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1. Implications of disease-modifying therapies for multiple sclerosis on immune cells and response to COVID-19 vaccination

Author

Valeria Orrù, Valentina Serra, Michele Marongiu, Sandra Lai, Valeria Lodde, Magdalena Zoledziewska, Maristella Steri, Annalisa Loizedda, Monia Lobina, Maria Grazia Piras, Francesca Virdis, Giuseppe Delogu, Maria Giuseppina Marini, Maura Mingoia, Matteo Floris, Marco Masala, M. Paola Castelli, Rafaela Mostallino, Jessica Frau, Lorena Lorefice, Gabriele Farina, Marzia Fronza, Daniele Carmagnini, Elisa Carta, Silvy Pilotto, Paola Chessa, Marcella Devoto, Paolo Castiglia, Paolo Solla, Roberto Ignazio Zarbo, Maria Laura Idda, Maristella Pitzalis, Eleonora Cocco, Edoardo Fiorillo, and Francesco Cucca

Subjects
SARS-CoV-2, multiple sclerosis, disease-modifying therapy, immune response, immune-phenotyping, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionDisease-modifying therapies (DMTs) have been shown to improve disease outcomes in multiple sclerosis (MS) patients. They may also impair the immune response to vaccines, including the SARS-CoV-2 vaccine. However, available data on both the intrinsic immune effects of DMTs and their influence on cellular response to the SARS-CoV-2 vaccine are still incomplete.MethodsHere, we evaluated the immune cell effects of 3 DMTs on the response to mRNA SARS-CoV-2 vaccination by comparing MS patients treated with one specific therapy (fingolimod, dimethyl fumarate, or natalizumab) with both healthy controls and untreated patients. We profiled 23 B-cell traits, 57 T-cell traits, and 10 cytokines, both at basal level and after stimulation with a pool of SARS-CoV-2 spike peptides, in 79 MS patients, treated with DMTs or untreated, and 32 healthy controls. Measurements were made before vaccination and at three time points after immunization.Results and DiscussionMS patients treated with fingolimod showed the strongest immune cell dysregulation characterized by a reduction in all measured lymphocyte cell classes; the patients also had increased immune cell activation at baseline, accompanied by reduced specific immune cell response to the SARS-CoV-2 vaccine. Also, anti-spike specific B cells progressively increased over the three time points after vaccination, even when antibodies measured from the same samples instead showed a decline. Our findings demonstrate that repeated booster vaccinations in MS patients are crucial to overcoming the immune cell impairment caused by DMTs and achieving an immune response to the SARS-CoV-2 vaccine comparable to that of healthy controls.

Published
2024
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2. Thalamic atrophy and dysconnectivity are associated with cognitive impairment in a multi-center, clinical routine, real-word study of people with relapsing-remitting multiple sclerosis

Author

Robert Zivadinov, Niels Bergsland, Dejan Jakimovski, Bianca Weinstock-Guttman, Lorena Lorefice, Menno M. Schoonheim, Sarah A. Morrow, Mary Ann Picone, Gabriel Pardo, Myassar Zarif, Mark Gudesblatt, Jacqueline A. Nicholas, Andrew Smith, Samuel Hunter, Stephen Newman, Mahmoud A. AbdelRazek, Ina Hoti, Jon Riolo, Diego Silva, Tom A. Fuchs, Michael G. Dwyer, and Ralph HB. Benedict

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract

Background: Prior research has established a link between thalamic pathology and cognitive impairment (CI) in people with multiple sclerosis (pwMS). However, the translation of these findings to pwMS in everyday clinical settings has been insufficient. Objective: To assess which global and/or thalamic imaging biomarkers can be used to identify pwMS at risk for CI and cognitive worsening (CW) in a real-world setting. Methods: This was an international, multi-center (11 centers), longitudinal, retrospective, real-word study of people with relapsing-remitting MS (pwRRMS). Brain MRI exams acquired at baseline and follow-up were collected. Cognitive status was evaluated using the Symbol Digit Modalities Test (SDMT). Thalamic volume (TV) measurement was performed on T2-FLAIR, as well as on T1-WI, when available. Thalamic dysconnectivity, T2-lesion volume (T2-LV), and volumes of gray matter (GM), whole brain (WB) and lateral ventricles (LVV) were also assessed. Results: 332 pwMS were followed for an average of 2.8 years. At baseline, T2-LV, LVV, TV and thalamic dysconnectivity on T2-FLAIR (p

Published
2024
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3. Menopausal transition in multiple sclerosis: relationship with disease activity and brain volume measurements

Author

Lorena Lorefice, Giuseppe Fenu, Marzia Fronza, Federica Murgia, Jessica Frau, Giancarlo Coghe, Maria Antonietta Barracciu, Luigi Atzori, Stefano Angioni, and Eleonora Cocco

Subjects
aging, brain atrophy, menopause, multiple sclerosis, neurodegeneration, oestrogen deprivation, Neurology. Diseases of the nervous system, RC346-429
Abstract

BackgroundRecent evidence has shown a significant association between menopause and multiple sclerosis (MS) progression. This study investigated the possible role of menopause in influencing MS from clinical and neuroradiological perspectives. Notably, the possible association between menopause and brain atrophy has been evaluated.Materials and methodsThis study included women with MS whose ages ranged from 45 to 55 years. Demographic and clinical characteristics were collected, and the reproductive phase was defined as non-menopausal or menopausal based on the final menstrual period. Thus, MS activity over the past year was reported as the annualised relapse rate (ARR), and MRI activity (defined as new T2 lesions and/or the presence of gadolinium-enhancing lesions at the last MRI assessment in comparison with the MRI performed within the previous 12 months) were compared between non-menopausal women (non-MW) and menopausal women (MW). Volume measurements of the whole brain (WB), white matter (WM), grey matter (GM), and cortical GM were estimated using the SIENAX software, and the possible relationship with menopausal status was assessed by regression analysis.ResultsThe study included 147 women with MS. Eighty-four (57.1%) were MW, with a mean age of 48.5 ± 4.3 years at menopause onset and a mean duration of menopause of 4.1 ± 1.1 years. When compared for ARR, MW reported a lower rate than the non-MW (ARR of 0.29 ± 0.4 vs. 0.52 ± 0.5; p

Published
2023
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4. Brain-reactive autoantibodies in neuropsychiatric systemic lupus erythematosus

Author

Cristina Cocco, Elias Manca, Giulia Corda, Maria Maddalena Angioni, Barbara Noli, Mattia Congia, Francesco Loy, Michela Isola, Elisabetta Chessa, Alberto Floris, Lorena Lorefice, Luca Saba, Alessandro Mathieu, Gian Luca Ferri, Alberto Cauli, and Matteo Piga

Subjects
systemic lupus erythematosus, neuropsychiatric syndromes, autoantibodies, brain, neurons, immunofluorescence, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionThe pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) is widely unknown, and the role of autoantibodies is still undetermined.MethodsTo identify brain-reactive autoantibodies possibly related to NPSLE, immunofluorescence (IF) and transmission electron microscopy (TEM) on rat and human brains were performed. ELISA was used to reveal the presence of known circulating autoantibodies, while western blot (WB) was applied to characterize potential unknown autoantigen(s).ResultsWe enrolled 209 subjects, including patients affected by SLE (n=69), NPSLE (n=36), Multiple Sclerosis (MS, n=22), and 82 age- and gender-matched healthy donors (HD). Autoantibody reactivity by IF was observed in almost the entire rat brain (cortex, hippocampus, and cerebellum) using sera from NPSLE and SLE patients and was virtually negative in MS and HD. NPSLE showed higher prevalence (OR 2.4; p = 0.047), intensity, and titer of brain-reactive autoantibodies than SLE patients. Most of the patient sera with brain-reactive autoantibodies (75%) also stained human brains. Double staining experiments on rat brains mixing patients’ sera with antibodies directed against neuronal (NeuN) or glial markers showed autoantibody reactivity restricted to NeuN-containing neurons. Using TEM, the targets of brain-reactive autoantibodies were located in the nuclei and, to a lesser extent, in the cytoplasm and mitochondria. Given the high degree of colocalization between NeuN and brain-reactive autoantibodies, we assumed NeuN was a possible autoantigen. However, WB analysis with HEK293T cell lysates expressing or not expressing the gene encoding for NeuN protein (RIBFOX3) showed that patients’ sera carrying brain-reactive autoantibodies did not recognize the NeuN corresponding band size. Among the panel of NPSLE-associated autoantibodies (e.g., anti-NR2, anti-P-ribosomal protein, antiphospholipid) investigated by ELISA assay, only the anti-β2-glycoprotein-I (aβ2GPI) IgG was exclusively found in those sera containing brain-reactive autoantibodies.ConclusionIn conclusion, SLE and NPSLE patients possess brain-reactive autoantibodies but with higher frequency and titers found in NPSLE patients. Although many target antigens of brain-reactive autoantibodies are still undetermined, they likely include β2GPI.

Published
2023
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5. Cybersickness in People with Multiple Sclerosis Exposed to Immersive Virtual Reality

Author

Massimiliano Pau, Federico Arippa, Bruno Leban, Micaela Porta, Giulia Casu, Jessica Frau, Lorena Lorefice, Giancarlo Coghe, and Eleonora Cocco

Subjects
virtual reality (VR), cybersickness, multiple sclerosis (MS), postural sway, Technology, Biology (General), QH301-705.5
Abstract

Together with the wide range of possible benefits for the rehabilitation/training of people with multiple sclerosis (pwMS) and other neurologic conditions, exposure to immersive virtual reality (VR) has often been associated with unpleasant symptoms, such as transient dizziness, headache, nausea, disorientation and impaired postural control (i.e., cybersickness). Since these symptoms can significantly impact the safety and tolerability of the treatment, it appears important to correctly estimate their presence and magnitude. Given the existing data scarcity, this study aims to assess the existence and severity of possible adverse effects associated with exposure to immersive VR in a cohort of pwMS using both objective measurements of postural control effectiveness and subjective evaluations of perceived symptoms. To this aim, postural sway under upright quiet posture (in the presence and absence of visual input) of 56 pwMS with an Expanded Disability Status Scale score (EDSS) in the range of 0–6.5 (mean EDSS 2.3) and 33 unaffected individuals was measured before and after a 10-min immersive VR session and at 10 min follow-up on the basis of center of pressure (COP) trajectories. The severity of cybersickness symptoms associated with VR exposure was also self-rated by the participants using the Italian version of the Simulator Sickness Questionnaire (SSQ). Temporary impairments of postural control in terms of significantly increased sway area were observed after the VR session only in pwMS with mild–moderate disability (i.e., EDSS in the range of 2.5–6.5) in the presence of visual input. No changes were observed in pwMS with low disability (EDSS 0–2) and unaffected individuals. In contrast, when the visual input was removed, there was a decrease in sway area (pwMS with mild–moderate disability) and COP path length relating to the use of VR (pwMS with mild–moderate disability and unaffected individuals), thus suggesting a sort of “balance training effect”. Even in this case, the baseline values were restored at follow-up. All participants, regardless of their status, experienced significant post-VR side effects, especially in terms of blurred vision and nausea. Taken together, the findings of the present study suggest that a short immersive VR session negatively (eyes open) and positively (eyes closed) impacts the postural control of pwMS and causes significant disorientation. However, such effects are of limited duration. While it is reasonable to state that immersive VR is sufficiently safe and tolerable to not be contraindicated in the rehabilitation/training of pwMS, in order to reduce possible negative effects and maximize the efficacy, safety and comfort of the treatment, it appears necessary to develop specific guidelines that consider important factors like individual susceptibility, maximum exposure time according to the specific features of the simulation, posture to adopt and protocols to assess objective and perceived effects on participants.

Published
2024
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6. Omics approaches to understanding the efficacy and safety of disease-modifying treatments in multiple sclerosis

Author

Lorena Lorefice, Maristella Pitzalis, Federica Murgia, Giuseppe Fenu, Luigi Atzori, and Eleonora Cocco

Subjects
multiple sclerosis, genomics, transcriptomics, proteomics, metabolomics, disease-modifying treatments, Genetics, QH426-470
Abstract

From the perspective of precision medicine, the challenge for the future is to improve the accuracy of diagnosis, prognosis, and prediction of therapeutic responses through the identification of biomarkers. In this framework, the omics sciences (genomics, transcriptomics, proteomics, and metabolomics) and their combined use represent innovative approaches for the exploration of the complexity and heterogeneity of multiple sclerosis (MS). This review examines the evidence currently available on the application of omics sciences to MS, analyses the methods, their limitations, the samples used, and their characteristics, with a particular focus on biomarkers associated with the disease state, exposure to disease-modifying treatments (DMTs), and drug efficacies and safety profiles.

