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1. 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

2. 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

3. Pain, quality of life, and religiosity in people with multiple sclerosis

Author

Abbadessa Gianmarco, Bonavita Simona, Trojsi Francesca, Sparaco Maddalena, Lavorgna Luigi, Miele Giuseppina, Ippolito Domenico, Sparaco, Maddalena, Miele, Giuseppina, Abbadessa, Gianmarco, Ippolito, Domenico, Trojsi, Francesca, Lavorgna, Luigi, and Bonavita, Simona

Subjects
Multiple Sclerosis, Visual analogue scale, media_common.quotation_subject, Pain, Dermatology, Religiosity, Faith, Quality of life (healthcare), Surveys and Questionnaires, Spirituality, Humans, Medicine, Multiple sclerosi, media_common, Expanded Disability Status Scale, business.industry, Multiple sclerosis, General Medicine, medicine.disease, Prayer, Religion, Psychiatry and Mental health, Quality of Life, Neurology (clinical), business, Clinical psychology
Abstract

Purpose To investigate in multiple sclerosis (MS) patients, the relationship between pain and religiosity and to determine whether distinct dimensions of religiosity were associated with quality of life. Methods MS patients during clinical follow-up filled out the visual analogue scale for pain (VAS), the Mc Gill questionnaire (McGQ), the 36-Item Short Form Health Survey (SF-36), and the religious attitude scale (RAS), and expanded disability status scale (EDSS) was assessed. Results Ninety-two MS patients were enrolled, only two declined. There was a negative correlation between religious practice and faith and some domains of the SF-36 and a positive correlation between sensory, affective, and evaluative aspects of pain (at McGQ) and religious practices, and between evaluative aspects of pain (at McGQ) and faith. EDSS was significantly higher in practitioner believers compared to not practitioners. Conclusions More disabled MS patients, with worse quality of life, also due to physical pain, find a source of comfort in faith and religious practices. Pain is not relieved by prayer; therefore, we may guess that in MS the poor beneficial effect of religiosity and practice on pain perception may be linked to a structural/functional damage of neural circuits involved in reducing pain during prayer.

Published
2021

4. Telemedicine application to headache: a critical review

Author

Spina, Emanuele, Tedeschi, Gioacchino, Russo, Antonio, Trojsi, Francesca, Iodice, Rosa, Tozza, Stefano, Iovino, Aniello, Iodice, Francesco, Abbadessa, Gianmarco, di Lorenzo, Francesco, Miele, Giuseppina, Maida, Elisabetta, Cerullo, Giovanni, Sparaco, Maddalena, Silvestro, Marcello, Leocani, Letizia, Bonavita, Simona, Manganelli, Fiore, Lavorgna, Luigi, Spina, E., Tedeschi, G., Russo, A., Trojsi, F., Iodice, R., Tozza, S., Iovino, A., Iodice, F., Abbadessa, G., di Lorenzo, F., Miele, G., Maida, E., Cerullo, G., Sparaco, M., Silvestro, M., Leocani, L., Bonavita, S., Manganelli, F., and Lavorgna, L.

Subjects
Migraine Disorders, Headache, COVID-19, Reproducibility of Results, Tele-rehabilitation, Dermatology, General Medicine, Telemedicine, Psychiatry and Mental health, Telehealth, Humans, Original Article, Neurology (clinical), Child, Pandemics, Migraine
Abstract

Background Migraine affects more than a billion people all over the world and requires critical employment of healthcare resources. Telemedicine could be a reasonable tool to manage people suffering from headaches, and it received a big push from the COVID-19 pandemic. Objective This review aims to propose a practical approach for the virtual management of these patients. Methods To do this, we conducted a literature search, including 32 articles relevant to the topic treated in this review. Results The most challenging step in telemedicine applied to practical neurology remains the clinical assessment, but through a careful headache history and a recently proposed entirely virtual neurological assessment, this hitch can be easily overcome. Electronic diary compilations and virtual administration of disability-measuring scales, conversely, are the key features of effective long-term follow-up although we do not have apps that met the criteria of scientific reliability. Furthermore, tele-rehabilitation seems to be effective and has demonstrated to be a solution to alternatively treat chronic patients at home, and can be considered part of the remote management of headache patients. Moreover, virtual management of headaches finds an application in specific communities of patients, as pediatric patients and for rural communities of low- and middle-income countries suffer from health disparities, with inadequate resources and knowledge gaps. Conclusion Telemedicine could be promising for patients with no regular or convenient access to headache specialists and seems to be a priority in managing migraine patients to avoid non-urgent hospitalizations

Published
2022

5. Clinical effectiveness of different natalizumab interval dosing schedules in a large Italian population of patients with multiple sclerosis

Author

Chisari, CLARA GRAZIA, Grimaldi Luigi Maria, Salemi, Giuseppe, Ragonese, Paolo, Iaffaldano, Pietro, Bonavita, Simona, Sparaco, Maddalena, Rovaris, Marco, D'Arma, Alessia, Lugaresi, Alessandra, Ferrò Maria Teresa, Grossi, Paola, Di Sapio Alessia, Cocco, Eleonora, Granella, Franco, Curti, Erica, Lepore, Vito, Trojano, Maria, Patti, Francesco, on behalf of the Italian MS Register Study Group, Chisari, Clara Grazia, Grimaldi, Luigi Maria, Salemi, Giuseppe, Ragonese, Paolo, Iaffaldano, Pietro, Bonavita, Simona, Sparaco, Maddalena, Rovaris, Marco, D'Arma, Alessia, Lugaresi, Alessandra, Ferrò, Maria Teresa, Grossi, Paola, Di Sapio, Alessia, Cocco, Eleonora, Granella, Franco, Curti, Erica, Lepore, Vito, Trojano, Maria, Patti, Francesco, Chisari C.G., Grimaldi L.M., Salemi G., Ragonese P., Iaffaldano P., Bonavita S., Sparaco M., Rovaris M., D'Arma A., Lugaresi A., Ferro M.T., Grossi P., DI Sapio A., Cocco E., Granella F., Curti E., Lepore V., Trojano M., and Patti F.

Subjects
Adult, medicine.medical_specialty, Population, multiple sclerosis, Drug Administration Schedule, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, natalizumab, 0302 clinical medicine, Natalizumab, Dosing schedules, Internal medicine, medicine, Humans, Immunologic Factors, natalizumab, risk stratification, multiple sclerosis, safety, effectiveness, Dosing, education, Proportional Hazards Models, Retrospective Studies, 030304 developmental biology, 0303 health sciences, education.field_of_study, Proportional hazards model, business.industry, Multiple sclerosis, Retrospective cohort study, Middle Aged, medicine.disease, Psychiatry and Mental health, Treatment Outcome, Italy, Tolerability, Settore MED/26 - Neurologia, Surgery, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract

IntroductionNatalizumab (NTZ) is one of the most effective treatment options for multiple sclerosis (MS) treatment. Our study aimed to evaluate the effectiveness of NTZ when administered according to the extended dosing strategy compared with standard 4-weekly administration in a large Italian MS population.Materials and methodsThis retrospective multicentre study included patients with relapsing-remitting MS (RR-MS) who received NTZ administrations between the 1 June 2012 and the 15 May 2018 and were followed by the ‘Italian MS Register’. All patients with MS were stratified into two groups based on NTZ administration schedule: standard interval dosing (SID) patients who received infusions on average from 28 to 32 days (median 30) and extended interval dosing (EID) including patients who have been infused with interval between 33 and 49 days (median 43). Clinical data were assessed at baseline (before starting NTZ), after 12 (T1) and 24 months (T2) of treatment.ResultsOut of 5231 patients with RR-MS screened, 2092 (mean age 43.2±12.0, 60.6% women) were enrolled. A total of 1254 (59.9%) received NTZ according to SID, and 838 (40.1%) according to EID. At 12 and 24 months, no differences in terms of annualised relapse rate and disability status were found between the two groups. Progression index and confirmed disability worsening were similar between the two groups.DiscussionThe use of NTZ with an extended interval schedule showed similar effectiveness compared with SID. Unchanged clinical efficacy of EID schedule may raise the question of a possible advantage in terms of tolerability and safety.

Published
2020

6. Telemedicine for management of patients with amyotrophic lateral sclerosis through COVID-19 tail

Author

Bombaci, Alessandro, Abbadessa, Gianmarco, Trojsi, Francesca, Leocani, Letizia, Bonavita, Simona, Lavorgna, Luigi, Gioacchino Tedeschi, Giovanni Mancardi, Alessandro Padovani, Marinella Clerico, Francesco Brigo, Roberta Lanzillo, Antonio Russo, Bruno Giometto, Giulia Straccia, Rosa Iodice, Sebastiano Bucello, Pietro Annovazzi, Marcello Moccia, Luca Prosperini, Maria Laura Stromillo, Anna Maria Repice, Giuseppina Miele, Alberto Lerario, Antonio De Martino, Francesco Iodice, Francesco Di Lorenzo, Luca Cuffaro, Michele Romoli, Marcello Silvestro, Carlo Alberto Artusi, Bombaci, Alessandro, Abbadessa, Gianmarco, Trojsi, Francesca, Leocani, Letizia, Bonavita, Simona, Lavorgna, Luigi, Bombaci, A., Abbadessa, G., Trojsi, F., Leocani, L., Bonavita, S., Lavorgna, L., Tedeschi, G., Mancardi, G., Padovani, A., Clerico, M., Brigo, F., Lanzillo, R., Russo, A., Giometto, B., Straccia, G., Iodice, R., Bucello, S., Annovazzi, P., Moccia, M., Prosperini, L., Stromillo, M. L., Repice, A. M., Miele, G., Lerario, A., De Martino, A., Iodice, F., Di Lorenzo, F., Cuffaro, L., Romoli, M., Silvestro, M., Artusi, C. A., Bombaci, A, Abbadessa, G, Trojsi, F, Leocani, L, Bonavita, S, Lavorgna, L, Tedeschi, G, Mancardi, G, Padovani, A, Clerico, M, Brigo, F, Lanzillo, R, Russo, A, Giometto, B, Straccia, G, Iodice, R, Bucello, S, Annovazzi, P, Moccia, M, Prosperini, L, Stromillo, M, Repice, A, Miele, G, Lerario, A, De Martino, A, Iodice, F, Di Lorenzo, F, Cuffaro, L, Romoli, M, Silvestro, M, Artusi, C, Alessandro, Bombaci, Gianmarco, Abbadessa, Francesca, Trojsi, Letizia, Leocani, Simona, Bonavita, Luigi, Lavorgna, Tedeschi, Gioacchino, Mancardi, Giovanni, Padovani, Alessandro, Clerico, Marinella, Brigo, Francesco, Lanzillo, Roberta, Russo, Antonio, Giometto, Bruno, Straccia, Giulia, Iodice, Rosa, Bucello, Sebastiano, Annovazzi, Pietro, Moccia, Marcello, Prosperini, Luca, Laura Stromillo, Maria, Maria Repice, Anna, Miele, Giuseppina, Lerario, Alberto, De Martino, Antonio, Iodice, Francesco, Di Lorenzo, Francesco, Cuffaro, Luca, Romoli, Michele, Silvestro, Marcello, and Alberto Artusi, Carlo

Subjects
medicine.medical_specialty, Telemedicine, Neurology, Coronavirus disease 2019 (COVID-19), Clinical Neurology, Monitoring, Ambulatory, Context (language use), Disease, Review Article, Dermatology, Tele-health, Teleneurology, ALS patients, COVID-19, Remote monitoring, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Pandemic, medicine, Humans, 030212 general & internal medicine, Amyotrophic lateral sclerosis, Intensive care medicine, business.industry, Amyotrophic Lateral Sclerosis, General Medicine, medicine.disease, Psychiatry and Mental health, ALS patient, Neurology (clinical), Neurosurgery, business, 030217 neurology & neurosurgery
Abstract

Over the last months, due to coronavirus disease (COVID-19) pandemic, containment measures have led to important social restriction. Healthcare systems have faced a complete rearrangement of resources and spaces, with the creation of wards devoted to COVID-19 patients. In this context, patients affected by chronic neurological diseases, such as amyotrophic lateral sclerosis (ALS), are at risk to be lost at follow-up, leading to a higher risk of morbidity and mortality. Telemedicine may allow meet the needs of these patients. In this commentary, we briefly discuss the digital tools to remotely monitor and manage ALS patients. Focusing on detecting disease progression and preventing life-threatening conditions, we propose a toolset able to improve ALS management during this unprecedented situation.

Published
2020
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7. Telemedicine in Parkinson's Disease: How to Ensure Patient Needs and Continuity of Care at the Time of COVID-19 Pandemic

Author

Miele, Giuseppina, Straccia, Giulia, Moccia, Marcello, Leocani, Letizia, Tedeschi, Gioacchino, Bonavita, Simona, Lavorgna, Luigi, Padovani, Alessandro, Clerico, Marinella, Brigo, Francesco, Cocco, Eleonora, Lanzillo, Roberta, Russo, Antonio, Giometto, Bruno, Trojsi, Francesca, Iodice, Rosa, Bucello, Sebastiano, Annovazzi, Pietro, Prosperini, Luca, Stromillo, Maria Laura, Repice, Anna Maria, Abbadessa, Gianmarco, Lerario, Alberto, DeMartino, Antonio, Bombaci, Alessandro, Iodice, Francesco, Di Lorenzo, Francesco, Cuffaro, Luca, Romoli, Michele, Silvestro, Marcello, Alberto Artusi, Carlo, Miele, Giuseppina, Straccia, Giulia, Moccia, Marcello, Leocani, Letizia, Tedeschi, Gioacchino, Bonavita, Simona, Lavorgna, Luigi, Padovani, Alessandro, Clerico, Marinella, Brigo, Francesco, Cocco, Eleonora, Lanzillo, Roberta, Russo, Antonio, Giometto, Bruno, Trojsi, Francesca, Iodice, Rosa, Bucello, Sebastiano, Annovazzi, Pietro, Prosperini, Luca, Stromillo, Maria Laura, Repice, Anna Maria, Abbadessa, Gianmarco, Lerario, Alberto, Demartino, Antonio, Bombaci, Alessandro, Iodice, Francesco, Di Lorenzo, Francesco, Cuffaro, Luca, Romoli, Michele, Silvestro, Marcello, and Alberto Artusi, Carlo

Subjects
Adult, Male, Telemedicine, Parkinson's disease, 020205 medical informatics, Coronavirus disease 2019 (COVID-19), telemedicine COVID-19, Parkinson disease, pandemic, Vulnerability, Health Informatics, Neurological examination, 02 engineering and technology, Disease, Health Information Management, Health care, Pandemic, 0202 electrical engineering, electronic engineering, information engineering, medicine, Humans, Pandemics, Aged, Aged, 80 and over, medicine.diagnostic_test, business.industry, SARS-CoV-2, COVID-19, General Medicine, Continuity of Patient Care, Middle Aged, medicine.disease, Italy, Practice Guidelines as Topic, Female, Medical emergency, business, Needs Assessment
Abstract

Introduction: With the spread of the SARS-CoV2 pandemic, telemedicine has become the safest way to guarantee care continuity, especially for chronic disabling diseases requiring frequent medical consultations and therapeutic adjustments, such as Parkinson's disease (PD). The age-related prevalence of PD, combined with increased vulnerability due to age-related comorbidities, makes PD patients protection a priority. Methodology: We reviewed potentials and limitations of teleneurology in PD and suggested a specific battery of tests, including patient-reported outcomes, smartphone applications, and neurological examination through telemedicine. Conclusions: These tools can provide full neurological consultations, with the engagement of both patients and caregivers, and can support clinicians in defining whether patients need to access diagnostic and therapeutic procedures. Telemedicine will also carry a value in the future, within conventional health care, to support clinicians in decision making, enabling more efficacious follow-up, reducing burden for caregivers, and delivering neurological expertise to local realities. These advantages are very important when there is physical distance between patients and neurologists, and when patients are not recommended to attend in-person consultations.

Published
2020

8. Cladribine vs other drugs in MS

Author

Signori, Alessio, Saccà, Francesco, Lanzillo, Roberta, Maniscalco, Giorgia Teresa, Signoriello, Elisabetta, Repice, Anna Maria, Annovazzi, Pietro, Baroncini, Damiano, Clerico, Marinella, Binello, Eleonora, Cerqua, Raffaella, Mataluni, Giorgia, Perini, Paola, Bonavita, Simona, Lavorgna, Luigi, Zarbo, Ignazio Roberto, Laroni, Alice, Pareja-Gutierrez, Lorena, La Gioia, Sara, Frigeni, Barbara, Barcella, Valeria, Frau, Jessica, Cocco, Eleonora, Fenu, Giuseppe, Clerici, Valentina Torri, Sartori, Arianna, Rasia, Sarah, Cordioli, Cinzia, Stromillo, Maria Laura, Di Sapio, Alessia, Pontecorvo, Simona, Grasso, Roberta, Barone, Stefania, Barrilà, Caterina, Russo, Cinzia Valeria, Esposito, Sabrina, Ippolito, Domenico, Landi, Doriana, Visconti, Andrea, and Sormani, Maria Pia

Subjects
Adult, Male, Databases, Factual, Datasets as Topic, Middle Aged, Severity of Illness Index, Article, Observational Studies as Topic, Multiple Sclerosis, Relapsing-Remitting, Outcome Assessment, Health Care, Disease Progression, Cladribine, Humans, Immunologic Factors, Multicenter Studies as Topic, Female, Randomized Controlled Trials as Topic, Retrospective Studies
Abstract

Objective Cladribine tablets were tested against placebo in randomized controlled trials (RCTs). In this study, the effectiveness of cladribine vs other approved drugs in patients with relapsing-remitting MS (RRMS) was compared by matching RCT to observational data. Methods Data from the pivotal trial assessing cladribine tablets vs placebo (CLARITY) were propensity score matched to data from the Italian multicenter database i-MuST. This database included 3,150 patients diagnosed between 2010 and 2018 at 24 Italian MS centers who started a disease-modifying drug. The annualized relapse rate (ARR) over 2 years from treatment start and the 24-week confirmed disability progression were compared between patients treated with cladribine and other approved drugs (interferon, glatiramer acetate, fingolimod, natalizumab, and dimethyl fumarate), with comparisons with placebo as a reference. Treatment effects were estimated by the inverse probability weighting negative binomial regression model for ARR and Cox model for disability progression. The treatment effect has also been evaluated according to baseline disease activity. Results All weighted baseline characteristics were well balanced between groups. All drugs tested had an effect vs placebo close to that detected in the RCT. Patients treated with cladribine had a significantly lower ARR compared with interferon (relapse ratio [RR] = 0.48; p < 0.001), glatiramer acetate (RR = 0.49; p < 0.001), and dimethyl fumarate (RR = 0.6; p = 0.001); a similar ARR to that with fingolimod (RR = 0.74; p = 0.24); and a significantly higher ARR than natalizumab (RR = 2.13; p = 0.014), confirming results obtained by indirect treatment comparisons from RCTs (network meta-analyses). The relative effect of cladribine tablets 10 mg (cumulative dose 3.5 mg/kg over 2 years) was higher in patients with high disease activity vs all treatments except fingolimod and natalizumab. Effects on disability progression were largely nonsignificant, probably due to lack of power for such analysis. Conclusion In patients with RRMS, cladribine tablets showed lower ARR compared with matched patients who started interferon, glatiramer acetate, or dimethyl fumarate; was similar to fingolimod; and was higher than natalizumab. The beneficial effect of cladribine tablets was generally amplified in the subgroup of patients with high disease activity. Classification of evidence This study provides Class III evidence that for patients with RRMS, cladribine-treated patients had lower ARR compared with interferon, glatiramer acetate, or dimethyl fumarate; similar ARR compared with fingolimod; and higher ARR compared with natalizumab.

Published
2020

9. Health-care disparities stemming from sexual orientation of Italian patients with Multiple Sclerosis: A cross-sectional web-based study

Author

Luigi, Lavorgna, MOCCIA, MARCELLO, Russo, Antonio, PALLADINO, RAFFAELE, Riccio, Lucia, LANZILLO, ROBERTA, BRESCIA MORRA, VINCENZO, Tedeschi, Gioacchino, Bonavita, Simona, Palladino, R., Lavorgna, Luigi, Moccia, Marcello, Russo, Antonio, Palladino, Raffaele, Riccio, Lucia, Lanzillo, Roberta, Brescia Morra, Vincenzo, Tedeschi, Gioacchino, Bonavita, Simona, Luigi, Lavorgna, BRESCIA MORRA, Vincenzo, and Palladino, R.

