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1. Disease‐Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Author: Sormani, Maria P, De Rossi, Nicola, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Moiola, Lucia, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, Trojano, Maria, Zaratin, Paola, Tedeschi, Gioacchino, Comi, Giancarlo, Battaglia, Mario A, Patti, Francesco, Salvetti, Marco, Nozzolillo, Agostino, Bellacosa, Alessandra, Protti, Alessandra, Di Sapio, Alessia, Signori, Alessio, Petrone, Alfredo, Bisecco, Alvino, Iovino, Aniello, Dutto, Anna, Repice, Anna Maria, Conte, Antonella, Bertolotto, Antonio, Bosco, Antonio, Gallo, Antonio, Zito, Antonio, Sartori, Arianna, Giometto, Bruno, Tortorella, Carla, Antozzi, Carlo, Pozzilli, Carlo, Mancinelli, Chiara Rosa, Zanetta, Chiara, Cordano, Christian, Scandellari, Cinzia, Guaschino, Clara, Gasperini, Claudio, Solaro, Claudio, Fioretti, Cristina, Bezzini, Daiana, Marastoni, Damiano, Paolicelli, Damiano, Vecchio, Domizia, Landi, Doriana, Bucciantini, Elisabetta, Pedrazzoli, Elisabetta, Signoriello, Elisabetta, Sbragia, Elvira, Susani, Emanuela Laura, Curti, Erica, Milano, Eva, Marinelli, Fabiana, Camilli, Federico, Boneschi, Filippo Martinelli, Govone, Flora, Bovis, Francesca, Calabria, Francesca, Caleri, Francesca, Rinaldi, Francesca, Vitetta, Francesca, Corea, Francesco, Crescenzo, Francesco, Teatini, Francesco, Tabiadon, Giulietta, Granella, Franco, Boffa, Giacomo, Lus, Giacomo, Brichetto, Giampaolo, Maniscalco, Giorgia Teresa, Borriello, Giovanna, De Luca, Giovanna, Konrad, Giovanna, Vaula, Giovanna, Marfia, Girolama Alessandra, Mallucci, Giulia, Liberatore, Giuseppe, Salemi, Giuseppe, Miele, Giuseppina, Sibilia, Grazia, Pesci, Ilaria, Brambilla, Laura, Lopiano, Leonardo, Sinisi, Leonardo, Pasquali, Livia, Saraceno, Lorenzo, Chiveri, Luca, Mancinelli, Luca, and Grimaldi, Luigi ME
Subjects: Pneumonia & Influenza, Neurodegenerative, Clinical Research, Autoimmune Disease, Brain Disorders, Lung, Multiple Sclerosis, Pneumonia, Neurosciences, Neurological, Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, COVID-19, Dimethyl Fumarate, Female, Fingolimod Hydrochloride, Hospitalization, Humans, Immunologic Factors, Immunosuppressive Agents, Intensive Care Units, Interferons, Male, Middle Aged, Mortality, Natalizumab, SARS-CoV-2, Severity of Illness Index, Young Adult, Musc-19 Study Group, Clinical Sciences, Neurology & Neurosurgery
Abstract: ObjectiveThis study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS).MethodsWe retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results.ResultsOf 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (
Published: 2021

2. Relation of sensorimotor and cognitive cerebellum functional connectivity with brain structural damage in patients with multiple sclerosis and no disability

Author: Tommasin, Silvia, Iakovleva, Viktoriia, Maria Assunta Rocca, Gianni', Costanza, Gioacchino, Tedeschi, De Stefano, Nicola, Pozzilli, Carlo, Massimo, Filippi, Pantano, Patrizia, Petsas, Nikolaos, Ruggieri, Serena, Piervincenzi, Claudia, Paola, Valsasina, Mauro, Sibilia, Preziosa, Paolo, Loredana, Storelli, Gallo, Antonio, Alvino, Bisecco, D'Ambrosio, Alessandro, Maria Laura Stromillo, Riccardo Tappa Brocci and, Tommasin, Silvia, Iakovleva, Viktoriia, Rocca, Maria Assunta, Giannì, Costanza, Tedeschi, Gioacchino, De Stefano, Nicola, Pozzilli, Carlo, Filippi, Massimo, and Pantano, Patrizia
Subjects: Multiple Sclerosis, Brain, Relapsing-Remitting, cognitive cerebellum, disability, functional magnetic resonance imaging, multiples sclerosis, neural plasticity, sensorimotor cerebellum, brain, cerebellum, cognition, Gray Matter, Humans, Magnetic Resonance Imaging, Brain Injuries, Multiple Sclerosis, Relapsing-Remitting, White Matter, Cognition, Neurology, Cerebellum, Neurology (clinical)
Abstract: Background and purpose: To investigate the relationship between the functional connectivity (FC) of the sensorimotor and cognitive cerebellum and measures of structural damage in patients with multiple sclerosis (MS) and no physical disability. Methods: We selected 144 relapsing-remitting MS patients with an Expanded Disability Status Scale score of ≤1.5 and 98 healthy controls from the Italian Neuroimaging Network Initiative database. From multimodal 3T magnetic resonance imaging (MRI), including functional MRI at rest, we calculated lesion load, cortical thickness, and white matter, cortical gray matter, and caudate, putamen, thalamic, and cerebellar volumes. Voxel-wise FC of the sensorimotor and cognitive cerebellum was assessed with seed-based analysis, and multiple regression analysis was used to evaluate the relationship between FC and structural damage. Results: Whole brain, white matter, caudate, putamen, and thalamic volumes were reduced in patients compared to controls, whereas cortical gray matter was not significantly different in patients versus controls. Both the sensorimotor and cognitive cerebellum showed a widespread pattern of increased and decreased FC that were negatively associated with structural measures, indicating that the lower the FC, the greater the tissue loss. Lastly, among multiple structural measures, cortical gray matter and white matter volumes were the best predictors of cerebellar FC alterations. Conclusions: Increased and decreased cerebellar FC with several brain areas coexist in MS patients with no disability. Our data suggest that white matter loss hampers FC, whereas, in the absence of atrophy, cortical volume represents the framework for FC to increase.
Published: 2022

3. Impact of post-contrast MRI in the definition of active multiple sclerosis

Author: Gentili, Lucia, Capuano, Rocco, Gaetani, Lorenzo, Fiacca, Andrea, Bisecco, Alvino, d'Ambrosio, Alessandro, Mancini, Andrea, Guercini, Giorgio, Tedeschi, Gioacchino, Parnetti, Lucilla, Gallo, Antonio, Di Filippo, Massimiliano, Gentili, Lucia, Capuano, Rocco, Gaetani, Lorenzo, Fiacca, Andrea, Bisecco, Alvino, D'Ambrosio, Alessandro, Mancini, Andrea, Guercini, Giorgio, Tedeschi, Gioacchino, Parnetti, Lucilla, Gallo, Antonio, and Di Filippo, Massimiliano
Subjects: Multiple sclerosis, Multiple Sclerosis, Relapsing-Remitting, Phenotype, Neurology, Brain, Humans, Multiple sclerosi, Gadolinium, Neurology (clinical), Magnetic Resonance Imaging, Retrospective Studies, MRI
Abstract: Background: For multiple sclerosis (MS) phenotypes classification, the presence of "disease activity" can be defined by clinical relapses and/or by magnetic resonance imaging (MRI) through gadolinium-enhancing (Gd+) lesions or new/enlarged T2 lesions. Recent MRI and pathology findings have demonstrated Gd deposition in the brain, suggesting to avoid Gd administration when dispensable. In this scenario, we aimed to evaluate the contribution of post-contrast MRIs to the definition of "active" MS phenotype. Methods: We retrospectively selected 84 "active" relapsing-remitting MS (RRMS) patients according to Lublin 2013, calculating both the number of Gd+ lesions not detectable as new/unequivocally enlarged on T2 images and the proportion of patients who would be still correctly classified as "active" without Gd administration. Results: 13 out of 164 (7.9%) Gd+ lesions did not correspond to a new/enlarged T2 lesion. Gd administration did not modify the classification of MS as "active" in 83 out of 84 subjects (98.8%). Conclusion: The contribution of Gd+ lesions to the correct classification of RRMS patients as "active" is marginal, thus limiting the need of routine Gd administration for this scope. Further studies are warranted to support these conclusions.
Published: 2022