Published
2023
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7. The Role of Microorganisms in the Etiopathogenesis of Demyelinating Diseases

Author

Jessica Frau, Giancarlo Coghe, Lorena Lorefice, Giuseppe Fenu, and Eleonora Cocco

Subjects
multiple sclerosis, neuromyelitis optica, myelin oligodendrocyte glycoprotein-associated diseases, infections, viruses, Epstein–Barr virus, Science
Abstract

Multiple sclerosis (MS), neuromyelitis optica (NMO) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are inflammatory diseases of the central nervous system (CNS) with a multifactorial aetiology. Environmental factors are important for their development and microorganisms could play a determining role. They can directly damage the CNS, but their interaction with the immune system is even more important. The possible mechanisms involved include molecular mimicry, epitope spreading, bystander activation and the dual cell receptor theory. The role of Epstein–Barr virus (EBV) in MS has been definitely established, since being seropositive is a necessary condition for the onset of MS. EBV interacts with genetic and environmental factors, such as low levels of vitamin D and human endogenous retrovirus (HERV), another microorganism implicated in the disease. Many cases of onset or exacerbation of neuromyelitis optica spectrum disorder (NMOSD) have been described after infection with Mycobacterium tuberculosis, EBV and human immunodeficiency virus; however, no definite association with a virus has been found. A possible role has been suggested for Helicobacter pylori, in particular in individuals with aquaporin 4 antibodies. The onset of MOGAD could occur after an infection, mainly in the monophasic course of the disease. A role for the HERV in MOGAD has been hypothesized. In this review, we examined the current understanding of the involvement of infectious factors in MS, NMO and MOGAD. Our objective was to elucidate the roles of each microorganism in initiating the diseases and influencing their clinical progression. We aimed to discuss both the infectious factors that have a well-established role and those that have yielded conflicting results across various studies.

Published
2023
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8. Cross-sectional analysis of the humoral response after SARS-CoV-2 vaccination in Sardinian multiple sclerosis patients, a follow-up study

Author

Maria Laura Idda, Maristella Pitzalis, Valeria Lodde, Annalisa Loizedda, Jessica Frau, Monia Lobina, Magdalena Zoledziewska, Francesca Virdis, Giuseppe Delogu, Maria Giuseppina Marini, Maura Mingoia, Marco Masala, Lorena Lorefice, Marzia Fronza, Daniele Carmagnini, Elisa Carta, Silvy Pilotto, Paolo Castiglia, Paola Chessa, Sergio Uzzau, Gabriele Farina, Paolo Solla, Maristella Steri, Marcella Devoto, Edoardo Fiorillo, Matteo Floris, Roberto Ignazio Zarbo, Eleonora Cocco, and Francesco Cucca

Subjects
SARS-CoV-2, multiple sclerosis, humoral immunity, disease-modifying therapy (DMT), vaccine efficacy and effectiveness, BNT162b2 messenger RNA (mRNA), Immunologic diseases. Allergy, RC581-607
Abstract

Monitoring immune responses to SARS-CoV-2 vaccination and its clinical efficacy over time in Multiple Sclerosis (MS) patients treated with disease-modifying therapies (DMTs) help to establish the optimal strategies to ensure adequate COVID-19 protection without compromising disease control offered by DMTs. Following our previous observations on the humoral response one month after two doses of BNT162b2 vaccine (T1) in MS patients differently treated, here we present a cross-sectional and longitudinal follow-up analysis six months following vaccination (T2, n=662) and one month following the first booster (T3, n=185). Consistent with results at T1, humoral responses were decreased in MS patients treated with fingolimod and anti-CD20 therapies compared with untreated patients also at the time points considered here (T2 and T3). Interestingly, a strong upregulation one month after the booster was observed in patients under every DMTs analyzed, including those treated with fingolimod and anti-CD20 therapies. Although patients taking these latter therapies had a higher rate of COVID-19 infection five months after the first booster, only mild symptoms that did not require hospitalization were reported for all the DMTs analyzed here. Based on these findings we anticipate that additional vaccine booster shots will likely further improve immune responses and COVID-19 protection in MS patients treated with any DMT.

Published
2022
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9. Breakthrough SARS-CoV-2 infections after COVID-19 mRNA vaccination in MS patients on disease modifying therapies during the Delta and the Omicron waves in Italy

Author

Maria Pia Sormani, Irene Schiavetti, Matilde Inglese, Luca Carmisciano, Alice Laroni, Caterina Lapucci, Valeria Visconti, Carlo Serrati, Ilaria Gandoglia, Tiziana Tassinari, Germana Perego, Giampaolo Brichetto, Paola Gazzola, Antonio Mannironi, Maria Laura Stromillo, Cinzia Cordioli, Doriana Landi, Marinella Clerico, Elisabetta Signoriello, Eleonora Cocco, Jessica Frau, Maria Teresa Ferrò, Alessia Di Sapio, Livia Pasquali, Monica Ulivelli, Fabiana Marinelli, Matteo Pizzorno, Graziella Callari, Rosa Iodice, Giuseppe Liberatore, Francesca Caleri, Anna Maria Repice, Susanna Cordera, Mario Alberto Battaglia, Marco Salvetti, Diego Franciotta, Antonio Uccelli, Alessandro Maglione, Alessio Signori, Aniello Iovino, Carolina Gabri Nicoletti, Chiara Rosa Mancinelli, Daiana Bezzini, Daniele Carmagnini, Davide Brogi, Eduardo Nobile Orazio, Enri Nako, Ester Assandrir, Federica Baldi, Filippo Ansaldi, Francesca Bovis, Gabriele Siciliano, Gaia Cola, Giacomo Lus, Giancarlo Icardi, Gianmarco Bellucci, Giorgio Da Rin, Girolama Alessandra Marfia, Giulia Vazzoler, Giuseppe Trivelli, Ilaria Maietta, Laura Sticchi, Lorena Lorefice, Lucia Ruggiero, Marcello Manzino, Margherita Monti Bragadin, Maria Chiara Buscarinu, Maria Gagliardi, Maria Teresa Rilla, Marta Ponzano, Marzia Fronza, Massimo Del Sette, Matteo Scialabba, Michele Bedognetti, Nicola De Rossi, Nicola De Stefano, Rachele Bigi, Raffaele Dubbioso, Roberta Reniè, Sabrina Fabbri, Sarah Rasia, Simona Rolla, Stefan Platzgummer, and Valentina Carlini

Subjects
Breakthrough infections, Multiple Sclerosis, COVID-19, Disease Modifying Treatments, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in patients with MS (pwMS) under different DMTs and to identify correlates of reduced protection. Methods: This is a prospective Italian multicenter cohort study, long-term clinical follow-up of the CovaXiMS (Covid-19 vaccine in Multiple Sclerosis) study. 1855 pwMS scheduled for SARS-CoV-2 mRNA vaccination were enrolled and followed up to a mean time of 10 months. The cumulative incidence of breakthrough Covid-19 cases in pwMS was calculated before and after December 2021, to separate the Delta from the Omicron waves and to account for the advent of the third vaccine dose. Findings: 1705 pwMS received 2 m-RNA vaccine doses, 21/28 days apart. Of them, 1508 (88.5%) had blood assessment 4 weeks after the second vaccine dose and 1154/1266 (92%) received the third dose after a mean interval of 210 days (range 90-342 days) after the second dose. During follow-up, 131 breakthrough Covid-19 infections (33 during the Delta and 98 during the Omicron wave) were observed. The probability to be infected during the Delta wave was associated with SARS-CoV-2 antibody levels measured after 4 weeks from the second vaccine dose (HR=0.57, p

Published
2022
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10. Metabolomic Changes in Patients Affected by Multiple Sclerosis and Treated with Fingolimod

Author

Federica Murgia, Lorena Lorefice, Antonio Noto, Martina Spada, Jessica Frau, Giuseppe Fenu, Giancarlo Coghe, Antonella Gagliano, Luigi Atzori, and Eleonora Cocco

Subjects
multiple sclerosis, Fingolimod treatment, metabolomics, nuclear magnetic resonance, aminoacids metabolism, energy homeostasis, Microbiology, QR1-502
Abstract

Current treatment for Multiple Sclerosis (MS) consists of a multidisciplinary approach including disease-modifying therapies. The response to treatment is heterogeneous, representing a crucial challenge in the classification of patients. Metabolomics is an innovative tool that can identifies biomarkers/predictors of treatment response. We aimed to evaluate plasma metabolic changes in a group of naïve Relapsing-Remitting MS patients starting Fingolimod treatment, to find specific metabolomic features that predict the therapeutic response as well as the possible side effects. The study included 42 Relapsing-Remitting MS blood samples, of which 30 were classified as responders after two years of FINGO treatment, whereas 12 patients were Not-Responders. For fifteen patients, samples were collected at four time points: before starting the therapy; at six months after the initiation; at twelve months after; and at twenty-four months after initiation. The serum was analysed through Nuclear Magnetic Resonance and multivariate and univariate statistical analysis. Considering the single comparison between each time point, it was possible to identify a set of metabolites changing their concentrations based on the drug intake. FINGO influences aminoacidic and energy metabolisms and reduces oxidative stress and the activity of the immune system, both typical features of MS.

Published
2023
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11. Effect of Different Disease-Modifying Therapies on Humoral Response to BNT162b2 Vaccine in Sardinian Multiple Sclerosis Patients

Author

Maristella Pitzalis, Maria Laura Idda, Valeria Lodde, Annalisa Loizedda, Monia Lobina, Magdalena Zoledziewska, Francesca Virdis, Giuseppe Delogu, Federica Pirinu, Maria Giuseppina Marini, Maura Mingoia, Jessica Frau, Lorena Lorefice, Marzia Fronza, Daniele Carmagnini, Elisa Carta, Valeria Orrù, Sergio Uzzau, Paolo Solla, Federica Loi, Marcella Devoto, Maristella Steri, Edoardo Fiorillo, Matteo Floris, Ignazio Roberto Zarbo, Eleonora Cocco, and Francesco Cucca

Subjects
SARS-CoV-2, multiple sclerosis, humoral immunity, disease-modifying therapy, vaccine efficacy, BNT162b2, Immunologic diseases. Allergy, RC581-607
Abstract

ObjectivesVaccination against COVID-19 is highly recommended to patients affected by multiple sclerosis (MS); however, the impact of MS disease-modifying therapies (DMTs) on the immune response following vaccination has been only partially investigated. Here, we aimed to elucidate the effect of DMTs on the humoral immune response to mRNA-based anti-SARS-CoV-2 vaccines in MS patients.MethodsWe obtained sera from 912 Sardinian MS patients and 63 healthy controls 30 days after the second dose of BNT162b2 vaccine and tested them for SARS-CoV-2 response using anti-Spike (S) protein-based serology. Previous SARS-CoV-2 infection was assessed by anti-Nucleocapsid (N) serology. Patients were either untreated or undergoing treatment with a total of 13 different DMTs. Differences between treatment groups comprised of at least 10 patients were assessed by generalized linear mixed-effects model. Demographic and clinical data and smoking status were analyzed as additional factors potentially influencing humoral immunity from COVID-19 vaccine.ResultsMS patients treated with natalizumab, teriflunomide, azathioprine, fingolimod, ocrelizumab, and rituximab showed significantly lower humoral responses compared to untreated patients. We did not observe a statistically significant difference in response between patients treated with the other drugs (dimethyl fumarate, interferon, alemtuzumab and glatiramer acetate) and untreated patients. In addition, older age, male sex and active smoking were significantly associated with lower antibody titers against SARS-CoV-2. MS patients previously infected with SARS-CoV-2 had significantly higher humoral responses to vaccine than uninfected patients.ConclusionHumoral response to BNT162b2 is significantly influenced by the specific DMTs followed by patients, as well as by other factors such as previous SARS-CoV-2 infection, age, sex, and smoking status. These results are important to inform targeted strategies to prevent clinically relevant COVID-19 in MS patients.

