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1. Exploring the Impact of Environmental Pollutants on Multiple Sclerosis Progression

Author

Marinello, Elena, Tavazzi, Erica, Longato, Enrico, Bosoni, Pietro, Dagliati, Arianna, Vazifehdan, Mahin, Bellazzi, Riccardo, Trescato, Isotta, Guazzo, Alessandro, Vettoretti, Martina, Tavazzi, Eleonora, Ahmad, Lara, Bergamaschi, Roberto, Cavalla, Paola, Manera, Umberto, Chio, Adriano, and Di Camillo, Barbara

Subjects
Computer Science - Machine Learning
Abstract

Multiple Sclerosis (MS) is a chronic autoimmune and inflammatory neurological disorder characterised by episodes of symptom exacerbation, known as relapses. In this study, we investigate the role of environmental factors in relapse occurrence among MS patients, using data from the H2020 BRAINTEASER project. We employed predictive models, including Random Forest (RF) and Logistic Regression (LR), with varying sets of input features to predict the occurrence of relapses based on clinical and pollutant data collected over a week. The RF yielded the best result, with an AUC-ROC score of 0.713. Environmental variables, such as precipitation, NO2, PM2.5, humidity, and temperature, were found to be relevant to the prediction.

Published
2024

2. Evaluation of Predictive Reliability to Foster Trust in Artificial Intelligence. A case study in Multiple Sclerosis

Author

Peracchio, Lorenzo, Nicora, Giovanna, Parimbelli, Enea, Buonocore, Tommaso Mario, Bergamaschi, Roberto, Tavazzi, Eleonora, Dagliati, Arianna, and Bellazzi, Riccardo

Subjects
Computer Science - Machine Learning
Abstract

Applying Artificial Intelligence (AI) and Machine Learning (ML) in critical contexts, such as medicine, requires the implementation of safety measures to reduce risks of harm in case of prediction errors. Spotting ML failures is of paramount importance when ML predictions are used to drive clinical decisions. ML predictive reliability measures the degree of trust of a ML prediction on a new instance, thus allowing decision-makers to accept or reject it based on its reliability. To assess reliability, we propose a method that implements two principles. First, our approach evaluates whether an instance to be classified is coming from the same distribution of the training set. To do this, we leverage Autoencoders (AEs) ability to reconstruct the training set with low error. An instance is considered Out-of-Distribution (OOD) if the AE reconstructs it with a high error. Second, it is evaluated whether the ML classifier has good performances on samples similar to the newly classified instance by using a proxy model. We show that this approach is able to assess reliability both in a simulated scenario and on a model trained to predict disease progression of Multiple Sclerosis patients. We also developed a Python package, named relAI, to embed reliability measures into ML pipelines. We propose a simple approach that can be used in the deployment phase of any ML model to suggest whether to trust predictions or not. Our method holds the promise to provide effective support to clinicians by spotting potential ML failures during deployment., Comment: 20 pages, 7 figures

Published
2024

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

Author

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, Group, MuSC‐19 Study, Abbadessa, Gianmarco, Aguglia, Umberto, Allegorico, Lia, Allegri, Beatrice Maria Rossi, Alteno, Anastasia, Amato, Maria Pia, Annovazzi, Pietro, Antozzi, Carlo, Appendino, Lucia, Arena, Sebastiano, Baione, Viola, Balgera, Roberto, Barcella, Valeria, Baroncini, Damiano, Barrilà, Caterina, Bellacosa, Alessandra, Bellucci, Gianmarco, Bergamaschi, Valeria, Bezzini, Daiana, Biolzi, Beatrice, Bisecco, Alvino, Bonavita, Simona, Borriello, Giovanna, Bosa, Chiara, Bosco, Antonio, Bovis, Francesca, Bozzali, Marco, Brambilla, Laura, Morra, Vincenzo Brescia, Buccafusca, Maria, Bucciantini, Elisabetta, Bucello, Sebastiano, Buscarinu, Maria Chiara, Cabboi, Maria Paola, Calabrese, Massimiliano, Calabria, Francesca, Caleri, Francesca, Camilli, Federico, Caniatti, Luisa Maria, Cantello, Roberto, Capra, Ruggero, Capuano, Rocco, Carta, Patrizia, Celani, Maria Grazia, Cellerino, Maria, Cerqua, Raffaella, Chisari, Clara, Clerici, Raffaella, Clerico, Marinella, Cola, Gaia, Conte, Antonella, Conti, Marta Zaffira, Cordano, Christian, Cordera, Susanna, Corea, Francesco, Correale, Claudio, Cottone, Salvatore, Crescenzo, Francesco, Curti, Erica, d’Ambrosio, Alessandro, D’Amico, Emanuele, Danni, Maura Chiara, d’Arma, Alessia, Dattola, Vincenzo, de Biase, Stefano, De Luca, Giovanna, De Mercanti, Stefania Federica, De Mitri, Paolo, De Stefano, Nicola, Della Cava, Fabio Maria, Della Cava, Marco, and Di Lemme, Sonia

Subjects
Neurosciences, Multiple Sclerosis, Brain Disorders, Pain Research, Neurodegenerative, Good Health and Well Being, Humans, Aged, COVID-19, Ageusia, SARS-CoV-2, Anosmia, MuSC-19 Study Group, demyelinating diseases, disease-modifying treatment, multiple sclerosis, neurological disorders, Clinical Sciences, Neurology & Neurosurgery
Abstract

Background and purposeClinical 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.MethodLogistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number.ResultsFrom 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

Published
2022

4. Long-term effectiveness of natalizumab in secondary progressive multiple sclerosis: A propensity-matched study

Author

Avolio, Carlo, Balgera, Roberto, Banfi, Paola, Bellantonio, Paolo, Bramanti, Placido, Capone, Lorenzo, Cavalletti, Guido, Chiveri, Luca, Clerici, Raffaella, Clerico, Marinella, Corea, Francesco, Dattola, Vincenzo, De Robertis, Francesca, Di Battista, Giancarlo, Galgani, Simonetta, Gatto, Maurizia, Grasso, Maria Grazia, Inglese, Matilde, Lo Russo, Lorenzo, Logullo, Francesco Ottavio, Mantegazza, Renato, Protti, Alessandra, Rezzonico, Monica, Rottoli, Mariarosa, Salvetti, Marco, Scarpini, Elio, Sinisi, Leonardo, Sparaco, Maddalena, Spitaleri, Daniele, Tassinari, Tiziana, Tonietti, Simone, Valentino, Paola, Valzania, Franco, Venturi, Simonetta, Chisari, Clara G., Aguglia, Umberto, Amato, Maria Pia, Bergamaschi, Roberto, Bertolotto, Antonio, Bonavita, Simona, Morra, Vincenzo Brescia, Cavalla, Paola, Cocco, Eleonora, Conte, Antonella, Cottone, Salvatore, De Luca, Giovanna, Di Sapio, Alessia, Filippi, Massimo, Gallo, Antonio, Gasperini, Claudio, Granella, Franco, Lus, Giacomo, Maimone, Davide, Maniscalco, Giorgia Teresa, Marfia, Girolama, Moiola, Lucia, Paolicelli, Damiano, Pesci, Ilaria, Ragonese, Paolo, Rovaris, Marco, Salemi, Giuseppe, Solaro, Claudio, Totaro, Rocco, Trojano, Maria, Vianello, Marika, Zaffaroni, Mauro, Lepore, Vito, and Patti, Francesco

Published
2024
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6. 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, Morra, Vincenzo Brescia, Pisoni, Enrico, Tedeschi, Gioacchino, Comi, Giancarlo, Battaglia, Mario Alberto, Patti, Francesco, Salvetti, Marco, Sormani, Maria Pia, Abbadessa, Gianmarco, Aguglia, Umberto, Allegorico, Lia, Allegri, Rossi Beatrice Maria, Alteno, Anastasia, Amato, Maria Pia, Annovazzi, Pietro, Antozzi, Carlo, Appendino, Lucia, Arena, Sebastiano, Baione, Viola, Balgera, Roberto, Barcella, Valeria, Baroncini, Damiano, Barrilà, Caterina, Battaglia, Mario A, Bellacosa, Alessandra, Bellucci, Gianmarco, Bergamaschi, Valeria, Bezzini, Daiana, Biolzi, Beatrice, Bisecco, Alvino, Bonavita, Simona, Borriello, Giovanna, Bosa, Chiara, Bosco, Antonio, Bovis, Francesca, Bozzali, Marco, Brambilla, Laura, Brescia, Morra Vincenzo, Buccafusca, Maria, Bucciantini, Elisabetta, Bucello, Sebastiano, Buscarinu, Maria Chiara, Cabboi, Maria Paola, Calabrese, Massimiliano, Calabria, Francesca, Caleri, Francesca, Camilli, Federico, Caniatti, Luisa Maria, Cantello, Roberto, Capra, Ruggero, Capuano, Rocco, Carta, Patrizia, Celani, Maria Grazia, Cellerino, Maria, Cerqua, Raffaella, Chisari, Clara, Clerici, Raffaella, Clerico, Marinella, Cola, Gaia, Conte, Antonella, Conti, Marta Zaffira, Cordano, Christian, Cordera, Susanna, Corea, Francesco, Correale, Claudio, Cottone, Salvatore, Crescenzo, Francesco, Curti, Erica, d'Ambrosio, Alessandro, and D'Amico, Emanuele

Subjects
Clinical Research, Neurosciences, Multiple Sclerosis, Brain Disorders, Autoimmune Disease, Neurodegenerative, Climate-Related Exposures and Conditions, Good Health and Well Being, Sustainable Cities and Communities, Air Pollution, COVID-19, Humans, Particulate Matter, SARS-CoV-2, MuSC-19 study group, air pollution, coronavirus, multiple sclerosis, Clinical Sciences, Neurology & Neurosurgery
Abstract

Background and purposeSome 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.MethodsData 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.ResultsIn 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).ConclusionsEven 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

