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22 results on '"Bertolotto, Antonio"'

1. Coverage of the requirements of first and second level stroke unit in Italy.

Author

Bandettini di Poggio M, Toni D, Gandolfo C, Paolicelli D, Zini A, Agostoni E, Bandini F, Ragno M, Altavista MC, Bertolotto A, Siciliano G, Vecchio M, Tambasco N, Gambardella A, Manganotti P, Melis M, Onofrj M, De Michele G, Reale N, Tedeschi G, and Mancardi G

Subjects
Humans, Italy epidemiology, Surveys and Questionnaires, Cerebrovascular Disorders, Neurology, Stroke epidemiology, Stroke therapy
Abstract

Background and Aim: In the scientific literature, there is unanimous consensus that hospitalization in stroke unit (SU) is the most important treatment for stroke patients. In this regard, the Act number 70/2015 by the Italian government identified specific skills that contribute to a classification of SU and outlined a "hub and spoke" stroke network. The aim of our study was to check the coverage of requirements of first and second level SU in the national territory and to shed light on any deficit or misdistribution of resources., Material and Methods: In 2019, a survey on the current situation related to stroke care in Italy was carried out by the Italian Society of Neurology (SIN), The Italian Stroke Organization (ISO), and the Association for the Fight against Stroke (A.L.I.Ce)., Results: First level SU was found to be 58 against a requirement, according to the Act 70/2015, of 240. Second level SU was found to be 52 compared with an expected requirement of 60. Neurointerventionists were 280 nationally, with a requirement of 240. A misdistribution of resources within individual regions was often seen., Conclusions: The survey demonstrated a severe shortage of beds dedicated to cerebrovascular diseases, mainly because of lack of first level SU, especially in central and southern Italy. It also suggests that the current hub and spoke system is not yet fully implemented across the country and that resources should be better distributed in order to ensure uniform and fair care for all stroke patients on the whole territory.

Published
2021
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2. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author

Rheenen, Wouter van, Spek, Rick A. A. van der, Bakker, Mark K., Vugt, Joke J. F. A. van, Hop, Paul J., Zwamborn, Ramona A. J., Klein, Niek de, Westra, Harm Jan, Bakker, Olivier B., Deelen, Patrick, Shireby, Gemma, Needham, Merrilee, Ceroni, Mauro, Simoncini, Costanza, Gagliardi, Stella, Corrado, Lucia, Garton, Fleur C., Mazzini, Letizia, Westeneng, Henk Jan, Ross, Jay P., Valluzzi, Francesco, Aguggia, Marco, Raggi, Flavia, Rini, Augusto, Traynor, Bryan J., Singleton, Andrew B., Ngo, Shyuan T., Corcia, Philippe, Olsen, Catherine M., Hofman, Albert, Van Eijk, Kristel R., Pasterkamp, R. Jeroen, Tittmann, Lukas, Iacoangeli, Alfredo, Mitne Neto, Miguel, Sproviero, Daisy, Cauchi, Ruben J., Ophoff, Roel A., Wiedau Pazos, Martina, Lomen-Hoerth, Catherine, Deerlin, Vivianna M. van, Nicholson, Garth A., Brylev, Lev, Whiteman, David C., Grosskreutz, Julian, Fan, Dongsheng, Couratier, Philippe, Roediger, Annekathrin, Gaur, Nayana, D’alfonso, Sandra, Uitterlinden, André G., Pamphlett, Roger, Fominykh, Vera, Byrne, Ross P., Lieb, Wolfgang, Iazzolino, Barbara, Dekker, Annelot M., Slap Consortium, Demeshonok, Vera, Millecamps, Stéphanie, Ataulina, Anastasia, Rogelj, Boris, Koritnik, Blaž, Zidar, Janez, Ravnik-Glavač, Metka, Franke, Andre, Mcrae, Allan F., Rowe, Dominic B., Peotta, Laura, Cooper-Knock, Johnathan, Glavač, Damjan, Doherty, Mark, Rietschel, Marcella, Stević, Zorica, Drory, Vivian, Meininger, Vincent, Zarrelli, Michele, Povedano, Monica, Gaunt, Tom R., Steyn, Frederik J., Williams, Kelly L., Smith, Bradley N., Cugnasco, Paolo, Papurello, Diego Maria, Nozzoli, Cecilia, Sorarù, Gianni, Mather, Karen A., Ripke, Stephan, Nöthen, Markus M., Sachdev, Perminder S., Henders, Anjali K., Wallace, Leanne, Carvalho, Mamede de, Gromicho, Marta, Pinto, Susana, Marco, Giovanni de, Al Khleifat, Ahmad, Eberle, Michael A., Braun, Alice, Gusmaroli, Graziano, Siciliano, Gabriele, Petri, Susanne, Breen, Gerome, Weber, Markus, Rouleau, Guy A., Rojas García, Ricardo, Silani, Vincenzo, Amouyel, Philippe, Ghiglione, Paolo, Davey Smith, George, Curtis, Charles J., Shatunov, Aleksey, Mill, Jonathan, Mclaughlin, Russell L., Filosto, Massimiliano, Comi, Cristoforo, Gerfo, Annalisa lo, Ferlini, Alessandra, Riva, Nilo, Mora Pardina, Jesus S., Chiveri, Luca, Hardiman, Orla, Torrieri, Maria Claudia, Kenna, Kevin P., Wray, Naomi R., Tsai, Ellen, Runz, Heiko, Franke, Lude, Padovani, Alessandro, Chandran, Siddharthan, Al Chalabi, Ammar, Assialioui, Abdelilah, Labate, Carmelo, Damme, Philip van, Ticozzi, Nicola, Palumbo, Francesca, Inghilleri, Maurizio, Chiò, Adriano, Pal, Suvankar, Lunetta, Christian, Jörk, Alexander, Cichon, Sven, Kraft, Julia, Morrison, Karen E., Ruiz, Luigi, Shaw, Pamela J., Hardy, John, Orrell, Richard W., Sendtner, Michael, Meyer, Thomas, Dion, Patrick A., Calvo, Andrea, Kooyman, Maarten, Başak, Nazli, Gerardi, Francesca, Simone, Isabella L., Kooi, Anneke J. van der, Ratti, Antonia, Ferrandi, Delfina, Fogh, Isabella, Ludolph, Albert C., Moglia, Cristina, Brunetti, Maura, Diamanti, Luca, Barthel, Tabea, Blair, Ian P., Es, Michael A. van, Gallone, Salvatore, Canosa, Antonio, Guerra, Vito, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Ferrarese, Carlo, Nefussy, Beatrice, Theele, Erik, Rinaldi, Fabrizio, Weishaupt, Jochen H., Kiernan, Matthew C., Barberis, Marco, Osmanovic, Alma, Baloh, Robert H., Nordin, Angelica, Lerner, Yossef, Vito, Nicoletta di, Zabari, Michal, Zoccolella, Stefano, Heverin, Mark, Gotkine, Marc, Guaita, Maria Cristina, Brenner, David, Freischmidt, Axel, Sbaiz, Luca, Benyamin, Beben, Glass, Jonathan D., Landers, John E., Tazelaar, Gijs H. P., Rota, Eugenia, Bensimon, Gilbert, Ilse, Benjamin, Brice, Alexis, Durr, Alexandra, Payan, Christine A. M., Saker-Delye, Safa, Wood, Nicholas W., Gentile, Salvatore, Moisse, Matthieu, Topp, Simon, Henderson, Robert D., Rademakers, Rosa, Perrone, Patrizia, Stubendorff, Beatrice, Brown, Robert H., Restuadi, Restuadi, Tremolizzo, Lucio, Mundi, Ciro, Berg, Leonard H. van den, Passarella, Bruno, Delodovici, Maria Luisa, Furlong, Sarah, Bono, Giorgio, Manera, Umberto, Vasta, Rosario, Bombaci, Alessandro, Meineri, Piero, Mauro, Alessandro, Hannon, Eilis, Casale, Federico, Leone, Maurizio, Shaw, Christopher E., Fuda, Giuseppe, Salamone, Paolina, Mathers, Susan, Baird, Denis, Launaro, Nicola, Marchi, Fabiola de, Veldink, Jan H., Gellera, Cinzia, Salachas, François, Witte, Otto W., Andersen, Peter M., Bertolotto, Antonio, Gionco, Maurizio, Leotta, Daniela, Odddenino, Enrico, Slalom Consortium, Tamma, Filippo, Dotta, Michele, Lauria, Giuseppe, Steinbach, Robert, Imperiale, Daniele, Geda, Claudio, Dolzhenko, Egor, Cavallo, Roberto, Pignatta, Pietro, Groen, Ewout J. N., Cotelli, Maria Sofia, Mattei, Marco de, Calabrese, Gianluigi, Sapio, Alessia di, Giardini, Guido, Hübner, Christian A., Corti, Stefania, Bell, Shaughn, Comi, Giancarlo, Mccombe, Pamela A., Tiloca, Cinzia, Parals Consortium, Gawor, Klara, Peverelli, Silvia, Taroni, Franco, Pensato, Viviana, Castellotti, Barbara, Graff, Caroline, Comi, Giacomo P., Cereda, Cristina, Bo, Roberto del, Boero, Giovanni, Slagen Consortium, Vourc’h, Patrick, Stem Cell Aging Leukemia and Lymphoma (SALL), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), van Rheenen, Wouter, van der Spek, Rick AA, Bakker, Mark K, van Vugt, Joke JFA, Benyamin, Beben, Veldink, Jan H, SLALOM Consortium, PARALS Consortium, SLAGEN Consortium, SLAP Consortium, van Rheenen, W, van der Spek, R, Bakker, M, van Vugt, J, Hop, P, Zwamborn, R, de Klein, N, Westra, H, Bakker, O, Deelen, P, Shireby, G, Hannon, E, Moisse, M, Baird, D, Restuadi, R, Dolzhenko, E, Dekker, A, Gawor, K, Westeneng, H, Tazelaar, G, van Eijk, K, Kooyman, M, Byrne, R, Doherty, M, Heverin, M, Al Khleifat, A, Iacoangeli, A, Shatunov, A, Ticozzi, N, Cooper-Knock, J, Smith, B, Gromicho, M, Chandran, S, Pal, S, Morrison, K, Shaw, P, Hardy, J, Orrell, R, Sendtner, M, Meyer, T, Basak, N, van der Kooi, A, Ratti, A, Fogh, I, Gellera, C, Lauria, G, Corti, S, Cereda, C, Sproviero, D, D'Alfonso, S, Soraru, G, Siciliano, G, Filosto, M, Padovani, A, Chio, A, Calvo, A, Moglia, C, Brunetti, M, Canosa, A, Grassano, M, Beghi, E, Pupillo, E, Logroscino, G, Nefussy, B, Osmanovic, A, Nordin, A, Lerner, Y, Zabari, M, Gotkine, M, Baloh, R, Bell, S, Vourc'H, P, Corcia, P, Couratier, P, Millecamps, S, Meininger, V, Salachas, F, Mora Pardina, J, Assialioui, A, Rojas-Garcia, R, Dion, P, Ross, J, Ludolph, A, Weishaupt, J, Brenner, D, Freischmidt, A, Bensimon, G, Brice, A, Durr, A, Payan, C, Saker-Delye, S, Wood, N, Topp, S, Rademakers, R, Tittmann, L, Lieb, W, Franke, A, Ripke, S, Braun, A, Kraft, J, Whiteman, D, Olsen, C, Uitterlinden, A, Hofman, A, Rietschel, M, Cichon, S, Nothen, M, Amouyel, P, Traynor, B, Singleton, A, Mitne Neto, M, Cauchi, R, Ophoff, R, Wiedau-Pazos, M, Lomen-Hoerth, C, van Deerlin, V, Grosskreutz, J, Roediger, A, Gaur, N, Jork, A, Barthel, T, Theele, E, Ilse, B, Stubendorff, B, Witte, O, Steinbach, R, Hubner, C, Graff, C, Brylev, L, Fominykh, V, Demeshonok, V, Ataulina, A, Rogelj, B, Koritnik, B, Zidar, J, Ravnik-Glavac, M, Glavac, D, Stevic, Z, Drory, V, Povedano, M, Blair, I, Kiernan, M, Benyamin, B, Henderson, R, Furlong, S, Mathers, S, Mccombe, P, Needham, M, Ngo, S, Nicholson, G, Pamphlett, R, Rowe, D, Steyn, F, Williams, K, Mather, K, Sachdev, P, Henders, A, Wallace, L, de Carvalho, M, Pinto, S, Petri, S, Weber, M, Rouleau, G, Silani, V, Curtis, C, Breen, G, Glass, J, Brown, R, Landers, J, Shaw, C, Andersen, P, Groen, E, van Es, M, Pasterkamp, R, Fan, D, Garton, F, Mcrae, A, Davey Smith, G, Gaunt, T, Eberle, M, Mill, J, Mclaughlin, R, Hardiman, O, Kenna, K, Wray, N, Tsai, E, Runz, H, Franke, L, Al-Chalabi, A, Van Damme, P, van den Berg, L, Veldink, J, Ferrarese, C, Neurology, ANS - Neuroinfection & -inflammation, APH - Methodology, APH - Quality of Care, EURO-NMD, Internal Medicine, Epidemiology, Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512), van Rheenen, W., Van der Spek, R.A.A., Bakker, M.K., van Vugt, J.J.F.A., Hop, P.J., Zwamborn, R.A.J., de Klein, N., Westra, H.J., Bakker, O.B., Deelen, P., Shireby, G., Hannon, E., Moisse, M., Baird, D., Restuadi, R., Dolzhenko, E., Dekker, A.M., Gawor, K., Westeneng, H.J., Tazelaar, G.H.P., van Eijk, K.R., Kooyman, M., Byrne, R.P., Doherty, M., Heverin, M., Al Khleifat, A., Iacoangeli, A., Shatunov, A., Ticozzi, N., Cooper-Knock, J., Smith, B.N., Gromicho, M., Chandran, S., Pal, S., Morrison, K.E., Shaw, P.J., Hardy, J., Orrell, R.W., Sendtner, M., Meyer, T., van der Kooi, A.J., Ratti, A., Fogh, I., Gellera, C., Lauria, G., Corti, S., Cereda, C., Sproviero, D., D'Alfonso, S., Sorarù, G., Siciliano, G., Filosto, M., Padovani, A., Chiò, A., Calvo, A., Moglia, C., Brunetti, M., Canosa, A., Grassano, M., Beghi, E., Pupillo, E., Logroscino, G., Nefussy, B., Osmanovic, A., Nordin, A., Lerner, Y., Zabari, M., Gotkine, M., Baloh, R.H., Bell, S., Vourc'h, P., Corcia, P., Couratier, P., Millecamps, S., Meininger, V., Salachas, F., Mora Pardina, J.S., Assialioui, A., Rojas-García, R., Dion, P.A., Ross, J.P., Ludolph, A.C., Weishaupt, J.H., Brenner, D., Freischmidt, A., Bensimon, G., Brice, A., Durr, A., Payan, C.A.M., Saker-Delye, S., Wood, N.W., Topp, S., Rademakers, R., Tittmann, L., Lieb, W., Franke, A., Ripke, S., Kraft, J.,Whiteman, David C., Olsen, Catherine M., Uitterlinden, A.G., Hofman, A., Rietschel, M., Cichon, S., Nothen, M.M., Amouyel, P., Comi, G., Riva, N., Lunetta, C., Gerardi, F., Cotelli, M.S., Rinaldi, F., Chiveri, L., Guaita, M.C., Perrone, P., Ceroni, M., Diamanti, L., Ferrarese, C., Tremolizzo, L., Delodovici, M.L., Bono, G., Manera, U., Vasta, R., Bombaci, A., Casale, F., Fuda, G., Salamone, P., Iazzolino, B., Peotta, L., Cugnasco, P., De Marco, G., Torrieri, M.C., Palumbo, F., Gallone, S., Barberis, M., Sbaiz, L., Gentile, S., Mauro, A., Mazzini, L., De Marchi, F., Corrado, L., Bertolotto, A., Gionco, M., Leotta, D., Odddenino, E., Imperiale, D., Cavallo, R., Pignatta, P., De Mattei, M., Geda, C., Papurello, D.M., Gusmaroli, G., Comi, C., Labate, C., Ruiz, L., Ferrandi, D., Rota, E., Aguggia, M., Di Vito, N., Meineri, P., Ghiglione, P., Launaro, N., Dotta, M., Di Sapio, A., Giardini, G., Tiloca, C., Peverelli, S., Taroni, F., Pensato, V., Castellotti, B., Comi, G.P., Del Bo, R., Gagliardi, S., Raggi, F., Simoncini, C., Lo Gerfo, A., Inghilleri, M., Ferlini, A., Simone, I.L., Passarella, B., Guerra, V., Zoccolella, S., Nozzoli, C., Mundi, C., Leone, M., Zarrelli, M., Tamma, F., Valluzzi, F., Calabrese, G., Boero, G., Rini, A., Traynor, B.J., Singleton, A.B., Neto, M.M., Cauchi, R.J., Ophoff, R.A., Wiedau-Pazos, M., Lomen-Hoerth, C., van Deerlin, V.M., Grosskreutz, J., Roediger, A., Gaur, N., Jork, A., Barthel, T., Theele, E., Ilse, B., Stubendorff, B., Witte, O.W., Steinbach, R., Hubner, C.A., Graff, C., Brylev, L., Fominykh, V., Demeshonok, V., Ataulina, A., Rogelj, B., Koritnik, B., Zidar, J., Ravnik-Glavac, M., Glavac, D., Stevic, Z., Drory, V., Povedano, M., Blair, I.P., Kiernan, M.C., Benyamin, B., Henderson, R.D., Furlong, S., Mathers, S., McCombe, P.A, Needham, M., Ngo, S.T., Nicholson, G.A., Pamphlett, R., Rowe, D.B., Steyn, F.J., Williams, K.L., Mather, K.A., Sachdev, P.S., Henders, A.K., Wallace, L., de Carvalho, M., Pinto, S., Petri, S., Weber, M., Rouleau, G.A., Silani, V., Curtis, C.J., Breen, G., Glass, J.D., Brown, R.H., Landers, J.E., Shaw, C.E., Andersen, P.M., Groen, E.J.N, van Es, M.A., Pasterkamp, R.J., Fan, D.S., Garton, F.C., McRae, A.F., Smith, G.D., Gaunt, T.R., Eberle, M.A., Mill, J., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Wray, N.R., Tsai, E.L., Runz, H., Franke, L., Al-Chalabi, A., Van Damme, P., van den Berg, L.H., Veldink, J.H., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), and School of Medicine

