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3. Do patients’ and referral centers’ characteristics influence multiple sclerosis phenotypes? Results from the Italian multiple sclerosis and related disorders register

Author

Bergamaschi, Roberto, Beghi, Ettore, Bosetti, Cristina, Ponzio, Michela, Santucci, Claudia, Lepore, Vito, Mosconi, Paola, Aguglia, U., Amato, M. P., Ancona, A. L., Ardito, B., Avolio, C., Balgera, R., Banfi, P., Barcella, V., Barone, P., Bellantonio, P., Berardinelli, A., Bergamaschi, R., Bertora, P., Bianchi, M., Bramanti, P., Morra, V. Brescia, Brichetto, G., Brioschi, A. M., Buccafusca, M., Bucello, S., Busillo, V., Calchetti, B., Cantello, R., Capobianco, M., Capone, F., Capone, L., Cargnelutti, D., Carrozzi, M., Cartechini, E., Cavaletti, G., Cavalla, P., Celani, M. G., Clerici, R., Clerico, M., Cocco, E., Confalonieri, P., Coniglio, M. G., Conte, A., Corea, F., Cottone, S., Crociani, P., D’Andrea, F., Danni, M. C., De Luca, G., de Pascalis, D., De Riz, M., De Robertis, F., De Rosa, G., De Stefano, N., Corte, M. Della, Di Sapio, A., Docimo, R., Falcini, M., Falcone, N., Fermi, S., Ferraro, E., Ferrò, M. T., Fortunato, M., Foschi, M., Gajofatto, A., Gallo, A., Gallo, P., Gatto, M., Gazzola, P., Giordano, A., Granella, F., Grasso, M. F., Grasso, M. G., Grimaldi, L. M. E., Iaffaldano, P., Imperiale, D., Inglese, M., Iodice, R., Leva, S., Luezzi, V., Lugaresi, A., Lus, G., Maimone, D., Mancinelli, L., Maniscalco, G. T., Marfia, G. A., Marini, B., Marson, A., Mascoli, N., Massacesi, L., Melani, F., Merello, M., Meucci, G., Mirabella, M., Montepietra, S., Nasuelli, D., Nicolao, P., Passantino, F., Patti, F., Peresson, M., Pesci, I., Piantadosi, C., Piras, M. L., Pizzorno, M., Plewnia, K., Pozzilli, C., Protti, A., Quatrale, R., Realmuto, S., Ribizzi, G., Rinalduzzi, S., Rini, A., Romano, S., Romeo, M., Ronzoni, M., Rossi, P., Rovaris, M., Salemi, G., Santangelo, G., Santangelo, M., Santuccio, G., Sarchielli, P., Sinisi, L., Sola, P., Solaro, C., Spitaleri, D., Strumia, S., Tassinari, T., Tonietti, S., Tortorella, C., Totaro, R., Tozzo, A., Trivelli, G., Ulivelli, M., Valentino, P., Venturi, S., Vianello, M., Zaffaroni, M., Zarbo, R., Trojano, Maria, Battaglia, Mario Alberto, Capobianco, Marco, Pugliatti, Maura, Ulivelli, Monica, Mosconi, Paola, Gasperini, Claudio, Patti, Francesco, Amato, Maria Pia, Bergamaschi, Roberto, and Comi, Giancarlo

Published
2022
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4. Sexual dysfunction in multiple sclerosis: the impact of different MSISQ-19 cut-offs on prevalence and associated risk factors

Author

Petracca, M, Carotenuto, A, Scandurra, C, Moccia, M, Rosa, L, Arena, S, Ianniello, A, Nozzolillo, A, Turrini, M, LM, Streito, Abbadessa, G, Cellerino, M, Bucello, S, Ferraro, E, Mattioli, M, Chiodi, A, Inglese, M, Bonavita, S, Clerico, M, Cordioli, C, Moiola, L, Patti, F, Lavorgna, L, Filippi, M, Borriello, G, D'Amico, E, Pozzilli, C, Brescia Morra, V, and Lanzillo, R

Published
2023
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8. Clinical validation in multiple sclerosis of the lumipulse immunoassay for plasma neurofilament light chain

Author

Fiorenza, M., primary, Carbone, G., additional, La Civita, E., additional, Felicelli, G., additional, Sansone, R., additional, Delle Cave, T., additional, D’Angelo, M., additional, Sirica, R., additional, Jannuzzi, G., additional, Nicolella, V., additional, Moccia, M., additional, Brescia Morra, V., additional, and Terracciano, D., additional

Published
2024
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9. Evaluation of drivers of treatment switch in relapsing multiple sclerosis: a study from the Italian MS Registry

Author

Iaffaldano, P, Lucisano, G, Guerra, T, Patti, F, Cocco, E, De Luca, G, Brescia Morra, V, Pozzilli, C, Zaffaroni, M, Ferraro, D, Gasperini, C, Salemi, G, Bergamaschi, R, Lus, G, Inglese, M, Romano, S, Bellantonio, P, Di Monte, E, Maniscalco, G, Conte, A, Lugaresi, A, Vianello, M, Torri Clerici, V, Di Sapio, A, Pesci, I, Granella, F, Totaro, R, Marfia, G, Danni, M, Cavalla, P, Valentino, P, Aguglia, U, Montepietra, S, Ferraro, E, Protti, A, Spitaleri, D, Avolio, C, De Riz, M, Maimone, D, Cavaletti, G, Gazzola, P, Tedeschi, G, Sessa, M, Rovaris, M, Di Palma, F, Gatto, M, Cargnelutti, D, De Robertis̄, F, Logullo, F, Rini, A, Meucci, G, Ardito, B, Banfi, P, Nasuelli, D, Paolicelli, D, Rocca, M, Portaccio, E, Chisari, C, Fenu, G, Onofrj, M, Carotenuto, A, Ruggieri, S, Tortorella, C, Ragonese, P, Nica, M, Amato, M, Filippi, M, Trojano, M, Iaffaldano P., Lucisano G., Guerra T., Patti F., Cocco E., De Luca G., Brescia Morra V., Pozzilli C., Zaffaroni M., Ferraro D., Gasperini C., Salemi G., Bergamaschi R., Lus G., Inglese M., Romano S., Bellantonio P., Di Monte E., Maniscalco G. T., Conte A., Lugaresi A., Vianello M., Torri Clerici V. L. A., Di Sapio A., Pesci I., Granella F., Totaro R., Marfia G. A., Danni M. C., Cavalla P., Valentino P., Aguglia U., Montepietra S., Ferraro E., Protti A., Spitaleri D., Avolio C., De Riz M., Maimone D., Cavaletti G., Gazzola P., Tedeschi G., Sessa M., Rovaris M., Di Palma F., Gatto M., Cargnelutti D., De Robertis̄ F., Logullo F. O., Rini A., Meucci G., Ardito B., Banfi P., Nasuelli D., Paolicelli D., Rocca M. A., Portaccio E., Chisari C. G., Fenu G., Onofrj M., Carotenuto A., Ruggieri S., Tortorella C., Ragonese P., Nica M., Amato M. P., Filippi M., Trojano M., Iaffaldano, P, Lucisano, G, Guerra, T, Patti, F, Cocco, E, De Luca, G, Brescia Morra, V, Pozzilli, C, Zaffaroni, M, Ferraro, D, Gasperini, C, Salemi, G, Bergamaschi, R, Lus, G, Inglese, M, Romano, S, Bellantonio, P, Di Monte, E, Maniscalco, G, Conte, A, Lugaresi, A, Vianello, M, Torri Clerici, V, Di Sapio, A, Pesci, I, Granella, F, Totaro, R, Marfia, G, Danni, M, Cavalla, P, Valentino, P, Aguglia, U, Montepietra, S, Ferraro, E, Protti, A, Spitaleri, D, Avolio, C, De Riz, M, Maimone, D, Cavaletti, G, Gazzola, P, Tedeschi, G, Sessa, M, Rovaris, M, Di Palma, F, Gatto, M, Cargnelutti, D, De Robertis̄, F, Logullo, F, Rini, A, Meucci, G, Ardito, B, Banfi, P, Nasuelli, D, Paolicelli, D, Rocca, M, Portaccio, E, Chisari, C, Fenu, G, Onofrj, M, Carotenuto, A, Ruggieri, S, Tortorella, C, Ragonese, P, Nica, M, Amato, M, Filippi, M, Trojano, M, Iaffaldano P., Lucisano G., Guerra T., Patti F., Cocco E., De Luca G., Brescia Morra V., Pozzilli C., Zaffaroni M., Ferraro D., Gasperini C., Salemi G., Bergamaschi R., Lus G., Inglese M., Romano S., Bellantonio P., Di Monte E., Maniscalco G. T., Conte A., Lugaresi A., Vianello M., Torri Clerici V. L. A., Di Sapio A., Pesci I., Granella F., Totaro R., Marfia G. A., Danni M. C., Cavalla P., Valentino P., Aguglia U., Montepietra S., Ferraro E., Protti A., Spitaleri D., Avolio C., De Riz M., Maimone D., Cavaletti G., Gazzola P., Tedeschi G., Sessa M., Rovaris M., Di Palma F., Gatto M., Cargnelutti D., De Robertis̄ F., Logullo F. O., Rini A., Meucci G., Ardito B., Banfi P., Nasuelli D., Paolicelli D., Rocca M. A., Portaccio E., Chisari C. G., Fenu G., Onofrj M., Carotenuto A., Ruggieri S., Tortorella C., Ragonese P., Nica M., Amato M. P., Filippi M., and Trojano M.

Abstract

Background: Active relapsing–remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) are currently defined as “relapsing MS” (RMS). The aim of this cross-sectional study was to assess drivers of treatment switches due to clinical relapses in a population of RMS patients collected in the Italian MS and Related Disorders Register (I-MS&RD). Methods: RRMS and SPMS patients with at least one relapse in a time window of 2 years before of data extraction were defined as RMS. Factors associated with disease-modifying therapy (DMT) switching due to clinical activity were assessed through multivariable logistic regression models in which treatment exposure was included as the last recorded DMT and the last DMT’s class [moderate-efficacy (ME), high-efficacy (HE) DMTs and anti-CD20 drugs]. Results: A cohort of 4739 RMS patients (4161 RRMS, 578 SPMS) was extracted from the I-MS&RD. A total of 2694 patients switching DMTs due to relapses were identified. Switchers were significantly (p < 0.0001) younger, less disabled, more frequently affected by an RR disease course in comparison to non-switcher patients. The multivariable logistic regression models showed that Alemtuzumab (OR 0.08, 95% CI 0.02–0.37), Natalizumab (0.48, 0.30–0.76), Ocrelizumab (0.1, 0.02–0.45) and Rituximab (0.23, 0.06–0.82) exposure was a protective factor against treatment switch due to relapses. Moreover, the use of HE DMTs (0.43, 0.31–0.59), especially anti-CD20 drugs (0.14, 0.05–0.37), resulted to be a protective factor against treatment switch due to relapses in comparison with ME DMTs. Conclusions: More than 50% of RMS switched therapy due to disease activity. HE DMTs, especially anti-CD20 drugs, significantly reduce the risk of treatment switch.

Published
2023

10. Data monitoring roadmap. The experience of the Italian Multiple Sclerosis and Related Disorders Register

Author

Mosconi, P, Guerra, T, Paletta, P, D'Ettorre, A, Ponzio, M, Battaglia, M, Amato, M, Bergamaschi, R, Capobianco, M, Comi, G, Gasperini, C, Patti, F, Pugliatti, M, Ulivelli, M, Trojano, M, Lepore, V, Aguglia, U, Ancona, A, Ardito, B, Avolio, C, Balgera, R, Banfi, P, Barcella, V, Barone, P, Bellantonio, P, Berardinelli, A, Bertora, P, Bianchi, M, Bramanti, P, Brescia Morra, V, Brichetto, G, Brioschi, A, Buccafusca, M, Bucello, S, Busillo, V, Calchetti, B, Cantello, R, Capone, F, Capone, L, Cargnelutti, D, Carozzi, M, Cartechini, E, Cavaletti, G, Cavalla, P, Celani, M, Clerici, R, Clerico, M, Cocco, E, Torri Clerici, V, Coniglio, M, Conte, A, Corea, F, Cottone, S, Crociani, P, D'Andrea, F, Danni, M, De Luca, G, de Pascalis, D, De Riz, M, De Robertis, F, De Rosa, G, De Stefano, N, Della Corte, M, Di Sapio, A, Docimo, R, Falcini, M, Falcone, N, Fermi, S, Ferraro, E, Ferro, M, Fortunato, M, Foschi, M, Gajofatto, A, Gallo, A, Gallo, P, Gatto, M, Gazzola, P, Giordano, A, Granella, F, Grasso, M, Grimaldi, L, Iaffaldano, P, Immovilli, P, Imperiale, D, Inglese, M, Iodice, R, Leva, S, Leuzzi, V, Lugaresi, A, Lus, G, Maimone, D, Mancinelli, L, Maniscalco, G, Marfia, G, Margari, L, Marinelli, F, Marini, B, Marson, A, Mascoli, N, Massacesi, L, Melani, F, Merello, M, Fioretti, C, Mirabella, M, Montepietra, S, Nasuelli, D, Nicolao, P, Pasquali, L, Passantino, F, Pecori, C, Peresson, M, Pesci, I, Piantadosi, C, Piras, M, Pizzorno, M, Plewnia, K, Pozzilli, C, Protti, A, Quatrale, R, Realmuto, S, Ribizzi, G, Rinalduzzi, S, Rini, A, Romano, S, Filippi, M, Ronzoni, M, Rossi, P, Rovaris, M, Salemi, G, Santangelo, G, Santangelo, M, Leone, A, Sarchielli, P, Sinisi, L, Ferraro, D, Solaro, C, Spitaleri, D, Strumia, S, Tassinari, T, Santuccio, G, Tortorella, C, Totaro, R, Tozzo, A, Trivelli, G, Turano, G, Valentino, P, Venturi, S, Vianello, M, Zaffaroni, M, Zarbo, R, Mosconi P., Guerra T., Paletta P., D'Ettorre A., Ponzio M., Battaglia M. A., Amato M. P., Bergamaschi R., Capobianco M., Comi G., Gasperini C., Patti F., Pugliatti M., Ulivelli M., Trojano M., Lepore V., Aguglia U., Amato M., Ancona A., Ardito B., Avolio C., Balgera R., Banfi P., Barcella V., Barone P., Bellantonio P., Berardinelli A., Bertora P., Bianchi M., Bramanti P., Brescia Morra V., Brichetto G., Brioschi A., Buccafusca M., Bucello S., Busillo V., Calchetti B., Cantello R., Capone F., Capone L., Cargnelutti D., Carozzi M., Cartechini E., Cavaletti G., Cavalla P., Celani M., Clerici R., Clerico M., Cocco E., Torri Clerici V., Coniglio M., Conte A., Corea F., Cottone S., Crociani P., D'Andrea F., Danni M., De Luca G., de Pascalis D., De Riz M., De Robertis F., De Rosa G., De Stefano N., Della Corte M., Di Sapio A., Docimo R., Falcini M., Falcone N., Fermi S., Ferraro E., Ferro M., Fortunato M., Foschi M., Gajofatto A., Gallo A., Gallo P., Gatto M., Gazzola P., Giordano A., Granella F., Grasso M., Grimaldi L., Iaffaldano P., Immovilli P., Imperiale D., Inglese M., Iodice R., Leva S., Leuzzi V., Lugaresi A., Lus G., Maimone D., Mancinelli L., Maniscalco G., Marfia G., Margari L., Marinelli F., Marini B., Marson A., Mascoli N., Massacesi L., Melani F., Merello M., Fioretti C., Mirabella M., Montepietra S., Nasuelli D., Nicolao P., Pasquali L., Passantino F., Pecori C., Peresson M., Pesci I., Piantadosi C., Piras M., Pizzorno M., Plewnia K., Pozzilli C., Protti A., Quatrale R., Realmuto S., Ribizzi G., Rinalduzzi S., Rini A., Romano S., Filippi M., Ronzoni M., Rossi P., Rovaris M., Salemi G., Santangelo G., Santangelo M., Leone A., Sarchielli P., Sinisi L., Ferraro D., Solaro C., Spitaleri D., Strumia S., Tassinari T., Santuccio G., Tortorella C., Totaro R., Tozzo A., Trivelli G., Turano G., Valentino P., Venturi S., Vianello M., Zaffaroni M., Zarbo R., Mosconi, P, Guerra, T, Paletta, P, D'Ettorre, A, Ponzio, M, Battaglia, M, Amato, M, Bergamaschi, R, Capobianco, M, Comi, G, Gasperini, C, Patti, F, Pugliatti, M, Ulivelli, M, Trojano, M, Lepore, V, Aguglia, U, Ancona, A, Ardito, B, Avolio, C, Balgera, R, Banfi, P, Barcella, V, Barone, P, Bellantonio, P, Berardinelli, A, Bertora, P, Bianchi, M, Bramanti, P, Brescia Morra, V, Brichetto, G, Brioschi, A, Buccafusca, M, Bucello, S, Busillo, V, Calchetti, B, Cantello, R, Capone, F, Capone, L, Cargnelutti, D, Carozzi, M, Cartechini, E, Cavaletti, G, Cavalla, P, Celani, M, Clerici, R, Clerico, M, Cocco, E, Torri Clerici, V, Coniglio, M, Conte, A, Corea, F, Cottone, S, Crociani, P, D'Andrea, F, Danni, M, De Luca, G, de Pascalis, D, De Riz, M, De Robertis, F, De Rosa, G, De Stefano, N, Della Corte, M, Di Sapio, A, Docimo, R, Falcini, M, Falcone, N, Fermi, S, Ferraro, E, Ferro, M, Fortunato, M, Foschi, M, Gajofatto, A, Gallo, A, Gallo, P, Gatto, M, Gazzola, P, Giordano, A, Granella, F, Grasso, M, Grimaldi, L, Iaffaldano, P, Immovilli, P, Imperiale, D, Inglese, M, Iodice, R, Leva, S, Leuzzi, V, Lugaresi, A, Lus, G, Maimone, D, Mancinelli, L, Maniscalco, G, Marfia, G, Margari, L, Marinelli, F, Marini, B, Marson, A, Mascoli, N, Massacesi, L, Melani, F, Merello, M, Fioretti, C, Mirabella, M, Montepietra, S, Nasuelli, D, Nicolao, P, Pasquali, L, Passantino, F, Pecori, C, Peresson, M, Pesci, I, Piantadosi, C, Piras, M, Pizzorno, M, Plewnia, K, Pozzilli, C, Protti, A, Quatrale, R, Realmuto, S, Ribizzi, G, Rinalduzzi, S, Rini, A, Romano, S, Filippi, M, Ronzoni, M, Rossi, P, Rovaris, M, Salemi, G, Santangelo, G, Santangelo, M, Leone, A, Sarchielli, P, Sinisi, L, Ferraro, D, Solaro, C, Spitaleri, D, Strumia, S, Tassinari, T, Santuccio, G, Tortorella, C, Totaro, R, Tozzo, A, Trivelli, G, Turano, G, Valentino, P, Venturi, S, Vianello, M, Zaffaroni, M, Zarbo, R, Mosconi P., Guerra T., Paletta P., D'Ettorre A., Ponzio M., Battaglia M. A., Amato M. P., Bergamaschi R., Capobianco M., Comi G., Gasperini C., Patti F., Pugliatti M., Ulivelli M., Trojano M., Lepore V., Aguglia U., Amato M., Ancona A., Ardito B., Avolio C., Balgera R., Banfi P., Barcella V., Barone P., Bellantonio P., Berardinelli A., Bertora P., Bianchi M., Bramanti P., Brescia Morra V., Brichetto G., Brioschi A., Buccafusca M., Bucello S., Busillo V., Calchetti B., Cantello R., Capone F., Capone L., Cargnelutti D., Carozzi M., Cartechini E., Cavaletti G., Cavalla P., Celani M., Clerici R., Clerico M., Cocco E., Torri Clerici V., Coniglio M., Conte A., Corea F., Cottone S., Crociani P., D'Andrea F., Danni M., De Luca G., de Pascalis D., De Riz M., De Robertis F., De Rosa G., De Stefano N., Della Corte M., Di Sapio A., Docimo R., Falcini M., Falcone N., Fermi S., Ferraro E., Ferro M., Fortunato M., Foschi M., Gajofatto A., Gallo A., Gallo P., Gatto M., Gazzola P., Giordano A., Granella F., Grasso M., Grimaldi L., Iaffaldano P., Immovilli P., Imperiale D., Inglese M., Iodice R., Leva S., Leuzzi V., Lugaresi A., Lus G., Maimone D., Mancinelli L., Maniscalco G., Marfia G., Margari L., Marinelli F., Marini B., Marson A., Mascoli N., Massacesi L., Melani F., Merello M., Fioretti C., Mirabella M., Montepietra S., Nasuelli D., Nicolao P., Pasquali L., Passantino F., Pecori C., Peresson M., Pesci I., Piantadosi C., Piras M., Pizzorno M., Plewnia K., Pozzilli C., Protti A., Quatrale R., Realmuto S., Ribizzi G., Rinalduzzi S., Rini A., Romano S., Filippi M., Ronzoni M., Rossi P., Rovaris M., Salemi G., Santangelo G., Santangelo M., Leone A., Sarchielli P., Sinisi L., Ferraro D., Solaro C., Spitaleri D., Strumia S., Tassinari T., Santuccio G., Tortorella C., Totaro R., Tozzo A., Trivelli G., Turano G., Valentino P., Venturi S., Vianello M., Zaffaroni M., and Zarbo R.