Published
2021
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12. Sex Hormones as Key Modulators of the Immune Response in Multiple Sclerosis: A Review

Author

Federica Murgia, Florianna Giagnoni, Lorena Lorefice, Paola Caria, Tinuccia Dettori, Maurizio N. D’Alterio, Stefano Angioni, Aran J. Hendren, Pierluigi Caboni, Monica Pibiri, Giovanni Monni, Eleonora Cocco, and Luigi Atzori

Subjects
multiple sclerosis, sex hormones, gender differences, pregnancy, puerperium, Biology (General), QH301-705.5
Abstract

Background: A variety of autoimmune diseases, including MS, amplify sex-based physiological differences in immunological responsiveness. Female MS patients experience pathophysiological changes during reproductive phases (pregnancy and menopause). Sex hormones can act on immune cells, potentially enabling them to modify MS risk, activity, and progression, and to play a role in treatment. Methods: Scientific papers (published between 1998 and 2021) were selected through PubMed, Google Scholar, and Web of Science literature repositories. The search was limited to publications analyzing the hormonal profile of male and female MS patients during different life phases, in particular focusing on sex hormone treatment. Results: Both men and women with MS have lower testosterone levels compared to healthy controls. The levels of estrogens and progesterone increase during pregnancy and then rapidly decrease after delivery, possibly mediating an immune-stabilizing process. The literature examined herein evidences the neuroprotective effect of testosterone and estrogens in MS, supporting further examinations of their potential therapeutic uses. Conclusions: A correlation has been identified between sex hormones and MS clinical activity. The combination of disease-modifying therapies with estrogen or estrogen plus a progestin receptor modulator promoting myelin repair might represent an important strategy for MS treatment in the future.

Published
2022
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13. Infections and Multiple Sclerosis: From the World to Sardinia, From Sardinia to the World

Author

Jessica Frau, Giancarlo Coghe, Lorena Lorefice, Giuseppe Fenu, and Eleonora Cocco

Subjects
multiple sclerosis, Epstein - Barr virus, human endogeneous retrovirus-W, mycobacterium avium subspecies paratuberculosis, infections, genetic, Immunologic diseases. Allergy, RC581-607
Abstract

Multiple Sclerosis (MS) is an inflammatory disease of the central nervous system. Sardinia, an Italian island, is one of the areas with the highest global prevalence of MS. Genetic factors have been widely explored to explain this greater prevalence among some populations; the genetic makeup of the Sardinians appears to make them more likely to develop autoimmune diseases. A strong association between MS and some infections have been reported globally. The most robust evidence indicating the role of infections is MS development concerns the Epstein-Barr virus (EBV). Anti-EBV antibodies in patients once infected by EBV are associated with the development of MS years later. These features have also been noted in Sardinian patients with MS. Many groups have found an increased expression of the Human endogenous retroviruses (HERV) family in patients with MS. A role in pathogenesis, prognosis, and prediction of treatment response has been proposed for HERV. A European multi-centre study has shown that their presence was variable among populations, ranging from 59% to 100% of patients, with higher HERV expression noted in Sardinian patients with MS. The mycobacterium avium subspecies paratuberculosis (MAP) DNA and antibodies against MAP2694 protein were found to be associated with MS in Sardinian patients. More recently, this association has also been reported in Japanese patients with MS. In this study, we analysed the role of infectious factors in Sardinian patients with MS and compared it with the findings reported in other populations.

Published
2021
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14. Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies

Author

Maria Pia Sormani, Matilde Inglese, Irene Schiavetti, Luca Carmisciano, Alice Laroni, Caterina Lapucci, Giorgio Da Rin, Carlo Serrati, Ilaria Gandoglia, Tiziana Tassinari, Germana Perego, Giampaolo Brichetto, Paola Gazzola, Antonio Mannironi, Maria Laura Stromillo, Cinzia Cordioli, Doriana Landi, Marinella Clerico, Elisabetta Signoriello, Jessica Frau, Maria Teresa Ferrò, Alessia Di Sapio, Livia Pasquali, Monica Ulivelli, Fabiana Marinelli, Graziella Callari, Rosa Iodice, Giuseppe Liberatore, Francesca Caleri, Anna Maria Repice, Susanna Cordera, Mario Alberto Battaglia, Marco Salvetti, Diego Franciotta, Antonio Uccelli, Alessandro Maglione, Alessio Signori, Aniello Iovino, Carolina Gabri Nicoletti, Chiara Rosa Mancinelli, Daiana Bezzini, Daniele Carmagnini, Davide Brogi, Eduardo Nobile Orazio, Eleonora Cocco, Enri Nako, Ester Assandri, Federica Baldi, Filippo Ansaldi, Francesca Bovis, Gabriele Siciliano, Gaia Cola, Giacomo Lus, Giancarlo Icardi, gianmarco bellucci, Girolama Alessandra Marfia, Giulia Vazzoler, Giuseppe Trivelli, Ilaria Maietta, Laura Sticchi, Lorena Lorefice, Lucia Ruggiero, Marcello Manzino, Margherita Monti Bragadin, Maria Chiara Buscarinu, Maria Gagliardi, Maria Teresa Rilla, Marta Ponzano, Marzia Fronza, Massimo Del Sette, Matteo Scialabba, Michele Bedognetti, Nicola De Rossi, Nicola De Stefano, Rachele Bigi, Raffaele Dubbioso, Roberta Reniè, Sabrina Fabbri, Sarah Rasia, Simona Rolla, Stefan Platzgummer, and Valentina Carlini

Subjects
Multiple sclerosis, Coronavirus, Immunomodulatory therapies, Medicine, Medicine (General), R5-920
Abstract

Background: In patients with Multiple Sclerosis (pwMS) disease-modifying therapies (DMTs) affects immune response to antigens. Therefore, post-vaccination serological assessments are needed to evaluate the effect of the vaccine on SARS-CoV-2 antibody response. Methods: We designed a prospective multicenter cohort study enrolling pwMS who were scheduled for SARS-Cov-2 vaccination with mRNA vaccines (BNT162b2, Pfizer/BioNTech,Inc or mRNA-1273, Moderna Tx,Inc). A blood collection before the first vaccine dose and 4 weeks after the second dose was planned, with a centralized serological assessment (electrochemiluminescence immunoassay, ECLIA, Roche-Diagnostics). The log-transform of the antibody levels was analyzed by multivariable linear regression. Findings: 780 pwMS (76% BNT162b2 and 24% mRNA-1273) had pre- and 4-week post-vaccination blood assessments. 87 (11·2%) were untreated, 154 (19·7%) on ocrelizumab, 25 (3·2%) on rituximab, 85 (10·9%) on fingolimod, 25 (3·2%) on cladribine and 404 (51·7%) on other DMTs. 677 patients (86·8%) had detectable post-vaccination SARS-CoV-2 antibodies. At multivariable analysis, the antibody levels of patients on ocrelizumab (201-fold decrease (95%CI=128–317), p

Published
2021
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15. The Dimethyl Fumarate Experience: A Handy Drug With Broad Clinical Utility

Author

Lorena Lorefice, Elisa Casaglia, Marzia Fronza, Jessica Frau, Giuseppe Fenu, Silvy Pilotto, Giancarlo Coghe, Maria A. Barracciu, and Eleonora Cocco

Subjects
multiple sclerosis, dimethyl fumarate, real world study, efficacy, NEDA 3, Neurology. Diseases of the nervous system, RC346-429
Abstract

Objectives: The aim of this study was to characterize multiple sclerosis (MS) patients exposed to dimethyl fumarate (DMF) and to evaluate the predictors of therapeutic response. In addition, the study offers a picture of how DMF use has changed over the past few years in naive or switcher patients.Methods: In this observational monocentric study, we examined the prescription flow of DMF in MS patients categorized as naive or switchers (for safety/tolerability, ineffectiveness, and de-escalation strategy) from 2015 to 2019. Clinical and magnetic resonance imaging data of DMF-treated patients were analyzed, and NEDA-3 status at 24 months was evaluated by the three assessment components (absence of clinical relapses, no Expanded Disability Status Scale progression, no radiological activity). Determinants of therapeutic response were also evaluated using regression analysis.Results: The sample included 595 MS patients exposed to DMF categorized as naive (158; 26.5%) and switchers for reasons of safety/tolerability (198; 33.3%), inefficacy (175; 29.4%), and de-escalation strategy (64; 10.8%). A 15% increase in DMF use in naive and horizontal shift groups was observed in the last 3 years of observation, whereas there was a drop, with prescription passed from ~20% to

Published
2021
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16. Brain Volume and Perception of Cognitive Impairment in People With Multiple Sclerosis and Their Caregivers

Author

Giuseppe Fenu, Lorena Lorefice, Elisa Carta, Mauro Arru, Alice Carta, Marzia Fronza, Giancarlo Coghe, Jessica Frau, Franco Contu, Maria Antonietta Barracciu, and Eleonora Cocco

Subjects
multiple sclerosis, cognitive impairment, caregiver, brain volume, patients, Neurology. Diseases of the nervous system, RC346-429
Abstract

Background: Cognitive impairment (CI) is common in people with multiple sclerosis (pwMS). The assessment of CI is based on neuropsychological tests and accurate anamnesis, involving the patients and caregivers (CG). This study aimed to assess the complex interplay between self-perception of CI, objective CI and the brain atrophy of MS patients, also exploring the possible differences with CI evaluated by caregivers.Methods: Relapsing pwMS were enrolled in this study. Subjects underwent neuropsychological examination using the Brief Cognitive Assessment for Multiple Sclerosis (BICAMS) and evaluation of self-reported cognitive status using the patient-version of the Multiple Sclerosis Neuropsychological Questionnaire (p-MSNQ). Depression and anxiety were also evaluated using the Back Depression Inventory-version II (BDI-II) and Zung Anxiety Scale. Brain MRI images were acquired and brain volumes estimated. For each patient that was enrolled, we spoke to a caregiver and collected their perception of the patient's CI using the MSNQ- Caregiver version.Results: Ninety-five MS subjects with their caregivers were enrolled. CI was detected in 51 (53.7%) patients. We found a significant correlation (p < 0.001) between BICAMS T scores and lower whole brain (Rho = 0.51), gray matter (Rho = 0.54), cortical gray matter (Rho = 0.51) volumes and lower p-MSNQ (Rho = 0.31), and cg-MSNQ (Rho = 0.41) scores. Multivariate logistic regression showed that p-MSNQ is related to a patient's anxiety to evaluate by Zung Score (p < 0.001) while cg-MSNQ to patient's brain volume (p = 0.01).Conclusion: Our data confirm that neuropsychological evaluation results are related to the perception of CI and brain volume measures and highlight the importance of the caregiver's perception for cognitive assessment of pwMS.

Published
2021
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17. A cross-sectional and longitudinal study evaluating brain volumes, RNFL, and cognitive functions in MS patients and healthy controls

Author

Jessica Frau, Giuseppe Fenu, Alessio Signori, Giancarlo Coghe, Lorena Lorefice, Maria Antonietta Barracciu, Vincenzo Sechi, Federico Cabras, Mauro Badas, Maria Giovanna Marrosu, and Eleonora Cocco

Subjects
Multiple sclerosis, Brain volume, Retinal nerve Fiber layer thickness, Cognitive impairments, BICAMS, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background The principal biomarker of neurodegeneration in multiple sclerosis (MS) is believed to be brain volume, which is associated with cognitive functions and retinal nerve fibre layer (RNFL). A cross-sectional and longitudinal assessment of the relationship between RNFL, cognitive functions and brain volume. Methods At baseline, relapsing patients and healthy controls underwent 1.5 T MRI to estimate the normalized volume of brain (NBV), grey (NGV), white (NWV) and peripheral grey (pNGV) matter. Cognitive functions were evaluated by BICAMS, RNFL by Spectral-Domain OCT. Patients were re-evaluated after 12 months. Results Cognitive functions, brain volume, and RNFL differed between the group of 66 patients and that of 16 healthy controls. In the MS group, at baseline, an association was found between: p-NGV and symbol-digit (SDMT) (p = 0.022); temporal-RNFL and NBV (p = 0.007), NWV (p = 0.012), NGV (p = 0.048), and p-NGV (p = 0.021); papillo-macular bundle-RNFL and NBV (p = 0.013), NWV (p = 0.02), NGV (p = 0.049), and p-NGV (p = 0.032). Over the observational period, we found a reduction of brain volume (p

Published
2018
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18. Is There Any Relationship between Upper and Lower Limb Impairments in People with Multiple Sclerosis? A Kinematic Quantitative Analysis

Author

Giancarlo Coghe, Federica Corona, Giuseppina Pilloni, Micaela Porta, Jessica Frau, Lorena Lorefice, Giuseppe Fenu, Eleonora Cocco, and Massimiliano Pau

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Background. In people with multiple sclerosis (pwMS), disability is generally assessed on the basis of ambulation abilities, whereas upper limb motor dysfunctions are less frequently considered. Nevertheless, they can severely affect the quality of life of pwMS. To date, it remains mostly unknown whether a relationship exists between upper and lower limb impairments. Aim. To investigate the existence of a relationship between upper and lower limb impairments in pwMS based on two fundamental motor tasks, namely walking and hand-to-mouth (HTM) movement. Methods. Twenty-eight pwMS with Expanded Disability Status Scale (EDSS) scores in the range of 1–6, and 21 healthy controls (HC) underwent a kinematic analysis of gait and HTM movement performed with a motion capture system. The spatiotemporal parameters for the two tasks were calculated and correlated using Spearman’s rank correlation coefficients. Results. The pwMS performed worse than HC on both tasks. Small to large correlations were found between the total HTM movement duration and most of the gait parameters (rho, 0.35–0.68; p

Published
2019
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19. Is Geo-Environmental Exposure a Risk Factor for Multiple Sclerosis? A Population-Based Cross-Sectional Study in South-Western Sardinia.