Subjects
Male, Genetics and heredity, amyotrophic lateral sclerosis, Neurologi, Glutamine, Medizin, Genome-wide association study, Disease, SUSCEPTIBILITY, Genome-wide association studies, DISEASE, Genètica mèdica, 0302 clinical medicine, neurodegenerative disease, genome-wide association study, ALS, gene, autophagy, Risk Factors, amyotrophic lateral sclerosi, RNA-Seq, Amyotrophic lateral sclerosis, disease-modifying therapies, blood [Cholesterol], Genetics, Genetics & Heredity, Neurons, 0303 health sciences, Medical genetics, Neurodegenerative diseases, Genome-wide association, Mendelian randomization, Frontotemporal dementia, Hexanucleotide repeat, Mutant SOD1, Metaanalysis, ALS, Susceptibility, Identification, Brain, Amyotrophic Lateral Sclerosis, Cholesterol, Disease Progression, Female, Humans, Mendelian Randomization Analysis, Microsatellite Repeats, Neurodegenerative Diseases, Quantitative Trait Loci, Genome-Wide Association Study, Mutation, MUTANT SOD1, genetics [Amyotrophic Lateral Sclerosis], medicine.anatomical_structure, Neurology, risk factor, metabolism [Neurons], MENDELIAN RANDOMIZATION, nerve cell, Life Sciences & Biomedicine, quantitative trait locu, Biology, 03 medical and health sciences, Amyotrophic lateral sclerosis -- Diagnosis, blood, ddc:570, medicine, degenerative disease, Motor neuron disease, human, Genomes, GENOME-WIDE ASSOCIATION, gene, Gene, metabolism [Glutamine], METAANALYSIS, 030304 developmental biology, Mendelian randomization analysi, Science & Technology, HEXANUCLEOTIDE REPEAT, meta analysi, IDENTIFICATION, metabolism [Amyotrophic Lateral Sclerosis], FRONTOTEMPORAL DEMENTIA, medicine.disease, metabolism [Brain], genetics [Neurodegenerative Diseases], Expression quantitative trait loci, disease exacerbation, Neuron, gemone, genetic, Vesicle-mediated transport, metabolism, Nervous system -- Degeneration, Esclerosi lateral amiotròfica, 030217 neurology & neurosurgery
Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons., Dutch Research Council (NWO); VENI Scheme Grant; VIDI Grant; Prinses Beatrix Spierfonds; Neuromuscular Fellowship Grant; Medical Research Council (MRC); Clinical Infrastructure Award; Epidemiology Unit; Integrative Epidemiology Unit; Canadian Institutes of Health Research; IWT; National Institute on Aging; National Health and Medical Research Council (NHMRC); Enabling Grant; NHMRC/Australian Research Council Strategic Award; NHMRC; NHMRC Centre of Research Excellence Grant; National Health and Medical Research Council of Australia (NHMRC) Research Fellowship; United Kingdom, Medical Research Council; Economic and Social Research Council; European Union (EU); Horizon 2020; European Community's Health Seventh Framework Programme; EuroMOTOR; European Research Council (ERC); Research and Innovation Programme; EScORIAL; ALS Foundation Netherlands; Alzheimer’s Society PhD Studentship; ARSla Funding; Biogen; University of Bristol; Motor Neurone Disease Association (MNDA); NIHR Maudsley Biomedical Research Centre; Dutch Ministry of Education, Culture, and Science; Netherlands Organization for Scientific Research (NWO; BRAINSCAPES); Gravitation Program; ALS Liga België; National Lottery of Belgium; KU Leuven Opening the Future Fund; KU Leuven Funds, “Een Hart voor ALS”, “Laeversfonds voor ALS Onderzoek” and the “Valéry Perrier Race against ALS Fund”; E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders; ALS Liga België; “Live now” Charity Foundation; Moscow ALS palliative Care Service; Canadian Institutes of Health; Research Australia; Ice Bucket Challenge Grant; NIH Intramural Research Programs; FightMND Mid-Career Fellowship; NIHR Senior Investigator; Sheffield NIHR Biomedical Research Centre; Motor Neurone Disease Association; National Institute for Health Research (NIHR) Biomedical Research Centre; Maudsley NHS Foundation Trust; King’s College London; NIHR Senior Investigator Award; Netherlands Organization for Health Research and Development; Vici Scheme; Netherlands Organization for Health Research and Development STRENGTH Project; PPP Allowance