Abstract

Introduction: Over the years, disease registers have been increasingly considered a source of reliable and valuable population studies. However, the validity and reliability of data from registers may be limited by missing data, selection bias or data quality not adequately evaluated or checked. This study reports the analysis of the consistency and completeness of the data in the Italian Multiple Sclerosis and Related Disorders Register. Methods: The Register collects, through a standardized Web-based Application, unique patients. Data are exported bimonthly and evaluated to assess the updating and completeness, and to check the quality and consistency. Eight clinical indicators are evaluated. Results: The Register counts 77,628 patients registered by 126 centres. The number of centres has increased over time, as their capacity to collect patients. The percentages of updated patients (with at least one visit in the last 24 months) have increased from 33% (enrolment period 2000–2015) to 60% (enrolment period 2016–2022). In the cohort of patients registered after 2016, there were ≥ 75% updated patients in 30% of the small centres (33), in 9% of the medium centres (11), and in all the large centres (2). Clinical indicators show significant improvement for the active patients, expanded disability status scale every 6 months or once every 12 months, visits every 6 months, first visit within 1 year and MRI every 12 months. Conclusions: Data from disease registers provide guidance for evidence-based health policies and research, so methods and strategies ensuring their quality and reliability are crucial and have several potential applications.

Published
2023

11. Utilization of peginterferon-β-1a in the real-world practice for relapsing-remitting multiple sclerosis.

Author

MOCCIA, M., SANTONI, L., VACCARI, I., AFFINITO, G., CALIENDO, D., RUBBA, F., LANZILLO, R., TRIASSI, M., MORRA, V. BRESCIA, and PALLADINO, R.

Abstract

OBJECTIVE: Peginterferon β-1a (PEG-IFN-β-1a) is the most recent interferon beta formulation approved for treating relapsing-remitting multiple sclerosis (RRMS). We aim to describe the real-world utilization of PEG-IFN-β-1a in RRMS and compare it with other injectable disease-modifying therapies (DMTs). PATIENTS AND METHODS: In this population-based study, we used 2015-2019 routinely collected healthcare data of the Campania region of Italy from National Healthcare System DMT prescriptions, inpatient and outpatient clinical records of hospitals in Campania, and the Federico II University MS clinical registry for a subset of patients. We included individuals with RRMS receiving new prescriptions of PEG-IFN-β-1a [n=281; age = 38.8±12.3 years; females=70.5%; disease duration = 8 .4±8.3 years; Expanded Disability S tatus Scale (EDSS) at baseline=2.0 (1.0-6.5)], glatiramer acetate [n=751; age = 46.0±11.4 years; females= 67.1%; disease duration = 9.8±8.2 years; EDSS=4.0 (1.5-8.5)], and subcutaneous (SC) IFN-β-1a [n=1,226; a ge = 3 9.7±11.7 y ears; f emales= 66.5%; disease duration = 8.2±6.5 years; EDSS 2.5 (1.5-6.5)]. Adherence [medication possession ratio (MPR)], escalation to more effective DMTs, hospitalization rates and costs were measured. We used mixed-effect linear regression models (for adherence, hospitalization rates and costs) and Cox regression models (for escalation) to assess differences between PEGIFN-β-1a (statistical reference), glatiramer acetate, and SC IFN-β-1a. All models included age, sex, previous treatment/untreated, year of treatment initiation, treatment duration, and adherence as covariates. RESULTS: Adherence was lower in glatiramer acetate (MPR = 0.91±0.1; Coeff=-0.11; p<0.01), and IFN-β-1a (MPR = 0.92±0.1; Coeff=-0.08; p<0.01), compared with PEG-IFN-β-1a (MPR = 1.01±0.1). The probability of escalating to more effective DMTs was higher for glatiramer acetate (14.9%; HR=4.09; p<0.01) and IFN-β-1a (9.1%; HR=3.35; p=0.01), compared with PEG-IFN-β-1a (4.9%). No differences in annualized hospitalization rates were identified between glatiramer acetate [annualized hospitalization rates (AHR) = 0.05±0.30; Coeff=0.02; p=0.31), IFN-β-1a (AHR = 0.02±0.21; Coeff=0.01; p=0.97], and P EG-IFN-β-1a (AHR = 0 .02±0.24); h owever, monthly costs for MS admissions were higher for glatiramer acetate (€49.45±€195.27; Coeff=-29.89; p=0.03), compared with IFN-β-1a (€29.42±€47.83; Coeff=6.79; p=0.61), and PEGIFN-β-1a (€23.91±€43.90). CONCLUSIONS: SC PEG-IFN-β-1a and IFN-β-1a were used in relatively similar populations, while glatiramer acetate was preferred in older and more disabled patients. PEG-IFN-β-1a was associated with higher adherence and lower escalation rates toward more effective (and costly) DMTs. [ABSTRACT FROM AUTHOR]

Published
2024

12. Disease-Modifying Treatments and Time to Loss of Ambulatory Function in Patients with Primary Progressive Multiple Sclerosis

Author

Portaccio, E, Fonderico, M, Iaffaldano, P, Pasto, L, Razzolini, L, Bellinvia, A, De Luca, G, Ragonese, P, Patti, F, Brescia Morra, V, Cocco, E, Sola, P, Inglese, M, Lus, G, Pozzilli, C, Maimone, D, Lugaresi, A, Gazzola, P, Comi, G, Pesci, I, Spitaleri, D, Rezzonico, M, Vianello, M, Avolio, C, Logullo, F, Granella, F, Salvetti, M, Zaffaroni, M, Lucisano, G, Filippi, M, Trojano, M, Amato, M, Cavaletti, G, Portaccio E., Fonderico M., Iaffaldano P., Pasto L., Razzolini L., Bellinvia A., De Luca G., Ragonese P., Patti F., Brescia Morra V., Cocco E., Sola P., Inglese M., Lus G., Pozzilli C., Maimone D., Lugaresi A., Gazzola P., Comi G., Pesci I., Spitaleri D., Rezzonico M., Vianello M., Avolio C., Logullo F. O., Granella F., Salvetti M., Zaffaroni M., Lucisano G., Filippi M., Trojano M., Amato M. P., Cavaletti G., Portaccio, E, Fonderico, M, Iaffaldano, P, Pasto, L, Razzolini, L, Bellinvia, A, De Luca, G, Ragonese, P, Patti, F, Brescia Morra, V, Cocco, E, Sola, P, Inglese, M, Lus, G, Pozzilli, C, Maimone, D, Lugaresi, A, Gazzola, P, Comi, G, Pesci, I, Spitaleri, D, Rezzonico, M, Vianello, M, Avolio, C, Logullo, F, Granella, F, Salvetti, M, Zaffaroni, M, Lucisano, G, Filippi, M, Trojano, M, Amato, M, Cavaletti, G, Portaccio E., Fonderico M., Iaffaldano P., Pasto L., Razzolini L., Bellinvia A., De Luca G., Ragonese P., Patti F., Brescia Morra V., Cocco E., Sola P., Inglese M., Lus G., Pozzilli C., Maimone D., Lugaresi A., Gazzola P., Comi G., Pesci I., Spitaleri D., Rezzonico M., Vianello M., Avolio C., Logullo F. O., Granella F., Salvetti M., Zaffaroni M., Lucisano G., Filippi M., Trojano M., Amato M. P., and Cavaletti G.

Abstract

Importance: Except for ocrelizumab, treatment options in primary progressive multiple sclerosis (PPMS) are lacking. Objective: To investigate the effectiveness of DMTs on the risk of becoming wheelchair dependent in a real-world population of patients with PPMS. Design, Setting, and Participants: This was a multicenter, observational, retrospective, comparative effectiveness research study. Data were extracted on November 28, 2018, from the Italian multiple sclerosis register and analyzed from June to December 2021. Mean study follow-up was 11 years. Included in the study cohort were patients with a diagnosis of PPMS and at least 3 years of Expanded Disability Status Scale (EDSS) evaluations and 3 years of follow-up. Main Outcomes and Measures: The risk of reaching an EDSS score of 7.0 was assessed through multivariable Cox regression models. Exposures: Patients who received DMT before the outcome were considered treated. DMT was assessed as a time-dependent variable and by class of DMT (moderately and highly effective). Results: From a total of 3298 patients with PPMS, 2633 were excluded because they did not meet the entry criteria for the phase 3, multicenter, randomized, parallel-group, double-blind, placebo-controlled study to evaluate the efficacy and safety of ocrelizumab in adults with PPMS (ORATORIO) trial. Among the remaining 665 patients (mean [SD] age, 43.0 [10.7] years; 366 female patients [55.0%]), 409 were further selected for propensity score matching (288 treated and 121 untreated patients). In the matched cohort, during the study follow-up, 37% of patients (152 of 409) reached an EDSS score of 7.0 after a mean (SD) follow-up of 10.6 (5.6) years. A higher EDSS score at baseline (adjusted hazard ratio [aHR], 1.32; 95% CI, 1.13-1.55; P <.001), superimposed relapses (aHR, 2.37; 95% CI, 1.24-4.54; P =.009), and DMT exposure (aHR, 1.75; 95% CI, 1.04-2.94; P =.03) were associated with a higher risk of an EDSS score of 7.0, whereas the interaction term b

Published
2022

13. Do patients' and referral centers' characteristics influence multiple sclerosis phenotypes? Results from the Italian multiple sclerosis and related disorders register

Author

Bergamaschi, R, Beghi, E, Bosetti, C, Ponzio, M, Santucci, C, Lepore, V, Mosconi, P, Aguglia, U, Amato, M, Ancona, A, Ardito, B, Avolio, C, Balgera, R, Banfi, P, Barcella, V, Barone, P, Bellantonio, P, Berardinelli, A, Bertora, P, Bianchi, M, Bramanti, P, Morra, V, Brichetto, G, Brioschi, A, Buccafusca, M, Bucello, S, Busillo, V, Calchetti, B, Cantello, R, Capobianco, M, Capone, F, Capone, L, Cargnelutti, D, Carrozzi, M, Cartechini, E, Cavaletti, G, Cavalla, P, Celani, M, Clerici, R, Clerico, M, Cocco, E, Confalonieri, P, Coniglio, M, Conte, A, Corea, F, Cottone, S, Crociani, P, D'Andrea, F, Danni, M, De Luca, G, de Pascalis, D, De Riz, M, De Robertis, F, De Rosa, G, De Stefano, N, Corte, M, Di Sapio, A, Docimo, R, Falcini, M, Falcone, N, Fermi, S, Ferraro, E, Ferrò, M, Fortunato, M, Foschi, M, Gajofatto, A, Gallo, A, Gallo, P, Gatto, M, Gazzola, P, Giordano, A, Granella, F, Grasso, M, Grimaldi, L, Iaffaldano, P, Imperiale, D, Inglese, M, Iodice, R, Leva, S, Luezzi, V, Lugaresi, A, Lus, G, Maimone, D, Mancinelli, L, Maniscalco, G, Marfia, G, Marini, B, Marson, A, Mascoli, N, Massacesi, L, Melani, F, Merello, M, Meucci, G, Mirabella, M, Montepietra, S, Nasuelli, D, Nicolao, P, Passantino, F, Patti, F, Peresson, M, Pesci, I, Piantadosi, C, Piras, M, Pizzorno, M, Plewnia, K, Pozzilli, C, Protti, A, Quatrale, R, Realmuto, S, Ribizzi, G, Rinalduzzi, S, Rini, A, Romano, S, Romeo, M, Ronzoni, M, Rossi, P, Rovaris, M, Salemi, G, Santangelo, G, Santangelo, M, Santuccio, G, Sarchielli, P, Sinisi, L, Sola, P, Solaro, C, Spitaleri, D, Strumia, S, Tassinari, T, Tonietti, S, Tortorella, C, Totaro, R, Tozzo, A, Trivelli, G, Ulivelli, M, Valentino, P, Venturi, S, Vianello, M, Zaffaroni, M, Zarbo, R, Trojano, M, Battaglia, M, Pugliatti, M, Gasperini, C, Comi, G, Bergamaschi, Roberto, Beghi, Ettore, Bosetti, Cristina, Ponzio, Michela, Santucci, Claudia, Lepore, Vito, Mosconi, Paola, Amato, M P, Ancona, A L, Morra, V Brescia, Brioschi, A M, Celani, M G, Coniglio, M G, Danni, M C, Corte, M Della, Ferrò, M T, Grasso, M F, Grasso, M G, Grimaldi, L M E, Maniscalco, G T, Marfia, G A, Piras, M L, Trojano, Maria, Battaglia, Mario Alberto, Capobianco, Marco, Pugliatti, Maura, Ulivelli, Monica, Gasperini, Claudio, Patti, Francesco, Amato, Maria Pia, Comi, Giancarlo, Bergamaschi, R, Beghi, E, Bosetti, C, Ponzio, M, Santucci, C, Lepore, V, Mosconi, P, Aguglia, U, Amato, M, Ancona, A, Ardito, B, Avolio, C, Balgera, R, Banfi, P, Barcella, V, Barone, P, Bellantonio, P, Berardinelli, A, Bertora, P, Bianchi, M, Bramanti, P, Morra, V, Brichetto, G, Brioschi, A, Buccafusca, M, Bucello, S, Busillo, V, Calchetti, B, Cantello, R, Capobianco, M, Capone, F, Capone, L, Cargnelutti, D, Carrozzi, M, Cartechini, E, Cavaletti, G, Cavalla, P, Celani, M, Clerici, R, Clerico, M, Cocco, E, Confalonieri, P, Coniglio, M, Conte, A, Corea, F, Cottone, S, Crociani, P, D'Andrea, F, Danni, M, De Luca, G, de Pascalis, D, De Riz, M, De Robertis, F, De Rosa, G, De Stefano, N, Corte, M, Di Sapio, A, Docimo, R, Falcini, M, Falcone, N, Fermi, S, Ferraro, E, Ferrò, M, Fortunato, M, Foschi, M, Gajofatto, A, Gallo, A, Gallo, P, Gatto, M, Gazzola, P, Giordano, A, Granella, F, Grasso, M, Grimaldi, L, Iaffaldano, P, Imperiale, D, Inglese, M, Iodice, R, Leva, S, Luezzi, V, Lugaresi, A, Lus, G, Maimone, D, Mancinelli, L, Maniscalco, G, Marfia, G, Marini, B, Marson, A, Mascoli, N, Massacesi, L, Melani, F, Merello, M, Meucci, G, Mirabella, M, Montepietra, S, Nasuelli, D, Nicolao, P, Passantino, F, Patti, F, Peresson, M, Pesci, I, Piantadosi, C, Piras, M, Pizzorno, M, Plewnia, K, Pozzilli, C, Protti, A, Quatrale, R, Realmuto, S, Ribizzi, G, Rinalduzzi, S, Rini, A, Romano, S, Romeo, M, Ronzoni, M, Rossi, P, Rovaris, M, Salemi, G, Santangelo, G, Santangelo, M, Santuccio, G, Sarchielli, P, Sinisi, L, Sola, P, Solaro, C, Spitaleri, D, Strumia, S, Tassinari, T, Tonietti, S, Tortorella, C, Totaro, R, Tozzo, A, Trivelli, G, Ulivelli, M, Valentino, P, Venturi, S, Vianello, M, Zaffaroni, M, Zarbo, R, Trojano, M, Battaglia, M, Pugliatti, M, Gasperini, C, Comi, G, Bergamaschi, Roberto, Beghi, Ettore, Bosetti, Cristina, Ponzio, Michela, Santucci, Claudia, Lepore, Vito, Mosconi, Paola, Amato, M P, Ancona, A L, Morra, V Brescia, Brioschi, A M, Celani, M G, Coniglio, M G, Danni, M C, Corte, M Della, Ferrò, M T, Grasso, M F, Grasso, M G, Grimaldi, L M E, Maniscalco, G T, Marfia, G A, Piras, M L, Trojano, Maria, Battaglia, Mario Alberto, Capobianco, Marco, Pugliatti, Maura, Ulivelli, Monica, Gasperini, Claudio, Patti, Francesco, Amato, Maria Pia, and Comi, Giancarlo

Abstract

Background: Multiple sclerosis (MS) is characterized by phenotypical heterogeneity, partly resulting from demographic and environmental risk factors. Socio-economic factors and the characteristics of local MS facilities might also play a part. Methods: This study included patients with a confirmed MS diagnosis enrolled in the Italian MS and Related Disorders Register in 2000–2021. Patients at first visit were classified as having a clinically isolated syndrome (CIS), relapsing–remitting (RR), primary progressive (PP), progressive-relapsing (PR), or secondary progressive MS (SP). Demographic and clinical characteristics were analyzed, with centers’ characteristics, geographic macro-areas, and Deprivation Index. We computed the odds ratios (OR) for CIS, PP/PR, and SP phenotypes, compared to the RR, using multivariate, multinomial, mixed effects logistic regression models. Results: In all 35,243 patients from 106 centers were included. The OR of presenting more advanced MS phenotypes than the RR phenotype at first visit significantly diminished in relation to calendar period. Females were at a significantly lower risk of a PP/PR or SP phenotype. Older age was associated with CIS, PP/PR, and SP. The risk of a longer interval between disease onset and first visit was lower for the CIS phenotype, but higher for PP/PR and SP. The probability of SP at first visit was greater in the South of Italy. Discussion: Differences in the phenotype of MS patients first seen in Italian centers can be only partly explained by differences in the centers’ characteristics. The demographic and socio-economic characteristics of MS patients seem to be the main determinants of the phenotypes at first referral.