7. Longitudinal modeling of MS patient trajectories improves predictions of disability progression

Author

De Brouwer, Edward, Becker, Thijs, Moreau, Yves, Havrdova, Eva Kubala, Trojano, Maria, Eichau, Sara, Ozakbas, Serkan, Onofrj, Marco, Grammond, Pierre, Kuhle, Jens, Kappos, Ludwig, Sola, Patrizia, Cartechini, Elisabetta, Lechner-Scott, Jeannette, Alroughani, Raed, Gerlach, Oliver, Kalincik, Tomas, Granella, Franco, GrandMaison, Francois, Bergamaschi, Roberto, Sa, Maria Jose, Van Wijmeersch, Bart, Soysal, Aysun, Sanchez-Menoyo, Jose Luis, Solaro, Claudio, Boz, Cavit, Iuliano, Gerardo, Buzzard, Katherine, Aguera-Morales, Eduardo, Terzi, Murat, Trivio, Tamara Castillo, Spitaleri, Daniele, Van Pesch, Vincent, Shaygannej, Vahid, Moore, Fraser, Guevara, Celia Oreja, Maimone, Davide, Gouider, Riadh, Csepany, Tunde, Ramo-Tello, Cristina, and Peeters, Liesbet

Subjects
Computer Science - Machine Learning
Abstract

Research in Multiple Sclerosis (MS) has recently focused on extracting knowledge from real-world clinical data sources. This type of data is more abundant than data produced during clinical trials and potentially more informative about real-world clinical practice. However, this comes at the cost of less curated and controlled data sets. In this work, we address the task of optimally extracting information from longitudinal patient data in the real-world setting with a special focus on the sporadic sampling problem. Using the MSBase registry, we show that with machine learning methods suited for patient trajectories modeling, such as recurrent neural networks and tensor factorization, we can predict disability progression of patients in a two-year horizon with an ROC-AUC of 0.86, which represents a 33% decrease in the ranking pair error (1-AUC) compared to reference methods using static clinical features. Compared to the models available in the literature, this work uses the most complete patient history for MS disease progression prediction.

Published
2020

8. Long-term effectiveness of natalizumab in secondary progressive multiple sclerosis: A propensity-matched study

Author

Chisari, Clara G., primary, Aguglia, Umberto, additional, Amato, Maria Pia, additional, Bergamaschi, Roberto, additional, Bertolotto, Antonio, additional, Bonavita, Simona, additional, Morra, Vincenzo Brescia, additional, Cavalla, Paola, additional, Cocco, Eleonora, additional, Conte, Antonella, additional, Cottone, Salvatore, additional, De Luca, Giovanna, additional, Di Sapio, Alessia, additional, Filippi, Massimo, additional, Gallo, Antonio, additional, Gasperini, Claudio, additional, Granella, Franco, additional, Lus, Giacomo, additional, Maimone, Davide, additional, Maniscalco, Giorgia Teresa, additional, Marfia, Girolama, additional, Moiola, Lucia, additional, Paolicelli, Damiano, additional, Pesci, Ilaria, additional, Ragonese, Paolo, additional, Rovaris, Marco, additional, Salemi, Giuseppe, additional, Solaro, Claudio, additional, Totaro, Rocco, additional, Trojano, Maria, additional, Vianello, Marika, additional, Zaffaroni, Mauro, additional, Lepore, Vito, additional, Patti, Francesco, additional, Avolio, Carlo, additional, Balgera, Roberto, additional, Banfi, Paola, additional, Bellantonio, Paolo, additional, Bramanti, Placido, additional, Capone, Lorenzo, additional, Cavalletti, Guido, additional, Chiveri, Luca, additional, Clerici, Raffaella, additional, Clerico, Marinella, additional, Corea, Francesco, additional, Dattola, Vincenzo, additional, De Robertis, Francesca, additional, Di Battista, Giancarlo, additional, Galgani, Simonetta, additional, Gatto, Maurizia, additional, Grasso, Maria Grazia, additional, Inglese, Matilde, additional, Lo Russo, Lorenzo, additional, Logullo, Francesco Ottavio, additional, Mantegazza, Renato, additional, Protti, Alessandra, additional, Rezzonico, Monica, additional, Rottoli, Mariarosa, additional, Salvetti, Marco, additional, Scarpini, Elio, additional, Sinisi, Leonardo, additional, Sparaco, Maddalena, additional, Spitaleri, Daniele, additional, Tassinari, Tiziana, additional, Tonietti, Simone, additional, Valentino, Paola, additional, Valzania, Franco, additional, and Venturi, Simonetta, additional

Published
2024
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10. Budget impact analysis of natalizumab biosimilar on pharmaceutical expenditure for the treatment of relapsing-remitting multiple sclerosis in Italy

Author

Bergamaschi, Roberto, Capobianco , Marco, Ravasio, Roberto, Bergamaschi, Roberto, Capobianco , Marco, and Ravasio, Roberto

Abstract

Background: The availability of high-efficacy disease-modifying therapy (DMT), including natalizumab, improved treatment efficacy in adults with highly-active relapsing-remitting multiple sclerosis (RRMS). Natalizumab patent protection has expired, and the natalizumab biosimilar (Tyruko®) has been recently reimbursed by AIFA. As the price of natalizumab biosimilar is expected to be lower as compared with natalizumab originator’s price, a budget impact analysis was conducted to assess the economic impact associated to the introduction of natalizumab biosimilar for patients with highly-active RRMS. Methods: A budget impact model was developed, considering the INHS perspective and a 5-years time horizon. The number of patients treated with natalizumab was estimated based on historical natalizumab consumption data, disease prevalence rates and natalizumab market share. The budget impact population was divided into prevalent and incident patients. The model assumes that some patients in treatment with natalizumab originator will switch to natalizumab biosimilar and that some naïve patients will directly start treatment with natalizumab biosimilar. The ex-factory price of natalizumab originator (intravenous and subcutaneous) and biosimilar (intravenous) and the corresponding administration costs were included. All assumptions were validated by expert opinion. Results: Eligible population was estimated at 7,552, 7,779, 8,090, 8,494 and 8,834 in years 1, 2, 3, 4 and 5 respectively. The introduction of natalizumab biosimilar, considering a progressive increase in market share from 9.6% (year 1) to 40.5% (year 5), would provide an overall savings (5-years time horizon) over € 47 million to the INHS. The scenario analysis highlights that the lower treatment cost of biosimilar natalizumab compared to originator natalizumab would offset the higher cost associated with intravenous versus subcutaneous administration. Conclusion: Considering the results of this budget impact analys

Published
2024

11. Inadvertent laparoscopic lavage of perforated colon cancer: a systematic review

Author

Gachabayov, Mahir, Kajmolli, Agon, Quintero, Luis, Felsenreich, Daniel M., Popa, Dorin E., Ignjatovic, Dejan, Bergamaschi, Roberto, Gachabayov, Mahir, Kajmolli, Agon, Quintero, Luis, Felsenreich, Daniel M., Popa, Dorin E., Ignjatovic, Dejan, and Bergamaschi, Roberto

Abstract

BackgroundAlthough laparoscopic lavage for perforated diverticulitis with peritonitis has been grabbing the headlines, it is known that the clinical presentation of peritonitis can also be caused by an underlying perforated carcinoma. The aim of this study was to determine the incidence of patients undergoing inadvertent laparoscopic lavage of perforated colon cancer as well as the delay in cancer diagnosis.MethodsThe PubMed database was systematically searched to include all studies meeting inclusion criteria. Studies were screened through titles and abstracts with potentially eligible studies undergoing full-text screening. The primary endpoints of this meta-analysis were the rates of perforated colon cancer patients having undergone inadvertent laparoscopic lavage as well as the delay in cancer diagnosis. This was expressed in pooled rate % and 95% confidence intervals.ResultsEleven studies (three randomized, two prospective, six retrospective) totaling 642 patients met inclusion criteria. Eight studies reported how patients were screened for cancer and the number of patients who completed follow-up. The pooled cancer rate was 3.4% (0.9%, 5.8%) with low heterogeneity (Isquare2 = 34.02%) in eight studies. Cancer rates were 8.2% (0%, 3%) (Isquare2 = 58.2%) and 1.7% (0%, 4.5%) (Isquare2 = 0%) in prospective and retrospective studies, respectively. Randomized trials reported a cancer rate of 7.2% (3.1%, 11.2%) with low among-study heterogeneity (Isquare2 = 0%) and a median delay to diagnosis of 2 (1.5-5) months.ConclusionsThis systematic review found that 7% of patients undergoing laparoscopic lavage for peritonitis had perforated colon cancer with a delay to diagnosis of up to 5 months.

Published
2024
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12. Disclosing the Novel Protective Mechanisms of Ocrelizumab in Multiple Sclerosis: The Role of PKC Beta and Its Down-Stream Targets.

Author

Campagnoli, Lucrezia Irene Maria, Ahmad, Lara, Marchesi, Nicoletta, Greco, Giacomo, Boschi, Federica, Masi, Francesco, Mallucci, Giulia, Bergamaschi, Roberto, Colombo, Elena, and Pascale, Alessia

Subjects
MONONUCLEAR leukocytes, PROTEIN kinase C, ENDOTHELIAL growth factors, B cells, SUPEROXIDE dismutase
Abstract

Ocrelizumab (OCR) is a humanized anti-CD20 monoclonal antibody approved for both Relapsing and Primary Progressive forms of Multiple Sclerosis (MS) treatment. OCR is postulated to act via rapid B cell depletion; however, by analogy with other anti-CD20 agents, additional effects can be envisaged, such as on Protein Kinase C (PKC). Hence, this work aims to explore novel potential mechanisms of action of OCR in peripheral blood mononuclear cells from MS patients before and after 12 months of OCR treatment. We first assessed, up-stream, PKCβII and subsequently explored two down-stream pathways: hypoxia-inducible factor 1 alpha (HIF-1α)/vascular endothelial growth factor (VEGF), and human antigen R (HuR)/manganese-dependent superoxide dismutase (MnSOD) and heat shock proteins 70 (HSP70). At baseline, higher levels of PKCβII, HIF-1α, and VEGF were found in MS patients compared to healthy controls (HC); interestingly, the overexpression of this inflammatory cascade was counteracted by OCR treatment. Conversely, at baseline, the content of HuR, MnSOD, and HSP70 was significantly lower in MS patients compared to HC, while OCR administration induced the up-regulation of these neuroprotective pathways. These results enable us to disclose the dual positive action of OCR: anti-inflammatory and neuroprotective. Therefore, in addition to B cell depletion, the effect of OCR on these molecular cascades can contribute to counteracting disease progression. [ABSTRACT FROM AUTHOR]

