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1. 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

2. Long-term applicability of the new ILAE definition of epilepsy. Results from the PRO-LONG study

Author

Beretta, Simone, Carone, Davide, Zanchi, Clara, Bianchi, Elisa, Pirovano, Marta, Trentini, Claudia, Padovano, Giada, Colombo, Matteo, Cereda, Diletta, Scanziani, Sofia, Giussani, Giorgia, Gasparini, Sara, Bogliun, Graziella, Ferrarese, Carlo, Beghi, Ettore, Romeo, Antonino, Viri, Maurizio, Lodi, Monica, Specchio, Luigi, Trivisano, Marina, Mecarelli, Oriano, Zarabla, Alessia, Capovilla, Giuseppe, Beccaria, Francesca, Sasanelli, Francesco, Andrea Galimberti, Carlo, Tartara, Elena, Zamponi, Nelia, Cappanera, Silvia, Aguglia, Umberto, Pustorino, Giuseppe, Ferlazzo, Edoardo, La Neve, Angela, Luisi, Concetta, Pontrelli, Giuseppe, Basso, Pierfranco, Pozzi, Annalisa, Cantisani, Anna Teresa, Papetti, Rossella, De Maria, Giovanni, DiFrancesco, Jacopo C., Albanese, Yasmin, Beretta, S, Carone, D, Zanchi, C, Bianchi, E, Pirovano, M, Trentini, C, Padovano, G, Colombo, M, Cereda, D, Scanziani, S, Giussani, G, Gasparini, S, Bogliun, G, Ferrarese, C, Beghi, E, Romeo, A, Viri, M, Lodi, M, Specchio, L, Trivisano, M, Mecarelli, O, Zarabla, A, Capovilla, G, Beccaria, F, Sasanelli, F, Andrea Galimberti, C, Tartara, E, Zamponi, N, Cappanera, S, Aguglia, U, Pustorino, G, Ferlazzo, E, La Neve, A, Luisi, C, Pontrelli, G, Basso, P, Pozzi, A, Cantisani, A, Papetti, R, De Maria, G, Difrancesco, J, and Albanese, Y

Subjects
Male, Pediatrics, medicine.medical_specialty, Neurology, Adolescent, diagnosis, Early remission, Definition, epilepsy, first seizure, long term, adolescent, child, child, preschool, female, humans, infant, infant, newborn, male, recurrence, retrospective studies, seizures, terminology as topic, Electroencephalography, preschool, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Neuroimaging, Retrospective Studie, newborn, Recurrence, Seizures, Terminology as Topic, medicine, Single unprovoked seizure, Humans, In patient, 030212 general & internal medicine, Child, Retrospective Studies, medicine.diagnostic_test, business.industry, Infant, Newborn, Infant, Retrospective cohort study, medicine.disease, Seizure, Child, Preschool, Physical therapy, Female, Neurology (clinical), business, Diagnosis, First seizure, Long term, 030217 neurology & neurosurgery, Diagnosi, Human
Abstract

SummaryObjective The new epilepsy definition adopted by the International League Against Epilepsy (ILAE) includes patients with one unprovoked seizure with a probability of further seizures, similar to the general recurrence risk after two unprovoked seizures, occurring in a 10-year period. Long-term follow-up of patients diagnosed after a single seizure is needed to assess the applicability of the new epilepsy definition in clinical practice. Methods Patients with newly diagnosed epilepsy were recruited retrospectively with a minimum follow-up of 10 years. Patients were stratified in two groups depending on the occurrence of one (new definition, ND) or two or more unprovoked seizures (traditional definition, TD) at the time of epilepsy diagnosis and compared for disease characteristics and factors predicting seizure recurrence. The primary outcome was the occurrence of a new unprovoked seizure during follow-up in the ND group. The secondary outcome was the achievement of an early remission in both groups. Results Among 1,006 patients with newly diagnosed epilepsy, 152 (15.1%) were diagnosed after a single seizure. Compared to patients diagnosed using the TD, patients diagnosed according to the ND showed a higher proportion of subjects with an abnormal neurologic examination (19.9% vs. 13.7%, p = 0.0504) and with focal seizures (69.3% vs. 60.4%, p = 0.0021). The two samples differed in the presence of at least one of the factors predicting seizure recurrence (focal seizures or abnormal findings in at least one among the following: neurologic examination, electroencephalography [EEG], and neuroimaging) (94.6% vs. 89.1%, p = 0.0376). Long-term recurrence in patients diagnosed with the new definition was 83.6% at 10 years and 89.1% at 15 years. The probability of early remission did not differ between the two groups. Significance Our results support the applicability of the new epilepsy definition in clinical practice. Individual patient characteristics and a personalized diagnostic approach can justify treatment after a single unprovoked seizure.