Subjects
Adult, Male, PEOPLES EXPERIENCES, Multiple Sclerosis, Clinical Neurology, Affect (psychology), 03 medical and health sciences, Sexual and Gender Minorities, 0302 clinical medicine, Quality of life (healthcare), PHYSICIANS, QUALITY-OF-LIFE, Surveys and Questionnaires, Transgender, Health care, medicine, Humans, 030212 general & internal medicine, Healthcare Disparities, Internet, Science & Technology, LGBT, business.industry, Multiple sclerosis, Gender, General Medicine, Health Status Disparities, medicine.disease, Inequalitie, CENTERS, Cross-Sectional Studies, GAY, Neurology, Italy, Sexual orientation, PAPER, Female, Neurology (clinical), Neurosciences & Neurology, Lesbian, Inequalities, Lifestyle habits, business, Attitude to Health, Sexuality, Life Sciences & Biomedicine, 030217 neurology & neurosurgery, Clinical psychology
Abstract

Lesbian, gay, bisexual and transgender (LGBT) patients might experience unique difficulties and barriers to treatment of chronic diseases related to their sexual orientation. Thus, we investigated concerns experienced by LGBT patients with multiple sclerosis (MS). We conducted a web-based survey using a multi-choice questionnaire published in an Italian social-network (www.smsocialnetwork.com) for MS patients. The survey investigated: socio-demographic factors, lifestyle habits, MS-related health status and LGBT specific issues (e.g. friendliness to their sexual orientation and eventual homophobic behaviors in the MS Center). Among MS patients willing to use psychological services, LGBT patients were associated with a smaller number of psychological consultations, compared to heterosexuals (Coeff.=-0.449; p < 0.001; 95% CI=-0.682 to -0. 217). LGBT patients were more likely to change MS Center, compared to heterosexuals (OR=2.064; p=0.046; 95% CI=1.011-4.212). The number of MS Center changes was associated with MS Center friendliness (p=0.037; rho=-0.229) and with the occurrence of homophobic behaviors (p=0.036; rho=0.234). LGBT MS patients more frequently changed MS Center and had a reduced use of psychological services, compared to heterosexuals. The attitude towards LGBT MS patients might affect resource utilizations and LGBTs health status.

Published
2017

10. Gene conversion events in adult-onset spinal muscular atrophy

Author

MAZZEI R, GAMBARDELLA A, CONFORTI FL, MAGARIELLO A, PATITUCCI A, GABRIELE AL, SPROVIERI T, LABATE A, VALENTINO P, BONO F, ZAPPIA M, MUGLIA M, QUATTRONE A., BONAVITA, Simona, Mazzei, R, Gambardella, A, Conforti, Fl, Magariello, A, Patitucci, A, Gabriele, Al, Sprovieri, T, Labate, A, Valentino, P, Bono, F, Bonavita, Simona, Zappia, M, Muglia, M, and Quattrone, A.

Subjects
Adult, Male, RNA-Binding Proteins, Nerve Tissue Proteins, SMN Complex Proteins, Exons, Telomere, Polymerase Chain Reaction, Severity of Illness Index, Survival of Motor Neuron 1 Protein, Muscular Atrophy, Spinal, Phenotype, Humans, Age of Onset, Cyclic AMP Response Element-Binding Protein, Gene Deletion, Aged
Abstract

To investigate the possible occurrence of a conversion event in three patients with adult-onset spinal muscular atrophy (SMA) type IV, which represents the mildest form within the spectrum of the SMA phenotype.We observed three patients with adult onset SMA and apparent isolated deletion of telomeric survival motor neuron (SMN1) exon 7. To distinguish between a deletion and a sequence conversion event of exon 7, these patients were analyzed in greater detail by a simple PCR-based assay.Analysis by DdeI digestion showed products for both telomeric and centromeric copies of exon 8. These findings indicated a gene conversion event as the site for primer R111 was retained at least in one of two alleles.These results provide first evidence that a conversion event may be also associated with adult-onset SMA, and further support the notion that a gene conversion event is usually associated with a milder SMA phenotype and a later onset of disease.

Published
2004

11. Anti-GM1 ganglioside antibodies in Parkinson's disease

Author

ZAPPIA M, CRESCIBENE L, BOSCO D, ARABIA G, NICOLETTI G, BAGALA A, BASTONE L, NAPOLI ID, CARACCIOLO M, DI COSTANZO A, GAMBARDELLA A, QUATTRONE A., BONAVITA, Simona, Zappia, M, Crescibene, L, Bosco, D, Arabia, G, Nicoletti, G, Bagala, A, Bastone, L, Napoli, Id, Caracciolo, M, Bonavita, Simona, DI COSTANZO, A, Gambardella, A, and Quattrone, A.

Subjects
Male, Enzyme-Linked Immunosorbent Assay, Parkinson Disease, G(M1) Ganglioside, Middle Aged, Immunoglobulin M, Reference Values, Immunoglobulin G, Tremor, Humans, Female, Serologic Tests, Aged, Autoantibodies
Abstract

OBJECTIVES: To determine whether anti-GM1 antibodies are increased in Parkinson's disease (PD). METHODS: Serum immunoglobulin M (IgM) and IgG anti-GM1 antibodies were detected by enzyme-linked immunosorbent assay (ELISA) in 147 patients with PD and in 186 age-matched normal control subjects. Sera were assayed at initial dilution of 1:800 for IgM and 1:200 for IgG and were considered positive at absorbance values exceeding the value of 0.05 for IgM and 0.1 for IgG. RESULTS: Forty patients with PD (27.2%) had sera positive for IgM anti-GM1 antibodies, whereas only five normal controls (2.7%) resulted positive (P < 0.0001). Most of patients (75%) with positive sera had a tremor-dominant form of PD. Only two patients with PD (1.4%) and none of normal controls had sera positive for IgG anti-GM1 antibodies. CONCLUSION: A consistent portion of parkinsonians, mainly with a tremor-dominant form of PD, may have increased circulating IgM anti-GM1 antibodies.

Published
2002

12. Is It Time for Ocrelizumab Extended Interval Dosing in Relapsing Remitting MS? Evidence from An Italian Multicenter Experience During the COVID-19 Pandemic

Author

Aurora Zanghì, Carlo Avolio, Elisabetta Signoriello, Gianmarco Abbadessa, Maria Cellerino, Diana Ferraro, Christian Messina, Stefania Barone, Graziella Callari, Elena Tsantes, Patrizia Sola, Paola Valentino, Franco Granella, Francesco Patti, Giacomo Lus, Simona Bonavita, Matilde Inglese, Emanuele D’Amico, Zanghì, Aurora, Avolio, Carlo, Signoriello, Elisabetta, Abbadessa, Gianmarco, Cellerino, Maria, Ferraro, Diana, Messina, Christian, Barone, Stefania, Callari, Graziella, Tsantes, Elena, Sola, Patrizia, Valentino, Paola, Granella, Franco, Patti, Francesco, Lus, Giacomo, Bonavita, Simona, Inglese, Matilde, and D'Amico, Emanuele

Subjects
Pharmacology, Multiple Sclerosis, Pandemic, COVID-19, Gadolinium, Extended interval dosing, Standard interval dosing, Cytidine Diphosphate, Immunologic Factor, Multiple Sclerosis, Relapsing-Remitting, Recurrence, Humans, Immunologic Factors, Pharmacology (medical), Disease activity, Ocrelizumab, Neurology (clinical), Pandemics, Sudden Infant Death, MRI, Human
Abstract

In the COVID-19 pandemic era, safety concerns have been raised regarding the risk of severe infection following administration of ocrelizumab (OCR), a B-cell-depleting therapy. We enrolled all relapsing remitting multiple sclerosis (RRMS) patients who received maintenance doses of OCR from January 2020 to June 2021. Data were extracted in December 2021. Standard interval dosing (SID) was defined as a regular maintenance interval of OCR infusion every 6 months, whereas extended interval dosing (EID) was defined as an OCR infusion delay of at least 4 weeks. Three infusions were considered in defining SID vs. EID (infusions A, B, and C). Infusion A was the last infusion before January 2020. The primary study outcome was a comparison of disease activity during the A-C interval, which was defined as either clinical (new relapses) or radiological (new lesions on T1-gadolinium or T2-weighted magnetic resonance imaging (MRI) sequences). Second, we aimed to assess confirmed disability progression (CDP). A total cohort of 278 patients (174 on SID and 104 on EID) was enrolled. Patients who received OCR on EID had a longer disease duration and a higher rate of vaccination against severe acute respiratory syndrome-coronavirus 2 (p

Published
2022

13. Unmet needs and gaps in the identification of secondary progression in multiple sclerosis: a Southern Italy healthcare professionals' perspective

Author

Giacomo Lus, Marco André Bassano, Vincenzo Brescia Morra, Simona Bonavita, Antonio Gallo, Davide Maimone, Laura Malerba, Giorgia Teresa Maniscalco, Francesco Saccà, Giuseppe Salemi, Renato Turrini, Salvatore Cottone, Edoardo Sessa, Maria Buccafusca, Luigi Maria Edoardo Grimaldi, Lus, Giacomo, Bassano, Marco André, Brescia Morra, Vincenzo, Bonavita, Simona, Gallo, Antonio, Maimone, Davide, Malerba, Laura, Maniscalco, Giorgia Teresa, Saccà, Francesco, Salemi, Giuseppe, Turrini, Renato, Cottone, Salvatore, Sessa, Edoardo, Buccafusca, Maria, and Grimaldi, Luigi Maria Edoardo

Subjects
Secondary progressive multiple sclerosis (SPMS), Dermatology, General Medicine, Biomarker, Multiple Sclerosis, Chronic Progressive, Multiple sclerosis, Psychiatry and Mental health, Multiple Sclerosis, Relapsing-Remitting, Italy, Expert opinion, Diagnosis, Quality of Life, Disease Progression, Humans, Multiple sclerosi, Settore MED/26 - Neurologia, Neurology (clinical), Neoplasm Recurrence, Local, Atrophy, Delivery of Health Care, Biomarkers, Diagnosi
Abstract

Objective Multiple sclerosis (MS) is a chronic disease with different clinical courses and a tendency to worsening. The relapsing–remitting MS presents acute onset and relapses of neurological symptoms, followed by their remission. This form can convert to secondary progressive MS (SPMS) with irreversible neurological worsening and disability. The identification of signs, symptoms, markers of progression, and strategies to manage MS patients is mandatory to allow early identification of those at higher risk of conversion to SPMS, for prompt intervention to cope with the progression of the disease. Methods A panel of Italian experts from Southern Italy have reviewed the current knowledge on MS and its management and identified the crucial tools for SPMS recognition. Results More effective communication between patients and clinicians should be established, with the support of digital tools. Moreover, the improvement in the clinical use of biomarkers for progression (cellular structures and tissue organization, such as neurofilaments and chitinase 3-like 1, axonal and neurons density) and of instrumental analyses for recognition of whole-brain atrophy, chronic active lesions, spinal cord lesions and atrophy, and the improvement the combination of the Expanded Disability Status Scale and the evaluation of cognitive dysfunction are discussed. Conclusion Given the availability of a pharmacological option, adequate education both for patients, regarding the evolution of the disease and the specific treatment, and for professionals, to allow more effective and sensitive communication and the best use of diagnostic and management tools, could represent a strategy to improve patient management and their quality of life.

Published
2023

14. 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

15. A real‐world study of alemtuzumab in a cohort of Italian patients

Author

Paola Cavalla, Laura Brambilla, Roberta Grasso, Cinzia Cordioli, Alice Laroni, Alessia Giugno, Valentina Torri Clerici, Maria Pia Sormani, Pietro Annovazzi, Francesco Saccà, Eleonora Cocco, Jessica Frau, Elisabetta Signoriello, Antonio Gallo, Marinella Clerico, Stefania Federica De Mercanti, Antonio Carotenuto, Simona Bonavita, Cinzia Valeria Russo, Giuseppe Fenu, Caterina Lapucci, Giorgia Teresa Maniscalco, Arianna Sartori, Francesca Caleri, Marco Capobianco, Alessio Signori, Rosa Iodice, Sara La Gioia, Giacomo Lus, Mauro Zaffaroni, Damiano Baroncini, Valeria Di Francescantonio, Russo, C. V., Sacca, F., Frau, J., Annovazzi, P., Signoriello, E., Bonavita, S., Grasso, R., Clerico, M., Cordioli, C., Laroni, A., Capobianco, M., Torri Clerici, V., Sartori, A., Cavalla, P., Maniscalco, G. T., La Gioia, S., Caleri, F., Giugno, A., Iodice, R., Carotenuto, A., Cocco, E., Fenu, G., Zaffaroni, M., Baroncini, D., Lus, G., Gallo, A., De Mercanti, S. F., Lapucci, C., Di Francescantonio, V., Brambilla, L., Sormani, M. P., Signori, A., Russo, CINZIA VALERIA, Sacca', Francesco, Frau, Jessica, Annovazzi, Pietro, Signoriello, Elisabetta, Bonavita, Simona, Grasso, Roberta, Clerico, Marinella, Cordioli, Cinzia, Laroni, Alice, Capobianco, Marco, Torri Clerici, Valentina, Sartori, Arianna, Cavalla, Paola, Teresa Maniscalco, Giorgia, La Gioia, Sara, Caleri, Francesca, Giugno, Alessia, Iodice, Rosa, Carotenuto, Antonio, Cocco, Eleonora, Fenu, Giuseppe, Zaffaroni, Mauro, Baroncini, Damiano, Lus, Giacomo, Gallo, Antonio, Federica De Mercanti, Stefania, Lapucci, Caterina, Di Francescantonio, Valeria, Brambilla, Laura, Pia Sormani, Maria, and Signori, Alessio

Subjects
Adult, safety, medicine.medical_specialty, efficacy, Multiple Sclerosis, Relapsing-Remitting, Natalizumab, Internal medicine, alemtuzumab, medicine, Humans, Glatiramer acetate, real-world evidence, Retrospective Studies, Expanded Disability Status Scale, Fingolimod Hydrochloride, business.industry, Multiple sclerosis, Glatiramer Acetate, cohort, medicine.disease, Fingolimod, Neurology, Relative risk, Cohort, Alemtuzumab, Neurology (clinical), business, medicine.drug
Abstract

Background and purpose: Real-world data on alemtuzumab are limited and do not provide evidence of its effectiveness after various disease-modifying therapies (DMTs). Our aim was to provide real-world data on the impact of clinical variables and previous DMTs on clinical response to alemtuzumab. Methods: Sixteen Italian multiple sclerosis centers retrospectively included patients who started alemtuzumab from January 2015 to December 2018, and recorded demographics, previous therapies, washout duration, relapses, Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging data. Negative binomial regression models were used to assess the effect of factors on annualized relapse (ARR) after alemtuzumab initiation. Results: We studied 322 patients (mean age 36.8years, median EDSS score 3, median follow-up 1.94years). Previous treatments were: fingolimod (106), natalizumab (80), first-line oral agents (56), first-line injectables (interferon/glatiramer acetate; 30), and other drugs (15). Thirty-five patients were treatment-naïve. The pre-alemtuzumab ARR was 0.99 and decreased to 0.13 during alemtuzumab treatment (p&nbsp

Published
2021

16. Between-sex variability of resting state functional brain networks in amyotrophic lateral sclerosis (ALS)

Author

Fabrizio Esposito, Francesca Trojsi, Giuseppina Caiazzo, Federica Di Nardo, Mattia Siciliano, Carla Passaniti, Giulia D'Alvano, Antonio Russo, Mario Cirillo, Gioacchino Tedeschi, Simona Bonavita, Trojsi, Francesca, Di Nardo, Federica, Caiazzo, Giuseppina, Siciliano, Mattia, D’Alvano, Giulia, Passaniti, Carla, Russo, Antonio, Bonavita, Simona, Cirillo, Mario, Esposito, Fabrizio, and Tedeschi, Gioacchino

Subjects
Resting-state functional MRI, Male, Brain networks, Precuneus, Neurology and Preclinical Neurological Studies - Original Article, Gyrus Cinguli, Functional connectivity, Atrophy, Gyrus, Cortex (anatomy), medicine, Humans, Amyotrophic lateral sclerosis, Biological Psychiatry, Anterior cingulate cortex, Default mode network, Brain Mapping, Resting state fMRI, business.industry, Amyotrophic Lateral Sclerosis, Brain, medicine.disease, Magnetic Resonance Imaging, Psychiatry and Mental health, medicine.anatomical_structure, Neurology, Sex, Female, Neurology (clinical), business, Neuroscience
Abstract

The organization of brain functional connectivity (FC) has been shown to differ between sexes. Amyotrophic lateral sclerosis (ALS) is characterized by sexual dimorphism, showing sex-specific trends in site of onset, phenotypes, and prognosis. Here, we explored resting state (RS) FC differences within major large-scale functional networks between women and men in a sample of ALS patients, in comparison to healthy controls (HCs). A group-level independent component analysis (ICA) was performed on RS-fMRI time-series enabling spatial and spectral analyses of large-scale RS FC networks in 45 patients with ALS (20 F; 25 M) and 31 HCs (15 F; 16 M) with a focus on sex-related differences. A whole-brain voxel-based morphometry (VBM) was also performed to highlight atrophy differences. Between-sex comparisons showed: decreased FC in the right middle frontal gyrus and in the precuneus within the default mode network (DMN), in affected men compared to affected women; decreased FC in the right post-central gyrus (sensorimotor network), in the right inferior parietal gyrus (right fronto-parietal network) and increased FC in the anterior cingulate cortex and right insula (salience network), in both affected and non-affected men compared to women. When comparing affected men to affected women, VBM analysis revealed atrophy in men in the right lateral occipital cortex. Our results suggest that in ALS sex-related trends of brain functional and structural changes are more heavily represented in DMN and in the occipital cortex, suggesting that sex is an additional dimension of functional and structural heterogeneity in ALS.

Published
2021

18. Optimal retreatment schedule of rituximab for neuromyelitis optica spectrum disorder: A systematic review

Author

Gianmarco Abbadessa, Giuseppina Miele, Elisabetta Maida, Giuseppe Minervini, Luigi Lavorgna, Simona Bonavita, Abbadessa, Gianmarco, Miele, Giuseppina, Maida, Elisabetta, Minervini, Giuseppe, Lavorgna, Luigi, and Bonavita, Simona

Subjects
Aquaporin 4, B cell, Treatment schedule, Neuromyelitis Optica, General Medicine, Neurology, Recurrence, Immunoglobulin G, Retreatment, Leukocytes, Mononuclear, Humans, Neurology (clinical), Rituximab, NMSOD, Biomarkers
Abstract

Several studies have shown the efficacy of rituximab (RTX) in preventing relapses in patients suffering from Neuromyelitis Optica spectrum disorder (NMSOD) and have explored different therapeutic schemes. Given the extreme inter-individual variability of the disease course, there is the need to identify biomarkers to tailor the retreatment schedule and dosage. This review aimed to identify the most useful biomarker to guide reinfusion and, in turn, the optimal retreatment schedule of RTX for NMSOD.The literature search was conducted in the Web of Science, Scopus and Pubmed electronic databases. We limited document type to articles written in English and published up to 28 February 2022. Inclusion criteria were: (i) Patients affected by NMSOD and treated with RTX, (ii) followed up for at least one year and for whom Annualized Relapse rate (ARR) was collected over a period of at least 12 months before and after therapy initiation and (iii) induction protocols consisting of 375 mg / m2 / week for four weeks or 1000 mg infused once or twice two weeks apart. Collected information was: first authors' name, publication year, study design, sample size, sex, age, percentage of patients positive for antibodies to aquaporin 4 (AQP4-IgG), maintenance regimen, primary outcome, mean ARR pre-therapy and mean ARR post-therapy initiation, percentage of relapse-free patients. The primary outcome that we considered was the ARR reduction. Further, we considered the number of relapses that occurred when B cells and memory B cells were under the chosen threshold and the percentage of relapse-free patients when available.Among 31 potentially eligible studies, 9 fulfilled the inclusion criteria. ARR reduction was not comparable between studies. The studies that monitored CD19+ and CD27+ cell kinetics showed a higher number of relapses when CD19+ lymphocyte count was below the threshold compared to the number of relapses that occurred when CD27+ cell count was below the threshold. Further, a higher percentage of patients achieved the relapse-free condition with a reinfusion schedule when CD27+ reached 0, 05% of peripheral blood mononuclear cells (PBMCs) compared to the reinfusion when CD19+ reached 0, 1% of PBMCs.To date, the optimal retreatment schedule for RTX in NMOSD has not yet been determined. However, the presented findings suggest that CD27+ B cells might be a reliable biomarker to guide retreatment in AQP4-IgG positive patients, at least in the first six months from the infusion. Further effort is needed to identify those factors influencing anti-CD20 therapy effectiveness to tailor dosage and treatment schedule to achieve the most favourable risk/benefit ratio.