Author

Maria Cristina Monti, Davide Guido, Cristina Montomoli, Claudia Sardu, Alessandro Sanna, Salvatore Pretti, Lorena Lorefice, Maria Giovanna Marrosu, Paolo Valera, and Eleonora Cocco

Subjects
Medicine, Science
Abstract

BACKGROUND:South-Western Sardinia (SWS) is a high risk area for Multiple Sclerosis (MS) with high prevalence and spatial clustering; its population is genetically representative of Sardinians and presents a peculiar environment. We evaluated the MS environmental risk of specific heavy metals (HM) and geographical factors such as solar UV exposure and urbanization by undertaking a population-based cross-sectional study in SWS. METHODS:Geochemical data on HM, UV exposure, urbanization and epidemiological MS data were available for all SWS municipalities. Principal Component Analysis (PCA) was applied to the geochemical data to reduce multicollinearity and confounding criticalities. Generalized Linear Mixed Models (GLMM) were applied to evaluate the causal effects of the potential risk factors, and a model selection was performed using Akaike Information Criterion. RESULTS:The PCA revealed that copper (Cu) does not cluster, while two component scores were extracted: 'basic rocks', including cobalt, chromium and nickel, and 'ore deposits', including lead and zinc. The selected multivariable GLMM highlighted Cu and sex as MS risk factors, adjusting for age and 'ore deposits'. When the Cu concentration increases by 50 ppm, the MS odds are 2.827 (95% CI: 1.645; 5.07) times higher; females have a MS odds 2.04 times (95% CI: 1.59; 2.60) higher than males. CONCLUSIONS:The high frequency of MS in industrialized countries, where pollution by HM and CO poisoning is widespread, suggests a relationship between environmental exposure to metals and MS. Hence, we suggested a role of Cu homeostasis in MS. This is a preliminary study aimed at generating hypotheses that will need to be confirmed further.

Published
2016
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20. Interaction between HLA-DRB1-DQB1 haplotypes in Sardinian multiple sclerosis population.

Author

Eleonora Cocco, Raffaele Murru, Gianna Costa, Amit Kumar, Enrico Pieroni, Cristina Melis, Luigi Barberini, Claudia Sardu, Lorena Lorefice, Giuseppe Fenu, Jessica Frau, Giancarlo Coghe, Nicola Carboni, and Maria Giovanna Marrosu

Subjects
Medicine, Science
Abstract

We performed a case-control study in 2,555 multiple sclerosis (MS) Sardinian patients and 1,365 healthy ethnically matched controls, analyzing the interactions between HLA-DRB1-DQB1 haplotypes and defining a rank of genotypes conferring a variable degree of risk to the disease. Four haplotypes were found to confer susceptibility (*13:03-*03:01 OR = 3.3, Pc 5.1 × 10(-5), *04:05-*03:01 OR = 2.1, Pc 9.7 × 10(-8), *15:01-*06:02 OR = 2.0, Pc = 9.1 × 10(-3), *03:01-*02:01 OR = 1.7 Pc = 7.9 × 10(-22)) and protection (*11, OR = 0.8, Pc = 2.7 × 10(-2), *16:01-*05:02 OR = 0.6, Pc = 4.8 × 10(-16), *14:01-4-*05:031 = OR = 0.5, Pc = 9.8 × 10(-4) and *15:02-*06:01 OR = 0.4, Pc = 5.1 × 10(-4)). The relative predispositional effect method confirms all the positively associated haplotypes and showed that also *08 and *04 haplotypes confers susceptibility, while the *11 was excluded as protective haplotype. Genotypic ORs highlighted two typologies of interaction between haplotypes: i) a neutral interaction, in which the global risk is coherent with the sum of the single haplotype risks; ii) a negative interaction, in which the genotypic OR observed is lower than the sum of the OR of the two haplotypes. The phylogenic tree of the MS-associated DRB1 alleles found in Sardinian patients revealed a cluster represented by *14:01, *04:05, *13∶03, *08:01 and *03:01 alleles. Sequence alignment analysis showed that amino acids near pocket P4 and pocket P9 differentiated protective from predisposing alleles under investigation. Furthermore, molecular dynamics simulation performed on alleles revealed that position 70 is crucial in binding of MBP 85-99 peptide. All together, these data suggest that propensity to MS observed in Sardinian population carried by the various HLA-DRB1-DQB1 molecules can be due to functional peculiarity in the antigen presentation mechanisms.

Published
2013
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21. Vitamin D responsive elements within the HLA-DRB1 promoter region in Sardinian multiple sclerosis associated alleles.

Author

Eleonora Cocco, Alessandra Meloni, Maria Rita Murru, Daniela Corongiu, Stefania Tranquilli, Elisabetta Fadda, Raffaele Murru, Lucia Schirru, Maria Antonietta Secci, Gianna Costa, Isadora Asunis, Stefania Cuccu, Giuseppe Fenu, Lorena Lorefice, Nicola Carboni, Gioia Mura, Maria Cristina Rosatelli, and Maria Giovanna Marrosu

Subjects
Medicine, Science
Abstract

Vitamin D response elements (VDREs) have been found in the promoter region of the MS-associated allele HLA-DRB1*15:01, suggesting that with low vitamin D availability VDREs are incapable of inducing *15:01 expression allowing in early life autoreactive T-cells to escape central thymic deletion. The Italian island of Sardinia exhibits a very high frequency of MS and high solar radiation exposure. We test the contribution of VDREs analysing the promoter region of the MS-associated DRB1 *04:05, *03:01, *13:01 and *15:01 and non-MS-associated *16:01, *01, *11, *07:01 alleles in a cohort of Sardinians (44 MS patients and 112 healthy subjects). Sequencing of the DRB1 promoter region revealed a homozygous canonical VDRE in all *15:01, *16:01, *11 and in 45/73 *03:01 and in heterozygous state in 28/73 *03:01 and all *01 alleles. A new mutated homozygous VDRE was found in all *13:03, *04:05 and *07:01 alleles. Functionality of mutated and canonical VDREs was assessed for its potential to modulate levels of DRB1 gene expression using an in vitro transactivation assay after stimulation with active vitamin D metabolite. Vitamin D failed to increase promoter activity of the *04:05 and *03:01 alleles carrying the new mutated VDRE, while the *16:01 and *03:01 alleles carrying the canonical VDRE sequence showed significantly increased transcriptional activity. The ability of VDR to bind the mutant VDRE in the DRB1 promoter was evaluated by EMSA. Efficient binding of VDR to the VDRE sequence found in the *16:01 and in the *15:01 allele reduced electrophoretic mobility when either an anti-VDR or an anti-RXR monoclonal antibody was added. Conversely, the Sardinian mutated VDRE sample showed very low affinity for the RXR/VDR heterodimer. These data seem to exclude a role of VDREs in the promoter region of the DRB1 gene in susceptibility to MS carried by DRB1* alleles in Sardinian patients.

Published
2012
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22. The impact of PM2.5, PM10 and NO2 on Covid-19 severity in a sample of patients with multiple sclerosis: A case-control study

Author

Gianmarco, Abbadessa, Umberto, Aguglia, Lia, Allegorico, Maria, Allegri Rossi Beatrice, Anastasia, Alteno, Pia, Amato Maria, 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, Vincenzo, Brescia Morra, Giampaolo, Brichetto, Maria, Buccafusca, Elisabetta, Bucciantini, Sebastiano, Bucello, Chiara, Buscarinu Maria, Paola, Cabboi Maria, Massimiliano, Calabrese, Francesca, Calabria, Francesca, Caleri, Federico, Camilli, Maria, Caniatti Luisa, Roberto, Cantello, Marco, Capobianco, Ruggero, Capra, Rocco, Capuano, Luca, Carmisciano, Patrizia, Carta, Paola, Cavalla, Grazia, Celani Maria, Maria, Cellerino, Raffaella, Cerqua, Clara, Chisari, Raffaella, Clerici, Marinella, Clerico, Eleonora, Cocco, Gaia, Cola, Giancarlo, Comi, Paolo, Confalonieri, Antonella, Conte, Zaffira, Conti Marta, Christian, Cordano, Susanna, Cordera, Cinzia, Cordioli, Francesco, Corea, Claudio, Correale, Salvatore, Cottone, Francesco, Crescenzo, Erica, Curti, Alessandro, d'Ambrosio, Emanuele, D'Amico, Chiara, Danni Maura, Alessia, d'Arma, Vincenzo, Dattola, Stefano, de Biase, Giovanna, De Luca, Federica, De Mercanti Stefania, Paolo, De Mitri, Nicola, De Rossi, Nicola, De Stefano, Maria, Della Cava Fabio, Marco, Della Cava, Sonia, Di Lemme, Mario, di Napoli, Alessia, Di Sapio, Renato, Docimo, Anna, Dutto, Luana, Evangelista, Salvatore, Fanara, Roberta, Fantozzi, Diana, Ferraro, Teresa, Ferrò Maria, 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, Grazia, Grasso Maria, Luigi ME, Grimaldi, Angelica, Guareschi, Clara, Guaschino, Simone, Guerrieri, Donata, Guidetti, Barbara, Juergenson Ina, Pietro, Iaffaldano, Antonio, Ianniello, Luigi, Iasevoli, Paolo, Immovilli, Daniele, Imperiale, Teresa, Infante Maria, Matilde, Inglese, Rosa, Iodice, Aniello, Iovino, Giovanna, Konrad, Doriana, Landi, 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, Rosa, Mancinelli Chiara, Luca, Mancinelli, Paolo, Manganotti, Teresa, Maniscalco Giorgia, Vittorio, Mantero, Sabrina, Marangoni, Damiano, Marastoni, Alessandra, Marfia Girolama, 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, Gabri, Nicoletti Carolina, Eduardo, Nobile-Orazio, Agostino, Nozzolillo, Marco, Onofrj, Riccardo, Orlandi, Anna, Palmieri, Damiano, Paolicelli, Livia, Pasquali, Fulvio, Pasquin, 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, Eugenio, Pucci, Marta, Radaelli, Paolo, Ragonese, Sarah, Rasia, Sabrina, Realmuto, Anna, Repice, Eleonora, Rigoni, Teresa, Rilla Maria, Francesca, Rinaldi, Marcello, Romano Calogero, Marco, Ronzoni, Marco, Rovaris, Francesca, Ruscica, Loredana, Sabattini, Giuseppe, Salemi, Marco, Salvetti, Lorenzo, Saraceno, Alessia, Sartori, Arianna, Sartori, Elvira, Sbragia, Cinzia, Scandellari, Ilaria, Scarano Giuditta, Valentina, Scarano, Irene, Schiavetti, Maria, Sessa, Caterina, Sgarito, Grazia, Sibilia, Gabriele, Siciliano, Alessio, Signori, Elisabetta, Signoriello, Leonardo, Sinisi, Francesca, Sireci, Patrizia, Sola, Claudio, Solaro, Pia, Sormani Maria, Stefano, Sotgiu, Maddalena, Sparaco, Laura, Stromillo Maria, Silvia, Strumia, Laura, Susani Emanuela, Giulietta, Tabiadon, Francesco, Teatini, Gioacchino, Tedeschi, Valentina, Tomassini, Simone, Tonietti, Valentina, Torri Clerici, Carla, Tortorella, Simona, Toscano, Rocco, Totaro, Maria, Trojano, Maria, Trotta, Gabriella, Turano, Monica, Ulivelli, Manzo, Valentino, Giovanna, Vaula, Domizia, Vecchio, Marco, Vercellino, Pinuccia, Verrengia Elena, Marika, Vianello, Eleonora, Virgilio, Francesca, Vitetta, Stefano, Vollaro, Mauro, Zaffaroni, Mauro, Zampolini, Roberto, Zarbo Ignazio, Antonio, Zito, Luigi, Zuliani, Ponzano, Marta, Schiavetti, Irene, Bergamaschi, Roberto, Pisoni, Enrico, Bellavia, Andrea, Mallucci, Giulia, Carmisciano, Luca, Inglese, Matilde, Cordioli, Cinzia, Marfia, Girolama Alessandra, Cocco, Eleonora, Immovilli, Paolo, Pesci, Ilaria, Scandellari, Cinzia, Cavalla, Paola, Radaelli, Marta, Vianello, Marika, Vitetta, Francesca, Montepietra, Sara, Amato, Maria Pia, Fioretti, Cristina, Filippi, Massimo, Sartori, Arianna, Caleri, Francesca, Clerico, Marinella, Gallo, Antonio, Conte, Antonella, Clerici, Raffaella, De Luca, Giovanna, Boneschi, Filippo Martinelli, Cantello, Roberto, Calabrese, Massimiliano, Tortorella, Carla, Rovaris, Marco, Verrengia, Elena Pinuccia, Patti, Francesco, Morra, Vincenzo Brescia, Salvetti, Marco, and Sormani, Maria Pia