Published
2022

14. MR Imaging Signs of Gadolinium Retention Are Not Associated with Long-Term Motor and Cognitive Outcomes in Multiple Sclerosis

Author

Scaravilli, A., primary, Tranfa, M., additional, Pontillo, G., additional, Falco, F., additional, Criscuolo, C., additional, Moccia, M., additional, Monti, S., additional, Lanzillo, R., additional, Brescia Morra, V., additional, Palma, G., additional, Petracca, M., additional, Tedeschi, E., additional, Elefante, A., additional, Brunetti, A., additional, and Cocozza, S., additional

Published
2023
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15. Data monitoring roadmap. The experience of the Italian Multiple Sclerosis and Related Disorders Register

Author

Mosconi, P., Guerra, T., Paletta, P., D’Ettorre, A., Ponzio, M., Battaglia, M. A., Amato, M. P., Bergamaschi, R., Capobianco, M., Comi, G., Gasperini, C., Patti, F., Pugliatti, M., Ulivelli, M., Trojano, M., Lepore, V., Aguglia, U., Amato, M., Ancona, A., Ardito, B., Avolio, C., Balgera, R., Banfi, P., Barcella, V., Barone, P., Bellantonio, P., Berardinelli, A., Bertora, P., Bianchi, M., Bramanti, P., Brescia Morra, V., Brichetto, G., Brioschi, A., Buccafusca, M., Bucello, S., Busillo, V., Calchetti, B., Cantello, R., Capone, F., Capone, L., Cargnelutti, D., Carozzi, M., Cartechini, E., Cavaletti, G., Cavalla, P., Celani, M., Clerici, R., Clerico, M., Cocco, E., Torri Clerici, V., Coniglio, M., Conte, A., Corea, F., Cottone, S., Crociani, P., D’Andrea, F., Danni, M., De Luca, G., de Pascalis, D., De Riz, M., De Robertis, F., De Rosa, G., De Stefano, N., Della Corte, M., Di Sapio, A., Docimo, R., Falcini, M., Falcone, N., Fermi, S., Ferraro, E., Ferrò, M., Fortunato, M., Foschi, M., Gajofatto, A., Gallo, A., Gallo, P., Gatto, M., Gazzola, P., Giordano, A., Granella, F., Grasso, M., Grimaldi, L., Iaffaldano, P., Immovilli, P., Imperiale, D., Inglese, M., Iodice, R., Leva, S., Leuzzi, V., Lugaresi, A., Lus, G., Maimone, D., Mancinelli, L., Maniscalco, G., Marfia, G., Margari, L., Marinelli, F., Marini, B., Marson, A., Mascoli, N., Massacesi, L., Melani, F., Merello, M., Fioretti, C., Mirabella, Massimiliano, Montepietra, S., Nasuelli, D., Nicolao, P., Pasquali, L., Passantino, F., Pecori, C., Peresson, M., Pesci, I., Piantadosi, C., Piras, M. L., Pizzorno, M., Plewnia, K., Pozzilli, C., Protti, A., Quatrale, R., Realmuto, S., Ribizzi, G., Rinalduzzi, S., Rini, A., Romano, S., Filippi, M., Ronzoni, M., Rossi, P., Rovaris, M., Salemi, G., Santangelo, G., Santangelo, M., Leone, A., Sarchielli, P., Sinisi, L., Ferraro, D., Solaro, C., Spitaleri, D., Strumia, S., Tassinari, T., Santuccio, G., Tortorella, C., Totaro, R., Tozzo, A., Trivelli, G., Turano, G., Valentino, P., Venturi, S., Vianello, M., Zaffaroni, M., Zarbo, R., Mirabella M. (ORCID:0000-0002-7783-114X), Mosconi, P., Guerra, T., Paletta, P., D’Ettorre, A., Ponzio, M., Battaglia, M. A., Amato, M. P., Bergamaschi, R., Capobianco, M., Comi, G., Gasperini, C., Patti, F., Pugliatti, M., Ulivelli, M., Trojano, M., Lepore, V., Aguglia, U., Amato, M., Ancona, A., Ardito, B., Avolio, C., Balgera, R., Banfi, P., Barcella, V., Barone, P., Bellantonio, P., Berardinelli, A., Bertora, P., Bianchi, M., Bramanti, P., Brescia Morra, V., Brichetto, G., Brioschi, A., Buccafusca, M., Bucello, S., Busillo, V., Calchetti, B., Cantello, R., Capone, F., Capone, L., Cargnelutti, D., Carozzi, M., Cartechini, E., Cavaletti, G., Cavalla, P., Celani, M., Clerici, R., Clerico, M., Cocco, E., Torri Clerici, V., Coniglio, M., Conte, A., Corea, F., Cottone, S., Crociani, P., D’Andrea, F., Danni, M., De Luca, G., de Pascalis, D., De Riz, M., De Robertis, F., De Rosa, G., De Stefano, N., Della Corte, M., Di Sapio, A., Docimo, R., Falcini, M., Falcone, N., Fermi, S., Ferraro, E., Ferrò, M., Fortunato, M., Foschi, M., Gajofatto, A., Gallo, A., Gallo, P., Gatto, M., Gazzola, P., Giordano, A., Granella, F., Grasso, M., Grimaldi, L., Iaffaldano, P., Immovilli, P., Imperiale, D., Inglese, M., Iodice, R., Leva, S., Leuzzi, V., Lugaresi, A., Lus, G., Maimone, D., Mancinelli, L., Maniscalco, G., Marfia, G., Margari, L., Marinelli, F., Marini, B., Marson, A., Mascoli, N., Massacesi, L., Melani, F., Merello, M., Fioretti, C., Mirabella, Massimiliano, Montepietra, S., Nasuelli, D., Nicolao, P., Pasquali, L., Passantino, F., Pecori, C., Peresson, M., Pesci, I., Piantadosi, C., Piras, M. L., Pizzorno, M., Plewnia, K., Pozzilli, C., Protti, A., Quatrale, R., Realmuto, S., Ribizzi, G., Rinalduzzi, S., Rini, A., Romano, S., Filippi, M., Ronzoni, M., Rossi, P., Rovaris, M., Salemi, G., Santangelo, G., Santangelo, M., Leone, A., Sarchielli, P., Sinisi, L., Ferraro, D., Solaro, C., Spitaleri, D., Strumia, S., Tassinari, T., Santuccio, G., Tortorella, C., Totaro, R., Tozzo, A., Trivelli, G., Turano, G., Valentino, P., Venturi, S., Vianello, M., Zaffaroni, M., Zarbo, R., and Mirabella M. (ORCID:0000-0002-7783-114X)

Abstract

IntroductionOver the years, disease registers have been increasingly considered a source of reliable and valuable population studies. However, the validity and reliability of data from registers may be limited by missing data, selection bias or data quality not adequately evaluated or checked.This study reports the analysis of the consistency and completeness of the data in the Italian Multiple Sclerosis and Related Disorders Register.MethodsThe Register collects, through a standardized Web-based Application, unique patients.Data are exported bimonthly and evaluated to assess the updating and completeness, and to check the quality and consistency. Eight clinical indicators are evaluated.ResultsThe Register counts 77,628 patients registered by 126 centres. The number of centres has increased over time, as their capacity to collect patients.The percentages of updated patients (with at least one visit in the last 24 months) have increased from 33% (enrolment period 2000-2015) to 60% (enrolment period 2016-2022). In the cohort of patients registered after 2016, there were >= 75% updated patients in 30% of the small centres (33), in 9% of the medium centres (11), and in all the large centres (2).Clinical indicators show significant improvement for the active patients, expanded disability status scale every 6 months or once every 12 months, visits every 6 months, first visit within 1 year and MRI every 12 months.ConclusionsData from disease registers provide guidance for evidence-based health policies and research, so methods and strategies ensuring their quality and reliability are crucial and have several potential applications.

Published
2023

16. Signs and symptoms of COVID-19 in patients with multiple sclerosis

Author

Schiavetti I., Carmisciano L., Ponzano M., Cordioli C., Cocco E., Marfia G. A., Inglese M., Filippi M., Radaelli M., Bergamaschi R., Immovilli P., Capobianco M., De Rossi N., Brichetto G., Scandellari C., Cavalla P., Pesci I., Confalonieri P., Perini P., Trojano M., Lanzillo R., Tedeschi G., Comi G., Battaglia M. A., Patti F., Salvetti M., Sormani M. P., Abbadessa G., Aguglia U., Allegorico L., Rossi Allegri B. M., Alteno A., Amato M. P., Annovazzi P., Antozzi C., Appendino L., Arena S., Baione V., Balgera R., Barcella V., Baroncini D., Barrila C., Bellacosa A., Bellucci G., Bergamaschi V., Bezzini D., Biolzi B., Bisecco A., Bonavita S., Borriello G., Bosa C., Bosco A., Bovis F., Bozzali M., Brambilla L., Brescia Morra V., Buccafusca M., Bucciantini E., Bucello S., Buscarinu M. C., Cabboi M. P., Calabrese M., Calabria F., Caleri F., Camilli F., Caniatti L. M., Cantello R., Capra R., Capuano R., Carta P., Celani M. G., Cellerino M., Cerqua R., Chisari C., Clerici R., Clerico M., Cola G., Conte A., Conti M. Z., Cordano C., Cordera S., Corea F., Correale C., Cottone S., Crescenzo F., Curti E., d'Ambrosio A., D'Amico E., Danni M. C., d'Arma A., Dattola V., de Biase S., De Luca G., De Mercanti S. F., De Mitri P., De Stefano N., Della Cava F. M., Cava M. D., Di Lemme S., di Napoli M., Di Sapio A., Docimo R., Dutto A., Evangelista L., Fanara S., Fantozzi R., Ferraro D., Ferro M. T., Fioretti C., Fratta M., Frau J., Fronza M., Furlan R., Gajofatto A., Gallo A., Gallo P., Gasperini C., Ghazaryan A., Giometto B., Gobbin F., Govone F., Granella F., Grange E., Grasso M. G., Grimaldi L. M. E., Guareschi A., Guaschino C., Guerrieri S., Guidetti D., Juergenson I. B., Iaffaldano P., Ianniello A., Iasevoli L., Imperiale D., Infante M. T., Iodice R., Iovino A., Konrad G., Landi D., Lapucci C., Lavorgna L., L'Episcopo M. R., Leva S., Liberatore G., Lo Re M., Longoni M., Lopiano L., Lorefice L., Lucchini M., Lus G., Maimone D., Malentacchi M., Mallucci G., Malucchi S., Mancinelli C. R., Mancinelli L., Manganotti P., Maniscalco G. T., Mantero V., Marangoni S., Marastoni D., Marinelli F., Marti A., Boneschi Martinelli F., Masserano Z. F., Matta F., Mendozzi L., Meucci G., Miante S., Miele G., Milano E., Mirabella M., Missione R., Moccia M., Moiola L., Montepietra S., MontiBragadin M., Montini F., Motta R., Nardone R., Gabri Nicoletti C., Nobile-Orazio E., Nozzolillo A., Onofrj M., Orlandi R., Palmieri A., Paolicelli D., Pasquali L., Pasto L., Pedrazzoli E., Petracca M., Petrone A., Piantadosi C., Pietroboni A. M., Pinardi F., Portaccio E., Pozzato M., Pozzilli C., Prosperini L., Protti A., Ragonese P., Rasia S., Realmuto S., Repice A., Rigoni E., Rilla M. T., Rinaldi F., Romano C. M., Ronzoni M., Rovaris M., Ruscica F., Sabattini L., Salemi G., Saraceno L., Sartori A., Sbragia E., Scarano G. I., Scarano V., Sessa M., Sgarito C., Sibilia G., Siciliano G., Signori A., Signoriello E., Sinisi L., Sireci F., Sola P., Solaro C., Sotgiu S., Sparaco M., Stromillo M. L., Strumia S., Susani E. L., Tabiadon G., Teatini F., Tomassini V., Tonietti S., Torri V., Tortorella C., Toscano S., Totaro R., Trotta M., Turano G., Ulivelli M., Valentino M., Vaula G., Vecchio D., Vercellino M., Verrengia E. P., Vianello M., Virgilio E., Vitetta F., Vollaro S., Zaffaroni M., Zampolini M., Zarbo I. R., Zito A., Zuliani L., Schiavetti, Irene, Carmisciano, Luca, Ponzano, Marta, Cordioli, Cinzia, Cocco, Eleonora, Marfia, Girolama Alessandra, Inglese, Matilde, Filippi, Massimo, Radaelli, Marta, Bergamaschi, Roberto, Immovilli, Paolo, Capobianco, Marco, De Rossi, Nicola, Brichetto, Giampaolo, Scandellari, Cinzia, Cavalla, Paola, Pesci, Ilaria, Confalonieri, Paolo, Perini, Paola, Trojano, Maria, Lanzillo, Roberta, Tedeschi, Gioacchino, Comi, Giancarlo, Battaglia, Mario Alberto, Patti, Francesco, Salvetti, Marco, Sormani, Maria Pia, Gianmarco, Abbadessa, Umberto, Aguglia, Allegorico, Lia, Beatrice Maria Rossi Allegri, Anastasia, Alteno, Amato, MARIA PIA, Pietro, Annovazzi, Carlo, Antozzi, Lucia, Appendino, Sebastiano, Arena, Viola, Baione, Roberto, Balgera, Valeria, Barcella, Damiano, Baroncini, Caterina, Barrilà, Alessandra, Bellacosa, Gianmarco, Bellucci, Valeria, Bergamaschi, Daiana, Bezzini, Beatrice, Biolzi, Bisecco, Alvino, Simona, Bonavita, Giovanna, Borriello, Chiara, Bosa, Antonio, Bosco, Francesca, Bovi, Marco, Bozzali, Laura, Brambilla, BRESCIA MORRA, Vincenzo, 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, Fabio Maria Della Cava, Marco Della Cava, Sonia Di Lemme, Mario di Napoli, Alessia Di Sapio, Renato, Docimo, Anna, Dutto, Luana, Evangelista, Salvatore, Fanara, Roberta, Fantozzi, Diana, Ferraro, Maria Teresa Ferrò, Cristina, Fioretti, Mario, Fratta, 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, Grasso, MARIA GRAZIA, Grimaldi, Luigi M. E., Angelica, Guareschi, Clara, Guaschino, Simone, Guerrieri, Donata, Guidetti, Ina Barbara Juergenson, Pietro, Iaffaldano, Ianniello, Antonio, Luigi, Iasevoli, Daniele, Imperiale, Maria Teresa Infante, Iodice, Rosa, Iovino, Aniello, Giovanna, Konrad, Doriana, Landi, Caterina, Lapucci, Luigi, Lavorgna, Maria Rita L’Episcopo, Serena, Leva, Giuseppe, Liberatore, Marianna Lo Re, Marco, Longoni, Leonardo, Lopiano, Lorena, Lorefice, Matteo, Lucchini, Lus, Giacomo, Maimone, Davide, Maria, Malentacchi, Giulia, Mallucci, Simona, Malucchi, Chiara Rosa Mancinelli, Luca, Mancinelli, Paolo, Manganotti, Giorgia Teresa Maniscalco, Vittorio, Mantero, Sabrina, Marangoni, Damiano, Marastoni, Fabiana, Marinelli, Marti, NICOLA ALESSANDRO, Filippo Boneschi Martinelli, Zoli Federco Masserano, Francesca, Matta, Laura, Mendozzi, Giuseppe, Meucci, Silvia, Miante, Giuseppina, Miele, Eva, Milano, Massimiliano, Mirabella, Rosanna, Missione, Moccia, Marcello, Lucia, Moiola, Sara, Montepietra, Margherita, Montibragadin, Federico, Montini, Roberta, Motta, Raffaele, Nardone, Carolina Gabri Nicoletti, Eduardo, Nobile‐orazio, Nozzolillo, Agostino, Marco, Onofrj, Riccardo, Orlandi, Anna, Palmieri, Damiano, Paolicelli, Livia, Pasquali, Luisa, Pastò, Elisabetta, Pedrazzoli, Petracca, Maria, Alfredo, Petrone, Carlo, Piantadosi, Pietroboni, Anna M., Federica, Pinardi, Emilio, Portaccio, Mattia, Pozzato, Pozzilli, Carlo, Luca, Prosperini, Alessandra, Protti, Paolo, Ragonese, Sarah, Rasia, Sabrina, Realmuto, Anna, Repice, Eleonora, Rigoni, Maria Teresa Rilla, DELLA RATTA RINALDI, Francesca, Calogero Marcello Romano, Marco, Ronzoni, Marco, Rovari, Francesca, Ruscica, Loredana, Sabattini, Giuseppe, Salemi, Lorenzo, Saraceno, Alessia, Sartori, Arianna, Sartori, Elvira, Sbragia, Giuditta Ilaria Scarano, Valentina, Scarano, Maria, Sessa, Caterina, Sgarito, Sibilia, Grazia, Gabriele, Siciliano, Alessio, Signori, Signoriello, Elisabetta, Sinisi, Leonardo, 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, Valentina, Torri, Tortorella, Carla, 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, Vollaro, Stefano, Mauro, Zaffaroni, Mauro, Zampolini, Ignazio Roberto Zarbo, Antonio, Zito, and Luigi Zuliani, Schiavetti, I., Carmisciano, L., Ponzano, M., Cordioli, C., Cocco, E., Marfia, G. A., Inglese, M., Filippi, M., Radaelli, M., Bergamaschi, R., Immovilli, P., Capobianco, M., De Rossi, N., Brichetto, G., Scandellari, C., Cavalla, P., Pesci, I., Confalonieri, P., Perini, P., Trojano, M., Lanzillo, R., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., Sormani, M. P., Abbadessa, G., Aguglia, U., Allegorico, L., Rossi Allegri, B. M., Alteno, A., Amato, M. P., Annovazzi, P., Antozzi, C., Appendino, L., Arena, S., Baione, V., Balgera, R., Barcella, V., Baroncini, D., Barrila, C., Bellacosa, A., Bellucci, G., Bergamaschi, V., Bezzini, D., Biolzi, B., Bisecco, A., Bonavita, S., Borriello, G., Bosa, C., Bosco, A., Bovis, F., Bozzali, M., Brambilla, L., Brescia Morra, V., Buccafusca, M., Bucciantini, E., Bucello, S., Buscarinu, M. C., Cabboi, M. P., Calabrese, M., Calabria, F., Caleri, F., Camilli, F., Caniatti, L. M., Cantello, R., Capra, R., Capuano, R., Carta, P., Celani, M. G., Cellerino, M., Cerqua, R., Chisari, C., Clerici, R., Clerico, M., Cola, G., Conte, A., Conti, M. Z., Cordano, C., Cordera, S., Corea, F., Correale, C., Cottone, S., Crescenzo, F., Curti, E., D'Ambrosio, A., D'Amico, E., Danni, M. C., D'Arma, A., Dattola, V., de Biase, S., De Luca, G., De Mercanti, S. F., De Mitri, P., De Stefano, N., Della Cava, F. M., Cava, M. D., Di Lemme, S., di Napoli, M., Di Sapio, A., Docimo, R., Dutto, A., Evangelista, L., Fanara, S., Fantozzi, R., Ferraro, D., Ferro, M. T., Fioretti, C., Fratta, M., Frau, J., Fronza, M., Furlan, R., Gajofatto, A., Gallo, A., Gallo, P., Gasperini, C., Ghazaryan, A., Giometto, B., Gobbin, F., Govone, F., Granella, F., Grange, E., Grasso, M. G., Grimaldi, L. M. E., Guareschi, A., Guaschino, C., Guerrieri, S., Guidetti, D., Juergenson, I. B., Iaffaldano, P., Ianniello, A., Iasevoli, L., Imperiale, D., Infante, M. T., Iodice, R., Iovino, A., Konrad, G., Landi, D., Lapucci, C., Lavorgna, L., L'Episcopo, M. R., Leva, S., Liberatore, G., Lo Re, M., Longoni, M., Lopiano, L., Lorefice, L., Lucchini, M., Lus, G., Maimone, D., Malentacchi, M., Mallucci, G., Malucchi, S., Mancinelli, C. R., Mancinelli, L., Manganotti, P., Maniscalco, G. T., Mantero, V., Marangoni, S., Marastoni, D., Marinelli, F., Marti, A., Boneschi Martinelli, F., Masserano, Z. F., Matta, F., Mendozzi, L., Meucci, G., Miante, S., Miele, G., Milano, E., Mirabella, M., Missione, R., Moccia, M., Moiola, L., Montepietra, S., Montibragadin, M., Montini, F., Motta, R., Nardone, R., Gabri Nicoletti, C., Nobile-Orazio, E., Nozzolillo, A., Onofrj, M., Orlandi, R., Palmieri, A., Paolicelli, D., Pasquali, L., Pasto, L., Pedrazzoli, E., Petracca, M., Petrone, A., Piantadosi, C., Pietroboni, A. M., Pinardi, F., Portaccio, E., Pozzato, M., Pozzilli, C., Prosperini, L., Protti, A., Ragonese, P., Rasia, S., Realmuto, S., Repice, A., Rigoni, E., Rilla, M. T., Rinaldi, F., Romano, C. M., Ronzoni, M., Rovaris, M., Ruscica, F., Sabattini, L., Salemi, G., Saraceno, L., Sartori, A., Sbragia, E., Scarano, G. I., Scarano, V., Sessa, M., Sgarito, C., Sibilia, G., Siciliano, G., Signori, A., Signoriello, E., Sinisi, L., Sireci, F., Sola, P., Solaro, C., Sotgiu, S., Sparaco, M., Stromillo, M. L., Strumia, S., Susani, E. L., Tabiadon, G., Teatini, F., Tomassini, V., Tonietti, S., Torri, V., Tortorella, C., Toscano, S., Totaro, R., Trotta, M., Turano, G., Ulivelli, M., Valentino, M., Vaula, G., Vecchio, D., Vercellino, M., Verrengia, E. P., Vianello, M., Virgilio, E., Vitetta, F., Vollaro, S., Zaffaroni, M., Zampolini, M., Zarbo, I. R., Zito, A., and Zuliani, L.