4. Myocardial fibrosis assessed by magnetic resonance imaging in asymptomatic heterozygous familial hypercholesterolemia: the cholcoeur study

Author: Gallo, Antonio, Giral, Philippe, Rosenbaum, David, Mattina, Alessandro, Kilinc, Ali, Giron, Alain, Bouazizi, Khaoula, Gueda Moussa, Moussa, Salem, Joe-Elie, Carrié, Alain, Carreau, Valérie, Béliard, Sophie, Bittar, Randa, Cluzel, Philippe, Bruckert, Eric, Redheuil, Alban, Kachenoura, Nadjia, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Tel Aviv University [Tel Aviv], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], Service de Chirurgie cardiaque et thoracique [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Tel Aviv University (TAU), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Service d'Endocrinologie, Métabolisme et Prévention des Maladies Cardio-vasculaires [CHU Pitié-Salpêtrière], Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Gestionnaire, HAL Sorbonne Université 5, Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (UPMC), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), and Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)
Subjects: Adult, Male, cardiovascular risk, Medicine (General), Research paper, [SDV]Life Sciences [q-bio], Familial hypercholesterolemia, primary prevention, Magnetic Resonance Imaging, Cine, cardiac magnetic resonance, Hyperlipoproteinemia Type II, R5-920, Predictive Value of Tests, Prevalence, Humans, Prospective Studies, cardiovascular diseases, cardiovascular imaging, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Myocardium, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Fibrosis, Case-Control Studies, Medicine, Female, genetic dyslipidaemia
Abstract: International audience; Background: Familial Hypercholesterolemia (FH) is an underdiagnosed condition with an increased cardiovascular risk. It is unknown whether lipid accumulation plays a role in structural myocardial changes. Cardiovascular Magnetic Resonance (CMR) is the reference technique for the morpho-functional evaluation of heart chambers through cine sequences and for myocardial tissue characterization through late gadolinium enhancement (LGE) and T1 mapping images. We aimed to assess the prevalence of myocardial fibrosis in FH patients.Methods: Seventy-two asymptomatic subjects with genetically confirmed FH (mean age 49·24, range 40 to 60 years) were prospectively recruited along with 31 controls without dyslipidaemia matched for age, sex, BMI, and other cardiovascular risk factors. All underwent CMR including cine, LGE, pre- and post-contrast T1 mapping. Extracellular volume (ECV) and enhancement rate of the myocardium (ERM = difference between pre- and post-contrast myocardial T1, normalized by pre-contrast myocardial T1) were calculated.Findings: Five FH patients and none of the controls had intramyocardial LGE (p= 0·188). While no changes in Native T1 and ECV were found, post-contrast T1 was significantly lower (430·6 ± 55ms vs. 476·1 ± 43ms, p
Published: 2021

5. Reduced accuracy of MRI deep grey matter segmentation in multiple sclerosis : an evaluation of four automated methods against manual reference segmentations in a multi-center cohort

Author: de Sitter, Alexandra, Verhoeven, Tom, Burggraaff, Jessica, Liu, Yaou, Simoes, Jorge, Ruggieri, Serena, Palotai, Miklos, Brouwer, Iman, Versteeg, Adriaan, Wottschel, Viktor, Ropele, Stefan, Rocca, Mara A., Gasperini, Claudio, Gallo, Antonio, Yiannakas, Marios C., Rovira, Alex, Enzinger, Christian, Filippi, Massimo, De Stefano, Nicola, Kappos, Ludwig, Frederiksen, Jette L., Uitdehaag, Bernard M. J., Barkhof, Frederik, Guttmann, Charles R. G., Vrenken, Hugo, Universitat Autònoma de Barcelona, de Sitter, Alexandra, Verhoeven, Tom, Burggraaff, Jessica, Liu, Yaou, Simoes, Jorge, Ruggieri, Serena, Palotai, Miklo, Brouwer, Iman, Versteeg, Adriaan, Wottschel, Viktor, Ropele, Stefan, Rocca, Mara A, Gasperini, Claudio, Gallo, Antonio, Yiannakas, Marios C, Rovira, Alex, Enzinger, Christian, Filippi, Massimo, De Stefano, Nicola, Kappos, Ludwig, Frederiksen, Jette L, Uitdehaag, Bernard M J, Barkhof, Frederik, Guttmann, Charles R G, Vrenken, Hugo, de Sitter, A., Verhoeven, T., Burggraaff, J., Liu, Y., Simoes, J., Ruggieri, S., Palotai, M., Brouwer, I., Versteeg, A., Wottschel, V., Ropele, S., Rocca, M. A., Gasperini, C., Gallo, A., Yiannakas, M. C., Rovira, A., Enzinger, C., Filippi, M., De Stefano, N., Kappos, L., Frederiksen, J. L., Uitdehaag, B. M. J., Barkhof, F., Guttmann, C. R. G., Vrenken, H., Radiology and nuclear medicine, Neurology, and Amsterdam Neuroscience - Brain Imaging
Subjects: Correlation coefficient, Caudate nucleus, Grey matter, 030218 nuclear medicine & medical imaging, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Automated segmentation methods, Deep grey matter, Medicine, Humans, Segmentation, Multiple sclerosi, Gray Matter, Neuroradiology, Original Communication, business.industry, Putamen, Brain, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Neurology, Brain size, Automated segmentation method, Neurology (clinical), business, Nuclear medicine, 030217 neurology & neurosurgery, Human
Abstract: Background Deep grey matter (DGM) atrophy in multiple sclerosis (MS) and its relation to cognitive and clinical decline requires accurate measurements. MS pathology may deteriorate the performance of automated segmentation methods. Accuracy of DGM segmentation methods is compared between MS and controls, and the relation of performance with lesions and atrophy is studied. Methods On images of 21 MS subjects and 11 controls, three raters manually outlined caudate nucleus, putamen and thalamus; outlines were combined by majority voting. FSL-FIRST, FreeSurfer, Geodesic Information Flow and volBrain were evaluated. Performance was evaluated volumetrically (intra-class correlation coefficient (ICC)) and spatially (Dice similarity coefficient (DSC)). Spearman's correlations of DSC with global and local lesion volume, structure of interest volume (ROIV), and normalized brain volume (NBV) were assessed. Results ICC with manual volumes was mostly good and spatial agreement was high. MS exhibited significantly lower DSC than controls for thalamus and putamen. For some combinations of structure and method, DSC correlated negatively with lesion volume or positively with NBV or ROIV. Lesion-filling did not substantially change segmentations. Conclusions Automated methods have impaired performance in patients. Performance generally deteriorated with higher lesion volume and lower NBV and ROIV, suggesting that these may contribute to the impaired performance.
Published: 2020

6. Manual and automated tissue segmentation confirm the impact of thalamus atrophy on cognition in multiple sclerosis: A multicenter study

