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1. The effect of air pollution on COVID‐19 severity in a sample of patients with multiple sclerosis

Author: Bergamaschi, Roberto, Ponzano, Marta, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Filippi, Massimo, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, De Rossi, Nicola, Brichetto, Giampaolo, Cocco, Eleonora, Scandellari, Cinzia, Cavalla, Paola, Pesci, Ilaria, Zito, Antonio, Confalonieri, Paolo, Marfia, Girolama Alessandra, Perini, Paola, Inglese, Matilde, Trojano, Maria, Brescia Morra, Vincenzo, Pisoni, Enrico, Tedeschi, Gioacchino, Comi, Giancarlo, Battaglia, Mario Alberto, Patti, Francesco, Salvetti, Marco, Sormani, Maria Pia, Gianmarco Abbadessa, Umberto Aguglia, Lia Allegorico, Rossi Beatrice Maria Allegri, Anastasia Alteno, Maria Pia Amato, Pietro Annovazzi, Carlo Antozzi, Lucia Appendino, Sebastiano Arena, Viola Baione, Roberto Balgera, Valeria Barcella, Damiano Baroncini, Caterina Barrilà, Mario A Battaglia, Alessandra Bellacosa, Gianmarco Bellucci, Roberto Bergamaschi, Valeria Bergamaschi, Daiana Bezzini, Beatrice Biolzi, Alvino Bisecco, Simona Bonavita, Giovanna Borriello, Chiara Bosa, Antonio Bosco, Francesca Bovis, Marco Bozzali, Laura Brambilla, Morra Vincenzo Brescia, Giampaolo Brichetto, Maria Buccafusca, Elisabetta Bucciantini, Sebastiano Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano Calabrese, Francesca Calabria, Francesca Caleri, Federico Camilli, Luisa Maria Caniatti, Roberto Cantello, Marco Capobianco, Ruggero Capra, Rocco Capuano, Luca Carmisciano, Patrizia Carta, Paola Cavalla, Maria Grazia Celani, Maria Cellerino, Raffaella Cerqua, Clara Chisari, Raffaella Clerici, Marinella Clerico, Eleonora Cocco, Gaia Cola, Giancarlo Comi, Paolo Confalonieri, Antonella Conte, Marta Zaffira Conti, Christian Cordano, Susanna Cordera, Cinzia Cordioli, Francesco Corea, Claudio Correale, Salvatore Cottone, Francesco Crescenzo, Erica Curti, Alessandro d'Ambrosio, Emanuele D'Amico, Maura Chiara Danni, Alessia d'Arma, Vincenzo Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Rossi, Nicola De Stefano, Cava Marco Della, Mario di Napoli, Alessia Di Sapio, Renato Docimo, Anna Dutto, Luana Evangelista, Salvatore Fanara, Diana Ferraro, Maria Teresa Ferrò, Massimo Filippi, Cristina Fioretti, Mario Fratta, Jessica Frau, Marzia Fronza, Roberto Furlan, Alberto Gajofatto, Antonio Gallo, Paolo Gallo, Claudio Gasperini, Anna Ghazaryan, Bruno Giometto, Francesca Gobbin, Flora Govone, Franco Granella, Erica Grange, Maria Grazia Grasso, Angelica Guareschi, Clara Guaschino, Simone Guerrieri, Donata Guidetti, Pietro Iaffaldano, Antonio Ianniello, Luigi Iasevoli, Paolo Immovilli, Daniele Imperiale, Maria Teresa Infante, Matilde Inglese, Rosa Iodice, Aniello Iovino, Giovanna Konrad, Doriana Landi, Roberta Lanzillo, Caterina Lapucci, Luigi Lavorgna, Maria Rita L'Episcopo, Serena Leva, Giuseppe Liberatore, Re Marianna Lo, Marco Longoni, Leonardo Lopiano, Lorena Lorefice, Matteo Lucchini, Giacomo Lus, Davide Maimone, Maria Malentacchi, Giulia Mallucci, Simona Malucchi, Chiara Rosa Mancinelli, Luca Mancinelli, Paolo Manganotti, Giorgia Teresa Maniscalco, Vittorio Mantero, Sabrina Marangoni, Damiano Marastoni, Girolama Alessandra Marfia, Fabiana Marinelli, Alessandro Marti, Boneschi Filippo Martinelli, Zoli Federco Masserano, Francesca Matta, Laura Mendozzi, Giuseppe Meucci, Silvia Miante, Giuseppina Miele, Eva Milano, Massimiliano Mirabella, Rosanna Missione, Marcello Moccia, Lucia Moiola, Sara Montepietra, Margherita MontiBragadin, Federico Montini, Roberta Motta, Raffaele Nardone, Carolina Gabri Nicoletti, Eduardo Nobile-Orazio, Agostino Nozzolillo, Marco Onofrj, Riccardo Orlandi, Anna Palmieri, Damiano Paolicelli, Livia Pasquali, Luisa Pastò, Francesco Patti, Elisabetta Pedrazzoli, Paola Perini, Ilaria Pesci, Maria Petracca, Alfredo Petrone, Carlo Piantadosi, Anna M Pietroboni, Federica Pinardi, Marta Ponzano, Emilio Portaccio, Mattia Pozzato, Carlo Pozzilli, Luca Prosperini, Alessandra Protti, Marta Radaelli, Paolo Ragonese, Sarah Rasia, Sabrina Realmuto, Anna Repice, Eleonora Rigoni, Maria Teresa Rilla, Francesca Rinaldi, Calogero Marcello Romano, Marco Ronzoni, Marco Rovaris, Francesca Ruscica, Loredana Sabattini, Giuseppe Salemi, Marco Salvetti, Lorenzo Saraceno, Alessia Sartori, Arianna Sartori, Elvira Sbragia, Cinzia Scandellari, Giuditta Ilaria Scarano, Valentina Scarano, Irene Schiavetti, Maria Sessa, Caterina Sgarito, Grazia Sibilia, Gabriele Siciliano, Alessio Signori, Elisabetta Signoriello, Leonardo Sinisi, Francesca Sireci, Patrizia Sola, Claudio Solaro, Maria Pia Sormani, Stefano Sotgiu, Maddalena Sparaco, Maria Laura Stromillo, Silvia Strumia, Emanuela Laura Susani, Giulietta Tabiadon, Francesco Teatini, Gioacchino Tedeschi, Valentina Tomassini, Simone Tonietti, Clerici Valentina Torri, Carla Tortorella, Simona Toscano, Rocco Totaro, Maria Trojano, Maria Trotta, Gabriella Turano, Monica Ulivelli, Manzo Valentino, Giovanna Vaula, Domizia Vecchio, Marco Vercellino, Elena Pinuccia Verrengia, Marika Vianello, Eleonora Virgilio, Francesca Vitetta, Stefano Vollaro, Mauro Zaffaroni, Mauro Zampolini, Ignazio Roberto Zarbo, Antonio Zito, Luigi Zuliani, Bergamaschi, R, Ponzano, M, Schiavetti, I, Carmisciano, L, Cordioli, C, Filippi, M, Radaelli, M, Immovilli, P, Capobianco, M, De Rossi, N, Brichetto, G, Cocco, E, Scandellari, C, Cavalla, P, Pesci, I, Zito, A, Confalonieri, P, Marfia, Ga, Perini, P, Inglese, M, Trojano, M, Brescia Morra, V, Pisoni, E, Tedeschi, G, Comi, G, Battaglia, Ma, Patti, F, Salvetti, M, Sormani, Mp, Abbadessa, Gianmarco, Umberto, Aguglia, Lia, Allegorico, Rossi Beatrice Maria Allegri, Anastasia, Alteno, Maria Pia Amato, Pietro, Annovazzi, Carlo, Antozzi, Lucia, Appendino, Sebastiano, Arena, Viola, Baione, Roberto, Balgera, Valeria, Barcella, Damiano, Baroncini, Caterina, Barrilà, Mario, A Battaglia, Alessandra, Bellacosa, Gianmarco, Bellucci, Roberto, Bergamaschi, Valeria, Bergamaschi, Daiana, Bezzini, Beatrice, Biolzi, Bisecco, Alvino, Bonavita, Simona, Giovanna, Borriello, Chiara, Bosa, Bosco, Antonio, Francesca, Bovi, Marco, Bozzali, Laura, Brambilla, Morra Vincenzo Brescia, Giampaolo, Brichetto, Maria, Buccafusca, Elisabetta, Bucciantini, Sebastiano, Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano, Calabrese, Francesca, Calabria, Francesca, Caleri, Federico, Camilli, Luisa Maria Caniatti, Roberto, Cantello, Marco, Capobianco, Ruggero, Capra, Capuano, Rocco, Luca, Carmisciano, Patrizia, Carta, Paola, Cavalla, Maria Grazia Celani, Maria, Cellerino, Raffaella, Cerqua, Clara, Chisari, Raffaella, Clerici, Marinella, Clerico, Eleonora, Cocco, Gaia, Cola, Giancarlo, Comi, Paolo, Confalonieri, Antonella, Conte, Marta Zaffira Conti, Christian, Cordano, Susanna, Cordera, Cinzia, Cordioli, Corea, Francesco, Claudio, Correale, Salvatore, Cottone, Francesco, Crescenzo, Erica, Curti, Alessandro, D'Ambrosio, Emanuele, D'Amico, Maura Chiara Danni, Alessia, D'Arma, Vincenzo, Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Rossi, Nicola De Stefano, Cava Marco Della, Mario di Napoli, Alessia Di Sapio, Docimo, Renato, Anna, Dutto, Luana, Evangelista, Salvatore, Fanara, Diana, Ferraro, Maria Teresa Ferrò, Massimo, Filippi, Cristina, Fioretti, Fratta, Mario, Jessica, Frau, Marzia, Fronza, Roberto, Furlan, Alberto, Gajofatto, Gallo, Antonio, Paolo, Gallo, Claudio, Gasperini, Anna, Ghazaryan, Bruno, Giometto, Francesca, Gobbin, Flora, Govone, Franco, Granella, Erica, Grange, Maria Grazia Grasso, Angelica, Guareschi, Clara, Guaschino, Simone, Guerrieri, Donata, Guidetti, Pietro, Iaffaldano, Antonio, Ianniello, Luigi, Iasevoli, Paolo, Immovilli, Daniele, Imperiale, Maria Teresa Infante, Matilde, Inglese, Rosa, Iodice, Aniello, Iovino, Giovanna, Konrad, Doriana, Landi, Roberta, Lanzillo, Caterina, Lapucci, Luigi, Lavorgna, Maria Rita L'Episcopo, Serena, Leva, Giuseppe, Liberatore, Re Marianna Lo, Marco, Longoni, Leonardo, Lopiano, Lorena, Lorefice, Matteo, Lucchini, Lus, Giacomo, Davide, Maimone, Maria, Malentacchi, Giulia, Mallucci, Simona, Malucchi, Chiara Rosa Mancinelli, Luca, Mancinelli, Paolo, Manganotti, Giorgia Teresa Maniscalco, Vittorio, Mantero, Sabrina, Marangoni, Damiano, Marastoni, Girolama Alessandra Marfia, Fabiana, Marinelli, Alessandro, Marti, Boneschi Filippo Martinelli, Zoli Federco Masserano, Francesca, Matta, Laura, Mendozzi, Giuseppe, Meucci, Silvia, Miante, Miele, Giuseppina, Eva, Milano, Massimiliano, Mirabella, Missione, Rosanna, Marcello, Moccia, Lucia, Moiola, Sara, Montepietra, Margherita, Montibragadin, Federico, Montini, Roberta, Motta, Raffaele, Nardone, Carolina Gabri Nicoletti, Eduardo, Nobile-Orazio, Agostino, Nozzolillo, Marco, Onofrj, Riccardo, Orlandi, Palmieri, Anna, Damiano, Paolicelli, Livia, Pasquali, Luisa, Pastò, Francesco, Patti, Elisabetta, Pedrazzoli, Paola, Perini, Ilaria, Pesci, Maria, Petracca, Alfredo, Petrone, Carlo, Piantadosi, Anna, M Pietroboni, Federica, Pinardi, Marta, Ponzano, Emilio, Portaccio, Mattia, Pozzato, Carlo, Pozzilli, Luca, Prosperini, Alessandra, Protti, Marta, Radaelli, Paolo, Ragonese, Sarah, Rasia, Sabrina, Realmuto, Anna, Repice, Eleonora, Rigoni, Maria Teresa Rilla, Francesca, Rinaldi, Calogero Marcello Romano, Marco, Ronzoni, Marco, Rovari, Francesca, Ruscica, Loredana, Sabattini, Giuseppe, Salemi, Marco, Salvetti, Lorenzo, Saraceno, Alessia, Sartori, Arianna, Sartori, Elvira, Sbragia, Cinzia, Scandellari, Giuditta Ilaria Scarano, Valentina, Scarano, Irene, Schiavetti, Maria, Sessa, Caterina, Sgarito, Grazia, Sibilia, Gabriele, Siciliano, Alessio, Signori, Signoriello, Elisabetta, Leonardo, Sinisi, Francesca, Sireci, Patrizia, Sola, Claudio, Solaro, Maria Pia Sormani, Stefano, Sotgiu, Sparaco, Maddalena, Maria Laura Stromillo, Silvia, Strumia, Emanuela Laura Susani, Giulietta, Tabiadon, Francesco, Teatini, Tedeschi, Gioacchino, Valentina, Tomassini, Simone, Tonietti, Clerici Valentina Torri, Carla, Tortorella, Simona, Toscano, Rocco, Totaro, Maria, Trojano, Trotta, Maria Consiglia, Gabriella, Turano, Monica, Ulivelli, Manzo, Valentino, Giovanna, Vaula, Domizia, Vecchio, Marco, Vercellino, Elena Pinuccia Verrengia, Marika, Vianello, Eleonora, Virgilio, Francesca, Vitetta, Stefano, Vollaro, Mauro, Zaffaroni, Mauro, Zampolini, Ignazio Roberto Zarbo, Zito, Guido Antonio, Bergamaschi, R., Ponzano, M., Schiavetti, I., Carmisciano, L., Cordioli, C., Filippi, M., Radaelli, M., Immovilli, P., Capobianco, M., De Rossi, N., Brichetto, G., Cocco, E., Scandellari, C., Cavalla, P., Pesci, I., Zito, A., Confalonieri, P., Marfia, G. A., Perini, P., Inglese, M., Trojano, M., Brescia Morra, V., Pisoni, E., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., Sormani, M. P., Bergamaschi, Roberto, Ponzano, Marta, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Filippi, Massimo, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, De Rossi, Nicola, Brichetto, Giampaolo, Cocco, Eleonora, Scandellari, Cinzia, Cavalla, Paola, Pesci, Ilaria, Zito, Antonio, Confalonieri, Paolo, Marfia, Girolama Alessandra, Perini, Paola, Inglese, Matilde, Trojano, Maria, Brescia Morra, Vincenzo, Pisoni, Enrico, Comi, Giancarlo, Battaglia, Mario Alberto, Patti, Francesco, Salvetti, Marco, Sormani, Maria, Pia, Gianmarco, Abbadessa, Alvino, Bisecco, Simona, Bonavita, Antonio, Bosco, Rocco, Capuano, Francesco, Corea, Renato, Docimo, Mario, Fratta, Antonio, Gallo, Iodice, Rosa, Iovino, Aniello, Lanzillo, Roberta, Giacomo, Lu, Giuseppina, Miele, Rosanna, Missione, Moccia, Marcello, Anna, Palmieri, Elisabetta, Signoriello, Maddalena, Sparaco, Gioacchino, Tedeschi, Maria, Trotta, Antonio, Zito, and Luigi, Zuliani
Subjects: air pollution, coronavirus, multiple sclerosis, medicine.medical_specialty, Multivariate analysis, Coronavirus disease 2019 (COVID-19), Clinical Sciences, Air pollution, Sample (statistics), Neurodegenerative, Settore MED/26, medicine.disease_cause, Autoimmune Disease, law.invention, Sustainable Cities and Communities, Clinical Research, law, Humans, Medicine, Climate-Related Exposures and Conditions, Neurology & Neurosurgery, MuSC-19 study group, SARS-CoV-2, business.industry, Multiple sclerosis, Neurosciences, COVID-19, Retrospective cohort study, Original Articles, medicine.disease, Intensive care unit, Particulate Matter, Air Pollution, Multiple Sclerosis, Brain Disorders, coronaviru, Settore MED/26 - NEUROLOGIA, Good Health and Well Being, Neurology, multiple sclerosi, Emergency medicine, Original Article, Neurology (clinical), Ordered logit, business, Human
Abstract: Background and purpose Some studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 µg/m3 (PM2.5), may contribute to severe COVID‐19 courses, as well as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID‐19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID‐19 severity amongst PwMS. Methods Data were retrieved from an Italian web‐based platform (MuSC‐19) which includes PwMS with COVID‐19. PM2.5 2016–2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID‐19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID‐19 severity. Results In all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID‐19 course (odds ratio 1.90; p = 0.009). Conclusions Even if several other factors explain the unfavourable course of COVID‐19 in PwMS, the role of air pollutants must be considered and further investigated., Air pollution, often assessed by particulate matter with diameter below 2.5 µg/m3, may contribute to severe COVID‐19 courses. 1087 patients were included, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died. Even if several other factors explain the unfavourable course of COVID‐19 in patients with multiple sclerosis, the role of air pollutants must be considered and further investigated.
Published: 2021
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2. Characterizing 1-year development of cervical cord atrophy across different MS phenotypes

Author: Paola Valsasina, Claudio Gobbi, Chiara Zecca, Alex Rovira, Jaume Sastre-Garriga, Hugh Kearney, Marios Yiannakas, Lucy Matthews, Jacqueline Palace, Antonio Gallo, Alvino Bisecco, Achim Gass, Philipp Eisele, Massimo Filippi, Maria A Rocca, Frederik Barkhof, Olga Ciccarelli, Nicola De Stefano, Christian Enzinger, Claudio Gasperini, Ludwig Kappos, Hugo Vrenken, Tarek Yousry, Anatomy and neurosciences, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Neuroinfection & -inflammation, CCA - Cancer Treatment and quality of life, CCA - Imaging and biomarkers, Valsasina, P., Gobbi, C., Zecca, C., Rovira, A., Sastre-Garriga, J., Kearney, H., Yiannakas, M., Matthews, L., Palace, J., Gallo, A., Bisecco, A., Gass, A., Eisele, P., Filippi, M., Rocca, M. A., Barkhof, F., Ciccarelli, O., De Stefano, N., Enzinger, C., Gasperini, C., Kappos, L., Vrenken, H., and Yousry, T.
Subjects: Pathology, medicine.medical_specialty, Cord, Multiple Sclerosis, Cervical cord, computer.software_genre, Multiple sclerosis, Atrophy, Multiple Sclerosis, Relapsing-Remitting, Voxel, medicine, Distribution (pharmacology), Humans, Multiple sclerosi, business.industry, spinal cord, Brain, Cervical Cord, Spinal cord, medicine.disease, Phenotype, Magnetic Resonance Imaging, medicine.anatomical_structure, disability, Neurology, Spinal Cord, voxel-wise analysis, Disease Progression, Neurology (clinical), business, computer, MRI, Demyelinating Diseases
Abstract: Background: Spatio-temporal evolution of cord atrophy in multiple sclerosis (MS) has not been investigated yet. Objective: To evaluate voxel-wise distribution and 1-year changes of cervical cord atrophy in a multicentre MS cohort. Methods: Baseline and 1-year 3D T1-weighted cervical cord scans and clinical evaluations of 54 healthy controls (HC) and 113 MS patients (14 clinically isolated syndromes (CIS), 77 relapsing-remitting (RR), 22 progressive (P)) were used to investigate voxel-wise cord volume loss in patients versus HC, 1-year volume changes and clinical correlations (SPM12). Results: MS patients exhibited baseline cord atrophy versus HC at anterior and posterior/lateral C1/C2 and C4–C6 ( p < 0.05, corrected). While CIS patients showed baseline volume increase at C4 versus HC ( p < 0.001, uncorrected), RRMS exhibited posterior/lateral C1/C2 atrophy versus CIS, and PMS showed widespread cord atrophy versus RRMS ( p < 0.05, corrected). At 1 year, 13 patients had clinically worsened. Cord atrophy progressed in MS, driven by RRMS, at posterior/lateral C2 and C3–C6 ( p < 0.05, corrected). CIS patients showed no volume changes, while PMS showed circumscribed atrophy progression. Baseline cord atrophy at posterior/lateral C1/C2 and C3–C6 correlated with concomitant and 1-year disability ( r = −0.40/–0.62, p < 0.05, corrected). Conclusions: Voxel-wise analysis characterized spinal cord neurodegeneration over 1 year across MS phenotypes and helped to explain baseline and 1-year disability.
Published: 2022
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3. Humoral- and T-Cell–Specific Immune Responses to SARS-CoV-2 mRNA Vaccination in Patients With MS Using Different Disease-Modifying Therapies