Subjects
Multiple Sclerosis, Anosmia, Clinical Sciences, neurological disorders, Neurodegenerative, Settore MED/26, demyelinating disease, COVID-19, demyelinating diseases, disease-modifying treatment, multiple sclerosis, Humans, neurological disorder, Aged, Neurology & Neurosurgery, SARS-CoV-2, Pain Research, Neurosciences, Brain Disorders, Settore MED/26 - NEUROLOGIA, Good Health and Well Being, Neurology, multiple sclerosi, Neurology (clinical), MuSC-19 Study Group, Ageusia, Human
Abstract

Background and purpose: Clinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID-19) have been thoroughly investigated, but a further analysis on main signs and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID-19 in MS patients and identify all factors associated with their manifestation. Method: Logistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number. Results: From March 2020 to November 2021, data were collected from 1354 MS patients with confirmed infection of COVID-19. Ageusia and anosmia was less frequent in older people (odds ratio [OR] 0.98; p=0.005) and more in smoker patients (OR 1.39; p=0.049). Smoke was also associated with an incremental number of symptoms (OR 1.24; p=0.031), substance abuse (drugs or alcohol), conjunctivitis and rash (OR 5.20; p=0.042) and the presence of at least one comorbidity with shortness of breath, tachycardia or chest pain (OR 1.24; p=0.008). Some disease-modifying therapies were associated with greater frequencies of certain COVID-19 symptoms (association between anti-CD20 therapies and increment in the number of concomitant symptoms: OR 1.29; p=0.05). Differences in frequencies between the three waves were found for flu-like symptoms (G1, p=0.024), joint or muscle pain (G2, p=0.013) and ageusia and anosmia (G5, p < 0.001). All cases should be referred to variants up to Delta. Conclusion: Several factors along with the choice of specific therapeutic approaches might have a different impact on the occurrence of some COVID-19 symptoms.

Published
2022

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

Author

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., Abbadessa, G., Aguglia, U., Allegorico, L., Allegri, R. B. M., Alteno, A., Amato, M. P., Annovazzi, P., Antozzi, C., Appendino, L., Arena, S., Baione, V., Balgera, R., Barcella, V., Baroncini, D., Barrilà, C., Bellacosa, A., Bellucci, G., Bergamaschi, V., Bezzini, D., Biolzi, B., Bisecco, A., Bonavita, S., Borriello, G., Bosa, C., Bosco, A., Bovis, F., Bozzali, M., Brambilla, L., Brescia, M. V., Buccafusca, M., Bucciantini, E., Bucello, S., Buscarinu, M. C., Cabboi, M. P., Calabrese, M., Calabria, F., Caleri, F., Camilli, F., Caniatti, L. M., Cantello, R., Capra, R., Capuano, R., Carta, P., Celani, M. G., Cellerino, M., Cerqua, R., Chisari, C., Clerici, R., Clerico, M., Cola, G., Conte, A., Conti, M. Z., Cordano, C., Cordera, S., Corea, F., Correale, C., Cottone, S., Crescenzo, F., Curti, E., D'Ambrosio, A., D'Amico, E., Danni, M. C., D'Arma, A., Dattola, V., de Biase, S., De Luca, G., De Mercanti, S. F., De Mitri, P., De Stefano, N., Della, C. M., Mirabella, Massimiliano, MuSC-19 study, Group., Mirabella M. (ORCID:0000-0002-7783-114X), 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., Abbadessa, G., Aguglia, U., Allegorico, L., Allegri, R. B. M., Alteno, A., Amato, M. P., Annovazzi, P., Antozzi, C., Appendino, L., Arena, S., Baione, V., Balgera, R., Barcella, V., Baroncini, D., Barrilà, C., Bellacosa, A., Bellucci, G., Bergamaschi, V., Bezzini, D., Biolzi, B., Bisecco, A., Bonavita, S., Borriello, G., Bosa, C., Bosco, A., Bovis, F., Bozzali, M., Brambilla, L., Brescia, M. V., Buccafusca, M., Bucciantini, E., Bucello, S., Buscarinu, M. C., Cabboi, M. P., Calabrese, M., Calabria, F., Caleri, F., Camilli, F., Caniatti, L. M., Cantello, R., Capra, R., Capuano, R., Carta, P., Celani, M. G., Cellerino, M., Cerqua, R., Chisari, C., Clerici, R., Clerico, M., Cola, G., Conte, A., Conti, M. Z., Cordano, C., Cordera, S., Corea, F., Correale, C., Cottone, S., Crescenzo, F., Curti, E., D'Ambrosio, A., D'Amico, E., Danni, M. C., D'Arma, A., Dattola, V., de Biase, S., De Luca, G., De Mercanti, S. F., De Mitri, P., De Stefano, N., Della, C. M., Mirabella, Massimiliano, MuSC-19 study, Group., and Mirabella M. (ORCID:0000-0002-7783-114X)

Abstract

Background and purpose Some studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 mu g/m(3) (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.

Published
2022

19. Signs and symptoms of COVID-19 in patients with multiple sclerosis

Author

Schiavetti, I., Carmisciano, L., Ponzano, M., Cordioli, C., Cocco, E., Marfia, G. A., Inglese, M., Filippi, M., Radaelli, M., Bergamaschi, R., Immovilli, P., Capobianco, M., De Rossi, N., Brichetto, G., Scandellari, C., Cavalla, P., Pesci, I., Confalonieri, P., Perini, P., Trojano, M., Lanzillo, R., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., Sormani, M. P., Abbadessa, G., Aguglia, U., Allegorico, L., Rossi Allegri, B. M., Alteno, A., Amato, M. P., Annovazzi, P., Antozzi, C., Appendino, L., Arena, S., Baione, V., Balgera, R., Barcella, V., Baroncini, D., Barrila, C., Bellacosa, A., Bellucci, G., Bergamaschi, V., Bezzini, D., Biolzi, B., Bisecco, A., Bonavita, S., Borriello, G., Bosa, C., Bosco, A., Bovis, F., Bozzali, M., Brambilla, L., Brescia Morra, V., Buccafusca, M., Bucciantini, E., Bucello, S., Buscarinu, M. C., Cabboi, M. P., Calabrese, M., Calabria, F., Caleri, F., Camilli, F., Caniatti, L. M., Cantello, R., Capra, R., Capuano, R., Carta, P., Celani, M. G., Cellerino, M., Cerqua, R., Chisari, C., Clerici, R., Clerico, M., Cola, G., Conte, A., Conti, M. Z., Cordano, C., Cordera, S., Corea, F., Correale, C., Cottone, S., Crescenzo, F., Curti, E., D'Ambrosio, A., D'Amico, E., Danni, M. C., D'Arma, A., Dattola, V., de Biase, S., De Luca, G., De Mercanti, S. F., De Mitri, P., De Stefano, N., Della Cava, F. M., Cava, M. D., Di Lemme, S., di Napoli, M., Di Sapio, A., Docimo, R., Dutto, A., Evangelista, L., Fanara, S., Fantozzi, R., Ferraro, D., Ferro, M. T., Fioretti, C., Fratta, M., Frau, J., Fronza, M., Furlan, R., Gajofatto, A., Gallo, A., Gallo, P., Gasperini, C., Ghazaryan, A., Giometto, B., Gobbin, F., Govone, F., Granella, F., Grange, E., Grasso, M. G., Grimaldi, L. M. E., Guareschi, A., Guaschino, C., Guerrieri, S., Guidetti, D., Juergenson, I. B., Iaffaldano, P., Ianniello, A., Iasevoli, L., Imperiale, D., Infante, M. T., Iodice, R., Iovino, A., Konrad, G., Landi, D., Lapucci, C., Lavorgna, L., L'Episcopo, M. R., Leva, S., Liberatore, G., Lo Re, M., Longoni, M., Lopiano, L., Lorefice, L., Lucchini, Matteo, Lus, G., Maimone, D., Malentacchi, M., Mallucci, G., Malucchi, S., Mancinelli, C. R., Mancinelli, L., Manganotti, P., Maniscalco, G. T., Mantero, V., Marangoni, S., Marastoni, D., Marinelli, F., Marti, A., Boneschi Martinelli, F., Masserano, Z. F., Matta, F., Mendozzi, L., Meucci, G., Miante, S., Miele, G., Milano, E., Mirabella, Massimiliano, Missione, R., Moccia, M., Moiola, L., Montepietra, S., Montibragadin, M., Montini, F., Motta, R., Nardone, R., Gabri Nicoletti, C., Nobile-Orazio, E., Nozzolillo, A., Onofrj, M., Orlandi, R., Palmieri, A., Paolicelli, D., Pasquali, L., Pasto, L., Pedrazzoli, E., Petracca, M., Petrone, A., Piantadosi, C., Pietroboni, A. M., Pinardi, F., Portaccio, E., Pozzato, M., Pozzilli, C., Prosperini, L., Protti, A., Ragonese, P., Rasia, S., Realmuto, S., Repice, A., Rigoni, E., Rilla, M. T., Rinaldi, F., Romano, C. M., Ronzoni, M., Rovaris, M., Ruscica, F., Sabattini, L., Salemi, G., Saraceno, L., Sartori, A., Sbragia, E., Scarano, G. I., Scarano, V., Sessa, M., Sgarito, C., Sibilia, G., Siciliano, G., Signori, A., Signoriello, E., Sinisi, L., Sireci, F., Sola, P., Solaro, C., Sotgiu, S., Sparaco, M., Stromillo, M. L., Strumia, S., Susani, E. L., Tabiadon, G., Teatini, F., Tomassini, V., Tonietti, S., Torri, V., Tortorella, C., Toscano, S., Totaro, R., Trotta, M., Turano, G., Ulivelli, M., Valentino, M., Vaula, G., Vecchio, D., Vercellino, M., Verrengia, E. P., Vianello, M., Virgilio, E., Vitetta, F., Vollaro, S., Zaffaroni, M., Zampolini, M., Zarbo, I. R., Zito, A., Zuliani, L., Lucchini M. (ORCID:0000-0002-0447-2297), Mirabella M. (ORCID:0000-0002-7783-114X), Schiavetti, I., Carmisciano, L., Ponzano, M., Cordioli, C., Cocco, E., Marfia, G. A., Inglese, M., Filippi, M., Radaelli, M., Bergamaschi, R., Immovilli, P., Capobianco, M., De Rossi, N., Brichetto, G., Scandellari, C., Cavalla, P., Pesci, I., Confalonieri, P., Perini, P., Trojano, M., Lanzillo, R., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., Sormani, M. P., Abbadessa, G., Aguglia, U., Allegorico, L., Rossi Allegri, B. M., Alteno, A., Amato, M. P., Annovazzi, P., Antozzi, C., Appendino, L., Arena, S., Baione, V., Balgera, R., Barcella, V., Baroncini, D., Barrila, C., Bellacosa, A., Bellucci, G., Bergamaschi, V., Bezzini, D., Biolzi, B., Bisecco, A., Bonavita, S., Borriello, G., Bosa, C., Bosco, A., Bovis, F., Bozzali, M., Brambilla, L., Brescia Morra, V., Buccafusca, M., Bucciantini, E., Bucello, S., Buscarinu, M. C., Cabboi, M. P., Calabrese, M., Calabria, F., Caleri, F., Camilli, F., Caniatti, L. M., Cantello, R., Capra, R., Capuano, R., Carta, P., Celani, M. G., Cellerino, M., Cerqua, R., Chisari, C., Clerici, R., Clerico, M., Cola, G., Conte, A., Conti, M. Z., Cordano, C., Cordera, S., Corea, F., Correale, C., Cottone, S., Crescenzo, F., Curti, E., D'Ambrosio, A., D'Amico, E., Danni, M. C., D'Arma, A., Dattola, V., de Biase, S., De Luca, G., De Mercanti, S. F., De Mitri, P., De Stefano, N., Della Cava, F. M., Cava, M. D., Di Lemme, S., di Napoli, M., Di Sapio, A., Docimo, R., Dutto, A., Evangelista, L., Fanara, S., Fantozzi, R., Ferraro, D., Ferro, M. T., Fioretti, C., Fratta, M., Frau, J., Fronza, M., Furlan, R., Gajofatto, A., Gallo, A., Gallo, P., Gasperini, C., Ghazaryan, A., Giometto, B., Gobbin, F., Govone, F., Granella, F., Grange, E., Grasso, M. G., Grimaldi, L. M. E., Guareschi, A., Guaschino, C., Guerrieri, S., Guidetti, D., Juergenson, I. B., Iaffaldano, P., Ianniello, A., Iasevoli, L., Imperiale, D., Infante, M. T., Iodice, R., Iovino, A., Konrad, G., Landi, D., Lapucci, C., Lavorgna, L., L'Episcopo, M. R., Leva, S., Liberatore, G., Lo Re, M., Longoni, M., Lopiano, L., Lorefice, L., Lucchini, Matteo, Lus, G., Maimone, D., Malentacchi, M., Mallucci, G., Malucchi, S., Mancinelli, C. R., Mancinelli, L., Manganotti, P., Maniscalco, G. T., Mantero, V., Marangoni, S., Marastoni, D., Marinelli, F., Marti, A., Boneschi Martinelli, F., Masserano, Z. F., Matta, F., Mendozzi, L., Meucci, G., Miante, S., Miele, G., Milano, E., Mirabella, Massimiliano, Missione, R., Moccia, M., Moiola, L., Montepietra, S., Montibragadin, M., Montini, F., Motta, R., Nardone, R., Gabri Nicoletti, C., Nobile-Orazio, E., Nozzolillo, A., Onofrj, M., Orlandi, R., Palmieri, A., Paolicelli, D., Pasquali, L., Pasto, L., Pedrazzoli, E., Petracca, M., Petrone, A., Piantadosi, C., Pietroboni, A. M., Pinardi, F., Portaccio, E., Pozzato, M., Pozzilli, C., Prosperini, L., Protti, A., Ragonese, P., Rasia, S., Realmuto, S., Repice, A., Rigoni, E., Rilla, M. T., Rinaldi, F., Romano, C. M., Ronzoni, M., Rovaris, M., Ruscica, F., Sabattini, L., Salemi, G., Saraceno, L., Sartori, A., Sbragia, E., Scarano, G. I., Scarano, V., Sessa, M., Sgarito, C., Sibilia, G., Siciliano, G., Signori, A., Signoriello, E., Sinisi, L., Sireci, F., Sola, P., Solaro, C., Sotgiu, S., Sparaco, M., Stromillo, M. L., Strumia, S., Susani, E. L., Tabiadon, G., Teatini, F., Tomassini, V., Tonietti, S., Torri, V., Tortorella, C., Toscano, S., Totaro, R., Trotta, M., Turano, G., Ulivelli, M., Valentino, M., Vaula, G., Vecchio, D., Vercellino, M., Verrengia, E. P., Vianello, M., Virgilio, E., Vitetta, F., Vollaro, S., Zaffaroni, M., Zampolini, M., Zarbo, I. R., Zito, A., Zuliani, L., Lucchini M. (ORCID:0000-0002-0447-2297), and Mirabella M. (ORCID:0000-0002-7783-114X)

Abstract

Background and purpose Clinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID-19) have been thoroughly investigated, but a further analysis on main signs and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID-19 in MS patients and identify all factors associated with their manifestation. Method Logistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number. Results From March 2020 to November 2021, data were collected from 1354 MS patients with confirmed infection of COVID-19. Ageusia and anosmia was less frequent in older people (odds ratio [OR] 0.98; p = 0.005) and more in smoker patients (OR 1.39; p = 0.049). Smoke was also associated with an incremental number of symptoms (OR 1.24; p = 0.031), substance abuse (drugs or alcohol), conjunctivitis and rash (OR 5.20; p = 0.042) and the presence of at least one comorbidity with shortness of breath, tachycardia or chest pain (OR 1.24; p = 0.008). Some disease-modifying therapies were associated with greater frequencies of certain COVID-19 symptoms (association between anti-CD20 therapies and increment in the number of concomitant symptoms: OR 1.29; p = 0.05). Differences in frequencies between the three waves were found for flu-like symptoms (G1, p = 0.024), joint or muscle pain (G2, p = 0.013) and ageusia and anosmia (G5, p < 0.001). All cases should be referred to variants up to Delta. Conclusion Several factors along with the choice of specific therapeutic approaches might have a different impact on the occurrence of some COVID-19 symptoms.