Published
2022

19. Perceived stress and social support in a large population of people with multiple sclerosis recruited online through the COVID‐19 pandemic

Author

Simona Bonavita, Maddalena Sparaco, Giovanna Borriello, Antonio Russo, Luigi Lavorgna, Bonavita, Simona, Sparaco, Maddalena, Russo, Antonio, Borriello, Giovanna, and Lavorgna, Luigi

Subjects
medicine.medical_specialty, Stress management, Multiple Sclerosis, stress management, Clinical Neurology, Perceived Stress Scale, Social group, 03 medical and health sciences, Social support, 0302 clinical medicine, stre, Multiple Sclerosi, Humans, Medicine, 030212 general & internal medicine, Pandemics, Depression (differential diagnoses), SARS-CoV-2, business.industry, Multiple sclerosis, COVID-19, social support, medicine.disease, Patient Health Questionnaire, Neurology, Migraine, Physical therapy, Neurology (clinical), Neoplasm Recurrence, Local, business, COVID 19, Stress, Psychological, 030217 neurology & neurosurgery
Abstract

BACKGROUND AND PURPOSE: The COVID-19 emergency may cause post-traumatic stress disorder (PTSD), and with regard to people with MS (pwMS) chronic exposure to a wide range of challenging life events has been shown to be correlated with worsening of neurological symptoms, increased lesion burden on brain magnetic resonance imaging and relapses. The aim was to investigate perceived stress, depression, perceived social support, habits and behaviour changes in pwMS through COVID-19 in comparison to a control group. METHODS: A web-based survey was posted on SMsocialnetwork.com to investigate perceived stress (using the Perceived Stress Scale), depression (with Patient Health Questionnaire 2) and perceived social support (using Social Provision Scale 10 item) in pwMS and a control group through the COVID-19 pandemic. A secondary group of people with migraine was investigated. RESULTS: In all, 1286 answers from 612 pwMS and 674 control people were included in the final analysis. The answers from 318 people with migraine were included for a secondary analysis. A higher proportion of pwMS were depressed (43.1% vs. 23.1%; p

Published
2021

20. Association of vitamin D serum levels and vitamin D supplementation with B cell kinetics and disease activity in Multiple Sclerosis patients treated with ocrelizumab: an Italian multi-center study

Author

Giuseppina Miele, Gianmarco Abbadessa, Paola Cavalla, Paola Valentino, Girolama Alessandra Marfia, Doriana Landi, Chiara Bosa, Marco Vercellino, Antonio De Martino, Marta Ponzano, Luigi Lavorgna, Simona Bonavita, Miele, Giuseppina, Abbadessa, Gianmarco, Cavalla, Paola, Valentino, Paola, Marfia, Girolama Alessandra, Landi, Doriana, Bosa, Chiara, Vercellino, Marco, De Martino, Antonio, Ponzano, Marta, Lavorgna, Luigi, and Bonavita, Simona

Subjects
B cell, Vitamin D supplementation, Multiple Sclerosis, General Medicine, Vitamin D Deficiency, Settore MED/26, Neurology, Dietary Supplements, Multiple Sclerosi, Humans, Ocrelizumab, Neurology (clinical), Vitamin D, Retrospective Studies
Abstract

Background: Several observational studies have shown an association between low circulating levels of 25-hydroxy- vitamin D (25(OH)D) and an increase in inflammatory activity in Multiple Sclerosis (MS). Among its immunomodulatory functions, 25(OH)D suppresses proliferation and immunoglobulin production of B cells. 25(OH)D supplementation has been associated with better radiological outcomes in MS patients treated with interferon (IFN)-B, glatiramer acetate, fingolimod, natalizumab and rituximab. Our study is aimed at analyzing the association of 25(OH)D serum levels and supplementation with B cell kinetics and clinical-radiological outcomes of people with MS treated with ocrelizumab. Methods: We have retrospectively collected clinical and radiological data from 136 MS patients who have been treated with ocrelizumab, have undergone at least two treatment cycles and for whom data on serum 25(OH)D levels and intake were available. The patients were divided into three groups according to baseline 25(OH)D serum levels: deficient (≤19,9 ng/ml), insufficient (20-29,9 ng/ml), and normal range 25(OH)D (>30 ng/ml). According to 25(OH)D intake, we divided our population into users and non-users. To explore B cell kinetics at six- and twelve-month follow-ups, the patients were divided into two groups: with fast repopulation (FR) and slow repopulation rate (SR), based on the reappearance or non- appearance of CD19 at each time point. Results: When considering the entire population, the mean 25(OH)D serum level (sd) was 26.27 ng/ml (14.15). 43 (31,62%) patients were classified as deficient, 52 (38,24%) were classified as insufficient, and 41 (30,14%) showed 25(OH)D serum levels within the normal range. 60.29% (82/136) of the patients were classified as users, and 39.70% (54/136) as non-users. Over the eighteen-month treatment period, we observed a significant difference between the 25(OH)D users and the non-users as concerns the number of scans with at least one new/enlarging T2 lesion (2% vs 15.38%, respectively; p= 0.025). In the multinomial regression model, 25(OH)D deficiency (serum levels ≤19,9 ng/ml) was significantly associated with a higher likelihood of disease activity during a follow-up of eighteen months (p=0.029, RRR=4.84, Confidence Interval (CI) 1.17 - 20.01). After six months, there were 30/136 FR patients (22,05%), whereas only 22/136 (16,17%) showed early B cell reappearance at twelve month follow up. 86.66% of the patients in the FR group showed 25(OH)D levels lower than 30 ng/ml (25(OH)D deficiency or insufficiency), whereas only 65.09% of the SR patients presented vitamin D levels lower than 30 ng/ml (p= 0.024). In the logistic regression model, 25(OH)D serum levels below 30 ng/ml were associated with a higher likelihood of early B cell reappearance at six month follow up (p= 0.042). Conclusions: 25(OH)D supplementation and serum levels might be associated with B cell kinetics and radiological activity of patients with MS treated with ocrelizumab.

Published
2022

21. The progressive loss of brain network fingerprints in Amyotrophic Lateral Sclerosis predicts clinical impairment

Author

Antonella Romano, Emahnuel Trosi Lopez, Marianna Liparoti, Arianna Polverino, Roberta Minino, Francesca Trojsi, Simona Bonavita, Laura Mandolesi, Carmine Granata, Enrico Amico, Giuseppe Sorrentino, Pierpaolo Sorrentino, Università degli Studi di Napoli 'Parthenope' = University of Naples (PARTHENOPE), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Istituto di Scienze Applicate e Sistemi Intelligenti 'Eduardo Caianiello' (ISASI), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, University of Naples Federico II = Università degli studi di Napoli Federico II, Ecole Polytechnique Fédérale de Lausanne (EPFL), Université de Genève = University of Geneva (UNIGE), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Consiglio Nazionale delle Ricerche (CNR), RAMOS, Giovanna, Romano, Antonella, Trosi Lopez, Emahnuel, Liparoti, Marianna, Polverino, Arianna, Minino, Roberta, Trojsi, Francesca, Bonavita, Simona, Mandolesi, Laura, Granata, Carmine, Amico, Enrico, Sorrentino, Giuseppe, and Sorrentino, Pierpaolo

Subjects
Male, Brain network identifiability, Clinical connectome fingerprintFunctional connectomeBrain network identifiabilityNeurodegenerative diseasesMotor neurons diseaseMagnetoencephalography, Phase Linearity Measurement, Cognitive Neuroscience, disease progression, Clinical connectome fingerprint, Magnetoencephalography, Phase Linearity Measurement, Connectome, Humans, Radiology, Nuclear Medicine and imaging, patterns, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Clinical connectome fingerprintFunctional connectomeBrain network identifiabilityNeurodegenerative diseasesMotor neurons diseaseMagnetoencephalography, dysfunction, Motor neurons disease, behavior, Amyotrophic Lateral Sclerosis, functional connectivity, Neurodegenerative diseases, Brain, Magnetoencephalography, phase linearity, Functional connectome, Phase Linearity Measurement, Neurology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), measurement
Abstract

International audience; Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by functional connectivity alterations in both motor and extra-motor brain regions. Within the framework of network analysis, fingerprinting represents a reliable approach to assess subject-specific connectivity features within a given population (healthy or diseased). Here, we applied the Clinical Connectome Fingerprint (CCF) analysis to source-reconstructed magnetoencephalography (MEG) signals in a cohort of seventy-eight subjects: thirty-nine ALS patients and thirty-nine healthy controls. We set out to develop an identifiability matrix to assess the extent to which each patient was recognisable based on his/her connectome, as compared to healthy controls. The analysis was performed in the five canonical frequency bands. Then, we built a multilinear regression model to test the ability of the "clinical fingerprint" to predict the clinical evolution of the disease, as assessed by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-r), the King's disease staging system, and the Milano-Torino Staging (MiToS) disease staging system. We found a drop in the identifiability of patients in the alpha band compared to the healthy controls. Furthermore, the "clinical fingerprint" was predictive of the ALSFRS-r (p = 0.0397; β = 32.8), the King's (p = 0.0001; β = − 7.40), and the MiToS (p = 0.0025; β = − 4.9) scores. Accordingly, it negatively correlated with the King's (Spearman's rho =-0.6041, p = 0.0003) and MiToS scales (Spearman's rho = − 0.4953, p = 0.0040). Our results demonstrated the ability of the CCF approach to predict the individual motor impairment in patients affected by ALS. Given the subject-specificity of our approach, we hope to further exploit it to improve disease management.

Published
2022

22. Breakthrough SARS-CoV-2 infections in MS patients on disease-modifying therapies

Author

Schiavetti, I., Cordioli, C., Stromillo, M. L., Teresa Ferro, M., Laroni, A., Cocco, E., Cola, G., Pasquali, L., Rilla, M. T., Signoriello, E., Iodice, R., Di Sapio, A., Lanzillo, R., Caleri, F., Annovazzi, P., Conte, A., Liberatore, G., Ruscica, F., Docimo, R., Bonavita, S., Ulivelli, M., Cavalla, P., Patti, F., Ferraro, D., Clerico, M., Immovilli, P., Di Filippo, M., Salvetti, M., Sormani, M. P., the Breakthrough infections in MS study group, De Stefano, N., Bezzini, D., Giannotta, A., Schiavetti, Irene, Cordioli, Cinzia, Stromillo, Maria Laura, Teresa Ferrò, Maria, Laroni, Alice, Cocco, Eleonora, Cola, Gaia, Pasquali, Livia, Rilla, Maria Teresa, Signoriello, Elisabetta, Iodice, Rosa, Di Sapio, Alessia, Lanzillo, Roberta, Caleri, Francesca, Annovazzi, Pietro, Conte, Antonella, Liberatore, Giuseppe, Ruscica, Francesca, Docimo, Renato, Bonavita, Simona, Ulivelli, Monica, Cavalla, Paola, Patti, Francesco, Ferraro, Diana, Clerico, Marinella, Immovilli, Paolo, Di Filippo, Massimiliano, Salvetti, Marco, and Sormani, Maria Pia

Subjects
COVID-19 Vaccines, COVID-19 vaccination, Fingolimod Hydrochloride, SARS-CoV-2, COVID-19 Vaccine, breakthrough infections, breakthrough infection, COVID-19, Multiple sclerosis, Neurology, Retrospective Studie, Humans, Multiple sclerosi, Neurology (clinical), Human, Retrospective Studies
Abstract

Background: Patients with multiple sclerosis (pwMS) treated with anti-CD20 or fingolimod showed a reduced humoral response to SARS-CoV-2 vaccines. Objective: In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in pwMS on different disease-modifying therapies (DMTs). Methods: Data on the number of vaccinated patients and the number of patients with a breakthrough infection were retrospectively collected in 27 Italian MS centers. We estimated the rate of breakthrough infections and of infection requiring hospitalization per DMT. Results: 19,641 vaccinated pwMS were included in the database. After a median follow-up of 8 months, we observed 137 breakthrough infections. Compared with other DMTs, the rate of breakthrough infections was significantly higher on ocrelizumab (0.57% vs 2.00%, risk ratio (RR) = 3.55, 95% CI = 2.74–4.58, p Conclusions: The risk of breakthrough SARS-CoV-2 infections is higher in patients treated with ocrelizumab and fingolimod, and the rate of severe infections was significantly reduced in all the DMTs excluding ocrelizumab.

Published
2022

23. Whole-Brain Propagation Delays in Multiple Sclerosis, a Combined Tractography-Magnetoencephalography Study

Author

P. Sorrentino, S. Petkoski, M. Sparaco, E. Troisi Lopez, E. Signoriello, F. Baselice, S. Bonavita, M.A. Pirozzi, M. Quarantelli, G. Sorrentino, V. Jirsa, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Project: 945539,HBP, Sorrentino, Pierpaolo, Petkoski, Spase, Sparaco, Maddalena, Troisi Lopez, Emahnuel, Signoriello, Elisabetta, Baselice, Fabio, Bonavita, Simona, Pirozzi, Maria Agnese, Quarantelli, Mario, Sorrentino, Giuseppe, and Jirsa, Viktor

Subjects
magnetoencephalography, conduction velocities, General Neuroscience, [SCCO.NEUR]Cognitive science/Neuroscience, Brain, Electroencephalography, multiple sclerosis, brain networks, brain criticality, brain dynamics, Connectome, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Abstract

Two structurally connected brain regions are more likely to interact, with the lengths of the structural bundles, their widths, myelination, and the topology of the structural connectome influencing the timing of the interactions. We introduce anin vivoapproach for measuring functional delays across the whole brain in humans (of either sex) using magneto/electroencephalography (MEG/EEG) and integrating them with the structural bundles. The resulting topochronic map of the functional delays/velocities shows that larger bundles have faster velocities. We estimated the topochronic map in multiple sclerosis patients, who have damaged myelin sheaths, and controls, demonstrating greater delays in patients across the network and that structurally lesioned tracts were slowed down more than unaffected ones. We provide a novel framework for estimating functional transmission delaysin vivoat the single-subject and single-tract level.SIGNIFICANCE STATEMENTThis article provides a straightforward way to estimate patient-specific delays and conduction velocities in the CNS, at the individual level, in healthy and diseased subjects. To do so, it uses a principled way to merge magnetoencephalography (MEG)/electroencephalography (EEG) and tractography.

Published
2022

24. Coping strategies in relapsing–remitting multiple sclerosis non-depressed patients and their associations with disease activity

Author

Marida Della Corte, Gioacchino Tedeschi, Antonio Gallo, Luigi Lavorgna, Sabrina Esposito, Maria Cropano, Simona Bonavita, Maddalena Sparaco, Gabriella Santangelo, Giuseppina Miele, Federica Garramone, Santangelo, Gabriella, Corte, Marida Della, Sparaco, Maddalena, Miele, Giuseppina, Garramone, Federica, Cropano, Maria, Esposito, Sabrina, Lavorgna, Luigi, Gallo, Antonio, Tedeschi, Gioacchino, and Bonavita, Simona

Subjects
Adult, Male, medicine.medical_specialty, Coping (psychology), Neurology, Physical disability, Neuropsychological Tests, Correlation, Disease activity, Coping strategie, 03 medical and health sciences, Social support, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Clinical activity, Adaptation, Psychological, medicine, Humans, Multiple sclerosi, Prospective Studies, 030212 general & internal medicine, Depression, business.industry, Multiple sclerosis, Cognition, General Medicine, Middle Aged, medicine.disease, Cognitive impairment, Disease Progression, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Relapses, Clinical psychology
Abstract

Few studies evaluated coping strategies in people with multiple sclerosis (pwMS) in relation to annualized relapse rate (ARR) and lesion load (LL). Overall, results might have been influenced by the inclusion of depressed patients. To investigate the coping strategies and their association to disease activity, we studied relapsing-remitting pwMS accurately selected to avoid the confounding effect of depression. Sixty-seven relapsing-remitting pwMS and 67 healthy subjects (HS) underwent to Coping Orientation to Problems Experienced (I-COPE) and Coping Inventory for Stressful Situation (CISS) and Beck Depression Inventory-II. Cognitive performances, ARR, physical disability and magnetic resonance imaging T2-LL were assessed for correlation with coping and depression scores. pwMS showed lower scores than HSs on social support and turning to religion subscales of I-COPE and on emotion dimension of CISS. In pwMS, higher ARR was related to higher positive attitude and lower score on the turning to religion subscale of I-COPE. The present study revealed a less employment of emotion-based coping strategies in pwMS. A scarce use of faith for support and a frequent adoption of a positive attitude were associated with an increase of MS activity in terms of ARR.

Published
2019

25. The structural connectome constrains fast brain dynamics

Author

Rosaria Rucco, Marianna Liparoti, Caio Seguin, Viktor K. Jirsa, Giuseppe Sorrentino, Andrew Zalesky, Pierpaolo Sorrentino, Emahnuel Troisi Lopez, Simona Bonavita, Mario Quarantelli, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Melbourne, Università degli Studi di Napoli 'Parthenope' = University of Naples (PARTHENOPE), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, Institute of biostructures and bioimaging (IBB), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Consiglio Nazionale delle Ricerche (CNR), Otten, Lisa, Sorrentino, Pierpaolo, Seguin, Caio, Rucco, Rosaria, Liparoti, Marianna, Troisi Lopez, Emahnuel, Bonavita, Simona, Quarantelli, Mario, Sorrentino, Giuseppe, Jirsa, Viktor, and Zalesky, Andrew

Subjects
Male, magnetoencephalography, 0301 basic medicine, Brain activity and meditation, computational biology, 0302 clinical medicine, structural connectome, neuronal avalanches, Biology (General), Neurons, Systems neuroscience, medicine.diagnostic_test, brain dynamics, brain networks, human, systems biology, systems neuroscience, Adult, Brain, Connectome, Female, Humans, Magnetic Resonance Imaging, Magnetoencephalography, Nerve Net, Systems Biology, General Neuroscience, Human Connectome, General Medicine, Human brain, medicine.anatomical_structure, Medicine, Computational and Systems Biology, Human, Tractography, QH301-705.5, Science, Short Report, General Biochemistry, Genetics and Molecular Biology, brain dynamic, 03 medical and health sciences, medicine, brain network, General Immunology and Microbiology, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, 030104 developmental biology, Neuroscience, 030217 neurology & neurosurgery, Diffusion MRI
Abstract

International audience; Brain activity during rest displays complex, rapidly evolving patterns in space and time. Structural connections comprising the human connectome are hypothesized to impose constraints on the dynamics of this activity. Here, we use magnetoencephalography (MEG) to quantify the extent to which fast neural dynamics in the human brain are constrained by structural connections inferred from diffusion MRI tractography. We characterize the spatio-temporal unfolding of whole-brain activity at the millisecond scale from source-reconstructed MEG data, estimating the probability that any two brain regions will significantly deviate from baseline activity in consecutive time epochs. We find that the structural connectome relates to, and likely affects, the rapid spreading of neuronal avalanches, evidenced by a significant association between these transition probabilities and structural connectivity strengths (r=0.37, p

Published
2021

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

Author

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

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

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

Published
2021

27. The impact of COVID-19 on people with multiple sclerosis: A comparison of Italian and United States cohorts

Author

Schwartz, Ce, Rapkin, Bd, Bonavita, S, Bossa, M, Buscarinu, Mc, Grasso, Mg, Luca, M, Nozzolillo, A, Nocentini, U, Schwartz, Carolyn E, Rapkin, Bruce D, Bonavita, Simona, Bossa, Michela, Buscarinu, Maria Chiara, Grasso, Maria Grazia, Luca, Maria, Nozzolillo, Agostino, and Nocentini, Ugo

Subjects
Disability, Multiple Sclerosis, Depression, COVID-19, General Medicine, Anxiety, United States, Settore MED/34, Cross-Sectional Studies, Neurology, International, Post-traumatic growth, Humans, Mental health, Multiple sclerosi, Neurology (clinical)
Abstract

The present cross-national study addressed the relationship among three pandemic-related variables and multiple sclerosis (MS) disability outcomes among people with MS in Italy and the United States (US).This cross-sectional web-based study was administered to 708 patients with MS from the US and Italy in late Spring through mid-Summer of 2020. Pandemic-related variables assessed worry, self-protection, and post-traumatic growth. The Performance Scales© assessed MS disability. Multivariate multiple regression models addressed, separately by country, the relationship among worry, protection, and post-traumatic growth with MS disability, after covariate adjustment.The Italian sample (n = 292) was younger and less disabled than the US group (n = 416). After covariate adjustment, all three pandemic-related variables were associated with MS disability outcomes in the US sample, but only worry and post-traumatic growth were associated in the Italian sample. Worse cognitive and depression symptoms were associated with worry, and lesser mobility disability was associated with endorsed growth in both countries. More disability variables were associated with worry and growth in the Italian sample.The pandemic's negative aspects were associated with worse disability in both countries, and reported post-traumatic growth was associated with lesser disability. These findings may suggest directions for clinical intervention.