Published
2022
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24. 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

25. The impact of PM2.5, PM10 and NO2 on Covid-19 severity in a sample of patients with multiple sclerosis: A case-control study

Author

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

Published
2022
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26. The impact of cognitive impairment on Health-Related Quality of Life in Systemic Lupus Erythematosus: a cross-sectional study

Author

Giulia Costanzo, Lorena Lorefice, Davide Firinu, Elisa Carta, Giuseppe Murgia, Maria Rita Messina, Mario Torrazza, Carlotta Locci, Maria Pina Barca, Stefano Del Giacco, Eleonora Cocco, and Giuseppe Fenu

Abstract

Purpose: To correlate the cognitive functions evaluated by the Symbol Digit Modalities Test (SDMT)with the principal clinical features and Health-related Quality of Life (HRQoL) measures of SLE. Material and methods: We recruited consecutive outpatients with SLE from a third-level Lupus Clinic in Italy to undergo neuropsychological evaluation using SDMT and the LupusQoL-IT as HRQoL questionnaire. Patients were defined as either neuropsychiatric-SLE (NPSLE) or as non-neuropsychiatric-SLE (non-NPSLE); they were also classified as cognitive-impaired and cognitive-preserved based on SDMT score alteration corrected for age, gender and education. In this cross-sectional study we included and studied 140 consecutive patients; 30 patients had NPSLE. Inclusion criteria were 4 or more ACR criteria for SLE, exclusion criteria were non–italian speaking, ocular disease interfering with reading capacity, the onset of any major medical condition (e.g. requiring hospitalization) or overt new neuropsychiatric event within the study period. Results: The mean SDMT score was 41.4±12.8. Alteration of SDMT score was detected in 29.9% of patients. Pearson test showed a correlation between SDMT score and Systemic Lupus International Collaborating Clinics/ACR Damage Index (SLICC/ACR-SDI) score (r:-0.373, p< 0.001) and specific HRQoL domains. Cognitive-impaired and cognitive-preserved patients showed a significant difference in physical health (p=0.03), pain (p=0.04) and planning (p=0.02) domains of the HRQol. A multiple linear regression (dependent variable: SDMT score) revealed a relationship with SLICC/ACR-SDI (p=0.005) and with other clinical features, after adjustment. SDMT score was significantly more frequently altered among patients with NPSLE (p=0.009) and the mean was significantly different in comparison to non-NPSLE patients (p=0.01). Conclusions: Our data demonstrate the correlation between cognitive impairment captured using SDMT and HRQoL of SLE patients and show a correlation of measures such as SLICC/ACR-SDI with SDMT score.

Published
2023

27. Effects of Pregnancy and Breastfeeding on Clinical Outcomes and MRI Measurements of Women with Multiple Sclerosis: An Exploratory Real-World Cohort Study

Author

M.A. Barracciu, Marzia Fronza, Eleonora Cocco, Lorena Lorefice, Jessica Frau, Federica Murgia, Stefano Angioni, Giuseppe Fenu, Maurizio Nicola D'Alterio, and Giancarlo Coghe

Subjects
Pregnancy, medicine.medical_specialty, Neurology, medicine.diagnostic_test, business.industry, Obstetrics, Multiple sclerosis, Breastfeeding, Magnetic resonance imaging, Disease, medicine.disease, Cohort, medicine, Neurology (clinical), business, Cohort study
Abstract

Pregnancy represents an important event for women with multiple sclerosis (MS) and is often accompanied by post-partum disease reactivation. To date, the influence of this reproductive phase on long-term MS outcomes is still largely unexplored. The objective of the study was characterise a large real-world cohort of women with MS to evaluate the effects of pregnancy and breastfeeding on short- and long-term clinical and magnetic resonance imaging (MRI) outcomes while exploring the relationships with MRI measurements of brain atrophy. MS patients with and without pregnancy were recruited. Clinical relapses and MRI activity of the year before conception versus the year after delivery were evaluated. Regression models were performed to investigate the relationships between long-term MS outcomes (EDSS score and MRI brain measurements obtained by SIENAX software) and pregnancy and breastfeeding duration. Two hundred ten women with MS were enrolled; of them, 129 (61.4%) had at least one pregnancy. Of all pregnancies (n = 212), those that occurred after MS onset (90 [42.4%]) were examined to evaluate the short-term outcomes. A higher annualised relapse rate in the post-partum year versus the pre-conception year (0.54 ± 0.84 vs. 0.45 ± 0.71; p = 0.04) was observed. A regression analysis showed that clinical activity after delivery was associated with clinical activity of the year before conception (p = 0.001) as well as duration of breastfeeding (p = 0.022). Similarly, post-partum MRI activity was associated with pre-conception MRI activity (p = 0.026) and shorter breastfeeding duration (p = 0.013). Regarding long-term outcomes, having had at least one pregnancy during MS was associated with a lower EDSS score (p = 0.021), while no relationships were reported with MRI measurements. Conversely, a breastfeeding duration > 6 months was associated with lower white matter volume (p = 0.008). Our study underlines the importance of considering the effects of pregnancy and breastfeeding on short- and long-term MS outcomes. In the current therapeutic landscape, pregnancy planning and treatment optimisation in the post-partum period, in particular for women who choose to breastfeed, are fundamental for the management of these biological phases so central in a woman’s life.

Published
2021

28. The impact of the secondary infections in ICU patients affected by COVID-19 during three different phases of the SARS-CoV-2 pandemic

Author

Federica Murgia, Maura Fiamma, Silvia Serra, Giulia Marras, Raul Argiolas, Chiara Mattana, Maria Grazia Mattu, Maria Cristina Garau, Sonia Doneddu, Sabrina Olla, Eleonora Cocco, Lorena Lorefice, Sandro Muntoni, Peppino Paffi, Stefano Porru, Marta Abis, Saverio Bellizzi, Antonello Pani, Andrea Angioi, Michele Mussap, Orietta Massidda, Franco Carta, and Luigi Atzori

Abstract

Purpose Microbial secondary infections can contribute to an increase in the risk of mortality in COVID-19 patients, particularly in case of severe diseases. In this study, we collected and evaluated the clinical, laboratory and microbiological data of COVID-19 critical ill patients requiring intensive care (ICU) to evaluate the significance and the prognostic value of these parameters. Methods One hundred seventy-eight ICU patients with severe COVID-19, hospitalized at the S. Francesco Hospital of Nuoro (Italy) in the period from March 2020 to May 2021, were enrolled in this study. Clinical data and microbiological results were collected. Blood chemistry parameters, relative to three different time points, were analyzed through multivariate and univariate statistical approaches. Results Seventy-four percent of the ICU COVID-19 patients had a negative outcome, while 26% had a favorable prognosis. A correlation between the laboratory parameters and days of hospitalization of the patients was observed with significant differences between the two groups. Moreover, Staphylococcus aureus, Enterococcus faecalis, Candida spp, Pseudomonas aeruginosa and Klebsiella pneumonia were the most frequently isolated microorganisms from all clinical specimens. Conclusions Secondary infections play an important role in the clinical outcome. The analysis of the blood chemistry tests was found useful in monitoring the progression of COVID-19.

Published
2022

29. An Overview of the Efficacy and Safety of Ozanimod for the Treatment of Relapsing Multiple Sclerosis

Author

Marzia Fronza, Lorena Lorefice, Jessica Frau, and Eleonora Cocco

Subjects
Sphingosine 1 Phosphate Receptor Modulators, safety, 0301 basic medicine, Ozanimod, Central nervous system, Administration, Oral, Pharmaceutical Science, Inflammation, Review, Disease, Bioinformatics, 03 medical and health sciences, chemistry.chemical_compound, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, disease modifying therapy, Drug Discovery, medicine, Animals, Humans, Young adult, Pharmacology, Oxadiazoles, business.industry, Multiple sclerosis, Neurodegeneration, Inflammatory Bowel Diseases, medicine.disease, Ulcerative colitis, 030104 developmental biology, medicine.anatomical_structure, chemistry, S1PR modulators, 030220 oncology & carcinogenesis, Indans, medicine.symptom, business, brain atrophy
Abstract

Multiple sclerosis (MS) is a complex disease of the central nervous system that can cause permanent disability in young adults. A large armamentarium is available for its management and is increasing over time. Ozanimod is an oral drug belonging to the sphingosine-1-phosphate receptor (S1PR) modulator family recently approved in different countries for MS with active disease. It selectively modulates S1PR1 and S1PR5 to prevent autoreactive lymphocytes from entering the central nervous system (CNS), where they can determine inflammation and neurodegeneration. Ozanimod was tested in one Phase II and two Phase III pivotal trials and was shown to be effective and well tolerated. Moreover, further investigations, including comparative trials with other S1P modulators and MS disease-modifying drugs, are needed to better define placement in MS treatment. Furthermore, ozanimod is currently under evaluation for inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease, in international phase III studies. This article retraces the itinerary leading to the approval of ozanimod for MS treatment and its peculiarities and potentiality inside the S1PR modulator family.

Published
2021

30. Symptomatic COVID-19 course and outcomes after three mRNA vaccine doses in multiple sclerosis patients treated with high-efficacy DMTs

Author

Rocco Capuano, Luca Prosperini, Manuela Altieri, Lorena Lorefice, Roberta Fantozzi, Paola Cavalla, Clara Guaschino, Marta Radaelli, Cinzia Cordioli, Viviana Nociti, Laura Boffa, Paolo Ragonese, Maria Di Gregorio, Federica Pinardi, Valentina Torri Clerici, Giovanna De Luca, Alberto Gajofatto, Damiano Paolicelli, Carla Tortorella, Claudio Gasperini, Claudio Solaro, Eleonora Cocco, Alvino Bisecco, and Antonio Gallo

Subjects
Neurology, ocrelizumab, third booster vaccine dose, Neurology (clinical), COVID-19 course, fingolimod, multiple sclerosis, COVID-19 outcomes
Abstract

Background: Little is known about COVID-19 course and outcomes after a third booster dose of mRNA vaccine against SARS-CoV-2 (mRNA-Vax) in patients with multiple sclerosis (pwMS) treated with ocrelizumab (OCR) and fingolimod (FNG), which showed a weakened immune response to mRNA-vax. Objectives: The aim of this study was to evaluate COVID-19 course and outcomes in pwMS on OCR and FNG after receiving the third dose of mRNA-Vax and to compare it with pwMS on natalizumab (NTZ). Methods: Inclusion criteria: >18 years of age, being treated with OCR/FNG/NTZ since the first mRNA-Vax dose; COVID-19 after a third booster dose of mRNA-Vax; no steroids use. Results: Overall, 290 pwMS (79 NTZ, 126 OCR, and 85 FNG) from 17 Italian MS centers were included. Age, Expanded Disability Status Scale (EDSS) score, MS phenotype, disease, and treatment duration were significantly different across groups. PwMS who had COVID-19 on OCR and FNG compared with those on NTZ were slightly more symptomatic with higher hospitalization rates (11.1% vs 7.1% vs 1.3%, respectively). Regression models showed that the majority of the differences observed were not related to the disease-modifying treatments (DMTs) used. No fatal cases were observed. Conclusion: Our results support the effectiveness of the third booster dose of mRNA-Vax against severe forms of COVID-19 in pwMS treated with OCR and FNG.