Published
2022

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

Author

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., Abbadessa, G., Aguglia, U., Allegorico, L., Allegri, R. B. M., Amato, M. P., Annovazzi, P., Antozzi, C., Appendino, L., Arena, S., Baione, V., Balgera, R., Barcella, V., Baroncini, D., Barrila, C., Bellacosa, A., Bellucci, G., Bergamaschi, R., Bergamaschi, V., Bezzini, D., Biolzi, B., Bisecco, A., Bonavita, S., Borriello, G., Bosa, C., Bosco, A., Bovis, F., Bozzali, M., Brambilla, L., Brescia, M. V., Brichetto, G., Buccafusca, M., Bucciantini, E., Bucello, S., Buscarinu, M. C., Cabboi, M. P., Calabrese, M., Calabria, F., Caleri, F., Camilli, F., Caniatti, L. M., Cantello, R., Capra, R., Capuano, R., Carta, P., Cavalla, P., Celani, M. G., Cellerino, M., Cerqua, R., Chisari, C., Clerici, R., Clerico, M., Cocco, E., Cola, G., Confalonieri, P., Conte, A., Conti, M. Z., Cordano, C., Cordera, S., Corea, F., Correale, C., Cottone, S., Crescenzo, F., Curti, E., D'Ambrosio, A., D'Amico, E., Danni, M. C., D'Arma, A., Dattola, V., de Biase, S., De Luca, G., De Mercanti, S. F., De Mitri, P., De Stefano, N., Della Cava, M., di Napoli, M., Di Sapio, A., Docimo, R., Dutto, A., Evangelista, L., Fanara, S., Ferraro, D., Ferro, M. T., Filippi, M., Fioretti, C., Fratta, M., Frau, J., Fronza, M., Gajofatto, A., Gallo, A., Gallo, P., Gasperini, C., Ghazaryan, A., Giometto, B., Gobbin, F., Govone, F., Granella, F., Grange, E., Grasso, M. G., Guareschi, A., Guaschino, C., Guerrieri, S., Guidetti, D., Iaffaldano, P., Ianniello, A., Iasevoli, L., Imperiale, D., Infante, M. T., Inglese, M., Iodice, R., Iovino, A., Konrad, G., Lanzillo, R., Lapucci, C., Lavorgna, L., L'Episcopo Maria, R., Leva, S., Liberatore, G., Lo Re, M., Longoni, M., Lopiano, L., Lorefice, L., Lucchini, Matteo, Lus, G., Maimone, D., Malentacchi, M., Mallucci, G., Malucchi, S., Mancinelli, C. R., Mancinelli, L., Manganotti, P., Maniscalco, T. G., Mantero, V., Marangoni, S., Marastoni, D., Marfia, A. G., Marinelli, F., Marti, A., Martinelli Boneschi, F., Masserano Zoli, F., Matta, F., Mendozzi, L., Meucci, G., Miante, S., Miele, G., Milano, E., Mirabella, Massimiliano, Missione, R., Moccia, M., Montepietra, S., Monti Bragadin, M., Montini, F., Motta, R., Nardone, R., Nicoletti, C. G., Nobile-Orazio, E., Nozzolillo, A., Onofrj, M., Orlandi, R., Palmieri, A., Paolicelli, D., Pasquali, L., Pasto, L., Pedrazzoli, E., Perini, P., Pesci, I., Petracca, M., Petrone, A., Piantadosi, C., Pietroboni, A. M., Pinardi, F., Ponzano, M., Portaccio, E., Pozzato, M., Pozzilli, C., Prosperini, L., Protti, A., Ragonese, P., Rasia, S., Realmuto, S., Repice, A., Rigoni, E., Rilla, M. T., Rinaldi, F., Romano, C. M., Ronzoni, M., Rovaris, M., Ruscica, F., Sabattini, L., Salemi, G., Saraceno, L., Sartori, A., Sbragia, E., Scandellari, C., Scarano Giuditta, I., Scarano, V., Schillaci, V., Sessa, M., Sgarito, C., Sibilia, G., Siciliano, G., Signori, A., Signoriello, E., Sinisi, L., Sireci, F., Sola, P., Solaro, C., Sotgiu, S., Sparaco, M., Stromillo, M. L., Strumia, S., Susani, L. E., Tabiadon, G., Teatini, F., Tomassini, V., Tonietti, S., Torri, C. V., Tortorella, C., Toscano, S., Totaro, R., Trotta, M., Turano, G., Ulivelli, M., Valentino, M., Vaula, G., Vecchio, D., Vercellino, M., Verrengia, E. P., Vianello, M., Virgilio, E., Vitetta, F., Vollaro, S., Zaffaroni, M., Zampolini, M., Zarbo, I. R., Zito, A., Zuliani, L., Lucchini M. (ORCID:0000-0002-0447-2297), Mirabella M. (ORCID:0000-0002-7783-114X), 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., Abbadessa, G., Aguglia, U., Allegorico, L., Allegri, R. B. M., Amato, M. P., Annovazzi, P., Antozzi, C., Appendino, L., Arena, S., Baione, V., Balgera, R., Barcella, V., Baroncini, D., Barrila, C., Bellacosa, A., Bellucci, G., Bergamaschi, R., Bergamaschi, V., Bezzini, D., Biolzi, B., Bisecco, A., Bonavita, S., Borriello, G., Bosa, C., Bosco, A., Bovis, F., Bozzali, M., Brambilla, L., Brescia, M. V., Brichetto, G., Buccafusca, M., Bucciantini, E., Bucello, S., Buscarinu, M. C., Cabboi, M. P., Calabrese, M., Calabria, F., Caleri, F., Camilli, F., Caniatti, L. M., Cantello, R., Capra, R., Capuano, R., Carta, P., Cavalla, P., Celani, M. G., Cellerino, M., Cerqua, R., Chisari, C., Clerici, R., Clerico, M., Cocco, E., Cola, G., Confalonieri, P., Conte, A., Conti, M. Z., Cordano, C., Cordera, S., Corea, F., Correale, C., Cottone, S., Crescenzo, F., Curti, E., D'Ambrosio, A., D'Amico, E., Danni, M. C., D'Arma, A., Dattola, V., de Biase, S., De Luca, G., De Mercanti, S. F., De Mitri, P., De Stefano, N., Della Cava, M., di Napoli, M., Di Sapio, A., Docimo, R., Dutto, A., Evangelista, L., Fanara, S., Ferraro, D., Ferro, M. T., Filippi, M., Fioretti, C., Fratta, M., Frau, J., Fronza, M., Gajofatto, A., Gallo, A., Gallo, P., Gasperini, C., Ghazaryan, A., Giometto, B., Gobbin, F., Govone, F., Granella, F., Grange, E., Grasso, M. G., Guareschi, A., Guaschino, C., Guerrieri, S., Guidetti, D., Iaffaldano, P., Ianniello, A., Iasevoli, L., Imperiale, D., Infante, M. T., Inglese, M., Iodice, R., Iovino, A., Konrad, G., Lanzillo, R., Lapucci, C., Lavorgna, L., L'Episcopo Maria, R., Leva, S., Liberatore, G., Lo Re, M., Longoni, M., Lopiano, L., Lorefice, L., Lucchini, Matteo, Lus, G., Maimone, D., Malentacchi, M., Mallucci, G., Malucchi, S., Mancinelli, C. R., Mancinelli, L., Manganotti, P., Maniscalco, T. G., Mantero, V., Marangoni, S., Marastoni, D., Marfia, A. G., Marinelli, F., Marti, A., Martinelli Boneschi, F., Masserano Zoli, F., Matta, F., Mendozzi, L., Meucci, G., Miante, S., Miele, G., Milano, E., Mirabella, Massimiliano, Missione, R., Moccia, M., Montepietra, S., Monti Bragadin, M., Montini, F., Motta, R., Nardone, R., Nicoletti, C. G., Nobile-Orazio, E., Nozzolillo, A., Onofrj, M., Orlandi, R., Palmieri, A., Paolicelli, D., Pasquali, L., Pasto, L., Pedrazzoli, E., Perini, P., Pesci, I., Petracca, M., Petrone, A., Piantadosi, C., Pietroboni, A. M., Pinardi, F., Ponzano, M., Portaccio, E., Pozzato, M., Pozzilli, C., Prosperini, L., Protti, A., Ragonese, P., Rasia, S., Realmuto, S., Repice, A., Rigoni, E., Rilla, M. T., Rinaldi, F., Romano, C. M., Ronzoni, M., Rovaris, M., Ruscica, F., Sabattini, L., Salemi, G., Saraceno, L., Sartori, A., Sbragia, E., Scandellari, C., Scarano Giuditta, I., Scarano, V., Schillaci, V., Sessa, M., Sgarito, C., Sibilia, G., Siciliano, G., Signori, A., Signoriello, E., Sinisi, L., Sireci, F., Sola, P., Solaro, C., Sotgiu, S., Sparaco, M., Stromillo, M. L., Strumia, S., Susani, L. E., Tabiadon, G., Teatini, F., Tomassini, V., Tonietti, S., Torri, C. V., Tortorella, C., Toscano, S., Totaro, R., Trotta, M., Turano, G., Ulivelli, M., Valentino, M., Vaula, G., Vecchio, D., Vercellino, M., Verrengia, E. P., Vianello, M., Virgilio, E., Vitetta, F., Vollaro, S., Zaffaroni, M., Zampolini, M., Zarbo, I. R., Zito, A., Zuliani, L., Lucchini M. (ORCID:0000-0002-0447-2297), and Mirabella M. (ORCID:0000-0002-7783-114X)

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
2022

23. 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

24. Comparing Natural History of Early and Late Onset Pediatric Multiple Sclerosis

Author

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

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

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

Published
2022

25. MR Imaging Signs of Gadolinium Retention Are Not Associated with Long-Term Motor and Cognitive Outcomes in Multiple Sclerosis

Author

A. Scaravilli, M. Tranfa, G. Pontillo, F. Falco, C. Criscuolo, M. Moccia, S. Monti, R. Lanzillo, V. Brescia Morra, G. Palma, M. Petracca, E. Tedeschi, A. Elefante, A. Brunetti, S. Cocozza, Scaravilli, A., Tranfa, M., Pontillo, G., Falco, F., Criscuolo, C., Moccia, M., Monti, S., Lanzillo, R., Brescia Morra, V., Palma, G., Petracca, M., Tedeschi, E., Elefante, A., Brunetti, A., and Cocozza, S.

Subjects
Radiology, Nuclear Medicine and imaging, Neurology (clinical)
Abstract

Background and purpose: The long-term impact of gadolinium retention in the dentate nuclei of patients undergoing administration of seriate gadolinium-based contrast agents is still widely unexplored. The aim of this study was to evaluate the impact of gadolinium retention on motor and cognitive disability in patients with MS during long-term follow-up. Materials and methods: In this retrospective study, clinical data were obtained from patients with MS followed in a single center from 2013 to 2022 at different time points. These included the Expanded Disability Status Scale score to evaluate motor impairment and the Brief International Cognitive Assessment for MS battery to investigate cognitive performances and their respective changes with time. The association with qualitative and quantitative MR imaging signs of gadolinium retention (namely, the presence of dentate nuclei T1-weighted hyperintensity and changes in longitudinal relaxation R1 maps, respectively) was probed using different General Linear Models and regression analyses. Results: No significant differences in motor or cognitive symptoms emerged between patients showing dentate nuclei hyperintensity and those without visible changes on T1WIs (P = .14 and 0.92, respectively). When we tested possible relationships between quantitative dentate nuclei R1 values and both motor and cognitive symptoms, separately, the regression models including demographic, clinical, and MR imaging features explained 40.5% and 16.5% of the variance, respectively, without any significant effect of dentate nuclei R1 values (P = .21 and 0.30, respectively). Conclusions: Our findings suggest that gadolinium retention in the brains of patients with MS is not associated with long-term motor or cognitive outcomes.

Published
2023

26. Prognostic Markers of Ocrelizumab Effectiveness in Multiple Sclerosis: A Real World Observational Multicenter Study

Author

Roberta Lanzillo, Antonio Carotenuto, Elisabetta Signoriello, Rosa Iodice, Giuseppina Miele, Alvino Bisecco, Giorgia Teresa Maniscalco, Leonardo Sinisi, Felice Romano, Maria Di Gregorio, Luigi Lavorgna, Francesca Trojsi, Marcello Moccia, Mario Fratta, Nicola Capasso, Raffaele Dubbioso, Maria Petracca, Antonio Luca Spiezia, Antonio Gallo, Martina Petruzzo, Marcello De Angelis, Simona Bonavita, Giacomo Lus, Gioacchino Tedeschi, Vincenzo Brescia Morra, Lanzillo, R., Carotenuto, A., Signoriello, E., Iodice, R., Miele, G., Bisecco, A., Maniscalco, G. T., Sinisi, L., Romano, F., Di Gregorio, M., Lavorgna, L., Trojsi, F., Moccia, M., Fratta, M., Capasso, N., Dubbioso, R., Petracca, M., Spiezia, A. L., Gallo, A., Petruzzo, M., De Angelis, M., Bonavita, S., Lus, G., Tedeschi, G., Morra, V. B., Lanzillo, Roberta, Carotenuto, Antonio, Signoriello, Elisabetta, Iodice, Rosa, Miele, Giuseppina, Bisecco, Alvino, Maniscalco, Giorgia Teresa, Sinisi, Leonardo, Romano, Felice, Di Gregorio, Maria, Lavorgna, Luigi, Trojsi, Francesca, Moccia, Marcello, Fratta, Mario, Capasso, Nicola, Dubbioso, Raffaele, Petracca, Maria, Spiezia, Antonio Luca, Gallo, Antonio, Petruzzo, Martina, De Angelis, Marcello, Bonavita, Simona, Lus, Giacomo, Tedeschi, Gioacchino, and Brescia Morra, Vincenzo

Subjects
real-world, ocrelizumab, multiple sclerosi, disease-modifying treatment, progression, General Medicine, multiple sclerosis
Abstract

Pivotal trials showed the effectiveness of the monoclonal antibody ocrelizumab in relapsing and progressive multiple sclerosis (MS). However, data on everyday practice in MS patients and markers of treatment effectiveness are scarce. We aimed to collect real-world data from ocrelizumab-treated MS patients, relapsing-remitting (RR) and progressive MS patients (PMS), including active secondary progressive MS (aSPMS) and primary progressive MS (PPMS) patients, and to explore potential prognostic factors of clinical outcome. Patients were enrolled at MS centres in the Campania region, Italy. We collected clinic-demographic features retrospectively one year before ocrelizumab start (T−1), at ocrelizumab start (T0), and after one year from ocrelizumab start (T1). We explored possible clinical markers of treatment effectiveness in those patients receiving ocrelizumab treatment for at least one year using multilevel-mixed models. We included a total of 383 MS patients (89 RRMS and 294 PMS; 205 females, mean age: 45.8 ± 11.2, disease duration: 12.7 ± 11.6 years). Patients had a mean follow-up of 12.4 ± 8.2 months, and 217 patients completed one-year ocrelizumab treatment. Overall, EDSS increased from T−1 to T0 (coeff. = 0.30, 95% coefficient interval [CI] = 0.19–0.41, p < 0.001) without a further change between T0 and T1 (p = 0.61). RRMS patients did not show an EDSS change between T−1 and T0 nor between T0 and T1. Conversely, PMS patients showed EDSS increase from T−1 to T0 (coeff. = 0.34, 95% CI = 0.22–0.45, p < 0.001) without a further change between T0 and T1 (p = 0.21). PMS patients with a time from conversion shorter than 2 years showed increased EDSS from T−1 to T0 (coeff. = 0.63, 95% CI = 0.18–1.08, p = 0.006) without a further change between T0 and T1 (p = 0.94), whereas PMS patients with a time from conversion longer than 2 years showed increased EDSS from T0 to T1 (coeff. = 0.30, 95% CI = 0.11–0.49, p = 0.002). Naïve patients showed an EDSS decrease between T0 and T1 (coeff. = −0.30, 95% CI = −0.50–−0.09, p = 0.004). In conclusion, our study highlighted that early ocrelizumab treatment is effective in modifying the disability accrual in MS patients.

Published
2022

27. Emergency medical care for multiple sclerosis: A five-year population study in the Campania Region (South Italy)

Author

Marcello Moccia, Giuseppina Affinito, Bruno Ronga, Roberta Giordana, Maria Grazia Fumo, Roberta Lanzillo, Maria Petracca, Antonio Carotenuto, Maria Triassi, Vincenzo Brescia Morra, Raffaele Palladino, Moccia, M., Affinito, G., Ronga, B., Giordana, R., Fumo, M. G., Lanzillo, R., Petracca, M., Carotenuto, A., Triassi, M., Brescia Morra, V., and Palladino, R.

Subjects
treatment, emergency, Fingolimod Hydrochloride, Glatiramer Acetate, Interferon-beta, Multiple sclerosis, Immunosuppressive Agent, Multiple Sclerosis, Relapsing-Remitting, Neurology, death, cost, Multiple Sclerosi, Neurology (clinical), adherence, Human
Abstract

Background: Emergency hospital admissions are common in multiple sclerosis (MS), and can highlight unmet medical needs. Objectives: To evaluate burden, predictors and outcomes of MS emergency admissions. Methods: This is a population-based study, conducted in the Campania Region (South Italy) from 2015 to 2019, using hospital discharge records, drug prescriptions and outpatients. The risk of emergency hospital admissions and the likelihood of worse outcomes were evaluated using the Cox regression and multinomial logistic regression models, respectively, in relation to age, sex, disease-modifying treatments (DMTs), comorbidities and adherence. Results: We recorded 1225 emergency admissions for 1001 patients (out of 5765 prevalent MS patients), overall costing 4,143,764.67 EUR. The risk of emergency admissions increased with age (hazard ratio (HR) = 1.02; 95% confidence interval (CI) = 1.01, 1.03; p Conclusion: With 17% people with MS requiring emergency medical care over 5 years, improved management of DMTs and comorbidities could potentially reduce their medical, social and financial burden.

Published
2022

28. Roman technological expertise in the construction of perpetual buildings: new insights into the wall paintings of a banquet scene from a tomb in Cumae (southern Italy)

Author

Chiara Germinario, Sabrina Pagano, Mariano Mercurio, Francesco Izzo, Alberto De Bonis, Vincenzo Morra, Priscilla Munzi, Marcella Leone, Elisa Conca, Celestino Grifa, Germinario, C., Pagano, S., Mercurio, M., Izzo, F., De Bonis, A., Morra, V., Munzi, P., Leone, M., Conca, E., and Grifa, C.