Published
2021

3. Prognostic indicators in pediatric clinically isolated syndrome

Author

Iaffaldano, Pietro, Simone, Marta, Lucisano, Giuseppe, Ghezzi, Angelo, Coniglio, Gabriella, Brescia Morra, Vincenzo, Salemi, Giuseppe, Patti, Francesco, Lugaresi, Alessandra, Izquierdo, Guillermo, Bergamaschi, Roberto, Cabrera-Gomez, Jose Antonio, Pozzilli, Carlo, Millefiorini, Enrico, Alroughani, Raed, Boz, Cavit, Pucci, Eugenio, Zimatore, Giovanni Bosco, Sola, Patrizia, Lus, Giacomo, Maimone, Davide, Avolio, Carlo, Cocco, Eleonora, Sajedi, Seyed Aidin, Costantino, Gianfranco, Duquette, Pierre, Shaygannejad, Vahid, Petersen, Thor, Fernández Bolaños, Ricardo, Paolicelli, Damiano, Tortorella, Carla, Spelman, Tim, Margari, Lucia, Amato, Maria Pia, Comi, Giancarlo, Butzkueven, Helmut, Trojano, Maria, Spitaleri, Daniele, Rottoli, Maria Rosa, Ardito, Bonaventura, Iuliano, Gerardo, Montanari, Enrico, Granieri, Enrico, Tedeschi, Gioacchino, Bertolotto, Antonio, Granella, Franco, Di Battista, Giancarlo, Gallo, Paolo, Cavalla, Paola, Bellantonio, Paolo, De Robertis, Francesca, Durelli, Luca, Scarpini, Elio, Rezzonico, Monica, Protti, Alessandra, Solaro, Claudio, Corea, Francesco, Bosco, Antonio, Vianello, Marika, Ferrò, Maria Teresa, Balgera, Roberto, Grasso, Roberta, De Luca, Giovanna, Farina, Deboah, Travaglini, Daniela, di Ioia, Maria, Di Tommaso, Valeria, Mancinelli, Luca, Pietrolongo, Erika, Hupperts, Raymond, Rio, Maria Edite, Terzi, Murat, Barnett, Michael, Slee, Mark, Van Pesch, Vincent, Savino, Aldo, Lechner-Scott, Jeannette, Grammond, Pierre, Singhal, Bhim, Zwanikken, Cees, Fiol, Marcela, Patrucco, Liliana, Paine, Mark, Mccombefrom, Pamela, Grand'Maison, Francois, Iaffaldano, Pietro, Simone, Marta, Lucisano, Giuseppe, Ghezzi, Angelo, Coniglio, Gabriella, Brescia Morra, Vincenzo, Salemi, Giuseppe, Patti, Francesco, Lugaresi, Alessandra, Izquierdo, Guillermo, Bergamaschi, Roberto, Cabrera-Gomez, Jose Antonio, Pozzilli, Carlo, Millefiorini, Enrico, Alroughani, Raed, Boz, Cavit, Pucci, Eugenio, Zimatore, Giovanni Bosco, Sola, Patrizia, Lus, Giacomo, Maimone, Davide, Avolio, Carlo, Cocco, Eleonora, Sajedi, Seyed Aidin, Costantino, Gianfranco, Duquette, Pierre, Shaygannejad, Vahid, Petersen, Thor, Fernández Bolaños, Ricardo, Paolicelli, Damiano, Tortorella, Carla, Spelman, Tim, Margari, Lucia, Amato, Maria Pia, Comi, Giancarlo, Butzkueven, Helmut, Trojano, Maria, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Neurologie (9), Klinische Neurowetenschappen, Morra, Vincenzo Brescia, Cabrera Gomez, Jose Antonio, and Bolaños, Ricardo Fernández

Subjects
Registrie, Male, Multiple Sclerosis, Adolescent, Age of Onset, Child, Demyelinating Diseases, Female, Follow-Up Studies, Humans, Prognosis, Retrospective Studies, Risk Factors, Disease Progression, Registries, Neurology, Neurology (clinical), Prognosi, ONSET MULTIPLE-SCLEROSIS, CHILDHOOD, CHILDREN, PARACLINICAL FEATURES, DISABILITY PROGRESSION, NO, Follow-Up Studie, Retrospective Studie, prognostic indicators, Multiple Sclerosi, pediatric, multiple sclerosis, prognosis, indicators, OPTIC NEURITIS, Risk Factor, Demyelinating Disease, NATURAL-HISTORY, multiple sclerosis, clinically isolated syndrome, prognostic indicators, TRANSVERSE MYELITIS, clinically isolated syndrome, INTERFERON BETA-1B, Settore MED/26 - Neurologia, FOLLOW-UP, Human
Abstract

To assess prognostic factors for a second clinical attack and a first disability worsening event in pediatric clinically isolated syndrome (pCIS) suggestive of Multiple Sclerosis (MS) patients. Objective: To assess prognostic factors for a second clinical attack and a first disability-worsening event in pediatric clinically isolated syndrome (pCIS) suggestive of multiple sclerosis (MS) patients. Methods: A cohort of 770 pCIS patients was followed up for at least 10 years. Cox proportional hazard models and Recursive Partitioning and Amalgamation (RECPAM) tree-regression were used to analyze data. Results: In pCIS, female sex and a multifocal onset were risk factors for a second clinical attack (hazard ratio [HR], 95% confidence interval [CI] = 1.28, 1.06–1.55; 1.42, 1.10–1.84, respectively), whereas disease-modifying drug (DMD) exposure reduced this risk (HR, 95% CI = 0.75, 0.60–0.95). After pediatric onset MS (POMS) diagnosis, age at onset younger than 15 years and DMD exposure decreased the risk of a first Expanded Disability Status Scale (EDSS)-worsening event (HR, 95% CI = 0.59, 0.42–0.83; 0.75, 0.71–0.80, respectively), whereas the occurrence of relapse increased this risk (HR, 95% CI = 5.08, 3.46–7.46). An exploratory RECPAM analysis highlighted a significantly higher incidence of a first EDSS-worsening event in patients with multifocal or isolated spinal cord or optic neuritis involvement at onset in comparison to those with an isolated supratentorial or brainstem syndrome. A Cox regression model including RECPAM classes confirmed DMD exposure as the most protective factor against EDSS-worsening events and relapses as the most important risk factor for attaining EDSS worsening. Interpretation: This work represents a step forward in identifying predictors of unfavorable course in pCIS and POMS and supports a protective effect of early DMD treatment in preventing MS development and disability accumulation in this population. Ann Neurol 2017;81:729–739.

Published
2017

4. To do or not to do? plasma exchange and timing of steroid administration in progressive multifocal leukoencephalopathy

Author

Scarpazza, Cristina, Prosperini, Luca, De Rossi, Nicola, Moiola, Lucia, Sormani, Maria Pia, Gerevini, Simonetta, Capra, Ruggero, Altieri, Marta, Amato, Maria Pia, Artusi, Carlo Alberto, Bandini, Fabio, Barcella, Valeria, Bertolotto, Antonio, Morra, Vincenzo Brescia, Capobianco, Marco, Cavaletti, Guido, Cavalla, Paola, Centonze, Diego, Clerico, Marinella, Cocco, Eleonora, Cordioli, Cinzia, Cosottini, Mirco, D'Aleo, Giangaetano, de Luca, Giovanna, de Riz, Marilena, Deotto, Luciano, Durelli, Luca, Falcini, Mario, Ferrari, Ernesta, Ferrante, Claudio, Fusco, Maria Luisa, Gasperini, Claudio, Ghezzi, Angelo, Grimaldi, Luigi, Guidotti, Mario, Laroni, Alice, Lugaresi, Alessandra, Naldi, Paola, Pane, Chiara, Perrone, Patrizia, Pizzorno, Matteo, Pozzilli, Carlo, Rezzonico, Monica, Rovaris, Marco, Salemi, Giuseppe, Salvetti, Marco, Santuccio, Giuseppe, Scarpini, Elio, Sessa, Edoardo, Solaro, Claudio, Tabiadon, Giulia, Tortorella, Carla, Trojano, Maria, Valentino, Paola, Scarpazza, Cristina, Prosperini, Luca, De Rossi, Nicola, Moiola, Lucia, Sormani, Maria Pia, Gerevini, Simonetta, and Capra, Ruggero, Amato MP, Artusi CA, Bandini F, Barcella V, Bertolotto A, Bresciamorra V, Capobianco M, Cavaletti G, Cavalla P, Centonze D, Clerico M, Cordioli C, D’Aleo G, de Riz M, Deotto L, Durelli L, Falcini M, Ferrari E, Fusco ML, Gasperini C, Ghezzi A, Grimaldi L, Guidotti M, Laroni A, Lugaresi A, Naldi P, Pane C, Perrone P, Pizzorno M, Pozzilli C, Prosperini L, Rezzonico M, Rovaris M, Salemi G, Salvetti M, Santuccio G, Scarpini E, Sessa E, Solaro C, Tabiadon G, Tortorella C, Trojano M, Valentino P

Subjects
Adult, Male, Databases, Factual, Disability Evaluation, Female, Humans, Immune Reconstitution Inflammatory Syndrome, Leukoencephalopathy, Progressive Multifocal, Plasma Exchange, Retrospective Studies, Steroids, Young Adult, Neurology, Neurology (clinical), Progressive Multifocal, Databases, Leukoencephalopathy, Retrospective Studie, Settore MED/26 - Neurologia, Steroid, Factual, Human
Abstract

OBJECTIVE: To retrospectively analyze the effect of plasma exchange (PLEX; yes = PLEX+ , no = PLEX- ) and steroids administration timing (prophylactically [proST] or therapeutically [therST]) on the longitudinal clinical course of patients with natalizumab-related progressive multifocal leukoencephalopathy (PML) and full-blown immune reconstitution inflammatory syndrome (PML-IRIS). METHODS: Clinical and radiological data of 42 Italian patients with PML were analyzed. Patient's data are available until 12 months after PML diagnosis. PLEX and steroids treatment as time-dependent covariates were entered in: (1) a Cox model to investigate their impact on full-blown PML-IRIS latency; (2) an analysis of variance ANOVA to investigate their impact on IRIS duration; and (3) a linear mixed model to assess their impact on the longitudinal clinical course (measured by means of Expanded Disability Status Scale [EDSS]). RESULTS: Treatment with PLEX was not associated to PML-IRIS latency (hazard ratio [HR] = 1.05; p = 0.92), but once IRIS emerged, its duration was significantly longer in patients who underwent PLEX (101 vs 54 days in PLEX+ and PLEX- patients; p = 0.028). Receiving proST versus therST was not associated to IRIS latency (HR = 0.67; p = 0.39) or duration (p = 0.95). Patients who underwent proST had a significantly higher EDSS increase during PML (0.09 EDSS points per month; p = 0.04) as compared to those who had therST. INTERPRETATION: This study highlights that: (1) caution on the use of PLEX should be considered as the current data do not support a beneficial effect of PLEX and (2) caution on the early use of steroids is suggested because their prophylactic use to prevent full-blown PML-IRIS seems to negatively impact on the longitudinal disability course.