Published
2022

28. How to manage with telemedicine people with neuromuscular diseases?

Author

Francesca Trojsi, Gianmarco Abbadessa, Fiore Manganelli, Rosa Iodice, Emanuele Spina, Aniello Iovino, Carla Passaniti, Simona Bonavita, Luigi Lavorgna, Letizia Leocani, Gioacchino Tedeschi, Stefano Tozza, Spina, Emanuele, Trojsi, Francesca, Tozza, Stefano, Iovino, Aniello, Iodice, Rosa, Passaniti, Carla, Abbadessa, Gianmarco, Bonavita, Simona, Leocani, Letizia, Tedeschi, Gioacchino, Manganelli, Fiore, Lavorgna, Luigi, Spina, E., Trojsi, F., Tozza, S., Iovino, A., Iodice, R., Passaniti, C., Abbadessa, G., Bonavita, S., Leocani, L., Tedeschi, G., Manganelli, F., and Lavorgna, L.

Subjects
Telemedicine, medicine.medical_specialty, Neuromuscular disease, business.product_category, Neurology, Coronavirus disease 2019 (COVID-19), TeleRehabilitation, Dermatology, Review Article, Tele-health, 03 medical and health sciences, 0302 clinical medicine, Telerehabilitation, Pandemic, Internet access, Medicine, Humans, Social media, 030212 general & internal medicine, Pandemics, business.industry, SARS-CoV-2, COVID-19, Correction, General Medicine, Neuromuscular Diseases, medicine.disease, Neuromuscular Disease, Psychiatry and Mental health, Neurology (clinical), Medical emergency, business, 030217 neurology & neurosurgery, Human
Abstract

Introduction COVID-19 pandemic radically transformed our daily clinical practice, raising the need not to lose close contact with patients without being able to see them face-to-face. These issues are even more felt and evident in fragile patients, as those affected by neuromuscular disease. An important help came from new digital technologies that allow clinicians to remotely monitor health status and any deterioration of chronically ill patients. Methods In this mini-review, an initiative of the “Digital Technologies, Web and Social Media Study Group” of the Italian Society of Neurology, we propose to analyze the approach to neuromuscular patients by looking over raising evidence on the main cornerstones of Telemedicine (TM): clinician-patient interaction, remote clinical assessment, remote monitoring, and digital therapeutics. In particular, we explored the strategies developed by researchers and their impact on the physical and emotional status of the patients, with particular focusing on their adherence to the program of virtual monitoring. Results TM plays an important role in each of four stages of approach to neuromuscular disease, having demonstrated validity in keep close clinical patient interaction, clinical assessment, remote monitoring, and telerehabilitation. Nevertheless, there is no remote alternative to electrophysiological testing neither validate tools to assess disability. Conclusion The role of TM in neuromuscular care is yet underestimated but is crucial, beyond the pandemic era. Further development of TM is advisable, through making specific apps, remotely controlled by clinicians, and making more engaging clinicians-patients interaction. Last, it is necessary to ensure adequate internet access to everyone.

Published
2021

29. Hemostatic factors in the pathogenesis of neuroinflammation in multiple sclerosis

Author

Simona Bonavita, Gianmarco Abbadessa, Caterina Mainero, Constantina A. Treaba, Luigi Lavorgna, Abbadessa, Gianmarco, Lavorgna, Luigi, Treaba, Constantina Andrada, Bonavita, Simona, and Mainero, Caterina

Subjects
biology, business.industry, Multiple sclerosis, Neuroimaging, medicine.disease, multiple sclerosis, Fibrin, Hemostatics, Pathogenesis, Neurology, Coagulation, Neuroinflammation, Hemostasis, Immunology, Neuroinflammatory Diseases, medicine, biology.protein, Humans, Neurology (clinical), fibrin, coagulation, business, hemostasi, Biomarkers
Abstract

Background: A growing body of evidence has shed light on the role of the hemostatic pathway and its components in the pathogenesis of multiple sclerosis (MS), particularly in enhancing and sustaining neuroinflammation. Objective: To review the clinical, experimental, and neuroimaging evidence supporting the role of different components of the hemostatic pathway in the pathogenesis of neuroinflammation in MS and discuss their translational potential as disease biomarkers and therapeutic targets. Methods: A literature search for most relevant articles from 1956 to 2020 was conducted in PubMed and Scopus. Results: Hemostasis components appear to be involved in different key events of neuroinflammation in MS including mononuclear cell diapedesis, microglia activation, and neuronal damage. Conclusion: The findings on the interplay between hemostatic and thrombotic molecular pathways in the pathogenesis of neuroinflammation in MS open new opportunities for developing novel biomarkers for disease monitoring and prognosis, as well as novel therapeutic targets.

Published
2021

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

Author

Maria Pia Sormani, Irene Schiavetti, Doriana Landi, Luca Carmisciano, Nicola De Rossi, Cinzia Cordioli, Lucia Moiola, Marta Radaelli, Paolo Immovilli, Marco Capobianco, Vincenzo Brescia Morra, Maria Trojano, Gioacchino Tedeschi, Giancarlo Comi, Mario Alberto Battaglia, Francesco Patti, Yara Dadalti Fragoso, Sedat Sen, Aksel Siva, Roberto Furlan, Marco Salvetti, Gianmarco Abbadessa, Umberto Aguglia, Lia Allegorico, Rossi Beatrice Maria Allegri, Maria Pia Amato, Pietro Annovazzi, Carlo Antozzi, Lucia Appendino, Sebastiano Arena, Viola Baione, Roberto Balgera, Valeria Barcella, Damiano Baroncini, Caterina Barrilà, Mario A. Battaglia, Alessandra Bellacosa, Gianmarco Bellucci, Roberto Bergamaschi, Valeria Bergamaschi, Daiana Bezzini, Beatrice Biolzi, Alvino Bisecco, Simona Bonavita, Giovanna Borriello, Chiara Bosa, Antonio Bosco, Francesca Bovis, Marco Bozzali, Laura Brambilla, Morra Vincenzo Brescia, Giampaolo Brichetto, Maria Buccafusca, Elisabetta Bucciantini, Sebastiano Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano Calabrese, Francesca Calabria, Francesca Caleri, Federico Camilli, Luisa Maria Caniatti, Roberto Cantello, Ruggero Capra, Rocco Capuano, Patrizia Carta, Paola Cavalla, Maria Grazia Celani, Maria Cellerino, Raffaella Cerqua, Clara Chisari, Raffaella Clerici, Marinella Clerico, Eleonora Cocco, Gaia Cola, Paolo Confalonieri, Antonella Conte, Marta Zaffira Conti, Christian Cordano, Susanna Cordera, Francesco Corea, Claudio Correale, Salvatore Cottone, Francesco Crescenzo, Erica Curti, Alessandro d’Ambrosio, Emanuele D’Amico, Maura Chiara Danni, Alessia d’Arma, Vincenzo Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Stefano, Marco Della Cava, Mario di Napoli, Alessia Di Sapio, Renato Docimo, Anna Dutto, Luana Evangelista, Salvatore Fanara, Diana Ferraro, Maria Teresa Ferrò, Massimo Filippi, Cristina Fioretti, Mario Fratta, Jessica Frau, Marzia Fronza, Alberto Gajofatto, Antonio Gallo, Paolo Gallo, Claudio Gasperini, Anna Ghazaryan, Bruno Giometto, Francesca Gobbin, Flora Govone, Franco Granella, Erica Grange, Maria Grazia Grasso, Angelica Guareschi, Clara Guaschino, Simone Guerrieri, Donata Guidetti, Pietro Iaffaldano, Antonio Ianniello, Luigi Iasevoli, Daniele Imperiale, Maria Teresa Infante, Matilde Inglese, Rosa Iodice, Aniello Iovino, Giovanna Konrad, Roberta Lanzillo, Caterina Lapucci, Luigi Lavorgna, Rita L’Episcopo Maria, Serena Leva, Giuseppe Liberatore, Marianna Lo Re, Marco Longoni, Leonardo Lopiano, Lorena Lorefice, Matteo Lucchini, Giacomo Lus, Davide Maimone, Maria Malentacchi, Giulia Mallucci, Simona Malucchi, Chiara Rosa Mancinelli, Luca Mancinelli, Paolo Manganotti, Teresa Giorgia Maniscalco, Vittorio Mantero, Sabrina Marangoni, Damiano Marastoni, Alessandra Girolama Marfia, Fabiana Marinelli, Alessandro Marti, Filippo Martinelli Boneschi, Federco Masserano Zoli, Francesca Matta, Laura Mendozzi, Giuseppe Meucci, Silvia Miante, Giuseppina Miele, Eva Milano, Massimiliano Mirabella, Rosanna Missione, Marcello Moccia, Sara Montepietra, Margherita Monti Bragadin, Federico Montini, Roberta Motta, Raffaele Nardone, Carolina Gabri Nicoletti, Eduardo Nobile-Orazio, Agostino Nozzolillo, Marco Onofrj, Riccardo Orlandi, Anna Palmieri, Damiano Paolicelli, Livia Pasquali, Luisa Pastò, Elisabetta Pedrazzoli, Paola Perini, Ilaria Pesci, Maria Petracca, Alfredo Petrone, Carlo Piantadosi, Anna M. Pietroboni, Federica Pinardi, Marta Ponzano, Emilio Portaccio, Mattia Pozzato, Carlo Pozzilli, Luca Prosperini, Alessandra Protti, Paolo Ragonese, Sarah Rasia, Sabrina Realmuto, Anna Repice, Eleonora Rigoni, Maria Teresa Rilla, Francesca Rinaldi, Calogero Marcello Romano, Marco Ronzoni, Marco Rovaris, Francesca Ruscica, Loredana Sabattini, Giuseppe Salemi, Lorenzo Saraceno, Alessia Sartori, Arianna Sartori, Elvira Sbragia, Cinzia Scandellari, Ilaria Scarano Giuditta, Valentina Scarano, Valentina Schillaci, Maria Sessa, Caterina Sgarito, Grazia Sibilia, Gabriele Siciliano, Alessio Signori, Elisabetta Signoriello, Leonardo Sinisi, Francesca Sireci, Patrizia Sola, Claudio Solaro, Stefano Sotgiu, Maddalena Sparaco, Maria Laura Stromillo, Silvia Strumia, Laura Emanuela Susani, Giulietta Tabiadon, Francesco Teatini, Valentina Tomassini, Simone Tonietti, Clerici Valentina Torri, Carla Tortorella, Simona Toscano, Rocco Totaro, Maria Trotta, Gabriella Turano, Monica Ulivelli, Manzo Valentino, Giovanna Vaula, Domizia Vecchio, Marco Vercellino, Elena Pinuccia Verrengia, Marika Vianello, Eleonora Virgilio, Francesca Vitetta, Stefano Vollaro, Mauro Zaffaroni, Mauro Zampolini, Ignazio Roberto Zarbo, Antonio Zito, Luigi Zuliani, Sormani, M. P., Schiavetti, I., Landi, D., Carmisciano, L., De Rossi, N., Cordioli, C., Moiola, L., Radaelli, M., Immovilli, P., Capobianco, M., Brescia Morra, V., Trojano, M., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Fragoso, Y. D., Sen, S., Siva, A., Furlan, R., Salvetti, M., Bisecco, Alvino, Pia Sormani, Maria, Schiavetti, Irene, Landi, Doriana, Carmisciano, Luca, De Rossi, Nicola, Cordioli, Cinzia, Moiola, Lucia, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, Brescia Morra, Vincenzo, Trojano, Maria, Tedeschi, Gioacchino, Comi, Giancarlo, Alberto Battaglia, Mario, Patti, Francesco, Dadalti Fragoso, Yara, Sen, Sedat, Siva, Aksel, Furlan, Roberto, Salvetti, Marco, Study Group Gianmarco Abbadessa, MuSC-19, Aguglia, Umberto, Allegorico, Lia, Beatrice Maria Allegri, Rossi, Pia Amato, Maria, Annovazzi, Pietro, Antozzi, Carlo, Appendino, Lucia, Arena, Sebastiano, Baione, Viola, Balgera, Roberto, Barcella, Valeria, Baroncini, Damiano, Barrilà, Caterina, A Battaglia, Mario, Bellacosa, Alessandra, Bellucci, Gianmarco, Bergamaschi, Roberto, Bergamaschi, Valeria, Bezzini, Daiana, Biolzi, Beatrice, Bonavita, Simona, Borriello, Giovanna, Bosa, Chiara, Bosco, Antonio, Bovis, Francesca, Bozzali, Marco, Brambilla, Laura, Vincenzo Brescia, Morra, Brichetto, Giampaolo, Buccafusca, Maria, Bucciantini, Elisabetta, Bucello, Sebastiano, Chiara Buscarinu, Maria, Paola Cabboi, Maria, Calabrese, Massimiliano, Calabria, Francesca, Caleri, Francesca, Camilli, Federico, Maria Caniatti, Luisa, Cantello, Roberto, Capra, Ruggero, Capuano, Rocco, Carta, Patrizia, Cavalla, Paola, Grazia Celani, Maria, Cellerino, Maria, Cerqua, Raffaella, Chisari, Clara, Clerici, Raffaella, Clerico, Marinella, Cocco, Eleonora, Cola, Gaia, Confalonieri, Paolo, Conte, Antonella, Zaffira Conti, Marta, Cordano, Christian, Cordera, Susanna, Corea, Francesco, Correale, Claudio, Cottone, Salvatore, Crescenzo, Francesco, Curti, Erica, D'Ambrosio, Alessandro, D'Amico, Emanuele, Chiara Danni, Maura, D'Arma, Alessia, Dattola, Vincenzo, de Biase, Stefano, De Luca, Giovanna, Federica De Mercanti, Stefania, De Mitri, Paolo, De Stefano, Nicola, Della Cava, Marco, di Napoli, Mario, Di Sapio, Alessia, Docimo, Renato, Dutto, Anna, Evangelista, Luana, Fanara, Salvatore, Ferraro, Diana, Teresa Ferrò, Maria, Filippi, Massimo, Fioretti, Cristina, Fratta, Mario, Frau, Jessica, Fronza, Marzia, Gajofatto, Alberto, Gallo, Antonio, Gallo, Paolo, Gasperini, Claudio, Ghazaryan, Anna, Giometto, Bruno, Gobbin, Francesca, Govone, Flora, Granella, Franco, Grange, Erica, Grazia Grasso, Maria, Guareschi, Angelica, Guaschino, Clara, Guerrieri, Simone, Guidetti, Donata, Iaffaldano, Pietro, Ianniello, Antonio, Iasevoli, Luigi, Imperiale, Daniele, Teresa Infante, Maria, Inglese, Matilde, Iodice, Rosa, Iovino, Aniello, Konrad, Giovanna, Lanzillo, Roberta, Lapucci, Caterina, Lavorgna, Luigi, L'Episcopo Maria, Rita, Leva, Serena, Liberatore, Giuseppe, Lo Re, Marianna, Longoni, Marco, Lopiano, Leonardo, Lorefice, Lorena, Lucchini, Matteo, Lus, Giacomo, Maimone, Davide, Malentacchi, Maria, Mallucci, Giulia, Malucchi, Simona, Rosa Mancinelli, Chiara, Mancinelli, Luca, Manganotti, Paolo, Giorgia Maniscalco, Teresa, Mantero, Vittorio, Marangoni, Sabrina, Marastoni, Damiano, Girolama Marfia, Alessandra, Marinelli, Fabiana, Marti, Alessandro, Martinelli Boneschi, Filippo, Masserano Zoli, Federco, Matta, Francesca, Mendozzi, Laura, Meucci, Giuseppe, Miante, Silvia, Miele, Giuseppina, Milano, Eva, Mirabella, Massimiliano, Missione, Rosanna, Moccia, Marcello, Montepietra, Sara, Monti Bragadin, Margherita, Montini, Federico, Motta, Roberta, Nardone, Raffaele, Gabri Nicoletti, Carolina, Nobile-Orazio, Eduardo, Nozzolillo, Agostino, Onofrj, Marco, Orlandi, Riccardo, Palmieri, Anna, Paolicelli, Damiano, Pasquali, Livia, Pastò, Luisa, Pedrazzoli, Elisabetta, Perini, Paola, Pesci, Ilaria, Petracca, Maria, Petrone, Alfredo, Piantadosi, Carlo, M Pietroboni, Anna, Pinardi, Federica, Ponzano, Marta, Portaccio, Emilio, Pozzato, Mattia, Pozzilli, Carlo, Prosperini, Luca, Protti, Alessandra, Ragonese, Paolo, Rasia, Sarah, Realmuto, Sabrina, Repice, Anna, Rigoni, Eleonora, Teresa Rilla, Maria, Rinaldi, Francesca, Marcello Romano, Calogero, Ronzoni, Marco, Rovaris, Marco, Ruscica, Francesca, Sabattini, Loredana, Salemi, Giuseppe, Saraceno, Lorenzo, Sartori, Alessia, Sartori, Arianna, Sbragia, Elvira, Scandellari, Cinzia, Scarano Giuditta, Ilaria, Scarano, Valentina, Schillaci, Valentina, Sessa, Maria, Sgarito, Caterina, Sibilia, Grazia, Siciliano, Gabriele, Signori, Alessio, Signoriello, Elisabetta, Sinisi, Leonardo, Sireci, Francesca, Sola, Patrizia, Solaro, Claudio, Sotgiu, Stefano, Sparaco, Maddalena, Laura Stromillo, Maria, Strumia, Silvia, Emanuela Susani, Laura, Tabiadon, Giulietta, Teatini, Francesco, Tomassini, Valentina, Tonietti, Simone, Valentina Torri, Clerici, Tortorella, Carla, Toscano, Simona, Totaro, Rocco, Trotta, Maria, Turano, Gabriella, Ulivelli, Monica, Valentino, Manzo, Vaula, Giovanna, Vecchio, Domizia, Vercellino, Marco, Pinuccia Verrengia, Elena, Vianello, Marika, Virgilio, Eleonora, Vitetta, Francesca, Vollaro, Stefano, Zaffaroni, Mauro, Zampolini, Mauro, Roberto Zarbo, Ignazio, Zito, Antonio, Zuliani, Luigi, Abbadessa, Gianmarco, Trotta, Maria Consiglia, and Zito, Guido Antonio

Subjects
0301 basic medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), immunosuppressive therapie, coronavirus, Settore MED/26, medicine.disease_cause, Antibodies, Viral, immunosuppressive therapies, Antibodies, Serology, Cohort Studies, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Seroepidemiologic Studies, Pandemic, Medicine, Humans, Multiple sclerosi, Viral, Coronavirus, business.industry, immunomodulatory therapie, immunomodulatory therapies, COVID-19, medicine.disease, Virology, coronaviru, Settore MED/26 - NEUROLOGIA, Sars-COV-2, 030104 developmental biology, Neurology, Neurology (clinical), business, SARS-CoV-2, Multiple Sclerosis, 030217 neurology & neurosurgery, Cohort study
Abstract

Background: The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, serological tests became routinely available. Objective: To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test. Methods: We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model. Results: Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20, p = 0.002). Conclusion: Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination.