Author: Valentina Vanini, Carla Tortorella, Claudio Gasperini, Anna Maria Gerarda Altera, Chiara Agrati, Giulia Matusali, Vincenzo Puro, Nazario Bevilacqua, Silvia Meschi, Francesca Colavita, Concetta Castilletti, Shalom Haggiag, Flavia Cristofanelli, Andrea Salmi, Angela Corpolongo, Serena Ruggieri, Alessandra D'Abramo, Delia Goletti, Maria Esmeralda Quartuccio, Giuseppe Ippolito, Alessandra Aiello, Luca Prosperini, Chiara Farroni, Eleonora Tartaglia, Simona Galgani, Maria Rosaria Capobianchi, Eleonora Cimini, Federica Repele, Gilda Cuzzi, Francesco Vaia, and Emanuele Nicastri
Subjects: classe III, business.industry, Multiple sclerosis, Antibody titer, COVID-19, multiple sclerosis, medicine.disease, Fingolimod, Vaccination, Titer, Immune system, autommune diseaae, Immunology, Medicine, Ocrelizumab, Neurology (clinical), business, Cladribine, medicine.drug
Abstract: Background and ObjectivesTo evaluate the immune-specific response after full severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination of patients with multiple sclerosis (MS) treated with different disease-modifying drugs by the detection of both serologic and T-cell responses.MethodsHealthcare workers (HCWs) and patients with MS, having completed the 2-dose schedule of an mRNA-based vaccine against SARS-CoV-2 in the past 2–4 weeks, were enrolled from 2 parallel prospective studies conducted in Rome, Italy, at the National Institute for Infectious diseases Spallanzani–IRCSS and San Camillo Forlanini Hospital. Serologic response was evaluated by quantifying the region-binding domain (RBD) and neutralizing antibodies. Cell-mediated response was analyzed by a whole-blood test quantifying interferon (IFN)–γ response to spike peptides. Cells responding to spike stimulation were identified by fluorescence-activated cell sorting analysis.ResultsWe prospectively enrolled 186 vaccinated individuals: 78 HCWs and 108 patients with MS. Twenty-eight patients with MS were treated with IFN-β, 35 with fingolimod, 20 with cladribine, and 25 with ocrelizumab. A lower anti-RBD antibody response rate was found in patients treated with ocrelizumab (40%, p < 0.0001) and fingolimod (85.7%, p = 0.0023) compared to HCWs and patients treated with cladribine or IFN-β. Anti-RBD antibody median titer was lower in patients treated with ocrelizumab (p < 0.0001), fingolimod (p < 0.0001), and cladribine (p = 0.010) compared to HCWs and IFN-β–treated patients. Serum neutralizing activity was present in all the HCWs tested and in only a minority of the fingolimod-treated patients (16.6%). T-cell–specific response was detected in the majority of patients with MS (62%), albeit with significantly lower IFN-γ levels compared to HCWs. The lowest frequency of T-cell response was found in fingolimod-treated patients (14.3%). T-cell–specific response correlated with lymphocyte count and anti-RBD antibody titer (ρ = 0.554, p < 0.0001 and ρ = 0.255, p = 0.0078 respectively). IFN-γ T-cell response was mediated by both CD4+ and CD8+ T cells.DiscussionmRNA vaccines induce both humoral and cell-mediated specific immune responses against spike peptides in all HCWs and in the majority of patients with MS. These results carry relevant implications for managing vaccinations, suggesting promoting vaccination in all treated patients with MS.Classification of EvidenceThis study provides Class III data that SARS-CoV-2 mRNA vaccination induces both humoral and cell-mediated specific immune responses against viral spike proteins in a majority of patients with MS.
Published: 2021
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4. Increased risk of death from COVID-19 in multiple sclerosis: a pooled analysis of observational studies

Author: Simonetta Galgani, Carla Tortorella, Shalom Haggiag, Claudio Gasperini, Luca Prosperini, and Serena Ruggieri
Subjects: Adult, Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Population, Cohort Studies, Multiple sclerosis, Internal medicine, medicine, Humans, COVID-19, SARS-COV-2, education, Pandemics, education.field_of_study, Original Communication, SARS-CoV-2, business.industry, Mortality rate, medicine.disease, Confidence interval, Pooled analysis, Neurology, Female, Observational study, Neurology (clinical), business, Cohort study
Abstract: Objective To estimate whether the risk of death from COVID-19 in patients with multiple sclerosis (MS) exceeds that of the general population. Methods We conducted a pooled analysis of cohort studies on COVID-19 in patients with MS published until July 31, 2021. We calculated the pooled crude death rate (CDR) and estimated the indirectly-adjusted age-standardized lethality ratio (SLR) to assess the risk of death from COVID-19 in patients with MS as compared to general population. Results Out of 520 articles, 18 fulfilled criteria for pooled analysis, with a total of 5634 patients (28.6% males, mean age 41.8 years). Of them, 111 died, yielding a CDR of 1.97% (95% confidence intervals [CIs] 1.61–2.33). The estimated SLR was 1.24 (95% CIs 1.01–1.48) after indirect age-standardization using case-fatality rates obtained from the detailed surveillance data available at the World Health Organization (WHO) website. A leave-one-out sensitivity analysis and the analysis of temporal trends of SLR from March 2020 to July 2021 provided consistent findings. Conclusions Our pooled analysis suggests a 24%-increased risk of death from COVID-19 in patients with MS. These findings must be interpreted with caution, mainly because of the difficulties in COVID-19 case detection (especially in the first pandemic wave) and heterogeneity of the analyzed cohorts. Confirmation in larger population-based studies is warranted.
Published: 2021
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5. Job satisfaction among physicians and nurses involved in the management of multiple sclerosis: the role of happiness and meaning at work

Author: Beatrice Allegri, Eleonora Minacapelli, Maria Esmeralda Quartuccio, Marianna Pattini, Giovanna De Luca, Monica Falautano, Maria Pia Amato, Sabina Cilia, Claudio Gasperini, Monica Grobberio, Miriam Benin, Rosa Gemma Viterbo, Luca Negri, Francesco Patti, Erika Pietrolongo, Marta Bassi, Claudia Niccolai, and Maria Trojano
Subjects: media_common.quotation_subject, Happiness, Dermatology, Eudaimonia, Multiple sclerosis, Promotion (rank), Physicians, Surveys and Questionnaires, Healthcare professionals, Health care, Humans, Quality (business), Meaning (existential), media_common, business.industry, Multilevel model, Job happiness, General Medicine, Psychiatry and Mental health, Job satisfaction, Original Article, Neurology (clinical), Job meaning, Psychology, business, Social psychology
Abstract: Objective Health professionals caring for persons with multiple sclerosis (MS) are faced with increasingly complex working conditions that can undermine their job satisfaction and the quality of their healthcare services. The aim of this study was to delve into health professionals’ job satisfaction by assessing the predictive role of happiness and meaning at work. Specifically, it was hypothesized that job meaning would moderate the relationship between job happiness and satisfaction. Methods The study hypothesis was tested among 108 healthcare professionals (53 physicians and 55 nurses) working in eight MS centers in Italy. Participants were administered the Eudaimonic and Hedonic Happiness Investigation and the Job Satisfaction Questionnaire. Hierarchical regression analysis was performed to test the moderating role of job meaning between job happiness and satisfaction. Results A significant interaction effect of job happiness and meaning on job satisfaction was identified for both physicians and nurses. When work was attributed low meaning, participants experiencing high job happiness were more satisfied with their work than those reporting low happiness; by contrast, when work was perceived as highly meaningful, participants’ levels of job happiness did not significantly contribute to job satisfaction. Conclusions Focusing on the interplay between job happiness and meaning, findings bring forward practical suggestions for the preservation and promotion of job satisfaction among health professionals working with MS patients. Particularly, they suggest the need to strengthen those job-related aspects that may enhance job meaning, thus providing health professionals with significant reasons to persevere in their work in the face of daily challenges.
Published: 2021
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6. 2021 MAGNIMS–CMSC–NAIMS consensus recommendations on the use of MRI in patients with multiple sclerosis

Author: Mike P Wattjes, Olga Ciccarelli, Daniel S Reich, Brenda Banwell, Nicola de Stefano, Christian Enzinger, Franz Fazekas, Massimo Filippi, Jette Frederiksen, Claudio Gasperini, Yael Hacohen, Ludwig Kappos, David K B Li, Kshitij Mankad, Xavier Montalban, Scott D Newsome, Jiwon Oh, Jacqueline Palace, Maria A Rocca, Jaume Sastre-Garriga, Mar Tintoré, Anthony Traboulsee, Hugo Vrenken, Tarek Yousry, Frederik Barkhof, Àlex Rovira, María A Rocca, Mar Tintore, Alex Rovira, Wattjes, Mike P, Ciccarelli, Olga, Reich, Daniel S, Banwell, Brenda, de Stefano, Nicola, Enzinger, Christian, Fazekas, Franz, Filippi, Massimo, Frederiksen, Jette, Gasperini, Claudio, Hacohen, Yael, Kappos, Ludwig, Li, David K B, Mankad, Kshitij, Montalban, Xavier, Newsome, Scott D, Oh, Jiwon, Palace, Jacqueline, Rocca, Maria A, Sastre-Garriga, Jaume, Tintoré, Mar, Traboulsee, Anthony, Vrenken, Hugo, Yousry, Tarek, Barkhof, Frederik, Rovira, Àlex, Rocca, María A, Tintore, Mar, and Rovira, Alex
Subjects: Adult, Male, medicine.medical_specialty, Consensus, Multiple Sclerosis, Adolescent, MEDLINE, Contrast Media, Gadolinium, Inversion recovery, Appropriate use, Pediatrics, 030218 nuclear medicine & medical imaging, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, medicine, Humans, Medical physics, In patient, Child, Aged, Monitoring, Physiologic, medicine.diagnostic_test, business.industry, Multiple sclerosis, Reproducibility of Results, Magnetic resonance imaging, Middle Aged, Prognosis, medicine.disease, Research findings, Magnetic Resonance Imaging, Clinical Practice, Treatment Outcome, Disease Progression, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: The 2015 Magnetic Resonance Imaging in Multiple Sclerosis and 2016 Consortium of Multiple Sclerosis Centres guidelines on the use of MRI in diagnosis and monitoring of multiple sclerosis made an important step towards appropriate use of MRI in routine clinical practice. Since their promulgation, there have been substantial relevant advances in knowledge, including the 2017 revisions of the McDonald diagnostic criteria, renewed safety concerns regarding intravenous gadolinium-based contrast agents, and the value of spinal cord MRI for diagnostic, prognostic, and monitoring purposes. These developments suggest a changing role of MRI for the management of patients with multiple sclerosis. This 2021 revision of the previous guidelines on MRI use for patients with multiple sclerosis merges recommendations from the Magnetic Resonance Imaging in Multiple Sclerosis study group, Consortium of Multiple Sclerosis Centres, and North American Imaging in Multiple Sclerosis Cooperative, and translates research findings into clinical practice to improve the use of MRI for diagnosis, prognosis, and monitoring of individuals with multiple sclerosis. We recommend changes in MRI acquisition protocols, such as emphasising the value of three dimensional-fluid-attenuated inversion recovery as the core brain pulse sequence to improve diagnostic accuracy and ability to identify new lesions to monitor treatment effectiveness, and we provide recommendations for the judicious use of gadolinium-based contrast agents for specific clinical purposes. Additionally, we extend the recommendations to the use of MRI in patients with multiple sclerosis in childhood, during pregnancy, and in the post-partum period. Finally, we discuss promising MRI approaches that might deserve introduction into clinical practice in the near future.
Published: 2021
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7. Scoring the 10‐year risk of ambulatory disability in multiple sclerosis: the RoAD score

Author: Mar Tintoré, Alex Rovira, Xavier Montalban, Simonetta Galgani, Luca Prosperini, Carla Tortorella, Ruggero Capra, Claudio Gasperini, Shalom Haggiag, Jordi Río, Carlo Pozzilli, and Jaume Sastre-Garriga
Subjects: Treatment response, medicine.medical_specialty, Multiple Sclerosis, Contrast Media, Gadolinium, Disability Evaluation, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Milestone (project management), Humans, Medicine, 030212 general & internal medicine, Glatiramer acetate, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Glatiramer Acetate, medicine.disease, Neurology, Cohort, Ambulatory, Physical therapy, T2 lesions, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: BACKGROUND AND PURPOSE Both baseline prognostic factors and short-term predictors of treatment response can influence the long-term risk of disability accumulation in patients with relapsing-remitting multiple sclerosis (RRMS). The objective was to develop and validate a scoring system combining baseline prognostic factors and 1-year variables of treatment response into a single numeric score predicting the long-term risk of disability. METHODS We analysed two independent datasets of patients with RRMS who started interferon beta or glatiramer acetate, had an Expanded Disability Status Scale (EDSS) score
Published: 2021
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8. Ozone‐induced encephalopathy: A novel iatrogenic entity

Author: Alessandro Stasolla, Carmela Gerace, Carla Tortorella, Shalom Haggiag, Claudio Gasperini, and Luca Prosperini
Subjects: Adult, Male, Anterograde amnesia, Iatrogenic Disease, Encephalopathy, Foramen Ovale, Patent, Neurological examination, 03 medical and health sciences, Ozone, 0302 clinical medicine, Lumbar, Blurred vision, medicine, Humans, 030212 general & internal medicine, Stroke, Brain Diseases, medicine.diagnostic_test, Cortical blindness, business.industry, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Neurology, Migraine, Anesthesia, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: BACKGROUND AND PURPOSE Ozone-based treatments can be associated with central nervous system toxicity, which we have termed ozone-induced encephalopathy (OIE). A detailed description of its phenotype is lacking. METHODS Three cases with findings suggestive of OIE are presented, and the literature is reviewed. RESULTS Case 1 is a healthy 59-year-old man presenting with loss of consciousness, cortical blindness, restlessness, and anterograde amnesia immediately following a cervical ozone-therapy (OT) session for chronic neck pain. Brain magnetic resonance imaging (MRI) on admission was normal. A follow-up scan demonstrated a subtle increased T2 fluid-attenuated inversion recovery signal within the left cerebellum; an echocardiography showed a patent foramen ovale (PFO). Case 2 is a 56-year-old woman with history of migraine, PFO, and lumbar pain who presented with headache, bilateral visual impairment, motor dysphasia, and agitation. All her symptoms began immediately after lumbar OT. Her brain MRI was negative. Case 3 is a healthy 27-year-old man who complained of vertigo and mild blurred vision 5 min following a cervical ozone injection. His neurological examination and brain MRI were normal. All three patients had full recovery within 48 h. We found eight additional cases of OIE in the literature. CONCLUSIONS OIE should be considered in patients presenting with neurological symptoms in close relation to OT. OIE is likely a novel iatrogenic entity with a complex pathogenesis; it is probably underreported because it mimics other neurological conditions.
Published: 2021
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9. Clinical course of central nervous system demyelinating neurological adverse events associated with anti-TNF therapy

Author: Carla Tortorella, Isabella Laura Simone, Claudio Gasperini, Alessandro Stasolla, Luca Prosperini, Veronica Villani, Shalom Haggiag, and Rosa Cortese
Subjects: Central Nervous System, medicine.medical_specialty, Neurology, Necrosis, Central nervous system, Biologics, Autoimmune Diseases, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Demyelination, Tumor necrosis factor alpha inhibitors, Demyelinating Diseases, Humans, Multiple Sclerosis, Tumor Necrosis Factor Inhibitors, Internal medicine, medicine, Demyelinating disease, 030212 general & internal medicine, Adverse effect, Neuroradiology, business.industry, medicine.disease, Discontinuation, medicine.anatomical_structure, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Previous studies have reported an association between anti-tumor necrosis factor alpha (anti-TNFα) treatment and central nervous system (CNS) events. We described eight patients presenting with demyelinating CNS events while on treatment with anti-TNFα for autoimmune diseases and followed up for a medium period of 4 years. Four patients presented with isolated demyelinating events, three patients fulfilled the criteria for multiple sclerosis (MS), and one patient showed worsening of pre-existing MS after anti-TNF therapy initiation. All patients except one, showed a good medium-term prognosis. Our observation supports an association between anti-TNFα treatment and demyelinating events and suggests that a prompt discontinuation of the drug may lead to a favorable demyelinating disease outcome.
Published: 2021
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10. Dynamics of pseudo‐atrophy in RRMS reveals predominant gray matter compartmentalization

Author: Maria Pia Sormani, Antonio Giorgio, Giordano Gentile, Andrea Visconti, Marco Battaglini, Claudio Gasperini, Maria Laura Stromillo, Rosa Cortese, and Nicola De Stefano
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Multiple Sclerosis, Atrophy, Double-Blind Method, Female, Gray Matter, Humans, Immunologic Factors, Interferon beta-1a, Magnetic Resonance Imaging, Middle Aged, Multiple Sclerosis, Relapsing-Remitting, White Matter, Neurosciences. Biological psychiatry. Neuropsychiatry, Relapsing-Remitting, Placebo, Gastroenterology, White matter, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, In patient, RC346-429, Research Articles, medicine.diagnostic_test, business.industry, General Neuroscience, Multiple sclerosis, Magnetic resonance imaging, medicine.disease, Clinical trial, 030104 developmental biology, medicine.anatomical_structure, Neurology. Diseases of the nervous system, Neurology (clinical), Volume loss, business, 030217 neurology & neurosurgery, RC321-571, Research Article
Abstract: Objective To assess the dynamics of “pseudo‐atrophy,” the accelerated brain volume loss observed after initiation of anti‐inflammatory therapies, in patients with multiple sclerosis (MS). Methods Monthly magnetic resonance imaging (MRI) data of patients from the IMPROVE clinical study (NCT00441103) comparing relapsing‐remitting MS patients treated with interferon beta‐1a (IFNβ‐1a) for 40 weeks versus those receiving placebo (16 weeks) and then IFNβ‐1a (24 weeks) were used to assess percentage of gray (PGMVC) and white matter (PWMVC) volume changes. Comparisons of PGMVC and PWMVC slopes were performed with a mixed effect linear model. In the IFNβ‐1a‐treated arm, a quadratic term was included in the model to evaluate the plateauing effect over 40 weeks. Results Up to week 16, PGMVC was −0.14% per month in the placebo and −0.27% per month in treated patients (P
Published: 2021
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11. Efficacy of levetiracetam on upper limb movement in multiple sclerosis patients with cerebellar signs: a multicenter double‐blind, placebo‐controlled, crossover study

Author: Margit Mueller, Roberto Bergamaschi, Maria Rosaria Stabile, Francesco Patti, Domenico A. Restivo, A. de Sire, Claudio Solaro, Claudio Gasperini, and M. Messmer Uccelli
Subjects: Adult, levetiracetam, medicine.medical_treatment, multiple sclerosis, Placebo, rehabilitation, Double blind, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, upper extremity, medicine, Humans, 030212 general & internal medicine, Cross-Over Studies, Rehabilitation, business.industry, Multiple sclerosis, Middle Aged, medicine.disease, Piracetam, Crossover study, Treatment Outcome, medicine.anatomical_structure, Neurology, kinematics, Anesthesia, Upper limb, Anticonvulsants, Neurology (clinical), Levetiracetam, Cerebellar signs, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: BACKGROUND AND PURPOSE The literature provides contrasting results on the efficacy of levetiracetam (LEV) in multiple sclerosis (MS) patients with cerebellar signs. It was sought to evaluate the efficacy of LEV on upper limb movement in MS patients. METHODS In this multicenter double-blind placebo-controlled crossover study, MS patients with prevalently cerebellar signs were randomly allocated into two groups: LEV followed by placebo (group 1) or placebo followed by LEV (group 2). Clinical assessments were performed by a blinded physician at T0 (day 1), T1 (day 22), T2 (2-week wash-out period, day 35) and T3 (day 56). The primary outcome was dexterity in the arm with greater deficit, assessed by the nine-hole peg test (9HPT). Secondary clinical outcomes included responders on the 9HPT (∆9HPT >20%), tremor activity of the daily living questionnaire and self-defined upper limb impairment, through a numeric rating scale. Kinematic evaluation was performed using a digitizing tablet, providing data on normalized jerk, aiming error and centripetal acceleration. RESULTS Forty-eight subjects (45.2 ± 10.4 years) were randomly allocated into two groups (n = 24 each). 9HPT significantly improved in the LEV phase in both groups (P
Published: 2020
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12. Effects of THC/CBD oromucosal spray on spasticity-related symptoms in people with multiple sclerosis: results from a retrospective multicenter study