Published
2017

5. The still under-investigated role of cognitive deficits in PML diagnosis

Author

Scarpazza, Cristina, De Rossi, Nicola, Moiola, Lucia, Gerevini, Simonetta, Cosottini, Mirco, Capra, Ruggero, Mattioli, Flavia, Amato, Maria Pia, Artusi, Carlo Alberto, Bandini, Fabio, Barcella, Valeria, Bertolotto, Antonio, Bresciamorra, Vincenzo, Capobianco, Marco, Cavaletti, Guido, Cavalla, Paola, Centonze, Diego, Clerico, Marinella, Cordioli, Cinzia, D'Aleo, Giangaetano, de Riz, Marilena, Deotto, Luciano, Durelli, Luca, Falcini, Mario, Ferrari, Ernesta, Fusco, Maria Luisa, Gasperini, Claudio, Ghezzi, Angelo, Grimaldi, Luigi, Guidotti, Mario, Laroni, Alice, Lugaresi, Alessandra, Naldi, Paola, Pane, Chiara, Perrone, Patrizia, Pizzorno, Matteo, Pozzilli, Carlo, Prosperini, Luca, Rezzonico, Monica, Rovaris, Marco, Salemi, Giuseppe, Salvetti, Marco, Santuccio, Giuseppe, Scarpini, Elio, Sessa, Edoardo, Solaro, Claudio, Tabiadon, Giulia, Tortorella, Carla, Trojano, Maria, Valentino, Paola, Scarpazza C, De Rossi N, Gerevini S, Cosottini M, Capra R, Mattioli F, Amato MP, Artusi CA, Bandini F, Barcella V, Bertolotto A, Bresciamorra V, Capobianco M, Cavaletti G, Cavalla P, Centonze D, Clerico M, Cordioli C, D’Aleo G, de Riz M, Deotto L, Durelli L, Falcini M, Ferrari E, Fusco ML, Gasperini C, Ghezzi A, Grimaldi L, Guidotti M, Laroni A, Lugaresi A, Naldi P, Pane C, Perrone P, Pizzorno M, Pozzilli C, Prosperini L, Rezzonico M, Rovaris M, Salemi G, Salvetti M, Santuccio G, Scarpini E, Sessa E, Solaro C, Tabiadon G, Tortorella C, Trojano M, Valentino P., Scarpazza, C, De Rossi, N, Moiola, L, Gerevini, S, Cosottini, M, Capra, R, Mattioli, F, Amato, M, Artusi, C, Bandini, F, Barcella, V, Bertolotto, A, Bresciamorra, V, Capobianco, M, Cavaletti, G, Cavalla, P, Centonze, D, Clerico, M, Cordioli, C, D'Aleo, G, de Riz, M, Deotto, L, Durelli, L, Falcini, M, Ferrari, E, Fusco, M, Gasperini, C, Ghezzi, A, Grimaldi, L, Guidotti, M, Laroni, A, Lugaresi, A, Naldi, P, Pane, C, Perrone, P, Pizzorno, M, Pozzilli, C, Prosperini, L, Rezzonico, M, Rovaris, M, Salemi, G, Salvetti, M, Santuccio, G, Scarpini, E, Sessa, E, Solaro, C, Tabiadon, G, Tortorella, C, Trojano, M, and Valentino, P

Subjects
0301 basic medicine, cognition, medicine.medical_specialty, Pediatrics, italian database, natalizumab, neuropsychological impairment, progressive multifocal leukoencephalopathy, neurology (clinical), neurology, immunology, immunology and allergy, Neurology, Settore MED/17 - Malattie Infettive, Asymptomatic, Apraxia, 03 medical and health sciences, 0302 clinical medicine, medicine, Dementia, Psychiatry, Cognitive deficit, Progressive multifocal leukoencephalopathy, Neuropsychology, Cognition, Progressive multifocal leukoencephalopathy Natalizumab Cognition Neuropsychological impairment Italian database, medicine.disease, 030104 developmental biology, Italian database, Natalizumab, Neuropsychological impairment, Cognition, Italian database, Natalizumab, Neuropsychological impairment, Progressive multifocal leukoencephalopathy, Immunology and Allergy, Immunology, Neurology (clinical), Settore MED/26 - Neurologia, medicine.symptom, Psychology, 030217 neurology & neurosurgery
Abstract

Background: Despite cognitive deficits frequently represent the first clinical manifestations of Progressive Multifocal Leukoencephalopathy (PML) in Natalizumab-treated MS patients, the importance of cognitive deficits in PML diagnosis is still under-investigated. The aim of the current study is to investigate the cognitive deficits at PML diagnosis in a group of Italian patients with PML. Methods: Thirty-four PML patients were included in the study. The demographic and clinical data, the lesion load and localization, and the longitudinal clinical course was compared between patients with (n = 13) and without (n = 15) cognitive deficit upon PML suspicion (the remaining six patients were asymptomatic). Clinical presentation of cognitive symptoms was described in detail. Result: After symptoms detection, the time to diagnosis resulted to be shorter for patients presenting with cognitive than for patients with non cognitive onset (p = 0.03). Within patients with cognitive onset, six patients were presenting with language and/or reading difficulties (46.15%); five patients with memory difficulties (38.4%); three patients with apraxia (23.1%); two patients with disorientation (15.3%); two patients with neglect (15.3%); one patients with object agnosia (7.7%), one patient with perseveration (7.7%) and one patient with dementia (7.7%). Frontal lesions were less frequent (p = 0.03), whereas temporal lesions were slightly more frequent (p = 0.06) in patients with cognitive deficits. The longitudinal PML course seemed to be more severe in cognitive than in non cognitive patients (F = 2.73, p = 0.03), but differences disappeared (F = 1.24, p = 0.29) when balancing for the incidence of immune reconstitution syndrome and for other treatments for PML (steroids, plasma exchange (PLEX) and other therapies (Mefloquine, Mirtazapine, Maraviroc). Conclusion: Cognitive deficits at PML onset manifest with symptoms which are absolutely rare in MS. Their appearance in MS patients should strongly suggest PML. Clinicians should be sensitive to the importance of formal neuropsychological evaluation, with particular focus on executive function, which are not easily detected without a formal assessment.

Published
2017

7. Neurology and Therapy: Looking Back on 2018 and Forward to 2019.

Author

Sabbagh, Marwan and Bertolotto, Antonio

Subjects
*NEUROLOGY
Abstract

An introduction is presented in which the authors discuss various reports within the issue including the guidelines for treatment of multiple sclerosis, evidence-based recommendations for multiple sclerosis patients and practical treatment of lewy body disease.

Published
2019
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8. Development of a Short Version of MSQOL-54 Using Factor Analysis and Item Response Theory.

Author

Rosato, Rosalba, Testa, Silvia, Bertolotto, Antonio, Confalonieri, Paolo, Patti, Francesco, Lugaresi, Alessandra, Grasso, Maria Grazia, Toscano, Anna, Giordano, Andrea, and Solari, Alessandra

Subjects
MULTIPLE sclerosis, QUALITY of life, ITEM response theory, CONFIRMATORY factor analysis, DIFFERENTIAL item functioning (Research bias)
Abstract

Background: The Multiple Sclerosis Quality of Life-54 (MSQOL-54, 52 items grouped in 12 subscales plus two single items) is the most used MS specific health related quality of life inventory. Objective: To develop a shortened version of the MSQOL-54. Methods: MSQOL-54 dimensionality and metric properties were investigated by confirmatory factor analysis (CFA) and Rasch modelling (Partial Credit Model, PCM) on MSQOL-54s completed by 473 MS patients. Their mean age was 41 years, 65% were women, and median Expanded Disability Status Scale (EDSS) score was 2.0 (range 0–9.5). Differential item functioning (DIF) was evaluated for gender, age and EDSS. Dimensionality of the resulting short version was assessed by exploratory factor analysis (EFA) and CFA. Cognitive debriefing of the short instrument (vs. the original) was then performed on 12 MS patients. Results: CFA of MSQOL-54 subscales showed that the data fitted the overall model well. Two subscales (Role Limitations—Physical, Role Limitations—Emotional) did not fit the PCM, and were removed; two other subscales (Health Perceptions, Social Function) did not fit the model, but were retained as single items. Sexual Satisfaction (single-item subscale) was also removed. The resulting MSQOL-29 consisted of 25 items grouped in 7 subscales, plus 4 single items. PCM fit statistics were within the acceptability range for all MSQOL-29 items except one which had significant DIF by age. EFA and CFA indicated adequate fit to the original two-factor (Physical and Mental Health Composites) hypothesis. Cognitive debriefing confirmed that MSQOL-29 was acceptable and had lost no key items. Conclusions: The proposed MSQOL-29 is 50% shorter than MSQOL-54, yet preserves key quality of life dimensions. Prospective validation on a large, independent MS patient sample is ongoing. [ABSTRACT FROM AUTHOR]

Published
2016
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9. The use of the 25 Sprotte needle markedly reduces post-dural puncture headache in routine neurological practice.

Author

Bertolotto, Antonio, Malentacchi, Maria, Capobianco, Marco, di Sapio, Alessia, Malucchi, Simona, Motuzova, Yana, Pulizzi, Annalisa, Berchialla, Paola, and Sperli, Francesca

Subjects
*HEADACHE treatment, *NEUROLOGY, *LUMBAR puncture, *PAIN perception, *NEUROLOGISTS, *HEADACHE, *CLINICAL trials, *COMPARATIVE studies, *HYPODERMIC needles, *LONGITUDINAL method, *RESEARCH methodology, *MEDICAL cooperation, *RESEARCH, *EVALUATION research, *EQUIPMENT & supplies, *PREVENTION
Abstract

Objectives: The objectives of this article are to test the feasibility of lumbar puncture (LP) using 25-gauge (G) needles in daily neurological practice and to compare the risk of post-dural puncture headache (PDPH) with four types of needles.Methods: In a prospective rater-blind study, pros and cons of four different LP needles, the 20G Quincke (20Q), 22G Sprotte (22S), 25G Whitacre (25W) and 25G Sprotte (25S), were evaluated in 394 LPs performed by seven neurologists. The neurologist performing the LP recorded the type and size of needle, intensity of pain, safety, time of the procedure and failure or success. Between five and 15 days later another neurologist, blind to the type of needle used, completed an ad-hoc questionnaire for PDPH.Results: PDPH developed in 35.9% patients when using a 20Q needle, and in 12.9%, 6.8% and 1.6%, respectively, when using a 22S, 25W or 25S needle. The difference in incidence of PDPH following LP performed with the 20Q needle and the 25S or 22S was statistically significant (p < 0.001 and p = 0.008, respectively) and it approached significance when comparing the 25S and 25W (p = 0.06). As 25W and 25S needles need CSF aspiration, LP requires more time and skill. Pain caused by LP was similar with the four needles.Conclusion: The use of the 25S needle in diagnostic LP reduces the frequency and severity of PDPH. [ABSTRACT FROM AUTHOR]

Published
2016
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10. Presence and Significant Determinants of Cognitive Impairment in a Large Sample of Patients with Multiple Sclerosis.

Author

Borghi, Martina, Cavallo, Marco, Carletto, Sara, Ostacoli, Luca, Zuffranieri, Marco, Picci, Rocco Luigi, Scavelli, Francesco, Johnston, Harriet, Furlan, Pier Maria, Bertolotto, Antonio, and Malucchi, Simona

Subjects
MILD cognitive impairment, MULTIPLE sclerosis, NEUROPSYCHOLOGICAL tests, NEUROPSYCHIATRY, INTELLIGENCE levels, DEMYELINATION, CONTROL groups
Abstract

Objectives: To investigate the presence and the nature of cognitive impairment in a large sample of patients with Multiple Sclerosis (MS), and to identify clinical and demographic determinants of cognitive impairment in MS. Methods: 303 patients with MS and 279 healthy controls were administered the Brief Repeatable Battery of Neuropsychological tests (BRB-N); measures of pre-morbid verbal competence and neuropsychiatric measures were also administered. Results: Patients and healthy controls were matched for age, gender, education and pre-morbid verbal Intelligence Quotient. Patients presenting with cognitive impairment were 108/303 (35.6%). In the overall group of participants, the significant predictors of the most sensitive BRB-N scores were: presence of MS, age, education, and Vocabulary. The significant predictors when considering MS patients only were: course of MS, age, education, vocabulary, and depression. Using logistic regression analyses, significant determinants of the presence of cognitive impairment in relapsing-remitting MS patients were: duration of illness (OR = 1.053, 95% CI = 1.010–1.097, p = 0.015), Expanded Disability Status Scale score (OR = 1.247, 95% CI = 1.024–1.517, p = 0.028), and vocabulary (OR = 0.960, 95% CI = 0.936–0.984, p = 0.001), while in the smaller group of progressive MS patients these predictors did not play a significant role in determining the cognitive outcome. Conclusions: Our results corroborate the evidence about the presence and the nature of cognitive impairment in a large sample of patients with MS. Furthermore, our findings identify significant clinical and demographic determinants of cognitive impairment in a large sample of MS patients for the first time. Implications for further research and clinical practice were discussed. [ABSTRACT FROM AUTHOR]

Published
2013
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11. Assessment of Normal-Appearing White and Gray Matter in Patients With Primary Progressive Multiple Sclerosis: A Diffusion-Tensor Magnetic Resonance Imaging Study.