Published
2017

3. Relevance of clinical context in the diagnostic-therapeutic approach to status epilepticus

Author

Aguglia, Umberto, Sueri, Chiara, Gasparini, Sara, Beghi, Ettore, Labate, Angelo, Gambardella, Antonio, Specchio, Luigi M., Ferlazzo, Edoardo, Aloisi, Paolo, Belcastro, Vincenzo, Benna, Paolo, Bianchi, Amedeo, Bogliun, Graziella, Brigo, Francesco, Buttinelli, Carla, Campostrini, Roberto, Cantello, Roberto, Anna, Teresa Cantisani, Cianci, Vittoria, Congia, Socrate, Consoli, Domenico, Costanzo, Erminio, De Falco Fabrizio, A., De Maria, Giovanni, Bonaventura, Carlo Di, Di Francesco Jacopo, C., Elia, Maurizio, Carlo, Andrea Galimberti, Giallonardo Anna, Teresa, Gigli Gian, Luigi, Iannacchero, Rosario, Iudice, Alfonso, La Neve, Angela, Latella Maria, Adele, Le Piane, Emilio, Marciani Maria, Grazia, Marino, Daniela, Mecarelli, Oriano, Michelucci, Roberto, Minicucci, Fabio, Monti, Fabrizio, Mumoli, Laura, Paciello, Nicola, Paladin, Francesco, Palumbo, Pasquale, Pisani, Francesco, Pisani Laura, Rosa, Sartucci, Ferdinando, Sasanelli, Francesco, Sofia, Vito, Striano, Pasquale, Striano, Salvatore, Strigaro, Gionata, Tinuper, Paolo, Verri, Annapia, Villani, Flavio, Zaccara, Gaetano, Capovilla, Giuseppe, Ferlisi, Monica, Aguglia, U, Sueri, C, Gasparini, S, Beghi, E, Labate, A, Gambardella, A, Specchio, L.M, Ferlazzo, E, Epilepsy Study Group of the Italian Neurological Society and of the Subcommission on Status Epilepticus of the Italian League Against Epilepsy [, Tinuper, P., and ]

Subjects
0301 basic medicine, medicine.medical_specialty, MEDLINE, Context (language use), Status epilepticus, Neurology, Neurology (clinical), 03 medical and health sciences, Therapeutic approach, 0302 clinical medicine, Text mining, Status Epilepticus, medicine, Humans, Relevance (information retrieval), Electroencephalography, Intensive care medicine, SE, Epilepsy, business.industry, 030104 developmental biology, status epilepticu, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

n.a.

Published
2016
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4. Clinical pregenetic screening for stroke monogenic diseases: Results from lombardia GENS registry