Published
2021

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

Author

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

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Coronavirus disease 2019 (COVID-19), Population, Intensive Care Unit, COVID-19, Cohort Studies, Comorbidity, Female, Hospitalization, Humans, Intensive Care Units, Italy, Middle Aged, Retrospective Studies, Risk Factors, Severity of Illness Index, Context (language use), Settore MED/26, Lower risk, Retrospective Studie, Internal medicine, Multiple Sclerosi, Medicine, In patient, National level, education, education.field_of_study, Expanded Disability Status Scale, business.industry, Risk Factor, Ethics committee, medicine.disease, Icu admission, Settore MED/26 - NEUROLOGIA, Neurology, Relative risk, Family medicine, Cohort, Honorarium, Observational study, Neurology (clinical), Cohort Studie, business, Human
Abstract

Background: It is unclear how multiple sclerosis (MS) affects the severity of Covid-19. Methods: Hospitalization, Intensive Care Unit (ICU) admission and death after Covid-19 diagnosis of 1362 MS patients were compared to the age and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher-risk: EDSS>3 or at least one comorbidity, lower-risk: EDSS

Published
2021

32. Exit Strategies in Natalizumab-Treated RRMS at High Risk of Progressive Multifocal Leukoencephalopathy: a Multicentre Comparison Study

Author

Gianmarco Abbadessa, Carlo Avolio, Patrizia Sola, Franco Granella, Graziella Callari, Stefania Barone, Elisabetta Signoriello, Simona Bonavita, Francesco Patti, Aurora Zanghì, Maria Buccafusca, Valeria Di Francescantonio, Antonio Gallo, Rocco Capuano, Diana Ferraro, Roberta Lanzillo, Paola Valentino, Matteo Lucchini, Erica Curti, Giuseppe Pontillo, Massimiliano Mirabella, Emanuele D'Amico, Maria Petracca, Giacomo Lus, Zanghì, Aurora, Gallo, Antonio, Avolio, Carlo, Capuano, Rocco, Lucchini, Matteo, Petracca, Maria, Bonavita, Simona, Lanzillo, Roberta, Ferraro, Diana, Curti, Erica, Buccafusca, Maria, Callari, Graziella, Barone, Stefania, Pontillo, Giuseppe, Abbadessa, Gianmarco, Di Francescantonio, Valeria, Signoriello, Elisabetta, Lus, Giacomo, Sola, Patrizia, Granella, Franco, Valentino, Paola, Mirabella, Massimiliano, Patti, Francesco, D'Amico, Emanuele, Zanghi, A., Gallo, A., Avolio, C., Capuano, R., Lucchini, M., Petracca, M., Bonavita, S., Lanzillo, R., Ferraro, D., Curti, E., Buccafusca, M., Callari, G., Barone, S., Pontillo, G., Abbadessa, G., Di Francescantonio, V., Signoriello, E., Lus, G., Sola, P., Granella, F., Valentino, P., Mirabella, M., Patti, F., and D'Amico, E.

Subjects
0301 basic medicine, Male, Immunosuppressive Agent, 0302 clinical medicine, Natalizumab, Immunologic Factor, Risk Factors, Retrospective Studie, Pharmacology (medical), Prospective Studies, Disease activity, Ocrelizumab, Drug Substitution, Progressive multifocal leukoencephalopathy, Leukoencephalopathy, Progressive Multifocal, Settore MED/26 - NEUROLOGIA, Original Article, Rituximab, Female, Immunosuppressive Agents, medicine.drug, Human, Adult, medicine.medical_specialty, Adolescent, Lower risk, Antibodies, Monoclonal, Humanized, Cladribine, Exit strategy, Follow-Up Studie, 03 medical and health sciences, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, Post-hoc analysis, medicine, Humans, Immunologic Factors, Retrospective Studies, Pharmacology, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Risk Factor, medicine.disease, Prospective Studie, 030104 developmental biology, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

The main aim of the study is to evaluate the efficacy and safety profile of ocrelizumab (OCR), rituximab (RTX), and cladribine (CLA), employed as natalizumab (NTZ) exit strategies in relapsing–remitting multiple sclerosis (RRMS) patients at high-risk for progressive multifocal leukoencephalopathy (PML). This is a multicentre, retrospective, real-world study on consecutive RRMS patients from eleven tertiary Italian MS centres, who switched from NTZ to OCR, RTX, and CLA from January 1st, 2019, to December 31st, 2019. The primary study outcomes were the annualized relapse rate (ARR) and magnetic resonance imaging (MRI) outcome. Treatment effects were estimated by the inverse probability treatment weighting (IPTW), based on propensity-score (PS) approach. Additional endpoint included confirmed disability progression (CDP) as measured by Expanded Disability Status Scale and adverse events (AEs). Patients satisfying predefined inclusion and exclusion criteria were 120; 64 switched to OCR, 36 to RTX, and 20 to CLA. Patients from the 3 groups did not show differences for baseline characteristics, also after post hoc analysis. The IPTW PS-adjusted models revealed that patients on OCR had a lower risk for ARR than patients on CLA (ExpBOCR0.485, CI 95% 0.264–0.893,p = 0.020). This result was confirmed also for 12-month MRI activity (ExpBOCR0.248 CI 95% 0.065–0.948,p = 0.042). No differences were found in other pairwise comparisons (OCR vs RTX and RTX vs CLA) for the investigated outcomes. AEs were similar among the 3 groups. Anti-CD20 drugs were revealed to be effective and safe options as NTZ exit strategies. All investigated DMTs showed a good safety profile.

Published
2021

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

Author

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

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

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

Published
2021

34. Myasthenia gravis and telemedicine: a lesson from COVID-19 pandemic

Author

Gianmarco Abbadessa, Francesco Iodice, Bianca Orlando, Giovanni Cirillo, Simona Bonavita, Giuseppina Miele, Marinella Clerico, Francesca Trojsi, Luigi Lavorgna, Marco Bozzali, Silvia Casagrande, Letizia Leocani, Gioacchino Tedeschi, Dario Ricciardi, Ricciardi, Dario, Casagrande, Silvia, Iodice, Francesco, Orlando, Bianca, Trojsi, Francesca, Cirillo, Giovanni, Clerico, Marinella, Bozzali, Marco, Leocani, Letizia, Abbadessa, Gianmarco, Miele, Giuseppina, Tedeschi, Gioacchino, Bonavita, Simona, Lavorgna, Luigi, Ricciardi, D., Casagrande, S., Iodice, F., Orlando, B., Trojsi, F., Cirillo, G., Clerico, M., Bozzali, M., Leocani, L., Abbadessa, G., Miele, G., Tedeschi, G., Bonavita, S., and Lavorgna, L.

Subjects
medicine.medical_specialty, Telemedicine, Neurology, Coronavirus disease 2019 (COVID-19), Myasthenia gravi, Dermatology, Disease, Tele-health, Pandemic, Myasthenia Gravis, medicine, Humans, Intensive care medicine, Adverse effect, Myasthenia gravis, Pandemics, business.industry, SARS-CoV-2, COVID-19, General Medicine, medicine.disease, Psychiatry and Mental health, Neurology (clinical), Neurosurgery, Tele-neurology, business
Abstract

COVID-19 pandemic has induced an urgent reorganization of the healthcare system to ensure continuity of care for patients affected by chronic neurological diseases including myasthenia gravis (MG). Due to the fluctuating nature of the disease, early detection of disease worsening, adverse events, and possibly life-threatening complications is mandatory. This work analyzes the main unresolved issues in the management of the myasthenic patient, the possibilities offered so far by digital technologies, and proposes an online evaluation protocol based on 4 simple tests to improve MG management. Telemedicine and Digital Technology might help neurologists in the clinical decision-making process of MG management, avoiding unnecessary in presence consultations and allowing a rational use of the time and space reduced by the pandemic.

Published
2021

35. Stroke and digital technology: a wake-up call from COVID-19 pandemic

Author

Marinella Clerico, Michele Romoli, Simona Bonavita, Francesco Iodice, Letizia Leocani, Gioacchino Tedeschi, Bruno Giometto, Luigi Lavorgna, Iodice, Francesco, Romoli, Michele, Giometto, Bruno, Clerico, Marinella, Tedeschi, Gioacchino, Bonavita, Simona, Leocani, Letizia, Lavorgna, Luigi, Iodice, F., Romoli, M., Giometto, B., Clerico, M., Tedeschi, G., Bonavita, S., Leocani, L., and Lavorgna, L.

Subjects
Telemedicine, medicine.medical_specialty, medicine.medical_treatment, Clinical Neurology, COVID-19, Stroke, Telehealth, Teleneurology, Telerehabilitation, Humans, Italy, Neurology, SARS-CoV-2, Stroke Rehabilitation, Dermatology, 03 medical and health sciences, 0302 clinical medicine, Acute care, Pandemic, medicine, Social media, 030212 general & internal medicine, Rehabilitation, business.industry, General Medicine, medicine.disease, Psychiatry and Mental health, Neurology (clinical), Medical emergency, business, 030217 neurology & neurosurgery, Human
Abstract

Introduction: The pandemic has implemented the need for new digital technologies as useful tools during the emergency and the long recovery phase that will follow. SARS-CoV-2 has strongly impacted stroke care with significant contraction in a number of patients treated. Methods: This mini-review is an initiative of the “Digital Technologies, Web and Social Media Study Group” of the Italian Society of Neurology and briefly discusses digital tools for managing the acute phase and the rehabilitation after stroke, even considering the new apps that will improve the process of remote monitoring of patients after discharge at home. Results: Telemedicine and digital technologies could play a role in each of the three stroke-belt stages: hyperacute treatment and reperfusion, acute care, etiological classification and secondary prevention and rehabilitation. Conclusion: The global emergency represented by the COVID-19 pandemic can be the stimulus to accelerate the digitalization process in the field of stroke for the use of new methods on a large scale.

Published
2021

36. Switch from sequestering to anti-CD20 depleting treatment: disease activity outcomes during wash-out and in the first 6 months of ocrelizumab therapy

Author

Maria Pia Sormani, Antonio Carotenuto, Jessica Frau, Doriana Landi, Girolama Alessandra Marfia, Alessio Signori, Erica Curti, Francesco Saccà, Giorgia Teresa Maniscalco, Simone Cepparulo, Elisabetta Signoriello, Francesca Caleri, Mauro Zaffaroni, Damiano Baroncini, Carolina Gabri Nicoletti, Simona Bonavita, Giacomo Lus, Roberta Lanzillo, Viviana Nociti, Arianna Sartori, Signoriello, E., Lus, G., Bonavita, S., Lanzillo, R., Sacca, F., Landi, D., Frau, J., Baroncini, D., Zaffaroni, M., Maniscalco, G. T., Curti, E., Sartori, A., Cepparulo, S., Marfia, G. A., Nicoletti, C. G., Carotenuto, A., Nociti, V., Caleri, F., Sormani, M. P., Signori, A., Signoriello, Elisabetta, Lus, Giacomo, Bonavita, Simona, Lanzillo, Roberta, Sacc??, Francesco, Landi, Doriana, Frau, Jessica, Baroncini, Damiano, Zaffaroni, Mauro, Teresa Maniscalco, Giorgia, Curti, Erica, Sartori, Arianna, Cepparulo, Simone, Alessandra Marfia, Girolama, Gabri Nicoletti, Carolina, Carotenuto, Antonio, Nociti, Viviana, Caleri, Francesca, Pia Sormani, Maria, and Signori, Alessio

Subjects
Oncology, medicine.medical_specialty, Antibodies, Monoclonal, Humanized, Settore MED/26, Disease activity, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, natalizumab, ocrelizumab, Internal medicine, medicine, Humans, Multiple sclerosi, 030212 general & internal medicine, Anti cd20, fingolimod, switch, Retrospective Studies, business.industry, Fingolimod Hydrochloride, medicine.disease, Fingolimod, Disease control, Neurology, Ocrelizumab, Neurology (clinical), business, 030217 neurology & neurosurgery, Immunosuppressive Agents, medicine.drug
Abstract

Objectives: Switching between treatments is an opportunity for patients with multiple sclerosis (MS) to ameliorate disease control or safety. The aim of this study was to investigate the impact of switching from fingolimod (FTY) or natalizumab (NTZ) to ocrelizumab (OCR) on disease activity. Methods: We retrospectively enrolled 165 patients treated with OCR from 11 MS centres. We assessed the association of demographic and clinical characteristics on relapse rate (RR) and activity on magnetic resonance imaging (MRI) during wash-out and after 6 months of treatment with OCR through univariable and multivariable negative binomial regression models. Results: We registered a total of 35 relapses during the wash-out period. Previous treatment with FTY, relapses in the previous year, and relapsing-remitting course were associated with higher RR. In the first 6 months of OCR, 12 patients had clinical or MRI disease activity. Higher Expanded Disability Status Scale (EDSS) and higher lymphocyte count at OCR start were associated with a reduced probability of relapse. Discussion and Conclusion: This study confirms that withdrawal from sequestering agents as FTY increases the risk of relapses in the wash-out period. Nevertheless, starting OCR before achieving complete immune reconstitution could limit its effectiveness in the first 6 months probably because trapped lymphocytes escape the CD20-mediated depletion.

Published
2021

37. Screening neuromyelitis optica patients for COVID-19 infection

Author

Saeed Vaheb, Mahdi Barzegar, Omid Mirmosayyeb, Vahid Shaygannejad, Mahsa Ghajarzadeh, Simona Bonavita, Mirmosayyeb, Omid, Vaheb, Saeed, Barzegar, Mahdi, Shaygannejad, Vahid, Bonavita, Simona, and Ghajarzadeh, Mahsa

Subjects
2019-20 coronavirus outbreak, Neuromyelitis optica, Coronavirus disease 2019 (COVID-19), biology, business.industry, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Neuromyelitis Optica, Pneumonia, Viral, Immunology, COVID-19, medicine.disease, biology.organism_classification, Virology, Article, Betacoronavirus, Pandemic, Medicine, Humans, Immunology and Allergy, business, Coronavirus Infections, Pandemics
Published
2020
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38. The Rise of the GRN C157KfsX97 Mutation in Southern Italy: Going Back to the Fall of the Western Roman Empire

Author

Veronica Redaelli, Giorgio Giaccone, Isabelle Le Ber, Giacomina Rossi, Jérémie Pariente, Matteo Carrara, Luisa Benussi, Pietro Tiraboschi, Martina Ricci, Gianfranco Puoti, Simona Bonavita, Mariano Oliva, Giacomo Lus, Cinzia Coppola, Alessandro Tessitore, Dario Saracino, Paola Caroppo, Roberta Ghidoni, Coppola, Cinzia, Saracino, Dario, Oliva, Mariano, Puoti, Gianfranco, Lus, Giacomo, Le Ber, Isabelle, Pariente, Jérémie, Tessitore, Alessandro, Benussi, Luisa, Ghidoni, Roberta, Carrara, Matteo, Ricci, Martina, Redaelli, Veronica, Tiraboschi, Pietro, Caroppo, Paola, Giaccone, Giorgio, Bonavita, Simona, and Rossi, Giacomina

Subjects
Most recent common ancestor, Male, haplotype, Common founder, Genetic counseling, Population, Biology, Roman World, Cohort Studies, Progranulins, mental disorders, mutation dating, medicine, Humans, education, Aged, Genetics, education.field_of_study, Genetic heterogeneity, General Neuroscience, Haplotype, General Medicine, Frontotemporal lobar degeneration, Middle Aged, medicine.disease, nervous system diseases, Psychiatry and Mental health, Clinical Psychology, Haplotypes, Italy, Mutation (genetic algorithm), Mutation, Intercellular Signaling Peptides and Proteins, Female, Geriatrics and Gerontology, Frontotemporal Lobar Degeneration, GRN, Founder effect
Abstract

Background: Frontotemporal lobar degeneration (FTLD) designates a group of neurodegenerative diseases with remarkable clinical, pathological, and genetic heterogeneity. Mutations in progranulin gene (GRN) are among the most common causes of familial FTLD. The GRN C157KfsX97 mutation is the most frequent mutation occurring in Southern Italy and has been already described in a previous work. Objective: In this study, we reported on additional cases carrying the same mutation and performed a genetic study on the whole cohort, aiming at demonstrating the existence of a founder effect and estimating the age of this mutation. Methods/Results: Based on the haplotype sharing analysis, a founder effect was highly probable, while the age of the mutation, estimated by means of DMLE+ software, resulted in a range between 52 and 82 generations, with the highest frequency at about 62 generations, 1,550 years ago. Conclusion: This is the first study that reports the age estimation of the most recent common ancestor for the GRN C157KfsX97 mutation recurring in Southern Italy. Mutation dating in a geographically restricted population may be useful in order to plan genetic counseling and screening programs in the field of public health.