Author

Rovaris, Marco, Bozzali, Marco, Iannucci, Giuseppe, Ghezzi, Angelo, Caputo, Domenico, Montanari, Enrico, Bertolotto, Antonio, Bergamaschi, Roberto, Capra, Ruggero, Mancardi, Giovanni Luigi, Martinelli, Vittorio, Comi, Giancarlo, and Filippi, Massimo

Subjects
MULTIPLE sclerosis, NEUROLOGY, MAGNETIC resonance imaging
Abstract

Background: Diffusion-tensor magnetic resonance imaging is sensitive to the more destructive aspects of multiple sclerosis (MS) evolution occurring outside and within T2-visible lesions and, as a consequence, holds promise for providing a more complete picture of primary progressive (PP) MS-related tissue damage than conventional magnetic resonance imaging. Objective: To improve our understanding of PPMS by assessing the extent of occult pathological features in the normal-appearing white and gray matter of the brain using diffusion-tensor magnetic resonance imaging. Methods: Ninety-six patients with PPMS, 47 patients with secondary progressive (SP) MS, and 44 healthy control subjects were studied. T2-hyperintense and Tl-hypointense lesion volumes were calculated, and the volume of the whole brain tissue was measured. Diffusiontensor magnetic resonance imaging scans were postprocessed and analyzed to obtain the mean diffusivity and fractional anisotropy histograms from the brain and from the normal-appearing white and gray matter in isolation. Results: The mean T2-hyperintense and T1-hypointense lesion volumes were lower in patients with PPMS than in patients with SPMS, while the mean absolute brain volumes were similar in the 2 groups. The average lesion diffusivity was significantly higher in patients with SPMS than in patients with PPMS (P<.001). Histogram-derived metrics of the brain tissue and normal-appearing white and gray matter were significantly different between patients with PPMS and healthy subjects (range, P=.004 to <.001). Average diffusivity values were significantly higher in patients with SPMS than in patients with PPMS for all the tissues studied (range, P=.001 to <.001). Fractional anisotropy histogram-derived quantities did not significantly differ between the 2 patient groups (range, P=.94 to .03). Concluslon: This study confirms that, in patients with PPMS, normal-appearing white and gray matter are not spared by disease-related... [ABSTRACT FROM AUTHOR]

Published
2002
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12. The pharmacovigilance program on natalizumab in Italy: 2 years of experience.

Author

Tedeschi, G., Amato, M. P., D'Alessandro, R., Drago, F., Milanese, C., Popoli, P., Rossi, P., Savettieri, G., Tola, M. R., Vanacore, N., Covezzoli, A., De Rosa, M., Comi, G., Pozzilli, Carlo, Bertolotto, Antonio, Marrosu, Maria Giovanna, Grimaldi, Luigi M. E., Piccinni, C., Montanaro, N., and Periotto, Laura

Subjects
MULTIPLE sclerosis, DRUGS, NEUROLOGY, IMMUNOREGULATION
Abstract

At the end of 2006 a country-based surveillance program on natalizumab therapy in multiple sclerosis was settled in Italy by a collaborative effort of the Italian Drug Agency (AIFA) and a group of experts and neurologists appointed by the National Society of Neurology (SIN). After 2 years, 1,818 patients are registered in the database. The majority of cases (88.6%) failed the therapy with beta interferon or glatiramer acetate and had relapses or accumulated disability during immunomodulating treatment, while 11.4% of patients enrolled in the surveillance study were not previously treated with immunomodulating therapies and had a rapidly evolving clinical course. Almost 10% of the patients treated with natalizumab interrupted, for various different reasons, the therapy. Treatment was well tolerated and side effects were similar to those reported in the registrative studies. The majority of treated cases are stable or ameliorated. [ABSTRACT FROM AUTHOR]

Published
2009
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13. Acute myeloid leukemia induced by mitoxantrone treatment for aggressive multiple sclerosis.

Author

Capobianco, Marco, Malucchi, Simona, Ulisciani, Stefano, Fava, Carmen, Cambrin, Giovanna, Avonto, Luigina, Saglio, Giuseppe, and Bertolotto, Antonio

Subjects
MYELOID leukemia, MULTIPLE sclerosis, COMBINATION drug therapy, BONE marrow transplantation, NEUROLOGY
Abstract

Acute myeloid leukemia ( t-AML) is one of the worst adverse events of mitoxantrone treatment, but the exact risk in multiple sclerosis (MS) patients is not yet known. We describe a case wherein the patient developed t-AML 11 months after mitoxantrone had been discontinued. The patient was treated by polychemotherapy and autologous bone marrow transplantation with complete recovery of t-AML and stabilization of the neurological disease. [ABSTRACT FROM AUTHOR]

Published
2008
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14. Comparing Natural History of Early and Late Onset Pediatric Multiple Sclerosis

Author

Ermelinda De Meo, Massimo Filippi, Maria Trojano, Giancarlo Comi, Francasco Patti, Vincenzo Brescia Morra, Giuseppe Salemi, Marco Onofrj, Giacomo Lus, Eleonora Cocco, Mattia Fonderico, Valentina Torri Clerici, Giorgia Teresa Maniscalco, Paola Valentino, Antonio Bertolotto, Alessandra Lugaresi, Roberto Bergamaschi, Marco Rovaris, Patrizia Sola, Gioacchino Tedeschi, Ilaria Pesci, Umberto Aguglia, Paola Cavalla, Davide Maimone, Franco Granella, Marika Vianello, Marta Simone, Emilio Portaccio, Maria Pia Amato, De Meo, E., Filippi, M., Trojano, M., Comi, G., Patti, F., Brescia Morra, V., Salemi, G., Onofrj, M., Lus, G., Cocco, E., Fonderico, M., Torri Clerici, V., Maniscalco, G. T., Valentino, P., Bertolotto, A., Lugaresi, A., Bergamaschi, R., Rovaris, M., Sola, P., Tedeschi, G., Pesci, I., Aguglia, U., Cavalla, P., Maimone, D., Granella, F., Vianello, M., Simone, M., Portaccio, E., Amato, M. P., De Meo, Ermelinda, Filippi, Massimo, Trojano, Maria, Comi, Giancarlo, Patti, Francasco, Brescia Morra, Vincenzo, Salemi, Giuseppe, Onofrj, Marco, Lus, Giacomo, Cocco, Eleonora, Fonderico, Mattia, Torri Clerici, Valentina, Maniscalco, Giorgia Teresa, Valentino, Paola, Bertolotto, Antonio, Lugaresi, Alessandra, Bergamaschi, Roberto, Rovaris, Marco, Sola, Patrizia, Tedeschi, Gioacchino, Pesci, Ilaria, Aguglia, Umberto, Cavalla, Paola, Maimone, Davide, Granella, Franco, Vianello, Marika, Simone, Marta, Portaccio, Emilio, Amato, Maria Pia, De Meo, E, Filippi, M, Trojano, M, Comi, G, Patti, F, Brescia Morra, V, Salemi, G, Onofrj, M, Lus, G, Cocco, E, Fonderico, M, Torri Clerici, V, Maniscalco, Gt, Valentino, P, Bertolotto, A, Lugaresi, A, Bergamaschi, R, Rovaris, M, Sola, P, Tedeschi, G, Pesci, I, Aguglia, U, Cavalla, P, Maimone, D, Granella, F, Vianello, M, Simone, M, Portaccio, E, and Amato, Mp

Subjects
Male, Natural History of Multiple Sclerosis, Multiple Sclerosis, Neurology, Recurrence, Pediatric Multiple Sclerosis, Disease Progression, Humans, Disabled Persons, Settore MED/26 - Neurologia, Neurology (clinical), Child, Prognosis
Abstract

Objective: This study was undertaken to describe and compare disease course and prognosis of early (ie, disease onset before age 11 years) and late (ie, disease onset after age 11 years) onset pediatric multiple sclerosis. Methods: Prospectively collected clinical information from Italian Multiple Sclerosis Register of 1993 pediatric multiple sclerosis patients, of whom 172 had early onset, was analyzed. Cox models adjusted for sex, baseline Expanded Disability Status Scale score, and disease-modifying treatments and stratified for diagnostic criteria adopted (Poser vs McDonald) were used to assess the risk of reaching irreversible Expanded Disability Status Scale scores of 3, 4, and 6, and conversion to secondary progressive phenotype in early versus late onset pediatric patients. Prognostic factors were also evaluated. Results: A greater proportion of males, isolated brainstem involvement, and longer time interval between first and second clinical episode were observed in early versus late onset pediatric patients. Compared to late onset, early onset pediatric patients took longer from disease onset to convert to secondary progressive phenotype and to reach all disability milestones. Recovery from first demyelinating event, time to first relapse, annualized relapse rate during the first 3 years of disease, and disease-modifying treatment exposure were independent predictors for long-term disability in early onset pediatric patients. In late onset pediatric patients, isolated optic neuritis, multifocal symptoms, and progressive course at disease onset were additional predictors for long-term disability. Interpretation: These findings point toward the existence of a different natural history in early versus late onset pediatric multiple sclerosis patients. ANN NEUROL 2022.

Published
2022

15. PML risk is the main factor driving the choice of discontinuing natalizumab in a large multiple sclerosis population: results from an Italian multicenter retrospective study

Author

Clara G, Chisari, Giancarlo, Comi, Massimo, Filippi, Damiano, Paolicelli, Pietro, Iaffaldano, Mauro, Zaffaroni, Vincenzo, Brescia Morra, Eleonora, Cocco, Girolama Alessandra, Marfia, Luigi Maria, Grimaldi, Matilde, Inglese, Simona, Bonavita, Alessandra, Lugaresi, Giuseppe, Salemi, Giovanna, De Luca, Salvatore, Cottone, Antonella, Conte, Patrizia, Sola, Umberto, Aguglia, Giorgia Teresa, Maniscalco, Claudio, Gasperini, Maria Teresa, Ferrò, Ilaria, Pesci, Maria Pia, Amato, Marco, Rovaris, Claudio, Solaro, Giacomo, Lus, Davide, Maimone, Roberto, Bergamaschi, Franco, Granella, Alessia, Di Sapio, Antonio, Bertolotto, Rocco, Totaro, Marika, Vianello, Paola, Cavalla, Paolo, Bellantonio, Vito, Lepore, Francesco, Patti, Simonetta, Venturi, Chisari, Clara G, Comi, Giancarlo, Filippi, Massimo, Paolicelli, Damiano, Iaffaldano, Pietro, Zaffaroni, Mauro, Brescia Morra, Vincenzo, Cocco, Eleonora, Marfia, Girolama Alessandra, Grimaldi, Luigi Maria, Inglese, Matilde, Bonavita, Simona, Lugaresi, Alessandra, Salemi, Giuseppe, De Luca, Giovanna, Cottone, Salvatore, Conte, Antonella, Sola, Patrizia, Aguglia, Umberto, Maniscalco, Giorgia Teresa, Gasperini, Claudio, Ferrò, Maria Teresa, Pesci, Ilaria, Amato, Maria Pia, Rovaris, Marco, Solaro, Claudio, Lus, Giacomo, Maimone, Davide, Bergamaschi, Roberto, Granella, Franco, Di Sapio, Alessia, Bertolotto, Antonio, Totaro, Rocco, Vianello, Marika, Cavalla, Paola, Bellantonio, Paolo, Lepore, Vito, Patti, Francesco, and DIPARTIMENTO DI SCIENZE BIOMEDICHE E NEUROMOTORIE