Published
2023

32. Exposure to natalizumab throughout pregnancy: effectiveness and safety in an Italian cohort of women with multiple sclerosis

Author

Doriana Landi, Francesca Bovis, Alfonso Grimaldi, Pietro Osvaldo Annovazzi, Antonio Bertolotto, Alessia Bianchi, Giovanna Borriello, Vincenzo Brescia Morra, Sebastiano Bucello, Maria Chiara Buscarinu, Francesca Caleri, Marco Capobianco, Ruggero Capra, Maria Cellerino, Diego Centonze, Raffaella Cerqua, Clara Grazia Chisari, Marinella Clerico, Eleonora Cocco, Gaia Cola, Cinzia Cordioli, Erica Curti, Alessandro d'Ambrosio, Emanuele D'Amico, Giovanna De Luca, Massimiliano Di Filippo, Sonia Di Lemme, Roberta Fantozzi, Diana Ferraro, Elisabetta Ferraro, Antonio Gallo, Claudio Gasperini, Franco Granella, Matilde Inglese, Roberta Lanzillo, Lorena Lorefice, Giacomo Lus, Simona Malucchi, Monica Margoni, Giorgia Mataluni, Massimiliano Mirabella, Lucia Moiola, Carolina Gabri Nicoletti, Viviana Nociti, Francesco Patti, Federica Pinardi, Emilio Portaccio, Carlo Pozzilli, Paolo Ragonese, Sarah Rasia, Giuseppe Salemi, Elisabetta Signoriello, Francesca Vitetta, Rocco Totaro, Maria Pia Sormani, Maria Pia Amato, Girolama Alessandra Marfia, Landi, Doriana, Bovis, Francesca, Grimaldi, Alfonso, Annovazzi, Pietro Osvaldo, Bertolotto, Antonio, Bianchi, Alessia, Borriello, Giovanna, Brescia Morra, Vincenzo, Bucello, Sebastiano, Buscarinu, Maria Chiara, Caleri, Francesca, Capobianco, Marco, Capra, Ruggero, Cellerino, Maria, Centonze, Diego, Cerqua, Raffaella, Chisari, Clara Grazia, Clerico, Marinella, Cocco, Eleonora, Cola, Gaia, Cordioli, Cinzia, Curti, Erica, d'Ambrosio, Alessandro, D'Amico, Emanuele, De Luca, Giovanna, Di Filippo, Massimiliano, Di Lemme, Sonia, Fantozzi, Roberta, Ferraro, Diana, Ferraro, Elisabetta, Gallo, Antonio, Gasperini, Claudio, Granella, Franco, Inglese, Matilde, Lanzillo, Roberta, Lorefice, Lorena, Lus, Giacomo, Malucchi, Simona, Margoni, Monica, Mataluni, Giorgia, Mirabella, Massimiliano, Moiola, Lucia, Nicoletti, Carolina Gabri, Nociti, Viviana, Patti, Francesco, Pinardi, Federica, Portaccio, Emilio, Pozzilli, Carlo, Ragonese, Paolo, Rasia, Sarah, Salemi, Giuseppe, Signoriello, Elisabetta, Vitetta, Francesca, Totaro, Rocco, Sormani, Maria Pia, Amato, Maria Pia, Marfia, Girolama Alessandra, and D'Ambrosio, Alessandro

Subjects
Psychiatry and Mental health, Settore MED/26 - NEUROLOGIA, obstetrics, multiple sclerosi, obstetric, Surgery, Neurology (clinical), MRI, multiple sclerosis, Settore MED/26
Abstract

ObjectiveAssessing the risk of clinical and radiological reactivation during pregnancy and post partum in women with multiple sclerosis (MS) treated with natalizumab (NTZ) throughout pregnancy (LONG_EXP) compared with women interrupting treatment before (NO_EXP) and within >−30 days and ≤90 days from conception (SHORT_EXP), and describing newborns’ outcomes.MethodsMaternal clinical and radiological outcomes and obstetric and fetal outcomes were retrospectively collected and compared among groups (NO_EXP, SHORT_EXP, LONG_EXP). Predictors of clinical and radiological reactivation were investigated through univariable and multivariable analysis.Results170 eligible pregnancies from 163 women referring to 29 Italian MS centres were included. Annualised relapse rate (ARR) was significantly lower in LONG_EXP (n=66, 0.02 (0.001–0.09)) compared with NO_EXP (n=31, 0.43 (0.21–0.75), p=0.002) and SHORT_EXP (n=73, 0.46 (0.30–0.66), p=0.0004) during pregnancy, and in LONG_EXP (0.12 (0.05–0.24)) compared with SHORT_EXP (0.30 (0.17–0.50), p=0.008) during post partum. Gadolinium-enhancing (Gd+) lesions were less frequent in LONG_EXP (n=6/50, 2.00%) compared with NO_EXP (n=9/21, 42.86%) and SHORT_EXP after delivery (n=17/49, 34.69%, p=0.010).Delaying NTZ resumption after delivery significantly increased the risk of relapses (OR=1.29 (95% CI 1.07 to 1.57), p=0.009) and Gd+ lesions (OR=1.49 (95% CI 1.17 to 1.89, p=0.001). Newborns’ weight, length, head circumference and gestational age did not differ among groups after adjusting for confounders. Anaemia was tracked in 4/69 LONG_EXP newborns. Congenital anomaly rate was within the expected range for the untreated MS population.ConclusionsOur findings indicate that in women with MS treated with NTZ before conception, continuation of NTZ throughout pregnancy and its early resumption after delivery mitigate the risk of clinical and radiological reactivation. This approach has no major impact on newborns’ outcomes.

Published
2022

33. The impact of secondary infections in COVID-19 critically ill patients

Author

Federica Murgia, Maura Fiamma, Silvia Serra, Sabrina Olla, Maria Cristina Garau, Eleonora Cocco, Lorena Lorefice, Sandro Muntoni, Peppino Paffi, Stefano Porru, Marta Abis, Gabriele Finco, Saverio Bellizzi, Orietta Massidda, Franco Carta, and Luigi Atzori

Subjects
Microbiology (medical), Intensive Care Units, Infectious Diseases, Coinfection, SARS-CoV-2, Critical Illness, COVID-19, Humans
Published
2022

34. Relationship between CSF tau biomarkers and structural brain MRI measures in frontotemporal lobar degeneration

Author

Giuseppe Fenu, Valentina Oppo, Giulia Serra, Lorena Lorefice, Francesca Di Sfefano, Dario Deagostini, Cristina Mancosu, Elisabetta Fadda, Cristina Melis, Paolo Siotto, Eleonora Cocco, Maurizio Melis, and Giovanni Cossu

Subjects
Male, Amyloid beta-Peptides, Brain, tau Proteins, Neuroimaging, Middle Aged, Magnetic Resonance Imaging, Neurology, Alzheimer Disease, Frontotemporal Dementia, Humans, Female, Neurology (clinical), Frontotemporal Lobar Degeneration, Biomarkers, Aged
Abstract

Recently in the field neurodegenerative diseases increasing attention has been pointed to CSF biomarkers and their integration with neuroimaging (1). Frontotemporal lobar degeneration (FTLD) refers to a heterogeneous group of clinical syndromes with different underlying proteinopathies including tau pathology. CSF biomarkers have been proposed as diagnostic and prognostic factors. Aim of our study was to evaluate the relationship between CSF tau biomarkers and structural MRI brain measures in FTLD.We included early FTLD patient. All included patients underwent lumbar puncture to evaluate amyloid, total-tau (t-tau), phospho-tau 181 (p-tau); p-tau/t-tau ratio was also calculated; brain MRI was performed to estimate whole brain volume, volume of principal deep grey matter structures and regional cortical thickness.Demographic characteristics of the 28 included patients were as follows: female/male: 9/19; mean ± SD age: 68.1 ± 7.8 years. The p-tau/t-tau ratio was significantly correlated with whole brain volume (r = 0.69; p: 0.001), left putamen volume (r = 0.55 p: 0.009), left pallidum volume (r = 0.41; p: 0.01), right accumbens area (r = 0.47; p: 0.02). P-tau/t tau ratio showed also a significant correlation with cortical thickness of left temporal lobe (r = 0.74; p: 0.001) and right lateral orbital frontal cortex (r = 0.45; p: 0.03). Linear regression showed a significant relationship between p-tau/t-tau ratio and left temporal pole (p = 0.01; rOur data suggest that CSF biomarkers, especially p-tau/t-tau ratio, could play a role as prognostic factor in FTLD. Further longitudinal investigations are needed to confirm these findings.

Published
2022

35. Infections and Multiple Sclerosis: From the World to Sardinia, From Sardinia to the World

Author

Giancarlo Coghe, Jessica Frau, Eleonora Cocco, Lorena Lorefice, and Giuseppe Fenu

Subjects
Epstein-Barr Virus Infections, Herpesvirus 4, Human, human endogeneous retrovirus-W, Treatment response, Mini Review, Immunology, Autoimmunity, Disease, Biology, Global Health, multiple sclerosis, medicine.disease_cause, Risk Assessment, Virus, Pathogenesis, Sardinia (Italy), Risk Factors, mycobacterium avium subspecies paratuberculosis, Paratuberculosis, medicine, Humans, Immunology and Allergy, infections, Epstein - Barr virus, Multiple sclerosis, Endogenous Retroviruses, RC581-607, Prognosis, medicine.disease, biology.organism_classification, Epstein–Barr virus, Mycobacterium avium subspecies paratuberculosis, Mycobacterium avium subsp. paratuberculosis, Italy, Host-Pathogen Interactions, biology.protein, genetic, Immunologic diseases. Allergy, Antibody, Retroviridae Infections
Abstract

Multiple Sclerosis (MS) is an inflammatory disease of the central nervous system. Sardinia, an Italian island, is one of the areas with the highest global prevalence of MS. Genetic factors have been widely explored to explain this greater prevalence among some populations; the genetic makeup of the Sardinians appears to make them more likely to develop autoimmune diseases. A strong association between MS and some infections have been reported globally. The most robust evidence indicating the role of infections is MS development concerns the Epstein-Barr virus (EBV). Anti-EBV antibodies in patients once infected by EBV are associated with the development of MS years later. These features have also been noted in Sardinian patients with MS. Many groups have found an increased expression of the Human endogenous retroviruses (HERV) family in patients with MS. A role in pathogenesis, prognosis, and prediction of treatment response has been proposed for HERV. A European multi-centre study has shown that their presence was variable among populations, ranging from 59% to 100% of patients, with higher HERV expression noted in Sardinian patients with MS. The mycobacterium avium subspecies paratuberculosis (MAP) DNA and antibodies against MAP2694 protein were found to be associated with MS in Sardinian patients. More recently, this association has also been reported in Japanese patients with MS. In this study, we analysed the role of infectious factors in Sardinian patients with MS and compared it with the findings reported in other populations.

Published
2021

36. Assessing the Metabolomic Profile of Multiple Sclerosis Patients Treated with Interferon Beta 1a by 1H-NMR Spectroscopy

Author

Eleonora Cocco, Maria Rita Murru, Stefania Tranquilli, Luigi Atzori, Federica Murgia, Lorena Lorefice, Jessica Frau, Giuseppe Fenu, Maria Giovanna Marrosu, Giancarlo Coghe, and Andrea Visconti

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Magnetic Resonance Spectroscopy, Multiple Sclerosis, Neurology, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Metabolomics, Internal medicine, Metabolome, Humans, Medicine, Distribution (pharmacology), Pharmacology (medical), Pharmacology, medicine.diagnostic_test, business.industry, Multiple sclerosis, Interferon beta-1a, Magnetic resonance imaging, medicine.disease, Treatment Outcome, 030104 developmental biology, Case-Control Studies, Proton NMR, Original Article, Neurology (clinical), business, Biomarkers, 030217 neurology & neurosurgery, medicine.drug
Abstract

Metabolomic research has emerged as a promising approach to identify potential biomarkers in multiple sclerosis (MS). The aim of the present study was to determine the effect of interferon beta (IFN ß) on the metabolome of MS patients to explore possible biomarkers of disease activity and therapeutic response. Twenty-one MS patients starting IFN ß therapy (Rebif® 44 μg; s.c. 3 times per week) were enrolled. Blood samples were obtained at baseline and after 6, 12, and 24 months of IFN ß treatment and were analyzed by high-resolution nuclear magnetic resonance spectroscopy. Changes in metabolites were analyzed. After IFN ß exposure, patients were divided into responders and nonresponders according to the “no evidence of disease activity” (NEDA-3) definition (absence of relapses, disability progression, and magnetic resonance imaging activity), and samples obtained at baseline were analyzed to evaluate the presence of metabolic differences predictive of IFN ß response. The results of the investigation demonstrated differential distribution of baseline samples compared to those obtained during IFN ß exposure, particularly after 24 months of treatment (R(2)X = 0.812, R(2)Y = 0.797, Q(2) = 0.613, p = 0.003). In addition, differences in the baseline metabolome between responder and nonresponder patients with respect to lactate, acetone, 3-OH-butyrate, tryptophan, citrate, lysine, and glucose levels were found (R(2)X = 0.442, R(2)Y = 0.768, Q(2) = 0.532, p = 0.01). In conclusion, a metabolomic approach appears to be a promising, noninvasive tool that could potentially contribute to predicting the efficacy of MS therapies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-019-00721-8) contains supplementary material, which is available to authorized users.