Published
2024
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13. COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Author

Sormani, Maria Pia, 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, Tedeschi, Gioacchino, Comi, Giancarlo, Battaglia, Mario Alberto, Patti, Francesco, Salvetti, Marco, Abbadessa, Gianmarco, Aguglia, Umberto, Allegorico, Lia, Allegri Rossi, Beatrice Maria, Amato, Maria Pia, Annovazzi, Pietro, Antozzi, Carlo, Appendino, Lucia, Arena, Sebastiano, Baione, Viola, Balgera, Roberto, Barcella, Valeria, Baroncini, Damiano, Barrilà, Caterina, Bellacosa, Alessandra, Bellucci, Gianmarco, Bergamaschi, Roberto, Bergamaschi, Valeria, Bezzini, Daiana, Biolzi, Beatrice, Bisecco, Alvino, Bonavita, Simona, Borriello, Giovanna, Bosa, Chiara, Bosco, Antonio, Bovis, Francesca, Bozzali, Marco, Brambilla, Laura, Buccafusca, Maria, Bucciantini, Elisabetta, Bucello, Sebastiano, Buscarinu, Maria Chiara, Cabboi, Maria Paola, Calabrese, Massimiliano, Calabria, Francesca, Caleri, Francesca, Camilli, Federico, Caniatti, Luisa Maria, Cantello, Roberto, Capra, Ruggero, Capuano, Rocco, Carta, Patrizia, Celani, Maria Grazia, Cellerino, Maria, Cerqua, Raffaella, Chisari, Clara, Clerici, Raffaella, Clerico, Marinella, Cola, Gaia, Conte, Antonella, Conti, Marta Zaffira, Cordano, Christian, Cordera, Susanna, Corea, Francesco, Correale, Claudio, Cottone, Salvatore, Crescenzo, Francesco, Curti, Erica, dʼAmbrosio, Alessandro, DʼAmico, Emanuele, Danni, Maura Chiara, dʼArma, Alessia, Dattola, Vincenzo, de Biase, Stefano, Luca, Giovanna De, Mercanti, Stefania Federica De, De Mitri, Paolo, De Stefano, Nicola, Cava, Marco Della, Napoli, Mario di, Sapio, Alessia Di, Docimo, Renato, Dutto, Anna, Evangelista, Luana, Fanara, Salvatore, Diana, Ferraro, Ferrò, Maria Teresa, Fioretti, Cristina, Fratta, Mario, Frau, Jessica, Fronza, Marzia, Furlan, Roberto, Gajofatto, Alberto, Gallo, Antonio, Gallo, Paolo, Gasperini, Claudio, Ghazaryan, Anna, Giometto, Bruno, Gobbin, Francesca, Govone, Flora, Granella, Franco, Grange, Erica, Grasso, Maria Grazia, Guareschi, Angelica, Guaschino, Clara, Guerrieri, Simone, Guidetti, Donata, Iaffaldano, Pietro, Ianniello, Antonio, Iasevoli, Luigi, Imperiale, Daniele, Infante, Maria Teresa, Iodice, Rosa, Iovino, Aniello, Konrad, Giovanna, Landi, Doriana, Lanzillo, Roberta, Lapucci, Caterina, Lavorgna, Luigi, LʼEpiscopo, Maria Rita, Leva, Serena, Liberatore, Giuseppe, Lo Re, Marianna, Longoni, Marco, Lopiano, Leonardo, Lorefice, Lorena, Lucchini, Matteo, Lus, Giacomo, Maimone, Davide, Malentacchi, Maria, Mallucci, Giulia, Malucchi, Simona, Mancinelli, Chiara Rosa, Mancinelli, Luca, Manganotti, Paolo, Maniscalco, Giorgia Teresa, Mantero, Vittorio, Marangoni, Sabrina, Marastoni, Damiano, Marinelli, Fabiana, Marti, Alessandro, Boneschi, Filippo Martinelli, Masserano Zoli, Federco, Matta, Francesca, Mendozzi, Laura, Meucci, Giuseppe, Miante, Silvia, Miele, Giuseppina, Milano, Eva, Mirabella, Massimiliano, Missione, Rosanna, Moccia, Marcello, Moiola, Lucia, Montepietra, Sara, MontiBragadin, Margherita, Montini, Federico, Motta, Roberta, Nardone, Raffaele, Nicoletti, Carolina Gabri, Nobile-Orazio, Eduardo, Nozzolillo, Agostino, Onofrj, Marco, Orlandi, Riccardo, Palmieri, Anna, Paolicelli, Damiano, Pasquali, Livia, Pastò, Luisa, Pedrazzoli, Elisabetta, Petracca, Maria, Petrone, Alfredo, Piantadosi, Carlo, Pietroboni, Anna M, Pinardi, Federica, Ponzano, Marta, Portaccio, Emilio, Pozzato, Mattia, Pozzilli, Carlo, Prosperini, Luca, Protti, Alessandra, Ragonese, Paolo, Rasia, Sarah, Realmuto, Sabrina, Repice, Anna, Rigoni, Eleonora, Rilla, Maria Teresa, Rinaldi, Francesca, Romano, Calogero Marcello, Ronzoni, Marco, Rovaris, Marco, Ruscica, Francesca, Sabattini, Loredana, Salemi, Giuseppe, Saraceno, Lorenzo, Sartori, Alessia, Sartori, Arianna, Sbragia, Elvira, Scarano, Giuditta Ilaria, Scarano, Valentina, Schillaci, Valentina, Sessa, Maria, Sgarito, Caterina, Sibilia, Grazia, Siciliano, Gabriele, Signori, Alessio, Signoriello, Elisabetta, Sinisi, Leonardo, Sireci, Francesca, Sola, Patrizia, Solaro, Claudio, Sotgiu, Stefano, Sparaco, Maddalena, Stromillo, Maria Laura, Strumia, Silvia, Susani, Emanuela Laura, Tabiadon, Giulietta, Teatini, Francesco, Tomassini, Valentina, Tonietti, Simone, Torri, Clerici Valentina, Tortorella, Carla, Toscano, Simona, Totaro, Rocco, Trotta, Maria, Turano, Gabriella, Ulivelli, Monica, Valentino, Manzo, Vaula, Giovanna, Vecchio, Domizia, Vercellino, Marco, Verrengia, Elena Pinuccia, Vianello, Marika, Virgilio, Eleonora, Vitetta, Francesca, Vollaro, Stefano, Zaffaroni, Mauro, Zampolini, Mauro, Zarbo, Ignazio Roberto, and Zuliani, Luigi

Published
2022
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15. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Author

International Multiple Sclerosis Genetics Consortium, Wellcome Trust Case Control Consortium 2, Sawcer, Stephen, Hellenthal, Garrett, Pirinen, Matti, Spencer, Chris CA, Patsopoulos, Nikolaos A, Moutsianas, Loukas, Dilthey, Alexander, Su, Zhan, Freeman, Colin, Hunt, Sarah E, Edkins, Sarah, Gray, Emma, Booth, David R, Potter, Simon C, Goris, An, Band, Gavin, Oturai, Annette Bang, Strange, Amy, Saarela, Janna, Bellenguez, Céline, Fontaine, Bertrand, Gillman, Matthew, Hemmer, Bernhard, Gwilliam, Rhian, Zipp, Frauke, Jayakumar, Alagurevathi, Martin, Roland, Leslie, Stephen, Hawkins, Stanley, Giannoulatou, Eleni, D'alfonso, Sandra, Blackburn, Hannah, Martinelli Boneschi, Filippo, Liddle, Jennifer, Harbo, Hanne F, Perez, Marc L, Spurkland, Anne, Waller, Matthew J, Mycko, Marcin P, Ricketts, Michelle, Comabella, Manuel, Hammond, Naomi, Kockum, Ingrid, McCann, Owen T, Ban, Maria, Whittaker, Pamela, Kemppinen, Anu, Weston, Paul, Hawkins, Clive, Widaa, Sara, Zajicek, John, Dronov, Serge, Robertson, Neil, Bumpstead, Suzannah J, Barcellos, Lisa F, Ravindrarajah, Rathi, Abraham, Roby, Alfredsson, Lars, Ardlie, Kristin, Aubin, Cristin, Baker, Amie, Baker, Katharine, Baranzini, Sergio E, Bergamaschi, Laura, Bergamaschi, Roberto, Bernstein, Allan, Berthele, Achim, Boggild, Mike, Bradfield, Jonathan P, Brassat, David, Broadley, Simon A, Buck, Dorothea, Butzkueven, Helmut, Capra, Ruggero, Carroll, William M, Cavalla, Paola, Celius, Elisabeth G, Cepok, Sabine, Chiavacci, Rosetta, Clerget-Darpoux, Françoise, Clysters, Katleen, Comi, Giancarlo, Cossburn, Mark, Cournu-Rebeix, Isabelle, Cox, Mathew B, Cozen, Wendy, Cree, Bruce AC, Cross, Anne H, Cusi, Daniele, Daly, Mark J, Davis, Emma, de Bakker, Paul IW, Debouverie, Marc, D'hooghe, Marie Beatrice, Dixon, Katherine, Dobosi, Rita, Dubois, Bénédicte, and Ellinghaus, David

Subjects
International Multiple Sclerosis Genetics Consortium, Wellcome Trust Case Control Consortium 2, T-Lymphocytes, Helper-Inducer, Humans, Multiple Sclerosis, Genetic Predisposition to Disease, HLA-A Antigens, HLA-DR Antigens, Sample Size, Cell Differentiation, Immunity, Cellular, Major Histocompatibility Complex, Polymorphism, Single Nucleotide, Alleles, Genome, Human, Europe, Genome-Wide Association Study, HLA-DRB1 Chains, Genetics, Neurosciences, Neurodegenerative, Clinical Research, Brain Disorders, Autoimmune Disease, Human Genome, 2.1 Biological and endogenous factors, Neurological, Inflammatory and immune system, General Science & Technology
Abstract

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.