Subjects
Adult, medicine.medical_specialty, Discontinuation rate, Neurology, Reasons for discontinuation, Population, Progressive Multifocal, Relapsing-Remitting, Settore MED/26, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, Leukoencephalopathy, Internal medicine, parasitic diseases, medicine, Effective treatment, Humans, Immunologic Factors, Multiple sclerosi, 030212 general & internal medicine, education, Retrospective Studies, education.field_of_study, Female, Middle Aged, Leukoencephalopathy, Progressive Multifocal, Multiple Sclerosis, business.industry, Progressive multifocal leukoencephalopathy, Retrospective cohort study, medicine.disease, Discontinuation, Settore MED/26 - Neurologia, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract

none 38 no BACKGROUND: Natalizumab (NTZ) is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). However, patients and physicians may consider discontinuing NTZ therapy due to safety or efficacy issues. The aim of our study was to evaluate the NTZ discontinuation rate and reasons of discontinuation in a large Italian population of RRMS patients. MATERIALS AND METHODS: The data were extracted from the Italian MS registry in May 2018 and were collected from 51,845 patients in 69 Italian multiple sclerosis centers. MS patients with at least one NTZ infusion in the period between June 1st 2012 to May 15th 2018 were included. Discontinuation rates at each time point were calculated. Reasons for NTZ discontinuation were classified as "lack of efficacy", "progressive multifocal leukoencephalopathy (PML) risk" or "other". RESULTS: Out of 51,845, 5151 patients, 3019 (58.6%) females, with a mean age of 43.6 ± 10.1years (median 40), were analyzed. Out of 2037 (39.5%) who discontinued NTZ, a significantly higher percentage suspended NTZ because of PML risk compared to lack of efficacy [1682 (32.7% of 5151) vs 221 (4.3%), p

Published
2021

16. Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Author

Sormani, Maria P., Nicola De Rossi, Irene, Schiavetti, Luca, Carmisciano, Cinzia, Cordioli, Lucia, Moiola, Marta, Radaelli, Paolo, Immovilli, Marco, Capobianco, Maria, Trojano, Paola, Zaratin, Gioacchino, Tedeschi, Giancarlo, Comi, Battaglia, Mario A., Francesco, Patti, Marco, Salvetti, Agostino, Nozzolillo, Alessandra, Bellacosa, Alessandra, Protti, Alessia Di Sapio, Alessio, Signori, Alfredo, Petrone, Alvino, Bisecco, Aniello, Iovino, Anna, Dutto, Anna Maria Repice, Antonella, Conte, Antonio, Bertolotto, Antonio, Bosco, Antonio, Gallo, Antonio, Zito, Arianna, Sartori, Bruno, Giometto, Carla, Tortorella, Carlo, Antozzi, Carlo, Pozzilli, Chiara Rosa Mancinelli, Chiara, Zanetta, Christian, Cordano, Cinzia, Scandellari, Clara, Guaschino, Claudio, Gasperini, Claudio, Solaro, Cristina, Fioretti, Daiana, Bezzini, Damiano, Marastoni, Damiano, Paolicelli, Domizia, Vecchio, Doriana, Landi, Elisabetta, Bucciantini, Elisabetta, Pedrazzoli, Elisabetta, Signoriello, Elvira, Sbragia, Emanuela Laura Susani, Erica, Curti, Eva, Milano, Fabiana, Marinelli, Federico, Camilli, Filippo Martinelli Boneschi, Flora, Govone, Francesca, Bovis, Francesca, Calabria, Francesca, Caleri, Francesca, Rinaldi, Francesca, Vitetta, Francesco, Corea, Francesco, Crescenzo, Francesco, Teatini, Giulietta, Tabiadon, Franco, Granella, Giacomo, Boffa, Giacomo, Lus, Giampaolo, Brichetto, Giorgia Teresa Maniscalco, Giovanna, Borriello, Giovanna De Luca, Giovanna, Konrad, Giovanna, Vaula, Girolama Alessandra Marfia, Giulia, Mallucci, Giuseppe, Liberatore, Giuseppe, Salemi, Giuseppina, Miele, Grazia, Sibilia, Ilaria, Pesci, Laura, Brambilla, Leonardo, Lopiano, Leonardo, Sinisi, Pasquali, Livia, Lorenzo, Saraceno, Luca, Chiveri, Luca, Mancinelli, Grimaldi, Luigi M. E., Luisa Maria Caniatti, Marco Della Cava, Marco, Onofrj, Marco, Rovaris, Marco, Vercellino, Margherita Monti Bragadin, Maria, Buccafusca, Maria Chiara Buscarinu, Maria Grazia Celani, Maria Grazia Grasso, Maria Laura Stromillo, Maria, Petracca, Maria Pia Amato, Maria Pia Sormani, Maria Rita L'Episcopo, Maria, Sessa, Maria Teresa Ferrò, Maria Vittoria Ercolani, Mariangela, Bianco, Marianna Lo Re, Marika, Vianello, Marinella, Clerico, Mario Alberto Battaglia, Mario di Napoli, Marta, Ponzano, Marta Zaffira Conti, Massimiliano, Calabrese, Massimiliano, Mirabella, Massimo, Filippi, Matilde, Inglese, Matteo, Lucchini, Matteo, Pozzato, Maura Chiara Danni, Mauro, Zaffaroni, Mauro, Zampolini, Michela, Ponzio, Milena De Riz, Nicola De Stefano, Paola, Cavalla, Paola De Mitri, Paola, Grossi, Paolo, Confalonieri, Paolo, Gallo, Paolo, Ragonese, Patrizia, Sola, Pietro, Annovazzi, Pietro, Iaffaldano, Raffaele, Nardone, Raffaella, Cerqua, Raffaella, Clerici, Roberta, Lanzillo, Roberta, Motta, Roberto, Balgera, Roberto, Bergamaschi, Rocco, Totaro, Rosa, Iodice, Ruggero, Capra, Sabrina, Marangoni, Sabrina, Realmuto, Salvatore, Cottone, Sara, Montepietra, Sarah, Rasia, Sebastiano, Arena, Sebastiano, Bucello, Silvia, Banfi, Simona, Bonavita, Simona, Malucchi, Simone, Tonietti, Stefano, Vollaro, Susanna, Cordera, Umberto, Aguglia, Valentina Torri Clerici, Valeria, Barcella, Valeria, Bergamaschi, Vincenzo Brescia Morra, Vincenzo, Dattola, and Vittorio Mantero, Sormani, M. P., De Rossi, N., Schiavetti, I., Carmisciano, L., Cordioli, C., Moiola, L., Radaelli, M., Immovilli, P., Capobianco, M., Trojano, M., Zaratin, P., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., P Sormani, Maria, De Rossi, Nicola, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Moiola, Lucia, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, Trojano, Maria, Zaratin, Paola, Tedeschi, Gioacchino, Comi, Giancarlo, A Battaglia, Mario, Patti, Francesco, Salvetti, Marco, Nozzolillo, Agostino, Bellacosa, Alessandra, Protti, Alessandra, Di Sapio, Alessia, Signori, Alessio, Petrone, Alfredo, Bisecco, Alvino, Iovino, Aniello, Dutto, Anna, Maria Repice, Anna, Conte, Antonella, Bertolotto, Antonio, Bosco, Antonio, Gallo, Antonio, Zito, Antonio, Sartori, Arianna, Giometto, Bruno, Tortorella, Carla, Antozzi, Carlo, Pozzilli, Carlo, Rosa Mancinelli, Chiara, Zanetta, Chiara, Cordano, Christian, Scandellari, Cinzia, Guaschino, Clara, Gasperini, Claudio, Solaro, Claudio, Fioretti, Cristina, Bezzini, Daiana, Marastoni, Damiano, Paolicelli, Damiano, Vecchio, Domizia, Landi, Doriana, Bucciantini, Elisabetta, Pedrazzoli, Elisabetta, Signoriello, Elisabetta, Sbragia, Elvira, Laura Susani, Emanuela, Curti, Erica, Milano, Eva, Marinelli, Fabiana, Camilli, Federico, Martinelli Boneschi, Filippo, Govone, Flora, Bovis, Francesca, Calabria, Francesca, Caleri, Francesca, Rinaldi, Francesca, Vitetta, Francesca, Corea, Francesco, Crescenzo, Francesco, Teatini, Francesco, Tabiadon, Giulietta, Granella, Franco, Boffa, Giacomo, Lus, Giacomo, Brichetto, Giampaolo, Teresa Maniscalco, Giorgia, Borriello, Giovanna, De Luca, Giovanna, Konrad, Giovanna, Vaula, Giovanna, Alessandra Marfia, Girolama, Mallucci, Giulia, Liberatore, Giuseppe, Salemi, Giuseppe, Miele, Giuseppina, Sibilia, Grazia, Pesci, Ilaria, Brambilla, Laura, Lopiano, Leonardo, Sinisi, Leonardo, Pasquali, Livia, Saraceno, Lorenzo, Chiveri, Luca, Mancinelli, Luca, E Grimaldi, Luigi M, Maria Caniatti, Luisa, Della Cava, Marco, Onofrj, Marco, Rovaris, Marco, Vercellino, Marco, Monti Bragadin, Margherita, Buccafusca, Maria, Chiara Buscarinu, Maria, Grazia Celani, Maria, Grazia Grasso, Maria, Laura Stromillo, Maria, Petracca, Maria, Pia Amato, Maria, Pia Sormani, Maria, Rita L'Episcopo, Maria, Sessa, Maria, Teresa Ferrò, Maria, Vittoria Ercolani, Maria, Bianco, Mariangela, Lo Re, Marianna, Vianello, Marika, Clerico, Marinella, Alberto Battaglia, Mario, di Napoli, Mario, Ponzano, Marta, Zaffira Conti, Marta, Calabrese, Massimiliano, Mirabella, Massimiliano, Filippi, Massimo, Inglese, Matilde, Lucchini, Matteo, Pozzato, Matteo, Chiara Danni, Maura, Zaffaroni, Mauro, Zampolini, Mauro, Ponzio, Michela, De Riz, Milena, De Stefano, Nicola, Cavalla, Paola, De Mitri, Paola, Grossi, Paola, Confalonieri, Paolo, Gallo, Paolo, Ragonese, Paolo, Sola, Patrizia, Annovazzi, Pietro, Iaffaldano, Pietro, Nardone, Raffaele, Cerqua, Raffaella, Clerici, Raffaella, Lanzillo, Roberta, Motta, Roberta, Balgera, Roberto, Bergamaschi, Roberto, Totaro, Rocco, Iodice, Rosa, Capra, Ruggero, Marangoni, Sabrina, Realmuto, Sabrina, Cottone, Salvatore, Montepietra, Sara, Rasia, Sarah, Arena, Sebastiano, Bucello, Sebastiano, Banfi, Silvia, Bonavita, Simona, Malucchi, Simona, Tonietti, Simone, Vollaro, Stefano, Cordera, Susanna, Aguglia, Umberto, Torri Clerici, Valentina, Barcella, Valeria, Bergamaschi, Valeria, Brescia Morra, Vincenzo, Dattola, Vincenzo, Mantero, Vittorio, Mp, Sormani, N, De Rossi, I, Schiavetti, L, Carmisciano, C, Cordioli, L, Moiola, M, Radaelli, P, Immovilli, M, Capobianco, M, Trojano, P, Zaratin, G, Tedeschi, G, Comi, Ma, Battaglia, F, Patti, M, Salvetti, Study Group Agostino Nozzolillo, Musc-19, Grimaldi, Luigi M. E., Vittorio Mantero, And, Nozzolillo, A., Bellacosa, A., Protti, A., Di Sapio, A., Signori, A., Petrone, A., Bisecco, A., Iovino, A., Dutto, A., Repice, A. M., Conte, A., Bertolotto, A., Bosco, A., Gallo, A., Zito, A., Sartori, A., Giometto, B., Tortorella, C., Antozzi, C., Pozzilli, C., Mancinelli, C. R., Zanetta, C., Cordano, C., Scandellari, C., Guaschino, C., Gasperini, C., Solaro, C., Fioretti, C., Bezzini, D., Marastoni, D., Paolicelli, D., Vecchio, D., Landi, D., Bucciantini, E., Pedrazzoli, E., Signoriello, E., Sbragia, E., Susani, E. L., Curti, E., Milano, E., Marinelli, F., Camilli, F., Boneschi, F. M., Govone, F., Bovis, F., Calabria, F., Caleri, F., Rinaldi, F., Vitetta, F., Corea, F., Crescenzo, F., Teatini, F., Tabiadon, G., Granella, F., Boffa, G., Lus, G., Brichetto, G., Maniscalco, G. T., Borriello, G., De Luca, G., Konrad, G., Vaula, G., Marfia, G. A., Mallucci, G., Liberatore, G., Salemi, G., Miele, G., Sibilia, G., Pesci, I., Brambilla, L., Lopiano, L., Sinisi, L., Pasquali, L., Saraceno, L., Chiveri, L., Mancinelli, L., Grimaldi, L. M. E., Caniatti, L. M., Cava, M. D., Onofrj, M., Rovaris, M., Vercellino, M., Bragadin, M. M., Buccafusca, M., Buscarinu, M. C., Celani, M. G., Grasso, M. G., Stromillo, M. L., Petracca, M., Amato, M. P., L'Episcopo, M. R., Sessa, M., Ferro, M. T., Ercolani, M. V., Bianco, M., Re, M. L., Vianello, M., Clerico, M., di Napoli, M., Ponzano, M., Conti, M. Z., Calabrese, M., Mirabella, M., Filippi, M., Inglese, M., Lucchini, M., Pozzato, M., Danni, M. C., Zaffaroni, M., Zampolini, M., Ponzio, M., De Riz, M., De Stefano, N., Cavalla, P., De Mitri, P., Grossi, P., Confalonieri, P., Gallo, P., Ragonese, P., Sola, P., Annovazzi, P., Iaffaldano, P., Nardone, R., Cerqua, R., Clerici, R., Lanzillo, R., Motta, R., Balgera, R., Bergamaschi, R., Totaro, R., Iodice, R., Capra, R., Marangoni, S., Realmuto, S., Cottone, S., Montepietra, S., Rasia, S., Arena, S., Bucello, S., Banfi, S., Bonavita, S., Malucchi, S., Tonietti, S., Vollaro, S., Cordera, S., Aguglia, U., Clerici, V. T., Barcella, V., Bergamaschi, V., Morra, V. B., Dattola, V., Mantero, V., Sormani M.P., De Rossi N., Schiavetti I., Carmisciano L., Cordioli C., Moiola L., Radaelli M., Immovilli P., Capobianco M., Trojano M., Zaratin P., Tedeschi G., Comi G., Battaglia M.A., Patti F., Salvetti M., Nozzolillo A., Bellacosa A., Protti A., Di Sapio A., Signori A., Petrone A., Bisecco A., Iovino A., Dutto A., Repice A.M., Conte A., Bertolotto A., Bosco A., Gallo A., Zito A., Sartori A., Giometto B., Tortorella C., Antozzi C., Pozzilli C., Mancinelli C.R., Zanetta C., Cordano C., Scandellari C., Guaschino C., Gasperini C., Solaro C., Fioretti C., Bezzini D., Marastoni D., Paolicelli D., Vecchio D., Landi D., Bucciantini E., Pedrazzoli E., Signoriello E., Sbragia E., Susani E.L., Curti E., Milano E., Marinelli F., Camilli F., Boneschi F.M., Govone F., Bovis F., Calabria F., Caleri F., Rinaldi F., Vitetta F., Corea F., Crescenzo F., Teatini F., Tabiadon G., Granella F., Boffa G., Lus G., Brichetto G., Maniscalco G.T., Borriello G., De Luca G., Konrad G., Vaula G., Marfia G.A., Mallucci G., Liberatore G., Salemi G., Miele G., Sibilia G., Pesci I., Brambilla L., Lopiano L., Sinisi L., Pasquali L., Saraceno L., Chiveri L., Mancinelli L., Grimaldi L.M.E., Caniatti L.M., Cava M.D., Onofrj M., Rovaris M., Vercellino M., Bragadin M.M., Buccafusca M., Buscarinu M.C., Celani M.G., Grasso M.G., Stromillo M.L., Petracca M., Amato M.P., L'Episcopo M.R., Sessa M., Ferro M.T., Ercolani M.V., Bianco M., Re M.L., Vianello M., Clerico M., di Napoli M., Ponzano M., Conti M.Z., Calabrese M., Mirabella M., Filippi M., Inglese M., Lucchini M., Pozzato M., Danni M.C., Zaffaroni M., Zampolini M., Ponzio M., De Riz M., De Stefano N., Cavalla P., De Mitri P., Grossi P., Confalonieri P., Gallo P., Ragonese P., Sola P., Annovazzi P., Iaffaldano P., Nardone R., Cerqua R., Clerici R., Lanzillo R., Motta R., Balgera R., Bergamaschi R., Totaro R., Iodice R., Capra R., Marangoni S., Realmuto S., Cottone S., Montepietra S., Rasia S., Arena S., Bucello S., Banfi S., Bonavita S., Malucchi S., Tonietti S., Vollaro S., Cordera S., Aguglia U., Clerici V.T., Barcella V., Bergamaschi V., Morra V.B., Dattola V., and Mantero V.