Published
2020

39. Ofatumumab versus Teriflunomide in Multiple Sclerosis

Author

Hauser S. L., Bar-Or A., Cohen J. A., Comi G., Correale J., Coyle P. K., Cross A. H., de Seze J., Leppert D., Montalban X., Selmaj K., Wiendl H., Kerloeguen C., Willi R., Li B., Kakarieka A., Tomic D., Goodyear A., Pingili R., Haring D. A., Ramanathan K., Merschhemke M., Kappos L., Stephen L Hauser, Ludwig Kappos, Amit Bar-Or, Jeffrey A Cohen, Giancarlo Comi, Jorge Correale, Patricia K Coyle, Anne Cross, Jerome de Seze, Xavier Montalban, Krzysztof Selmaj, Heinz Wiendl, Stephen C Reingold, Garry R Cutter, Thomas Doerner, Hans-Peter Hartung, Per Soelberg Sørensen, Israel Steiner, Jerry S Wolinsky, Carlos Ballario, Christian Calvo Vildoso, Jorge Gustavo Jose, Norma Haydee Deri, Susana Liwacki, Jeannette Lechner-Scott, John Parratt, Suzanne Hodgkinson, Eva-Maria Maida, Fritz Leutmezer, Barbara Willekens, Bart Van Wijmeersch, Guy Laureys, Jo Caekebeke, Karine Geens, Ludo Vanopdenbosch, Olivier Deryck, Valerie Delvaux, Vincent Van Pesch, Ivan Milanov, Ivaylo Tarnev, Lyubomir Haralanov, Maria Manova Slavova, Penko Shotekov, Francois Emond, Francois Grandmaison, Francois Jacques, Liesly Lee, Marie Sarah Gagne Brosseau, Mark Freedman, Martin Cloutier, Robert Carruthers, Sarah Morrow, Yves Lapierre, Anton Vladic, Hana Bokun, Igor Antoncic, Marija Bosnjak Pasic, Mario Habek, Silva Butkovic Soldo, Vladimira Vuletic, Alena Martinkova, Eva Meluzinova, Ivana Stetkarova, Jan Mares, Jolana Markova, Marta Vachova, Martin Valis, Michaela Tyblova, Michal Dufek, Ondrej Skoda, Pavel Hradilek, Ana Voldsgaard Jensen, Helle Hvilsted Nielsen, Kristina Svendsen, Mads Ravnborg, Peter Vestergaard Rasmussen, Katrin Gross-Paju, Sulev Haldre, Juha Pekka Eralinna, Marja-Liisa Sumelahti, Bruno Brochet, Celine Louapre, Christine Lebrun-Frenay, David Axel Laplaud, Gilles Edan, Giovanni Castelnovo, Marc Debouverie, Patrick Vermersch, Pierre Clavelou, Pierre Labauge, Achim Berthele, Aiden Haghikia, Anselm Kornhuber, Arnfin Bergmann, Benedikt Frank, Birte Elias-Hamp, Bjoern Tackenberg, Brigitte Wildemann, Erik Strauss, Eugen Schlegel, Florian Then Bergh, Gereon Nelles, Hayrettin Tumani, Karl-Otto Sigel, Martin Stangel, Matthias Boehringer, Olaf Martin Hoffmann, Patrick Oschmann, Reinhard Hohlfeld, Silke Walter, Sylvia Menck, Till Sprenger, Tjalf Ziemssen, Veit Ulrich Becker, Vera Straeten, Konstantinos Kilidireas, Konstantinos Voumvourakis, Nikolaos Fakas, Nikolaos Grigoriadis, Agnes Koves, Csilla Rozsa, Krisztina Kovacs, Laszlo Vecsei, Satori Maria, Zita Biro, Anshu Rohatgi, Dheeraj Khurana, Jeyaraj Durai Pandian, Joy Dev Mukherji, Lekha Pandit, Meena Angamuthu Kanikannan, Pahari Ghosh, Rahul Chakor, Rahul Kulkarni, Roopkumar Gursahani, Sangeeta Ravat, Srinivasa Rangasetty, Suresh Kumar, Alla Shifrin, Arnon Karni, Radi Shahien, Ron Milo, Antonio Uccelli, Carlo Pozzilli, Francesco Sacca, Giacomo Lus, Girolama Alessandra Marfia, Laura Brambilla, Marco Salvetti, Massimo Filippi, Mauro Zaffaroni, Paolo Gallo, Silvia Rossi, Simona Bonavita, Valeria Studer, Andrejs Millers, Guntis Karelis, Jolanta Kalnina, Dalia Mickeviciene, Rasa Kizlaitiene, Angelica Carbajal Ramirez, Juan Jose Lopez Prieto, Beatrijs Wokke, Bob W Van Oosten, Peter Van Domburg, Raymond Hupperts, Rogier Q Hintzen, Astrid Edland, Cesar Castaneda, Julio Perez, Martin Gavidia, Andrzej Wiak, Bartosz Karaszewski, Elzbieta Jasinska, Halina Bartosik Psujek, Iwona Jastrzebska, Jaroslaw Slawek, Maciej Maciejowski, Miroslaw Dziki, Monika Adamczyk Sowa, Robert Bonek, Waldemar Fryze, Ana Martins Da Silva, Angela Timoteo, Antonio Vasco Salgado, Carlos Capela, Carlos Veira, Filipe Correia, Joao Cerqueira, Joao De Sa, Livia De Sousa, Raquel Gouveia, Alina Sergeevna Agafina, Anna Naumovna Belova, Denis Viktorovich Sazonov, Dmitry Pokhabov, Ekaterina Igorevna Kairbekova, Elena Gennadievna Arefieva, Farit Axatovich Khabirov, Igor Vyacheslavovich Litvinenko, Igor Stolyarov, Irina Aleksandrovna Sokolova, Larisa Ivanovna Volkova, Maria Vafaevna Davydovskaya, Maria Nikolaevna Zaharova, Nadezhda Alekseevna Malkova, Natalia Agafonovna Totolyan, Nikolay Vasilievich Dorogov, Stella Anatolievna Sivertseva, Egon Kurca, Georgi Krastev, Miroslav Brozman, Peter Koleda, Peter Turcani, Peter Valkovic, Viera Hancinova, Vladimir Donath, Chris Retief, Michael Isaacs, Albert Saiz Hinarejos, Alfredo Rodriguez Antigüedad, Bonaventura Casanova Estruch, Celia Oreja-Guevara, Gemma Reig Rosello, Jose Carlos Alvarez Cermeño, Jose Martinez Rodriguez, Jose Meca Lallana, Juan Antonio Garcia Merino, Lucia Forero Diaz, Lucienne Costa Frossard Franca, Luis Querol Gutierrez, Lluis Ramio Torrenta, Pedro Serrano Castro, Rafael Arroyo Gonzalez, Sara Eichau Madueño, Sergio Martinez Yelamos, Tamara Castillo Trivino, Virgina Meca Lallana, Xaviere Montalban Gairin, Fredrik Piehl, Jan Lycke, Chiara Zecca, Tobias Derfuss, Thy-Sheng Lin, Somsak Tiamkao, Ayse Nur Yuceyar, Aysun Soysal, Belgin Petek Balci, Cavit Boz, Husnu Efendi, Murat Terzi, Serhan Sevim, Serkan Ozakbas, Andrew Gale, Ben Turner, David Barnes, David Paling, Eli Silber, James Overell, Matthew Craner, Aaron Carlson, Adam Wolff, Adaeze Onuoha, Adnan Subei, Ahmad Ata, Aimee Borazanci, Akram Dastagir, Alberto Vasquez, Alison Brooke Allen, Andrew P Keegan, Angel Carrasco, Angel R Chinea Martinez, Ann Bass, Annette Okai, April Erwin, Ariel Antezana-Antezana, Barbara Green, Bharathy E Sundaram, Bhupendra Khatri, Bhupesh Dihenia, Bogdan Gheorghiu, Brian Costell, Brian Steingo, Bruce L Hughes, Carrie M Hersh, Christopher Laganke, Christopher Luzzio, Corey Ford, Craig Edward Herrman, Craig Senzon, Cynthia Huffman, Daniel R Wynn, David D O Bear, David Lesch, David H Mattson, David Weisman, Deborah A Burke, Dennis W Dietrich, Deren Huang, Derrick Robertson, Djamchid Lotfi, Don Joseph Alfonso, Dusan Stefoski, Edward J Fox, Emily Pharr, Enrique Alvarez, Evanthia Bernitsas, Faria Amjad, Gabriel Pardo, Geoffrey Eubank, Gerald Mcintosh, Giles F Crowell, Hemanth Rao, J Michael Hemphill, Jack H Florin, Jacqueline Nicholas, James Napier, James Scott, Jason M Silversteen, Javier Vasallo, Jean-Raphael Schneider, Jeanette Wendt, Jeffrey Cohen, Jeffrey Gross, Jeffrey Groves, Jeffrey Kaplan, Jessica Stulc, Joanna A Cooper, John Foley, John Scagnelli, Jonathan C Calkwood, Jose Pizarro Otero, Jose Rafecas, Joshua Katz, Juliette S Saad, Katherine Standley, Keith Edwards, Kenneth Sharlin, Khurram Bashir, Kimberly Wagner, Kore Liow, Larry Lee Blankenship Jr, Laszlo Mate, Liliana Montoya, Lon D Lynn, Mark Agius, Mark Cascione, Mark Allan Goldstein, Mark Janicki, Martin R Bialow, Mary Denise Hughes, Matthew J Baker, Michelle Apperson, Michelle B Kuczma, M Mateo Paz Soldan, Mirela Cerghet, Nathaniel Robb Whaley, Paul K Winner, Pavle Repovic, Praful Kelkar, Romero Rekha Pillai, Ricardo Ayala, Richard Sater, Randall Trudell, Robert Fairborn Armstrong, Robert Thomas Nahouraii, Robert Naismith, Ronald S Murray, Samuel Hunter, Sara Qureshi, Sharon Lynch, Sibyl Wray, Silvia R Delgado, Stacy Donlon, Stanley Cohan, Stanya Smith, Stuart James Shafer, Susan Azalone, Susan Hibbs, Tamara A Miller, Thomas Giancarlo, Troy Desai, Varun K Saxena, Virginia Simnad, William David Honeycutt, William Logan, William E McElveen, William Wagner, University of California [San Francisco] (UCSF), University of California, Perelman School of Medicine, University of Pennsylvania [Philadelphia], Cleveland Clinic, IRCCS Ospedale San Raffaele [Milan, Italy], Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia [Buenos Aires] (FLENI), FLENI, Stony Brook University [SUNY] (SBU), State University of New York (SUNY), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, University Hospital Basel [Basel], Vall d'Hebron University Hospital [Barcelona], University of Warmia and Mazury [Olsztyn], University of Münster, Novartis Pharma S.A.S., Novartis Pharmaceuticals, University of Basel (Unibas), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Willekens, Barbara, ASCLEPIOS I and ASCLEPIOS II Trial Groups, Hauser, S. L., Bar-Or, A., Cohen, J. A., Comi, G., Correale, J., Coyle, P. K., Cross, A. H., de Seze, J., Leppert, D., Montalban, X., Selmaj, K., Wiendl, H., Kerloeguen, C., Willi, R., Li, B., Kakarieka, A., Tomic, D., Goodyear, A., Pingili, R., Haring, D. A., Ramanathan, K., Merschhemke, M., Kappos, L., Asclepios, I and ASCLEPIOS II Trial Group, Filippi, M, L Hauser, Stephen, Kappos, Ludwig, Bar-Or, Amit, A Cohen, Jeffrey, Comi, Giancarlo, Correale, Jorge, K Coyle, Patricia, Cross, Anne, de Seze, Jerome, Montalban, Xavier, Selmaj, Krzysztof, Wiendl, Heinz, C Reingold, Stephen, R Cutter, Garry, Doerner, Thoma, Hartung, Hans-Peter, Soelberg Sørensen, Per, Steiner, Israel, S Wolinsky, Jerry, Ballario, Carlo, Calvo Vildoso, Christian, Gustavo Jose, Jorge, Haydee Deri, Norma, Liwacki, Susana, Lechner-Scott, Jeannette, Parratt, John, Hodgkinson, Suzanne, Maida, Eva-Maria, Leutmezer, Fritz, Van Wijmeersch, Bart, Laureys, Guy, Caekebeke, Jo, Geens, Karine, Vanopdenbosch, Ludo, Deryck, Olivier, Delvaux, Valerie, Van Pesch, Vincent, Milanov, Ivan, Tarnev, Ivaylo, Haralanov, Lyubomir, Manova Slavova, Maria, Shotekov, Penko, Emond, Francoi, Grandmaison, Francoi, Jacques, Francoi, Lee, Liesly, Sarah Gagne Brosseau, Marie, Freedman, Mark, Cloutier, Martin, Carruthers, Robert, Morrow, Sarah, Lapierre, Yve, Vladic, Anton, Bokun, Hana, Antoncic, Igor, Bosnjak Pasic, Marija, Habek, Mario, Butkovic Soldo, Silva, Vuletic, Vladimira, Martinkova, Alena, Meluzinova, Eva, Stetkarova, Ivana, Mares, Jan, Markova, Jolana, Vachova, Marta, Valis, Martin, Tyblova, Michaela, Dufek, Michal, Skoda, Ondrej, Hradilek, Pavel, Voldsgaard Jensen, Ana, Hvilsted Nielsen, Helle, Svendsen, Kristina, Ravnborg, Mad, Vestergaard Rasmussen, Peter, Gross-Paju, Katrin, Haldre, Sulev, Pekka Eralinna, Juha, Sumelahti, Marja-Liisa, Brochet, Bruno, Louapre, Celine, Lebrun-Frenay, Christine, Axel Laplaud, David, Edan, Gille, Castelnovo, Giovanni, Debouverie, Marc, Vermersch, Patrick, Clavelou, Pierre, Labauge, Pierre, Berthele, Achim, Haghikia, Aiden, Kornhuber, Anselm, Bergmann, Arnfin, Frank, Benedikt, Elias-Hamp, Birte, Tackenberg, Bjoern, Wildemann, Brigitte, Strauss, Erik, Schlegel, Eugen, Then Bergh, Florian, Nelles, Gereon, Tumani, Hayrettin, Sigel, Karl-Otto, 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Rasa, Carbajal Ramirez, Angelica, Jose Lopez Prieto, Juan, Wokke, Beatrij, W Van Oosten, Bob, Van Domburg, Peter, Hupperts, Raymond, Q Hintzen, Rogier, Edland, Astrid, Castaneda, Cesar, Perez, Julio, Gavidia, Martin, Wiak, Andrzej, Karaszewski, Bartosz, Jasinska, Elzbieta, Bartosik Psujek, Halina, Jastrzebska, Iwona, Slawek, Jaroslaw, Maciejowski, Maciej, Dziki, Miroslaw, Adamczyk Sowa, Monika, Bonek, Robert, Fryze, Waldemar, Martins Da Silva, Ana, Timoteo, Angela, Vasco Salgado, Antonio, Capela, Carlo, Veira, Carlo, Correia, Filipe, Cerqueira, Joao, De Sa, Joao, De Sousa, Livia, Gouveia, Raquel, Sergeevna Agafina, Alina, Naumovna Belova, Anna, Viktorovich Sazonov, Deni, Pokhabov, Dmitry, Igorevna Kairbekova, Ekaterina, Gennadievna Arefieva, Elena, Axatovich Khabirov, Farit, Vyacheslavovich Litvinenko, Igor, Stolyarov, Igor, Aleksandrovna Sokolova, Irina, Ivanovna Volkova, Larisa, Vafaevna Davydovskaya, Maria, Nikolaevna Zaharova, Maria, Alekseevna Malkova, Nadezhda, Agafonovna Totolyan, Natalia, Vasilievich Dorogov, Nikolay, Anatolievna Sivertseva, Stella, Kurca, Egon, Krastev, Georgi, Brozman, Miroslav, Koleda, Peter, Turcani, Peter, Valkovic, Peter, Hancinova, Viera, Donath, Vladimir, Retief, Chri, Isaacs, Michael, Saiz Hinarejos, Albert, Rodriguez Antigüedad, Alfredo, Casanova Estruch, Bonaventura, Oreja-Guevara, Celia, Reig Rosello, Gemma, Carlos Alvarez Cermeño, Jose, Martinez Rodriguez, Jose, Meca Lallana, Jose, Antonio Garcia Merino, Juan, Forero Diaz, Lucia, Costa Frossard Franca, Lucienne, Querol Gutierrez, Lui, Ramio Torrenta, Llui, Serrano Castro, Pedro, Arroyo Gonzalez, Rafael, Eichau Madueño, Sara, Martinez Yelamos, Sergio, Castillo Trivino, Tamara, Meca Lallana, Virgina, Montalban Gairin, Xaviere, Piehl, Fredrik, Lycke, Jan, Zecca, Chiara, Derfuss, Tobia, Lin, Thy-Sheng, Tiamkao, Somsak, Nur Yuceyar, Ayse, Soysal, Aysun, Petek Balci, Belgin, Boz, Cavit, Efendi, Husnu, Terzi, Murat, Sevim, Serhan, Ozakbas, Serkan, Gale, Andrew, Turner, Ben, Barnes, David, Paling, David, Silber, Eli, Overell, Jame, Craner, Matthew, Carlson, Aaron, Wolff, Adam, Onuoha, Adaeze, Subei, Adnan, Ata, Ahmad, Borazanci, Aimee, Dastagir, Akram, Vasquez, Alberto, Brooke Allen, Alison, P Keegan, Andrew, Carrasco, Angel, R Chinea Martinez, Angel, Bass, Ann, Okai, Annette, Erwin, April, Antezana-Antezana, Ariel, Green, Barbara, E Sundaram, Bharathy, Khatri, Bhupendra, Dihenia, Bhupesh, Gheorghiu, Bogdan, Costell, Brian, Steingo, Brian, L Hughes, Bruce, M Hersh, Carrie, Laganke, Christopher, Luzzio, Christopher, Ford, Corey, Edward Herrman, Craig, Senzon, Craig, Huffman, Cynthia, R Wynn, Daniel, O Bear, David D, Lesch, David, H Mattson, David, Weisman, David, A Burke, Deborah, W Dietrich, Denni, Huang, Deren, Robertson, Derrick, Lotfi, Djamchid, Joseph Alfonso, Don, Stefoski, Dusan, J Fox, Edward, Pharr, Emily, Alvarez, Enrique, Bernitsas, Evanthia, Amjad, Faria, Pardo, Gabriel, Eubank, Geoffrey, Mcintosh, Gerald, F Crowell, Gile, Rao, Hemanth, Michael Hemphill, J, H Florin, Jack, Nicholas, Jacqueline, Napier, Jame, Scott, Jame, M Silversteen, Jason, Vasallo, Javier, Schneider, Jean-Raphael, Wendt, Jeanette, Cohen, Jeffrey, Gross, Jeffrey, Groves, Jeffrey, Kaplan, Jeffrey, Stulc, Jessica, A Cooper, Joanna, Foley, John, Scagnelli, John, C Calkwood, Jonathan, Pizarro Otero, Jose, Rafecas, Jose, Katz, Joshua, S Saad, Juliette, Standley, Katherine, Edwards, Keith, Sharlin, Kenneth, Bashir, Khurram, Wagner, Kimberly, Liow, Kore, Lee Blankenship Jr, Larry, Mate, Laszlo, Montoya, Liliana, D Lynn, Lon, Agius, Mark, Cascione, Mark, Allan Goldstein, Mark, Janicki, Mark, R Bialow, Martin, Denise Hughes, Mary, J Baker, Matthew, Apperson, Michelle, B Kuczma, Michelle, Mateo Paz Soldan, M, Cerghet, Mirela, Robb Whaley, Nathaniel, K Winner, Paul, Repovic, Pavle, Kelkar, Praful, Rekha Pillai, Romero, Ayala, Ricardo, Sater, Richard, Trudell, Randall, Fairborn Armstrong, Robert, Thomas Nahouraii, Robert, Naismith, Robert, S Murray, Ronald, Hunter, Samuel, Qureshi, Sara, Lynch, Sharon, Wray, Sibyl, R Delgado, Silvia, Donlon, Stacy, Cohan, Stanley, Smith, Stanya, James Shafer, Stuart, Azalone, Susan, Hibbs, Susan, A Miller, Tamara, Giancarlo, Thoma, Desai, Troy, K Saxena, Varun, Simnad, Virginia, David Honeycutt, William, Logan, William, E McElveen, William, Wagner, William, Stephen, L Hauser, Ludwig, Kappo, Amit, Bar-Or, Jeffrey, A Cohen, Giancarlo, Comi, Jorge, Correale, Patricia, K Coyle, Anne, Cro, Jerome de Seze, Xavier, Montalban, Krzysztof, Selmaj, Heinz, Wiendl, Stephen, C Reingold, Garry, R Cutter, Thomas, Doerner, Hans-Peter, Hartung, Per Soelberg Sørensen, Israel, Steiner, Jerry, S Wolinsky, Carlos, Ballario, Christian Calvo Vildoso, Jorge Gustavo Jose, Norma Haydee Deri, Susana, Liwacki, Jeannette, Lechner-Scott, John, Parratt, Suzanne, Hodgkinson, Eva-Maria, Maida, Fritz, Leutmezer, Barbara, Willeken, Bart Van Wijmeersch, Guy, Laurey, Karine, Geen, Ludo, Vanopdenbosch, Olivier, Deryck, Valerie, Delvaux, Vincent Van Pesch, Ivan, Milanov, Ivaylo, Tarnev, Lyubomir, Haralanov, Maria Manova Slavova, Penko, Shotekov, Francois, Emond, Francois, Grandmaison, Francois, Jacque, Liesly, Lee, Marie Sarah Gagne Brosseau, Mark, Freedman, Martin, Cloutier, Robert, Carruther, Sarah, Morrow, Yves, Lapierre, Anton, Vladic, Hana, Bokun, Igor, Antoncic, Marija Bosnjak Pasic, Mario, Habek, Silva Butkovic Soldo, Vladimira, Vuletic, Alena, Martinkova, Eva, Meluzinova, Ivana, Stetkarova, Jan, Mare, Jolana, Markova, Marta, Vachova, Martin, Vali, Michaela, Tyblova, Michal, Dufek, Ondrej, Skoda, Pavel, Hradilek, Ana Voldsgaard Jensen, Helle Hvilsted Nielsen, Kristina, Svendsen, Mads, Ravnborg, Peter Vestergaard Rasmussen, Katrin, Gross-Paju, Sulev, Haldre, Juha Pekka Eralinna, Marja-Liisa, Sumelahti, Bruno, Brochet, Celine, Louapre, Christine, Lebrun-Frenay, David Axel Laplaud, Gilles, Edan, Giovanni, Castelnovo, Marc, Debouverie, Patrick, Vermersch, Pierre, Clavelou, Pierre, Labauge, Achim, Berthele, Aiden, Haghikia, Anselm, Kornhuber, Arnfin, Bergmann, Benedikt, Frank, Birte, Elias-Hamp, Bjoern, Tackenberg, Brigitte, Wildemann, Erik, Strau, Eugen, Schlegel, Florian Then Bergh, Gereon, Nelle, Hayrettin, Tumani, Karl-Otto, Sigel, Martin, Stangel, Matthias, Boehringer, Olaf Martin Hoffmann, Patrick, Oschmann, Reinhard, Hohlfeld, Silke, Walter, Sylvia, Menck, Till, Sprenger, Tjalf, Ziemssen, Veit Ulrich Becker, Vera, Straeten, Konstantinos, Kilidirea, Konstantinos, Voumvouraki, Nikolaos, Faka, Nikolaos, Grigoriadi, Agnes, Kove, Csilla, Rozsa, Krisztina, Kovac, Laszlo, Vecsei, Satori, Maria, Zita, Biro, Anshu, Rohatgi, Dheeraj, Khurana, Jeyaraj Durai Pandian, Joy Dev Mukherji, Lekha, Pandit, Meena Angamuthu Kanikannan, Pahari, Ghosh, Rahul, Chakor, Rahul, Kulkarni, Roopkumar, Gursahani, Sangeeta, Ravat, Srinivasa, Rangasetty, Suresh, Kumar, Alla, Shifrin, Arnon, Karni, Radi, Shahien, Ron, Milo, Antonio, Uccelli, Carlo, Pozzilli, Sacca', Francesco, Giacomo, Lu, Girolama Alessandra Marfia, Laura, Brambilla, Marco, Salvetti, Massimo, Filippi, Mauro, Zaffaroni, Paolo, Gallo, Silvia, Rossi, Simona, Bonavita, Valeria, Studer, Andrejs, Miller, Guntis, Kareli, Jolanta, Kalnina, Dalia, Mickeviciene, Rasa, Kizlaitiene, Angelica Carbajal Ramirez, Juan Jose Lopez Prieto, Beatrijs, Wokke, Bob, W Van Oosten, Peter Van Domburg, Raymond, Huppert, Rogier, Q Hintzen, Astrid, Edland, Cesar, Castaneda, Julio, Perez, Martin, Gavidia, Andrzej, Wiak, Bartosz, Karaszewski, Elzbieta, Jasinska, Halina Bartosik Psujek, Iwona, Jastrzebska, Jaroslaw, Slawek, Maciej, Maciejowski, Miroslaw, Dziki, Monika Adamczyk Sowa, Robert, Bonek, Waldemar, Fryze, Ana Martins Da Silva, Angela, Timoteo, Antonio Vasco Salgado, Carlos, Capela, Carlos, Veira, Filipe, Correia, Joao, Cerqueira, Joao De Sa, Livia De Sousa, Raquel, Gouveia, Alina Sergeevna Agafina, Anna Naumovna Belova, Denis Viktorovich Sazonov, Dmitry, Pokhabov, Ekaterina Igorevna Kairbekova, Elena Gennadievna Arefieva, Farit Axatovich Khabirov, Igor Vyacheslavovich Litvinenko, Igor, Stolyarov, Irina Aleksandrovna Sokolova, Larisa Ivanovna Volkova, Maria Vafaevna Davydovskaya, Maria Nikolaevna Zaharova, Nadezhda Alekseevna Malkova, Natalia Agafonovna Totolyan, Nikolay Vasilievich Dorogov, Stella Anatolievna Sivertseva, Egon, Kurca, Georgi, Krastev, Miroslav, Brozman, Peter, Koleda, Peter, Turcani, Peter, Valkovic, Viera, Hancinova, Vladimir, Donath, Chris, Retief, Michael, Isaac, Albert Saiz Hinarejos, Alfredo Rodriguez Antigüedad, Bonaventura Casanova Estruch, Celia, Oreja-Guevara, Gemma Reig Rosello, Jose Carlos Alvarez Cermeño, Jose Martinez Rodriguez, Jose Meca Lallana, Juan Antonio Garcia Merino, Lucia Forero Diaz, Lucienne Costa Frossard Franca, Luis Querol Gutierrez, Lluis Ramio Torrenta, Pedro Serrano Castro, Rafael Arroyo Gonzalez, Sara Eichau Madueño, Sergio Martinez Yelamos, Tamara Castillo Trivino, Virgina Meca Lallana, Xaviere Montalban Gairin, Fredrik, Piehl, Jan, Lycke, Chiara, Zecca, Tobias, Derfu, Thy-Sheng, Lin, Somsak, Tiamkao, Ayse Nur Yuceyar, Aysun, Soysal, Belgin Petek Balci, Cavit, Boz, Husnu, Efendi, Murat, Terzi, Serhan, Sevim, Serkan, Ozakba, Andrew, Gale, Ben, Turner, David, Barne, David, Paling, Eli, Silber, James, Overell, Matthew, Craner, Aaron, Carlson, Adam, Wolff, Adaeze, Onuoha, Adnan, Subei, Ahmad, Ata, Aimee, Borazanci, Akram, Dastagir, Alberto, Vasquez, Alison Brooke Allen, Andrew, P Keegan, Angel, Carrasco, Angel, R Chinea Martinez, Ann, Ba, Annette, Okai, April, Erwin, Ariel, Antezana-Antezana, Barbara, Green, Bharathy, E Sundaram, Bhupendra, Khatri, Bhupesh, Dihenia, Bogdan, Gheorghiu, Brian, Costell, Brian, Steingo, Bruce, L Hughe, Carrie, M Hersh, Christopher, Laganke, Christopher, Luzzio, Corey, Ford, Craig Edward Herrman, Craig, Senzon, Cynthia, Huffman, Daniel, R Wynn, David D, O Bear, David, Lesch, David, H Mattson, David, Weisman, Deborah, A Burke, Dennis, W Dietrich, Deren, Huang, Derrick, Robertson, Djamchid, Lotfi, Don Joseph Alfonso, Dusan, Stefoski, Edward, J Fox, Emily, Pharr, Enrique, Alvarez, Evanthia, Bernitsa, Faria, Amjad, Gabriel, Pardo, Geoffrey, Eubank, Gerald, Mcintosh, Giles, F Crowell, Hemanth, Rao, J Michael Hemphill, Jack, H Florin, Jacqueline, Nichola, James, Napier, James, Scott, Jason, M Silversteen, Javier, Vasallo, Jean-Raphael, Schneider, Jeanette, Wendt, Jeffrey, Cohen, Jeffrey, Gro, Jeffrey, Grove, Jeffrey, Kaplan, Jessica, Stulc, Joanna, A Cooper, John, Foley, John, Scagnelli, Jonathan, C Calkwood, Jose Pizarro Otero, Jose, Rafeca, Joshua, Katz, Juliette, S Saad, Katherine, Standley, Keith, Edward, Kenneth, Sharlin, Khurram, Bashir, Kimberly, Wagner, Kore, Liow, Larry Lee Blankenship Jr, Laszlo, Mate, Liliana, Montoya, Lon, D Lynn, Mark, Agiu, Mark, Cascione, Mark Allan Goldstein, Mark, Janicki, Martin, R Bialow, Mary Denise Hughes, Matthew, J Baker, Michelle, Apperson, Michelle, B Kuczma, M Mateo Paz Soldan, Mirela, Cerghet, Nathaniel Robb Whaley, Paul, K Winner, Pavle, Repovic, Praful, Kelkar, Romero Rekha Pillai, Ricardo, Ayala, Richard, Sater, Randall, Trudell, Robert Fairborn Armstrong, Robert Thomas Nahouraii, Robert, Naismith, Ronald, S Murray, Samuel, Hunter, Sara, Qureshi, Sharon, Lynch, Sibyl, Wray, Silvia, R Delgado, Stacy, Donlon, Stanley, Cohan, Stanya, Smith, Stuart James Shafer, Susan, Azalone, Susan, Hibb, Tamara, A Miller, Thomas, Giancarlo, Troy, Desai, Varun, K Saxena, Virginia, Simnad, William David Honeycutt, William, Logan, William, E McElveen, William, Wagner, University of California [San Francisco] (UC San Francisco), University of California (UC), University of Pennsylvania, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Herrada, Anthony, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
Male, MESH: Multiple Sclerosis, Relapsing-Remitting, T-Lymphocytes, Hydroxybutyrates, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Pharmacology, Relapsing-Remitting, MESH: Magnetic Resonance Imaging, chemistry.chemical_compound, 0302 clinical medicine, Teriflunomide, Monoclonal, MESH: Double-Blind Method, 030212 general & internal medicine, Humanized, MESH: Toluidines, B-Lymphocytes, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Subcutaneous, B-Lymphocyte, Brain, General Medicine, Magnetic Resonance Imaging, MESH: Crotonates, Crotonates, Pyrimidine metabolism, Disease Progression, Female, MESH: Disease Progression, Antibody, Human, Adult, Multiple Sclerosis, Toluidines, medicine.drug_class, Injections, Subcutaneous, Injections, Subcutaneou, Monoclonal antibody, Ofatumumab, Settore MED/26, Antibodies, Monoclonal, Humanized, Crotonate, Antibodies, Injections, 03 medical and health sciences, MESH: Brain, Multiple Sclerosis, Relapsing-Remitting, Double-Blind Method, MESH: B-Lymphocytes, Nitriles, medicine, Humans, MESH: Kaplan-Meier Estimate, MESH: Humans, business.industry, Multiple sclerosis, MESH: Injections, Subcutaneous, MESH: Adult, medicine.disease, MESH: Male, MESH: T-Lymphocytes, T-Lymphocyte, Multicenter study, chemistry, MESH: Antibodies, Monoclonal, Humanized, biology.protein, Human medicine, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Background: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known.Methods: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume.Results: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P

