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

Author

Bersano, A, Bedini, G, Markus, H, Vitali, P, Colli-Tibaldi, E, Taroni, F, Gellera, C, Baratta, S, Mosca, L, Carrera, P, Ferrari, M, Cereda, C, Grieco, G, Lanfranconi, S, Mazucchelli, F, Zarcone, D, De Lodovici, M, Bono, G, Boncoraglio, G, Parati, E, Calloni, M, Perrone, P, Bordo, B, Motto, C, Agostoni, E, Pezzini, A, Padovani, A, Micieli, G, Cavallini, A, Molini, G, Sasanelli, F, Sessa, M, Comi, G, Checcarelli, N, Carmerlingo, M, Corato, M, Marcheselli, S, Fusi, L, Grampa, G, Uccellini, D, Beretta, S, Ferrarese, C, Incorvaia, B, Tadeo, C, Adobbati, L, Silani, V, Faragò, G, Trobia, N, Grond-Ginsbach, C, Candelise, L, Mazzucchelli, F, Guidotti, M, Riva, M, Iurlaro, S, Maria, B, Braga, M, Meola, G, Carpo, M, Camerlingo, M, Borutti, G, Delodovici, M, Verrengia, E, Tancredi, L, Terruzzi, A, Magoni, M, Del Zotto, E, Bassi, P, Lattuada, P, Ballabio, E, Gambaro, P, Corrà, B, Canavero, I, Arbustini, E, Grasso, M, Corti, S, Ronchi, D, Merlini, G, Obici, L, Bassi, M, Tagliavini, F, Ginsbach, C, Bersano, Anna, BEDINI, GLORIA, Markus, Hugh Stephen, Vitali, Paolo, Colli-Tibaldi, Enrico, Taroni, Franco, Gellera, Cinzia, Baratta, Silvia, Mosca, Lorena, Carrera, Paola, FERRARI, MAURIZIO, Cereda, Cristina, Grieco, Gaetano, Lanfranconi, Silvia, Mazucchelli, Franca, Zarcone, Davide, De Lodovici, Maria Luisa, Bono, Giorgio, Boncoraglio, Giorgio Battista, Parati, Eugenio Agostino, Calloni, Maria Vittoria, Perrone, Patrizia, Bordo, Bianca Maria, Motto, Cristina, Agostoni, Elio, Pezzini, Alessandro, Padovani, Alessandro, Micieli, Giuseppe, Cavallini, Anna, Molini, Graziella, Sasanelli, Francesco, Sessa, Maria, Comi, Giancarlo, Checcarelli, Nicoletta, Carmerlingo, Massimo, CORATO, MANUEL, Marcheselli, Simona, Fusi, Laura, Grampa, Giampiero, Uccellini, Davide, Beretta, Simone, Ferrarese, Carlo, Incorvaia, Barbara, Tadeo, Carlo Sebastiano, Adobbati, Laura, Silani, Vincenzo, Faragò, Giuseppe, Trobia, Nadia, Grond-Ginsbach, Caspar, Candelise, Livia, Mazzucchelli, Franca, Guidotti, Mario, Riva, Maurizio, Iurlaro, Simona, Maria, Bianca Bordo, Braga, Massimiliano, Meola, Giovanni, Carpo, Marinella, Camerlingo, Massimo, Borutti, Giuseppina, Delodovici, Marialuisa, Verrengia, Elena Pinuccia, Tancredi, Lucia, Terruzzi, Alessandro, Magoni, Mauro, Del Zotto, Elisabetta, Bassi, Pietro, Lattuada, Patrizia, Ballabio, Elena, Gambaro, Paola, Lanfranconi, Sivia, Corrà, Barbara, Canavero, Isabella, Arbustini, Eloisa, Grasso, Maurizia, Comi, Giacomo Pietro, Corti, Stefania, Ronchi, Dario, Merlini, Giampaolo, Obici, Laura, Bassi, Maria Teresa, Tagliavini, Fabrizio, Ginsbach, Caspar