Published
2011

16. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

Author

Sawcer, Stephen, Hellenthal, Garrett, Pirinen, Matti, Spencer, Chris CA, Patsopoulos, Nikolaos A, Moutsianas, Loukas, Dilthey, Alexander, Su, Zhan, Freeman, Colin, Hunt, Sarah E, Edkins, Sarah, Gray, Emma, Booth, David R, Potter, Simon C, Goris, An, Band, Gavin, Oturai, Annette Bang, Strange, Amy, Saarela, Janna, Bellenguez, Celine, Fontaine, Bertrand, Gillman, Matthew, Hemmer, Bernhard, Gwilliam, Rhian, Zipp, Frauke, Jayakumar, Alagurevathi, Martin, Roland, Leslie, Stephen, Hawkins, Stanley, Giannoulatou, Eleni, D'alfonso, Sandra, Blackburn, Hannah, Boneschi, Filippo Martinelli, Liddle, Jennifer, Harbo, Hanne F, Perez, Marc L, Spurkland, Anne, Waller, Matthew J, Mycko, Marcin P, Ricketts, Michelle, Comabella, Manuel, Hammond, Naomi, Kockum, Ingrid, McCann, Owen T, Ban, Maria, Whittaker, Pamela, Kemppinen, Anu, Weston, Paul, Hawkins, Clive, Widaa, Sara, Zajicek, John, Dronov, Serge, Robertson, Neil, Bumpstead, Suzannah J, Barcellos, Lisa F, Ravindrarajah, Rathi, Abraham, Roby, Alfredsson, Lars, Ardlie, Kristin, Aubin, Cristin, Baker, Amie, Baker, Katharine, Baranzini, Sergio E, Bergamaschi, Laura, Bergamaschi, Roberto, Bernstein, Allan, Berthele, Achim, Boggild, Mike, Bradfield, Jonathan P, Brassat, David, Broadley, Simon A, Buck, Dorothea, Butzkueven, Helmut, Capra, Ruggero, Carroll, William M, Cavalla, Paola, Celius, Elisabeth G, Cepok, Sabine, Chiavacci, Rosetta, Clerget-Darpoux, Francoise, Clysters, Katleen, Comi, Giancarlo, Cossburn, Mark, Cournu-Rebeix, Isabelle, Cox, Mathew B, Cozen, Wendy, Cree, Bruce AC, Cross, Anne H, Cusi, Daniele, Daly, Mark J, Davis, Emma, de Bakker, Paul IW, Debouverie, Marc, D'hooghe, Marie Beatrice, Dixon, Katherine, Dobosi, Rita, Dubois, Benedicte, Ellinghaus, David, Elovaara, Irina, and Esposito, Federica

Subjects
Neurosciences, Prevention, Multiple Sclerosis, Biotechnology, Autoimmune Disease, Genetics, Brain Disorders, Human Genome, Neurodegenerative, 2.1 Biological and endogenous factors, Aetiology, Neurological, Inflammatory and immune system, Alleles, Cell Differentiation, Europe, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, HLA-A Antigens, HLA-DR Antigens, HLA-DRB1 Chains, Humans, Immunity, Cellular, Major Histocompatibility Complex, Polymorphism, Single Nucleotide, Sample Size, T-Lymphocytes, Helper-Inducer, International Multiple Sclerosis Genetics Consortium, Wellcome Trust Case Control Consortium 2, General Science & Technology
Abstract

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.

Published
2011

17. Visual System Involvement in Glial Fibrillary Acidic Protein Astrocytopathy

Author

Greco, Giacomo, primary, Masciocchi, Stefano, additional, Diamanti, Luca, additional, Bini, Paola, additional, Vegezzi, Elisa, additional, Marchioni, Enrico, additional, Colombo, Elena, additional, Rigoni, Eleonora, additional, Businaro, Pietro, additional, Ferraro, Ottavia E., additional, Bianchi Marzoli, Stefania, additional, Bergamaschi, Roberto, additional, Franciotta, Diego, additional, and Gastaldi, Matteo, additional

Published
2023
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21. Effectiveness of teriflunomide on No Evidence of Disease Activity and cognition in relapsing remitting multiple sclerosis: results of the NEDA3PLUS study

Author

Amato, Maria Pia, Bergamaschi, Roberto, Centonze, Diego, Mirabella, Massimiliano, Marfia, Girolama Alessandra, Totaro, Rocco, Lus, Giacomo, Brescia Morra, Vincenzo, Aguglia, Umberto, Comi, Cristoforo, Cavalla, Paola, Zaffaroni, Mauro, Rovaris, Marco, Grimaldi, Luigi Maria, Leoni, Stefania, Malucchi, Simona, Baldi, Eleonora, Romano, Marcello, Falcini, Mario, Perini, Paola, Assetta, Maurizio, Portaccio, Emilio, Sommacal, Sergio, Olivieri, Nunzio, Parodi, Franco, Todaro, Daniele Santo, Grassivaro, Nicoletta, Farina, Alberto, Mondino, Margaret Mary, Filippi, Massimo, Trojano, Maria, Mirabella, Massimiliano (ORCID:0000-0002-7783-114X), Amato, Maria Pia, Bergamaschi, Roberto, Centonze, Diego, Mirabella, Massimiliano, Marfia, Girolama Alessandra, Totaro, Rocco, Lus, Giacomo, Brescia Morra, Vincenzo, Aguglia, Umberto, Comi, Cristoforo, Cavalla, Paola, Zaffaroni, Mauro, Rovaris, Marco, Grimaldi, Luigi Maria, Leoni, Stefania, Malucchi, Simona, Baldi, Eleonora, Romano, Marcello, Falcini, Mario, Perini, Paola, Assetta, Maurizio, Portaccio, Emilio, Sommacal, Sergio, Olivieri, Nunzio, Parodi, Franco, Todaro, Daniele Santo, Grassivaro, Nicoletta, Farina, Alberto, Mondino, Margaret Mary, Filippi, Massimo, Trojano, Maria, and Mirabella, Massimiliano (ORCID:0000-0002-7783-114X)

Abstract

Background: Cognitive impairment (CI) is a prevalent and debilitating manifestation of multiple sclerosis (MS); however, it is not included in the widely used concept of No Evidence of Disease Activity (NEDA-3). We expanded the NEDA-3 concept to NEDA-3 + by encompassing CI assessed through the Symbol Digit Modality Test (SDMT) and evaluated the effect of teriflunomide on NEDA3 + in patients treated in a real-world setting. The value of NEDA-3 + in predicting disability progression was also assessed. Methods: This 96-weeks observational study enrolled patients already on treatment with teriflunomide for ≥ 24 weeks. The predictiveness of NEDA-3 and NEDA-3 + at 48 weeks on the change in motor disability at 96 weeks was compared through a two-sided McNemar test. Results: The full analysis set (n = 128; 38% treatment naïve) featured relatively low level of disability (baseline EDSS = 1.97 ± 1.33). NEDA-3 and NEDA-3 + statuses were achieved by 82.8% and 64.8% of patients, respectively at 48 weeks vs. baseline, and by 57.0% and 49.2% of patients, respectively at 96 weeks vs. baseline. All patients except one were free of disability progression at Week 96, and NEDA-3 and NEDA-3 + were equally predictive. Most patients were free of relapse (87.5%), disability progression (94.5%) and new MRI activity (67.2%) comparing 96 weeks with baseline. SDMT scores were stable in patients with baseline score ˃35 and improved significantly in those with baseline score ≤ 35. Treatment persistence was high (81.0% at Week 96). Conclusion: Teriflunomide confirmed its real-world efficacy and was found to have a potentially beneficial effect on cognition.

Published
2023

22. Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis

Author

Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), Diouf, Ibrahima; Malpas, Charles B.; Sharmin, Sifat; Roos, Izanne; Horakova, Dana; Havrdova, Eva Kubala; Patti, Francesco; Shaygannejad, Vahid; Ozakbas, Serkan; Izquierdo, Guillermo; Eichau, Sara; Onofrj, Marco; Lugaresi, Alessandra; Alroughani, Raed; Prat, Alexandre; Girard, Marc; Duquette, Pierre; Terzi, Murat; Boz, Cavit; Grand'Maison, Francois; Hamdy, Sherif; Sola, Patrizia; Ferraro, Diana; Grammond, Pierre; Turkoglu, Recai; Buzzard, Katherine; Skibina, Olga; Yamout, Bassem; Gerlach, Oliver; van Pesch, Vincent; Blanco, Yolanda; Maimone, Davide; Lechner-Scott, Jeannette; Bergamaschi, Roberto; Karabudak, Rana; Iuliano, Gerardo; McGuigan, Chris; Cartechini, Elisabetta; Barnett, Michael; Hughes, Stella; Sa, Maria Jose; Solaro, Claudio; Kappos, Ludwig; Ramo-Tello, Cristina; Cristiano, Edgardo; Hodgkinson, Suzanne; Spitaleri, Daniele; Soysal, Aysun; Petersen, Thor; Slee, Mark; Butler, Ernest; Granella, Franco; de Gans, Koen; McCombe, Pamela; Ampapa, Radek; Van Wijmeersch, Bart; van der Walt, Anneke; Butzkueven, Helmut; Prevost, Julie; Sinnige, L. G. F.; Sanchez-Menoyo, Jose Luis; Vucic, Steve; Laureys, Guy; Van Hijfte, Liesbeth; Khurana, Dheeraj; Macdonell, Richard; Gouider, Riadh; Castillo-Trivino, Tamara; Gray, Orla; Aguera-Morales, Eduardo; Al-Asmi, Abdullah; Shaw, Cameron; Deri, Norma; Al-Harbi, Talal; Fragoso, Yara; Csepany, Tunde; Sempere, Angel Perez; Trevino-Frenk, Irene; Schepel, Jan; Moore, Fraser; Kalincik, Tomas, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine, Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), Diouf, Ibrahima; Malpas, Charles B.; Sharmin, Sifat; Roos, Izanne; Horakova, Dana; Havrdova, Eva Kubala; Patti, Francesco; Shaygannejad, Vahid; Ozakbas, Serkan; Izquierdo, Guillermo; Eichau, Sara; Onofrj, Marco; Lugaresi, Alessandra; Alroughani, Raed; Prat, Alexandre; Girard, Marc; Duquette, Pierre; Terzi, Murat; Boz, Cavit; Grand'Maison, Francois; Hamdy, Sherif; Sola, Patrizia; Ferraro, Diana; Grammond, Pierre; Turkoglu, Recai; Buzzard, Katherine; Skibina, Olga; Yamout, Bassem; Gerlach, Oliver; van Pesch, Vincent; Blanco, Yolanda; Maimone, Davide; Lechner-Scott, Jeannette; Bergamaschi, Roberto; Karabudak, Rana; Iuliano, Gerardo; McGuigan, Chris; Cartechini, Elisabetta; Barnett, Michael; Hughes, Stella; Sa, Maria Jose; Solaro, Claudio; Kappos, Ludwig; Ramo-Tello, Cristina; Cristiano, Edgardo; Hodgkinson, Suzanne; Spitaleri, Daniele; Soysal, Aysun; Petersen, Thor; Slee, Mark; Butler, Ernest; Granella, Franco; de Gans, Koen; McCombe, Pamela; Ampapa, Radek; Van Wijmeersch, Bart; van der Walt, Anneke; Butzkueven, Helmut; Prevost, Julie; Sinnige, L. G. F.; Sanchez-Menoyo, Jose Luis; Vucic, Steve; Laureys, Guy; Van Hijfte, Liesbeth; Khurana, Dheeraj; Macdonell, Richard; Gouider, Riadh; Castillo-Trivino, Tamara; Gray, Orla; Aguera-Morales, Eduardo; Al-Asmi, Abdullah; Shaw, Cameron; Deri, Norma; Al-Harbi, Talal; Fragoso, Yara; Csepany, Tunde; Sempere, Angel Perez; Trevino-Frenk, Irene; Schepel, Jan; Moore, Fraser; Kalincik, Tomas, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), and School of Medicine