Author: Domenico Ippolito, Giorgia Teresa Maniscalco, Damiano Paolicelli, Daniele Spitaleri, Francesco Patti, Gianfranco Costantino, Margherita Russo, Clara Grazia Chisari, Letizia Castelli, Giovanna Salamone, Roberto Bruno Bossio, Maria Trotta, Claudio Solaro, Eliana Berra, Roberta Lanzillo, Elisabetta Signoriello, Raffaella Cerqua, Isabella Righini, Fabio Buttari, Gabriella Spinicci, Loredana Petrucci, Angelica Guareschi, Manuela Matta, Mario Zappia, Simona Pontecorvo, Maria Donata Benedetti, Paola Cavalla, Assunta Bianco, Claudio Gasperini, Eleonora Tavazzi, Francesco Saccà, Mauro Zaffaroni, Patti, F., Chisari, C. G., Solaro, C., Benedetti, M. D., Berra, E., Bianco, A., Bruno Bossio, R., Buttari, F., Castelli, L., Cavalla, P., Cerqua, R., Costantino, G., Gasperini, C., Guareschi, A., Ippolito, D., Lanzillo, R., Maniscalco, G. T., Matta, M., Paolicelli, D., Petrucci, L., Pontecorvo, S., Righini, I., Russo, M., Saccà, Francesco, Salamone, G., Signoriello, E., Spinicci, G., Spitaleri, D., Tavazzi, E., Trotta, M., Zaffaroni, M., Zappia, M., Patti, Francesco, Grazia Chisari, Clara, Solaro, Claudio, Donata Benedetti, Maria, Berra, Eliana, Bianco, Assunta, Bruno Bossio, Roberto, Buttari, Fabio, Castelli, Letizia, Cavalla, Paola, Cerqua, Raffaella, Costantino, Gianfranco, Gasperini, Claudio, Guareschi, Angelica, Ippolito, Domenico, Lanzillo, Roberta, Teresa Maniscalco, Giorgia, Matta, Manuela, Paolicelli, Damiano, Petrucci, Loredana, Pontecorvo, Simona, Righini, Isabella, Russo, Margherita, Salamone, Giovanna, Signoriello, Elisabetta, Spinicci, Gabriella, Spitaleri, Daniele, Tavazzi, Eleonora, Trotta, Maria, Zaffaroni, Mauro, and Zappia, Mario
Subjects: medicine.medical_specialty, Multiple Sclerosis, THC, Neurology, Dermatology, Clinical practice, Spasticity-related symptom, CBD, Multiple sclerosis, Spasticity-related symptoms, 03 medical and health sciences, 0302 clinical medicine, Rating scale, Internal medicine, medicine, Cannabidiol, Humans, Multiple sclerosi, Dronabinol, 030212 general & internal medicine, Spasticity, Oromucosal spray, Retrospective Studies, Plant Extracts, business.industry, General Medicine, medicine.disease, nervous system diseases, Clinical Practice, Drug Combinations, Psychiatry and Mental health, Italy, Muscle Spasticity, Neurology (clinical), Neurosurgery, medicine.symptom, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Introduction: The approval of 9-δ-tetrahydocannabinol (THC)+cannabidiol (CBD) oromucosal spray (Sativex®) in Italy as an add-on medication for the management of moderate to severe spasticity in multiple sclerosis (MS) has provided a new opportunity for MS patients with drug-resistant spasticity. We aimed to investigate the improvement of MS spasticity-related symptoms in a large cohort of patients with moderate to severe spasticity in daily clinical practice. Materials and methods: MS patients with drug-resistant spasticity were recruited from 30 Italian MS centers. All patients were eligible for THC:CBD treatment according to the approved label: ≥ 18 years of age, at least moderate spasticity (MS spasticity numerical rating scale [NRS] score ≥ 4) and not responding to the common antispastic drugs. Patients were evaluated at baseline (T0) and after 4 weeks of treatment (T1) with the spasticity NRS scale and were also asked about meaningful improvements in 6 key spasticity-related symptoms. Results: Out of 1615 enrolled patients, 1432 reached the end of the first month trial period (T1). Of these, 1010 patients (70.5%) reached a ≥ 20% NRS score reduction compared with baseline (initial responders; IR). We found that 627 (43.8% of 1432) patients showed an improvement in at least one spasticity-related symptom (SRSr group), 543 (86.6%) of them belonging to the IR group and 84 (13.4%) to the spasticity NRS non-responders group. Conclusion: Our study confirmed that the therapeutic benefit of cannabinoids may extend beyond spasticity, improving spasticity-related symptoms even in non-NRS responder patients. © 2020, Fondazione Società Italiana di Neurologia.
Published: 2020
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13. Performance of the 2017 and 2010 Revised McDonald Criteria in Predicting MS Diagnosis After a Clinically Isolated Syndrome:A MAGNIMS Study

Author: Serena Ruggieri, Jelena Drulovic, Stig P. Cramer, Jette L. Frederiksen, Massimo Filippi, Alex Rovira, Alessandro Meani, Frederik Barkhof, Enrico Fainardi, Maria Pia Amato, Gloria Dalla Costa, E. M. M. Strijbis, Maria A. Rocca, Vittorio Martinelli, Wallace J Brownlee, Christian Enzinger, Paolo Preziosa, Giancarlo Comi, Olga Ciccarelli, Xavier Montalban, Claudio Gasperini, Michael Khalil, Sarlota Mesaros, Jovana Ivanovic, Mar Tintoré, KA Miszkiel, Filippi, Massimo, Preziosa, Paolo, Meani, Alessandro, Costa, Gloria Dalla, Mesaros, Sarlota, Drulovic, Jelena, Ivanovic, Jovana, Rovira, Alex, Tintorè, Mar, Montalban, Xavier, Ciccarelli, Olga, Brownlee, Wallace, Miszkiel, Katherine, Enzinger, Christian, Khalil, Michael, Barkhof, Frederik, Strijbis, Eva M M, Frederiksen, Jette L, Cramer, Stig P, Fainardi, Enrico, Amato, Maria Pia, Gasperini, Claudio, Ruggieri, Serena, Martinelli, Vittorio, Comi, Giancarlo, Rocca, Maria A, MAGNIMS Study, Group, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Neuroinfection & -inflammation, and Neurology
Subjects: MULTIPLE-SCLEROSIS DIAGNOSIS, medicine.medical_specialty, Multiple Sclerosis, REVISIONS, MRI CRITERIA, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Brain mri, medicine, Humans, SPACE, In patient, 10. No inequality, 030304 developmental biology, 0303 health sciences, Clinically isolated syndrome, RELEVANT, multiple sclerosis, MRI, classe II, business.industry, Multiple sclerosis, Oligoclonal Bands, Area under the curve, Brain, DISSEMINATION, McDonald criteria, ADULTS, medicine.disease, Magnetic Resonance Imaging, CONVERSION, Median time, Disease Progression, SPINAL-CORD LESIONS, Neurology (clinical), business, 030217 neurology & neurosurgery, Time to diagnosis, Demyelinating Diseases
Abstract: Background and ObjectivesTo compare the performance of the 2017 revisions to the McDonald criteria with the 2010 McDonald criteria in establishing multiple sclerosis (MS) diagnosis and predicting prognosis in patients with clinically isolated syndrome (CIS) suggestive of MS.MethodsCSF examination and brain and spinal cord MRI obtained ≤5 months from CIS onset and a follow-up brain MRI acquired within 15 months from CIS onset were evaluated in 785 patients with CIS from 9 European centers. Date of second clinical attack and of reaching Expanded Disability Status Scale score (EDSS) ≥3.0, if they occurred, were also collected. Performance of the 2017 and 2010 McDonald criteria for dissemination in space (DIS), dissemination in time (DIT) (including oligoclonal bands assessment), and DIS plus DIT for predicting a second clinical attack (clinically definite MS [CDMS]) and EDSS ≥3.0 at follow-up was evaluated. Time to MS diagnosis for the different criteria was also estimated.ResultsAt follow-up (median 69.1 months), 406/785 patients with CIS developed CDMS. At 36 months, the 2017 DIS plus DIT criteria had higher sensitivity (0.83 vs 0.66), lower specificity (0.39 vs 0.60), and similar area under the curve values (0.61 vs 0.63). Median time to MS diagnosis was shorter with the 2017 vs the 2010 or CDMS criteria (2017 revision, 3.2; 2010 revision, 13.0; CDMS, 58.5 months). The 2 sets of criteria similarly predicted EDSS ≥3.0 milestone. Three periventricular lesions improved specificity in patients ≥45 years.DiscussionThe 2017 McDonald criteria showed higher sensitivity, lower specificity, and similar accuracy in predicting CDMS compared to 2010 McDonald criteria, while shortening time to diagnosis of MS.Classification of EvidenceThis study provides Class II evidence that the 2017 McDonald Criteria more accurately distinguish CDMS in patients early after a CIS when compared to the 2010 McDonald criteria.
Published: 2022
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14. mRNA COVID-19 vaccines do not increase the short-term risk of clinical relapses in multiple sclerosis

Author: Paola Cavalla, Fabio Buttari, Alice Laroni, Cinzia Cordioli, Claudio Gasperini, Alberto Gajofatto, Paolo Ragonese, Massimiliano Di Filippo, Lorena Lorefice, Angela Borrelli, Giorgia Teresa Maniscalco, Viviana Nociti, Valentina Torri Clerici, Massimiliano Calabrese, Marta Radaelli, Antonio Gallo, Laura Boffa, Claudio Solaro, Roberta Lanzillo, Carla Tortorella, Eleonora Cocco, Simona Malucchi, Diana Ferraro, Paola Gazzola, Giovanna De Luca, Valentina Tomassini, Marinella Clerico, Pietro Annovazzi, Damiano Paolicelli, Roberta Fantozzi, Marcello Moccia, Luca Prosperini, Di Filippo M., Cordioli C., Malucchi S., Annovazzi P., Cavalla P., Torri Clerici V., Ragonese P., Nociti V., Radaelli M., Laroni A., Buttari F., Lorefice L., Ferraro D., Gajofatto A., Prosperini L., Fantozzi R., Boffa L., Lanzillo R., Moccia M., Clerico M., De Luca G., Tomassini V., Calabrese M., Borrelli A., Paolicelli D., Maniscalco G.T., Gazzola P., Gallo A., Solaro C., Cocco E., Gasperini C., Tortorella C., Di Filippo, Massimiliano, Cordioli, Cinzia, Malucchi, Simona, Annovazzi, Pietro, Cavalla, Paola, Torri Clerici, Valentina, Ragonese, Paolo, Nociti, Viviana, Radaelli, Marta, Laroni, Alice, Buttari, Fabio, Lorefice, Lorena, Ferraro, Diana, Gajofatto, Alberto, Prosperini, Luca, Fantozzi, Roberta, Boffa, Laura, Lanzillo, Roberta, Moccia, Marcello, Clerico, Marinella, De Luca, Giovanna, Tomassini, Valentina, Calabrese, Massimiliano, Borrelli, Angela, Paolicelli, Damiano, Maniscalco, Giorgia Teresa, Gazzola, Paola, Gallo, Antonio, Solaro, Claudio, Cocco, Eleonora, Gasperini, Claudio, and Tortorella, Carla
Subjects: Pediatrics, medicine.medical_specialty, education.field_of_study, Expanded Disability Status Scale, Coronavirus disease 2019 (COVID-19), business.industry, Multiple sclerosis, COVID-19, multiple sclerosis, neuroimmunology, Population, medicine.disease, Vaccination, Psychiatry and Mental health, Infectious disease (medical specialty), multiple sclerosi, Pandemic, medicine, Surgery, Observational study, multiple sclerosis, neuroimmunology, COVID-19, Neurology (clinical), business, education
Abstract: Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system. A novel coronavirus, namely SARS-CoV-2, has been recently responsible for the highly infectious disease referred as COVID-19, rapidly spreading all over the world. Many vaccines have been developed to control COVID-19 pandemic, including the mRNA vaccines Pfizer/BioNTech (BNT162b2) and Moderna (mRNA1273).1 The vaccination of people with MS (pwMS) has been recommended by several national and international MS societies. However, effectiveness and safety of anti-COVID-19 mRNA vaccines in MS need to be confirmed. The aim of this study was to evaluate the short-term risk of clinical relapses in pwMS in the 2 months after the first administration of an mRNA COVID-19 vaccine. Twenty-five Italian MS tertiary centres participated to this prospective, self-controlled, multicentric observational study. In Italy, COVID-19 population vaccination started at the end of December 2020 and first involved healthcare professionals. All pwMS, diagnosed according to McDonald’s 2017 criteria, who underwent the first dose of an mRNA COVID-19 vaccine within January 2021 were recruited from each participating centre. All patients received Pfizer/BioNTech BNT162b2 vaccine according to vaccine availability in Italy. Database lock was planned on 31 March so that all patients were followed for at least 2 months after the first dose. The following data were collected: (1) sex; (2) age and disease duration; (3) disease course (relapsing remitting; secondary progressive; primary progressive); (4) disability score (Expanded Disability Status Scale, EDSS); (5) clinical relapses in the year before vaccination, with specific regard to the 2 months immediately preceding vaccination; (6) MRI activity in the year before vaccination (new T2 or Gd enhancing—Gd+—lesions); (7) previous molecular swab confirmed SARS-CoV-2 infection; (8) vaccine administration date and (9) disease-modifying treatments at the time of vaccination. The presence, characteristics and number of relapses in the 60 days after the first administration of …
Published: 2022

15. 'Better explanations' in multiple sclerosis diagnostic workup

Author: Massimiliano Calabrese 1, Claudio Gasperini 2, Carla Tortorella 2, Gianmarco Schiavi 2, Giovanni Frisullo 2, Paolo Ragonese, Roberta Fantozzi 2, Luca Prosperini 2, Pietro Annovazzi 2, Cinzia Cordioli 2, Massimiliano Di Filippo 2, Diana Ferraro 2, Alberto Gajofatto 2, Simona Malucchi 2, Salvatore Lo Fermo 2, Giovanna De Luca 2, Maria L Stromillo 2, Eleonora Cocco 2, Antonio Gallo 2, Damiano Paolicelli 2, Roberta Lanzillo 2, Valentina Tomassini 2, Ilaria Pesci 2, Maria E Rodegher 2, Claudio Solaro 2, RIREMS group (Rising Italian Researchers in Multiple Sclerosis), Massimiliano Calabrese 1 , Claudio Gasperini 2 , Carla Tortorella 2 , Gianmarco Schiavi 2 , Giovanni Frisullo 2 , Paolo Ragonese , Roberta Fantozzi 2 , Luca Prosperini 2 , Pietro Annovazzi 2 , Cinzia Cordioli 2 , Massimiliano Di Filippo 2 , Diana Ferraro 2 , Alberto Gajofatto 2 , Simona Malucchi 2 , Salvatore Lo Fermo 2 , Giovanna De Luca 2 , Maria L Stromillo 2 , Eleonora Cocco 2 , Antonio Gallo 2 , Damiano Paolicelli 2 , Roberta Lanzillo 2 , Valentina Tomassini 2 , Ilaria Pesci 2 , Maria E Rodegher 2 , Claudio Solaro 2 , RIREMS group (Rising Italian Researchers in Multiple Sclerosis), Calabrese, M., Gasperini, C., Tortorella, C., Schiavi, G., Frisullo, G., Ragonese, P., Fantozzi, R., Prosperini, L., Annovazzi, P., Cordioli, C., Di Filippo, M., Ferraro, D., Gajofatto, A., Malucchi, S., Lo Fermo, S., De Luca, G., Stromillo, M. L., Cocco, E., Gallo, A., Paolicelli, D., Lanzillo, R., Tomassini, V., Pesci, I., Rodegher, M. E., Solaro, C., Calabrese, Massimiliano, Gasperini, Claudio, Tortorella, Carla, Schiavi, Gianmarco, Frisullo, Giovanni, Ragonese, Paolo, Fantozzi, Roberta, Prosperini, Luca, Annovazzi, Pietro, Cordioli, Cinzia, Di Filippo, Massimiliano, Ferraro, Diana, Gajofatto, Alberto, Malucchi, Simona, Lo Fermo, Salvatore, De Luca, Giovanna, Stromillo, Maria L, Cocco, Eleonora, Gallo, Antonio, Paolicelli, Damiano, Lanzillo, Roberta, Tomassini, Valentina, Pesci, Ilaria, Rodegher, Maria E, and Solaro, Claudio
Subjects: Male, Longitudinal Studie, Disease, 0302 clinical medicine, Multiple Sclerosi, Diagnosis, Medicine, 030212 general & internal medicine, Prospective Studies, Longitudinal Studies, Prospective cohort study, medicine.diagnostic_test, Magnetic Resonance Imaging, clinical practice, atypical MRI lesions, MS mimics, Disease Progression, Female, Settore MED/26 - Neurologia, Radiology, Human, Adult, multiple sclerosis, diagnostic criteria, medicine.medical_specialty, Multiple Sclerosis, omarkers / metabolism Diagnosis, Differential Female Follow-Up Studies Humans Longitudinal Studies Magnetic Resonance Imaging Male Multiple Sclerosis / diagnosis* Prospective Studies, Article, Follow-Up Studie, Diagnosis, Differential, 03 medical and health sciences, Humans, Neuromyelitis optica, business.industry, Multiple sclerosis, Biomarkers, Follow-Up Studies, Magnetic resonance imaging, Odds ratio, Biomarker, medicine.disease, Migraine, Differential, Neurology (clinical), Differential diagnosis, business, 030217 neurology & neurosurgery
Abstract: BackgroundThe exclusion of other diseases that can mimic multiple sclerosis (MS) is the cornerstone of current diagnostic criteria. However, data on the frequency of MS mimics in real life are incomplete.MethodsA total of 695 patients presenting with symptoms suggestive of MS in any of the 22 RIREMS centers underwent a detailed diagnostic workup, including a brain and spinal cord MRI scan, CSF and blood examinations, and a 3-year clinical and radiologic follow-up.FindingsA total of 667 patients completed the study. Alternative diagnoses were formulated in 163 (24.4%) cases, the most frequent being nonspecific neurologic symptoms in association with atypical MRI lesions of suspected vascular origin (40 patients), migraine with atypical lesions (24 patients), and neuromyelitis optica (14 patients). MS was diagnosed in 401 (60.1%) patients according to the 2017 diagnostic criteria. The multivariate analysis revealed that the absence of CSF oligoclonal immunoglobulin G bands (IgG-OB) (odds ratio [OR] 18.113), the presence of atypical MRI lesions (OR 10.977), the absence of dissemination in space (DIS) of the lesions (OR 5.164), and normal visual evoked potentials (OR 3.550) were all independent predictors of an alternative diagnosis.InterpretationThis observational, unsponsored, real-life study, based on clinical practice, showed that diseases that mimicked MS were many, but more than 45% were represented by nonspecific neurologic symptoms with atypical MRI lesions of suspected vascular origin, migraine, and neuromyelitis optica. The absence of IgG-OB and DIS, the presence of atypical MRI lesions, and normal visual evoked potentials should be considered suggestive of an alternative disease and red flags for the misdiagnosis of MS.
Published: 2019

16. Minimal evidence of disease activity (MEDA) in relapsing-remitting multiple sclerosis

Author: Carla Tortorella, Serena Ruggieri, Sarah Rasia, Claudio Gasperini, Cinzia Cordioli, Shalom Haggiag, Laura De Giglio, Nicola De Rossi, Carlo Pozzilli, Chiara Rosa Mancinelli, Simonetta Galgani, and Luca Prosperini
Subjects: Adult, Male, medicine.medical_specialty, Severity of Illness Index, 030218 nuclear medicine & medical imaging, Disease activity, 03 medical and health sciences, chemistry.chemical_compound, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Internal medicine, Humans, Immunologic Factors, Medicine, Glatiramer acetate, Retrospective Studies, Interferon beta, business.industry, Multiple sclerosis, Early disease, Glatiramer Acetate, Interferon-beta, Prognosis, medicine.disease, Magnetic Resonance Imaging, Psychiatry and Mental health, Relapsing remitting, chemistry, Disease Progression, T2 lesions, Female, Surgery, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug, MEDA
Abstract: ObjectiveThis study aimed to define the minimal evidence of disease activity (MEDA) during treatment that can be tolerated without exposing patients with relapsing-remitting multiple sclerosis at risk of long-term disability.MethodsWe retrospectively collected data of patients followed up to 10 years after starting interferon beta or glatiramer acetate. Survival analyses explored the association between the long-term risk of reaching an Expanded Disability Status Scale≥6.0 and early clinical and MRI activity assessed after the first and second year of treatment. Early disease activity was classified by the so-called ‘MAGNIMS score’ (low: no relapses and medium: no relapses and ≥3 new T2 lesions or 1 relapse and 0–2 new T2 lesions; high: 1 relapse and ≥3 new T2 lesions or ≥2 relapses) and the absence or presence of contrast-enhancing lesions (CELs).ResultsAt follow-up, 148/1036 (14.3%) patients reached the outcome: 61/685 (8.9%) with low score (reference category), 57/241 (23.7%) with medium score (HR=1.94, p=0.002) and 30/110 (27.3%) with high score (HR=2.47, plow score subgroup, the risk was further reduced in the absence (49/607, 8.1%) than in the presence of CELs (12/78, 15.4%; HR=2.11, p=0.01). No evident disease activity and low score in the absence of CELs shared the same risk (p=0.54). Similar findings were obtained even after the second year of treatment.ConclusionsEarly marginal MRI activity of one to two new T2 lesions, in the absence of both relapses and CELs, is associated with a minor risk of future disability, thus representing a simple and valuable definition for MEDA.
Published: 2020
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17. Stroke: Should we treat images or symptoms? A call for trial

Author: Claudio Gasperini, Luca Bertaccini, Enrico Cotroneo, Sebastiano Fabiano, Gianluca De Rubeis, and Enrico Pampana
Subjects: Stroke, medicine.medical_specialty, Emergency Medical Services, business.industry, MEDLINE, Physical therapy, Medicine, Humans, Radiology, Nuclear Medicine and imaging, General Medicine, business, medicine.disease
Published: 2021

18. 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

19. Treatment response scoring systems to assess long-term prognosis in self-injectable DMTs relapsing-remitting multiple sclerosis patients

Author: Georgina Arrambide, Angela Vidal-Jordana, Ingrid Galán, Jaume Sastre-Garriga, Xavier Montalban, Susana Otero-Romero, Luca Prosperini, Manuel Comabella, Álvaro Cobo, Joaquim Castilló, Luciana Midaglia, Carlos Nos, Alex Rovira, Carmen Tur, Ana Zabalza, Breogán Rodríguez-Acevedo, Mar Tintoré, Jordi Río, Claudio Gasperini, and Cristina Auger
Subjects: medicine.medical_specialty, Treatment response, Neurology, Multiple Sclerosis, business.industry, Multiple sclerosis, medicine.disease, Prognosis, Predictive value, Magnetic Resonance Imaging, Multiple Sclerosis, Relapsing-Remitting, Relapsing remitting, Predictive Value of Tests, Internal medicine, medicine, Brain mri, Humans, Neurology (clinical), Significant risk, business, Neuroradiology
Abstract: Different treatment response scoring systems in treated MS patients exist. The objective was to assess the long-term predictive value of these systems in RRMS patients treated with self-injectable DMTs. RRMS-treated patients underwent brain MRI before the onset of therapy and 12 months thereafter, and neurological assessments every 6 months. Clinical and demographic characteristics were collected at baseline. After the first year of treatment, several scoring systems [Rio score (RS), modified Rio score (MRS), MAGNIMS score (MS), and ROAD score (RoS)] were calculated. Cox-Regression and survival analyses were performed to identify scores predicting long-term disability. We included 319 RRMS patients. Survival analyses showed that patients with RS > 1 and RoS > 3 had a significant risk of reaching an EDSS of 4.0 and 6.0 The score with the best sensitivity (61%) was the RoS, while the MRS showed the best specificity (88%). The RS showed the best positive predictive value (42%) and the best accuracy (81%). The combined measures integrated into different scores have an acceptable prognostic value for identifying patients with long-term disability. Thus, these data reinforce the concept of early treatment optimization to minimize the risk of long-term disability.
Published: 2021