Published
2019

37. Risk attitude and personality in people with multiple sclerosis facing the choice of different disease-modifying therapy scenarios

Author

Lorena Lorefice, Eleonora Minacapelli, Giancarlo Comi, Eleonora Cocco, Andrea Giordano, Francesca Sangalli, Alessandra Lugaresi, Monica Falautano, Erika Pietrolongo, Vittorio Martinelli, Massimo Filippi, DIPARTIMENTO DI SCIENZE BIOMEDICHE E NEUROMOTORIE, Minacapelli, E., Giordano, A., Falautano, M., Sangalli, F., Pietrolongo, E., Lorefice, L., Cocco, E., Lugaresi, A., Comi, G., Filippi, M., and Martinelli, V.

Subjects
Male, media_common.quotation_subject, Hostility, Neurosis, Disease, Affect (psychology), Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Personality, Disease-modifying therapies, 030212 general & internal medicine, Big Five personality traits, Shared decision-making, media_common, Expanded Disability Status Scale, Aggression, Decision-making, Risk attitude, medicine.disease, Attitude, Italy, Neurology, Impulsive Behavior, Neurology (clinical), medicine.symptom, Psychology, 030217 neurology & neurosurgery, Clinical psychology
Abstract

none 11 no Background: As available disease-modifying therapies (DMTs) increase, evaluating benefit/risk presents greater difficulties, requiring people with MS (PwMS) to play crucial roles in choosing treatment. Although individual attitude toward risk may predict this evaluation, its relation to personality is little studied in MS literature. Objective: To prospectively assess risk attitudes and personality traits of PwMS choosing a DMT. Methods: In three Italian MS centers (2012–2015), 420 PwMS completed an ad hoc questionnaire on socio-demographic variables, personality, and standard-gamble questions, to evaluate MS- and DMT-related risks through two hypothetical drug scenarios. We assessed the influence of previously collected socio-demographic/clinical characteristics, and personality factors on risk attitude. Results: Almost half of participants were mainly concerned about progressive multifocal leukoencephalopathy

Published
2021

38. 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

39. 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

40. Event-related potentials and deep grey matter atrophy in multiple sclerosis: Exploring the possible associations with cognition

Author

Giancarlo Coghe, Lorena Lorefice, G. Marrosu, Giuseppe Fenu, Eleonora Cocco, L. Canalis, E. Carta, Jessica Frau, M.A. Barracciu, R. Mammoliti, Mg Marrosu, and Vincenzo Sechi

Subjects
medicine.medical_specialty, Multiple Sclerosis, Hippocampus, Brain damage, Audiology, Grey matter, Neuropsychological Tests, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Cognition, Multiple Sclerosis, Relapsing-Remitting, Event-related potential, Cortex (anatomy), medicine, Humans, 030212 general & internal medicine, Gray Matter, Evoked Potentials, business.industry, Multiple sclerosis, Neuropsychology, General Medicine, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Neurology, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Background Event-related potentials (ERPs) have been proposed as a neurophysiological biomarker to capture cognitive dysfunction in multiple sclerosis (MS). Few studies have evaluated the relationships between ERPs and brain atrophy as known marker of structural brain damage related to cognitive impairment (CI). Objectives To explore the relationships of brain atrophy, including of the cortex and deep grey matter, with ERP abnormalities and cognitive function, as defined using the Brief Repeatable Battery of Neuropsychological Tests (BRBN). Results Seventy-eight patients with relapsing-remitting MS were enroled, of which 38 (48.7%) had CI. Independent t-test comparisons of the ERP parameters found a significant difference in P300 wave latency, with a latency of 343.7 ± 32.6 ms in the CI group vs. 320.3 ± 16.5 ms in the cognitively preserved (CP) group (p = 0.001). Significant differences in the MRI measurements, including the cortex (p = 0.02) and deep grey matter structures [thalamus (p = 0.001), amygdala (p = 0.030), and nucleus accumbens (p = 0.004)) were observed, with lower measurements in the CI group. Regression models were also performed to explore the impact of brain volumes on ERP parameters. This showed a relationship between P300 latency and the lower amygdala (p = 0.02) and hippocampus (p = 0.03) volumes, while the amplitude of the P300 was significantly associated with a lower cortex volume (p = 0.01). Conclusion Cortex volume emerged as the most significant predictor of the P300 amplitude. The amygdala and hippocampal volumes were found to influence P300 latency, highlighting the role of deep grey matter atrophy in ERPs for the first time. The combination of structural MRI and neurophysiological techniques, sensitive to diverse aspects of MS pathology, could improve the understanding of CI in MS and its neurodegenerative and inflammatory substrate.

Published
2020

41. Brain Volume and Perception of Cognitive Impairment in People With Multiple Sclerosis and Their Caregivers

Author

Marzia Fronza, Alice Carta, Giuseppe Fenu, Lorena Lorefice, Eleonora Cocco, M.A. Barracciu, E. Carta, M. Arru, F. Contu, Giancarlo Coghe, and Jessica Frau

Subjects
Anamnesis, medicine.medical_specialty, business.industry, Multiple sclerosis, Neuropsychology, brain volume, Brief Research Report, medicine.disease, Logistic regression, multiple sclerosis, patients, Atrophy, Neurology, Brain size, medicine, Physical therapy, Anxiety, Neurology. Diseases of the nervous system, Neurology (clinical), medicine.symptom, RC346-429, business, Depression (differential diagnoses), caregiver, cognitive impairment
Abstract

Background: Cognitive impairment (CI) is common in people with multiple sclerosis (pwMS). The assessment of CI is based on neuropsychological tests and accurate anamnesis, involving the patients and caregivers (CG). This study aimed to assess the complex interplay between self-perception of CI, objective CI and the brain atrophy of MS patients, also exploring the possible differences with CI evaluated by caregivers.Methods: Relapsing pwMS were enrolled in this study. Subjects underwent neuropsychological examination using the Brief Cognitive Assessment for Multiple Sclerosis (BICAMS) and evaluation of self-reported cognitive status using the patient-version of the Multiple Sclerosis Neuropsychological Questionnaire (p-MSNQ). Depression and anxiety were also evaluated using the Back Depression Inventory-version II (BDI-II) and Zung Anxiety Scale. Brain MRI images were acquired and brain volumes estimated. For each patient that was enrolled, we spoke to a caregiver and collected their perception of the patient's CI using the MSNQ- Caregiver version.Results: Ninety-five MS subjects with their caregivers were enrolled. CI was detected in 51 (53.7%) patients. We found a significant correlation (p < 0.001) between BICAMS T scores and lower whole brain (Rho = 0.51), gray matter (Rho = 0.54), cortical gray matter (Rho = 0.51) volumes and lower p-MSNQ (Rho = 0.31), and cg-MSNQ (Rho = 0.41) scores. Multivariate logistic regression showed that p-MSNQ is related to a patient's anxiety to evaluate by Zung Score (p < 0.001) while cg-MSNQ to patient's brain volume (p = 0.01).Conclusion: Our data confirm that neuropsychological evaluation results are related to the perception of CI and brain volume measures and highlight the importance of the caregiver's perception for cognitive assessment of pwMS.

Published
2020

42. Bipolar disorders and deep grey matter in multiple sclerosis: A preliminary quantitative MRI study

Author

Eleonora Cocco, Lorena Lorefice, Mauro Giovanni Carta, Giancarlo Coghe, E. Carta, Giuseppe Fenu, Jessica Frau, M.A. Barracciu, and F. Contu

Subjects
Oncology, medicine.medical_specialty, Bipolar Disorder, Multiple Sclerosis, Brain damage, Grey matter, Nucleus accumbens, White matter, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Internal medicine, medicine, Humans, 030212 general & internal medicine, Bipolar disorder, Gray Matter, business.industry, Putamen, Multiple sclerosis, Brain, General Medicine, medicine.disease, Magnetic Resonance Imaging, White Matter, medicine.anatomical_structure, Neurology, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Background Bipolar disorder (BD) is frequently observed in patients affected by multiple sclerosis (MS), presenting a lifetime estimate of around 8%. However, uncertainty exists on the brain damage associated with this psychiatric comorbidity. This study aimed to investigate the effect of brain atrophy, particularly that of the subcortical grey matter (scGM) structures that notoriously regulate the affective functioning, on the co-occurrence of BD in patients with MS. Methods A group of patients with MS affected by BD and a control group of patients with MS without any mood/psychiatric disorder, as defined using standardised diagnostic tools (Advanced Neuropsychiatric Tools and Assessment Schedule), were recruited. The patients underwent brain MRI, and the volumes of the whole brain (WB), white matter (WM), and grey matter (GM) were estimated using SIENAX. Thus, the scGM volumes of the putamen, caudate, thalamus, hippocampus, amygdala, nucleus accumbens, and pallidus were estimated using the FIRST tool. Results The sample included 61 patients with MS, amongst whom 15 (24.6%) had BD. No differences in the WB, WM, and cortical GM volumes were observed between the patients with MS with and without BD. Conversely, the multiple regression analysis revealed a significant association of BD with lower volumes of the putamen (p = 0.032), nucleus accumbens (p = 0.029), and pallidus (p = 0.061; with a trend towards significance), independently from the demographic and MS clinical features. Conclusions Our preliminary results indicated that the nucleus accumbens and putamen are smaller in MS patients with BD. Further investigations in larger cohorts of MS patients with affective disorders are necessary to confirm these data and understand the structural brain damage underlying this psychiatric comorbidity.

Published
2020

43. Multi-Platform Characterization of Cerebrospinal Fluid and Serum Metabolome of Patients Affected by Relapsing–Remitting and Primary Progressive Multiple Sclerosis

Author

Federica Murgia, Simone Poddighe, Maria Antonietta Secci, Maria Giovanna Marrosu, Eleonora Cocco, Luigi Atzori, Giuseppe Fenu, and Lorena Lorefice

Subjects
0301 basic medicine, lcsh:Medicine, Phenylalanine, Pharmacology, multiple sclerosis, Article, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Metabolomics, Metabolome, Medicine, Tyrosine, mass spectrometry, Receiver operating characteristic, business.industry, Multiple sclerosis, lcsh:R, biomarkers, General Medicine, Metabolism, medicine.disease, metabolomics, nuclear magnetic resonance, 030104 developmental biology, business, pathways analysis, 030217 neurology & neurosurgery
Abstract

Background: Multiple sclerosis (MS) is a chronic immunemediated disease of the central nervous system with a highly variable clinical presentation and disease progression. In this study, we investigate the metabolomics profile of patients affected by relapsing&ndash, remitting MS (RRMS)and primary progressive MS (PPMS), in order to find potential biomarkers to distinguish between the two forms. Methods: Cerebrospinal Fluid CSF and blood samples of 34 patients (RRMS n = 22, PPMS n = 12) were collected. Nuclear magnetic resonance (1H-NMR) and mass spectrometry (coupled with a gas chromatography and liquid chromatography) were used as analytical techniques. Subsequently, a multivariate statistical analysis was performed, the resulting significant variables underwent U-Mann&ndash, Whitney test and correction for multiple comparisons. Receiver Operating Characteristic ROC curves were built and the pathways analysis was conducted. Results: The analysis of the serum and the CSF of the two classes, allowed the identification of several altered metabolites (lipids, biogenic amines, and amino acids). The pathways analysis indicated the following pathways were affected: Glutathione metabolism, nitrogen metabolism, glutamine&ndash, glutamate metabolism, arginine&ndash, ornithine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis etc. Conclusion: The analysis allowed the identification of a set of metabolites able to classify RRMS and PPMS patients, each of whom express different patterns of metabolites in the two biofluids.