Subjects
Archeology, Anthropology
Published
2022

29. Alkaline rocks of the Bobaomby volcanic field point to a petrogenetic link between Comoros and northern Madagascar lithosphere

Author

Ciro Cucciniello, Celestino Grifa, Roberto de’Gennaro, Luigi Franciosi, Ivana Rocco, Vincenzo Morra, Leone Melluso, Cucciniello, C., Grifa, C., De'Gennaro, R., Franciosi, L., Rocco, I., Morra, V., and Melluso, L.

Subjects
Basanite, Northern Madagascar, Bobaomby, Nephelinite, Phonolite, Lamprophyre, General Earth and Planetary Sciences, Cumulate rock, Tephrite
Abstract

The Bobaomby volcanic field (10–11 Ma) is the northernmost volcanic area of Madagascar, and is a monogenetic volcanic field comprising outcrops of lava flows, dykes, scoria cones, tuff rings and plugs, widely scattered over an area of roughly 500 km2. The volcanic rocks range in composition from nephelinite, basanite and tephrite, through tephritic phonolite, to F- and Cl-rich peralkaline phonolite (MgO from 13 to 0.01 wt%), and the serial affinity varies from sodic to potassic. A few mica-amphibole-rich lamprophyric dykes have tephritic composition and ultrapotassic affinity. The mafic lavas host intrusive xenoliths with evident cumulate features (wehrlites, composite olivine gabbros s.l., amphibole clinopyroxenites and “kaersutitites”), as well as various types of mantle-derived xenoliths and xenocrysts in the most primitive rocks. The very wide compositional variations of the observed phases (olivine, clinopyroxene, amphibole, oxides, feldspars, feldspathoids, apatite, titanite, aenigmatite and other accessories) in lavas, dykes and cognate xenoliths are fully consistent with the variable degree of differentiation of the host lavas/dykes, and pointing out to limited open-system or polybaric crystallization. The mafic lavas have marked enrichment in incompatible elements and light rare-earth element (LREE) (e.g., Lan/Ybn = 19–27), whereas concave REE patterns are found in the peralkaline phonolites, as a result of removal of accessory titanite starting from tephritic phonolite magmas. The gabbroic/ultramafic xenoliths are interpreted as crustal cumulates of basanitic and tephritic magmas. Several liquid lines of descent in the basanites and tephrites are evident from the trace-element distribution, and from the differing geochemistry of the evolved rocks. The isotopic compositions reach extreme values (e.g., 206Pb/204Pb = 20.065 in the ultrapotassic lamprophyre) when compared to the rest of the Cenozoic/Recent Madagascan volcanic rocks, but similar to those of the Comoros archipelago, suggesting analogies of mantle sources and enrichment processes in the lithosphere of this volcanic archipelago. The origin of the Bobaomby mafic rocks is compatible from a derivation from low degree partial melting of an incompatible element-enriched peridotite source (possibly located in the lowermost lithospheric mantle) rich in volatile-rich phases (pargasite, locally also phlogopite and possibly carbonates), matching the sources of other Cenozoic volcanic areas throughout Madagascar, and perhaps Comoros.

Published
2022

30. Disease-Modifying Treatments and Time to Loss of Ambulatory Function in Patients with Primary Progressive Multiple Sclerosis

Author

Emilio, Portaccio, Mattia, Fonderico, Pietro, Iaffaldano, Luisa, Pastò, Lorenzo, Razzolini, Angelo, Bellinvia, Giovanna, De Luca, Paolo, Ragonese, Francesco, Patti, Vincenzo, Brescia Morra, Eleonora, Cocco, Patrizia, Sola, Matilde, Inglese, Giacomo, Lus, Carlo, Pozzilli, Davide, Maimone, Alessandra, Lugaresi, Paola, Gazzola, Giancarlo, Comi, Ilaria, Pesci, Daniele, Spitaleri, Marta, Rezzonico, Marika, Vianello, Carlo, Avolio, Francesco O, Logullo, Franco, Granella, Marco, Salvetti, Mauro, Zaffaroni, Giuseppe, Lucisano, Massimo, Filippi, Maria, Trojano, Maria Pia, Amato, Alessandra, Protti, Portaccio, E, Fonderico, M, Iaffaldano, P, Pasto, L, Razzolini, L, Bellinvia, A, De Luca, G, Ragonese, P, Patti, F, Brescia Morra, V, Cocco, E, Sola, P, Inglese, M, Lus, G, Pozzilli, C, Maimone, D, Lugaresi, A, Gazzola, P, Comi, G, Pesci, I, Spitaleri, D, Rezzonico, M, Vianello, M, Avolio, C, Logullo, F, Granella, F, Salvetti, M, Zaffaroni, M, Lucisano, G, Filippi, M, Trojano, M, Amato, M, Cavaletti, G, Portaccio, Emilio, Fonderico, Mattia, Iaffaldano, Pietro, Pastò, Luisa, Razzolini, Lorenzo, Bellinvia, Angelo, De Luca, Giovanna, Ragonese, Paolo, Patti, Francesco, Brescia Morra, Vincenzo, Cocco, Eleonora, Sola, Patrizia, Inglese, Matilde, Lus, Giacomo, Pozzilli, Carlo, Maimone, Davide, Lugaresi, Alessandra, Gazzola, Paola, Comi, Giancarlo, Pesci, Ilaria, Spitaleri, Daniele, Rezzonico, Marta, Vianello, Marika, Avolio, Carlo, Logullo, Francesco O, Granella, Franco, Salvetti, Marco, Zaffaroni, Mauro, Lucisano, Giuseppe, Filippi, Massimo, Trojano, Maria, and Amato, Maria Pia

Subjects
Adult, Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Recurrence, Retrospective Studie, Multiple Sclerosi, Disease Progression, Humans, Female, Neurology (clinical), Multiple Sclerosis, Chronic Progressive, Retrospective Studies, Human
Abstract

Importance: Except for ocrelizumab, treatment options in primary progressive multiple sclerosis (PPMS) are lacking. Objective: To investigate the effectiveness of DMTs on the risk of becoming wheelchair dependent in a real-world population of patients with PPMS. Design, Setting, and Participants: This was a multicenter, observational, retrospective, comparative effectiveness research study. Data were extracted on November 28, 2018, from the Italian multiple sclerosis register and analyzed from June to December 2021. Mean study follow-up was 11 years. Included in the study cohort were patients with a diagnosis of PPMS and at least 3 years of Expanded Disability Status Scale (EDSS) evaluations and 3 years of follow-up. Main Outcomes and Measures: The risk of reaching an EDSS score of 7.0 was assessed through multivariable Cox regression models. Exposures: Patients who received DMT before the outcome were considered treated. DMT was assessed as a time-dependent variable and by class of DMT (moderately and highly effective). Results: From a total of 3298 patients with PPMS, 2633 were excluded because they did not meet the entry criteria for the phase 3, multicenter, randomized, parallel-group, double-blind, placebo-controlled study to evaluate the efficacy and safety of ocrelizumab in adults with PPMS (ORATORIO) trial. Among the remaining 665 patients (mean [SD] age, 43.0 [10.7] years; 366 female patients [55.0%]), 409 were further selected for propensity score matching (288 treated and 121 untreated patients). In the matched cohort, during the study follow-up, 37% of patients (152 of 409) reached an EDSS score of 7.0 after a mean (SD) follow-up of 10.6 (5.6) years. A higher EDSS score at baseline (adjusted hazard ratio [aHR], 1.32; 95% CI, 1.13-1.55; P

Published
2022

31. Minero-petrographic investigation on Roman pottery found in a dump in the workshop area of Cumae (southern Italy)

Author

Maria Verde, Alberto De Bonis, Francesco D'Uva, Vincenza Guarino, Francesco Izzo, Concetta Rispoli, Giovanni Borriello, Marco Giglio, Stefano Iavarone, Vincenzo Morra, Verde, M., De Bonis, A., D'Uva, F., Guarino, V., Izzo, F., Rispoli, C., Borriello, G., Giglio, M., Iavarone, S., and Morra, V.

Subjects
Local production, Archeology, Cumae, Wasters, Production indicator, Somma-Vesuvius temper, Roman pottery
Abstract

The focus of this work is the archaeometric investigation of ceramic wasters found in a dump in the workshop area of Cumae that are mostly represented by important production indicators of pottery produced in the Augustean-Tiberian period. The fragments belong to different ceramic classes and productions, such as: pompeian red ware, common cookwares, parts of kiln vault, thin-walled pottery, terra sigillata, large container, bar, and graue Platten. Provenance of the raw materials used for each ceramic class and processing techniques were assessed via a multi-analytical minero-petrographic approach, which includes polarised light microscopy with modal analysis, chemical analysis (XRF), mineralogical analysis (XRPD), microstructural observation via SEM and SEM-EDS for microchemical analysis. All cookwares show different levels of firing and contains non-local temper from the Somma-Vesuvius area, marked by leucite-bearing scoriae and garnet. The geochemical comparisons with clays from the region allowed for definition of the likely clay raw materials sources, in particular for terra sigillata. Most of the samples were locally produced, except for a specimen of graue Platten which, on the contrary, is an exotic sample.

Published
2022

32. The geochemistry of recent Nyamulagira and Nyiragongo potassic lavas, Virunga Volcanic Province, and implications on the enrichment processes in the mantle lithosphere of the Tanzania-Congo craton

Author

S. Minissale, M. Casalini, C. Cucciniello, C. Balagizi, D. Tedesco, G. Boudoire, V. Morra, L. Melluso, Laboratoire Magmas et Volcans (LMV), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement et la société-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Observatoire de Physique du Globe de Clermont-Ferrand (OPGC), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Minissale, S., Casalini, M., Cucciniello, C., Balagizi, C., Tedesco, D., Boudoire, G., Morra, V., and Melluso, L.

Subjects
Potassic rocks, Nyiragongo, Lithosphere, Geochemistry and Petrology, [SDU]Sciences of the Universe [physics], Olivine melilitites, Geology, Basanites, Virunga, Nyamulagira
Abstract

International audience; We here investigate the geochemical and isotopic variability of primitive and evolved magmas of the Nyamulagira and Nyiragongo volcanic complexes (Virunga Volcanic Province, western branch of the east African Rift), including the very last products of the Nyiragongo's May 22, 2021 eruptive event and the Nyamulagira lava lake in February 2020. The different degree of silica undersaturation (i.e., potassic basanites/tephrites at Nyamulagira vs. potassic olivine melilitites/melilite nephelinites at Nyiragongo) and distinct incompatible element enrichment between the two volcanoes (e.g., Zr/Nb = 3.3-4 at Nyamulagira vs. Zr/Nb = 1.2-2.1 at Nyiragongo) are remarkable. Concentration of volatile elements (especially F and S) increases with the degree of magmatic evolution, and is also markedly different at the same level of magma evolution for the products of the two volcanic complexes, suggesting distinct volatile concentration of the primary magmas. The Sr-Nd-Pb isotopic range (e.g., 87Sr/86Sr = 0.7052-0.7059 at Nyamulagira vs. 87Sr/86Sr = 0.7045-0.7047 at Nyiragongo; 206Pb/204Pb = 19.19-19.31 at Nyamulagira vs. 206Pb/204Pb = 19.41-19.75 at Nyiragongo) overlaps with previous analyses obtained in the Virunga Volcanic Province (VVP), and is discussed with respect to other potassic/ultrapotassic rocks from different tectonic settings. The Ba/Nb and La/Nb ratios and Cs concentration of Nyamulagira and Nyiragongo indicate a negligible role for subducted sediments as a mantle-added geochemical component, as instead took place in the source of other primitive potassic/ ultrapotassic rocks such as those of the Roman Volcanic Province. The genesis of the primitive lavas of Nyamulagira and Nyiragongo is related to partial melting of a heterogeneous lithospheric peridotite hosting phlogopite and variable amounts of carbonates, which was moderately to highly enriched in incompatible elements, particularly Nb, Ta, LREE, (K), Ba and Sr. No high-temperature (plume), asthenospheric components or pyroxenites are evident or unambiguously detectable.

Published
2022

33. A banquet scene in a tomb of Cuma (southern Italy): the study of wall paintings to shed light on Roman technological skills in 'building for eternity'

Author

Chiara Germinario, Sabrina Pagano, Mariano Mercurio, Francesco Izzo, Alberto De Bonis, Vincenzo Morra, Priscilla Munzi, Marcella Leone, Elisa Conca, Celestino Grifa, Germinario, C., Pagano, S., Mercurio, M., Izzo, F., De Bonis, A., Morra, V., Munzi, P., Leone, M., Conca, E., and Grifa, C.

Abstract

Excavations at the north-eastern side of the city Cumae (modern Cuma) brought to light the Tomba del Banchetto per l’Eternità, a hypogeum chamber tomb with vaulted ceiling built in tuff blocks dated back to the first decades of the 1st century BCE. The exceptional nature of the discovery, resembling an Oscan tradition, is due to the peculiar decorative scheme, reporting a banquet scene and three funerary beds along with a table, reproducing a sort of triclinium.The investigation performed on decorated plasters, in situ by a spectroscopic approach and in-lab via minero-petrographic techniques, allowed us to infer the production technology of wall paintings and mortar-based support, and the type of pigments used for decorating the tomb.The multi-layered plasters were made with specific mix-designs in the different part of the tomb; similarly, different painting techniques were adopted according to the architectural scheme. In the lower part of the walls, lime cocciopesto mortars adhere on the tuff blocks, likely to lend better hydraulic properties to the mortar-based supports in humid and wet environments. This part of the tomb, as well as the funerary beds, was painted in red using the fresco technique. On the other hand, in the upper part of walls and on the vault, the arriccio layer, containing volcanic sand, was covered with a thick and white intonachino layer composed of lime binder, constituting the support for the pictorial layer, applied with a mezzo fresco technique.The investigation on pigments used for wall paintings points out to the use of a characteristic Roman palette, consisting of pure, natural and synthetic pigments (calcite, red and yellow ochre, hematite, organic black pigments, Egyptian blue), and skilful mixtures of colouring materials (mixture of yellow ochre and organic carbon black for the brown, mixture of kaolinite-rich clay, Egyptian blue, and Fe-oxides for grey and mixture of organic –madder- and inorganic pigments for pink).Geographical Coordinates: 40°51’3.13’’N; 14°3’27.33’’E

Published
2022

34. The early porcelain kilns of Arita: Identification of raw materials and their use from the 17th to the 19th century

Author

Riccardo Montanari, Nobuyuki Murakami, Alberto De Bonis, Philippe Colomban, Maria Francesca Alberghina, Celestino Grifa, Francesco Izzo, Vincenzo Morra, Claudia Pelosi, Salvatore Schiavone, Montanari, R., Murakami, N., De Bonis, A., Colomban, P., Alberghina, M. F., Grifa, C., Izzo, F., Morra, V., Pelosi, C., and Schiavone, S.

Subjects
Biomaterials, TP785-869, Ryumon, Arita clay, Materials Chemistry, Ceramics and Composites, Shirakawa, Clay industries. Ceramics. Glass, Izumiyama, Electronic, Optical and Magnetic Materials, Japanese porcelain
Abstract

Porcelain stone used at the early kilns of Arita, Japan, has never been identified due to the lack of written records. Ryumon and Shirakawa deposits are considered to have possibly been exploited before Izumiyama was discovered in the early 1630s, but there are no records or any previous scientific research aimed at resolving such crucial issue. This work presents the first systematic scientific study of clays from the three deposits and shards excavated at early kiln sites. Portable ED-XRF and SEM-EDS were used to identify the chemical compositions of bodies, glazes, and geochemical characteristics of clays. XRD, TG-DSC, and FTIR-ATR spectroscopy were also used for the mineralogical characterization of clay bodies. Results show that the earliest production was marked by the mineralogical characteristics of the available raw materials. A gradual improvement in material selection and processing will lead to the development of the nigoshide (milky-white) body in the mid-17th century.

Published
2022

35. Correlation between Retinal Vascularization and Disease Aggressiveness in Amyotrophic Lateral Sclerosis

Author

Gilda Cennamo, Daniela Montorio, Francesco Pio Ausiello, Luigifilippo Magno, Rosa Iodice, Alberto Mazzucco, Valentina Virginia Iuzzolino, Gianmaria Senerchia, Vincenzo Brescia Morra, Maria Nolano, Ciro Costagliola, Raffaele Dubbioso, Cennamo, G., Montorio, D., Ausiello, F. P., Magno, L., Iodice, R., Mazzucco, A., Iuzzolino, V. V., Senerchia, G., Brescia Morra, V., Nolano, M., Costagliola, C., and Dubbioso, R.

Subjects
disease progression, OCT, vascular, inflammation, ALS, biomarker, eye, angiography, choroid, retinal nerve fiber layer, Medicine (miscellaneous), General Biochemistry, Genetics and Molecular Biology
Abstract

Abnormalities in retinal vascularization and neural density have been found in many neurodegenerative diseases; however, conflicting results are described in Amyotrophic Lateral Sclerosis (ALS). The aim of the present study was, therefore, to systematically analyze retinal layers and vascularization by means of spectral-domain (SD-OCT) and optical coherence tomography angiography (OCT-A) in ALS patients. We enrolled 48 ALS patients and 45 healthy controls. ALS patients were divided into three groups: slow progressors (n = 10), intermediate progressors (n = 24) and fast progressors (n = 14), according to the disease progression rate. For SD-OCT, we evaluated the Subfoveal choroidal thickness (SFCT), ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL). Regarding the OCT-A, we assessed the vessel density (VD) in superficial and deep capillary plexuses, radial peripapillary capillary plexus, choriocapillary and the foveal avascular zone (FAZ) area. SD-OCT exam did not show any significant differences in GCC and RNFL thickness between patients and controls and among the three ALS groups. The SFCT was statistically greater in patients compared with controls (357.95 ± 55.15 µm vs. 301.3 ± 55.80 µm, p < 0.001); interestingly, the SFCT was thicker in patients with slow and intermediate disease progression than in those with fast disease progression (394.45 ± 53.73 µm vs. 393.09 ± 42.17 µm vs. 267.71 ± 56.24 µm, p < 0.001). OCT-A did not reveal any significant results. Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-r) and disease duration did not correlate with any of the OCT parameters, except for SFCT with ALSFRS-r (r = 0.753, p = 0.024). This study demonstrated the possible association between choroidal thickness and disease activity in ALS. OCT could be a useful biomarker in the management of the disease.

Published
2022

36. The Mediterranean trading centre of Vivara (southern Italy): New insights on the production and circulation of pottery during the Bronze Age (16th – 15th century BCE)

Author

Chiara Germinario, Alberto De Bonis, Celestino Grifa, Vincenza Guarino, Massimiliano Marazzi, Carla Pepe, Concetta Rispoli, Monica Scotto di Covella, Vincenzo Morra, Germinario, C., De Bonis, A., Grifa, C., Guarino, V., Marazzi, M., Pepe, C., Rispoli, C., Scotto di Covella, M., and Morra, V.