Subjects
Male, 0301 basic medicine, Dimethyl Fumarate, Neurodegenerative, multiple sclerosis, coronavirus, pneumonia, Severity of Illness Index, law.invention, Immunosuppressive Agent, Immunologic Factor, 0302 clinical medicine, Natalizumab, law, Monoclonal, Multiple Sclerosi, 80 and over, Lung, Humanized, Research Articles, Aged, 80 and over, Middle Aged, Intensive care unit, Hospitalization, Settore MED/26 - NEUROLOGIA, Intensive Care Units, Neurology, Methylprednisolone, Neurological, Pneumonia & Influenza, Interferon, Female, Immunosuppressive Agents, Research Article, Human, medicine.drug, Adult, medicine.medical_specialty, Musc-19 Study Group, Multiple Sclerosis, Adolescent, Clinical Sciences, Intensive Care Unit, Clinical Neurology, Settore MED/26, Antibodies, Monoclonal, Humanized, Autoimmune Disease, Antibodies, Young Adult, 03 medical and health sciences, Clinical Research, Internal medicine, Severity of illness, medicine, Humans, Immunologic Factors, Mortality, Aged, COVID-19, Fingolimod Hydrochloride, Interferons, SARS-CoV-2, Neurology & Neurosurgery, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Neurosciences, Pneumonia, Odds ratio, medicine.disease, Brain Disorders, Good Health and Well Being, 030104 developmental biology, Ocrelizumab, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18–4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (

Published
2021

17. eMSQOL-29: Prospective validation of the abbreviated, electronic version of MSQOL-54

Author

Francesco Patti, Ilaria Rossi, Silvia Testa, Paolo Confalonieri, Francesco Scavelli, Antonio Bertolotto, Andrea Giordano, Rosalba Rosato, Ambra Mara Giovannetti, Erika Pietrolongo, Clara Grazia Chisari, Alessandra Solari, Anna Toscano, Maria Grazia Grasso, Alessandra Lugaresi, Barbara Loera, Rosato, Rosalba, Testa, Silvia, Bertolotto, Antonio, Scavelli, Francesco, Giovannetti, Ambra M, Confalonieri, Paolo, Patti, Francesco, Chisari, Clara Grazia, Lugaresi, Alessandra, Pietrolongo, Erika, Grasso, Maria Grazia, Rossi, Ilaria, Toscano, Anna, Loera, Barbara, Giordano, Andrea, and Solari, Alessandra

Subjects
Adult, Male, Gerontology, Psychometrics, Health-related quality of life, psychometric assessment, MSQOL-54, patient reported outcomes, multiple sclerosis, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), Humans, Patient Reported Outcome Measures, Prospective Studies, 030212 general & internal medicine, electronic migration, Aged, Health related quality of life, Reproducibility of Results, Middle Aged, patient reported outcome, Cross-Sectional Studies, Neurology, multiple sclerosi, Quality of Life, Female, Neurology (clinical), Psychology, 030217 neurology & neurosurgery
Abstract

Background: We recently devised a shortened version of the 54-item Multiple Sclerosis Quality of Life (MSQOL-54) in paper (MSQOL-29, consisting of 25 items forming 7 subscales and 4 single items, and one filter question for 3 ‘sexual function’ items) and electronic format (eMSQOL-29). Objectives: To prospectively assess eMSQOL-29 psychometric properties, acceptability/equivalence versus MSQOL-29. Methods: Multiple sclerosis (MS) patients ( n = 623; Expanded Disability Status Scale (EDSS) range 0.0–9.0) completed eMSQOL-29, Hospital Anxiety and Depression Scale, Functional Assessment of MS (FAMS), European Quality of life Five Dimensions-3L, and received EDSS and Symbol Digit Modalities Test (SDMT). Equivalence versus MSQOL-29 was assessed in 242 patients (randomized cross-over design). Results: ‘Sexual function’ items were filtered out by 273 patients (47%). No multi-item scale had floor effect, while five had ceiling effect. Cronbach’s alpha range was 0.88–0.90. Confirmatory factor analysis showed good overall fit and the two-factor solution for composite scores was confirmed. Criterion validity was sub-optimal for ‘cognitive function’ (vs SDMT, r = 0.25) and ‘social function’ (vs FAMS social function, r = 0.38). eMSQOL-29 equivalence was confirmed and its acceptability was good. Conclusion: eMSQOL-29 showed good internal consistency, factor structure and no floor effect, while most subscales had some ceiling effect. Criterion validity was sub-optimal for two subscales. Equivalence and acceptability were good.

Published
2018

18. A Comprehensive Review on Copemyl®

Author

E. Montanari, Francesco Patti, Pierluigi Navarra, Angelo Ghezzi, Vincenzo Brescia Morra, Maria Pia Sormani, Antonio Bertolotto, Pietro Annovazzi, Claudio Gasperini, Annovazzi, Pietro, Bertolotto, Antonio, Brescia Morra, Vincenzo, Gasperini, Claudio, Montanari, Enrico, Navarra, Pierluigi, Patti, Francesco, Sormani, Maria Pia, and Ghezzi, Angelo

Subjects
0301 basic medicine, Drug, medicine.medical_specialty, Bioequivalence, Copemyl®, Glatiramer acetate, Glatiramoid, Multiple sclerosis, Non-biological complex drugs, Neurology, Neurology (clinical), Settore BIO/14 - FARMACOLOGIA, media_common.quotation_subject, Alternative medicine, Review, Pharmacology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Medicine, In patient, Multiple sclerosi, Non-biological complex drug, media_common, Class (computer programming), business.industry, Biosimilar, Copemyl®, 030104 developmental biology, Economic sustainability, Risk analysis (engineering), business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Economic sustainability is of paramount importance in the rapidly evolving therapeutic scenario of multiple sclerosis (MS). Glatiramoids are a class of drugs whose forefather, glatiramer acetate, has been used as a disease modifying drug (DMD) in patients with MS for over 20 years. Its patent expired in 2015; new versions of such drug are nowadays available on the market, potentially contributing to lowering prices and enhancing a better allocation of economic resources. In this review, we analyze the recommendations underlying the approval of both generic drugs and biosimilars by regulatory authorities, and we provide methodological tools to contextualize the design of studies on these new classes of drugs. We examine in more detail the preclinical and clinical data of Copemyl®, a new member of the glatiramoid class, focusing on its biological and immunological properties and illustrating randomized controlled trials that led to its authorization.