Abstract

Background and purpose: This study assessed the effect of patient characteristics on the response to disease-modifying therapy (DMT) in multiple sclerosis (MS). Methods: We extracted data from 61,810 patients from 135 centers across 35 countries from the MSBase registry. The selection criteria were: clinically isolated syndrome or definite MS, follow-up ? 1 year, and Expanded Disability Status Scale (EDSS) score ? 3, with ?1 score recorded per year. Marginal structural models with interaction terms were used to compare the hazards of 12-month confirmed worsening and improvement of disability, and the incidence of relapses between treated and untreated patients stratified by their characteristics. Results: Among 24,344 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.45–0.60), 46% lower risk of disability worsening (HR = 0.54, 95% CI = 0.41–0.71), and 32% greater chance of disability improvement (HR = 1.32, 95% CI = 1.09–1.59). The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The magnitude of the effect of DMT on suppressing relapses declined with higher prior relapse rate and prior cerebral magnetic resonance imaging activity. We did not find any evidence for the effect of age on the effectiveness of DMT. After inclusion of 1985 participants with progressive MS, the effect of DMT on disability mostly depended on MS phenotype, whereas its effect on relapses was driven mainly by prior relapse activity. Conclusions: DMT is generally most effective among patients with lower disability and in relapsing MS phenotypes. There is no evidence of attenuation of the effect of DMT with age., This study was financially supported by the National Health and Medical Research Council of Australia (1129189, 1140766, 1080518).

Published
2023

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. Sars-CoV2 infection in pregnant women with multiple sclerosis

Author

Aprea, Maria Grazia, Schiavetti, Irene, Portaccio, Emilio, Ballerini, Chiara, Battaglia, Mario Alberto, Bergamaschi, Roberto, Brichetto, Giampaolo, Bunul, S Destan, Calabrese, Massimiliano, Capobianco, Marco, Cavalla, Paola, Celani, Maria Grazia, Clerico, Marinella, Cocco, Eleonora, Comi, Giancarlo, Confalonieri, Paolo, Conte, Antonella, Cordioli, Cinzia, De Luca, Giovanna, De Rossi, Nicola, Filippi, Massimo, Gumes, Haluk, Immovilli, Paolo, Inglese, Matilde, Karabudak, Rana, Landi, Doriana, Lanzillo, Roberta, L'Episcopo, Maria Rita, Lorefice, Lorena, Mantero, Vittorio, Marangoni, Sabrina, Marfia, Girolama Alessandra, Masciulli, Camilla, Milano, Eva, Moiola, Lucia, Orlandi, Riccardo, Patti, Francesco, Perini, Paola, Pesci, Ilaria, Pucci, Eugenio, Puthenparampil, Marco, Radaelli, Marta, Salvetti, Marco, Sartori, Arianna, Scandellari, Cinzia, Sen, Sedat, Siva, Aksel, Strumia, Silvia, Teatini, Francesco, Tedeschi, Gioacchino, Trojano, Maria, Tutuncu, Melih, Vaula, Giovanna, Sormani, Maria Pia, and Amato, Maria Pia

Subjects
Multiple sclerosis, SARS-CoV-2 infection, COVID-19, COVID-19 outcomes, pregnancy, risk factors, Settore MED/26
Published
2023

25. Beyond Myelin Oligodendrocyte Glycoprotein and Aquaporin-4 Antibodies: Alternative Causes of Optic Neuritis.

Author

Greco, Giacomo, Colombo, Elena, Gastaldi, Matteo, Ahmad, Lara, Tavazzi, Eleonora, Bergamaschi, Roberto, and Rigoni, Eleonora

Subjects
MYELIN oligodendrocyte glycoprotein, OPTIC neuritis, OPTIC disc edema, AQUAPORINS, OPTIC disc, IMMUNOGLOBULINS, EYE movements, AUTOANTIBODIES
Abstract

Optic neuritis (ON) is the most common cause of vision loss in young adults. It manifests as acute or subacute vision loss, often accompanied by retrobulbar discomfort or pain during eye movements. Typical ON is associated with Multiple Sclerosis (MS) and is generally mild and steroid-responsive. Atypical forms are characterized by unusual features, such as prominent optic disc edema, poor treatment response, and bilateral involvement, and they are often associated with autoantibodies against aquaporin-4 (AQP4) or Myelin Oligodendrocyte Glycoprotein (MOG). However, in some cases, AQP4 and MOG antibodies will return as negative, plunging the clinician into a diagnostic conundrum. AQP4- and MOG-seronegative ON warrants a broad differential diagnosis, including autoantibody-associated, granulomatous, and systemic disorders. These rare forms need to be identified promptly, as their management and prognosis are greatly different. The aim of this review is to describe the possible rarer etiologies of non-MS-related and AQP4- and MOG-IgG-seronegative inflammatory ON and discuss their diagnoses and treatments. [ABSTRACT FROM AUTHOR]

Published
2023
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27. Disability accrual in primary and secondary progressive multiple sclerosis

Author

Harding-Forrester, Sam, Roos, Izanne, Nguyen, Ai-Lan, Malpas, Charles B, Diouf, Ibrahima, Moradi, Nahid, Sharmin, Sifat, Izquierdo, Guillermo, Eichau, Sara, Patti, Francesco, Horakova, Dana, Kubala Havrdova, Eva, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grand'Maison, Francois, Onofrj, Marco, Lugaresi, Alessandra, Grammond, Pierre, Ozakbas, Serkan, Amato, Maria Pia, Gerlach, Oliver, Sola, Patrizia, Ferraro, Diana, Buzzard, Katherine, Skibina, Olga, Lechner-Scott, Jeannette, Alroughani, Raed, Boz, Cavit, Van Pesch, Vincent, Cartechini, Elisabetta, Terzi, Murat, Maimone, Davide, Ramo-Tello, Cristina, Yamout, Bassem, Khoury, Samia Joseph, La Spitaleri, Daniele, Sa, Maria Jose, Blanco, Yolanda, Granella, Franco, Slee, Mark, Butler, Ernest, Sidhom, Youssef, Gouider, Riadh, Bergamaschi, Roberto, Karabudak, Rana, Ampapa, Radek, Sánchez-Menoyo, José Luis, Prevost, Julie, Castillo-Trivino, Tamara, McCombe, Pamela A, Macdonell, Richard, Laureys, Guy, Van Hijfte, Liesbeth, Oh, Jiwon, Altintas, Ayse, de Gans, Koen, Turkoglu, Recai, van der Walt, Anneke, Butzkueven, Helmut, Vucic, Steve, Barnett, Michael, Cristiano, Edgardo, Hodgkinson, Suzanne, Iuliano, Gerardo, Kappos, Ludwig, Kuhle, Jens, Shaygannejad, Vahid, Soysal, Aysun, Weinstock-Guttman, Bianca, Van Wijmeersch, Bart, Kalincik, Tomas, MSBase investigators, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
Psychiatry and Mental health, Surgery, Neurology (clinical), multiple sclerosis
Abstract

BackgroundSome studies comparing primary and secondary progressive multiple sclerosis (PPMS, SPMS) report similar ages at onset of the progressive phase and similar rates of subsequent disability accrual. Others report later onset and/or faster accrual in SPMS. Comparisons have been complicated by regional cohort effects, phenotypic differences in sex ratio and management and variable diagnostic criteria for SPMS.MethodsWe compared disability accrual in PPMS and operationally diagnosed SPMS in the international, clinic-based MSBase cohort. Inclusion required PPMS or SPMS with onset at age ≥18 years since 1995. We estimated Andersen-Gill hazard ratios for disability accrual on the Expanded Disability Status Scale (EDSS), adjusted for sex, age, baseline disability, EDSS score frequency and drug therapies, with centre and patient as random effects. We also estimated ages at onset of the progressive phase (Kaplan-Meier) and at EDSS milestones (Turnbull). Analyses were replicated with physician-diagnosed SPMS.ResultsIncluded patients comprised 1872 with PPMS (47% men; 50% with activity) and 2575 with SPMS (32% men; 40% with activity). Relative to PPMS, SPMS had older age at onset of the progressive phase (median 46.7 years (95% CI 46.2–47.3) vs 43.9 (43.3–44.4); pConclusionsWe demonstrate later onset of the progressive phase and slower disability accrual in SPMS versus PPMS. This may balance greater baseline disability in SPMS, yielding convergent disability trajectories across phenotypes. The different rates of disability accrual should be considered before amalgamating PPMS and SPMS in clinical trials.