Subjects
Vivara, Archeology, Tourmaline, Bronze age pottery, Mediterranean commercial route, Phlegraean field
Abstract

The important discoveries at the recent archaeological excavations at Punta d'Alaca site in the west side of the Vivara island (Campania region) highlighted the presence of a Bronze Age thriving settlement attesting the development of a flourishing ceramic production, mainly specialized in the manufacturing of common wares. The archaeometric study performed on twenty representative samples by means of chemical and minero-petrographic techniques revealed that pottery was produced in-situ; however, locally-manufactured vessels here coexisted with imported ones. Coarse-textured, local potteries were made by low-CaO clays mixed with volcanic temper consistent with the volcanic products of Campanian volcanoes. The firing (likely a pit firing) was done in rough conditions, as proved by mineralogical evidence that suggest variable firing temperatures. In fact, low firing temperatures (

Published
2022

37. Ceramic building materials from the ancient Témesa (Calabria region, Italy): Raw materials procurement, mix-design and firing processes from the Hellenistic to Roman period

Author

Chiara Germinario, Alberto De Bonis, Filippo Barattolo, Luigi Cicala, Luigi Franciosi, Francesco Izzo, Alessio Langella, Mariano Mercurio, Vincenzo Morra, Bianca Russo, Ilaria Cicchiello, Celestino Grifa, Germinario, C., De Bonis, A., Barattolo, F., Cicala, L., Franciosi, L., Izzo, F., Langella, A., Mercurio, M., Morra, V., Russo, B., Cicchiello, I., and Grifa, C.

Subjects
Calabria region, Archeology, Ceramic building material, Pian della Tirena, Ceramic technology, Provenance of raw materials
Abstract

Ceramic building materials (CBM) are interesting archaeological items for gathering the material culture identity and urban setting of the ancient populations since their production is generally related to the local availability of clayey raw materials and advancements of technological skills of ancient makers. This paper investigates the Hellenistic and Roman productions of ceramic building materials from the archaeological site of Témesa on the Tyrrhenian coastline of Calabria region (southern Italy), a settlement where a flourishing ceramic tradition has been attested for all of its occupation phases, from the late Archaic to the Roman period. Here, the local availability of clayey and sandy raw materials permitted the development of a thriving worksite. A combined study of mineralogical, petrographic and micropaleontological features of archaeological samples and geological raw materials collected nearby the archaeological settlement, permitted to constrain the raw materials sources, and investigate the technological level achieved between the second half of the 4th century BCE and the 3rd century CE. This study highlighted that most of CBM was made by mixing sands from a nearby fluvial deposit with upper Miocene clayey raw materials. Chemical composition and micropaleontological investigation of the foraminiferal content of archaeological samples and clays validated the possible exploitation of local raw materials. Textural parameters and the mineralogical assemblage of temper grains, characterized by the peculiar presence of metamorphic lithics, also attested the use of Savuto river sands. Ceramic technology accounts for a firing process at reasonably high temperatures, evidencing the good technological level of production. Moreover, the presence of samples characterized by mix-designs and mineralogical assemblages consistent with geological materials from Campania region witnesses the importation of ceramic materials from other sites, suggesting the existence of operating trades as already attested for other sites of Tyrrhenian coast.

Published
2022

38. Association between CD20 + T lymphocytes and neuropsychological findings in multiple sclerosis.

Author

Esposito A, Falco F, Scalia G, Gentile L, Spiezia AL, Corsini G, Manganiello R, Eliano M, Lamagna F, Moccia M, Petracca M, Lanzillo R, Brescia Morra V, and Carotenuto A

Abstract

Background and Purpose: CD20 + T lymphocytes are a subset of circulating T cells presenting the CD20 + receptor, a molecular marker of B lineage. CD20 + T lymphocytes are thought to play a pivotal role in multiple sclerosis (MS) pathology, especially at progressive stages. We aimed to investigate the correlation between CD20 + T lymphocytes and neuropsychological features (i.e., cognition, depression, anxiety, fatigue, and sleep quality) in MS patients., Methods: We enrolled 90 MS patients. Each patient underwent cognitive assessment (Brief International Cognitive Assessment for Multiple Sclerosis) and psychometric assessment (modified Fatigue Impact Scale, Beck Anxiety Inventory, Beck Depression Inventory, Pittsburgh Sleep Quality Index). Cognitive status was defined through the cerebral functional score., Results: Forty-four of 90 patients were relapsing-remitting (49%) and 46 were progressive patients (51%). Seventy patients (18.9%) showed CD20 + T lymphocytes in peripheral blood with a mean level of 0.38 ± 1.2%. Patients with CD20 + T lymphocytes were more likely to be at progressive phases (76.5% vs. 23.5%, p = 0.02) and showed a higher Expanded Disability Status Scale score (median [range] = 6.0 [1.5-7.5] vs. 3.5 [1-7.5], p = 0.001). Moreover, patients with CD20 + T lymphocytes showed worse cognitive functioning (p = 0.004), higher global fatigue symptoms (p = 0.02), higher cognitive fatigue (p = 0.01), higher psychosocial fatigue (p = 0.005), and a trend toward worse sleep quality (p = 0.06)., Conclusions: The presence of CD20 + T lymphocytes in the peripheral blood of MS patients was associated with worse neuropsychological functioning and progressive disease stages. Peripheral CD20 + T lymphocytes could potentially serve as markers for both disease progression and development of fatigue in MS patients., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Published
2024
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39. Disability trajectories by progression independent of relapse activity status differ in pediatric, adult and late-onset multiple sclerosis.

Author

Simone M, Lucisano G, Guerra T, Paolicelli D, Rocca MA, Brescia Morra V, Patti F, Annovazzi P, Gasperini C, De Luca G, Ferraro D, Margari L, Granella F, Pozzilli C, Romano S, Perini P, Bergamaschi R, Coniglio MG, Lus G, Vianello M, Lugaresi A, Portaccio E, Filippi M, Amato MP, and Iaffaldano P

Subjects
Humans, Male, Female, Adult, Child, Young Adult, Adolescent, Recurrence, Middle Aged, Longitudinal Studies, Italy, Follow-Up Studies, Registries, Multiple Sclerosis, Relapsing-Remitting physiopathology, Disease Progression, Age of Onset, Disability Evaluation, Multiple Sclerosis physiopathology
Abstract

Background: To compare Expanded Disability Status Scale (EDSS) trajectories over time between Multiple Sclerosis (MS) groups with pediatric (POMS), adult (AOMS) and late (LOMS) onset, and between patients with and without progression independent of relapse activity (PIRA)., Methods: Patients with a first visit within 1 year from onset, ≥ 5-year follow-up and ≥ 1 visit every 6 months were selected from the Italian MS Register. Adjusted disability trajectories were assessed by longitudinal models for repeated measures. Comparisons between groups and between patients with and without PIRA in subgroups were performed by evaluating the yearly differences of mean EDSS score changes versus baseline (delta-EDSS). A first CDA event was defined as a 6-months confirmed disability increase from study baseline, measured by EDSS (increase ≥ 1.5 points with baseline EDSS = 0; ≥ 1.0 with baseline EDSS score ≤ 5.0 and ≥ 0.5 point with baseline EDSS > 5.5). PIRA was defined as a CDA event occurring more than 90 days after and more than 30 days before the onset of a relapse., Results: 3777 MS patients (268 POMS, 3282 AOMS, 227 LOMS) were included. The slope of disability trajectories significantly diverged in AOMS vs POMS starting from the second year of follow-up (Year 2: delta2-EDSS 0.18 (0.05; 0.31), p = 0.0054) and then mean delta2-EDSS gradually increased up to 0.23 (0.07; 0.39, p = 0.004) at year 5. Patients with PIRA had significant (p < 0.0001) steeper increase in EDSS scores than those without PIRA in all groups, although in POMS, the disability trajectories began to diverge later and at a lesser extent with delta-EDSS score of 0.48 vs 0.83 in AOMS and 1.57 in LOMS, at 3 years after the first PIRA., Conclusions: Age is relevant in determining disability progression in MS. POMS shows a less steep increase in EDSS scores over time than older patients. The effect of PIRA in accelerating EDSS progression is less pronounced in POMS than in AOMS and LOMS., (© 2024. The Author(s).)

Published
2024
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40. Being highly sensitive person negatively impacts on cognitive and psychosocial fatigue in multiple sclerosis patients: A cross-sectional, monocenter study.

Author

Falco F, Lamagna F, Esposito A, Eliano M, Spiezia AL, Petracca M, Caliendo D, Moccia M, Lanzillo R, Brescia Morra V, and Carotenuto A

Subjects
Humans, Female, Male, Adult, Cross-Sectional Studies, Middle Aged, Personality physiology, Cognitive Dysfunction etiology, Cognitive Dysfunction physiopathology, Fatigue etiology, Fatigue physiopathology, Multiple Sclerosis complications, Multiple Sclerosis psychology
Abstract

Background: Fatigue is a common symptom in Multiple Sclerosis (MS), but its determinants are not clarified yet. Sensory processing sensitivity (SPS) is a personality trait characterized by enhanced sensitivity towards endogenous and exogenous stimuli, and higher attention toward minimal stimuli, resulting in overarousal and fatigue., Objective: to evaluate the association between SPS and fatigue in MS patients., Methods: 192 consecutive MS patients (age of 43.3 ± 12.1 years; females 67.2 %; median EDSS of 2.5 (0 - 7)) underwent clinical (EDSS, age, gender), cognitive (BICAMS, Trial Making Test [TMT]), psychosocial (Beck Anxiety Inventory [BAI], Beck Depression Inventory [BDI], Modified Fatigue Impact Scale [MFIS]) and sensitivity evaluation (Highly Sensitive Person [HSP]Scale). Patients were classified as HSP if the score was greater than 14. A stepwise regression model was applied to explore association between SPS and MFIS total scores and sub-scores, by accounting for age, gender, education, EDSS, Cerebral FS scores, TMT-Part A and part B scores, BAI, BDI, and Pittsburgh Sleep Quality Index (PSQI)., Results: Total HSP was 17.2 ± 6.8 and 129 patients (67 %) were classified as highly sensitive persons (HSP). HSP patients were more female patients (p = 0.02) with a longer disease duration (p = 0.03). HSP people showed higher total MFIS score (27.6 ± 20.6 vs 13.2 ± 14.1, p < 0.001), higher physical MFIS score (p < 0.001), higher cognitive MFIS score (p < 0.001), higher psychosocial MFIS score (p < 0.001) vs non-HSP patients. Higher total MFIS was associated with SPS trait (coeff. 6.9, p = 0.006). Specifically, SPS trait was associated with higher cognitive MFIS (coeff. 5.3, p < 0.001) and higher psychosocial MFIS (coeff. 0.7, p = 0.02)., Conclusion: SPS was associated with fatigue. Since SPS could be easily and quickly assessed in clinical settings, SPS could unveil a higher propensity of a patient toward fatigue occurrence over the disease course and could provide hints for possible preventive cognitive behavior therapy., Competing Interests: Declaration of competing interest MM has received research grants from the ECTRIMS-MAGNIMS, the UK MS Society, and Merck; honoraria from Biogen, BMS Celgene, Ipsen, Janssen, Merck, Novartis, Roche, and Sanofi-Genzyme. AC has received research grants from Almirall, research grants from ECTRIMS-MAGNIMS and honoraria from Almirall, Biogen, Roche, Sanofi-Genzyme, Merck, Ipsen and Novartis. MP has received research grants from Italian MS Foundation and Baroni Foundation, honoraria from HEALTH&LIFE S.r.l. and Biogen and sponsorship for travel/meeting expenses from Novartis, Roche and Merck. DC has received research grant from Merck. RL has received honoraria from Biogen, Merck, Novartis, Roche, and Teva. VBM has received research grants from the Italian MS Society, and Roche, and honoraria from Bayer, Biogen, Merck, Mylan, Novartis, Roche, Sanofi-Genzyme, and Teva. AE, ME, FL, ALS, FF have nothing to disclose., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Published
2024
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41. Pediatric-onset Multiple Sclerosis treatment: a multicentre observational study comparing natalizumab with fingolimod.

Author

Carotenuto A, Di Monaco C, Papetti L, Borriello G, Signoriello E, Masciulli C, Tomassini V, De Luca G, Ianniello A, Lus G, Novarella F, Spiezia AL, Di Somma D, Moccia M, Petracca M, Iacovazzo C, Servillo G, Portaccio E, Triassi M, Amato MP, Pozzilli C, Valeriani M, Brescia Morra V, and Lanzillo R

Subjects
Humans, Female, Male, Adolescent, Child, Longitudinal Studies, Immunosuppressive Agents therapeutic use, Age of Onset, Magnetic Resonance Imaging, Disability Evaluation, Treatment Outcome, Italy, Natalizumab therapeutic use, Fingolimod Hydrochloride therapeutic use, Immunologic Factors administration & dosage, Multiple Sclerosis drug therapy
Abstract

Background: Pediatric-onset Multiple Sclerosis (POMS) patients show more inflammatory disease compared with adult-onset MS. However, highly effective treatments are limited with only fingolimod being approved in Italy and natalizumab prescribed as off-label treatment., Objectives: to compare the efficacy of natalizumab versus fingolimod in POMS., Methods: This is an observational longitudinal multicentre study including natalizumab- and fingolimod-treated POMS patients (N-POMS and F-POMS, respectively). We collected Annual Relapse Rate (ARR), Expanded Disability Status Scale (EDSS), Symbol Digit Modality Test (SDMT), and MRI activity at baseline (T0), 12-18 months (T1), and last available observation (T2)., Results: We enrolled 57 N-POMS and 27 F-POMS patients from six Italian MS Centres. At T0, N-POMS patients showed higher ARR (p = 0.03), higher EDSS (p = 0.003) and lower SDMT (p = 0.04) at baseline compared with F-POMS. Between T 0 and T 1 ARR improved for both N-POMS and F-POMS (p < 0.001), while EDSS (p < 0.001) and SDMT (p = 0.03) improved only for N-POMS. At T 2 (66.1 ± 55.4 months) we collected data from 42 out of 57 N-POMS patients showing no further ARR decrease., Conclusion: Both natalizumab and fingolimod showed high and sustained efficacy in controlling relapses and natalizumab also associated to a disability decrease in POMS. This latter effect might be partly mediated by the high inflammatory activity at baseline in N-POMS., (© 2024. The Author(s).)

Published
2024
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42. Dysphagia assessment in patients with multiple sclerosis - an additional piece to disability burden.

Author

Ranucci D, Falco F, Nicolella V, Di Monaco C, Migliaccio L, Lamagna F, Caracciolo F, Eliano M, Petracca M, Moccia M, Brescia Morra V, Carotenuto A, and Lanzillo R

Abstract

Objective: People with multiple sclerosis (MS) might experience symptoms that are usually underestimated. Dysphagia should be evaluated within the Expanded Disability Status Scale (EDSS), but clinicians often do not assess it properly. The objectives of this study are as follows: To assess the prevalence of dysphagia in patients with MS utilizing the Swallowing Disturbance Questionnaire (SDQ); to examine the correlation with the EDSS; to investigate the relationship between dysphagia and clinico-demographic characteristics of MS., Methods: In total, 177 MS patients underwent evaluations with EDSS, SDQ, cognitive functions, anxiety, depression, fatigue, and sleep quality tests. We compared clinico-demographic data of patients with and without dysphagia and native-EDSS to SDQ-EDSS., Results: Out of the 177 MS patients, 56% of individuals were identified having dysphagia according to the SDQ with 41 patients exhibiting mild dysphagia, 31 showing moderate dysphagia and 27 patients having severe dysphagia. Only 6 patients had dysphagia recorded in the EDSS. SDQ-EDSS scores were significantly higher than native scores. Dysphagia was associated with depressive symptoms and sleep quality., Interpretation: Dysphagia affects up to 56% of MS patients. The SDQ questionnaire is useful for identifying dysphagia, which can help in capturing disease progression and preventing complications like aspiration pneumonia. The SDQ-EDSS was higher than the native-EDSS, reflecting the poor ability of the native-EDSS to evaluate certain symptoms such as dysphagia. The SDQ correlated with depressive symptoms, which are associated with a greater perception of MS symptoms, and poor sleep quality, which could be associated with the triggering of pathogenic mechanisms responsible for disease progression., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Published
2024
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43. Effects of fingolimod on focal and diffuse damage in patients with relapsing-remitting multiple sclerosis - The "EVOLUTION" study.

Author

Filippi M, Pagani E, Turrini R, Bartezaghi M, Brescia Morra V, Borriello G, Torri Clerici V, Mirabella M, Pasquali L, Patti F, Totaro R, Gallo P, and Rocca MA

Subjects
Humans, Female, Male, Adult, Middle Aged, Prospective Studies, Immunosuppressive Agents therapeutic use, Disease Progression, Brain diagnostic imaging, Brain pathology, Brain drug effects, White Matter diagnostic imaging, White Matter pathology, White Matter drug effects, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis, Relapsing-Remitting diagnostic imaging, Multiple Sclerosis, Relapsing-Remitting pathology, Fingolimod Hydrochloride therapeutic use, Magnetic Resonance Imaging
Abstract

Background and Objectives: In multiple sclerosis (MS), MRI markers can measure the potential neuroprotective effects of fingolimod beyond its anti-inflammatory activity. In this study we aimed to comprehensively explore, in the real-word setting, whether fingolimod not only reduces clinical/MRI inflammatory activity, but also influences the progression of irreversible focal and whole brain damage in relapsing-remitting [RR] MS patients., Methods: The "EVOLUTION" study, a 24-month observational, prospective, single-arm, multicenter study, enrolled 261 RRMS patients who started fingolimod at 32 Italian MS centers and underwent biannual neurological assessments and annual MRI evaluations. Study outcomes included the proportions of evaluable RRMS patients achieving at 24 months: (1) no new/enlarging T 2 -hyperintense white matter (WM) lesions and/or clinical relapses; (2) a modified classification of "No Evidence of Disease Activity 4" ("modified NEDA-4") defined as no new/enlarging T 2 -hyperintense WM lesions, clinical relapses, and 6-month confirmed disability progression, and a yearly percentage lateral ventricular volume change on T 2 -FLAIR images < 2%; (3) less than 40% of active lesions at baseline and month 12 evolving to permanent black holes (PBHs)., Results: At month 24, 76/160 (47.5%; 95% confidence interval [CI] = 39.8%;55.2%) RRMS patients had no clinical/MRI activity. Thirty-nine of 170 RRMS patients (22.9%; 95% CI = 16.6%;29.3%) achieved "modified NEDA-4" status. Forty-four of 72 RRMS patients (61.1%; 95% CI = 49.8%;72.4%) had less than 40% of active WM lesions evolving to PBHs. The study confirmed the established safety and tolerability profile of fingolimod., Discussion: By comparing our results with those from the literature, the EVOLUTION study seems to indicate a neuroprotective effect of fingolimod, limiting inflammatory activity, brain atrophy and PBH development., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2024
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44. A comparison of natalizumab and ocrelizumab on disease progression in multiple sclerosis.