Author

Giorgio Bono, Eloisa Arbustini, Patrizia Perrone, Silvia Baratta, Graziella Molini, Elena Pinuccia Verrengia, Massimiliano Braga, Manuel Corato, Erminio Capitani, Gaetano S. Grieco, Pierluigi Baron, Giampaolo Merlini, Simona Marcheselli, Giuseppe Micieli, Nadia Trobia, Davide Uccellini, Anna Cavallini, Elio Agostoni, Mario Guidotti, Carlo Ferrarese, Alessandro Padovani, Laura Fusi, Caspar Grond-Ginsbach, Giacomo P. Comi, Silvia Lanfranconi, Marco Arnaboldi, Barbara Incorvaia, Livia Candelise, Maria Teresa Bassi, Cristina Motto, Paola Carrera, Lorena Mosca, Nicoletta Checcarelli, Lucia Tancredi, Alessando Pezzini, Hugh S. Markus, Laura Obici, Giancarlo Comi, Bianca Maria Bordo, Maria Luisa De Lodovici, Giorgio B. Boncoraglio, Davide Zarcone, Maurizia Grasso, Dario Ronchi, Maria Sessa, Francesca Mazucchelli, Maria Vittoria Calloni, Stefania Corti, Francesco Sasanelli, Paolo Vitali, Giampiero Grampa, C. Gellera, Maurizio Ferrari, Cristina Cereda, Antonio Colombo, Silvana Penco, Anna Bersano, Franco Taroni, Simone Beretta, Carlo Sebastiano Tadeo, Silvana Quaglini, Eugenio Parati, Bersano, A, Markus, H, Quaglini, S, Arbustini, E, Lanfranconi, S, Micieli, G, Boncoraglio, G, Taroni, F, Gellera, C, Baratta, S, Penco, S, Mosca, L, Grasso, M, Carrera, P, Ferrari, M, Cereda, C, Grieco, G, Corti, S, Ronchi, D, Bassi, M, Obici, L, Parati, E, Pezzini, A, De Lodovici, M, Verrengia, E, Bono, G, Mazucchelli, F, Zarcone, D, Calloni, M, Perrone, P, Bordo, B, Colombo, A, Padovani, A, Cavallini, A, Beretta, S, Ferrarese, C, Motto, C, Agostoni, E, Molini, G, Sasanelli, F, Corato, M, Marcheselli, S, Sessa, M, Comi, G, Checcarelli, N, Guidotti, M, Uccellini, D, Capitani, E, Tancredi, L, Arnaboldi, M, Incorvaia, B, Tadeo, C, Fusi, L, Grampa, G, Merlini, G, Trobia, N, Braga, M, Vitali, P, Baron, P, Grond Ginsbach, C, Candelise, L, Bersano, Anna, Markus, Hugh Stephen, Quaglini, Silvana, Arbustini, Eloisa, Lanfranconi, Silvia, Micieli, Giuseppe, Boncoraglio, Giorgio B., Taroni, Franco, Gellera, Cinzia, Baratta, Silvia, Penco, Silvana, Mosca, Lorena, Grasso, Maurizia, Carrera, Paola, Ferrari, Maurizio, Cereda, Cristina, Grieco, Gaetano, Corti, Stefania, Ronchi, Dario, Bassi, Maria Teresa, Obici, Laura, Parati, Eugenio A., Pezzini, Alessando, De Lodovici, Maria Luisa, Verrengia, Elena P., Bono, Giorgio, Mazucchelli, Francesca, Zarcone, Davide, Calloni, Maria Vittoria, Perrone, Patrizia, Bordo, Bianca Maria, Colombo, Antonio, Padovani, Alessandro, Cavallini, Anna, Beretta, Simone, Ferrarese, Carlo, Motto, Cristina, Agostoni, Elio, Molini, Graziella, Sasanelli, Francesco, Corato, Manuel, Marcheselli, Simona, Sessa, Maria, Comi, Giancarlo, Checcarelli, Nicoletta, Guidotti, Mario, Uccellini, Davide, Capitani, Erminio, Tancredi, Lucia, Arnaboldi, Marco, Incorvaia, Barbara, Tadeo, Carlo Sebastiano, Fusi, Laura, Grampa, Giampiero, Merlini, Giampaolo, Trobia, Nadia, Comi, Giacomo Pietro, Braga, Massimiliano, Vitali, Paolo, Baron, Pierluigi, Grond Ginsbach, Caspar, and Candelise, Livia

Subjects
Adult, Male, Mitochondrial encephalomyopathy, Pediatrics, medicine.medical_specialty, Pathology, DNA Mutational Analysis, CADASIL, Disease, 030204 cardiovascular system & hematology, MELAS syndrome, Leukoencephalopathy, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, genetics, Genetic Testing, Registries, Stroke, cerebral amyloid angiopathy, Aged, Genetic testing, Advanced and Specialized Nursing, Fabry disease, medicine.diagnostic_test, business.industry, cerebral amyloid angiopathy, familial, Marfan syndrome, stroke, Neurology (clinical), Cardiology and Cardiovascular Medicine, familial, Middle Aged, medicine.disease, Mutation, Female, genetic, business, 030217 neurology & neurosurgery
Abstract

Background and Purpose— Lombardia GENS is a multicentre prospective study aimed at diagnosing 5 single-gene disorders associated with stroke (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], hereditary cerebral amyloid angiopathy, and Marfan syndrome) by applying diagnostic algorithms specific for each clinically suspected disease Methods— We enrolled a consecutive series of patients with ischemic or hemorrhagic stroke or transient ischemic attack admitted in stroke units in the Lombardia region participating in the project. Patients were defined as probable when presenting with stroke or transient ischemic attack of unknown etiopathogenic causes, or in the presence of Results— In 209 patients (57.4±14.7 years), the application of the disease-specific algorithm identified 227 patients with possible monogenic disease. Genetic testing identified pathogenic mutations in 7% of these cases. Familial history of stroke was the only significant specific feature that distinguished mutated patients from nonmutated ones. The presence of cerebrovascular risk factors did not exclude a genetic disease. Conclusions— In patients prescreened using a clinical algorithm for monogenic disorders, we identified monogenic causes of events in 7% of patients in comparison to the 1% to 5% prevalence reported in previous series.

Published
2016

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