Published
2020

40. Dementia care and COVID-19 pandemic: a necessary digital revolution

Author

Gioacchino Tedeschi, Francesco Di Lorenzo, Luca Cuffaro, Letizia Leocani, Luigi Lavorgna, Simona Bonavita, Cuffaro, L., Di Lorenzo, F., Bonavita, S., Tedeschi, G., Leocani, L., Lavorgna, L., Cuffaro, L, Di Lorenzo, F, Bonavita, S, Tedeschi, G, Leocani, L, Lavorgna, L, Cuffaro, Luca, Di Lorenzo, Francesco, Bonavita, Simona, Tedeschi, Gioacchino, Leocani, Letizia, and Lavorgna, Luigi

Subjects
Telemedicine, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, Clinical Neurology, Dermatology, Teleneurology, computer.software_genre, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, Videoconferencing, Pandemic, mental disorders, medicine, Digital technology, Dementia, Humans, 030212 general & internal medicine, Pandemics, COVID, business.industry, SARS-CoV-2, COVID-19, General Medicine, medicine.disease, Psychiatry and Mental health, Neurology, Smartphone app, Neurology (clinical), Medical emergency, Smartphone, business, Coronavirus Infections, Digital Revolution, computer, Alzheimer’s disease, 030217 neurology & neurosurgery, Clinical progression
Abstract

Due to the COVID-19 pandemic, most memory clinics have had to suspend their activities. On the other hand, international dementia experts have recommended to provide urgently worldwide support for people living with dementia. This situation urges to play out new strategies to guarantee adequate care. Telemedicine and digital technology (DT) devices, such as smartphones, can be very helpful in remote monitoring and care. Technological devices such as videoconference or smartphone apps might be used for follow-up visits and support to patients and caregivers and to acquire digital markers of clinical progression. Hopefully, this dramatic situation would facilitate the process of progressive familiarization of neurologists with telemedicine and DT approach.

Published
2020
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41. Unraveling diagnostic uncertainty in transition phase from relapsing-remitting to secondary progressive multiple sclerosis

Author

Giacomo Lus, Ylenia Vaia, Antonio Carotenuto, Elisabetta Signoriello, Marcello Moccia, Simona Bonavita, Roberta Lanzillo, Vincenzo Brescia Morra, Carotenuto, Antonio, Signoriello, Elisabetta, Lanzillo, Roberta, Vaia, Ylenia, Moccia, Marcello, Bonavita, Simona, Lus, Giacomo, Brescia Morra, Vincenzo, and BRESCIA MORRA, Vincenzo

Subjects
medicine.medical_specialty, Multiple Sclerosis, predictor, Logistic regression, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Recurrence, Internal medicine, medicine, Humans, In patient, Disabled Persons, 030212 general & internal medicine, First episode, business.industry, Proportional hazards model, Multiple sclerosis, Uncertainty, General Medicine, Multiple Sclerosis, Chronic Progressive, medicine.disease, Neurology, Relapsing remitting, disability, multiple sclerosi, Disease Progression, Secondary progressive multiple sclerosis, Biomarker (medicine), biomarker, Neurology (clinical), Progressive multiple sclerosis, business, 030217 neurology & neurosurgery
Abstract

Background: Clinicians struggle to timely diagnose secondary-progressive multiple sclerosis (SP-MS), with a ‘transition phase’ period of diagnostic uncertainty. We aimed at defining clinical markers predicting evolution to SP-MS. Methods:: We reviewed 210 newly diagnosed MS patients experiencing at least one confirmed disability worsening (CDW). CDWs were classified as disability worsening either due to incomplete recovery following relapse (r-CDW), or independent of relapse activity (nr-CDW). Logistic regression and Cox regression models were used to evaluate variables at CDW associated with SP-MS diagnosis. Results: On CDW, higher EDSS (OR: 2.73, p=0.002) and nr-CDW (OR: 2.63, p=0.03) were associated with conversion to SP-MS over the follow-up. In addition, the risk of SP-MS was higher in patients with EDSS>3.0 at CDW (HR: 2.26, p

Published
2020

42. Dimethyl fumarate vs Teriflunomide: an Italian time-to-event data analysis

Author

D'Amico E., Zanghi A., Sciandra M., Lanzillo R., Callari G., Cortese A., Lus G., Lucchini M., Buccafusca M., Bonavita S., Gallo A., Curti E., Gajofatto A., Signoriello E., Bisecco A., Gobbin F., Ferro M. T., Ferrazzano G., Sparaco M., Valentino P., Mirabella M., Granella F., Bresciamorra V., Grimaldi L. M. E., Patti F., Borriello G., Grossi P., Carotenuto A., Siena E., Tsantes E., Giugno A., Abbadessa G. M., Chisari C. G., D'Amico, Emanuele, Zanghì, Aurora, Sciandra, Mariangela, Lanzillo, Roberta, Callari, Graziella, Cortese, Antonio, Lus, Giacomo, Lucchini, Matteo, Buccafusca, Maria, Bonavita, Simona, Gallo, Antonio, Curti, Erica, Gajofatto, Alberto, Signoriello, Elisabetta, Bisecco, Alvino, Gobbin, Francesca, Ferrò, Maria Teresa, Ferrazzano, Gina, Sparaco, Maddalena, Valentino, Paola, Mirabella, Massimiliano, Granella, Franco, Brescia Morra, Vincenzo, Grimaldi, Luigi Maria Edoardo, Patti, Francesco, D'Amico, E., Zanghi, A., Sciandra, M., Lanzillo, R., Callari, G., Cortese, A., Lus, G., Lucchini, M., Buccafusca, M., Bonavita, S., Gallo, A., Curti, E., Gajofatto, A., Signoriello, E., Bisecco, A., Gobbin, F., Ferro, M. T., Ferrazzano, G., Sparaco, M., Valentino, P., Mirabella, M., Granella, F., Bresciamorra, V., Grimaldi, L. M. E., Patti, F., Borriello, G., Grossi, P., Carotenuto, A., Siena, E., Tsantes, E., Giugno, A., Abbadessa, G. M., and Chisari, C. G.

Subjects
Adult, Data Analysis, Male, medicine.medical_specialty, Neurology, Efficacy, Toluidines, Dimethyl Fumarate, Hydroxybutyrates, Relapsing-Remitting, Multiple sclerosis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, Teriflunomide, Nitriles, medicine, Humans, Multiple sclerosi, 030212 general & internal medicine, Neuroradiology, Dimethyl fumarate, Proportional hazards model, business.industry, Safety, Female, Italy, Middle Aged, Crotonates, Immunosuppressive Agents, medicine.disease, Settore MED/26 - NEUROLOGIA, Event data, chemistry, Cohort, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Background: The introduction of oral disease-modifying therapies (DMTs) for relapsing–remitting multiple sclerosis (RRMS) changed algorithms of RRMS treatment. Objectives: To compare the effectiveness of treatment with dimethyl fumarate (DMF) and teriflunomide (TRF) in a large multicentre Italian cohort of RRMS patients. Materials and Methods: Patients with RRMS who received treatment with DMF and TRF between January 1st, 2012 and December 31st, 2018 from twelve MS centers were identified. The events investigated were “time-to-first-relapse”, “time-to-Magnetic-Resonance-Imaging (MRI)-activity” and “time-to-disability-progression”. Results: 1445 patients were enrolled (1039 on DMF, 406 on TRF) and followed for a median of 34months. Patients on TRF were older (43.5 ± 8.6 vs 38.8 ± 9.2years), with a predominance of men and higher level of disability (p < 0.001 for all). Patients on DMF had a higher number of relapses and radiological activity (p 38DMF = 3.83, CI = 1.11 to 13.23, p = 0.033). Both DMTs controlled similarly MRI activity and disability progression. Conclusions: Patients on DMF had higher relapse-free survival time than TRF group after the first 38 months ontherapy.

Published
2020

43. Assessing disability and relapses in multiple sclerosis on tele-neurology

Author

Letizia Leocani, Gioacchino Tedeschi, Simona Bonavita, Luigi Lavorgna, Roberta Lanzillo, Marcello Moccia, Vincenzo Brescia Morra, Moccia, Marcello, Lanzillo, Roberta, Brescia Morra, Vincenzo, Bonavita, Simona, Tedeschi, Gioacchino, Leocani, Letizia, Lavorgna, Luigi, Moccia, M., Lanzillo, R., Brescia Morra, V., Bonavita, S., Tedeschi, G., Leocani, L., and Lavorgna, L.

Subjects
medicine.medical_specialty, Multiple Sclerosis, Neurology, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, Clinical Neurology, Neurological examination, Dermatology, Brief Communication, Betacoronavirus, Disability Evaluation, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, medicine, Humans, Multiple sclerosi, 030212 general & internal medicine, Pandemics, Neuroradiology, COVID, medicine.diagnostic_test, SARS-CoV-2, business.industry, Multiple sclerosis, COVID-19, General Medicine, Tele-medicine, medicine.disease, Telemedicine, Cognitive test, Psychiatry and Mental health, Physical therapy, Chronic disability, Neurology (clinical), Neurosurgery, Tele-neurology, Coronavirus Infections, business, 030217 neurology & neurosurgery
Abstract

Background: As a consequence of the coronavirus disease 2019 (COVID-19) pandemic, a large amount of consultations will be delivered through tele-medicine, especially for diseases causing chronic disability and requiring immunomodulatory treatments, such as multiple sclerosis (MS). Methods: We have hereby reviewed available tools for tele-neurology examination in MS, including components of neurological examination that can be assessed through video, patient-reported outcome measures (PROMs), and digital technology. Results: Overall, we have suggested a battery for assessing MS disability and relapses on tele-medicine, which brings together conventional examination, PROMs (e.g., Patient Determined Disease Steps, MS Impact Scale), and cognitive tests (Symbol Digit Modalities Test) that can be delivered remotely and in multiple languages. Discussion: The use of common tools for neurological examination could improve tele-neurology practice for both general neurologists and MS specialists, and quality of care for people with MS.