Author

Iaffaldano P, Lucisano G, Guerra T, Paolicelli D, Portaccio E, Inglese M, Foschi M, Patti F, Granella F, Romano S, Cavalla P, De Luca G, Gallo P, Bellantonio P, Gallo A, Montepietra S, Di Sapio A, Vianello M, Quatrale R, Spitaleri D, Clerici R, Torri Clerici V, Cocco E, Brescia Morra V, Marfia GA, Boccia VD, Filippi M, Amato MP, and Trojano M

Subjects
Humans, Female, Male, Adult, Middle Aged, Multiple Sclerosis drug therapy, Multiple Sclerosis, Relapsing-Remitting drug therapy, Registries, Italy, Natalizumab adverse effects, Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized pharmacology, Antibodies, Monoclonal, Humanized administration & dosage, Disease Progression, Immunologic Factors adverse effects, Immunologic Factors pharmacology, Immunologic Factors administration & dosage
Abstract

Objective: No direct comparisons of the effect of natalizumab and ocrelizumab on progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) events are currently available. We aimed to compare the risk of achieving first 6 months confirmed PIRA and RAW events and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 in a cohort of naïve patients treated with natalizumab or ocrelizumab from the Italian Multiple Sclerosis Register., Methods: Patients with a first visit within 1 year from onset, treated with natalizumab or ocrelizumab, and ≥3 visits were extracted. Pairwise propensity score-matched analyses were performed. Risk of reaching the first PIRA, RAW, and EDSS 4.0 and 6.0 events were estimated using multivariable Cox proportional hazards models. Kaplan-Meier curves were used to show cumulative probabilities of reaching outcomes., Results: In total, 770 subjects were included (natalizumab = 568; ocrelizumab = 212) and the propensity score-matching retrieved 195 pairs. No RAW events were found in natalizumab group and only 1 was reported in ocrelizumab group. A first PIRA event was reached by 23 natalizumab and 25 ocrelizumab exposed patients; 7 natalizumab- and 10 ocrelizumab-treated patients obtained an irreversible EDSS 4.0, while 13 natalizumab- and 15 ocrelizumab-treated patients reached an irreversible EDSS 6.0. No differences between the two groups were found in the risk (HR, 95%CI) of reaching a first PIRA (1.04, 0.59-1.84; p = 0.88) event, an irreversible EDSS 4.0 (1.23, 0.57-2.66; p = 0.60) and 6.0 (0.93, 0.32-2.68; p = 0.89)., Interpretation: Both medications strongly suppress RAW events and, in the short term, the risk of achieving PIRA events, EDSS 4.0 and 6.0 milestones is not significantly different., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Published
2024
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45. Progression independent of relapse activity in relapsing multiple sclerosis: impact and relationship with secondary progression.

Author

Portaccio E, Betti M, De Meo E, Addazio I, Pastò L, Razzolini L, Totaro R, Spitaleri D, Lugaresi A, Cocco E, Onofrj M, Di Palma F, Patti F, Maimone D, Valentino P, Torri Clerici V, Protti A, Ferraro D, Lus G, Maniscalco GT, Brescia Morra V, Salemi G, Granella F, Pesci I, Bergamaschi R, Aguglia U, Vianello M, Simone M, Lepore V, Iaffaldano P, Comi G, Filippi M, Trojano M, and Amato MP

Subjects
Humans, Male, Female, Adult, Middle Aged, Registries, Recurrence, Italy epidemiology, Follow-Up Studies, Disease Progression, Multiple Sclerosis, Relapsing-Remitting physiopathology, Multiple Sclerosis, Relapsing-Remitting epidemiology, Disability Evaluation
Abstract

Objectives: We investigated the occurrence and relative contribution of relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) to confirmed disability accrual (CDA) and transition to secondary progression (SP) in relapsing multiple sclerosis (MS)., Methods: Relapsing-onset MS patients with follow-up > / = 5 years (16,130) were extracted from the Italian MS Registry. CDA was a 6-month confirmed increase in Expanded Disability Status Scale (EDSS) score. Sustained disability accumulation (SDA) was a CDA with no EDSS improvement in all subsequent visits. Predictors of PIRA and RAW and the association between final EDSS score and type of CDA were assessed using logistic multivariable regression and multivariable ordinal regression models, respectively., Results: Over 11.8 ± 5.4 years, 16,731 CDA events occurred in 8998 (55.8%) patients. PIRA (12,175) accounted for 72.3% of CDA. SDA occurred in 8912 (73.2%) PIRA and 2583 (56.7%) RAW (p < 0.001). 4453 (27.6%) patients transitioned to SPMS, 4010 (73.2%) out of 5476 patients with sustained PIRA and 443 (24.8%) out of 1790 patients with non-sustained PIRA. In the multivariable ordinal regression analysis, higher final EDSS score was associated with PIRA (estimated coefficient 0.349, 95% CI 0.120-0.577, p = 0.003)., Discussion: In this real-world relapsing-onset MS cohort, PIRA was the main driver of disability accumulation and was associated with higher disability in the long term. Sustained PIRA was linked to transition to SP and could represent a more accurate PIRA definition and a criterion to mark the putative onset of the progressive phase., (© 2024. The Author(s).)

Published
2024
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46. Ocrelizumab in MS patients with persistence of disease activity after alemtuzumab: A multi-center Italian study.

Author

Lapucci C, Frau J, Cocco E, Coghe G, Petracca M, Lanzillo R, Brescia Morra V, Nicoletti CG, Landi D, Marfia G, Vercellino M, Cavalla P, Bianco A, Mirabella M, Torri Clerici V, Tomas E, Ferrò MT, Grossi P, Nozzolillo A, Moiola L, Zaffaroni M, Ronzoni M, Pinardi F, Novi G, Cellerino M, Uccelli A, and Inglese M

Subjects
Humans, Female, Male, Adult, Italy, Retrospective Studies, Middle Aged, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis drug therapy, Follow-Up Studies, Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized therapeutic use, Alemtuzumab adverse effects, Immunologic Factors adverse effects
Abstract

Background: The reason why some multiple sclerosis (MS) patients show disease activity after alemtuzumab (ALM) is still unclear, but ocrelizumab (OCR) could represent an interesting sequential therapeutic approach., Objectives: To investigate safety and efficacy of OCR in MS patients with disease activity after two ALM courses., Methods: Observational retrospective multi-centers Italian cohort study., Results: Seventy-two subjects were included. Mean follow-up (FU) was 2.4 (±1) years. Forty-five patients (62.5%) experienced at least one adverse event (AE), with infections accounting for 96.7% of cases. A reduction in total lymphocytes was observed between OCR start and 6 months FU, driven by BCD19+ lymphocytes depletion ( p < 0.001). Immunoglobulin M (IgM) levels decreased between OCR start and 6 months FU ( p < 0.001). At 2-year FU, relapse, magnetic resonance imaging (MRI) activity and disability worsening-free survival were 92.1%, 90.8%, and 89.2%. The evidence of inflammatory activity between the two ALM courses was associated with higher risk of relapse, MRI activity, and NEDA-3 status loss in relapsing-remitting multiple sclerosis (RRMS; p = 0.02, p = 0.05, p = 0.01, respectively)., Conclusions: OCR after two ALM courses seemed to be safe and effective. Early IgM hypogammaglobulinemia occurred in a high proportion of patients. The evidence of inflammatory activity between ALM courses seemed to increase the risk of MS re-activation on OCR treatment., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: C. Lapucci has received honoraria for speaking, travel grants, and for participating in the advisory board from Merck, Sanofi, Novartis, Roche, Alexion. J. Frau served on scientific advisory boards for Biogen and Genzyme, and has received honoraria as a speaker from Merck Serono, Genzyme, Biogen, and Teva. E. Cocco reported grants, personal fees, and non-financial support from Biogen and Merck; personal fees and non-financial support from Novartis; grants from Roche; and personal fees from Genzyme. G. Coghe received honoraria for consultancy or speaking from Biogen, Novartis, Sanofi, Genzyme, Serono, Teva, and Almirall. M. Petracca has received travel/meeting expenses from Novartis, Janssen, Roche, and Merck; speaking honoraria from HEALTH&LIFE S.r.l., AIM Education S.r.l., Biogen, Novartis, and FARECOMUNICAZIONE E20; honoraria for consulting services and advisory board participation from Biogen; research grants from Baroni Foundation and the Italian Ministry of University and Research. R. Lanzillo has received honoraria from Biogen, Merck, Novartis, Roche, and Teva. V. Brescia Morra has received research grants from the Italian MS Society and Roche, and honoraria from Bayer, Biogen, Merck, Mylan, Novartis, Roche, Sanofi-Genzyme, and Teva. C.G. Nicoletti received travel funding from Biogen, Merck Serono, Sanofi-Genzyme, Roche, Teva, Novartis, Bristol Mayer Squibb, Janssen, Almirall and consultation fees from Sanofi, Almirall, Merck- Serono, Roche, Novartis, and Biogen. She is a sub-investigator in clinical trials being conducted for Biogen, Merck Serono, Roche, Biogen, Sanofi, Novartis, Teva, Bristol Mayer Squibb. D. Landi has received travel funding from Biogen, Merck Serono, Sanofi, Teva, Bristol Myers Squibb, Mylan; speaking or consultations fees from Sanofi, Merck Serono, Teva, Biogen, Roche, Novartis, Bristol Myers Squibb, BayerSchering. G. Marfia has received travel funding, speaking or consultation fees from Almirall, Bayer-Schering, Biogen, Sanofi, Merck Serono, Novartis, Teva, Mylan, Bristol Mayers Squibb and research grants from Roche and Biogen. M. Vercellino has received congress grants, speaker fees and advisory board fees from Merck-Serono, Novartis, Roche, Biogen, Sanofi Genzyme. P. Cavalla has received honoraria as speaker or travel grants to attend national and international conferences or consultation for advisory boards from Alexion, Almirall, Bayer Schering, Biogen, Cellgene-BMS, Merck-Serono, Teva, Roche, Novartis, Sanof-Genzyme, and Janssen. A. Bianco has received honoraria for speaking, advisory board/consulting from Biogen, Novartis, Merck Serono, Roche, Sanofi Genzyme. M. Mirabella has received honoraria for speaking, advisory board/consulting from Biogen, Novartis, Merck Serono, Roche, Almirall, Sanofi Genzyme, Janssen, Bristol-Myers Squibb, Viatris, Alexion. He is principal investigator in clinical trials for Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, CSL Behring, Ultragenix, Argenx. V. Torri Clerici acted as an Advisory Board member of Biogen Idec, Novartis, Merck Serono, Roche, Sanofi Genzyme, Almirall, Lundbeck and Bristol Myers Squibb; she received funding for traveling and honoraria for speaking or writing from Novartis, Sanofi Genzyme, Horizon, Merck Serono, Roche, Bristol Myers Squibb, Janssen and Almirall. She received support for research project by Almirall. E. Tomas received funding for work contract from Roche. M.T. Ferrò has received consultancy fees or speaker compensation from Sanofi, Bristol, Biogen Idec, and Novartis. L. Moiola has received honoraria for speaking and for participating in advisory board from Merck, Celgene, Biogen, Sanofi, Novartis, Roche, Alexion. M. Zaffaroni has received advisory board membership, speakers honoraria, travel support, research grants, consulting fees or clinical trial support from Actelion, Almirall, Bayer Schering, Biogen, Celgene, Excemed, Genzyme, Merck, Novartis, Sanofi, Roche, Teva. M. Ronzoni has received travel grants for congresses participation from Biogen, Genzyme, Novartis e Merck. G. Novi has received speaker honoraria from Merck, Novartis, Roche, Alexion. M. Cellerino has received consulting fees from Novartis, Genzyme, Teva and Zambon. A. Uccelli has received grants (to his institution) from FISM, Biogen, Roche, Alexion, and Merck Serono and has participated on a data safety monitoring board or advisory board (to his institution) for BD, Biogen, Iqvia, Sanofi, Roche, Alexion, and Bristol Myers Squibb. M. Inglese received grants from NIH, NMSS, and FISM; received fees for consultation from BMS, Janssen, Roche, Genzyme, Merck, Biogen and Novartis. P. Grossi, A. Nozzolillo, and F. Pinardi have nothing to disclose.

Published
2024
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47. The ocrelizumab wearing-off phenomenon is associated with reduced immunomodulatory response and increased neuroaxonal damage in multiple sclerosis.

Author

Monteiro I, Nicolella V, Fiorenza M, Novarella F, Carotenuto A, Lanzillo R, Mauriello L, Scalia G, Castaldo G, Terracciano D, Brescia Morra V, and Moccia M

Subjects
Humans, Female, Male, Middle Aged, Adult, Cross-Sectional Studies, Multiple Sclerosis drug therapy, Multiple Sclerosis immunology, Multiple Sclerosis blood, Neurofilament Proteins blood, Antibodies, Monoclonal, Humanized pharmacology, Antibodies, Monoclonal, Humanized administration & dosage, Immunologic Factors pharmacology, Immunologic Factors administration & dosage
Abstract

Objective: The wearing-off phenomenon is common in people with multiple sclerosis (MS) treated with ocrelizumab. We aim to evaluate the presence and severity of wearing-off to ocrelizumab in relation to demographic and MS clinical variables, immune profiling, and a marker of neuroaxonal damage (plasma neurofilament light chain (pNfl))., Methods: This cross-sectional study included MS patients treated with ocrelizumab from at least 1 year. Wearing-off questionnaire and blood samples were collected between 21 and 23 weeks after the previous ocrelizumab infusion. Lymphocyte subpopulations were evaluated on peripheral blood using flow cytometry. PNfl was evaluated using fully automated chemiluminescent enzyme immunoassay., Results: We included 106 people with MS (age 49.5 ± 11.6 years; females 42.3%; wearing-off 57.6%). On regression models, wearing-off was associated with higher pNfl, CD8, CD3, and CD3CD27 lymphocytes. Most frequent wearing-off symptoms were cognitive, sensory, and balance problems; wearing-off started < 1 week (9.4%), 1-4 weeks (10.7%) or > 4 weeks (10.7%) before infusion; 44.8% of the complaints were moderate to severe. Severity of wearing-off was associated with higher pNfl and CD8 lymphocytes., Conclusions: Wearing-off is common in people with MS treated with ocrelizumab, and is associated with reduced immunomodulation (higher T lymphocytes) and increased neuroaxonal damage, suggesting reduced treatment response., (© 2024. The Author(s).)

Published
2024
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48. Deciphering the role of protein kinase A in the control of FoxP3 expression in regulatory T cells in health and autoimmunity.

Author

Lepore MT, Bruzzaniti S, La Rocca C, Fusco C, Carbone F, Mottola M, Zuccarelli B, Lanzillo R, Brescia Morra V, Maniscalco GT, De Simone S, Procaccini C, Porcellini A, De Rosa V, Galgani M, Cassano S, and Matarese G

Subjects
Humans, Phosphorylation, Gene Expression Regulation, Multiple Sclerosis immunology, Multiple Sclerosis metabolism, Female, Male, Forkhead Transcription Factors metabolism, Forkhead Transcription Factors genetics, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism, Cyclic AMP-Dependent Protein Kinases metabolism, Cyclic AMP Response Element-Binding Protein metabolism, Autoimmunity
Abstract

The molecular mechanisms that govern differential T cell development from CD4 + CD25 - conventional T (Tconv) into CD4 + CD25 + forkhead-box-P3 + (FoxP3 + ) inducible regulatory T (iTreg) cells remain unclear. Herein, we investigated the relative contribution of protein kinase A (PKA) in this process. Mechanistically, we found that PKA controlled the efficiency of human iTreg cell generation through the expression of different FoxP3 splicing variants containing or not the exon 2. We found that transient PKA inhibition reduced the recruitment of cAMP-responsive element-binding protein (CREB) on regulatory regions of the FoxP3 gene, a condition that is associated with an impaired acquisition of their suppressive capacity in vitro. To corroborate our findings in a human model of autoimmunity, we measured CREB phosphorylation and FoxP3 levels in iTreg cells from treatment-naïve relapsing-remitting (RR)-multiple sclerosis (MS) subjects. Interestingly, both phospho-CREB and FoxP3 induction directly correlated and were significantly reduced in RR-MS patients, suggesting a previously unknown mechanism involved in the induction and function of human iTreg cells., (© 2024. The Author(s).)

Published
2024
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49. Effect of siponimod on lymphocyte subsets in active secondary progressive multiple sclerosis and clinical implications.

Author

Spiezia AL, Scalia G, Petracca M, Caliendo D, Moccia M, Fiore A, Cerbone V, Lanzillo R, Brescia Morra V, and Carotenuto A

Subjects
Humans, Female, Male, Adult, Middle Aged, Retrospective Studies, Sphingosine 1 Phosphate Receptor Modulators pharmacology, Follow-Up Studies, Treatment Outcome, Multiple Sclerosis, Chronic Progressive drug therapy, Multiple Sclerosis, Chronic Progressive immunology, Multiple Sclerosis, Chronic Progressive blood, Azetidines pharmacology, Azetidines administration & dosage, Lymphocyte Subsets drug effects, Lymphocyte Subsets immunology, Benzyl Compounds pharmacology, Benzyl Compounds administration & dosage
Abstract

Background: Circulating immune cells play a pathogenic role in multiple sclerosis (MS). However, the role of specific lymphocyte subpopulations is not unveiled yet, especially in progressive stages. We aimed to investigate lymphocyte changes during siponimod treatment in active secondary progressive MS (aSPMS) and their associations with clinical outcomes., Methods: We enrolled 46 aSPMS patients starting on siponimod treatment with at least 6 months of follow-up and two visits within the scheduled timeframes and 14 sex- and age-matched healthy controls (HCs). Clinical and laboratory data were collected retrospectively at baseline, 3rd, 6th, 12th, and 24th month for MS patients, and at baseline for HCs., Results: At baseline SPMS patients presented with increased naïve regulatory T lymphocytes (p = 0.02) vs. HCs. Over time, SPMS patients showed decreased T CD4+ (coeff. range = -24/-17, 95% CI range = -31.60 to -10.40), B lymphocyte (coeff. range = -3.77/-2.54, 95% CI range = -6.02 to -0.35), memory regulatory B cells (coeff. range = -0.78/-0.57, 95% CI range = -1.24 to -0.17) and CD4/CD8 ratio (coeff. range = -4.44/-0.67, 95% CI range = -1.61 to -0.17) from month 3 thereafter vs. baseline, and reduced CD3+CD20+ lymphocytes from month 12 thereafter (coeff. range = -0.32/-0.24, 95% CI range = -0.59 to -0.03). Patients not experiencing disability progression while on siponimod treatment showed B lymphocyte reduction from month 3 (coeff. range = -4.23/-2.32, 95% CI range = -7.53 to -0.15) and CD3+CD20+ lymphocyte reduction from month 12 (coeff. range = -0.32/-0.24, 95% CI range = -0.59 to -0.03) vs. patients experiencing progression., Conclusions: Patients treated with siponimod showed a T and B lymphocyte reduction, especially CD4+, CD3+CD20+ and naïve regulatory T cells and memory regulatory B cells. Disability progression while on siponimod treatment was associated with a less pronounced effect on B and CD3+CD20+ lymphocytes., (© 2024. The Author(s).)

Published
2024
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50. Neurofilament in clinical practice: Is the multiple sclerosis community ready?

Author

Moccia M, Terracciano D, Brescia Morra V, and Castaldo G

Subjects
Humans, Intermediate Filaments metabolism, Biomarkers, Multiple Sclerosis, Neurofilament Proteins
Abstract

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Published
2024
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