20. Predictors of lymphocyte count recovery after dimethyl fumarate-induced lymphopenia in people with multiple sclerosis

Author: Matteo Lucchini, Girolama Alessandra Marfia, Viviana Nociti, Maria Chiara Buscarinu, Elisabetta Ferraro, Doriana Landi, Roberta Fantozzi, Massimiliano Mirabella, Carlo Pozzilli, Claudio Gasperini, Antonio Cortese, Carla Tortorella, Antonio Ianniello, Marco Salvetti, Antonella Conte, Giorgia Elia, Luca Prosperini, and Diego Centonze
Subjects: medicine.medical_specialty, Complete data, Neurology, Lymphocyte, Disease duration, Dimethyl Fumarate, Relapsing-Remitting, Settore MED/26, Dimethyl fumarate, Lymphopenia, Multiple sclerosis, Real-world study, Gastroenterology, chemistry.chemical_compound, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, medicine, Humans, In patient, Lymphocyte Count, Original Communication, business.industry, medicine.disease, Settore MED/26 - NEUROLOGIA, medicine.anatomical_structure, chemistry, Neurology (clinical), business, Oral retinoid, Immunosuppressive Agents
Abstract: Background Dimethyl fumarate (DMF) is an oral drug approved for Relapsing Multiple Sclerosis (RMS) patients. Grade III lymphopenia is reported in 5–10% DMF-treated patients. Data on lymphocyte count (ALC) recovery after DMF withdrawal following prolonged lymphopenia are still scarce. Objectives To characterize ALC recovery and to identify predictors of slower recovery after DMF interruption. Methods Multicenter data from RMS patients who started DMF and developed lymphopenia during treatment were collected. In patients with grade II–III lymphopenia, ALCs were evaluated from DMF withdrawal until reaching lymphocyte counts > 800/mm3. Results Among 1034 patients who started DMF, we found 198 (19.1%) patients with lymphopenia and 65 patients (6.3%) who discontinued DMF due to persistent grade II–III lymphopenia. Complete data were available for 51 patients. All patients recovered to ALC > 800 cells/mm3 with a median time of 3.4 months. Lower ALCs at DMF suspension (HR 0.98; p = 0.005), longer disease duration (HR 1.29; p = 0.014) and prior exposure to MS treatments (HR 0.03; p = 0.025) were found predictive of delayed ALC recovery. Conclusion ALC recovery after DMF withdrawal is usually rapid, nevertheless it may require longer time in patients with lower ALC count at DMF interruption, longer disease duration and previous exposure to MS treatments, potentially leading to delayed initiation of a new therapy.
Published: 2021

21. Is mRankin scale correlated with mTICI? A systematic review and meta-regression on RCTs and registries

Author: Claudio Gasperini, Saba L, Luca Prosperini, Luca Bertaccini, De Rubeis G, Sebastiano Fabiano, Enrico Pampana, Enrico Cotroneo, and S. Anticoli
Subjects: medicine.medical_specialty, Randomized controlled trial, law, Sample size determination, business.industry, Internal medicine, medicine, Meta-regression, Positive correlation, business, law.invention
Abstract: Background and PurposemTICI ≥2b/3 is one of the strongest positive predictors of mRS ≤2. Quantitative analysis is poorly investigated. Reconcile results from RCT and registries is still a challenge.The purpose was to evaluate the numeric correlation between mTICI≥2b/3 and mRS≤2 in RCT and registries.MethodsLiterature research was performed on Pubmed for studies in 2015-2020. mTICI, mRS and sample size were recorded. Exclusion criteria were monocentric study, not-human and not-English. Studies quality were assessed with MINORS and RoB2. Meta-logistic and meta-linear regressions were used to correlate mTICI and mRS in both RCTs and registries. Z-test was used for comparing coefficients between RCTs and registries.ResultsTwenty-six studies were evaluated (13 registries; 14 RCTs) for 24423 patients (21914 from registries [average per registry 1685±1277]; 2509 from RCTs [average per RCT 179±160]). RCTs involved anterior circulation only, 7/13 (53.8%) registries considered also posterior one.The OR of obtaining a mRS≤2 for a singular increased of mTICI ≥2b rate was 1.65 (CI95% 1.22-2.01) for all studies, 1.65 (CI95% 1.10-2.46) for RCTs and 1.50 (CI95% 1.00-2.23) for registries. mTICI≥2b and mRS had a positive correlation with a coefficient of 0.49 (CI95% 0.19-0.80, p=0.001) for all studies, 0.54 (CI95% 0.09-1.00) for RCTs and 0.42 (CI 95% 0.04-0.81) for registries. No differences were found in the coefficients between RCTs and registries (p=0.63; p=0.65; respectively).ConclusionsUnitary increased of mTICI≥2b rate correspond to an augment of mRS≤2 by 0.50 (CI95% 0.19-0.89) with OR of obtaining mRS≤2 of 1.65 (CI95% 1.22-2.01), without significantly differences in coefficients.
Published: 2021
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22. Dalfampridine improves slowed processing speed in multiple sclerosis patients with mild motor disability: post hoc analysis of a randomized controlled trial

Author: Luca Prosperini, Claudio Gasperini, Carlo Pozzilli, Elena Barbuti, Silvia Tommasin, and Laura De Giglio
Subjects: medicine.medical_specialty, multiple sclerosis, law.invention, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Randomized controlled trial, law, Post-hoc analysis, medicine, processing speed, RC346-429, Original Research, 030304 developmental biology, Pharmacology, 0303 health sciences, dalfampridine, response to treatment, business.industry, Multiple sclerosis, Information processing, Cognition, medicine.disease, Response to treatment, Neurology, Baseline characteristics, Neurology (clinical), Neurology. Diseases of the nervous system, business, 030217 neurology & neurosurgery, Motor disability
Abstract: Objective: To evaluate baseline characteristics predictive of improving information processing speed in multiple sclerosis (MS) and the relationship between cognitive and motor response to dalfampridine (DA) treatment. Methods: This is a post hoc analysis of a randomized, double-blind, placebo-controlled trial in patients with MS randomized to receive DA 10 mg or placebo twice daily for 12 consecutive weeks. Here, we include only data from 71 patients in the arm treated with DA. According to the median value of Symbol Digit Modalities Test (SDMT) response, patients were categorized as “full responders” (FR) or “partially responders” (PR). Results: There was higher possibility of being FR in the presence of a baseline lower Expanded Disability Status Scale [odds ratio (OR) 0.69; 95% confidence interval (CI) 0.5–0.97, p = 0.034], a higher Multiple Sclerosis Functional Composite value (OR 1.37; 95%CI 1.05–1.8, p = 0.022), a lower Timed 25-Foot Walk Test (OR 0.76; 95% CI 0.6–0.98, p = 0.033), and a lower 9-Hole Peg Test with dominant hand (OR 0.92; 95% CI 0.86–0.99, p = 0.029). FR group did not show any significant improvement of motor performance compared with PR group. Conclusion: The current analysis shows that in MS patients with cognitive deficit, the greatest improvement in SDMT provided by DA was observed in patients with milder motor impairment; cognitive and motor responses to treatments are not related. Trial registration: EU Clinical Trials Register; ID 2013-002558-64 ( https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-002558-64 )
Published: 2021

23. Therapeutic recommendations and seasonal influenza vaccine for multiple sclerosis patients in treatment with ocrelizumab: an expert consensus

Author: Maria A. Rocca, Carlo Pozzilli, Massimo Filippi, Antonio Uccelli, Francesco Patti, Diego Centonze, Claudio Gasperini, Ruggero Capra, Maria Trojano, Paola Perini, Filippi, M., Capra, R., Centonze, D., Gasperini, C., Patti, F., Perini, P., Pozzilli, C., Rocca, M. A., Uccelli, A., and Trojano, M.
Subjects: medicine.medical_specialty, 2019-20 coronavirus outbreak, Consensus, Multiple Sclerosis, Coronavirus disease 2019 (COVID-19), MEDLINE, Antibodies, Monoclonal, Humanized, Settore MED/26, Letter to the Editors, Antibodies, Seasonal influenza, Monoclonal, medicine, Humans, Intensive care medicine, Humanized, Neuroradiology, business.industry, Multiple sclerosis, Expert consensus, medicine.disease, Neurology, Influenza Vaccines, Ocrelizumab, Neurology (clinical), Seasons, business, medicine.drug
Published: 2021

24. Switch Strategy from Direct Aspiration First Pass Technique to Solumbra Improves Technical Outcome in Endovascularly Treated Stroke

Author: Luca Bertaccini, Claudio Gasperini, Alberto Pingi, Alessandro Stasolla, Enrico Cotroneo, Valeria Cozzolino, Marilena Mangiardi, Sebastiano Fabiano, Gianluca De Rubeis, Enrico Pampana, and Sabrina Anticoli
Subjects: medicine.medical_specialty, thrombolysis, Health, Toxicology and Mutagenesis, medicine.medical_treatment, Revascularization, Single Center, Article, Brain Ischemia, 030218 nuclear medicine & medical imaging, Cohort Studies, 03 medical and health sciences, cerebrovascular, 0302 clinical medicine, Internal medicine, medicine, Odd ratio, Humans, mechanical, Stroke, Retrospective Studies, First pass, aspiration, treatment, Cerebral infarction, business.industry, Public Health, Environmental and Occupational Health, Thrombolysis, medicine.disease, stroke, Treatment Outcome, thrombectomy, Cardiology, outcome, business, 030217 neurology & neurosurgery, Cohort study
Abstract: Background: The major endovascular mechanic thrombectomy (MT) techniques are: Stent-Retriever (SR), aspiration first pass technique (ADAPT) and Solumbra (Aspiration + SR), which are interchangeable (defined as switching strategy (SS)). The purpose of this study is to report the added value of switching from ADAPT to Solumbra in unsuccessful revascularization stroke patients. Methods: This is a retrospective, single center, pragmatic, cohort study. From December 2017 to November 2019, 935 consecutive patients were admitted to the Stroke Unit and 176/935 (18.8%) were eligible for MT. In 135/176 (76.7%) patients, ADAPT was used as the first-line strategy. SS was defined as the difference between first technique adopted and the final technique. Revascularization was evaluated with modified Thrombolysis In Cerebral Infarction (TICI) with success defined as mTICI ≥ 2b. Procedural time (PT) and time to reperfusion (TTR) were recorded. Results: Stroke involved: Anterior circulation in 121/135 (89.6%) patients and posterior circulation in 14/135 (10.4%) patients. ADAPT was the most common first-line technique vs. both SR and Solumbra (135/176 (76.7%) vs. 10/176 (5.7%) vs. 31/176 (17.6%), respectively). In 28/135 (20.7%) patients, the mTICI was ≤ 2a requiring switch to Solumbra. The vessel’s diameter positively predicted SS result (Odd Ratio [OR] 1.12, Confidence of Interval [CI] 95% 1.03–1.22, p = 0.006). The mean number of passes before SS was 2.0 ± 1.2. ADAPT to Solumbra improved successful revascularization by 13.3% (107/135 (79.3%) vs. 125/135 (92.6%)). PT was superior for SS comparing with ADAPT (71.1 min (CI 95% 53.2–109.0) vs. 40.0 min (CI 95% 35.0–45.2), p = 0.0004), although, TTR was similar (324.1 min (CI 95% 311.4–387.0) vs. 311.4 min (CI 95% 285.5–338.7), p = 0.23). Conclusion: Successful revascularization was improved by 13.3% after switching form ADAPT to Solumbra (final mTICI ≥ 2b was 92.6%). Vessel’s diameter positively predicted recourse to SS.
Published: 2021

25. Real world experience with teriflunomide in multiple sclerosis: the TER-Italy study

Author: Pietro Annovazzi, Fioravante Capone, Sofia Zywicki, Paola Cavalla, Claudio Gasperini, Roberta Fantozzi, Elisabetta Ferraro, Doriana Landi, Sebastiano Bucello, Maria Maddalena Filippi, Roberto Bergamaschi, Vincenzo Dattola, Luigi M.E. Grimaldi, Girolama Alessandra Marfia, Luca Prosperini, Paolo Ragonese, Paolo Manganotti, Cristina Zuliani, Marco Pisa, Maria Chiara Buscarinu, Giovanna Borriello, A. Bianchi, Massimiliano Mirabella, Antonio Cortese, Marta Altieri, Rosella Cavarretta, Valentina Liliana Adriana Torri-Clerici, Giovanna De Luca, Valentina Tomassini, Massimiliano Di Filippo, Graziella Callari, Massimo Filippi, Giulia Mallucci, Valeria Barcella, Mauro Zaffaroni, Marco Capobianco, Paola Perini, Margherita Russo, Sabrina Realmuto, Marianna Lo Re, Bucello S., Annovazzi P., Ragonese P., Altieri M., Barcella V., Bergamaschi R., Bianchi A., Borriello G., Buscarinu M.C., Callari G., Capobianco M., Capone F., Cavalla P., Cavarretta R., Cortese A., De Luca G., Di Filippo M., Dattola V., Fantozzi R., Ferraro E., Filippi M.M., Gasperini C., Grimaldi L.M.E., Landi D., Re M.L., Mallucci G., Manganotti P., Marfia G.A., Mirabella M., Perini P., Pisa M., Realmuto S., Russo M., Tomassini V., Torri-Clerici V.L.A., Zaffaroni M., Zuliani C., Zywicki S., Filippi M., and Prosperini L.
Subjects: medicine.medical_specialty, Neurology, Multiple Sclerosis, Toluidines, Hydroxybutyrates, Oral drugs, Disease, Relapsing-Remitting, Settore MED/26, Pregnancy planning, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, Teriflunomide, Nitriles, medicine, Humans, 030212 general & internal medicine, Adverse effect, Retrospective Studies, Expanded Disability Status Scale, business.industry, Multiple sclerosis, medicine.disease, Settore MED/26 - NEUROLOGIA, chemistry, Tolerability, Italy, Crotonates, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Objective: To identify baseline factors associated with disease activity in patients with relapsing–remitting multiple sclerosis (RRMS) under teriflunomide treatment. Methods: This was an independent, multi-centre, retrospective post-marketing study. We analysed data of 1,507 patients who started teriflunomide since October 2014 and were regularly followed in 28 Centres in Italy. We reported the proportions of patients who discontinued treatment (after excluding 32 lost to follow-up) and who experienced clinical disease activity, i.e., relapse(s) and/or confirmed disability worsening, as assessed by the Expanded Disability Status Scale (EDSS). Decision tree-based analysis was performed to identify baseline factors associated with clinical disease activity during teriflunomide treatment. Results: At database lock (September 2020), approximately 29% of patients (430 out of 1,475) discontinued teriflunomide because of disease activity (~ 46%), adverse events (~ 37%), poor tolerability (~ 15%), pregnancy planning (~ 2%). Approximately 28% of patients experienced disease activity over a median follow-up of 2.75years: ~ 9% had relapses but not disability worsening; ~ 13% had isolated disability worsening; ~ 6% had both relapses and disability worsening. The most important baseline factor associated with disease activity(especially disability worsening) was an EDSS > 4.0 (p < 0.001). In patients with moderate disability level (EDSS 2.0–4.0), disease activity occurred more frequently in case of ≥ 1 pre-treatment relapses (p = 0.025). In patients with milder disability level (EDSS < 2.0), disease activity occurred more frequently after previous exposure to ≥ 2 disease-modifying treatments (p = 0.007). Conclusions: Our study suggests a place-in-therapy for teriflunomide in naïve patients with mild disability level or in those who switched their initial treatment for poor tolerability. Adverse events related with teriflunomide were consistent with literature data, without any new safety concern.
Published: 2021

26. Development and evaluation of a manual segmentation protocol for deep grey matter in multiple sclerosis: Towards accelerated semi-automated references

Author: Massimo Filippi, Jessica Burggraaff, Jette L. Frederiksen, Claudio Gasperini, Jaume Sastre-Garriga, Frederik Barkhof, Marios C. Yiannakas, Christian Enzinger, Mike P. Wattjes, Menno M. Schoonheim, Bernard M. J. Uitdehaag, Maria A. Rocca, Antonio Gallo, Serena Ruggieri, Deborah Pareto, Hugo Vrenken, Yaou Liu, Ludwig Kappos, Alexandra de Sitter, Michael Amann, Miklos Palotai, Charles R.G. Guttmann, Stefan Ropele, Jorge Simoes, Fabian Bartel, Katharina Schregel, Radiology and nuclear medicine, Neurology, Amsterdam Neuroscience - Neuroinfection & -inflammation, Anatomy and neurosciences, Amsterdam Neuroscience - Brain Imaging, Other Research, de Sitter, A., Burggraaff, J., Bartel, F., Palotai, M., Liu, Y., Simoes, J., Ruggieri, S., Schregel, K., Ropele, S., Rocca, M. A., Gasperini, C., Gallo, A., Schoonheim, M. M., Amann, M., Yiannakas, M., Pareto, D., Wattjes, M. P., Sastre-Garriga, J., Kappos, L., Filippi, M., Enzinger, C., Frederiksen, J., Uitdehaag, B., Guttmann, C. R. G., Barkhof, F., and Vrenken, H.
Subjects: Atrophy, Deep grey matter, MRI, Multiple Sclerosis, Reference set, Segmentation, Jaccard index, Computer science, Cognitive Neuroscience, Computer applications to medicine. Medical informatics, R858-859.7, Reproducibility of Result, Grey matter, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Thalamus, Multiple Sclerosi, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Gray Matter, RC346-429, Thalamu, Reliability (statistics), Protocol (science), Reproducibility, business.industry, Multiple sclerosis, 05 social sciences, Reproducibility of Results, Regular Article, Pattern recognition, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Neurology, Manual segmentation, Neurology. Diseases of the nervous system, Neurology (clinical), Artificial intelligence, business, 030217 neurology & neurosurgery, Human
Abstract: Background Deep grey matter (dGM) structures, particularly the thalamus, are clinically relevant in multiple sclerosis (MS). However, segmentation of dGM in MS is challenging; labeled MS-specific reference sets are needed for objective evaluation and training of new methods. Objectives This study aimed to (i) create a standardized protocol for manual delineations of dGM; (ii) evaluate the reliability of the protocol with multiple raters; and (iii) evaluate the accuracy of a fast-semi-automated segmentation approach (FASTSURF). Methods A standardized manual segmentation protocol for caudate nucleus, putamen, and thalamus was created, and applied by three raters on multi-center 3D T1-weighted MRI scans of 23 MS patients and 12 controls. Intra- and inter-rater agreement was assessed through intra-class correlation coefficient (ICC); spatial overlap through Jaccard Index (JI) and generalized conformity index (CIgen). From sparse delineations, FASTSURF reconstructed full segmentations; accuracy was assessed both volumetrically and spatially. Results All structures showed excellent agreement on expert manual outlines: intra-rater JI > 0.83; inter-rater ICC ≥ 0.76 and CIgen ≥ 0.74. FASTSURF reproduced manual references excellently, with ICC ≥ 0.97 and JI ≥ 0.92. Conclusions The manual dGM segmentation protocol showed excellent reproducibility within and between raters. Moreover, combined with FASTSURF a reliable reference set of dGM segmentations can be produced with lower workload.
Published: 2021
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27. Defining the course of tumefactive multiple sclerosis: A large retrospective multicentre study

