uccellini; Erminio Capitani; Lucia Tancredi; Marco Arnaboldi; Barbara Incorvaia; Carlo Sebastiano Tadeo; Laura Fusi; Giampiero Grampa; Giampaolo Merlini; Nadia Trobia; Giacomo Pietro Comi; Massimiliano Braga; Paolo Vitali; Pierluigi Baron; Caspar Grond-Ginsbach; Livia Candelise Journal: Stroke Date: 2016-05-31 Impact factor: 7.914
Authors: H Chabriat; C Levy; H Taillia; M T Iba-Zizen; K Vahedi; A Joutel; E Tournier-Lasserve; M G Bousser Journal: Neurology Date: 1998-08 Impact factor: 9.910
Authors: M K Liem; S A J Lesnik Oberstein; J Haan; I L van der Neut; M D Ferrari; M A van Buchem; H A M Middelkoop; J van der Grond Journal: Neurology Date: 2009-01-13 Impact factor: 9.910
Authors: S Nannucci; F Pescini; B Bertaccini; S Bianchi; L Ciolli; R Valenti; M T Dotti; A Federico; D Inzitari; L Pantoni Journal: Acta Neurol Scand Date: 2014-08-11 Impact factor: 3.209
Authors: L Pantoni; F Pescini; S Nannucci; C Sarti; S Bianchi; M T Dotti; A Federico; D Inzitari Journal: Neurology Date: 2010-01-05 Impact factor: 9.910
Authors: A Bersano; M Kraemer; A Burlina; M Mancuso; J Finsterer; S Sacco; C Salvarani; L Caputi; H Chabriat; S Lesnik Oberstein; A Federico; E Tournier Lasserve; D Hunt; M Dichgans; M Arnold; S Debette; H S Markus Journal: J Neurol Date: 2020-04-21 Impact factor: 4.849