Published
2017

19. Authors' Response to the Letter to the Editor Regarding: A Comprehensive Review on Copemyl®

Author

Vincenzo Brescia Morra, Angelo Ghezzi, Pierluigi Navarra, Antonio Bertolotto, Claudio Gasperini, Maria Pia Sormani, Pietro Annovazzi, E. Montanari, Francesco Patti, Annovazzi, Pietro, Bertolotto, Antonio, Brescia Morra, Vincenzo, Gasperini, Claudio, Montanari, Enrico, Navarra, Pierluigi, Patti, Francesco, Pia Sormani, Maria, and Ghezzi, Angelo

Subjects
medicine.medical_specialty, Letter to the editor, Neurology, Letter, MEDLINE, Bioequivalence, ®, lcsh:RC346-429, Multiple sclerosis, Equivalence trial, 03 medical and health sciences, 0302 clinical medicine, Glatiramer acetate, medicine, Multiple sclerosi, Medical physics, 030212 general & internal medicine, Copemyl, Equivalence trials, Glatiramoid, Non-biological complex drugs, Copemyl®, lcsh:Neurology. Diseases of the nervous system, business.industry, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Published
2018

20. Management of pregnancy-related issues in multiple sclerosis patients: the need for an interdisciplinary approach

Author

Paola Cavalla, Nicola Strobelt, Maria Giovanna Marrosu, Roberto Brunelli, Maria Pia Amato, Leandro Provinciali, Maria Trojano, Antonio Bertolotto, Carlo Pozzilli, Giancarlo Comi, Francesco Patti, Benedetta Goretti, Nicola Rizzo, Gioacchino Tedeschi, Amato, Maria Pia, Bertolotto, Antonio, Brunelli, Roberto, Cavalla, Paola, Goretti, Benedetta, Marrosu, Maria Giovanna, Patti, Francesco, Pozzilli, Carlo, Provinciali, Leandro, Rizzo, Nicola, Strobelt, Nicola, Tedeschi, Gioacchino, Trojano, Maria, and Comi, Giancarlo

Subjects
medicine.medical_specialty, Neurology, Dermatology, Disease, Interdisciplinary approach, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Glatiramer acetate, Pregnancy, medicine, Animals, Humans, Multiple sclerosi, 030212 general & internal medicine, Young adult, Relapse, Intensive care medicine, Psychiatry, Contraindication, business.industry, Disease Management, General Medicine, medicine.disease, Discontinuation, Pregnancy Complications, Treatment, Psychiatry and Mental Health, Female, Neurology (clinical), business, 2708, 030217 neurology & neurosurgery, medicine.drug
Abstract

Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system (CNS), most probably autoimmune in origin, usually occurring in young adults with a female/male prevalence of approximately 3:1. Women with MS in the reproductive age may face challenging issues in reconciling the desire for parenthood with their condition, owing to the possible influence both on the ongoing or planned treatment with the possible consequences on the disease course and on the potential negative effects of treatments on foetal and pregnancy outcomes. At MS diagnosis, timely counselling should promote informed parenthood, while disease evolution should be assessed before making therapeutic decisions. Current guidelines advise the discontinuation of any treatment during pregnancy, with possible exceptions for some treatments in patients with very active disease. Relapses decline during pregnancy but are more frequent during puerperium, when MS therapy should be promptly resumed in most of the cases. First-line immunomodulatory agents, such as interferon-β (IFN-β) and glatiramer acetate (GA), significantly reduce the post-partum risk of relapse. Due to substantial evidence of safety with the use of GA during pregnancy, a recent change in European marketing authorization removed the pregnancy contraindication for GA. This paper reports a consensus of Italian experts involved in MS management, including neurologists, gynaecologists and psychologists. This consensus, based on a review of the available scientific evidence, promoted an interdisciplinary approach to the management of pregnancy in MS women.

Published
2017

21. Natalizumab treatment reduces L-selectin (CD62L) in CD4+ T cells

Author

Antonio Bertolotto, Michela Spadaro, Alessandra Lugaresi, Marzia Caldano, Fabiana Marnetto, Spadaro, Michela, Caldano, Marzia, Marnetto, Fabiana, Lugaresi, Alessandra, and Bertolotto, Antonio

Subjects
CD4-Positive T-Lymphocytes, Male, Pathology, Monocyte, Gastroenterology, Monocytes, Leukocyte Count, Immunologic Factor, Natalizumab, Immune Reconstitution Inflammatory Syndrome, Multiple Sclerosi, L-Selectin, biology, General Neuroscience, Progressive multifocal leukoencephalopathy, Middle Aged, Fingolimod, Neurology, CD4-Positive T-Lymphocyte, L-selectin, Rituximab, Female, medicine.symptom, Human, medicine.drug, Adult, medicine.medical_specialty, Multiple Sclerosis, Immunology, Asymptomatic, Cellular and Molecular Neuroscience, Young Adult, Internal medicine, parasitic diseases, medicine, Humans, Immunologic Factors, CD62L, Glatiramer acetate, Aged, Neuroscience (all), PML, business.industry, Fingolimod Hydrochloride, Multiple sclerosis, Research, IRIS, Glatiramer Acetate, Interferon-beta, medicine.disease, biology.protein, business
Abstract

Background The purpose of this research was to validate the low expression of L-selectin (CD62L) in natalizumab (NTZ)-treated patients. CD62L is involved in rolling and transmigration of leukocyte cells. A correlation between CD62LCD4+ T cells low expression and progressive multifocal leukoencephalopathy (PML) development has been suggested in multiple sclerosis (MS) patients treated with NTZ. Methods We performed a flow cytometric analysis on peripheral blood mononuclear cells (PBMC); we collected from 23 healthy donors and 225 MS patients: untreated (n = 19) or treated with NTZ (n = 113), interferon-beta (n = 26), glatiramer acetate (n = 26), fingolimod (n = 23) and rituximab (n = 18). We have also analysed two PML/IRIS (immune reconstitution inflammatory syndrome) patients and four longitudinal samples of a NTZ-treated patients before and during the development of a clinical asymptomatic magnetic resonance imaging (MRI) lesion confirmed as PML by cerebrospinal fluid (CSF) examination. Thirty-five NTZ-treated patients were studied longitudinally with three samples taken 4 months apart. Results The NTZ-treated patients showed a lower percentage of CD62L (33.68 %, n = 113) than first-line treated patients (44.24 %, n = 52, p = 0.0004). NTZ effect was already clear during the first year of treatment (34.68 %; p = 0.0184); it persisted in the following years and disappeared after drug withdrawal (44.08 %). Three percent of longitudinally analysed patients showed a percentage of CD62LCD4+ T cells under a hypothetical threshold and one patient with asymptomatic PML belongs to a group which expressed low percentage of CD62LCD4+ T cells. Conclusions Our research confirms that NTZ has a specific effect on CD62LCD4+ T cells consisting in decreasing of the number of positive cells. The low level of CD62L found in a clinically asymptomatic PML patient strengthens its potential usefulness as a biomarker of high PML risk in NTZ-treated patients. A larger study is required to better confirm the data. Electronic supplementary material The online version of this article (doi:10.1186/s12974-015-0365-x) contains supplementary material, which is available to authorized users.

Published
2015

22. Development of a Short Version of MSQOL-54 Using Factor Analysis and Item Response Theory

Author

Antonio Bertolotto, Paolo Confalonieri, Alessandra Lugaresi, Rosalba Rosato, Francesco Patti, Maria Grazia Grasso, Anna Toscano, Alessandra Solari, Silvia Testa, Andrea Giordano, Rosato, Rosalba, Testa, Silvia, Bertolotto, Antonio, Confalonieri, Paolo, Patti, Francesco, Lugaresi, Alessandra, Grasso, Maria Grazia, Toscano, Anna, Giordano, Andrea, and Solari, Alessandra

Subjects
Male, Psychometrics, lcsh:Medicine, Social Sciences, QUALITY-OF-LIFE, COMPOSITE MEASUREMENT SCALES, REPORTED OUTCOME MEASURES, MULTIPLE-SCLEROSIS, QUESTIONNAIRE MSQOL-54, RASCH ANALYSIS, VALIDATION, INSTRUMENT, Disability Evaluation, Cognition, Mathematical and Statistical Techniques, 0302 clinical medicine, Quality of life, Multiple Sclerosi, Item response theory, Medicine and Health Sciences, Psychology, Ethnicities, Prospective Studies, 030212 general & internal medicine, lcsh:Science, media_common, Multidisciplinary, Medicine (all), Neurodegenerative Diseases, Middle Aged, Italian People, Neurology, Physical Sciences, Female, Factor Analysis, Statistics (Mathematics), Human, Research Article, Clinical psychology, Adult, medicine.medical_specialty, Multiple Sclerosis, media_common.quotation_subject, Immunology, Research and Analysis Methods, behavioral disciplines and activities, Autoimmune Diseases, 03 medical and health sciences, Mental Health and Psychiatry, medicine, Humans, Quality (business), Statistical Methods, Psychiatry, Aged, Health related quality of life, Biochemistry, Genetics and Molecular Biology (all), lcsh:R, Cognitive Psychology, Biology and Life Sciences, Eigenvalues, Demyelinating Disorders, Health Care, Prospective Studie, Algebra, Agricultural and Biological Sciences (all), Linear Algebra, People and Places, Quality of Life, Cognitive Science, lcsh:Q, Clinical Immunology, Perception, Population Groupings, Clinical Medicine, Factor Analysis, Statistical, Psychomotor Performance, Mathematics, 030217 neurology & neurosurgery, Neuroscience
Abstract

Background: The Multiple Sclerosis Quality of Life-54 (MSQOL-54, 52 items grouped in 12 subscales plus two single items) is the most used MS specific health related quality of life inventory. Objective: To develop a shortened version of the MSQOL-54. Methods: MSQOL-54 dimensionality and metric properties were investigated by confirmatory factor analysis (CFA) and Rasch modelling (Partial Credit Model, PCM) on MSQOL-54s completed by 473 MS patients. Their mean age was 41 years, 65% were women, and median Expanded Disability Status Scale (EDSS) score was 2.0 (range 0-9.5). Differential item functioning (DIF) was evaluated for gender, age and EDSS. Dimensionality of the resulting short version was assessed by exploratory factor analysis (EFA) and CFA. Cognitive debriefing of the short instrument (vs. the original) was then performed on 12 MS patients. Results: CFA of MSQOL-54 subscales showed that the data fitted the overall model well. Two subscales (Role Limitations-Physical, Role Limitations-Emotional) did not fit the PCM, and were removed; two other subscales (Health Perceptions, Social Function) did not fit the model, but were retained as single items. Sexual Satisfaction (single-item subscale) was also removed. The resulting MSQOL-29 consisted of 25 items grouped in 7 subscales, plus 4 single items. PCM fit statistics were within the acceptability range for all MSQOL-29 items except one which had significant DIF by age. EFA and CFA indicated adequate fit to the original two-factor (Physical and Mental Health Composites) hypothesis. Cognitive debriefing confirmed that MSQOL-29 was acceptable and had lost no key items. Conclusions: The proposed MSQOL-29 is 50% shorter than MSQOL-54, yet preserves key quality of life dimensions. Prospective validation on a large, independent MS patient sample is ongoing.

Published
2016

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