Author: Burggraaff, Jessica, Liu, Yao, Prieto, Juan C., Simoes, Jorge, de Sitter, Alexandra, Ruggieri, Serena, Brouwer, Iman, Lissenberg-Witte, Birgit I., Rocca, Mara A., Valsasina, Paola, Ropele, Stefan, Gasperini, Claudio, Gallo, Antonio, Pareto, Deborah, Sastre-Garriga, Jaume, Enzinger, Christian, Filippi, Massimo, De Stefano, Nicola, Ciccarelli, Olga, Hulst, Hanneke E., Wattjes, Mike P., Barkhof, Frederik, Uitdehaag, Bernard M. J., Vrenken, Hugo, Guttmann, Charles R. G., Universitat Autònoma de Barcelona, Neurology, Amsterdam Neuroscience - Neuroinfection & -inflammation, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Epidemiology and Data Science, Anatomy and neurosciences, Other Research, APH - Methodology, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Service de chirurgie et transplantation abdominale, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, Institut Català de la Salut, [Burggraaff J, Simoes J] Department of Neurology, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Location VUmc, De Boelelaan 1117, 1118, 1081 HV Amsterdam, The Netherlands. [Liu Y, de Sitter A] Department of Radiology and Nuclear Medicine, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Location VUmc, De Boelelaan 1117, 1118, 1081 HV Amsterdam, The Netherlands. [Prieto JC] Center for Neurological Imaging, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, 1249 Boylston Street, Boston, MA 02215, USA. [Ruggieri S] Department of Human Neurosciences, 'Sapienza' University of Rome, Piazzale Aldo Moro, 5, 00185 Roma RM, Italy. Department of Neurosciences, San Camillo Forlanini Hospital, Circonvallazione Gianicolense, 87, 00152 Roma RM, Italy. [Pareto D] Secció de Neuroradiologia, Unitat de Ressonància Magnètica, Departament de Radiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Sastre-Garriga J] Servei de Neurologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Burggraaff, J., Liu, Y., Prieto, J. C., Simoes, J., de Sitter, A., Ruggieri, S., Brouwer, I., Lissenberg-Witte, B. I., Rocca, M. A., Valsasina, P., Ropele, S., Gasperini, C., Gallo, A., Pareto, D., Sastre-Garriga, J., Enzinger, C., Filippi, M., De Stefano, N., Ciccarelli, O., Hulst, H. E., Wattjes, M. P., Barkhof, F., Uitdehaag, B. M. J., Vrenken, H., and Guttmann, C. R. G.
Subjects: WLG, Word List Generation, SPM12, Statistical Parametric Mapping 12, Audiology, Tàlem - Imatgeria, Etiv, estimated total intracranial volume, lcsh:RC346-429, Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores], GIF, Geodesic Information Flows, 0302 clinical medicine, Cognition, Segmentation, Thalamus, CP, cognitively preserved, NBV, Normalized brain volume, Multiple Sclerosi, Other subheadings::/diagnosis [Other subheadings], Neuropsychological assessment, Cognitive decline, Generalized estimating equation, WMV, white matter volume, ICC, intraclass correlation coefficient, medicine.diagnostic_test, 05 social sciences, Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [DISEASES], sistema nervioso::sistema nervioso central::encéfalo::prosencéfalo::diencéfalo::tálamo [ANATOMÍA], Regular Article, Neuropsychological test, HC, healthy control, SDMT, Symbol Digit Modalities Test, Magnetic Resonance Imaging, Neurology, PASAT, Paced Auditory Serial Addition Test, enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES], lcsh:R858-859.7, VolBrain, MRI Brain Volumetry System, SRT, Selective Reminding Test, Human, MRI, Esclerosi múltiple - Complicacions, medicine.medical_specialty, CNR, contrast-to-noise ratio, Multiple Sclerosis, Cognitive Neuroscience, RRMS, Relapsing-Remitting Multiple Sclerosis, Otros calificadores::/diagnóstico [Otros calificadores], Nervous System::Central Nervous System::Brain::Prosencephalon::Diencephalon::Thalamus [ANATOMY], 10/36 SRT, 10/36 Spatial Recall Test, lcsh:Computer applications to medicine. Medical informatics, NGMV, Normalized grey matter volume, 050105 experimental psychology, SD, standard deviations, CII, cognitive impairment index, EDSS, Expanded Disability Status Scale, WCST, Wisconsin Card Sorting Test, 03 medical and health sciences, Atrophy, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, WM, white matter, lcsh:Neurology. Diseases of the nervous system, Thalamu, CI, cognitively impaired and preserved (CP), BRB-N, Brief Repeatable Battery of Neuropsychological Tests, business.industry, Multiple sclerosis, FSL-FIRST, FMRIB Integrated Registration and Segmentation Tool, eTIV, estimated total intracranial volume, CAT12, Computational Anatomy Toolbox for Statistical Parametric Mapping 12, GM, grey matter, medicine.disease, Deep grey matter, NWMV, Normalized white matter volume, MS, Multiple Sclerosis, GMV, grey matter volume, IPS, information processing speed, Neurology (clinical), business, 030217 neurology & neurosurgery, Other subheadings::Other subheadings::/complications [Other subheadings]
Abstract: Highlights • Thalamus atrophy is associated with cognitive impairment in multiple sclerosis. • This was confirmed by automated and manual segmentations, but effect sizes varied. • The algorithms work in a multi-center setting. • Automated techniques exhibit proportional bias with respect to thalamus size. • Differences between vendors can affect the robustness of these associations., Background and rationale Thalamus atrophy has been linked to cognitive decline in multiple sclerosis (MS) using various segmentation methods. We investigated the consistency of the association between thalamus volume and cognition in MS for two common automated segmentation approaches, as well as fully manual outlining. Methods Standardized neuropsychological assessment and 3-Tesla 3D-T1-weighted brain MRI were collected (multi-center) from 57 MS patients and 17 healthy controls. Thalamus segmentations were generated manually and using five automated methods. Agreement between the algorithms and manual outlines was assessed with Bland-Altman plots; linear regression assessed the presence of proportional bias. The effect of segmentation method on the separation of cognitively impaired (CI) and preserved (CP) patients was investigated through Generalized Estimating Equations; associations with cognitive measures were investigated using linear mixed models, for each method and vendor. Results In smaller thalami, automated methods systematically overestimated volumes compared to manual segmentations [ρ=(-0.42)-(-0.76); p-values
Published: 2021

7. [Asbestos in drinking water and hazards to human health: a narrative synthesis]

Author: Totaro, Michele, Giorgi, Serena, Filippetti, Elisa, Gallo, Antonio, Frendo, Lorenzo, Privitera, Gaetano, and Baggiani, Angelo.
Subjects: Mesothelioma, Lung Neoplasms, Drinking Water, Carcinogens, Humans, Asbestos, Environmental Exposure, Water Pollutants, Chemical
Abstract: The term asbestos refers to six unique fibrous minerals mostly used in the production of asbestos cement sheets and pipes. According to the World Health Organization and the International Agency for Research on Cancer (IARC), there exists at leastquot;sufficient evidencequot; that all types of asbestos may cause cancer in humans (mesothelioma, lung cancer, laryngeal tumor and ovarian cancer). The only asbestos limit in drinking water is 7 million fiber/liter. This study is a narrative synthesis about the possible hazards to human health related to the presence of asbestos in drinking water. The various scientific studies and epidemiological reports examined highlight that there is an ongoing debate on the possible carcinogenic risk associated with asbestos exposure through ingestion. Nevertheless, considering the latency with which diseases caused by asbestos may emerge, control measures should be adopted.
Published: 2019