Grond, Bersano, A, Bedini, G, Markus, H, Vitali, P, Colli-Tibaldi, E, Taroni, F, Gellera, C, Baratta, S, Mosca, L, Carrera, P, Ferrari, M, Cereda, C, Grieco, G, Lanfranconi, S, Mazucchelli, F, Zarcone, D, De Lodovici, M, Bono, G, Boncoraglio, G, Parati, E, Calloni, M, Perrone, P, Bordo, B, Motto, C, Agostoni, E, Pezzini, A, Padovani, A, Micieli, G, Cavallini, A, Molini, G, Sasanelli, F, Sessa, M, Comi, G, Checcarelli, N, Carmerlingo, M, Corato, M, Marcheselli, S, Fusi, L, Grampa, G, Uccellini, D, Beretta, S, Ferrarese, C, Incorvaia, B, Tadeo, C, Adobbati, L, Silani, V, Faragò, G, Trobia, N, Grond-Ginsbach, C, Candelise, L, Mazzucchelli, F, Guidotti, M, Riva, M, Iurlaro, S, Maria, B, Braga, M, Meola, G, Carpo, M, Camerlingo, M, Borutti, G, Delodovici, M, Verrengia, E, Tancredi, L, Terruzzi, A, Magoni, M, Del Zotto, E, Bassi, P, Lattuada, P, Ballabio, E, Gambaro, P, Corrà, B, Canavero, I, Arbustini, E, Grasso, M, Corti, S, Ronchi, D, Merlini, G, Obici, L, Bassi, M, Tagliavini, F, Ginsbach, C, Bersano, Anna, BEDINI, GLORIA, Markus, Hugh Stephen, Vitali, Paolo, Colli-Tibaldi, Enrico, Taroni, Franco, Gellera, Cinzia, Baratta, Silvia, Mosca, Lorena, Carrera, Paola, FERRARI, MAURIZIO, Cereda, Cristina, Grieco, Gaetano, Lanfranconi, Silvia, Mazucchelli, Franca, Zarcone, Davide, De Lodovici, Maria Luisa, Bono, Giorgio, Boncoraglio, Giorgio Battista, Parati, Eugenio Agostino, Calloni, Maria Vittoria, Perrone, Patrizia, Bordo, Bianca Maria, Motto, Cristina, Agostoni, Elio, Pezzini, Alessandro, Padovani, Alessandro, Micieli, Giuseppe, Cavallini, Anna, Molini, Graziella, Sasanelli, Francesco, Sessa, Maria, Comi, Giancarlo, Checcarelli, Nicoletta, Carmerlingo, Massimo, CORATO, MANUEL, Marcheselli, Simona, Fusi, Laura, Grampa, Giampiero, Uccellini, Davide, Beretta, Simone, Ferrarese, Carlo, Incorvaia, Barbara, Tadeo, Carlo Sebastiano, Adobbati, Laura, Silani, Vincenzo, Faragò, Giuseppe, Trobia, Nadia, Grond-Ginsbach, Caspar, Candelise, Livia, Mazzucchelli, Franca, Guidotti, Mario, Riva, Maurizio, Iurlaro, Simona, Maria, Bianca Bordo, Braga, Massimiliano, Meola, Giovanni, Carpo, Marinella, Camerlingo, Massimo, Borutti, Giuseppina, Delodovici, Marialuisa, Verrengia, Elena Pinuccia, Tancredi, Lucia, Terruzzi, Alessandro, Magoni, Mauro, Del Zotto, Elisabetta, Bassi, Pietro, Lattuada, Patrizia, Ballabio, Elena, Gambaro, Paola, Lanfranconi, Sivia, Corrà, Barbara, Canavero, Isabella, Arbustini, Eloisa, Grasso, Maurizia, Comi, Giacomo Pietro, Corti, Stefania, Ronchi, Dario, Merlini, Giampaolo, Obici, Laura, Bassi, Maria Teresa, Tagliavini, Fabrizio, and Ginsbach, Caspar Grond