Published
2020

44. Cladribine vs other drugs in MS: Merging randomized trial with real-life data

Author

Domenico Ippolito, Sara La Gioia, Sabrina Esposito, Valentina Torri Clerici, Giorgia Teresa Maniscalco, Cinzia Cordioli, Lorena Pareja-Gutierrez, Elisabetta Signoriello, Cinzia Valeria Russo, Roberta Grasso, Doriana Landi, B. Frigeni, Andrea Visconti, Caterina Barrilà, Valeria Barcella, Raffaella Cerqua, Alice Laroni, Simona Bonavita, Stefania Barone, P. Perini, Sarah Rasia, Arianna Sartori, Maria Laura Stromillo, Roberta Lanzillo, Damiano Baroncini, Jessica Frau, Francesco Saccà, Luigi Lavorgna, Alessio Signori, Ignazio Roberto Zarbo, Giorgia Mataluni, Eleonora Cocco, Maria Pia Sormani, E Binello, Pietro Annovazzi, M Clerico, Simona Pontecorvo, Giuseppe Fenu, Alessia Di Sapio, Anna Maria Repice, Signori, A., Sacca, F., Lanzillo, R., Maniscalco, G. T., Signoriello, E., Repice, A. M., Annovazzi, P., Baroncini, D., Clerico, M., Binello, E., Cerqua, R., Mataluni, G., Perini, P., Bonavita, S., Lavorgna, L., Zarbo, I. R., Laroni, A., Pareja-Gutierrez, L., La Gioia, S., Frigeni, B., Barcella, V., Frau, J., Cocco, E., Fenu, G., Clerici, V. T., Sartori, A., Rasia, S., Cordioli, C., Stromillo, M. L., Di Sapio, A., Pontecorvo, S., Grasso, R., Barone, S., Barrila, C., Russo, C. V., Esposito, S., Ippolito, D., Landi, D., Visconti, A., Sormani, M. P., Signori, Alessio, Saccà, Francesco, Lanzillo, Roberta, Maniscalco, Giorgia Teresa, Signoriello, Elisabetta, Repice, Anna Maria, Annovazzi, Pietro, Baroncini, Damiano, Clerico, Marinella, Binello, Eleonora, Cerqua, Raffaella, Mataluni, Giorgia, Perini, Paola, Bonavita, Simona, Lavorgna, Luigi, Zarbo, Ignazio Roberto, Laroni, Alice, Pareja-Gutierrez, Lorena, La Gioia, Sara, Frigeni, Barbara, Barcella, Valeria, Frau, Jessica, Cocco, Eleonora, Fenu, Giuseppe, Clerici, Valentina Torri, Sartori, Arianna, Rasia, Sarah, Cordioli, Cinzia, Stromillo, Maria Laura, Di Sapio, Alessia, Pontecorvo, Simona, Grasso, Roberta, Barone, Stefania, Barrilà, Caterina, Russo, Cinzia Valeria, Esposito, Sabrina, Ippolito, Domenico, Landi, Doriana, Visconti, Andrea, and Sormani, Maria Pia

Subjects
Adult, Male, medicine.medical_specialty, Databases, Factual, Datasets as Topic, Settore MED/26, Placebo, Severity of Illness Index, law.invention, Multiple Sclerosis, Relapsing-Remitting, Natalizumab, Randomized controlled trial, law, Internal medicine, Outcome Assessment, Health Care, Severity of illness, medicine, Humans, Immunologic Factors, Multicenter Studies as Topic, Glatiramer acetate, Cladribine, Randomized Controlled Trials as Topic, Retrospective Studies, business.industry, Middle Aged, Fingolimod, Observational Studies as Topic, Neurology, Propensity score matching, Disease Progression, Female, Neurology (clinical), business, medicine.drug
Abstract

ObjectiveCladribine tablets were tested against placebo in randomized controlled trials (RCTs). In this study, the effectiveness of cladribine vs other approved drugs in patients with relapsing-remitting MS (RRMS) was compared by matching RCT to observational data.MethodsData from the pivotal trial assessing cladribine tablets vs placebo (CLARITY) were propensity score matched to data from the Italian multicenter database i-MuST. This database included 3,150 patients diagnosed between 2010 and 2018 at 24 Italian MS centers who started a disease-modifying drug. The annualized relapse rate (ARR) over 2 years from treatment start and the 24-week confirmed disability progression were compared between patients treated with cladribine and other approved drugs (interferon, glatiramer acetate, fingolimod, natalizumab, and dimethyl fumarate), with comparisons with placebo as a reference. Treatment effects were estimated by the inverse probability weighting negative binomial regression model for ARR and Cox model for disability progression. The treatment effect has also been evaluated according to baseline disease activity.ResultsAll weighted baseline characteristics were well balanced between groups. All drugs tested had an effect vs placebo close to that detected in the RCT. Patients treated with cladribine had a significantly lower ARR compared with interferon (relapse ratio [RR] = 0.48; p < 0.001), glatiramer acetate (RR = 0.49; p < 0.001), and dimethyl fumarate (RR = 0.6; p = 0.001); a similar ARR to that with fingolimod (RR = 0.74; p = 0.24); and a significantly higher ARR than natalizumab (RR = 2.13; p = 0.014), confirming results obtained by indirect treatment comparisons from RCTs (network meta-analyses). The relative effect of cladribine tablets 10 mg (cumulative dose 3.5 mg/kg over 2 years) was higher in patients with high disease activity vs all treatments except fingolimod and natalizumab. Effects on disability progression were largely nonsignificant, probably due to lack of power for such analysis.ConclusionIn patients with RRMS, cladribine tablets showed lower ARR compared with matched patients who started interferon, glatiramer acetate, or dimethyl fumarate; was similar to fingolimod; and was higher than natalizumab. The beneficial effect of cladribine tablets was generally amplified in the subgroup of patients with high disease activity.Classification of evidenceThis study provides Class III evidence that for patients with RRMS, cladribine-treated patients had lower ARR compared with interferon, glatiramer acetate, or dimethyl fumarate; similar ARR compared with fingolimod; and higher ARR compared with natalizumab.

Published
2020

45. Treatment of multiple sclerosis with rituximab: A multicentric Italian–Swiss experience

Author

Antonio Gallo, Gianmarco Abbadessa, Chiara Zecca, Giancarlo Coghe, Giuseppe Salemi, Antonio Uccelli, Marco Capobianco, Stefania Barone, Rosaria Sacco, Lorena Lorefice, Claudia Mechi, Giorgia Mataluni, Elio Prestipino, Jessica Frau, Claudio Gobbi, Alessandro Barilaro, Giorgia Teresa Maniscalco, Erica Curti, E. Magnani, Bahia Hakiki, Maria Malentacchi, Simona Bonavita, Alessia Di Sapio, Francesca Bovis, Maria Cellerino, Franco Granella, Roberta Lanzillo, Anna Maria Repice, Marcello De Angelis, Isabella Maraffi, Laura Brambilla, Giuseppe Fenu, Elisabetta Signoriello, Alessio Signori, Paola Cavalla, Maria Pia Sormani, Agostino Nozzolillo, Giacomo Boffa, Simona Malucchi, Maria Pia Amato, Giovanni Novi, Sabrina Realmuto, Francesca Sperli, Ilaria Maietta, Vincenzo Brescia Morra, Zecca, C., Bovis, F., Novi, G., Capobianco, M., Lanzillo, R., Frau, J., Repice, A. M., Hakiki, B., Realmuto, S., Bonavita, S., Curti, E., Brambilla, L., Mataluni, G., Cavalla, P., Di Sapio, A., Signoriello, E., Barone, S., Maniscalco, G. T., Maietta, I., Maraffi, I., Boffa, G., Malucchi, S., Nozzolillo, A., Coghe, G., Mechi, C., Salemi, G., Gallo, A., Sacco, R., Cellerino, M., Malentacchi, M., De Angelis, M., Lorefice, L., Magnani, E., Prestipino, E., Sperli, F., Brescia Morra, V., Fenu, G., Barilaro, A., Abbadessa, G., Signori, A., Granella, F., Amato, M. P., Uccelli, A., Gobbi, C., Sormani, M. P., Zecca, Chiara, Bovis, Francesca, Novi, Giovanni, Capobianco, Marco, Lanzillo, Roberta, Frau, Jessica, Repice, Anna Maria, Hakiki, Bahia, Realmuto, Sabrina, Bonavita, Simona, Curti, Erica, Brambilla, Laura, Mataluni, Giorgia, Cavalla, Paola, Di Sapio, Alessia, Signoriello, Elisabetta, Barone, Stefania, Maniscalco, Giorgia T, Maietta, Ilaria, Maraffi, Isabella, Boffa, Giacomo, Malucchi, Simona, Nozzolillo, Agostino, Coghe, Giancarlo, Mechi, Claudia, Salemi, Giuseppe, Gallo, Antonio, Sacco, Rosaria, Cellerino, Maria, Malentacchi, Maria, De Angelis, Marcello, Lorefice, Lorena, Magnani, Eliana, Prestipino, Elio, Sperli, Francesca, Brescia Morra, Vincenzo, Fenu, Giuseppe, Barilaro, Alessandro, Abbadessa, Gianmarco, Signori, Alessio, Granella, Franco, Amato, Maria Pia, Uccelli, Antonio, Gobbi, Claudio, and Sormani, Maria Pia

Subjects
Multiple Sclerosis, medicine.drug_class, Lymphocyte depletion, relapsing–remitting, Monoclonal antibody, Primary progressive, 03 medical and health sciences, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, real life, medicine, Humans, Immunologic Factors, 030212 general & internal medicine, Secondary progressive, Retrospective Studies, primary progressive, business.industry, Multiple sclerosis, Rituximab, multiple sclerosis, secondary progressive, Treatment options, medicine.disease, Neurology, Relapsing remitting, Italy, multiple sclerosi, Immunology, Settore MED/26 - Neurologia, Neurology (clinical), business, 030217 neurology & neurosurgery, Switzerland, medicine.drug
Abstract

Background: Rituximab, an anti-CD20 monoclonal antibody leading to B lymphocyte depletion, is increasingly used as an off-label treatment option for multiple sclerosis (MS). Objective: To investigate the effectiveness and safety of rituximab in relapsing–remitting (RR) and progressive MS. Methods: This is a multicenter, retrospective study on consecutive MS patients treated off-label with rituximab in 22 Italian and 1 Swiss MS centers. Relapse rate, time to first relapse, Expanded Disability Status Scale (EDSS) progression, incidence of adverse events, and radiological outcomes from 2009 to 2019 were analyzed. Results: A total of 355/451 enrolled subjects had at least one follow-up visit and were included in the outcome analysis. Annualized relapse rate significantly decreases after rituximab initiation versus the pre-rituximab start year in RRMS (from 0.86 to 0.09, p Conclusion: Consistently with other observational studies, our data show effectiveness of rituximab in reducing disease activity in patients with MS.

Published
2020

46. Extending the Interval of Natalizumab Dosing: Is Efficacy Preserved?

Author

Marco Iudicello, Cinzia Cordioli, Marinella Clerico, Giorgia Teresa Maniscalco, Luigi Lavorgna, Martina Petruzzo, Giorgia Mataluni, Giacomo Lus, Massimiliano Mirabella, Rita Frangiamore, Damiano Baroncini, Erica Curti, Alice Laroni, Paola Cavalla, Eleonora Cocco, Ruggero Capra, Alessio Signori, Roberta Lanzillo, Gianfranco Costantini, Maria Pia Sormani, Stefania Federica De Mercanti, Viviana Nociti, Simona Bonavita, Ilaria Gandoglia, Arianna Sartori, Doriana Landi, Lorena Lorefice, Elisabetta Signoriello, Clerico, Marinella, De Mercanti, Stefania Federica, Signori, Alessio, Iudicello, Marco, Cordioli, Cinzia, Signoriello, Elisabetta, Lus, Giacomo, Bonavita, Simona, Lavorgna, Luigi, Maniscalco, Giorgia Teresa, Curti, Erica, Lorefice, Lorena, Cocco, Eleonora, Nociti, Viviana, Mirabella, Massimiliano, Baroncini, Damiano, Mataluni, Giorgia, Landi, Doriana, Petruzzo, Martina, Lanzillo, Roberta, Gandoglia, Ilaria, Laroni, Alice, Frangiamore, Rita, Sartori, Arianna, Cavalla, Paola, Costantini, Gianfranco, Sormani, Maria Pia, Capra, Ruggero, Clerico, M., De Mercanti, S. F., Signori, A., Iudicello, M., Cordioli, C., Signoriello, E., Lus, G., Bonavita, S., Lavorgna, L., Maniscalco, G. T., Curti, E., Lorefice, L., Cocco, E., Nociti, V., Mirabella, M., Baroncini, D., Mataluni, G., Landi, D., Petruzzo, M., Lanzillo, R., Gandoglia, I., Laroni, A., Frangiamore, R., Sartori, A., Cavalla, P., Costantini, G., Sormani, M. P., and Capra, R.

Subjects
0301 basic medicine, Standard interval, Adult, Male, medicine.medical_specialty, efficacy, progressive multifocal leukoencephalopathy, law.invention, Cohort Studies, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, natalizumab, Randomized controlled trial, law, Recurrence, Internal medicine, medicine, Humans, Immunologic Factors, Pharmacology (medical), Multiple sclerosi, extended dose, Dosing, Retrospective Studies, Pharmacology, business.industry, Progressive multifocal leukoencephalopathy, Leukoencephalopathy, Progressive Multifocal, Retrospective cohort study, medicine.disease, Settore MED/26 - NEUROLOGIA, 030104 developmental biology, Treatment Outcome, Italy, Observational study, Female, Original Article, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug, Cohort study
Abstract

Extending the natalizumab interval after the 24th administration could reduce the risk of progressive multifocal leukoencephalopathy (PML). The objective is to evaluate the noninferiority of the efficacy of an extended interval dosing (EID) compared with the standard interval dosing (SID) of natalizumab. It is an observational, multicenter (14 Italian centers), retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Patients were grouped in 2 categories according to the mean number of weeks between doses

Published
2020

47. Telemedicine and the challenge of epilepsy management at the time of COVID-19 pandemic

Author

Francesco, Brigo, Bonavita, S., Leocani, L., Gioacchino, Tedeschi, Lavorgna, L., Giovanni, Mancardi, Alessandro, Padovani, Clerico, Marinella, Roberta, Lanzillo, Antonio, Russo, Bruno, Giometto, Giulia, Straccia, Rosa, Iodice, Sebastiano, Bucello, Pietro, Annovazzi, Marcello, Moccia, Luca, Prosperini, Maria Laura Stromillo, Anna Maria Repice, Giuseppina, Miele, Alberto, Lerario, Antonio De Martino, Francesco, Iodice, Francesco Di Lorenzo, Luca, Cuffaro, Michele, Romoli, Marcello Silvestro, Artusi, Carlo Alberto, Brigo, F., Bonavita, S., Leocani, L., Tedeschi, G., Lavorgna, L., Brigo, Francesco, Bonavita, Simona, Leocani, Letizia, Tedeschi, Gioacchino, and Lavorgna, Luigi

Subjects
medicine.medical_specialty, 2019-20 coronavirus outbreak, Telemedicine, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, Clinical Neurology, COVID-19 pandemic, Mobile device, Article, Social media, Behavioral Neuroscience, Epilepsy, Betacoronavirus, Seizures, Pandemic, Medicine, Humans, Viral, Intensive care medicine, Mobile devices, Coronavirus Infections, Pandemics, biology, SARS-CoV-2, business.industry, COVID-19, Pneumonia, medicine.disease, biology.organism_classification, Seizure, Neurology, Neurology (clinical), business
Published
2020

48. Are patients with multiple sclerosis (MS) at higher risk of COVID-19 infection?

Author

Simona Bonavita, Mahsa Ghajarzadeh, Ghajarzadeh, Mahsa, and Bonavita, Simona

Subjects
medicine.medical_specialty, Pediatrics, Multiple Sclerosis, Neurology, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, Clinical Neurology, MEDLINE, Dermatology, Betacoronavirus, Risk Factors, Pandemic, medicine, Humans, Immunologic Factors, Pandemics, Neuroradiology, biology, SARS-CoV-2, business.industry, Multiple sclerosis, COVID-19, General Medicine, biology.organism_classification, medicine.disease, Psychiatry and Mental health, Neurology (clinical), Neurosurgery, Coronavirus Infections, business
Published
2020

49. Singular cases of Alzheimer's disease disclose new and old genetic 'acquaintances'

Author

Giorgio Giaccone, Sabina Pappatà, Lorenzo Cipriano, Giuseppe Di Fede, Marcella Catania, Giacomina Rossi, Cinzia Coppola, Sara Cimini, Dario Saracino, Simona Bonavita, Gianfranco Puoti, Mariano Oliva, Martina Ricci, Coppola, Cinzia, Saracino, Dario, Oliva, Mariano, Cipriano, Lorenzo, Puoti, Gianfranco, Pappatà, Sabina, Di Fede, Giuseppe, Catania, Marcella, Ricci, Martina, Cimini, Sara, Giaccone, Giorgio, Bonavita, Simona, and Rossi, Giacomina

Subjects
0301 basic medicine, medicine.medical_specialty, Amyloid, Neurology, Mutation, Missense, Dermatology, Disease, Neuropsychological Tests, Bioinformatics, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Genetic, Alzheimer Disease, PSEN2, Presenilin-2, medicine, PSEN1, Presenilin-1, Genetics, Dementia, Missense mutation, Humans, Genetic Testing, Sanger sequencing, business.industry, General Medicine, Biomarker, medicine.disease, Psychiatry and Mental health, 030104 developmental biology, Mutation, symbols, Original Article, Neurology (clinical), Age of onset, business, Alzheimer’s disease, 030217 neurology & neurosurgery, Biomarkers
Abstract

Background Alzheimer’s disease (AD) is the most common age-related dementia. Besides its typical presentation with amnestic syndrome at onset, atypical AD cases are being increasingly recognized, often in presenile age. Objectives To provide an extensive clinical and genetic characterization of six AD patients carrying one or more singular features, including age of onset, atypical phenotype and disease progression rate. By reviewing the pertinent literature and accessing publicly available databases, we aimed to assess the frequency and the significance of the identified genetic variants. Methods Biomarkers of amyloid-β deposition and neurodegeneration were used to establish the in vivo diagnosis of probable AD, in addition to neurological and neuropsychological evaluation, extensive laboratory assays and neuroradiological data. Considering the presenile onset of the majority of the cases, we hypothesized genetically determined AD and performed extensive genetic analyses by both Sanger sequencing and next generation sequencing (NGS). Results We disclosed two known missense variants, one in PSEN1 and the other in PSEN2, and a novel silent variant in PSEN2. Most notably, we identified several additional variants in other dementia-related genes by NGS. Some of them have never been reported in any control or disease databases, representing variants unique to our cases. Conclusions This work underlines the difficulties in reaching a confident in vivo diagnosis in cases of atypical dementia. Moreover, a wider genetic analysis by NGS approach may prove to be useful in specific cases, especially when the study of the so-far known AD causative genes produces negative or conflicting results.

Published
2020

50. In Amyotrophic Lateral Sclerosis Blood Cytokines Are Altered, but Do Not Correlate with Changes in Brain Topology

Author

Simona Bonavita, Manuela Grimaldi, Francesca Trojsi, Ilaria Stillitano, Pierpaolo Sorrentino, Matteo Pesoli, Anna Maria D'Ursi, Arianna Polverino, Giuseppe Sorrentino, Rosaria Rucco, Roberta Minino, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Polverino, Arianna, Rucco, Rosaria, Stillitano, Ilaria, Bonavita, Simona, Grimaldi, Manuela, Minino, Roberta, Pesoli, Matteo, Trojsi, Francesca, D'Ursi, Anna Maria, Sorrentino, Giuseppe, and Sorrentino, Pierpaolo

Subjects
Male, magnetoencephalography, amyotrophic lateral sclerosis, medicine.medical_treatment, Interleukin-1beta, Disease, Inflammatory diseases, neuroinflammation, Pathogenesis, 0302 clinical medicine, Image Processing, Computer-Assisted, Medicine, Magnetoencephalography (MEG), Amyotrophic lateral sclerosis, ComputingMilieux_MISCELLANEOUS, Brain Mapping, medicine.diagnostic_test, General Neuroscience, 05 social sciences, Brain, Interleukin, Middle Aged, brain networks, Inflammatory disease, Cytokine, connectivity, Encephalitis, Female, medicine.symptom, Resting-state networks, Human brain connectivity, Neurodegenerative disorders, Inflammation, Topology, 050105 experimental psychology, 03 medical and health sciences, Humans, 0501 psychology and cognitive sciences, cytokines, Neuroinflammation, Aged, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Magnetoencephalography, Neurodegenerative disorder, medicine.disease, Interferons, Interleukin-4, Nerve Net, business, Biomarkers, 030217 neurology & neurosurgery
Abstract

Aim: The present study aims at investigating the possible correlation between peripheral markers of inflammation and brain networks. Introduction: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease dominated by progressive motor impairment. Among the complex mechanisms contributing to the pathogenesis of the disease, neuroinflammation, which is associated with altered circulating cytokine levels, is suggested to play a prominent role. Methods: Based on magnetoencephalography data, we estimated topological properties of the brain networks in ALS patients and healthy controls. Subsequently, the blood levels of a subset of cytokines were assayed. Finally, we modeled the brain topological features in the function of the cytokine levels. Results: Significant differences were found in the levels of the cytokines interleukin (IL)-4, IL-1β, and interferon-gamma (IFN-γ) between patients and controls. In particular, IL-4 and IL-1β levels increased in ALS patients, while the IFN-γ level was higher in healthy controls. We also detected modifications in brain global topological parameters in terms of hyperconnectedness. Despite both blood cytokines and brain topology being altered in ALS patients, such changes do not appear to be in a direct relationship. Conclusion: Our results would be in line with the idea that topological changes relate to neurodegenerative processes. However, the absence of correlation between blood cytokines and topological parameters of brain networks does not preclude that inflammatory processes contribute to the alterations of the brain networks. Impact statement The progression of amyotrophic lateral sclerosis entails both neurodegenerative and inflammatory processes. Furthermore, disease progression induces global modifications of the brain networks, with advanced stages showing a more compact, hyperconnected network topology. The pathophysiological processes underlying topological changes are unknown. In this article, we hypothesized that the global inflammatory profile would relate to the topological alterations. Our results showed that this is not the case, as modeling the topological properties as a function of the inflammatory state did not yield good predictions. Hence, our results suggest that topological changes might directly relate to neurodegenerative processes instead.

Published
2020

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