8. The Italian Neuroimaging Network Initiative (INNI): enabling the use of advanced MRI techniques in patients with MS

Author: Filippi, M., Tedeschi, G., Pantano, Patrizia, de Stefano, N., Zaratin, P., Rocca, M. A., Valsasina, Paola, Sibilia, Mauro, Preziosa, Paolo, Gallo, Antonio, Bisecco, Alvino, Docimo, Renato, Petsas, Nikolaos, Ruggieri, Serena, Gianni', Costanza, Stromillo, Maria Laura, Brocci, Riccardo Tappa, Filippi, M., Tedeschi, G., Pantano, P., De Stefano, N., Zaratin, P., Rocca, M. A, For the INNI, Network, Tedeschi, Gioacchino, de Stefano, N., Rocca, M. A., Valsasina, Paola, Sibilia, Mauro, Preziosa, Paolo, Gallo, Antonio, Bisecco, Alvino, Docimo, Renato, Petsas, Nikolao, Ruggieri, Serena, Giannì, Costanza, Stromillo, Maria Laura, and Brocci, Riccardo Tappa
Subjects: Male, Pathology, Standardization, Advanced MRI technique, data sharing, Network, Neuropsychological Tests, multiple sclerosis, 030218 nuclear medicine & medical imaging, 0302 clinical medicine, magnetic resonance imaging, Cooperative Behavior, Societies, Medical, Neuroradiology, neurology (clinical), Neurologic Examination, medicine.diagnostic_test, Neuropsychology, Brain, General Medicine, psychiatry and mental Health, Diffusion Tensor Imaging, Databases as Topic, Italy, Neurology, Psychiatry and Mental Health, Female, Adult, medicine.medical_specialty, Neuroimaging, Dermatology, 03 medical and health sciences, Magnetic resonance imaging, medicine, Humans, Medical physics, Multiple sclerosi, advanced MRI techniques, network, 2708, Internet, Information Dissemination, business.industry, Multiple sclerosis, Online database, medicine.disease, Clinical trial, Data sharing, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Magnetic resonance imaging (MRI) is an important paraclinical tool to diagnose and monitor multiple sclerosis (MS). Conventional MRI measures lack of pathological specificity and are weakly correlated with MS clinical manifestations. Advanced MRI techniques are improving the understanding of the mechanisms underlying tissue injury, repair, and functional adaptation in MS; however, they require careful standardization. The definition of standardized methods for the collection and analysis of advanced MRI techniques is central not only to improve the understanding of disease pathophysiology and evolution, but also to generate research hypotheses, monitor treatment, increase cost-effectiveness and power of clinical trials. We promoted the Italian Neuroimaging Network Initiative (INNI), involving centers and investigators with an International recognized expertise, with the major goal to determine and validate novel MRI biomarkers to be utilized as predictors and/or outcomes in future MS studies. The INNI initiative supported the creation of a centralized repository, where advanced structural and functional MRI scans available at the participating sites, with the related clinical and neuropsychological data, are collected. These data will be used to perform research studies to identify clinical, neuropsychological and imaging biomarkers characteristics of the entire spectrum of MS. INNI will be instrumental to help to define standardized MRI and clinical protocols towards an increasing uptake of personalized interventions for people with MS at a national and international level. Upon approval of the INNI Steering Committee, the data collected in the online database will be shared with any research center detailing specific research proposals on disease pathophysiology or treatment effects.
Published: 2017

9. The effect of inflammation and its reduction on brain plasticity in multiple sclerosis: MRI evidence

Author: Tomassini, Valentina, D'Ambrosio, Alessandro, Petsas, Nikolaos, Wise, RICHARD GEOFFREY, Sbardella, Emilia, Allen, Marek, Tona, Francesca, Fanelli, Fulvia, Foster, Catherine, Carni', Marco, Gallo, Antonio, Pantano, Patrizia, Pozzilli, Carlo, Tomassini, Valentina, D'Ambrosio, Alessandro, Petsas, Nikolao, Wise, Richard G., Sbardella, Emilia, Allen, Marek, Tona, Francesca, Fanelli, Fulvia, Foster, Catherine, Carnì, Marco, Gallo, Antonio, Pantano, Patrizia, and Pozzilli, Carlo
Subjects: Adult, Male, Radiology, Nuclear Medicine and Imaging, Multiple Sclerosis, Contrast Media, Gadolinium, Motor Activity, Neuropsychological Tests, Cohort Studies, Nuclear Medicine and Imaging, Adaptation, Psychological, Humans, Immunologic Factors, Multiple sclerosi, Research Articles, Functional MRI, Inflammation, Brain Mapping, Brain plasticity, Neuronal Plasticity, Radiological and Ultrasound Technology, Brain, Interferon beta, Adaptation, Physiological, Magnetic Resonance Imaging, Multiple sclerosis, Neurology (clinical), Anatomy, Neurology, Treatment Outcome, Practice, Psychological, Visual Perception, RC0321, Female, Radiology, Interferon beta-1a, Research Article
Abstract: Brain plasticity is the basis for systems‐level functional reorganization that promotes recovery in multiple sclerosis (MS). As inflammation interferes with plasticity, its pharmacological modulation may restore plasticity by promoting desired patterns of functional reorganization. Here, we tested the hypothesis that brain plasticity probed by a visuomotor adaptation task is impaired with MS inflammation and that pharmacological reduction of inflammation facilitates its restoration. MS patients were assessed twice before (sessions 1 and 2) and once after (session 3) the beginning of Interferon beta (IFN beta), using behavioural and structural MRI measures. During each session, 2 functional MRI runs of a visuomotor task, separated by 25‐minutes of task practice, were performed. Within‐session between‐run change in task‐related functional signal was our imaging marker of plasticity. During session 1, patients were compared with healthy controls. Comparison of patients' sessions 2 and 3 tested the effect of reduced inflammation on our imaging marker of plasticity. The proportion of patients with gadolinium‐enhancing lesions reduced significantly during IFN beta. In session 1, patients demonstrated a greater between‐run difference in functional MRI activity of secondary visual areas and cerebellum than controls. This abnormally large practice‐induced signal change in visual areas, and in functionally connected posterior parietal and motor cortices, was reduced in patients in session 3 compared with 2. Our results suggest that MS inflammation alters short‐term plasticity underlying motor practice. Reduction of inflammation with IFN beta is associated with a restoration of this plasticity, suggesting that modulation of inflammation may enhance recovery‐oriented strategies that rely on patients' brain plasticity. Hum Brain Mapp 37:2431–2445, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
Published: 2016

10. Guidelines on the clinical use for the detection of neutralizing antibodies (NAbs) to IFN beta in multiple sclerosis therapy: report from the Italian Multiple Sclerosis Study group

Author: Bertolotto A, Capobianco M, Amato MP, Capello E, Capra R, Centonze D, Di Ioia M, Grimaldi L, Imberti L, Lugaresi A, Mancinelli C, Marrosu MG, Moiola L, Montanari E, Romano S, Musu L, Paolicelli D, Patti F, Pozzilli C, Rossi S, Salvetti M, Tola MR, Troiano M, Zaffaroni M, Malucchi S, Italian Multiple Sclerosis Study group, GALLO, Antonio, TEDESCHI, Gioacchino, Bertolotto A, Capobianco M, Amato MP, Capello E, Capra R, Centonze D, Di Ioia M, Gallo A, Grimaldi L, Imberti L, Lugaresi A, Mancinelli C, Marrosu MG, Moiola L, Montanari E, Romano S, Musu L, Paolicelli D, Patti F, Pozzilli C, Rossi S, Salvetti M, Tedeschi G, Tola MR, Troiano M, Zaffaroni M, Malucchi S, Bertolotto, A, Capobianco, M, Amato, Mp, Capello, E, Capra, R, Centonze, D, Di Ioia, M, Gallo, Antonio, Grimaldi, L, Imberti, L, Lugaresi, A, Mancinelli, C, Marrosu, Mg, Moiola, L, Montanari, E, Romano, S, Musu, L, Paolicelli, D, Patti, F, Pozzilli, C, Rossi, S, Salvetti, M, Tedeschi, Gioacchino, Tola, Mr, Troiano, M, Zaffaroni, M, Malucchi, S, and Italian Multiple Sclerosis Study, Group
Subjects: Myxovirus Resistance Proteins, Oncology, medicine.medical_specialty, Multiple Sclerosis, Neurology, neutralizing antibodies, guidelines, immunogenicity, ifnβ, multiple sclerosis, ifn beta, interferon, antibodies, multiple sclerosis, Dermatology, Disease activity, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, medicine, Humans, Immunologic Factors, Clinical significance, Beta (finance), Randomized Controlled Trials as Topic, medicine.diagnostic_test, biology, business.industry, Multiple sclerosis, Magnetic resonance imaging, Interferon-beta, General Medicine, medicine.disease, Antibodies, Neutralizing, Magnetic Resonance Imaging, Psychiatry and Mental health, Early Diagnosis, Italy, Immunology, biology.protein, Settore MED/26 - Neurologia, Neurology (clinical), Neurosurgery, Antibody, business
Abstract: Interferon beta (IFNβ) was the first specific disease-modifying treatment licensed for relapsing-remitting multiple sclerosis, and is still one of the most commonly prescribed treatments. A strong body of evidence supports the effectiveness of IFNβ preparations in reducing the annual relapse rate, magnetic resonance (MRI) disease activity and disease progression. However, the development of binding/neutralizing antibodies (BAbs/NAbs) during treatment negatively affects clinical and MRI outcomes. Therefore, guidelines for the clinical use for the detection of NAbs in MS may result in better treatment of these patients. In October 2012, a panel of Italian neurologists from 17 MS clinics convened in Milan to review and discuss data on NAbs and their clinical relevance in the treatment of MS. In this paper, we report the panel's recommendations for the use of IFNβ Nabs detection in the early identification of IFNβ non-responsiveness and the management of patients on IFNβ treatment in Italy, according to a model of therapeutically appropriate care.
Published: 2014