Published
2023

28. Barriers to exercise and the role of general practitioner: A cross-sectional survey among people with multiple sclerosis

Author

Correale, Luca, primary, Martinis, Luca, additional, Tavazzi, Eleonora, additional, Pedullà, Ludovico, additional, Mallucci, Giulia, additional, Brichetto, Giampaolo, additional, Bove, Marco, additional, Ponzio, Michela, additional, Borrelli, Paola, additional, Monti, Maria Cristina, additional, Bergamaschi, Roberto, additional, and Montomoli, Cristina, additional

Published
2022
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29. 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, 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

Subjects
Multiple Sclerosis, Centers’ characteristics, Italian Multiple Sclerosis Register, Multiple sclerosis phenotypes, Real-world data, Settore MED/42 - Igiene Generale e Applicata, Dermatology, General Medicine, Multiple Sclerosis, Chronic Progressive, Settore MED/26, Settore SECS-S/04 - Demografia, Multiple sclerosis phenotype, Settore MED/01 - Statistica Medica, Psychiatry and Mental health, Multiple Sclerosis, Relapsing-Remitting, Phenotype, Recurrence, Humans, Female, Settore MED/26 - Neurologia, Neurology (clinical), Centers’ characteristic, Referral and Consultation
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

30. American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Postoperative Gastrointestinal Dysfunction Within an Enhanced Recovery Pathway for Elective Colorectal Surgery

Author

Hedrick, Traci L., McEvoy, Matthew D., Mythen, Michael (Monty) G., Bergamaschi, Roberto, Gupta, Ruchir, Holubar, Stefan D., Senagore, Anthony J., Gan, Tong Joo, Shaw, Andrew D., Thacker, Julie K. M., Miller, Timothy E., Wischmeyer, Paul E., Carli, Franco, Evans, David C., Guilbert, Sarah, Kozar, Rosemary, Pryor, Aurora, Thiele, Robert H., Everett, Sotiria, Grocott, Mike, Abola, Ramon E., Bennett-Guerrero, Elliott, Kent, Michael L., Feldman, Liane S., and Fiore, Julio F., Jr

Published
2018
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31. American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Patient-Reported Outcomes in an Enhanced Recovery Pathway

Author

Abola, Ramon E., Bennett-Guerrero, Elliott, Kent, Michael L., Feldman, Liane S., Fiore, Julio F., Jr, Shaw, Andrew D., Thacker, Julie K. M., Gan, Tong J., Miller, Timothy E., Hedrick, Traci L., McEvoy, Matthew D., Mythen, Michael G., Bergamaschi, Roberto, Gupta, Ruchir, Holubar, Stefan D., Senagore, Anthony J., Wischmeyer, Paul E., Carli, Franco, Evans, David C., Guilbert, Sarah, Kozar, Rosemary, Pryor, Aurora, Thiele, Robert H., Everett, Sotiria, and Grocott, Mike

Published
2018
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32. American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Nutrition Screening and Therapy Within a Surgical Enhanced Recovery Pathway

Author

Wischmeyer, Paul E., Carli, Franco, Evans, David C., Guilbert, Sarah, Kozar, Rosemary, Pryor, Aurora, Thiele, Robert H., Everett, Sotiria, Grocott, Mike, Gan, Tong J., Shaw, Andrew D., Thacker, Julie K. M., Miller, Timothy E., Hedrick, Traci L., McEvoy, Matthew D., Mythen, Michael G., Bergamaschi, Roberto, Gupta, Ruchir, Holubar, Stefan D., Senagore, Anthony J., Abola, Ramon E., Bennett-Guerrero, Elliott, Kent, Michael L., Feldman, Liane S., and Fiore, Julio F., Jr

Published
2018
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33. A nurse-led, telephone-based patient support program for improving adherence in patients with relapsing-remitting multiple sclerosis using interferon beta-1a: Lessons from a consumer-based survey on adveva® PSP

Author

Barello, Serena, Paolicelli, Damiano, Bergamaschi, Roberto, Cottone, Salvatore, DAmico, Alessandra, Annibali, Viviana, Paolillo, Andrea, Bosio, Caterina, Panetta, Valentina, and Graffigna, Guendalina

Subjects
General Psychology
Abstract

BackgroundEvidence suggests that organizational models that provide care interventions including patient support programs may increase patient adherence to multiple sclerosis (MS) therapies by providing tailored symptom management, informational support, psychological and/or social support, lifestyle changes, emotional adjustment, health education, and tailored coaching, thus improving patients' overall quality of life across the disease course.ObjectiveThe main objective of this study was to describe MS patients' self-reported experience of a nurse-led, telephone-based PSP and to explore its potential role in improving disease and therapy management skills.MethodsSurvey data were analyzed from a subset of patients relapsing–remitting MS (RRMS) using interferon beta-1a already registered in the adveva® PSP from three Italian multiple sclerosis centers with a consolidated experience in RRMS disease, treatment management, and PSP programs.ResultsIn total, 244 patient data at baseline were analyzed, of which 115 had a follow-up of at least 6 months. Results from this study provide an early view into the role of this PSP in improving the patients reported overall experience regarding disease management and injectable therapy, thus potentially ameliorating treatment adherence and decreasing health care cost. Moreover, study findings confirm the role of providing a patient-focused support by addressing non-medication-related topics in the PSP consultations. Indeed, patients involved in the adveva® PSP program reported a better psychological status in the follow up as demonstrated by an increased optimism regarding their future, tolerance of disease uncertainty, and their perceived ability to benefit from external help and social support (informal caregivers).ConclusionsAs such, it is reasonable to conclude that the involvement in the adveva® PSP and the PSP's assistance in guiding patients on proper treatment self-management techniques is of great value to patients as it might contribute to improving engagement in their health care journey in terms of perceived self-care skills, emotional coping toward the future and the unpredictability of the disease course and their general attitudes toward the injection itself, involving pain tolerance.

Published
2022

36. Multiple Sclerosis Severity Score (MSSS) improves the accuracy of individualized prediction in MS

Author

Kalincik, Tomas, Kister, Ilya, Bacon, Tamar E, Malpas, Charles B, Sharmin, Sifat, Horakova, Dana, Kubala-Havrdova, Eva, Patti, Francesco, Izquierdo, Guillermo, Eichau, Sara, Ozakbas, Serkan, Onofrj, Marco, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grammond, Pierre, Sola, Patrizia, Ferraro, Diana, Alroughani, Raed, Terzi, Murat, Boz, Cavit, Grand'Maison, Francois, Bergamaschi, Roberto, Gerlach, Oliver, Sa, Maria J, Kappos, Ludwig, Cartechini, Elisabetta, Lechner-Scott, Jeannette, Van Pesch, Vincent, Shaygannejad, Vahid, Granella, Franco, Spitaleri, Daniele, Iuliano, Gerardo, Maimone, Davide, Prevost, Julie, Soysal, Aysun, Turkoglu, Recai, Ampapa, Radek, Butzkueven, Helmut, Cutter, Gary, for MSBase Study Group, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
Adult, Male, Multiple Sclerosis, Multiple Sclerosis Severity Score (MSSS), Middle Aged, Severity of Illness Index, Disability Evaluation, Neurology, prognostics, relapse prediction, Recurrence, Disease Progression, Humans, Female, Neurology (clinical), Prospective Studies
Abstract

Background: The MSBase prediction model of treatment response leverages multiple demographic and clinical characteristics to estimate hazards of relapses, confirmed disability accumulation (CDA), and confirmed disability improvement (CDI). The model did not include Multiple Sclerosis Severity Score (MSSS), a disease duration-adjusted ranked score of disability. Objective: To incorporate MSSS into the MSBase prediction model and compare model accuracy with and without MSSS. Methods: The associations between MSSS and relapse, CDA, and CDI were evaluated with marginal proportional hazards models adjusted for three principal components representative of patients’ demographic and clinical characteristics. The model fit with and without MSSS was assessed with penalized r2 and Harrell C. Results: A total of 5866 MS patients were started on disease-modifying therapy during prospective follow-up (age 38.4 ± 10.6 years; 72% female; disease duration 8.5 ± 7.7 years). Including MSSS into the model improved the accuracy of individual prediction of relapses by 31%, of CDA by 23%, and of CDI by 24% (Harrell C) and increased the amount of variance explained for relapses by 49%, for CDI by 11%, and for CDA by 10% as compared with the original model. Conclusion: Addition of a single, readily available metric, MSSS, to the comprehensive MSBase prediction model considerably improved the individual accuracy of prognostics in MS.