Author: Lorenzo Gaetani, Doriana Landi, Diana Ferraro, Paolo Ragonese, Alberto Gajofatto, Caterina Di Carmine, Paola Cavalla, Maria Pia Amato, Eleonora Cocco, Roberta Lanzillo, Alessia Manni, Roberta Fantozzi, Claudio Gasperini, D. Farina, Giuseppe Fenu, Sara Zagaglia, Raffaella Cerqua, Claudio Solaro, Antonio Gallo, Carolina Gabri Nicoletti, Pietro Iaffaldano, Federica Pinardi, Valentina Torri Clerici, Isabella Righini, Fabio Buttari, Damiano Paolicelli, Pietro Annovazzi, Carla Tortorella, Rocco Totaro, Giovanna De Luca, Chiara De Fino, Valentina Tomassini, Luca Prosperini, Marcello Moccia, Viviana Nociti, Maria Chiara Buscarinu, Maria Di Gregorio, Massimiliano Di Filippo, Di Gregorio M., Torri Clerici V.L.A., Fenu G., Gaetani L., Gallo A., Cavalla P., Ragonese P., Annovazzi P., Gajofatto A., Prosperini L., Landi D., Nicoletti C.G., Di Carmine C., Totaro R., Nociti V., De Fino C., Ferraro D., Tomassini V., Tortorella C., Righini I., Amato M.P., Manni A., Paolicelli D., Iaffaldano P., Lanzillo R., Moccia M., Buttari F., Fantozzi R., Cerqua R., Zagaglia S., Farina D., De Luca G., Buscarinu M.C., Pinardi F., Cocco E., Gasperini C., Solaro C.M., Di Filippo M., Di Gregorio, M., Torri Clerici, V. L. A., Fenu, G., Gaetani, L., Gallo, A., Cavalla, P., Ragonese, P., Annovazzi, P., Gajofatto, A., Prosperini, L., Landi, D., Nicoletti, C. G., Di Carmine, C., Totaro, R., Nociti, V., De Fino, C., Ferraro, D., Tomassini, V., Tortorella, C., Righini, I., Amato, M. P., Manni, A., Paolicelli, D., Iaffaldano, P., Lanzillo, R., Moccia, M., Buttari, F., Fantozzi, R., Cerqua, R., Zagaglia, S., Farina, D., De Luca, G., Buscarinu, M. C., Pinardi, F., Cocco, E., Gasperini, C., Solaro, C. M., and Di Filippo, M.
Subjects: Male, tumefactive demyelinating lesions (TDLs), 0302 clinical medicine, Retrospective Studie, Interquartile range, differential diagnosis, 030212 general & internal medicine, Prospective Studies, Young adult, Prospective cohort study, Child, treatment, Tumefactive multiple sclerosi, Tumefactive demyelinating lesions, Demyelinating Disease, Middle Aged, Magnetic Resonance Imaging, Differential diagnosis, Multiple sclerosis, Tumefactive demyelinating lesions, Tumefactive multiple sclerosis, Neurology, Multiple sclerosis, Tumefactive multiple sclerosis, Female, Human, Adult, medicine.medical_specialty, Multiple Sclerosis, Adolescent, differential diagnosi, Settore MED/26, 03 medical and health sciences, Young Adult, Oligoclonal Band, Internal medicine, medicine, Humans, Multiple sclerosi, Tumefactive multiple sclerosis (TuMS), Aged, Retrospective Studies, Tumefactive demyelinating lesion, Expanded Disability Status Scale, business.industry, Oligoclonal Bands, Retrospective cohort study, Odds ratio, medicine.disease, Confidence interval, Prospective Studie, Demyelinating Diseases, prognosis, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Background and purpose: Tumefactive multiple sclerosis (TuMS) (i.e., MS onset presenting with tumefactive demyelinating lesions [TDLs]) is a diagnostic and therapeutic challenge. We performed a multicentre retrospective study to describe the clinical characteristics and the prognostic factors of TuMS. Methods: One hundred two TuMS patients were included in this retrospective study. Demographic, clinical, magnetic resonance imaging (MRI), laboratory data and treatment choices were collected. Results: TuMS was found to affect women more than men (female:male: 2.4), with a young adulthood onset (median age: 29.5years, range: 11–68 years, interquartile range [IQR]: 38 years). At onset, 52% of TuMS patients presented with the involvement of more than one functional system and 24.5% of them with multiple TDLs. TDLs most frequently presented with an infiltrative MRI pattern (38.7%). Cerebrospinal fluid immunoglobulin G oligoclonal bands were often demonstrated (76.6%). In 25.3% of the cases, more than one acute-phase treatment was administered, and almost one-half of the patients (46.6%) were treated with high-efficacy treatments. After a median follow-up of 2.3years (range: 0.1–10.7 years, IQR: 3.4 years), the median Expanded Disability Status Scale (EDSS) score was 1.5 (range: 0–7, IQR: 2). Independent risk factors for reaching an EDSS score ≥3 were a higher age at onset (odds ratio [OR]: 1.08, 95% confidence interval [CI]: 1.03–1.14, p&nbsp
Published: 2021

28. SARS-CoV-2 serology after COVID-19 in multiple sclerosis: An international cohort study

Author: Maria Pia Sormani, Irene Schiavetti, Doriana Landi, Luca Carmisciano, Nicola De Rossi, Cinzia Cordioli, Lucia Moiola, Marta Radaelli, Paolo Immovilli, Marco Capobianco, Vincenzo Brescia Morra, Maria Trojano, Gioacchino Tedeschi, Giancarlo Comi, Mario Alberto Battaglia, Francesco Patti, Yara Dadalti Fragoso, Sedat Sen, Aksel Siva, Roberto Furlan, Marco Salvetti, Gianmarco Abbadessa, Umberto Aguglia, Lia Allegorico, Rossi Beatrice Maria Allegri, Maria Pia Amato, Pietro Annovazzi, Carlo Antozzi, Lucia Appendino, Sebastiano Arena, Viola Baione, Roberto Balgera, Valeria Barcella, Damiano Baroncini, Caterina Barrilà, Mario A. Battaglia, Alessandra Bellacosa, Gianmarco Bellucci, Roberto Bergamaschi, Valeria Bergamaschi, Daiana Bezzini, Beatrice Biolzi, Alvino Bisecco, Simona Bonavita, Giovanna Borriello, Chiara Bosa, Antonio Bosco, Francesca Bovis, Marco Bozzali, Laura Brambilla, Morra Vincenzo Brescia, Giampaolo Brichetto, Maria Buccafusca, Elisabetta Bucciantini, Sebastiano Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano Calabrese, Francesca Calabria, Francesca Caleri, Federico Camilli, Luisa Maria Caniatti, Roberto Cantello, Ruggero Capra, Rocco Capuano, Patrizia Carta, Paola Cavalla, Maria Grazia Celani, Maria Cellerino, Raffaella Cerqua, Clara Chisari, Raffaella Clerici, Marinella Clerico, Eleonora Cocco, Gaia Cola, Paolo Confalonieri, Antonella Conte, Marta Zaffira Conti, Christian Cordano, Susanna Cordera, Francesco Corea, Claudio Correale, Salvatore Cottone, Francesco Crescenzo, Erica Curti, Alessandro d’Ambrosio, Emanuele D’Amico, Maura Chiara Danni, Alessia d’Arma, Vincenzo Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Stefano, Marco Della Cava, Mario di Napoli, Alessia Di Sapio, Renato Docimo, Anna Dutto, Luana Evangelista, Salvatore Fanara, Diana Ferraro, Maria Teresa Ferrò, Massimo Filippi, Cristina Fioretti, Mario Fratta, Jessica Frau, Marzia Fronza, Alberto Gajofatto, Antonio Gallo, Paolo Gallo, Claudio Gasperini, Anna Ghazaryan, Bruno Giometto, Francesca Gobbin, Flora Govone, Franco Granella, Erica Grange, Maria Grazia Grasso, Angelica Guareschi, Clara Guaschino, Simone Guerrieri, Donata Guidetti, Pietro Iaffaldano, Antonio Ianniello, Luigi Iasevoli, Daniele Imperiale, Maria Teresa Infante, Matilde Inglese, Rosa Iodice, Aniello Iovino, Giovanna Konrad, Roberta Lanzillo, Caterina Lapucci, Luigi Lavorgna, Rita L’Episcopo Maria, Serena Leva, Giuseppe Liberatore, Marianna Lo Re, Marco Longoni, Leonardo Lopiano, Lorena Lorefice, Matteo Lucchini, Giacomo Lus, Davide Maimone, Maria Malentacchi, Giulia Mallucci, Simona Malucchi, Chiara Rosa Mancinelli, Luca Mancinelli, Paolo Manganotti, Teresa Giorgia Maniscalco, Vittorio Mantero, Sabrina Marangoni, Damiano Marastoni, Alessandra Girolama Marfia, Fabiana Marinelli, Alessandro Marti, Filippo Martinelli Boneschi, Federco Masserano Zoli, Francesca Matta, Laura Mendozzi, Giuseppe Meucci, Silvia Miante, Giuseppina Miele, Eva Milano, Massimiliano Mirabella, Rosanna Missione, Marcello Moccia, Sara Montepietra, Margherita Monti Bragadin, Federico Montini, Roberta Motta, Raffaele Nardone, Carolina Gabri Nicoletti, Eduardo Nobile-Orazio, Agostino Nozzolillo, Marco Onofrj, Riccardo Orlandi, Anna Palmieri, Damiano Paolicelli, Livia Pasquali, Luisa Pastò, Elisabetta Pedrazzoli, Paola Perini, Ilaria Pesci, Maria Petracca, Alfredo Petrone, Carlo Piantadosi, Anna M. Pietroboni, Federica Pinardi, Marta Ponzano, Emilio Portaccio, Mattia Pozzato, Carlo Pozzilli, Luca Prosperini, Alessandra Protti, Paolo Ragonese, Sarah Rasia, Sabrina Realmuto, Anna Repice, Eleonora Rigoni, Maria Teresa Rilla, Francesca Rinaldi, Calogero Marcello Romano, Marco Ronzoni, Marco Rovaris, Francesca Ruscica, Loredana Sabattini, Giuseppe Salemi, Lorenzo Saraceno, Alessia Sartori, Arianna Sartori, Elvira Sbragia, Cinzia Scandellari, Ilaria Scarano Giuditta, Valentina Scarano, Valentina Schillaci, Maria Sessa, Caterina Sgarito, Grazia Sibilia, Gabriele Siciliano, Alessio Signori, Elisabetta Signoriello, Leonardo Sinisi, Francesca Sireci, Patrizia Sola, Claudio Solaro, Stefano Sotgiu, Maddalena Sparaco, Maria Laura Stromillo, Silvia Strumia, Laura Emanuela Susani, Giulietta Tabiadon, Francesco Teatini, Valentina Tomassini, Simone Tonietti, Clerici Valentina Torri, Carla Tortorella, Simona Toscano, Rocco Totaro, Maria Trotta, Gabriella Turano, Monica Ulivelli, Manzo Valentino, Giovanna Vaula, Domizia Vecchio, Marco Vercellino, Elena Pinuccia Verrengia, Marika Vianello, Eleonora Virgilio, Francesca Vitetta, Stefano Vollaro, Mauro Zaffaroni, Mauro Zampolini, Ignazio Roberto Zarbo, Antonio Zito, Luigi Zuliani, Sormani, M. P., Schiavetti, I., Landi, D., Carmisciano, L., De Rossi, N., Cordioli, C., Moiola, L., Radaelli, M., Immovilli, P., Capobianco, M., Brescia Morra, V., Trojano, M., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Fragoso, Y. D., Sen, S., Siva, A., Furlan, R., Salvetti, M., Bisecco, Alvino, Pia Sormani, Maria, Schiavetti, Irene, Landi, Doriana, Carmisciano, Luca, De Rossi, Nicola, Cordioli, Cinzia, Moiola, Lucia, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, Brescia Morra, Vincenzo, Trojano, Maria, Tedeschi, Gioacchino, Comi, Giancarlo, Alberto Battaglia, Mario, Patti, Francesco, Dadalti Fragoso, Yara, Sen, Sedat, Siva, Aksel, Furlan, Roberto, Salvetti, Marco, Study Group Gianmarco Abbadessa, MuSC-19, Aguglia, Umberto, Allegorico, Lia, Beatrice Maria Allegri, Rossi, Pia Amato, Maria, Annovazzi, Pietro, Antozzi, Carlo, Appendino, Lucia, Arena, Sebastiano, Baione, Viola, Balgera, Roberto, Barcella, Valeria, Baroncini, Damiano, Barrilà, Caterina, A Battaglia, Mario, Bellacosa, Alessandra, Bellucci, Gianmarco, Bergamaschi, Roberto, Bergamaschi, Valeria, Bezzini, Daiana, Biolzi, Beatrice, Bonavita, Simona, Borriello, Giovanna, Bosa, Chiara, Bosco, Antonio, Bovis, Francesca, Bozzali, Marco, Brambilla, Laura, Vincenzo Brescia, Morra, Brichetto, Giampaolo, Buccafusca, Maria, Bucciantini, Elisabetta, Bucello, Sebastiano, Chiara Buscarinu, Maria, Paola Cabboi, Maria, Calabrese, Massimiliano, Calabria, Francesca, Caleri, Francesca, Camilli, Federico, Maria Caniatti, Luisa, Cantello, Roberto, Capra, Ruggero, Capuano, Rocco, Carta, Patrizia, Cavalla, Paola, Grazia Celani, Maria, Cellerino, Maria, Cerqua, Raffaella, Chisari, Clara, Clerici, Raffaella, Clerico, Marinella, Cocco, Eleonora, Cola, Gaia, Confalonieri, Paolo, Conte, Antonella, Zaffira Conti, Marta, Cordano, Christian, Cordera, Susanna, Corea, Francesco, Correale, Claudio, Cottone, Salvatore, Crescenzo, Francesco, Curti, Erica, D'Ambrosio, Alessandro, D'Amico, Emanuele, Chiara Danni, Maura, D'Arma, Alessia, Dattola, Vincenzo, de Biase, Stefano, De Luca, Giovanna, Federica De Mercanti, Stefania, De Mitri, Paolo, De Stefano, Nicola, Della Cava, Marco, di Napoli, Mario, Di Sapio, Alessia, Docimo, Renato, Dutto, Anna, Evangelista, Luana, Fanara, Salvatore, Ferraro, Diana, Teresa Ferrò, Maria, Filippi, Massimo, Fioretti, Cristina, Fratta, Mario, Frau, Jessica, Fronza, Marzia, Gajofatto, Alberto, Gallo, Antonio, Gallo, Paolo, Gasperini, Claudio, Ghazaryan, Anna, Giometto, Bruno, Gobbin, Francesca, Govone, Flora, Granella, Franco, Grange, Erica, Grazia Grasso, Maria, Guareschi, Angelica, Guaschino, Clara, Guerrieri, Simone, Guidetti, Donata, Iaffaldano, Pietro, Ianniello, Antonio, Iasevoli, Luigi, Imperiale, Daniele, Teresa Infante, Maria, Inglese, Matilde, Iodice, Rosa, Iovino, Aniello, Konrad, Giovanna, Lanzillo, Roberta, Lapucci, Caterina, Lavorgna, Luigi, L'Episcopo Maria, Rita, Leva, Serena, Liberatore, Giuseppe, Lo Re, Marianna, Longoni, Marco, Lopiano, Leonardo, Lorefice, Lorena, Lucchini, Matteo, Lus, Giacomo, Maimone, Davide, Malentacchi, Maria, Mallucci, Giulia, Malucchi, Simona, Rosa Mancinelli, Chiara, Mancinelli, Luca, Manganotti, Paolo, Giorgia Maniscalco, Teresa, Mantero, Vittorio, Marangoni, Sabrina, Marastoni, Damiano, Girolama Marfia, Alessandra, Marinelli, Fabiana, Marti, Alessandro, Martinelli Boneschi, Filippo, Masserano Zoli, Federco, Matta, Francesca, Mendozzi, Laura, Meucci, Giuseppe, Miante, Silvia, Miele, Giuseppina, Milano, Eva, Mirabella, Massimiliano, Missione, Rosanna, Moccia, Marcello, Montepietra, Sara, Monti Bragadin, Margherita, Montini, Federico, Motta, Roberta, Nardone, Raffaele, Gabri Nicoletti, Carolina, Nobile-Orazio, Eduardo, Nozzolillo, Agostino, Onofrj, Marco, Orlandi, Riccardo, Palmieri, Anna, Paolicelli, Damiano, Pasquali, Livia, Pastò, Luisa, Pedrazzoli, Elisabetta, Perini, Paola, Pesci, Ilaria, Petracca, Maria, Petrone, Alfredo, Piantadosi, Carlo, M Pietroboni, Anna, Pinardi, Federica, Ponzano, Marta, Portaccio, Emilio, Pozzato, Mattia, Pozzilli, Carlo, Prosperini, Luca, Protti, Alessandra, Ragonese, Paolo, Rasia, Sarah, Realmuto, Sabrina, Repice, Anna, Rigoni, Eleonora, Teresa Rilla, Maria, Rinaldi, Francesca, Marcello Romano, Calogero, Ronzoni, Marco, Rovaris, Marco, Ruscica, Francesca, Sabattini, Loredana, Salemi, Giuseppe, Saraceno, Lorenzo, Sartori, Alessia, Sartori, Arianna, Sbragia, Elvira, Scandellari, Cinzia, Scarano Giuditta, Ilaria, Scarano, Valentina, Schillaci, Valentina, Sessa, Maria, Sgarito, Caterina, Sibilia, Grazia, Siciliano, Gabriele, Signori, Alessio, Signoriello, Elisabetta, Sinisi, Leonardo, Sireci, Francesca, Sola, Patrizia, Solaro, Claudio, Sotgiu, Stefano, Sparaco, Maddalena, Laura Stromillo, Maria, Strumia, Silvia, Emanuela Susani, Laura, Tabiadon, Giulietta, Teatini, Francesco, Tomassini, Valentina, Tonietti, Simone, Valentina Torri, Clerici, Tortorella, Carla, Toscano, Simona, Totaro, Rocco, Trotta, Maria, Turano, Gabriella, Ulivelli, Monica, Valentino, Manzo, Vaula, Giovanna, Vecchio, Domizia, Vercellino, Marco, Pinuccia Verrengia, Elena, Vianello, Marika, Virgilio, Eleonora, Vitetta, Francesca, Vollaro, Stefano, Zaffaroni, Mauro, Zampolini, Mauro, Roberto Zarbo, Ignazio, Zito, Antonio, Zuliani, Luigi, Abbadessa, Gianmarco, Trotta, Maria Consiglia, and Zito, Guido Antonio
Subjects: 0301 basic medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), immunosuppressive therapie, coronavirus, Settore MED/26, medicine.disease_cause, Antibodies, Viral, immunosuppressive therapies, Antibodies, Serology, Cohort Studies, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Seroepidemiologic Studies, Pandemic, Medicine, Humans, Multiple sclerosi, Viral, Coronavirus, business.industry, immunomodulatory therapie, immunomodulatory therapies, COVID-19, medicine.disease, Virology, coronaviru, Settore MED/26 - NEUROLOGIA, Sars-COV-2, 030104 developmental biology, Neurology, Neurology (clinical), business, SARS-CoV-2, Multiple Sclerosis, 030217 neurology & neurosurgery, Cohort study
Abstract: Background: The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, serological tests became routinely available. Objective: To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test. Methods: We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model. Results: Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20, p = 0.002). Conclusion: Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination.
Published: 2021

29. COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Author: Maria Pia Sormani, Irene Schiavetti, Luca Carmisciano, Cinzia Cordioli, Massimo Filippi, Marta Radaelli, Paolo Immovilli, Marco Capobianco, Nicola De Rossi, Giampaolo Brichetto, Eleonora Cocco, Cinzia Scandellari, Paola Cavalla, Ilaria Pesci, Antonio Zito, Paolo Confalonieri, Girolama Alessandra Marfia, Paola Perini, Matilde Inglese, Maria Trojano, Vincenzo Brescia Morra, Gioacchino Tedeschi, Giancarlo Comi, Mario Alberto Battaglia, Francesco Patti, Marco Salvetti, Gianmarco Abbadessa, Umberto Aguglia, Lia Allegorico, Beatrice Maria Allegri Rossi, Maria Pia Amato, Pietro Annovazzi, Carlo Antozzi, Lucia Appendino, Sebastiano Arena, Viola Baione, Roberto Balgera, Valeria Barcella, Damiano Baroncini, Caterina Barrilà, Alessandra Bellacosa, Gianmarco Bellucci, Roberto Bergamaschi, Valeria Bergamaschi, Daiana Bezzini, Beatrice Biolzi, Alvino Bisecco, Simona Bonavita, Giovanna Borriello, Chiara Bosa, Antonio Bosco, Francesca Bovis, Marco Bozzali, Laura Brambilla, Maria Buccafusca, Elisabetta Bucciantini, Sebastiano Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano Calabrese, Francesca Calabria, Francesca Caleri, Federico Camilli, Luisa Maria Caniatti, Roberto Cantello, Ruggero Capra, Rocco Capuano, Patrizia Carta, Maria Grazia Celani, Maria Cellerino, Raffaella Cerqua, Clara Chisari, Raffaella Clerici, Marinella Clerico, Gaia Cola, Antonella Conte, Marta Zaffira Conti, Christian Cordano, Susanna Cordera, Francesco Corea, Claudio Correale, Salvatore Cottone, Francesco Crescenzo, Erica Curti, Alessandro d'Ambrosio, Emanuele D'Amico, Maura Chiara Danni, Alessia d'Arma, Vincenzo Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Stefano, Marco Della Cava, Mario di Napoli, Alessia Di Sapio, Renato Docimo, Anna Dutto, Luana Evangelista, Salvatore Fanara, Ferraro Diana, Maria Teresa Ferrò, Cristina Fioretti, Mario Fratta, Jessica Frau, Marzia Fronza, Roberto Furlan, Alberto Gajofatto, Antonio Gallo, Paolo Gallo, Claudio Gasperini, Anna Ghazaryan, Bruno Giometto, Francesca Gobbin, Flora Govone, Franco Granella, Erica Grange, Maria Grazia Grasso, Angelica Guareschi, Clara Guaschino, Simone Guerrieri, Donata Guidetti, Pietro Iaffaldano, Antonio Ianniello, Luigi Iasevoli, Daniele Imperiale, Maria Teresa Infante, Rosa Iodice, Aniello Iovino, Giovanna Konrad, Doriana Landi, Roberta Lanzillo, Caterina Lapucci, Luigi Lavorgna, Maria Rita L'Episcopo, Serena Leva, Giuseppe Liberatore, Marianna Lo Re, Marco Longoni, Leonardo Lopiano, Lorena Lorefice, Matteo Lucchini, Giacomo Lus, Davide Maimone, Maria Malentacchi, Giulia Mallucci, Simona Malucchi, Chiara Rosa Mancinelli, Luca Mancinelli, Paolo Manganotti, Giorgia Teresa Maniscalco, Vittorio Mantero, Sabrina Marangoni, Damiano Marastoni, Fabiana Marinelli, Alessandro Marti, Filippo Martinelli Boneschi, Federco Masserano Zoli, Francesca Matta, Laura Mendozzi, Giuseppe Meucci, Silvia Miante, Giuseppina Miele, Eva Milano, Massimiliano Mirabella, Rosanna Missione, Marcello Moccia, Lucia Moiola, Sara Montepietra, Margherita MontiBragadin, Federico Montini, Roberta Motta, Raffaele Nardone, Carolina Gabri Nicoletti, Eduardo Nobile-Orazio, Agostino Nozzolillo, Marco Onofrj, Riccardo Orlandi, Anna Palmieri, Damiano Paolicelli, Livia Pasquali, Luisa Pastò, Elisabetta Pedrazzoli, Maria Petracca, Alfredo Petrone, Carlo Piantadosi, Anna M Pietroboni, Federica Pinardi, Marta Ponzano, Emilio Portaccio, Mattia Pozzato, Carlo Pozzilli, Luca Prosperini, Alessandra Protti, Paolo Ragonese, Sarah Rasia, Sabrina Realmuto, Anna Repice, Eleonora Rigoni, Maria Teresa Rilla, Francesca Rinaldi, Calogero Marcello Romano, Marco Ronzoni, Marco Rovaris, Francesca Ruscica, Loredana Sabattini, Giuseppe Salemi, Lorenzo Saraceno, Alessia Sartori, Arianna Sartori, Elvira Sbragia, Giuditta Ilaria Scarano, Valentina Scarano, Valentina Schillaci, Maria Sessa, Caterina Sgarito, Grazia Sibilia, Gabriele Siciliano, Alessio Signori, Elisabetta Signoriello, Leonardo Sinisi, Francesca Sireci, Patrizia Sola, Claudio Solaro, Stefano Sotgiu, Maddalena Sparaco, Maria Laura Stromillo, Silvia Strumia, Emanuela Laura Susani, Giulietta Tabiadon, Francesco Teatini, Valentina Tomassini, Simone Tonietti, Clerici Valentina Torri, Carla Tortorella, Simona Toscano, Rocco Totaro, Maria Trotta, Gabriella Turano, Monica Ulivelli, Manzo Valentino, Giovanna Vaula, Domizia Vecchio, Marco Vercellino, Elena Pinuccia Verrengia, Marika Vianello, Eleonora Virgilio, Francesca Vitetta, Stefano Vollaro, Mauro Zaffaroni, Mauro Zampolini, Ignazio Roberto Zarbo, Luigi Zuliani, Pia Sormani, Maria, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Filippi, Massimo, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, De Rossi, Nicola, Brichetto, Giampaolo, Cocco, Eleonora, Scandellari, Cinzia, Cavalla, Paola, Pesci, Ilaria, Zito, Guido Antonio, Confalonieri, Paolo, Alessandra Marfia, Girolama, Perini, Paola, Inglese, Matilde, Trojano, Maria, Brescia Morra, Vincenzo, Tedeschi, Gioacchino, Comi, Giancarlo, Alberto Battaglia, Mario, Patti, Francesco, Salvetti, Marco, Abbadessa, Gianmarco, Aguglia, Umberto, Allegorico, Lia, Maria Allegri Rossi, Beatrice, Pia Amato, Maria, Annovazzi, Pietro, Antozzi, Carlo, Appendino, Lucia, Arena, Sebastiano, Baione, Viola, Balgera, Roberto, Barcella, Valeria, Baroncini, Damiano, Barrilà, Caterina, Bellacosa, Alessandra, Bellucci, Gianmarco, Bergamaschi, Roberto, Bergamaschi, Valeria, Bezzini, Daiana, Biolzi, Beatrice, Bisecco, Alvino, Bonavita, Simona, Borriello, Giovanna, Bosa, Chiara, Bosco, Antonio, Bovis, Francesca, Bozzali, Marco, Brambilla, Laura, Buccafusca, Maria, Bucciantini, Elisabetta, Bucello, Sebastiano, Chiara Buscarinu, Maria, Paola Cabboi, Maria, Calabrese, Massimiliano, Calabria, Francesca, Caleri, Francesca, Camilli, Federico, Maria Caniatti, Luisa, Cantello, Roberto, Capra, Ruggero, Capuano, Rocco, Carta, Patrizia, Grazia Celani, Maria, Cellerino, Maria, Cerqua, Raffaella, Chisari, Clara, Clerici, Raffaella, Clerico, Marinella, Cola, Gaia, Conte, Antonella, Zaffira Conti, Marta, Cordano, Christian, Cordera, Susanna, Corea, Francesco, Correale, Claudio, Cottone, Salvatore, Crescenzo, Francesco, Curti, Erica, D'Ambrosio, Alessandro, D'Amico, Emanuele, Chiara Danni, Maura, D'Arma, Alessia, Dattola, Vincenzo, de Biase, Stefano, De Luca, Giovanna, Federica De Mercanti, Stefania, De Mitri, Paolo, De Stefano, Nicola, Della Cava, Marco, di Napoli, Mario, Di Sapio, Alessia, Docimo, Renato, Dutto, Anna, Evangelista, Luana, Fanara, Salvatore, Diana, Ferraro, Teresa Ferrò, Maria, Fioretti, Cristina, Fratta, Mario, Frau, Jessica, Fronza, Marzia, Furlan, Roberto, Gajofatto, Alberto, Gallo, Antonio, Gallo, Paolo, Gasperini, Claudio, Ghazaryan, Anna, Giometto, Bruno, Gobbin, Francesca, Govone, Flora, Granella, Franco, Grange, Erica, Grazia Grasso, Maria, Guareschi, Angelica, Guaschino, Clara, Guerrieri, Simone, Guidetti, Donata, Iaffaldano, Pietro, Ianniello, Antonio, Iasevoli, Luigi, Imperiale, Daniele, Teresa Infante, Maria, Iodice, Rosa, Iovino, Aniello, Konrad, Giovanna, Landi, Doriana, Lanzillo, Roberta, Lapucci, Caterina, Lavorgna, Luigi, Rita L'Episcopo, Maria, Leva, Serena, Liberatore, Giuseppe, Lo Re, Marianna, Longoni, Marco, Lopiano, Leonardo, Lorefice, Lorena, Lucchini, Matteo, Lus, Giacomo, Maimone, Davide, Malentacchi, Maria, Mallucci, Giulia, Malucchi, Simona, Rosa Mancinelli, Chiara, Mancinelli, Luca, Manganotti, Paolo, Teresa Maniscalco, Giorgia, Mantero, Vittorio, Marangoni, Sabrina, Marastoni, Damiano, Marinelli, Fabiana, Marti, Alessandro, Martinelli Boneschi, Filippo, Masserano Zoli, Federco, Matta, Francesca, Mendozzi, Laura, Meucci, Giuseppe, Miante, Silvia, Miele, Giuseppina, Milano, Eva, Mirabella, Massimiliano, Missione, Rosanna, Moccia, Marcello, Moiola, Lucia, Montepietra, Sara, Montibragadin, Margherita, Montini, Federico, Motta, Roberta, Nardone, Raffaele, Gabri Nicoletti, Carolina, Nobile-Orazio, Eduardo, Nozzolillo, Agostino, Onofrj, Marco, Orlandi, Riccardo, Palmieri, Anna, Paolicelli, Damiano, Pasquali, Livia, Pastò, Luisa, Pedrazzoli, Elisabetta, Petracca, Maria, Petrone, Alfredo, Piantadosi, Carlo, M Pietroboni, Anna, Pinardi, Federica, Ponzano, Marta, Portaccio, Emilio, Pozzato, Mattia, Pozzilli, Carlo, Prosperini, Luca, Protti, Alessandra, Ragonese, Paolo, Rasia, Sarah, Realmuto, Sabrina, Repice, Anna, Rigoni, Eleonora, Teresa Rilla, Maria, Rinaldi, Francesca, Marcello Romano, Calogero, Ronzoni, Marco, Rovaris, Marco, Ruscica, Francesca, Sabattini, Loredana, Salemi, Giuseppe, Saraceno, Lorenzo, Sartori, Alessia, Sartori, Arianna, Sbragia, Elvira, Ilaria Scarano, Giuditta, Scarano, Valentina, Schillaci, Valentina, Sessa, Maria, Sgarito, Caterina, Sibilia, Grazia, Siciliano, Gabriele, Signori, Alessio, Signoriello, Elisabetta, Sinisi, Leonardo, Sireci, Francesca, Sola, Patrizia, Solaro, Claudio, Sotgiu, Stefano, Sparaco, Maddalena, Laura Stromillo, Maria, Strumia, Silvia, Laura Susani, Emanuela, Tabiadon, Giulietta, Teatini, Francesco, Tomassini, Valentina, Tonietti, Simone, Valentina Torri, Clerici, Tortorella, Carla, Toscano, Simona, Totaro, Rocco, Trotta, Maria Consiglia, Turano, Gabriella, Ulivelli, Monica, Valentino, Manzo, Vaula, Giovanna, Vecchio, Domizia, Vercellino, Marco, Pinuccia Verrengia, Elena, Vianello, Marika, Virgilio, Eleonora, Vitetta, Francesca, Vollaro, Stefano, Zaffaroni, Mauro, Zampolini, Mauro, Roberto Zarbo, Ignazio, Zuliani, Luigi, Sormani, M. P., Schiavetti, I., Carmisciano, L., Cordioli, C., Filippi, M., Radaelli, M., Immovilli, P., Capobianco, M., De Rossi, N., Brichetto, G., Cocco, E., Scandellari, C., Cavalla, P., Pesci, I., Zito, A., Confalonieri, P., Marfia, G. A., Perini, P., Inglese, M., Trojano, M., Brescia Morra, V., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., Zito, Antonio, BRESCIA MORRA, Vincenzo, Trotta, Maria, Sormani, Maria Pia, Marfia, Girolama Alessandra, and Battaglia, Mario Alberto
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Coronavirus disease 2019 (COVID-19), Population, Intensive Care Unit, COVID-19, Cohort Studies, Comorbidity, Female, Hospitalization, Humans, Intensive Care Units, Italy, Middle Aged, Retrospective Studies, Risk Factors, Severity of Illness Index, Context (language use), Settore MED/26, Lower risk, Retrospective Studie, Internal medicine, Multiple Sclerosi, Medicine, In patient, National level, education, education.field_of_study, Expanded Disability Status Scale, business.industry, Risk Factor, Ethics committee, medicine.disease, Icu admission, Settore MED/26 - NEUROLOGIA, Neurology, Relative risk, Family medicine, Cohort, Honorarium, Observational study, Neurology (clinical), Cohort Studie, business, Human
Abstract: Background: It is unclear how multiple sclerosis (MS) affects the severity of Covid-19. Methods: Hospitalization, Intensive Care Unit (ICU) admission and death after Covid-19 diagnosis of 1362 MS patients were compared to the age and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher-risk: EDSS>3 or at least one comorbidity, lower-risk: EDSS
Published: 2021

30. Prognostic Accuracy of NEDA-3 in Long-term Outcomes of Multiple Sclerosis

Author: Serena Ruggieri, Carla Tortorella, Luca Prosperini, Claudio Gasperini, Shalom Haggiag, and Carlo Pozzilli
Subjects: Adult, Male, multiple sclerosis, disease progression, NEDA, RAW, PIRA, medicine.medical_specialty, Disease, Severity of Illness Index, Article, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, Outcome Assessment, Health Care, medicine, Long term outcomes, Humans, Immunologic Factors, Cumulative incidence, Glatiramer acetate, Mri scan, Retrospective Studies, business.industry, Multiple sclerosis, Age Factors, Middle Aged, medicine.disease, Prognosis, Magnetic Resonance Imaging, Discontinuation, Neurology, Disease Progression, T2 lesions, Female, Neurology (clinical), business, medicine.drug, Follow-Up Studies
Abstract: Background and ObjectivesTo estimate the proportions of patients with relapsing-remitting multiple sclerosis who despite achieving the no evidence of disease activity-3 (NEDA-3) status in the first 2 treatment years experienced relapse-associated worsening (RAW) or progression independent from relapse activity (PIRA) in the following years.MethodsWe selected patients with NEDA-3—defined as no relapse, no disability worsening, and no MRI activity—in the first 2 years of either glatiramer acetate or interferon beta as initial treatment. We estimated the long-term probability of subsequent RAW and PIRA (considered as 2 contrasting outcomes) by cumulative incidence functions. Competing risk regressions were used to identify the baseline (i.e., at treatment start) predictors of RAW and PIRA.ResultsOf 687 patients, 224 (32.6%) had NEDA-3 in the first 2 treatment years. After a median follow-up time of 12 years from treatment start, 58 patients (26%) experienced disability accrual: 31 (14%) had RAW and 27 (12%) had PIRA. RAW was predicted by the presence of >9 T2 lesions (subdistribution hazard ratio [SHR] = 3.92, p = 0.012) and contrast-enhancing lesions (SHR = 2.38, p = 0.047) on baseline MRI scan and either temporary or permanent discontinuation of the initial treatment (SHR = 1.11, p = 0.015). PIRA was predicted by advancing age (SHR = 1.05, p = 0.036 for each year increase) and presence of ≥1 spinal cord lesion on baseline MRI scan (SHR = 4.08, p = 0.016).DiscussionThe adoption of NEDA-3 criteria led to prognostic misclassification in 1 of 4 patients. Different risk factors were associated with RAW and PIRA, suggesting alternative mechanisms for disability accrual.Classification of EvidenceThis study provides Class II evidence that in patients with RRMS who attained NEDA-3 status, subsequent RAW was associated with baseline MRI activity and discontinuation of treatment and PIRA was associated with age and the presence of baseline spinal cord lesions.
Published: 2021

31. 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

32. Disease-modifying therapies and SARS-CoV-2 vaccination in multiple sclerosis: an expert consensus

Author: Melinda Magyari, Massimo Filippi, Hans-Peter Hartung, Celia Oreja-Guevara, Diego Centonze, Ludwig Kappos, Claudio Gasperini, Heinz Wiendl, Maria Trojano, Maria A. Rocca, Centonze, Diego, Rocca, Maria A., Gasperini, Claudio, Kappos, Ludwig, Hartung, Hans-Peter, Magyari, Melinda, Oreja-Guevara, Celia, Trojano, Maria, Wiendl, Heinz, and Filippi, Massimo
Subjects: 0301 basic medicine, medicine.medical_specialty, Pediatrics, Neurology, COVID-19 Vaccines, Consensus, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), viruses, COVID-19 pandemic, Disease, medicine.disease_cause, Settore MED/26, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Pandemic, medicine, Humans, Coronavirus, Original Communication, business.industry, SARS-CoV-2, Vaccination, virus diseases, COVID-19, medicine.disease, 030104 developmental biology, Neurology (clinical), Disease-modifying treatments, business, Vaccine, 030217 neurology & neurosurgery
Abstract: Coronavirus disease (COVID-19) appeared in December 2019 in the Chinese city of Wuhan and has quickly become a global pandemic. The disease is caused by the severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), an RNA beta coronavirus phylogenetically similar to SARS coronavirus. To date, more than 132 million cases of COVID19 have been recorded in the world, of which over 2.8 million were fatal (https://coronavirus.jhu.edu/map.html). A huge vaccination campaign has started around the world since the end of 2020. The availability of vaccines has raised some concerns among neurologists regarding the safety and efficacy of vaccination in patients with multiple sclerosis (MS) taking immunomodulatory or immunosuppressive therapies.
Published: 2021

33. Neurological Emergencies in Pregnancy and Puerperium

Author: Alfonso Ciccone, Francesca Romana Pezzella, Claudio Gasperini, Elisa Ciceri, Giorgio Silvestrelli, Alessandra Bucci, and Marco Russo
Subjects: Therapeutic approach, Pregnancy, medicine.medical_specialty, business.industry, medicine, medicine.disease, business, Intensive care medicine
Abstract: Neurological diseases during pregnancy are rare but when they occur they are a real challenge both from a diagnostic and a therapeutic point of view. Pregnant women and children are regularly excluded from the trials so the diagnostic and therapeutic approach is guided both by pathophysiological considerations and by observations related to the available documentation on exposure during pregnancy.
Published: 2020
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34. Mapping the Progressive Treatment-Related Reduction of Active MRI Lesions in Multiple Sclerosis

Author: Marco Battaglini, Andrea Visconti, Andrea Paolillo, Giordano Gentile, Nicola De Stefano, Antonio Giorgio, Maria Laura Stromillo, and Claudio Gasperini
Subjects: brain, Placebo, multiple sclerosis, Placebo group, lcsh:RC346-429, 030218 nuclear medicine & medical imaging, Lesion, White matter, 03 medical and health sciences, 0302 clinical medicine, medicine, Patient group, lcsh:Neurology. Diseases of the nervous system, lesion probability map, business.industry, Multiple sclerosis, Brief Research Report, medicine.disease, Clinical trial, medicine.anatomical_structure, Neurology, MRI, white matter, Corticospinal tract, Neurology (clinical), medicine.symptom, Nuclear medicine, business, 030217 neurology & neurosurgery
Abstract: Objective: To assess treatment-related spatio-temporal dynamics of active MRI lesions in relapsing-remitting multiple sclerosis (RRMS) patients.Methods: We performed a post-hoc analysis of MRI data acquired at weeks 4, 8, 12, and 16, in RRMS patients from the multicenter randomized IMPROVE study, which compares patients treated with 44 mcg subcutaneous interferon β-1a three times weekly (n = 120) versus placebo (n = 60). We created lesion probability maps (LPMs) of the cumulative combined unique active (CUA) lesions in each patient group at each time point. Group differences were tested in terms of lesion spatial distribution and frequency of occurrence.Results: Spatial distribution of CUA lesions throughout the study was less widespread in the treated than placebo group, with a 50% lower lesion accrual (24 vs. 48 cm3/month). Similar results were obtained with the WM tract analysis, with a reduction ranging from −47 to −66% in the treated group (p < 0.001). On voxel-wise analysis, CUA lesion frequency was lower in the treated group than the placebo group at week 4 (p = 0.07, corrected), becoming particularly pronounced (p ≤ 0.03, corrected) from week 8 onwards in large clusters of WM tracts, with peaks along fronto-parietal parts of the corticospinal tract, thalamic radiation, and superior longitudinal fascicle.Conclusion: LPM showed, in the short term, a treatment-related reduction of MRI lesion activity in RRMS patients in specific, clinically relevant brain locations. Such a quantitative approach might be a promising additional endpoint in future MS studies alongside the number and volume of WM lesions.Clinical Trial Registration:ClinicalTrials.gov identifier NCT00441103.
Published: 2020
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35. EBV-specific CD8 T lymphocytes and B cells during glatiramer acetate therapy in patients with MS

Author: Luca Battistini, Gisella Guerrera, Giovanna Borsellino, Daniela F. Angelini, Roberta Placido, Serena Ruggieri, Eleonora Piras, Mario Picozza, Maria Chiara Buscarinu, Francesca Gargano, Claudio Gasperini, and Marco Salvetti
Subjects: Senescence, Adult, Male, Herpesvirus 4, Human, EBV specific CD8 T cells, CD8-Positive T-Lymphocytes, multiple sclerosis, Virus, Article, Multiple Sclerosis disease, Flow cytometry, Young Adult, Immune system, Multiple Sclerosis, Relapsing-Remitting, hemic and lymphatic diseases, medicine, Cytotoxic T cell, ebv, glatiramer acetate, Humans, Immunologic Factors, Longitudinal Studies, Glatiramer acetate, Aged, B-Lymphocytes, B cells, medicine.diagnostic_test, business.industry, Multiple sclerosis, Glatiramer Acetate, Middle Aged, medicine.disease, Cross-Sectional Studies, Neurology, Immunology, Female, Neurology (clinical), business, CD8, medicine.drug
Abstract: ObjectiveInfection with Epstein-Barr virus (EBV) has been associated with clinical activity and risk of developing MS. The purpose of this study is to investigate the impact of glatiramer acetate (GA) therapy on EBV-specific immune responses and disease course.MethodsWe characterized EBV-specific CD8 T lymphocytes and B cells during disease-modifying treatments in 2 groups of patients with MS. We designed a 2-pronged approach consisting of a cross-sectional study (39 untreated patients, 38 patients who had undergone 12 months of GA treatment, and 48 healthy donors compatible for age and sex with the patients with MS) and a 12-month longitudinal study (35 patients treated with GA). CD8 EBV-specific T cells and B lymphocytes were studied using pentamers and multiparametric flow cytometry.ResultsWe find that treatment with GA enhances viral recognition by inducing an increased number of circulating virus-specific CD8 T cells (p = 0.0043) and by relieving their features of exhaustion (p = 0.0053) and senescence (p < 0.0001, p = 0.0001). B cells, phenotypically and numerically tracked along the 1-year follow-up study, show a steady decrease in memory B-cell frequencies (p = 0.025), paralleled by an increase of the naive B subset.ConclusionGA therapy acts as a disease-modifying therapy restoring homeostasis in the immune system, including anti-EBV responses.
Published: 2020
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36. Age-related adverse events of disease-modifying treatments for multiple sclerosis: A meta-regression

Author: Carla Tortorella, Claudio Gasperini, Luca Prosperini, Shalom Haggiag, and Simonetta Galgani
Subjects: medicine.medical_specialty, Multiple Sclerosis, Disease, law.invention, Immunomodulation, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Age related, Internal medicine, medicine, Humans, Immunologic Factors, Meta-regression, In patient, Adverse effect, 030304 developmental biology, 0303 health sciences, business.industry, Multiple sclerosis, Middle Aged, medicine.disease, Neurology, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Objective: To verify the hypothesis of an age-dependent increase of infections and neoplasms in patients with multiple sclerosis (MS) under disease-modifying treatments (DMTs) with different mechanisms of action. Methods: We extracted relevant data from 45 randomized clinical trials (RCTs) on currently licensed DMTs. We fitted inverse-variance weighted meta-regressions with random-effects models to estimate whether age and/or mechanism of action (immunomodulatory, sequestrating, and depletive) of currently licensed DMTs influenced the difference between experimental arm and control arm in the incidence of specific adverse events, namely, overall infections, opportunistic infections, and neoplasms. Results: A higher incidence of overall infections was observed in RCTs with depletive DMTs (event-rate ratio = 1.25, p Discussion: Our study supports a detrimental effect of age on the safety profile of depletive DMTs, with an increased incidence of neoplasms especially over 45 years of age. We failed to demonstrate an age-related increased incidence of infections, possibly due to latency in their occurrence.
Published: 2020

37. Benefits of eculizumab in AQP4+ neuromyelitis optica spectrum disorder: Subgroup analyses of the randomized controlled phase 3 PREVENT trial