11. Adverse events after endovascular treatment of chronic cerebro-spinal venous insufficiency (CCSVI) in patients with multiple sclerosis

Author: Ghezzi A, Annovazzi P, Amato MP, Capello E, Cavalla P, Cocco E, Falcini M, Patti F, Perini P, Rodegher ME, Rovaris M, Rottoli MR, Comi G, MS Study Group Italian Society of Neurology, GALLO, Antonio, Ghezzi, A, Annovazzi, P, Amato, Mp, Capello, E, Cavalla, P, Cocco, E, Falcini, M, Gallo, Antonio, Patti, F, Perini, P, Rodegher, Me, Rovaris, M, Rottoli, Mr, Comi, G, MS Study Group Italian Society of, Neurology, Gallo, A, and Comi, Giancarlo
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Status epilepticus, Aspiration pneumonia, Internal medicine, medicine, Humans, Myocardial infarction, Adverse effect, Stroke, business.industry, Multiple sclerosis, Endovascular Procedures, Brain, medicine.disease, Thrombosis, Hydrocephalus, Surgery, Spinal Cord, Venous Insufficiency, Neurology, Cardiology, Female, Neurology (clinical), medicine.symptom, business
Abstract: Although it is debated whether chronic cerebro-spinal venous insufficiency (CCSVI) plays a role in multiple sclerosis (MS) development, many patients undergo endovascular treatment (ET) of CCSVI. A study is ongoing in Italy to evaluate the clinical outcome of ET. Severe adverse events (AEs) occurred in 15/462 subjects at a variable interval after ET: jugular thrombosis in seven patients, tetraventricular hydrocephalus, stroke, paroxysmal atrial fibrillation, status epilepticus, aspiration pneumonia, hypertension with tachicardia, or bleeding of bedsore in the remaining seven cases. One patient died because of myocardial infarction 10 weeks after ET. The risk of severe AEs related to ET for CCSVI must be carefully considered.
Published: 2013

12. Off-Adherence Keeping (OAK) observational study: intentional off-adherence immunomodulatory multiple sclerosis treatment

Author: Marco, Peresson, Salvatore, Cottone, Vincenzo, Brescia Morra, Giuseppe, Salemi, Antonio, Gallo, Paola, Valentino, Luca, Prosperini, Peresson, Marco, Cottone, Salvatore, Brescia Morra, Vincenzo, Salemi, Giuseppe, Gallo, Antonio, Valentino, Paola, and Prosperini, Luca
Subjects: relapses, Multiple Sclerosis, Relapsing-Remitting, Treatment Outcome, quality of life, Recurrence, Humans, Settore MED/26 - Neurologia, Interferon-beta, Neurology (clinical), multiple sclerosis, treatment adherence, Interferon beta-1a, intramuscular interferon beta-1a
Abstract: Aims: To evaluate how improved treatment adherence with a lower-frequency regimen/treatment of intramuscular (IM) IFN beta-1a impacts therapeutic effectiveness in relapsing-remitting multiple sclerosis (MS) patients switching from a higher-frequency injectable regimen/treatment. Patients & methods: Italian patients with relapsing-remitting MS and prior poor adherence to high-frequency injectable treatments (n = 181) were followed for 24 months after starting IM IFN beta-1a. Results: During the study, 97.4% of patients were treatment adherent; 22.1% of patients reported a relapse. The estimated probability of remaining relapse-free after 2 years was 78%. A high dropout rate (52.5%) led to small sample size and reduced statistical power. Conclusion: Intramuscular IFN beta-1a treatment was associated with high adherence and a low relapse rate. Unfortunately, low patient retention limited the generalizability of these findings.Plain language summary: Prior research suggests that taking the drug IFN beta-1a through less frequent muscle injections enables more patients to adhere to their prescription than taking other medications. This study included 181 Italian patients with relapsing-remitting multiple sclerosis (MS) who historically did not take medication as often as prescribed. Relapses of MS were counted among patients treated with muscle injections of IFN beta-1a for 2 years; 97.4% of patients followed their prescription and 22.1% experienced a relapse. From these data, 78% of patients were estimated not to experience a relapse during 2 years of IFN beta-1a muscle injections. However, an unusually high number of patients (52.5%) left the study within 2 years, which makes it difficult to draw firm conclusions.
Published: 2022

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

Author: Giacomo Lus, Marco André Bassano, Vincenzo Brescia Morra, Simona Bonavita, Antonio Gallo, Davide Maimone, Laura Malerba, Giorgia Teresa Maniscalco, Francesco Saccà, Giuseppe Salemi, Renato Turrini, Salvatore Cottone, Edoardo Sessa, Maria Buccafusca, Luigi Maria Edoardo Grimaldi, Lus, Giacomo, Bassano, Marco André, Brescia Morra, Vincenzo, Bonavita, Simona, Gallo, Antonio, Maimone, Davide, Malerba, Laura, Maniscalco, Giorgia Teresa, Saccà, Francesco, Salemi, Giuseppe, Turrini, Renato, Cottone, Salvatore, Sessa, Edoardo, Buccafusca, Maria, and Grimaldi, Luigi Maria Edoardo
Subjects: Secondary progressive multiple sclerosis (SPMS), Dermatology, General Medicine, Biomarker, Multiple Sclerosis, Chronic Progressive, Multiple sclerosis, Psychiatry and Mental health, Multiple Sclerosis, Relapsing-Remitting, Italy, Expert opinion, Diagnosis, Quality of Life, Disease Progression, Humans, Multiple sclerosi, Settore MED/26 - Neurologia, Neurology (clinical), Neoplasm Recurrence, Local, Atrophy, Delivery of Health Care, Biomarkers, Diagnosi
Abstract: Objective Multiple sclerosis (MS) is a chronic disease with different clinical courses and a tendency to worsening. The relapsing–remitting MS presents acute onset and relapses of neurological symptoms, followed by their remission. This form can convert to secondary progressive MS (SPMS) with irreversible neurological worsening and disability. The identification of signs, symptoms, markers of progression, and strategies to manage MS patients is mandatory to allow early identification of those at higher risk of conversion to SPMS, for prompt intervention to cope with the progression of the disease. Methods A panel of Italian experts from Southern Italy have reviewed the current knowledge on MS and its management and identified the crucial tools for SPMS recognition. Results More effective communication between patients and clinicians should be established, with the support of digital tools. Moreover, the improvement in the clinical use of biomarkers for progression (cellular structures and tissue organization, such as neurofilaments and chitinase 3-like 1, axonal and neurons density) and of instrumental analyses for recognition of whole-brain atrophy, chronic active lesions, spinal cord lesions and atrophy, and the improvement the combination of the Expanded Disability Status Scale and the evaluation of cognitive dysfunction are discussed. Conclusion Given the availability of a pharmacological option, adequate education both for patients, regarding the evolution of the disease and the specific treatment, and for professionals, to allow more effective and sensitive communication and the best use of diagnostic and management tools, could represent a strategy to improve patient management and their quality of life.
Published: 2023