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.

Published
2018

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

Author

Bersano, Anna, Bedini, Gloria, Markus, Hugh Stephen, Vitali, Paolo, Colli-Tibaldi, Enrico, Taroni, Franco, Gellera, Cinzia, Baratta, Silvia, Mosca, Lorena, Carrera, Paola, Ferrari, Maurizio, Cereda, Cristina, Grieco, Gaetano, Lanfranconi, Silvia, Mazucchelli, Franca, Zarcone, Davide, De Lodovici, Maria Luisa, Bono, Giorgio, Boncoraglio, Giorgio Battista, Parati, Eugenio Agostino, Calloni, Maria Vittoria, Perrone, Patrizia, Bordo, Bianca Maria, Motto, Cristina, Agostoni, Elio, Pezzini, Alessandro, Padovani, Alessandro, Micieli, Giuseppe, Cavallini, Anna, Molini, Graziella, Sasanelli, Francesco, Sessa, Maria, Comi, Giancarlo, Checcarelli, Nicoletta, Carmerlingo, Massimo, Corato, Manuel, Marcheselli, Simona, Fusi, Laura, Grampa, Giampiero, Uccellini, Davide, Beretta, Simone, Ferrarese, Carlo, Incorvaia, Barbara, Tadeo, Carlo Sebastiano, Adobbati, Laura, Silani, Vincenzo, Faragò, Giuseppe, Trobia, Nadia, Grond-Ginsbach, Caspar, Candelise, Livia, Mazzucchelli, Franca, Guidotti, Mario, Riva, Maurizio, Iurlaro, Simona, Maria, Bianca Bordo, Braga, Massimiliano, Meola, Giovanni, Carpo, Marinella, Camerlingo, Massimo, Borutti, Giuseppina, Delodovici, Marialuisa, Verrengia, Elena Pinuccia, Tancredi, Lucia, Terruzzi, Alessandro, Magoni, Mauro, Del Zotto, Elisabetta, Bassi, Pietro, Lattuada, Patrizia, Ballabio, Elena, Gambaro, Paola, Lanfranconi, Sivia, Corrà, Barbara, Canavero, Isabella, Arbustini, Eloisa, Grasso, Maurizia, Comi, Giacomo Pietro, Corti, Stefania, Ronchi, Dario, Merlini, Giampaolo, Obici, Laura, Bassi, Maria Teresa, Tagliavini, Fabrizio, Ginsbach, Caspar Grond, Bersano, Anna, Bedini, Gloria, Markus, Hugh Stephen, Vitali, Paolo, Colli-Tibaldi, Enrico, Taroni, Franco, Gellera, Cinzia, Baratta, Silvia, Mosca, Lorena, Carrera, Paola, Ferrari, Maurizio, Cereda, Cristina, Grieco, Gaetano, Lanfranconi, Silvia, Mazucchelli, Franca, Zarcone, Davide, De Lodovici, Maria Luisa, Bono, Giorgio, Boncoraglio, Giorgio Battista, Parati, Eugenio Agostino, Calloni, Maria Vittoria, Perrone, Patrizia, Bordo, Bianca Maria, Motto, Cristina, Agostoni, Elio, Pezzini, Alessandro, Padovani, Alessandro, Micieli, Giuseppe, Cavallini, Anna, Molini, Graziella, Sasanelli, Francesco, Sessa, Maria, Comi, Giancarlo, Checcarelli, Nicoletta, Carmerlingo, Massimo, Corato, Manuel, Marcheselli, Simona, Fusi, Laura, Grampa, Giampiero, Uccellini, Davide, Beretta, Simone, Ferrarese, Carlo, Incorvaia, Barbara, Tadeo, Carlo Sebastiano, Adobbati, Laura, Silani, Vincenzo, Faragò, Giuseppe, Trobia, Nadia, Grond-Ginsbach, Caspar, Candelise, Livia, Mazzucchelli, Franca, Guidotti, Mario, Riva, Maurizio, Iurlaro, Simona, Maria, Bianca Bordo, Braga, Massimiliano, Meola, Giovanni, Carpo, Marinella, Camerlingo, Massimo, Borutti, Giuseppina, Delodovici, Marialuisa, Verrengia, Elena Pinuccia, Tancredi, Lucia, Terruzzi, Alessandro, Magoni, Mauro, Del Zotto, Elisabetta, Bassi, Pietro, Lattuada, Patrizia, Ballabio, Elena, Gambaro, Paola, Lanfranconi, Sivia, Corrà, Barbara, Canavero, Isabella, Arbustini, Eloisa, Grasso, Maurizia, Comi, Giacomo Pietro, Corti, Stefania, Ronchi, Dario, Merlini, Giampaolo, Obici, Laura, Bassi, Maria Teresa, Tagliavini, Fabrizio, Ginsbach, Caspar Grond, Bersano, A, Bedini, G, Markus, H, Vitali, P, Colli-Tibaldi, E, Taroni, F, Gellera, C, Baratta, S, Mosca, L, Carrera, P, Ferrari, M, Cereda, C, Grieco, G, Lanfranconi, S, Mazucchelli, F, Zarcone, D, De Lodovici, M, Bono, G, Boncoraglio, G, Parati, E, Calloni, M, Perrone, P, Bordo, B, Motto, C, Agostoni, E, Pezzini, A, Padovani, A, Micieli, G, Cavallini, A, Molini, G, Sasanelli, F, Sessa, M, Comi, G, Checcarelli, N, Carmerlingo, M, Corato, M, Marcheselli, S, Fusi, L, Grampa, G, Uccellini, D, Beretta, S, Ferrarese, C, Incorvaia, B, Tadeo, C, Adobbati, L, Silani, V, Faragò, G, Trobia, N, Grond-Ginsbach, C, Candelise, L, Mazzucchelli, F, Guidotti, M, Riva, M, Iurlaro, S, Maria, B, Braga, M, Meola, G, Carpo, M, Camerlingo, M, Borutti, G, Delodovici, M, Verrengia, E, Tancredi, L, Terruzzi, A, Magoni, M, Del Zotto, E, Bassi, P, Lattuada, P, Ballabio, E, Gambaro, P, Corrà, B, Canavero, I, Arbustini, E, Grasso, M, Corti, S, Ronchi, D, Merlini, G, Obici, L, Bassi, M, Tagliavini, F, Ginsbach, C, Markus, Hugh [0000-0002-9794-5996], and Apollo - University of Cambridge Repository