Author: Jacqueline Palace, Dean M. Wingerchuk, Kazuo Fujihara, Achim Berthele, Celia Oreja-Guevara, Ho Jin Kim, Ichiro Nakashima, Michael Levy, Murat Terzi, Natalia Totolyan, Shanthi Viswanathan, Kai-Chen Wang, Amy Pace, Marcus Yountz, Larisa Miller, Róisín Armstrong, Sean Pittock, Daniel Julio Muñoz, Jorge David Amor, Carolina Bocchiardo, Julieta Iourno Danielle, Alfredo Laffue, Carolina Daniela Diaz Obregon, Maria Fernanda Paez, Roberto Martin Perez, Viviana Ana Maria Rocchi, Loreley Deborah Teijeiro, Jesica Gómez, Andres Maria Villa, Florencia Aguirre, Victoria Carla Fernández, Ramon F. Goicoechea, Luciana Melamud, Ana Stillman, Mariana de Virgiliis, Fatima Pagani Cassara, Marta Cordoba, Maria Teresa Gutierrez, Mariana Ingolotti, Natalia Larripa, Anahi Lupinacci, Josefina Arroyo, Alejandra Romano, Mariana Foa Torres, Carlos Héctor Ballario, Ana Elisa Chiesa, Hernán Gustavo Gómez, Hernán Gabriel Lattini, Carolina Natalia Mainella, Gisel Edith Bolner, María Soledad Eschoyez, Simon Andrew Broadley, Saman Heshmat, Arman Sabet, Andrew Swayne, Susan Freeman, Sofia Jimenez Sanchez, Neil Shuey, Linda Dalic, Ann French, Guru Kuma, Joshua Laing, Lai Yin Law, Jennifer MacIntyre, Andrew Neal, Christopher Plummer, Prashanth Ramachandran, Leslie Sedal, Ian Wilson, Antony Winkel, Wenwen Zhang, Tina Chen, Rani Watts, Michael Barnett, Joshua Barton, Heidi Beadnall, Justin Garber, Todd Andrew Hardy, Benjamin Trewin, Marinda Taha, Deleni Walters, Federico Arturo Silva Sieger, Nhora Patricia Ruiz Alfonso, Anna Maria Pinzon Camacho, Alexander Pabón Moreno, Jorge Armando Castellanos Prad, Adriana Paola Duarte Rueda, Tatiana Castillo, Karol Melissa Castillo Gonzalez, Martha Yolanda Moreno Pico, Judith Castill, Mario Habek, Ivan Adamec, Barbara Barun, Luka Crnosija, Tereza Gabelic, Petra Nytrova, Eva Krasulova, Jana Pavlickova, Michaela Tyblova, Jana Zubkova, Thor Petersen, Gro Helen Dale, Peter Vestergaard Rasmussen, Morten Stilund, Kristina Bacher Svendsen, Vivi Brandt, Nicolas Collongues, Marie-Celine Fleury, Laurent Kremer, Sandrine Bendele, Valérie Neff, Ricarda Diem, Michael Platten, Anne Berberich, Jonabelle Jansen, Hannah Jaschoneck, Brigitte Wildemann, Ursula Aures, Tanja Brandenburger, Tanja Haut, Maria-Lourdes Treceno Fernández, Lilian Aly, Kirsten Brinkhoff, Dorothea Buck, Daniel Golkowski, Mirjam Hermisson, Muna-Miriam Hoshi, Miriam Kaminski, Markus Christian Kowarik, Helena Kronsbein, Klaus Lehmann-Horn, Viola Maria Pongratz, Andreas Schweiker, Lisa-Ann Leddy, Silvia Mueller, Kim Obergfell, Marion Wanka, Uwe Klaus Zettl, Jan Klinke, Micha Loebermann, Stefanie Meister, Florian Rimmele, Alexander Winkelmann, Ina Schroeder, Alexander Yuk-Lun Lau, Lisa Wing-Chi Au, Florence Sin-Ying Fan, Vincent Hing-Lung Ip, Karen Ka-Yan Ma, Sze-Ho Ma, Vincent Chung-Tong Mok, Cheryl Chung-Kwan Au, Pauline Wing-Lam Kwan, Francesco Patti, Andrea Salvatore Caramma, Clara Grazia Chisari, Salvatore Lo Fermo, Silvia Messina, Maria Projetto, Cinzia Caserta, Alessandro Filla, Teresa Costabile, Chiara Pane, Francesco Sacca, Angela Marsili, Giorgia Puorro, Roberto Bergamaschi, Eliana Berra, Giulia Mallucci, Cinzia Fattore, Claudio Gasperini, Simonetta Galgani, Shalom Haggiag, Serena Ruggieri, Claudio Vento, Esmeralda Maria Quartuccio, Carlo Pozzilli, Valeria Teresa Barletta, Giovanna Borriello, Laura De Giglio, Fabiana Marinelli, Miriam Tasillo, Alessandra Amadori, Mariano Fischetti, Flavia Gurreri, Masahiro Mori, Hiroki Masuda, Ryohei Ohtani, Yukari Sekiguchi, Tomohiko Uchida, Akiyuki Uzawa, Hiromi Ito, Emi Kabasawa, Yoko Kaneko, Takuya Matsushita, Dai Matsuse, Hiroyuki Murai, Shintaro Hayashi, Katsuhisa Masak, Hidenori Ogata, Koji Shinoda, Taira Uehara, Mitsuru Watanabe, Hiroo Yamaguchi, Ryo Yamasaki, Tomomi Yonekawa, Maki Jingu, Makiko Nagano, Yumiko Nakamura, Yoshiko Sano, Manabu Araki, Youwei Lin, Madoka Mori, Yohei Mukai, Terunori Sano, Wakiro Sato, Naoya Gogun, Yuriko Maeda, Asami Nishimoto, Sachiko Tsukamoto, Ritsuko Yanagi, Takahiko Saida, Shinichi Nakamura, Tetsuya Nasu, Kyoko Saida, Yuko Shikata, Yoshimi Kodani, Megumi Saeki, Yukako Sawada, Hiroo Yoshikawa, Takashi Kimura, Masamitsu Nishi, Shun Sakamoto, Shinichiro Ukon, Shohei Watanabe, Saori Ebisuya, Nami Kimura, Manami Matsuura, Yukie Morisaki, Yoshiko Muroi, Kuniko Onishi, Ikuko Oshima, Yuki Washino, Tomomi Yamashita, Tatsuro Misu, Kimihiko Kaneko, Masaaki Kato, Hiroshi Kuroda, Kazuhiro Kurosawa, Shuhei Nishiyama, Hirohiko Ono, Yoshiki Takai, Keiko Abe, Hitomi Hoshi, Mari Jinushi, Azusa Oyama, Motonari Sakuma, Yuko Sawada, Satoru Ishibashi, Takanori Yokota, Yoichiro Nishida, Kokoro Ozaki, Nobuo Sanjo, Nozomu Sato, Fuki Denno, Haruko Hiraki, Yumi Matsubara, Takashi Kanda, Masaaki Abe, Masaya Honda, Motoharu Kawai, Michiaki Koga, Toshihiko Maeda, Junichi Ogasawara, Masatoshi Omoto, Yasuteru Sano, Ryota Sato, Fumitaka Shimizu, Hideki Arima, Sachie Fukui, Yoshiko Ishikawa, Tomoko Koyama, Shigemi Shimose, Hirokazu Shinozaki, Masanori Watanabe, Sachi Yasuda, Chieko Yoshiwaka, Suffian Adenan, Mohd Azman M Aris, Ahmad Shahir bin Mawardi, Muhammad Al Hafiz Adnan, Nanthini Munusamy, Siti Nur Omaira Razali, Punitha Somasundram, Jae Won Hyun, In Hye Jeong, Su-Hyun Kim, Hyun-June Shin, Ji Sung Yoo, HyunMin Jang, AeRan Joung, Byung-Jo Kim, Seol-Hee Baek, Jung Bin Kim, Yoo Hwan Kim, Yong Seo Koo, Chan Nyoung Lee, Hung Youl Seok, Jinhee Hwang, Sung Min Kim, So Hyun Ahn, Kyomin Choi, Seok-Jin Choi, Jun-Soon Kim, Young Nam Kwon, Je-Young Shin, Hyeonju Kwon, Byoung Joon Kim, Eun Bin Cho, Hye-Jin Cho, Misong Choi, DongSun Kim, Ju Hyeon Kim, SeungJu Ki, Hye Lim Lee, Kwang-Ho Lee, Ju-Hong Min, Ji-Hyung Park, Jinmyoung Seok, Eunhwa Choi, Sang Ae Park, Seung Min Kim, Ha-Neul Jeong, Bong Jeongbin, Jin Woo Jung, Seung Woo Kim, Yool-hee Kim, Hyung Seok Lee, Ha Young Shin, Yeon Jung, Min Jung Kim, Nou Ri Lee, MiJu Shin, Farit A Khabirov, Lyudmila Averyanova, Natalya Babicheva, Eugenii Granatov, Sergey Kazarov, Timur Khaybullin, Alexander Rogozhin, Dmitry V Pokhabov, Vladislav Abramov, Anastasia Amelina, Yulia Nesteroca, Tatyana Bozhenkina, Aleksey N Boyko, Elena G Demyan, Inessa Khoroshilova, Mikhail Melnikov, Ekaterina V Popova, Svetlana N Sharanova, Sergey G Shchur, Denis V Sazonov, Larisa Babenko, Elena Bayandina, Asya Yarmoschuk, Victor A Baliazin, Elena Baliazina, Elena Budaeva, Irina Chernikova, Zoya Goncharova, Vladimir Krasnov, Marina Myatleva, Olga V. Rodionova, Iuliana Samulyzhko, Alla A. Timofeeva, Sabas Boyero Duran, Maria Mar Mendibe Bilbao, Irene Diaz Cuervo, Jose Maria Losada Domingo, Amaia Gonzalez Eizaguirre, Jose Eulalio Barcena Llona, Roberto Valverde Moyano, Carmen Bahamonde, Fernando Sanchez Lopez, Raquel Pinar Morales, Eduardo Agüera Morales, Carmen Bahamonde Roman, Juan Jose Ochoa Sepulveda, Maria del Carmen Blanco Valero, Nazaret Pelaez Viña, Cristina Conde Gavilan, Ana Maria Jover Sanchez, Sara Vila Bedmar, Nuria Gonzalez Garcia, Aida Orviz Garcia, Ines Gonzalez-Suarez, Elena Miñano Guillamon, Miguel Kawiorski, Elena Guerra Schulz, Alba Garcia Alonso, Francisco Jesus Lopez Perez, Marta Palacios Sarmiento, Guillermo Izquierdo Ayuso, Guillermo Navarro Mascarell, Cristina Paramo Camino, Asuncion Varas Garcia, Yaiza Montserrat Mendoza, Veronica Ines Vargas Muñoz, Patricia Torres Tonda, Ching-Piao Tsai, Jiu-Haw Yin, Mei-Jung Chen, Shan-Ni Li, Fei-Ti Wang, Suwat Srisuwannanukorn, Thanatat Boonmongkol, Duangporn Borisutbuathip, Duangkamol Singwicha, Krittika Siritanan, Chidchanoke Thearapati, Kwanmuang Sornda, Metha Apiwattanakul, Saharat Aungsumart, Narupat Suanprasert, Kaona Suksuchano, Nittaya Parkinsee, Kongkiat Kulkantrakorn, Praween Lolekha, Artit Potigumjon, Puchit Sukphulloprat, Dararat Suksasunee, Chankawee Komaratat, Sunattana Luangtong, Arkhom Arayawichanont, Phanpaphon Konpan, Nathapol Riablershirun, Thaddao Wiroteurairuang, Panadda Jantaweesirirat, Aslı Kurne, Irem Erkent, Ebru Bekircan Kurt, Ezgi Saylam, Yagmur Caliskan, Gulsah Orsel, Yahya Celik, Canan Celebi, Aslan Tekatas, Tugce Banbal, Gulsen Akman Demir, Burcu Altunrende, Zeliha Matur, Baris Topcular, Tules Elmas, Aysenur Gulo, Selin Ozdemir, Cansu Ozkoklesen, Mahinur Ozturk, Mertkan Yanik, Elif Yildirim, Melih Tutuncu, Ayse Altintas, Abdulsamet Cam, Ayse Deniz Elmali, Sabahattin Saip, Aksel Siva, Uygur Tanrıverdi, Ugur Uygunoglu, Sinem Caliskan, Pinar Gulo, Esra Kozig, Sakine Sakiz, Ihsan Sukru Sengun, Egemen Idiman, Rahmi Tumay Ala, Duygu Arslan, Utku Bulut, Yasemin Karakaptan, Derya Kaya, Zaur Mehdiyev, Bengu Balkan, Berfu Kuku, Mujgan Ozhun, Celal Tuga, Muzeyyen Ugur, Husnu Efendi, Sena Destan Bunul, Hakan Cavus, Yunus Emre Gorke, Ayse Kutlu, Seda Ozturk, Cansu Egilmez Sarikaya, Gulsah Becerikli, Cansu Semiz, Ozlem Tun, Sehriban Ayer, Musa Kazim Onar, Mehlika Berra Ozberk, Sedat Sen, Tugce Kirbas Cavdar, Adife Veske, Cavit Boz, Didem Altiparmak, Cigdem Ozen Aydin, Sibel Gazioglu, Duygu Bekircan, Anu Jacob, Heike Arndt, Liene Elsone, Shahd Hassan Mahmoud Hamid, Daniel Hugh Whittam, Martin Wilson, Imelda O'Brien, Maria Isabel da Silva Leite, Pedro Maria Rodriguez Cruz, Damian Robert Jenkins, George Tackley, Ana Cavey, Rosie Everett, Joy Hodder, Abigail Koelewyn, Ellen Mowry, Walter Royal, Robert Shin, Christopher Bever, Daniel Harrison, Horea Rus, Wei Zheng, Karen Callison, Kerry Naunton, Benjamin M Frishberg, Andrew M Blumenfeld, Andrew Inocelda, Kalyani Korabathina, Michael Lobatz, Melissa M Mortin, Irene J Oh, Jay H Rosenberg, Mark Sadoff, Gregory A Sahagian, Anchi Wang, Yasmin Camberos, Guadalupe Sanchez, Estela Soto, Jacqueline A Nicholas, Aaron Boster, Geoffrey Eubank, Katy Groezinger, Meghan Lauf, Annette F Okai, Rashedul Hasan, Chaouki Khoury, Victoria Stokes, Stacey Clardy, Melissa Cortez, John Greenlee, John Rose, Mateo Paz Soldan, Amanda Emett, Lawanda Esquibel, Lilly Fagatele, Ka-Ho Wong, James C Stevens, Thomas M Banas, Marlene C Bultemeyer, Andrea Haller, Natalie Manalo, Keri Aeschliman, Debi Kocks, Michael Racke, Aaron Lee Boster, Michelle Bowman, Jaime Imitola, Yasushi Kisanuki, Misty Green, Stephanie Scarberry, Sharon G Lynch, Heather S Anderson, Gary S Gronseth, Nancy E Hammond, Yasir N Jassam, Manoj K Mittal, Muhammed M Nashatizadeh, Nicholas Levine, Lisa Schmidt, Jill Sibley, Vonda Whitley, James Winkley, Timothy Coleman, Gregory Cooper, Stephanie Sheffield, Keri Turner, Dana Galloway, Robert S Tillett, Geeta A Ganesh, Brian M Plato, Tad D Seifert, Diana Godwin, Deborah Lockridge, Kottil W Rammohan, William A Sheremata, Silvia Delgado, Jose Gonzalez, Alexis Lizarraga, Janice Maldonado, Melissa Ortega, Leticia Tornes, Yanet Babcock, Osmara Cailam, Yesica Campos, Irlisse Couvertier, Bettina Daneri, Jeremy Deni, Jeffrey Hernandez, Tatiana Jaramillo, Tenita Morris, Daniel Nobel, Anjelis Oliveira, Reshma Richardson, Gloria Rodriguez, Ana Romero, Carlos Sandova, Ruta Sawant, Lissett Tueros, Eric S Zetka, Chao Zheng, Daniel H Jacobs, Constance Easterling, Jennifer Fairbank, Revathi Iyengar, Mark Klafter, Justin Lindquist, Ahmed H Sadek, Elizabeth Carmona Toro, Navin Verma, Brigith Patino Castro, Nadia Sukhraj-Singh, Joseph Berger, Eric Williamson, Salim Chahin, Dina Jacobs, Clyde Markowitz, Jessica Dobbins, Lauren Mace, Maria Martin, Ashley Pinckney, Amber Roberts, Islam Zaydan, Galen W Mitchell, Rock A Heyman, Ryan L Orie, Valerie R Suski, Kerry Oddis, Darlene Punjack, Eoin Flanagan, Avi Gadoth, Andrew McKeon, W Oliver Tobin, Anastasia Zekeridou, Katie Dunlay, Jessica Sagen, Jonathan L Carter, Bachir Estephan, Brent P Goodman, Charlene R Hoffman Snyder, Andrea Francone, Irene Galasky, Martha Thomas, Pavle Repovic, James Bowen, Angeli Mayadev, Peiqing Qian, Yuriko Courtney, Lauren Lennox, Robert Thomas Naismith, Anne Haney Cross, Emily Evans, Erin E Longbrake, Megan E Orchard, Gregory F Wu, Linda Heinrich, Susan Sommers, Faria Amjad, Erika Mitchell, Carlos Mora, Bethany Schreiber, Carlo Tornatore, Alexis Carlson, Sacha McCarthy, and Alexandria Oliver
Subjects: Adult, medicine.medical_specialty, Population, Placebo, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Complement inhibitor, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, education, Aquaporin 4, education.field_of_study, Neuromyelitis optica, business.industry, Neuromyelitis Optica, General Medicine, Eculizumab, medicine.disease, Comorbidity, ddc, Neurology, Concomitant, Rituximab, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background Antibodies to the aquaporin-4 (AQP4) water channel in neuromyelitis optica spectrum disorder (NMOSD) are reported to trigger the complement cascade, which is implicated in astrocyte damage and subsequent neuronal injury. The PREVENT study demonstrated that the terminal complement inhibitor eculizumab reduces adjudicated relapse risk in patients with anti-AQP4 immunoglobulin G-positive (AQP4+) NMOSD. The objective of this analysis was to evaluate the efficacy of eculizumab in reducing relapse risk and its safety in AQP4+ NMOSD across clinically relevant subgroups in PREVENT. Methods In the randomized, double-blind, time-to-event, phase 3 PREVENT trial, 143 adults received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (2:1), with stable-dose concomitant immunosuppressive therapy (IST) permitted (except rituximab and mitoxantrone). Post hoc analyses of relapses and adverse events were performed for prespecified and post hoc subgroups based on concomitant IST and prior rituximab use, demographic and disease characteristics, and autoimmune comorbidity. Results The significant reduction in relapse risk observed for eculizumab versus placebo in the overall PREVENT population was consistently maintained across subgroups based on concomitant IST and previous rituximab use, age, sex, region, race, time since clinical onset of NMOSD, historical annualized relapse rate, baseline Expanded Disability Status Scale score, and history of another autoimmune disorder. The serious infection rate was lower with eculizumab than placebo regardless of rituximab use in the previous year, concomitant IST use, or history of another autoimmune disorder. Conclusion Across a wide range of clinically relevant AQP4+ NMOSD patient subgroups in PREVENT, eculizumab therapy was consistently effective versus placebo in reducing relapse risk, with no apparent increase in serious infection rate. Trial registration NCT01892345 (ClinicalTrials.gov).
Published: 2020

38. Induction Versus Escalation in Multiple Sclerosis: A 10-Year Real World Study

Author: Claudio Solaro, Serena Ruggieri, Viviana Nociti, Simonetta Galgani, Claudio Gasperini, Cinzia Cordioli, Nicola De Rossi, Massimiliano Mirabella, Carla Tortorella, Shalom Haggiag, Ruggero Capra, Chiara Rosa Mancinelli, Laura De Giglio, Sarah Rasia, and Luca Prosperini
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, escalation, Time Factors, Cyclophosphamide, Population, Multiple sclerosis, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, medicine, Product Surveillance, Postmarketing, Humans, Pharmacology (medical), Adverse effect, education, induction, Retrospective Studies, Pharmacology, Mitoxantrone, education.field_of_study, Expanded Disability Status Scale, Dose-Response Relationship, Drug, business.industry, Proportional hazards model, Remission Induction, medicine.disease, Settore MED/26 - NEUROLOGIA, 030104 developmental biology, therapeutic algorithm, Propensity score matching, Commentary, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Immunosuppressive Agents, medicine.drug, Follow-Up Studies
Abstract: In this independent, multicenter, post-marketing study, we directly compare induction immunosuppression versus escalation strategies on the risk of reaching the disability milestone of Expanded Disability Status Scale (EDSS) ≥ 6.0 over 10 years in previously untreated patients with relapsing-remitting multiple sclerosis. We collected data of patients who started interferon beta (escalation) versus mitoxantrone or cyclophosphamide (induction) as initial treatment. Main eligibility criteria included an EDSS score ≤ 4.0 at treatment start and either ≥ 2 relapses or 1 disabling relapse with evidence of ≥ 1 gadolinium-enhancing lesion at magnetic resonance imaging scan in the pre-treatment year. Since patients were not randomized to treatment group, we performed a propensity score (PS)–based matching procedure to select individuals with homogeneous baseline characteristics. Comparisons were then conducted using Cox models stratified by matched pairs. Overall, 75 and 738 patients started with induction and escalation, respectively. Patients in the induction group were older and more disabled than those in the escalation group (p
Published: 2020