14. Prediction of the information processing speed performance in multiple sclerosis using a machine learning approach in a large multicenter magnetic resonance imaging data set

Author: Chiara, Marzi, D'Ambrosio, Alessandro, Stefano, Diciotti, Alvino, Bisecco, Manuela, Altieri, Massimo, Filippi, Maria Assunta Rocca, Loredana, Storelli, Pantano, Patrizia, Tommasin, Silvia, Cortese, ROSA MARIA, De Stefano, Nicola, Gioacchino, Tedeschi, Antonio, Gallo, the INNI Network, Marzi, Chiara, D'Ambrosio, Alessandro, Diciotti, Stefano, Bisecco, Alvino, Altieri, Manuela, Filippi, Massimo, Rocca, Maria Assunta, Storelli, Loredana, Pantano, Patrizia, Tommasin, Silvia, Cortese, Rosa, De Stefano, Nicola, Tedeschi, Gioacchino, Gallo, Antonio, Marzi C., d'Ambrosio A., Diciotti S., Bisecco A., Altieri M., Filippi M., Rocca M.A., Storelli L., Pantano P., Tommasin S., Cortese R., De Stefano N., Tedeschi G., and Gallo A.
Subjects: MRI, artificial intelligence, cognitive performance, information processing speed, machine learning, multiple sclerosis, symbol digit modalities test, Radiological and Ultrasound Technology, Neuropsychological Tests, Magnetic Resonance Imaging, Neurology, multiple sclerosi, Humans, Radiology, Nuclear Medicine and imaging, Neurology (clinical), Anatomy, Cognition Disorders, Processing Speed
Abstract: Many patients with multiple sclerosis (MS) experience information processing speed (IPS) deficits, and the Symbol Digit Modalities Test (SDMT) has been recommended as a valid screening test. Magnetic resonance imaging (MRI) has markedly improved the understanding of the mechanisms associated with cognitive deficits in MS. However, which structural MRI markers are the most closely related to cognitive performance is still unclear. We used the multicenter 3T-MRI data set of the Italian Neuroimaging Network Initiative to extract multimodal data (i.e., demographic, clinical, neuropsychological, and structural MRIs) of 540 MS patients. We aimed to assess, through machine learning techniques, the contribution of brain MRI structural volumes in the prediction of IPS deficits when combined with demographic and clinical features. We trained and tested the eXtreme Gradient Boosting (XGBoost) model following a rigorous validation scheme to obtain reliable generalization performance. We carried out a classification and a regression task based on SDMT scores feeding each model with different combinations of features. For the classification task, the model trained with thalamus, cortical gray matter, hippocampus, and lesions volumes achieved an area under the receiver operating characteristic curve of 0.74. For the regression task, the model trained with cortical gray matter and thalamus volumes, EDSS, nucleus accumbens, lesions, and putamen volumes, and age reached a mean absolute error of 0.95. In conclusion, our results confirmed that damage to cortical gray matter and relevant deep and archaic gray matter structures, such as the thalamus and hippocampus, is among the most relevant predictors of cognitive performance in MS.
Published: 2023

15. 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

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

Author: Paola Cavalla, Laura Brambilla, Roberta Grasso, Cinzia Cordioli, Alice Laroni, Alessia Giugno, Valentina Torri Clerici, Maria Pia Sormani, Pietro Annovazzi, Francesco Saccà, Eleonora Cocco, Jessica Frau, Elisabetta Signoriello, Antonio Gallo, Marinella Clerico, Stefania Federica De Mercanti, Antonio Carotenuto, Simona Bonavita, Cinzia Valeria Russo, Giuseppe Fenu, Caterina Lapucci, Giorgia Teresa Maniscalco, Arianna Sartori, Francesca Caleri, Marco Capobianco, Alessio Signori, Rosa Iodice, Sara La Gioia, Giacomo Lus, Mauro Zaffaroni, Damiano Baroncini, Valeria Di Francescantonio, Russo, C. V., Sacca, F., Frau, J., Annovazzi, P., Signoriello, E., Bonavita, S., Grasso, R., Clerico, M., Cordioli, C., Laroni, A., Capobianco, M., Torri Clerici, V., Sartori, A., Cavalla, P., Maniscalco, G. T., La Gioia, S., Caleri, F., Giugno, A., Iodice, R., Carotenuto, A., Cocco, E., Fenu, G., Zaffaroni, M., Baroncini, D., Lus, G., Gallo, A., De Mercanti, S. F., Lapucci, C., Di Francescantonio, V., Brambilla, L., Sormani, M. P., Signori, A., Russo, CINZIA VALERIA, Sacca', Francesco, Frau, Jessica, Annovazzi, Pietro, Signoriello, Elisabetta, Bonavita, Simona, Grasso, Roberta, Clerico, Marinella, Cordioli, Cinzia, Laroni, Alice, Capobianco, Marco, Torri Clerici, Valentina, Sartori, Arianna, Cavalla, Paola, Teresa Maniscalco, Giorgia, La Gioia, Sara, Caleri, Francesca, Giugno, Alessia, Iodice, Rosa, Carotenuto, Antonio, Cocco, Eleonora, Fenu, Giuseppe, Zaffaroni, Mauro, Baroncini, Damiano, Lus, Giacomo, Gallo, Antonio, Federica De Mercanti, Stefania, Lapucci, Caterina, Di Francescantonio, Valeria, Brambilla, Laura, Pia Sormani, Maria, and Signori, Alessio
Subjects: Adult, safety, medicine.medical_specialty, efficacy, Multiple Sclerosis, Relapsing-Remitting, Natalizumab, Internal medicine, alemtuzumab, medicine, Humans, Glatiramer acetate, real-world evidence, Retrospective Studies, Expanded Disability Status Scale, Fingolimod Hydrochloride, business.industry, Multiple sclerosis, Glatiramer Acetate, cohort, medicine.disease, Fingolimod, Neurology, Relative risk, Cohort, Alemtuzumab, Neurology (clinical), business, medicine.drug
Abstract: Background and purpose: Real-world data on alemtuzumab are limited and do not provide evidence of its effectiveness after various disease-modifying therapies (DMTs). Our aim was to provide real-world data on the impact of clinical variables and previous DMTs on clinical response to alemtuzumab. Methods: Sixteen Italian multiple sclerosis centers retrospectively included patients who started alemtuzumab from January 2015 to December 2018, and recorded demographics, previous therapies, washout duration, relapses, Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging data. Negative binomial regression models were used to assess the effect of factors on annualized relapse (ARR) after alemtuzumab initiation. Results: We studied 322 patients (mean age 36.8years, median EDSS score 3, median follow-up 1.94years). Previous treatments were: fingolimod (106), natalizumab (80), first-line oral agents (56), first-line injectables (interferon/glatiramer acetate; 30), and other drugs (15). Thirty-five patients were treatment-naïve. The pre-alemtuzumab ARR was 0.99 and decreased to 0.13 during alemtuzumab treatment (p&nbsp
Published: 2021