Published
2022

37. Confirmed disability progression as a marker of permanent disability in multiple sclerosis.

Author

UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de biochimie médicale, UCL - (SLuc) Service de neurologie, Sharmin, Sifat, Bovis, Francesca, Malpas, Charles, Horakova, Dana, Havrdova, Eva Kubala, Izquierdo, Guillermo, Eichau, Sara, Trojano, Maria, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Onofrj, Marco, Lugaresi, Alessandra, Grand'Maison, Francois, Grammond, Pierre, Sola, Patrizia, Ferraro, Diana, Terzi, Murat, Gerlach, Oliver, Alroughani, Raed, Boz, Cavit, Shaygannejad, Vahid, van Pesch, Vincent, Cartechini, Elisabetta, Kappos, Ludwig, Lechner-Scott, Jeannette, Bergamaschi, Roberto, Turkoglu, Recai, Solaro, Claudio, Iuliano, Gerardo, Granella, Franco, Van Wijmeersch, Bart, Spitaleri, Daniele, Slee, Mark, McCombe, Pamela, Prevost, Julie, Ampapa, Radek, Ozakbas, Serkan, Sanchez-Menoyo, Jose Luis, Soysal, Aysun, Vucic, Steve, Petersen, Thor, de Gans, Koen, Butler, Ernest, Hodgkinson, Suzanne, Sidhom, Youssef, Gouider, Riadh, Cristiano, Edgardo, Castillo-Triviño, Tamara, Saladino, Maria Laura, Barnett, Michael, Moore, Fraser, Rozsa, Csilla, Yamout, Bassem, Skibina, Olga, van der Walt, Anneke, Buzzard, Katherine, Gray, Orla, Hughes, Stella, Sempere, Angel Perez, Singhal, Bhim, Fragoso, Yara, Shaw, Cameron, Kermode, Allan, Taylor, Bruce, Simo, Magdolna, Shuey, Neil, Al-Harbi, Talal, Macdonell, Richard, Dominguez, Jose Andres, Csepany, Tunde, Sirbu, Carmen Adella, Sormani, Maria Pia, Butzkueven, Helmut, Kalincik, Tomas, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de biochimie médicale, UCL - (SLuc) Service de neurologie, Sharmin, Sifat, Bovis, Francesca, Malpas, Charles, Horakova, Dana, Havrdova, Eva Kubala, Izquierdo, Guillermo, Eichau, Sara, Trojano, Maria, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Onofrj, Marco, Lugaresi, Alessandra, Grand'Maison, Francois, Grammond, Pierre, Sola, Patrizia, Ferraro, Diana, Terzi, Murat, Gerlach, Oliver, Alroughani, Raed, Boz, Cavit, Shaygannejad, Vahid, van Pesch, Vincent, Cartechini, Elisabetta, Kappos, Ludwig, Lechner-Scott, Jeannette, Bergamaschi, Roberto, Turkoglu, Recai, Solaro, Claudio, Iuliano, Gerardo, Granella, Franco, Van Wijmeersch, Bart, Spitaleri, Daniele, Slee, Mark, McCombe, Pamela, Prevost, Julie, Ampapa, Radek, Ozakbas, Serkan, Sanchez-Menoyo, Jose Luis, Soysal, Aysun, Vucic, Steve, Petersen, Thor, de Gans, Koen, Butler, Ernest, Hodgkinson, Suzanne, Sidhom, Youssef, Gouider, Riadh, Cristiano, Edgardo, Castillo-Triviño, Tamara, Saladino, Maria Laura, Barnett, Michael, Moore, Fraser, Rozsa, Csilla, Yamout, Bassem, Skibina, Olga, van der Walt, Anneke, Buzzard, Katherine, Gray, Orla, Hughes, Stella, Sempere, Angel Perez, Singhal, Bhim, Fragoso, Yara, Shaw, Cameron, Kermode, Allan, Taylor, Bruce, Simo, Magdolna, Shuey, Neil, Al-Harbi, Talal, Macdonell, Richard, Dominguez, Jose Andres, Csepany, Tunde, Sirbu, Carmen Adella, Sormani, Maria Pia, Butzkueven, Helmut, and Kalincik, Tomas

Abstract

The prevention of disability over the long term is the main treatment goal in multiple sclerosis (MS); however, randomized clinical trials evaluate only short-term treatment effects on disability. This study aimed to define criteria for 6-month confirmed disability progression events of MS with a high probability of resulting in sustained long-term disability worsening. In total, 14,802 6-month confirmed disability progression events were identified in 8741 patients from the global MSBase registry. For each 6-month confirmed progression event (13,321 in the development and 1481 in the validation cohort), a sustained progression score was calculated based on the demographic and clinical characteristics at the time of progression that were predictive of long-term disability worsening. The score was externally validated in the Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) trial. The score was based on age, sex, MS phenotype, relapse activity, disability score and its change from baseline, number of affected functional system domains and worsening in six of the domains. In the internal validation cohort, a 61% lower chance of improvement was estimated with each unit increase in the score (hazard ratio 0.39, 95% confidence interval 0.29-0.52; discriminatory index 0.89). The proportions of progression events sustained at 5 years stratified by the score were 1: 72%; 2: 88%; 3: 94%; 4: 100%. The results of the CLARITY trial were confirmed for reduction of disability progression that was >88% likely to be sustained (events with score ˃1.5). Clinicodemographic characteristics of 6-month confirmed disability progression events identify those at high risk of sustained long-term disability. This knowledge will allow future trials to better assess the effect of therapy on long-term disability accrual.

Published
2022

38. 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

40. Towards personalized therapy for multiple sclerosis: prediction of individual treatment response

Author

Kalincik, Tomas, Manouchehrinia, Ali, Sobisek, Lukas, Jokubaitis, Vilija, Spelman, Tim, Horakova, Dana, Havrdova, Eva, Trojano, Maria, Izquierdo, Guillermo, Lugaresi, Alessandra, Girard, Marc, Prat, Alexandre, Duquette, Pierre, Grammond, Pierre, Sola, Patrizia, Hupperts, Raymond, GrandʼMaison, Francois, Pucci, Eugenio, Boz, Cavit, Alroughani, Raed, Van Pesch, Vincent, Lechner-Scott, Jeannette, Terzi, Murat, Bergamaschi, Roberto, Iuliano, Gerardo, Granella, Franco, Spitaleri, Daniele, Shaygannejad, Vahid, Oreja-Guevara, Celia, Slee, Mark, Ampapa, Radek, Verheul, Freek, McCombe, Pamela, Olascoaga, Javier, Amato, Maria Pia, Vucic, Steve, Hodgkinson, Suzanne, Ramo-Tello, Cristina, Flechter, Shlomo, Cristiano, Edgardo, Rozsa, Csilla, Moore, Fraser, Sanchez-Menoyo, Jose Luis, Saladino, Maria Laura, Barnett, Michael, Hillert, Jan, and Butzkueven, Helmut

Published
2017
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41. A group resilience training program for people with multiple sclerosis: Study protocol of a multi-centre cluster-randomized controlled trial (multi-READY for MS)

Author

Giovannetti, Ambra Mara, primary, Pakenham, Kenneth Ian, additional, Presti, Giovambattista, additional, Quartuccio, Maria Esmeralda, additional, Confalonieri, Paolo, additional, Bergamaschi, Roberto, additional, Grobberio, Monica, additional, Di Filippo, Massimiliano, additional, Micheli, Mary, additional, Brichetto, Giampaolo, additional, Patti, Francesco, additional, Copetti, Massimiliano, additional, Kruger, Paola, additional, and Solari, Alessandra, additional

Published
2022
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42. Progression is independent of relapse activity in early multiple sclerosis: a real-life cohort study

Author

Portaccio, Emilio, primary, Bellinvia, Angelo, additional, Fonderico, Mattia, additional, Pastò, Luisa, additional, Razzolini, Lorenzo, additional, Totaro, Rocco, additional, Spitaleri, Daniele, additional, Lugaresi, Alessandra, additional, Cocco, Eleonora, additional, Onofrj, Marco, additional, Di Palma, Franco, additional, Patti, Francesco, additional, Maimone, Davide, additional, Valentino, Paola, additional, Confalonieri, Paolo, additional, Protti, Alessandra, additional, Sola, Patrizia, additional, Lus, Giacomo, additional, Maniscalco, Giorgia Teresa, additional, Brescia Morra, Vincenzo, additional, Salemi, Giuseppe, additional, Granella, Franco, additional, Pesci, Ilaria, additional, Bergamaschi, Roberto, additional, Aguglia, Umberto, additional, Vianello, Marika, additional, Simone, Marta, additional, Lepore, Vito, additional, Iaffaldano, Pietro, additional, Filippi, Massimo, additional, Trojano, Maria, additional, and Amato, Maria Pia, additional

Published
2022
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43. Association of Latitude and Exposure to Ultraviolet B Radiation With Severity of Multiple Sclerosis: An International Registry Study

Author

Vitkova, Marianna, Diouf, Ibrahima, Malpas, Charles, Horakova, Dana, Kubala Havrdova, Eva, Patti, Francesco, Ozakbas, Serkan, Izquierdo, Guillermo, Eichau, Sara, Shaygannejad, Vahid, Onofrj, Marco, Lugaresi, Alessandra, Alroughani, Raed, Prat, Alexandre, Larochelle, Catherine, Girard, Marc, Duquette, Pierre, Terzi, Murat, Boz, Cavit, Grand'Maison, Francois, Sola, Patrizia, Ferraro, Diana, Grammond, Pierre, Butzkueven, Helmut, Buzzard, Katherine, Skibina, Olga, Yamout, Bassem I, Karabudak, Rana, Gerlach, Oliver, Lechner-Scott, Jeannette, Maimone, Davide, Bergamaschi, Roberto, Van Pesch, Vincent, Iuliano, Gerardo, Cartechini, Elisabetta, José Sà, Maria, Ampapa, Radek, Barnett, Michael, Hughes, Stella E, Ramo-Tello, Cristina M, Hodgkinson, Suzanne, Spitaleri, Daniele L A, Petersen, Thor, Butler, Ernest Gerard, Slee, Mark, McGuigan, Chris, McCombe, Pamela Ann, Granella, Franco, Cristiano, Edgardo, Prevost, Julie, Taylor, Bruce V, Sãnchez-Menoyo, Josã Luis, Laureys, Guy, Van Hijfte, Liesbeth, Vucic, Steve, Macdonell, Richard A, Gray, Orla, Olascoaga, Javier, Deri, Norma, Fragoso, Yara Dadalti, Shaw, Cameron, Kalincik, Tomas, MSBase Study Group, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
Male, Disability Evaluation, Multiple Sclerosis, Ultraviolet Rays, Sunlight, Humans, Female, Neurology (clinical), Registries, Severity of Illness Index, Research Article
Abstract

Background and ObjectivesThe severity of multiple sclerosis (MS) varies widely among individuals. Understanding the determinants of this heterogeneity will help clinicians optimize the management of MS. The aim of this study was to investigate the association between latitude of residence, UV B radiation (UVB) exposure, and the severity of MS.MethodsThis observational study used the MSBase registry data. The included patients met the 2005 or 2010 McDonald diagnostic criteria for MS and had a minimum dataset recorded in the registry (date of birth, sex, clinic location, date of MS symptom onset, disease phenotype at baseline and censoring, and ≥1 Expanded Disability Status Scale score recorded). The latitude of each study center and cumulative annualized UVB dose at study center (calculated from National Aeronautics and Space Administration’s Total Ozone Mapping Spectrometer) at ages 6 and 18 years and the year of disability assessment were calculated. Disease severity was quantified with Multiple Sclerosis Severity Score (MSSS). Quadratic regression was used to model the associations between latitude, UVB, and MSSS.ResultsThe 46,128 patients who contributed 453,208 visits and a cumulative follow-up of 351,196 patient-years (70% women, mean age 39.2 ± 12 years, resident between latitudes 19°35′ and 56°16′) were included in this study. Latitude showed a nonlinear association with MS severity. In latitudes DiscussionIn temperate zones, MS severity is associated with latitude. This association is mainly, but not exclusively, driven by UVB exposure contributing to both MS susceptibility and severity.