39. MAGNIMS consensus recommendations on the use of brain and spinal cord atrophy measures in clinical practice

Author: Mar Tintoré, Olga Ciccarelli, Jaume Sastre-Garriga, Claudio Gasperini, Maria Pia Sormani, Jens Wuerfel, Tarek A. Yousry, Marco Battaglini, Massimo Filippi, Hugo Vrenken, Xavier Montalban, Alex Rovira, Deborah Pareto, Frederik Barkhof, Jackie Palace, Christian Enzinger, Nicola De Stefano, Ludwig Kappos, Jette L. Frederiksen, Jordi Río, Maria A. Rocca, Sastre-Garriga, J., Pareto, D., Battaglini, M., Rocca, M. A., Ciccarelli, O., Enzinger, C., Wuerfel, J., Sormani, M. P., Barkhof, F., Yousry, T. A., De Stefano, N., Tintore, M., Filippi, M., Gasperini, C., Kappos, L., Rio, J., Frederiksen, J., Palace, J., Vrenken, H., Montalban, X., and Rovira, A.
Subjects: medicine.medical_specialty, Multiple Sclerosis, Consensus, Prognosi, Consensu, Brain imaging, Disease, Severity of Illness Index, 030218 nuclear medicine & medical imaging, Multiple sclerosis, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Natalizumab, Atrophy, Physical medicine and rehabilitation, Neuroimaging, Multiple Sclerosi, medicine, Humans, Brain, Magnetic Resonance Imaging, Practice Guidelines as Topic, Prognosis, Randomized Controlled Trials as Topic, Spinal Cord, Expanded Disability Status Scale, medicine.diagnostic_test, business.industry, Consensus Statement, Magnetic resonance imaging, medicine.disease, Clinical trial, Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers, medicine.drug, Human
Abstract: Early evaluation of treatment response and prediction of disease evolution are key issues in the management of people with multiple sclerosis (MS). In the past 20 years, MRI has become the most useful paraclinical tool in both situations and is used clinically to assess the inflammatory component of the disease, particularly the presence and evolution of focal lesions — the pathological hallmark of MS. However, diffuse neurodegenerative processes that are at least partly independent of inflammatory mechanisms can develop early in people with MS and are closely related to disability. The effects of these neurodegenerative processes at a macroscopic level can be quantified by estimation of brain and spinal cord atrophy with MRI. MRI measurements of atrophy in MS have also been proposed as a complementary approach to lesion assessment to facilitate the prediction of clinical outcomes and to assess treatment responses. In this Consensus statement, the Magnetic Resonance Imaging in MS (MAGNIMS) study group critically review the application of brain and spinal cord atrophy in clinical practice in the management of MS, considering the role of atrophy measures in prognosis and treatment monitoring and the barriers to clinical use of these measures. On the basis of this review, the group makes consensus statements and recommendations for future research., In this Consensus statement, the Magnetic Resonance Imaging in MS (MAGNIMS) study group reviews the application of brain and spinal cord atrophy in clinical practice in the management of MS and makes consensus statements and recommendations for future research.
Published: 2020
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40. Induction treatment strategy in multiple sclerosis: a review of past experiences and future perspectives

Author: Simona Pontecorvo, Serena Ruggieri, Carla Tortorella, and Claudio Gasperini
Subjects: medicine.medical_specialty, Neurology, medicine.medical_treatment, Immunology, Disease, lcsh:RC346-429, 03 medical and health sciences, 0302 clinical medicine, medicine, Immunology and Allergy, 030212 general & internal medicine, Intensive care medicine, Cladribine, lcsh:Neurology. Diseases of the nervous system, business.industry, Multiple sclerosis, Immunosuppression, Stem-cell therapy, medicine.disease, Clinical trial, Induction strategy, Alemtuzumab, Neurology (clinical), Highly active multiple sclerosis, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: The scenario of multiple sclerosis (MS) treatment has changed profoundly in recent decades. In this setting, one of two strategies is usually used: escalation or induction. The first involves a pyramid of possible treatments of increasing efficacy (but also increasing safety risks) that are introduced progressively as needed. The induction strategy, on the other hand, immediately pursues higher efficacy, since drugs with a higher risk profile are used from the outset. Understanding which of these treatment strategies is the more suitable for a given patient is the first step in the therapeutic decision-making process. Prognostic factors evaluated on the basis of the clinical presentation and any disease activity on magnetic resonance imaging (MRI) should guide and help clinicians in making their choices. Even though the pathogenesis of MS is not yet completely understood, specific pathological changes are known to occur in the adaptive and innate immune system over the course of the disease. To date, treatment has been based mainly on two drugs, mitoxantrone and cyclophosphamide, autologous haematopoietic stem cell therapy (within clinical trial setting), but new compounds are now emerging. Among the new treatments, alemtuzumab and cladribine appear to be valid candidates as induction drugs. In this review we provide an overview of induction strategies based on literature evidence and our own past experiences, providing descriptions of clinical cases. We also outline the future perspectives in this field.
Published: 2018
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41. Abortion induces reactivation of inflammation in relapsing-remitting multiple sclerosis

Author: Laura Boffa, Fabrizia Monteleone, Simona Pontecorvo, Girolama Alessandra Marfia, Elisabetta Ferraro, Paolo Ragonese, Doriana Landi, Diego Centonze, Claudio Gasperini, Giancarlo Di Battista, Luca Prosperini, Massimiliano Mirabella, Viviana Nociti, Giuseppe Salemi, Carlo Pozzilli, Enrico Millefiorini, Giorgia Mataluni, Shalom Haggiag, Roberta Fantozzi, Maria Chiara Buscarinu, Marco Salvetti, Ada Francia, Antonio Cortese, Landi, Doriana, Ragonese, Paolo, Prosperini, Luca, Nociti, Viviana, Haggiag, Shalom, Cortese, Antonio, Fantozzi, Roberta, Pontecorvo, Simona, Ferraro, Elisabetta, Buscarinu, Maria Chiara, Mataluni, Giorgia, Monteleone, Fabrizia, Salvetti, Marco, Di Battista, Giancarlo, Francia, Ada, Millefiorini, Enrico, Gasperini, Claudio, Mirabella, Massimiliano, Salemi, Giuseppe, Boffa, Laura, Pozzilli, Carlo, Centonze, Diego, and Marfia, Girolama Alessandra
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Gadolinium, Neuroimaging, Disease, Relapsing-Remitting, Abortion, Settore MED/26, annualised relapse rate, Young Adult, 03 medical and health sciences, symbols.namesake, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Recurrence, medicine, Humans, Poisson regression, Retrospective Studies, Inflammation, Pregnancy, 030219 obstetrics & reproductive medicine, business.industry, Obstetrics, Multiple sclerosis, Induced, Abortion, Induced, Retrospective cohort study, medicine.disease, Magnetic Resonance Imaging, gadolinium enhancing lesion, Discontinuation, Psychiatry and Mental health, Pregnancy Maintenance, multiple sclerosi, symbols, Settore MED/26 - Neurologia, Female, Surgery, pregnancy, Neurology (clinical), business, 030217 neurology & neurosurgery, abortion, multiple sclerosis
Abstract: ObjectiveTo investigate clinical and radiological outcomes of women with relapsing-remitting multiple sclerosis (RRMS) undergoing abortion.MethodsAn independent, multicentre retrospective study was conducted collecting data from eight Italian MS centres. We compared the preconception and postabortion annualised relapse rate (ARR) and number of Gadolinium enhancing (Gd+) lesions, by analyses of covariance. Variables associated with postabortion clinical and MRI activity were investigated using Poisson regression models; each abortion was considered as a statistical unit.ResultsFrom 1995 to 2017, we observed 188 abortions (17 elective) in 153 women with RRMS. Abortions occurred after a mean time of 9.5 (4.4) weeks from estimated conception date. In 86 events out of 188, conception happened during treatment with disease modifying drugs. The mean postabortion ARR (0.63±0.74) was significantly increased (p=0.037) compared with the preconception year (0.50±0.71) as well as the postabortion mean number of new Gd+ lesions (0.77±1.40 vs 0.39±1.04; p=0.004). Higher likelihood of relapses was predicted by higher preconception ARR, discontinuation of preconception treatment and elective abortion; the occurrence of new Gd+ lesions was associated with higher preconception number of active lesions, discontinuation of preconception treatment, shorter length of pregnancy maintenance and elective abortion.ConclusionsAbortion was associated with clinical and radiological inflammatory rebound remarkably in the first 12 months postevent. Deregulated proinflammatory processes arising at the early stages of pregnancy might play a role both in MS reactivation and abortion. Women with MS should be counselled about these risks of abortion and followed up accordingly.
Published: 2018
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42. Increased risk of death from COVID-19 in multiple sclerosis: A meta-analysis of observational studies

Author: Shalom Haggiag, Carla Tortorella, Simonetta Galgani, Claudio Gasperini, Serena Ruggieri, and Luca Prosperini
Subjects: Oncology, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Multiple sclerosis, medicine.disease, Article, Increased risk, Neurology, Meta-analysis, Internal medicine, medicine, Observational study, Neurology (clinical), business
Published: 2021
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43. Comparative effectiveness of early intensive or escalation treatment strategies on long term disability trajectories in relapsing multiple sclerosis patients

Author: Roberto Bergamaschi, Damiano Paolicelli, Davide Mainome, F Caputo, Valentina Torri Clerici, Pietro Iaffaldano, Rocco Totaro, Mauro Zaffaroni, Paolo Bellantonio, Claudio Gasperini, Giancarlo Comi, Giuseppe Lucisano, Eleonora Cocco, Patrizia Sola, Giacomo Lus, Massimo Filippi, Marco Salvetti, Maria Trojano, Franco Granella, Marco Capobianco, Antonella Conte, Vincenzo Brescia Morra, Marco Rovaris, Francesco Patti, Giovanna De Luca, Maria Pia Amato, Carlo Pozzilli, Giorgia Teresa Maniscalco, Matilde Inglese, and Giuseppe Salemi
Subjects: medicine.medical_specialty, Neurology, business.industry, Multiple sclerosis, medicine, Treatment strategy, Neurology (clinical), Long term disability, Intensive care medicine, business, medicine.disease
Published: 2021
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44. Progressive multifocal leukoencephalopathy after daratumumab in multiple myeloma: A case report

Author: Pierluigi Galizia, Laura Di Clemente, Valeria Cozzolino, Luca Prosperini, Claudio Gasperini, Carla Tortorella, Nicoletta Giuseppa Caracciolo, and Silvia La Cesa
Subjects: Pathology, medicine.medical_specialty, Neurology, business.industry, Progressive multifocal leukoencephalopathy, medicine, Daratumumab, Neurology (clinical), medicine.disease, business, Multiple myeloma
Published: 2021
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45. Anti lingo 1 (opicinumab) a new monoclonal antibody tested in relapsing remitting multiple sclerosis

Author: Carla Tortorella, Claudio Gasperini, and Serena Ruggieri
Subjects: 0301 basic medicine, medicine.drug_class, Central nervous system, Nerve Tissue Proteins, Monoclonal antibody, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Demyelinating disease, medicine, Humans, Immunologic Factors, Pharmacology (medical), Remyelination, business.industry, General Neuroscience, Multiple sclerosis, Neurodegeneration, disability, multiple sclerosis, neurodegeneration, Opicinumab, remyelination, Neuroscience (all), Neurology (clinical), Antibodies, Monoclonal, Membrane Proteins, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Relapsing remitting, Immunology, business, 030217 neurology & neurosurgery
Abstract: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). The modern treatment era for MS witnessed a growing pool of drugs now available for use in clinical practice. These therapies work at different levels, however there is a lack of treatments acting on the neurodegenerative component or improving mechanism of repair. Areas covered: The latest knowledge about the pathophysiological changes occurring in MS have translated into novel treatments at different stages of development. Drugs for MS work mainly through modulating the inflammatory factors of the disease, but enhancing remyelination may be more successful in reducing long-term disability. Anti-LINGO-1 (opicinumab) is the first investigational product that achieved phase I trial with the aim of remyelination and axonal protection and/or repair in MS. Expert commentary: Over the past decade considerable strength has been applied to find more reliable strategies to improve myelin repair. The anti-LINGO-1 trial showed that the drug is safe and tolerable. A future phase II trial will provide more insights regarding the compound. The greatest challenge for myelin repair therapies will be how to monitor their efficacy. Eventually research will need to focus on consistent tools to assess the grade of remyelination in vivo.
Published: 2017
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46. Discrepancies between urinary symptoms assessment and objective bladder dysfunctions in multiple sclerosis

Author: Giovanni Bolla, Orietta Picconi, Shalom Haggiag, Simonetta Galgani, and Claudio Gasperini
Subjects: medicine.medical_specialty, Neurology, Urinary system, Immunology, Population, Urology, Urinary symptoms, lcsh:RC346-429, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, medicine, Immunology and Allergy, 030212 general & internal medicine, Prospective cohort study, education, Neurogenic bladder dysfunction, lcsh:Neurology. Diseases of the nervous system, education.field_of_study, business.industry, medicine.disease, medicine.anatomical_structure, Physical therapy, Sphincter, Neurology (clinical), business, Bladder dysfunction, 030217 neurology & neurosurgery
Abstract: Objective To assess the association between objective bladder function parameters in relation to urinary symptoms, and to analyze the sensitivity and specificity of subjective urinary symptom-assessment in predicting objective bladder dysfunction in a multiple sclerosis (MS) population. Methods Consecutive MS patients with Expanded Disability Status Score (EDSS) ≤7.0 were included in this prospective study. In a single visit, patients were evaluated for the presence of urinary symptoms, then assessed for the following urological parameters: maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), and detrusor sphincter dyssinergia (DSD). Results One hundred nine subjects were included with a mean disease duration of 12.5 ± 8.7 years, 90.8% had a relapsing-remitting course; the mean EDSS score was 2.6 ± 1.7. Overall, 53.5% complained of at least one urinary symptom, and the most reported one was urgency (40.7%), followed by frequency (15.7%) and incomplete emptying (12.0%). Abnormal values were found for Qmax in 34.9%, for PVR in 40.4% of participants; DSD was diagnosed in 33.9% of the cases. Only Qmax was found negatively associated with the EDSS score (p = 0.007), but no other association was observed. The presence of urinary symptoms was poor predictor of bladder dysfunction, urgency among the others showed relatively higher predicting value. Conclusions Subjective urinary symptoms assessment failed in predicting bladder function. Our results confirmed the value of objective urological assessment in patients with MS, irrespective of the presence of urinary symptoms.
Published: 2017
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47. 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, CopemylÂ®, 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

48. Unilateral meningitis: unusual central nervous system involvement in rheumatoid arthritis

Author: Claudio Gasperini, Carla Tortorella, Giandomenico Sebastiani, and Luca Prosperini
Subjects: medicine.medical_specialty, Pathology, business.industry, Central nervous system, General Medicine, Fluid-attenuated inversion recovery, medicine.disease, Certolizumab, Hyperintensity, Rheumatology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Rheumatoid arthritis, Internal medicine, medicine, Effective diffusion coefficient, Neurology (clinical), business, Meningitis, 030217 neurology & neurosurgery
Abstract: A 40-year-old woman developed acute onset of right-sided weakness with ipsilateral partial motor seizures. She had a 6-month history of well-controlled rheumatoid arthritis treated with certolizumab (a biological pegylated tumour necrosis factor (TNF)-α inhibitors). MR scan of brain showed diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) hyperintensity of the left fronto-parietal cortex without apparent diffusion coefficient (ADC) signal restriction and left-sided …
Published: 2020
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49. Characteristics and treatment of Multiple Sclerosis-related trigeminal neuralgia: An Italian multi-centre study

Author: Giorgia Teresa Maniscalco, Cinzia Cordioli, Maria Chiara Buscarinu, Diana Ferraro, Massimiliano Calabrese, Claudio Gasperini, Marcello Moccia, Alberto Gajofatto, Antonio Gallo, Eleonora Cocco, Valentina Camera, Pietro Annovazzi, Roberta Fantozzi, Marta Radaelli, Giovanna De Luca, Valentina Tomassini, Roberta Lanzillo, Claudio Solaro, Lorena Lorefice, Carla Tortorella, Federica Pinardi, Fabio Buttari, Paolo Ragonese, Paola Cavalla, Viviana Nociti, Salvatore Lo Fermo, Laura Boffa, Rirems, Damiano Paolicelli, Massimiliano Di Filippo, Ferraro, D., Annovazzi, P., Moccia, M., Lanzillo, R., De Luca, G., Nociti, V., Fantozzi, R., Paolicelli, D., Ragonese, P., Gajofatto, A., Boffa, L., Cavalla, P., Lo Fermo, S., Buscarinu, M. C., Lorefice, L., Cordioli, C., Calabrese, M., Gallo, A., Pinardi, F., Tortorella, C., Di Filippo, M., Camera, V., Maniscalco, G. T., Radaelli, M., Buttari, F., Tomassini, V., Cocco, E., Gasperini, C., Solaro, C., Ferraro D., Annovazzi P., Moccia M., Lanzillo R., De Luca G., Nociti V., Fantozzi R., Paolicelli D., Ragonese P., Gajofatto A., Boffa L., Cavalla P., Lo Fermo S., Buscarinu M.C., Lorefice L., Cordioli C., Calabrese M., Gallo A., Pinardi F., Tortorella C., Di Filippo M., Camera V., Maniscalco G.T., Radaelli M., Buttari F., Tomassini V., Cocco E., Gasperini C., and Solaro C.
Subjects: Pediatrics, medicine.medical_treatment, multiple sclerosis, microvascular decompression surgery, time factors, 0302 clinical medicine, Radiofrequency thermocoagulation, Trigeminal neuralgia, Multiple Sclerosi, Outcome Assessment, Health Care, italy, middle aged, pain, 030212 general & internal medicine, Oxcarbazepine, humans, education.field_of_study, trigeminal neuralgia, adult, Disability, Multiple Sclerosis, Pain, radiosurgery, General Medicine, Analgesics, Non-Narcotic, health care, follow-up studies, Settore MED/26 - NEUROLOGIA, aged, retrospective studies, female, Neurology, disability, analgesics, non-narcotic, male, severity of illness index, sex factors, neurosurgical procedures, outcome assessment, health care, analgesics, medicine.drug, medicine.medical_specialty, Population, Microvascular decompression, 03 medical and health sciences, medicine, education, outcome assessment, business.industry, Multiple sclerosis, Carbamazepine, medicine.disease, Discontinuation, non-narcotic, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Background The prevalence of trigeminal neuralgia (TN) in Multiple Sclerosis (MS) patients is higher than in the general population and its management can be particularly challenging. Our aim is to describe the characteristics, treatment and prognostic factors of MS-related TN in a retrospective multicentre study. Methods Neurologists members of the RIREMS group (Rising Researchers in MS) enrolled MS patients with a TN diagnosis and filled out a spreadsheet comprising their clinical data. Results Population consisted of 298 patients. First-choice preventive treatments were carbamazepine and oxcarbazepine. A surgical procedure was performed in 81 (30%) patients, most commonly gamma knife stereotactic radiosurgery (37%), followed by microvascular decompression (22%) and radiofrequency thermocoagulation (21%); one third of patients underwent at least two procedures. Surgery was associated with higher disability, male sex and longer interval between MS and TN onset. Patients (77%) who stayed on at least one preventive medication at most recent follow-up, after a mean period of 8 years, had a higher disability compared to the untreated group. Furthermore, patients with higher disability at TN onset were less likely to discontinue their first preventive medication due to pain remission, had bilateral TN more frequently and underwent surgical interventions earlier. Conclusion MS patients with a higher disability at TN onset and with a longer interval between MS and TN onset had differing clinical features and outcomes: pain was more frequently bilateral, surgery was more frequent and anticipated, and preventive medication discontinuation due to pain remission was less common.
Published: 2020

50. Natalizumab is associated with early improvement of working ability in relapsing-remitting multiple sclerosis patients: WANT observational study results

Author: Silvia Masera, Francesco Patti, Rocco Totaro, Nicola Rossi, Vincenzo Brescia Morra, Valentina Zipoli, Cinzia Scandellari, Want Investigators, Ruggero Capra, Massimiliano Mirabella, and Claudio Gasperini
Subjects: Quality of life, medicine.medical_specialty, Work productivity, Neurology, Dermatology, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, Clinical outcomes, Clinical endpoint, Medicine, Humans, Immunologic Factors, 030212 general & internal medicine, Prospective Studies, Adverse effect, Child, business.industry, General Medicine, medicine.disease, Psychiatry and Mental health, Settore MED/26 - NEUROLOGIA, Treatment Outcome, Italy, Absenteeism, Observational study, Neurology (clinical), Cognitive function, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: The Work Ability in Natalizumab-Treated MS Patients (WANT) study assessed work ability, quality of life, and cognitive processing speed during natalizumab treatment. WANT was a 1-year, prospective, multicenter observational study conducted in Italy. Inclusion criteria included relapsing-remitting multiple sclerosis (MS), natalizumab treatment, full-time worker status, and loss of working hours due to MS as measured by the Work Productivity and Activity Impairment Questionnaire for MS (WPAI:MS). The primary endpoint was change in WPAI:MS domain scores after 1 year on natalizumab. Secondary endpoints included change in annualized relapse rate (ARR), Multiple Sclerosis Impact Scale (MSIS-29) score, and Symbol Digit Modalities Test (SDMT) score. At enrollment, the 91 patients had a mean age of 38.3 (standard deviation [SD], 9.0) years and a mean ARR of 1.5 (SD, 0.8). After 1 year, improvements were observed in all WPAI:MS domains, with significant reductions in Absenteeism (−4.2 [SD, 26.0], p = 0.0190) and Work Productivity Loss (−7.2 [SD, 28.6]; p = 0.0456). These changes were accompanied by a low ARR (0.1), and 87.9% of patients were relapse free. Significant improvement was observed in MSIS-29 physical and psychological domains (reductions of 2.8 [SD, 11.6; p = 0.0295] and 6.3 [SD, 15.6; p = 0.0007], respectively) and SDMT score (increase of 2.4 [SD, 7.9; p = 0.0006]). Adverse events were reported in 32 of 104 patients (30.8%). The reductions in Absenteeism and Work Productivity Loss and the improved physical and psychological functioning reported after 1 year of natalizumab treatment in real-world settings extend our understanding of natalizumab’s effects on patient-centric and health economics outcomes.
Published: 2020

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