17. Investigating Functional Network Abnormalities and Associations with Disability in Multiple Sclerosis

Author: Carotenuto, Antonio, Paola, Valsasina, Menno, M Schoonheim, Jeroen J, G Geurts, Frederik, Barkhof, Antonio, Gallo, Gioacchino, Tedeschi, Tommasin, Silvia, Pantano, Patrizia, Massimo, Filippi, Maria, A Rocca, MAGNIMS Study Group, Carotenuto, Antonio, Valsasina, Paola, Schoonheim, Menno M, Geurts, Jeroen J G, Barkhof, Frederik, Gallo, Antonio, Tedeschi, Gioacchino, Tommasin, Silvia, Pantano, Patrizia, Filippi, Massimo, Rocca, Maria A, Executive board Vrije Universiteit, Anatomy and neurosciences, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Neuroinfection & -inflammation, Amsterdam Neuroscience - Neurodegeneration, and Radiology and nuclear medicine
Subjects: neuroimaging, Multiple Sclerosis, multiple sclerosis, resting state, graph theory, Brain, Multiple Sclerosis, Chronic Progressive, Magnetic Resonance Imaging, Cross-Sectional Studies, Multiple Sclerosis, Relapsing-Remitting, Humans, Female, Neurology (clinical), Atrophy
Abstract: Background and Objectives:In multiple sclerosis (MS), functional networks undergo continuous reconfiguration and topography changes over the disease course. Here, we aimed to investigate functional networks topography abnormalities in MS and their association with disease phenotype, clinical and cognitive disability, and structural MRI damage.Methods:This is a multi-centre cross-sectional study. Enrolled subjects performed MRI, neurological and neuropsychological assessment. Network topography was assessed on resting state fMRI data using degree centrality, which counted the number of functional connections of each grey matter voxel with the rest of the brain. SPM12 age-, sex-, scanner-, framewise displacement and grey matter volume adjusted ANOVA and multivariable regressions were employed (pResults:We enrolled 971 patients with MS (624 females; mean age=43.1 ±11.8 years; 47 clinically isolated syndrome [CIS], 704 relapsing-remitting [RRMS], 145 secondary progressive [SPMS] and 75 primary progressive [PPMS]) and 330 healthy controls (186 females; mean age=41.2 ± 13.3 years). Patients with MS showed reduced centrality in the salience and sensorimotor networks as well as increased centrality in the default mode network vs controls (pvs controls and in RRMS vs CIS (pvs RRMS (pvs controls (pvs cognitively preserved patients (pDiscussion:Patients with MS presented with reduced centrality in the salience and primary sensorimotor networks and increased centrality in the default mode network. Centrality abnormalities were specific for different disease phenotypes and associated with clinical and cognitive disability, hence suggesting that voxel-wise centrality analysis may reflect pathological substrates underpinning disability accrual.
Published: 2022