Subjects
Adult, Male, Brain hemorrhage, medicine.medical_specialty, Neurology, White matter lesion, Monogenic disorder, CADASIL, Neuroimaging, Gene mutation, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Diagnosis, Medicine, Dementia, Humans, cardiovascular diseases, Prospective Studies, Receptor, Notch3, Neuroradiology, Aged, Cerebral Hemorrhage, Stroke genetics, Monogenic disorders, business.industry, Brain, Middle Aged, medicine.disease, Magnetic Resonance Imaging, White Matter, Prospective Studie, Ischemic Attack, Transient, Stroke genetic, Stroke, Lacunar, Female, Neurology (clinical), Atrophy, business, Neuroscience, NOTCH3 gene, 030217 neurology & neurosurgery, Diagnosi, Human
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., The Lombardia GENS project has received funding from the Regione Lombardia Government as a Research Independent Project (DGR n°VIII/006128-12/12/2007). Lombardia GENS is an investigator-driven, academic, non-profit consortium and is publicly funded. Hugh Markus is supported by an NIHR Senior Investigator award and his work is supported by the Cambridge University Hospitals NIHR Biomedical Research Centre

Published
2018

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

Author

Bersano A, Bedini G, Markus HS, Vitali P, Colli-Tibaldi E, Taroni F, Gellera C, Baratta S, Mosca L, Carrera P, Ferrari M, Cereda C, Grieco G, Lanfranconi S, Mazucchelli F, Zarcone D, De Lodovici ML, Bono G, Boncoraglio GB, Parati EA, Calloni MV, Perrone P, Bordo BM, Motto C, Agostoni E, Pezzini A, Padovani A, Micieli G, Cavallini A, Molini G, Sasanelli F, Sessa M, Comi G, Checcarelli N, Carmerlingo M, Corato M, Marcheselli S, Fusi L, Grampa G, Uccellini D, Beretta S, Ferrarese C, Incorvaia B, Tadeo CS, Adobbati L, Silani V, Faragò G, Trobia N, Grond-Ginsbach C, and Candelise L

Subjects
Adult, Aged, Atrophy, CADASIL genetics, CADASIL physiopathology, Cerebral Hemorrhage diagnosis, Cerebral Hemorrhage genetics, Cerebral Hemorrhage physiopathology, Female, Humans, Ischemic Attack, Transient diagnosis, Ischemic Attack, Transient genetics, Ischemic Attack, Transient physiopathology, Magnetic Resonance Imaging, Male, Middle Aged, Prospective Studies, Stroke, Lacunar diagnosis, Stroke, Lacunar genetics, Stroke, Lacunar physiopathology, White Matter diagnostic imaging, Brain diagnostic imaging, CADASIL diagnosis, Neuroimaging, Receptor, Notch3 genetics
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.

Published
2018
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