Published
2022

44. Effect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years

Author

Kalincik, Tomas, Diouf, Ibrahima, Sharmin, Sifat, Malpas, Charles, Spelman, Tim, Horakova, Dana, Havrdova, Eva Kubala, Trojano, Maria, Izquierdo, Guillermo, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grammond, Pierre, Jokubaitis, Vilija, van der Walt, Anneke, Grand'Maison, Francois, Sola, Patrizia, Ferraro, Diana, Shaygannejad, Vahid, Alroughani, Raed, Hupperts, Raymond, Terzi, Murat, Boz, Cavit, Lechner-Scott, Jeannette, Pucci, Eugenio, Van Pesch, Vincent, Granella, Franco, Bergamaschi, Roberto, Spitaleri, Daniele, Slee, Mark, Vucic, Steve, Ampapa, Radek, McCombe, Pamela, Ramo-Tello, Cristina, Prevost, Julie, Olascoaga, Javier, Cristiano, Edgardo, Barnett, Michael, Saladino, Maria Laura, Sanchez-Menoyo, Jose Luis, Hodgkinson, Suzanne, Rozsa, Csilla, Hughes, Stella, Moore, Fraser, Shaw, Cameron, Butler, Ernest, Skibina, Olga, Gray, Orla, Kermode, Allan, Csepany, Tunde, Singhal, Bhim, Shuey, Neil, Piroska, Imre, Taylor, Bruce, Simo, Magdolna, Sirbu, Carmen-Adella, Sas, Attila, Butzkueven, Helmut, MSBase Study Group, UCL - (SLuc) Service de neurologie, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Kalincik, Toma, Diouf, Ibrahima, Sharmin, Sifat, Malpas, Charle, Spelman, Tim, Horakova, Dana, Havrdova, Eva Kubala, Trojano, Maria, Izquierdo, Guillermo, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grammond, Pierre, Jokubaitis, Vilija, van der Walt, Anneke, Grand'Maison, Francoi, Sola, Patrizia, Ferraro, Diana, Shaygannejad, Vahid, Alroughani, Raed, Hupperts, Raymond, Terzi, Murat, Boz, Cavit, Lechner-Scott, Jeannette, Pucci, Eugenio, Van Pesch, Vincent, Granella, Franco, Bergamaschi, Roberto, Spitaleri, Daniele, Slee, Mark, Vucic, Steve, Ampapa, Radek, McCombe, Pamela, Ramo-Tello, Cristina, Prevost, Julie, Olascoaga, Javier, Cristiano, Edgardo, Barnett, Michael, Saladino, Maria Laura, Sanchez-Menoyo, Jose Lui, Hodgkinson, Suzanne, Rozsa, Csilla, Hughes, Stella, Moore, Fraser, Shaw, Cameron, Butler, Ernest, Skibina, Olga, Gray, Orla, Kermode, Allan, Csepany, Tunde, Singhal, Bhim, Shuey, Neil, Piroska, Imre, Taylor, Bruce, Simo, Magdolna, Sirbu, Carmen-Adella, Sas, Attila, and Butzkueven, Helmut

Subjects
Adult, Male, medicine.medical_specialty, Article, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, multiple sclerosis, treatment, prognosis, Internal medicine, medicine, Humans, Immunologic Factors, Disease Progression, Female, Fingolimod Hydrochloride, Glatiramer Acetate, Immunosuppressive Agents, Interferon-beta, Longitudinal Studies, Middle Aged, Proportional Hazards Models, 030212 general & internal medicine, Glatiramer acetate, Expanded Disability Status Scale, Proportional hazards model, business.industry, Multiple sclerosis, Hazard ratio, medicine.disease, Confidence interval, Cohort, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract

ObjectiveTo test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients.MethodsWe studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously readjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability, and MRI activity.ResultsA total of 14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval [CI] 0.43–0.82, p = 0.0016), worsening of disability (0.56, 0.38–0.82, p = 0.0026), and progress to EDSS step 6 (0.33, 0.19–0.59, p = 0.00019). Among 1,085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50–0.70, p = 10−9) and worsening of disability (0.81, 0.67–0.99, p = 0.043).ConclusionContinued treatment with MS immunotherapies reduces disability accrual by 19%–44% (95% CI 1%–62%), the risk of need of a walking aid by 67% (95% CI 41%–81%), and the frequency of relapses by 40–41% (95% CI 18%–57%) over 15 years. This study provides evidence that disease-modifying therapies are effective in improving disability outcomes in relapsing-remitting MS over the long term.Classification of EvidenceThis study provides Class IV evidence that, for patients with relapsing-remitting MS, long-term exposure to immunotherapy prevents neurologic disability.

Published
2021

46. Etiological research in pediatric multiple sclerosis: A tool to assess environmental exposures (PEDiatric Italian Genetic and enviRonment ExposurE Questionnaire)

Author

Pilotto, Silvy, primary, Gencarelli, Jessica, additional, Bova, Stefania, additional, Gerosa, Leonardo, additional, Baroncini, Damiano, additional, Olivotto, Sara, additional, Alfei, Enrico, additional, Zaffaroni, Mauro, additional, Suppiej, Agnese, additional, Cocco, Eleonora, additional, Trojano, Maria, additional, Amato, Maria Pia, additional, D'Alfonso, Sandra, additional, Martinelli-Boneschi, Filippo, additional, Waubant, Emmanuelle, additional, Ghezzi, Angelo, additional, Bergamaschi, Roberto, additional, and Pugliatti, Maura, additional

Published
2021
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47. Fingolimod versus interferon beta/glatiramer acetate after natalizumab suspension in multiple sclerosis

Author

Iaffaldano, Pietro, Lucisano, Giuseppe, Pozzilli, Carlo, Brescia Morra, Vincenzo, Ghezzi, Angelo, Millefiorini, Enrico, Patti, Francesco, Lugaresi, Alessandra, Zimatore, Giovanni Bosco, Marrosu, Maria Giovanna, Amato, Maria Pia, Bertolotto, Antonio, Bergamaschi, Roberto, Granella, Franco, Coniglio, Gabriella, Tedeschi, Gioacchino, Sola, Patrizia, Lus, Giacomo, Ferrò, Maria Teresa, Iuliano, Gerardo, Corea, Francesco, Protti, Alessandra, Cavalla, Paola, Guareschi, Angelica, Rodegher, Mariaemma, Paolicelli, Damiano, Tortorella, Carla, Lepore, Vito, Prosperini, Luca, Saccà, Francesco, Baroncini, Damiano, Comi, Giancarlo, and Trojano, Maria

Published
2015
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48. Defining reliable disability outcomes in multiple sclerosis

Author

Kalincik, Tomas, Cutter, Gary, Spelman, Tim, Jokubaitis, Vilija, Havrdova, Eva, Horakova, Dana, Trojano, Maria, Izquierdo, Guillermo, Girard, Marc, Duquette, Pierre, Prat, Alexandre, Lugaresi, Alessandra, Grand’Maison, Francois, Grammond, Pierre, Hupperts, Raymond, Oreja-Guevara, Celia, Boz, Cavit, Pucci, Eugenio, Bergamaschi, Roberto, Lechner-Scott, Jeannette, Alroughani, Raed, Van Pesch, Vincent, Iuliano, Gerardo, Fernandez-Bolaños, Ricardo, Ramo, Cristina, Terzi, Murat, Slee, Mark, Spitaleri, Daniele, Verheul, Freek, Cristiano, Edgardo, Sánchez-Menoyo, José Luis, Fiol, Marcela, Gray, Orla, Cabrera-Gomez, Jose Antonio, Barnett, Michael, and Butzkueven, Helmut

Published
2015
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49. Association of Latitude and Exposure to Ultraviolet B Radiation with Severity of Multiple Sclerosis

Author

Vitkova, Marianna, Diouf, Ibrahima, Malpas, Charles, Horakova, Dana, Eva Kubala Havrdova, Patti, Francesco, Ozakbas, Serkan, Izquierdo Ayuso, Guillermo, Eichau Madueno, Sara, Shaygannejad, Vahid, Onofrj, Marco, Lugaresi, Alessandra, Alroughani, Raed, Prat, Alexandre, Larochelle, Catherine, Girard, Marc, Duquette, Pierre, Terzi, Murat, Boz, Cavit, Grand Maison, Francois, Sola, Patrizia, Ferraro, Diana, Grammond, Pierre, Butzkueven, Helmut, Buzzard, Katherine, Skibina, Olga, Yamout, Bassem, Karabudak, Rana, Gerlach, Oliver H. H., Lechner-Scott, Jeannette, Maimone, Davide, Bergamaschi, Roberto, Pesch, Vincent, Iuliano, Gerardo, Cartechini, Elisabetta, Sa, Maria Jose, Ampapa, Radek, Barnett, Michael, Hughes, Stella, Ramo-Tello, Cristina, Hodgkinson, Suzanne, Spitareli, Daniele, Petersen, Thor, Butler, Ernest, Slee, Mark, Mcguigan, Christopher, Mccombe, Pamela, Granella, Franco, Cristiano, Edgardo, Prevost, Julie, Taylor, Bruce, Luis Sanchez-Menoyo, Jose, Laureys, Guy, Hijfte, Liesbeth, Vucic, Steve, Macdonell, Richard, Gray, Orla, Olascoaga Urtaza, Francisco Javier, Deri, Norma, Fragoso, Yara, Shaw, Cameron, and Kalincik, Tomas

Published
2021

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