Published
2020
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44. P17 Anti-neuronal antibodies in patients with systemic lupus erythematosus: prevalence, clinical associations and searching for a specific target

Author

Maria Maddalena Angioni, Giulia Corda, Mattia Congia, Alessandro Mathieu, Lorena Lorefice, Silvia Pinna, Elias Manca, Matteo Piga, Elisabetta Chessa, Alberto Cauli, Alberto Floris, Cristina Cocco, and Gian-Luca Ferri

Subjects
Univariate analysis, medicine.medical_specialty, biology, business.industry, Multiple sclerosis, medicine.disease, Gastroenterology, Serology, Antigen, Internal medicine, Cohort, medicine, biology.protein, Immunohistochemistry, Clinical significance, Antibody, business
Abstract

Background The aim of this study was to evaluate the prevalence and clinical significance of Anti-neuronal antibodies (AnAb) in a cohort of neuropsychiatric (NP) Systemic Lupus Erythematosus (SLE) patients. Methods Overall, 28 SLE patients (age 45.6 ± 14.4 years) with inflammatory neuropsychiatric syndromes, classified according to existing criteria (1, 2) were enrolled and serum samples were collected before starting treatment for the specific NP event; 41 consecutive SLE patients (44.2 ± 14.2 years) without NP involvement, 22 Multiple Sclerosis patients (37.9 ± 11.0 years) and 82 healthy subjects (44.8 ± 15.0 years) served as controls. Search for AnAb was performed by tissue-based immunohistochemistry assays (IHC) on male Sprague Dawley rat’s brain sections and confirmed by cell-based immunocytochemistry assays on SH-SY5Y (human neuroblastoma) cell cultures. The association between serum positivity for AnAb by IHC and a large panel of data (demographic, serologic, SLEDAI, conventional brain MRI, treatment) was investigated by univariate analysis. Multivariate models were fitted with covariates with p Results AnAb were detected in 23 (82.1%) NPSLE patients and in 16 (39.0%) SLE patients without NP involvement resulting in 82% specificity (95%CI 71%-90%) and 61% sensitivity (95%CI 48%-72%) in differentiating NPSLE from SLE without NP involvement. None of the sera from MS patients (0%) and healthy subjects (0%) showed AnAb. Serum AnAb by IHC were independently associated with NPSLE (p Conclusion AnAb are significantly more frequent in patients with NPSLE than SLE. Further studies are needed to identify the unknown neuronal antigens targeted by AnAb in SLE patients.

Published
2020

45. Characteristics and treatment of Multiple Sclerosis-related trigeminal neuralgia: An Italian multi-centre study

Author

Giorgia Teresa Maniscalco, Cinzia Cordioli, Maria Chiara Buscarinu, Diana Ferraro, Massimiliano Calabrese, Claudio Gasperini, Marcello Moccia, Alberto Gajofatto, Antonio Gallo, Eleonora Cocco, Valentina Camera, Pietro Annovazzi, Roberta Fantozzi, Marta Radaelli, Giovanna De Luca, Valentina Tomassini, Roberta Lanzillo, Claudio Solaro, Lorena Lorefice, Carla Tortorella, Federica Pinardi, Fabio Buttari, Paolo Ragonese, Paola Cavalla, Viviana Nociti, Salvatore Lo Fermo, Laura Boffa, Rirems, Damiano Paolicelli, Massimiliano Di Filippo, Ferraro, D., Annovazzi, P., Moccia, M., Lanzillo, R., De Luca, G., Nociti, V., Fantozzi, R., Paolicelli, D., Ragonese, P., Gajofatto, A., Boffa, L., Cavalla, P., Lo Fermo, S., Buscarinu, M. C., Lorefice, L., Cordioli, C., Calabrese, M., Gallo, A., Pinardi, F., Tortorella, C., Di Filippo, M., Camera, V., Maniscalco, G. T., Radaelli, M., Buttari, F., Tomassini, V., Cocco, E., Gasperini, C., Solaro, C., Ferraro D., Annovazzi P., Moccia M., Lanzillo R., De Luca G., Nociti V., Fantozzi R., Paolicelli D., Ragonese P., Gajofatto A., Boffa L., Cavalla P., Lo Fermo S., Buscarinu M.C., Lorefice L., Cordioli C., Calabrese M., Gallo A., Pinardi F., Tortorella C., Di Filippo M., Camera V., Maniscalco G.T., Radaelli M., Buttari F., Tomassini V., Cocco E., Gasperini C., and Solaro C.

Subjects
Pediatrics, medicine.medical_treatment, multiple sclerosis, microvascular decompression surgery, time factors, 0302 clinical medicine, Radiofrequency thermocoagulation, Trigeminal neuralgia, Multiple Sclerosi, Outcome Assessment, Health Care, italy, middle aged, pain, 030212 general & internal medicine, Oxcarbazepine, humans, education.field_of_study, trigeminal neuralgia, adult, Disability, Multiple Sclerosis, Pain, radiosurgery, General Medicine, Analgesics, Non-Narcotic, health care, follow-up studies, Settore MED/26 - NEUROLOGIA, aged, retrospective studies, female, Neurology, disability, analgesics, non-narcotic, male, severity of illness index, sex factors, neurosurgical procedures, outcome assessment, health care, analgesics, medicine.drug, medicine.medical_specialty, Population, Microvascular decompression, 03 medical and health sciences, medicine, education, outcome assessment, business.industry, Multiple sclerosis, Carbamazepine, medicine.disease, Discontinuation, non-narcotic, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Background The prevalence of trigeminal neuralgia (TN) in Multiple Sclerosis (MS) patients is higher than in the general population and its management can be particularly challenging. Our aim is to describe the characteristics, treatment and prognostic factors of MS-related TN in a retrospective multicentre study. Methods Neurologists members of the RIREMS group (Rising Researchers in MS) enrolled MS patients with a TN diagnosis and filled out a spreadsheet comprising their clinical data. Results Population consisted of 298 patients. First-choice preventive treatments were carbamazepine and oxcarbazepine. A surgical procedure was performed in 81 (30%) patients, most commonly gamma knife stereotactic radiosurgery (37%), followed by microvascular decompression (22%) and radiofrequency thermocoagulation (21%); one third of patients underwent at least two procedures. Surgery was associated with higher disability, male sex and longer interval between MS and TN onset. Patients (77%) who stayed on at least one preventive medication at most recent follow-up, after a mean period of 8 years, had a higher disability compared to the untreated group. Furthermore, patients with higher disability at TN onset were less likely to discontinue their first preventive medication due to pain remission, had bilateral TN more frequently and underwent surgical interventions earlier. Conclusion MS patients with a higher disability at TN onset and with a longer interval between MS and TN onset had differing clinical features and outcomes: pain was more frequently bilateral, surgery was more frequent and anticipated, and preventive medication discontinuation due to pain remission was less common.

Published
2020

46. 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

47. 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

48. Harmonization of real-world studies in multiple sclerosis: Retrospective analysis from the rirems group

Author

Federica Pinardi, Simona Mallucchi, Paolo Ragonese, Eleonora Cocco, Valentina Tomassini, Alice Laroni, Lorena Lorefice, Claudio Solaro, Alberto Gajofatto, Cinzia Cordioli, Viviana Nociti, Maria Chiara Buscarinu, Claudio Gasperini, Marta Radaelli, Antonio Gallo, Luca Prosperini, Massimiliano Di Filippo, Massimiliano Calabrese, Damiano Paolicelli, Paola Cavalla, Diana Ferraro, Pietro Annovazzi, Roberta Lanzillo, Marcello Moccia, Carla Tortorella, Moccia, M., Annovazzi, P., Buscarinu, M. C., Calabrese, M., Cavalla, P., Cordioli, C., Di Filippo, M., Ferraro, D., Gajofatto, A., Gallo, A., Lanzillo, R., Laroni, A., Lorefice, L., Mallucchi, S., Nociti, V., Paolicelli, D., Pinardi, F., Prosperini, L., Radaelli, M., Ragonese, P., Tomassini, V., Tortorella, C., Cocco, E., Gasperini, C., Solaro, C., Moccia M., Annovazzi P., Buscarinu M.C., Calabrese M., Cavalla P., Cordioli C., Di Filippo M., Ferraro D., Gajofatto A., Gallo A., Lanzillo R., Laroni A., Lorefice L., Mallucchi S., Nociti V., Paolicelli D., Pinardi F., Prosperini L., Radaelli M., Ragonese P., Tomassini V., Tortorella C., Cocco E., Gasperini C., and Solaro C.

Subjects
Adult, Longitudinal study, medicine.medical_specialty, Harmonization, Outcome measures, Multiple sclerosis, Outcome measure, 03 medical and health sciences, 0302 clinical medicine, Real world, medicine, Humans, Multiple sclerosi, 030212 general & internal medicine, Age of Onset, Aged, Retrospective Studies, Expanded Disability Status Scale, business.industry, Retrospective cohort study, General Medicine, Variance (accounting), medicine.disease, Neurology, Italy, Family medicine, Observational study, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Multiple Sclerosis
Abstract

Background: Worldwide multiple sclerosis (MS) centers have coordinated their efforts to use data acquired in clinical practice for real-world observational studies. In this retrospective study, we aim to harmonize outcome measures, and to evaluate their heterogeneity within the Rising Italian Researchers in MS (RIReMS) study group. Methods: RIReMS members filled in a structured questionnaire evaluating the use of different outcome measures in clinical practice. Thereafter, thirty-four already-published papers from RIReMS centers were used for heterogeneity analyses, using the DerSimonian and Laird random-effects method to compute the between-study variance (τ2). Results: Based on questionnaire results, we defined basic modules for diagnosis and follow-up, consisting of outcome measures recorded by all participating centers at the time of diagnosis, and, then, at least annually; we also defined more detailed/optional modules, with outcome measures recorded less frequently and/or in the presence of specific clinical indications. Looking at heterogeneity, we found 5-year variance in age at onset (ES=27.34; 95%CI=26.18, 28.49; p41.4 years (ES=4.37; 95%CI=3.40, 5.35; p2 years (ES=5.41; 95%CI=3.22, 7.60; p = 0.02; τ2=1.00). Discussion: We suggest common sets of biomarkers to be acquired in clinical practice, that can be used for research purposes. Also, we provide researchers with specific indications for improving inclusion criteria and data analysis, ultimately allowing data harmonization and high-quality collaborative studies.

Published
2020

49. Quantifying gait impairment in individuals affected by Charcot-Marie-Tooth disease: the usefulness of gait profile score and gait variable score

Author

Giuseppina Pilloni, A. Vannelli, Giuseppe Fenu, Maria Giovanna Marrosu, Eleonora Cocco, Massimiliano Pau, Micaela Porta, Federica Corona, Lorena Lorefice, Jessica Frau, Giovanni Marrosu, Cinzia Pisano, E Mamusa, and Giancarlo Coghe

Subjects
030506 rehabilitation, Foot drop, medicine.medical_specialty, business.industry, Rehabilitation, Biomechanical Phenomena, Clinical Practice, 03 medical and health sciences, Tooth disease, 0302 clinical medicine, Gait (human), Gait impairment, Physical medicine and rehabilitation, Charcot-Marie-Tooth Disease, Gait analysis, medicine, Humans, Disabled Persons, medicine.symptom, Gait Analysis, 0305 other medical science, business, Gait, 030217 neurology & neurosurgery
Abstract

Background: Gait analysis is a reliable tool to characterise ambulation in Charcot-Marie-Tooth, the obtained are complex data makes its use scarce in clinical practice. The use of synthetic measure...

Published
2018

50. The impact of visible and invisible symptoms on employment status, work and social functioning in Multiple Sclerosis

Author

Eleonora Cocco, Giancarlo Coghe, Giuseppe Fenu, Lorena Lorefice, Jessica Frau, and Maria Giovanna Marrosu

Subjects
Adult, Employment, Male, Multiple Sclerosis, Activities of daily living, Physical disability, Psychometrics, Affect (psychology), Social Skills, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, medicine, Humans, Apathy, 030212 general & internal medicine, Young adult, Fatigue, Depression (differential diagnoses), Psychiatric Status Rating Scales, Expanded Disability Status Scale, Depression, business.industry, Rehabilitation, Public Health, Environmental and Occupational Health, McDonald criteria, Middle Aged, Logistic Models, Female, medicine.symptom, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract

BACKGROUND Frequently diagnosed in young adulthood, multiple sclerosis (MS) and several MS-related factors can influence patients' unemployment status and negatively affect work productivity and daily functioning. OBJECTIVE We examined MS patients' employment status and evaluated clinical features influencing it. Furthermore, we investigated patients' burdens due to visible and invisible MS symptoms through their worsening daily functioning. METHODS The study included outpatients affected by MS according to the 2010 McDonald criteria. The co-occurrence of invisible symptoms (fatigue, depression and apathy) was stated using validated, self-administered tools: Fatigue Severity Scale (FSS); Beck Depression Inventory-Second Edition (BDI-II); Apathy Evaluation Scale (AES). Impairment in daily functioning due to MS was assessed using the Work and Social Adjustment Scale (WSAS). Descriptive statistics, hierarchical regression analyses, Pearson's correlation, and the t-test were conducted. RESULTS Of the 123 participants, 52 (42.3%) were unemployed. Results showed employment to be positively associated with higher education levels (p 0.01); female gender (p 0.03) and higher disability (p 0.02) showed negative associations with employment. No associations were found between employment and fatigue or clinically relevant depressive and apathetic symptoms. High correlations were found between WSAS score and Expanded Disability Status Scale score (r = 565, p

Published
2018

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