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

Author: Schiavetti I., Carmisciano L., Ponzano M., Cordioli C., Cocco E., Marfia G. A., Inglese M., Filippi M., Radaelli M., Bergamaschi R., Immovilli P., Capobianco M., De Rossi N., Brichetto G., Scandellari C., Cavalla P., Pesci I., Confalonieri P., Perini P., Trojano M., Lanzillo R., Tedeschi G., Comi G., Battaglia M. A., Patti F., Salvetti M., Sormani M. P., Abbadessa G., Aguglia U., Allegorico L., Rossi Allegri B. M., Alteno A., Amato M. P., Annovazzi P., Antozzi C., Appendino L., Arena S., Baione V., Balgera R., Barcella V., Baroncini D., Barrila C., Bellacosa A., Bellucci G., Bergamaschi V., Bezzini D., Biolzi B., Bisecco A., Bonavita S., Borriello G., Bosa C., Bosco A., Bovis F., Bozzali M., Brambilla L., Brescia Morra V., Buccafusca M., Bucciantini E., Bucello S., Buscarinu M. C., Cabboi M. P., Calabrese M., Calabria F., Caleri F., Camilli F., Caniatti L. M., Cantello R., Capra R., Capuano R., Carta P., Celani M. G., Cellerino M., Cerqua R., Chisari C., Clerici R., Clerico M., Cola G., Conte A., Conti M. Z., Cordano C., Cordera S., Corea F., Correale C., Cottone S., Crescenzo F., Curti E., d'Ambrosio A., D'Amico E., Danni M. C., d'Arma A., Dattola V., de Biase S., De Luca G., De Mercanti S. F., De Mitri P., De Stefano N., Della Cava F. M., Cava M. D., Di Lemme S., di Napoli M., Di Sapio A., Docimo R., Dutto A., Evangelista L., Fanara S., Fantozzi R., Ferraro D., Ferro M. T., Fioretti C., Fratta M., Frau J., Fronza M., Furlan R., Gajofatto A., Gallo A., Gallo P., Gasperini C., Ghazaryan A., Giometto B., Gobbin F., Govone F., Granella F., Grange E., Grasso M. G., Grimaldi L. M. E., Guareschi A., Guaschino C., Guerrieri S., Guidetti D., Juergenson I. B., Iaffaldano P., Ianniello A., Iasevoli L., Imperiale D., Infante M. T., Iodice R., Iovino A., Konrad G., Landi D., Lapucci C., Lavorgna L., L'Episcopo M. R., Leva S., Liberatore G., Lo Re M., Longoni M., Lopiano L., Lorefice L., Lucchini M., Lus G., Maimone D., Malentacchi M., Mallucci G., Malucchi S., Mancinelli C. R., Mancinelli L., Manganotti P., Maniscalco G. T., Mantero V., Marangoni S., Marastoni D., Marinelli F., Marti A., Boneschi Martinelli F., Masserano Z. F., Matta F., Mendozzi L., Meucci G., Miante S., Miele G., Milano E., Mirabella M., Missione R., Moccia M., Moiola L., Montepietra S., MontiBragadin M., Montini F., Motta R., Nardone R., Gabri Nicoletti C., Nobile-Orazio E., Nozzolillo A., Onofrj M., Orlandi R., Palmieri A., Paolicelli D., Pasquali L., Pasto L., Pedrazzoli E., Petracca M., Petrone A., Piantadosi C., Pietroboni A. M., Pinardi F., Portaccio E., Pozzato M., Pozzilli C., Prosperini L., Protti A., Ragonese P., Rasia S., Realmuto S., Repice A., Rigoni E., Rilla M. T., Rinaldi F., Romano C. M., Ronzoni M., Rovaris M., Ruscica F., Sabattini L., Salemi G., Saraceno L., Sartori A., Sbragia E., Scarano G. I., Scarano V., Sessa M., Sgarito C., Sibilia G., Siciliano G., Signori A., Signoriello E., Sinisi L., Sireci F., Sola P., Solaro C., Sotgiu S., Sparaco M., Stromillo M. L., Strumia S., Susani E. L., Tabiadon G., Teatini F., Tomassini V., Tonietti S., Torri V., Tortorella C., Toscano S., Totaro R., Trotta M., Turano G., Ulivelli M., Valentino M., Vaula G., Vecchio D., Vercellino M., Verrengia E. P., Vianello M., Virgilio E., Vitetta F., Vollaro S., Zaffaroni M., Zampolini M., Zarbo I. R., Zito A., Zuliani L., Schiavetti, Irene, Carmisciano, Luca, Ponzano, Marta, Cordioli, Cinzia, Cocco, Eleonora, Marfia, Girolama Alessandra, Inglese, Matilde, Filippi, Massimo, Radaelli, Marta, Bergamaschi, Roberto, Immovilli, Paolo, Capobianco, Marco, De Rossi, Nicola, Brichetto, Giampaolo, Scandellari, Cinzia, Cavalla, Paola, Pesci, Ilaria, Confalonieri, Paolo, Perini, Paola, Trojano, Maria, Lanzillo, Roberta, Tedeschi, Gioacchino, Comi, Giancarlo, Battaglia, Mario Alberto, Patti, Francesco, Salvetti, Marco, Sormani, Maria Pia, Gianmarco, Abbadessa, Umberto, Aguglia, Allegorico, Lia, Beatrice Maria Rossi Allegri, Anastasia, Alteno, Amato, MARIA PIA, Pietro, Annovazzi, Carlo, Antozzi, Lucia, Appendino, Sebastiano, Arena, Viola, Baione, Roberto, Balgera, Valeria, Barcella, Damiano, Baroncini, Caterina, Barrilà, Alessandra, Bellacosa, Gianmarco, Bellucci, Valeria, Bergamaschi, Daiana, Bezzini, Beatrice, Biolzi, Bisecco, Alvino, Simona, Bonavita, Giovanna, Borriello, Chiara, Bosa, Antonio, Bosco, Francesca, Bovi, Marco, Bozzali, Laura, Brambilla, BRESCIA MORRA, Vincenzo, Maria, Buccafusca, Elisabetta, Bucciantini, Sebastiano, Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano, Calabrese, Francesca, Calabria, Francesca, Caleri, Federico, Camilli, Luisa Maria Caniatti, Roberto, Cantello, Ruggero, Capra, Rocco, Capuano, Patrizia, Carta, Maria Grazia Celani, Maria, Cellerino, Raffaella, Cerqua, Clara, Chisari, Raffaella, Clerici, Marinella, Clerico, Gaia, Cola, Antonella, Conte, Marta Zaffira Conti, Christian, Cordano, Susanna, Cordera, Francesco, Corea, Claudio, Correale, Salvatore, Cottone, Francesco, Crescenzo, Erica, Curti, Alessandro, D’Ambrosio, Emanuele, D’Amico, Maura Chiara Danni, Alessia, D’Arma, Vincenzo, Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Stefano, Fabio Maria Della Cava, Marco Della Cava, Sonia Di Lemme, Mario di Napoli, Alessia Di Sapio, Renato, Docimo, Anna, Dutto, Luana, Evangelista, Salvatore, Fanara, Roberta, Fantozzi, Diana, Ferraro, Maria Teresa Ferrò, Cristina, Fioretti, Mario, Fratta, Jessica, Frau, Marzia, Fronza, Roberto, Furlan, Alberto, Gajofatto, Gallo, Antonio, Paolo, Gallo, Claudio, Gasperini, Anna, Ghazaryan, Bruno, Giometto, Francesca, Gobbin, Flora, Govone, Franco, Granella, Erica, Grange, Grasso, MARIA GRAZIA, Grimaldi, Luigi M. E., Angelica, Guareschi, Clara, Guaschino, Simone, Guerrieri, Donata, Guidetti, Ina Barbara Juergenson, Pietro, Iaffaldano, Ianniello, Antonio, Luigi, Iasevoli, Daniele, Imperiale, Maria Teresa Infante, Iodice, Rosa, Iovino, Aniello, Giovanna, Konrad, Doriana, Landi, Caterina, Lapucci, Luigi, Lavorgna, Maria Rita L’Episcopo, Serena, Leva, Giuseppe, Liberatore, Marianna Lo Re, Marco, Longoni, Leonardo, Lopiano, Lorena, Lorefice, Matteo, Lucchini, Lus, Giacomo, Maimone, Davide, Maria, Malentacchi, Giulia, Mallucci, Simona, Malucchi, Chiara Rosa Mancinelli, Luca, Mancinelli, Paolo, Manganotti, Giorgia Teresa Maniscalco, Vittorio, Mantero, Sabrina, Marangoni, Damiano, Marastoni, Fabiana, Marinelli, Marti, NICOLA ALESSANDRO, Filippo Boneschi Martinelli, Zoli Federco Masserano, Francesca, Matta, Laura, Mendozzi, Giuseppe, Meucci, Silvia, Miante, Giuseppina, Miele, Eva, Milano, Massimiliano, Mirabella, Rosanna, Missione, Moccia, Marcello, Lucia, Moiola, Sara, Montepietra, Margherita, Montibragadin, Federico, Montini, Roberta, Motta, Raffaele, Nardone, Carolina Gabri Nicoletti, Eduardo, Nobile‐orazio, Nozzolillo, Agostino, Marco, Onofrj, Riccardo, Orlandi, Anna, Palmieri, Damiano, Paolicelli, Livia, Pasquali, Luisa, Pastò, Elisabetta, Pedrazzoli, Petracca, Maria, Alfredo, Petrone, Carlo, Piantadosi, Pietroboni, Anna M., Federica, Pinardi, Emilio, Portaccio, Mattia, Pozzato, Pozzilli, Carlo, Luca, Prosperini, Alessandra, Protti, Paolo, Ragonese, Sarah, Rasia, Sabrina, Realmuto, Anna, Repice, Eleonora, Rigoni, Maria Teresa Rilla, DELLA RATTA RINALDI, Francesca, Calogero Marcello Romano, Marco, Ronzoni, Marco, Rovari, Francesca, Ruscica, Loredana, Sabattini, Giuseppe, Salemi, Lorenzo, Saraceno, Alessia, Sartori, Arianna, Sartori, Elvira, Sbragia, Giuditta Ilaria Scarano, Valentina, Scarano, Maria, Sessa, Caterina, Sgarito, Sibilia, Grazia, Gabriele, Siciliano, Alessio, Signori, Signoriello, Elisabetta, Sinisi, Leonardo, Francesca, Sireci, Patrizia, Sola, Claudio, Solaro, Stefano, Sotgiu, Maddalena, Sparaco, Maria Laura Stromillo, Silvia, Strumia, Emanuela Laura Susani, Giulietta, Tabiadon, Francesco, Teatini, Valentina, Tomassini, Simone, Tonietti, Valentina, Torri, Tortorella, Carla, Simona, Toscano, Rocco, Totaro, Maria, Trotta, Gabriella, Turano, Monica, Ulivelli, Manzo, Valentino, Giovanna, Vaula, Domizia, Vecchio, Marco, Vercellino, Elena Pinuccia Verrengia, Marika, Vianello, Eleonora, Virgilio, Francesca, Vitetta, Vollaro, Stefano, Mauro, Zaffaroni, Mauro, Zampolini, Ignazio Roberto Zarbo, Antonio, Zito, and Luigi Zuliani, Schiavetti, I., Carmisciano, L., Ponzano, M., Cordioli, C., Cocco, E., Marfia, G. A., Inglese, M., Filippi, M., Radaelli, M., Bergamaschi, R., Immovilli, P., Capobianco, M., De Rossi, N., Brichetto, G., Scandellari, C., Cavalla, P., Pesci, I., Confalonieri, P., Perini, P., Trojano, M., Lanzillo, R., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., Sormani, M. P., Abbadessa, G., Aguglia, U., Allegorico, L., Rossi Allegri, B. M., Alteno, A., Amato, M. P., Annovazzi, P., Antozzi, C., Appendino, L., Arena, S., Baione, V., Balgera, R., Barcella, V., Baroncini, D., Barrila, C., Bellacosa, A., Bellucci, G., Bergamaschi, V., Bezzini, D., Biolzi, B., Bisecco, A., Bonavita, S., Borriello, G., Bosa, C., Bosco, A., Bovis, F., Bozzali, M., Brambilla, L., Brescia Morra, V., Buccafusca, M., Bucciantini, E., Bucello, S., Buscarinu, M. C., Cabboi, M. P., Calabrese, M., Calabria, F., Caleri, F., Camilli, F., Caniatti, L. M., Cantello, R., Capra, R., Capuano, R., Carta, P., Celani, M. G., Cellerino, M., Cerqua, R., Chisari, C., Clerici, R., Clerico, M., Cola, G., Conte, A., Conti, M. Z., Cordano, C., Cordera, S., Corea, F., Correale, C., Cottone, S., Crescenzo, F., Curti, E., D'Ambrosio, A., D'Amico, E., Danni, M. C., D'Arma, A., Dattola, V., de Biase, S., De Luca, G., De Mercanti, S. F., De Mitri, P., De Stefano, N., Della Cava, F. M., Cava, M. D., Di Lemme, S., di Napoli, M., Di Sapio, A., Docimo, R., Dutto, A., Evangelista, L., Fanara, S., Fantozzi, R., Ferraro, D., Ferro, M. T., Fioretti, C., Fratta, M., Frau, J., Fronza, M., Furlan, R., Gajofatto, A., Gallo, A., Gallo, P., Gasperini, C., Ghazaryan, A., Giometto, B., Gobbin, F., Govone, F., Granella, F., Grange, E., Grasso, M. G., Grimaldi, L. M. E., Guareschi, A., Guaschino, C., Guerrieri, S., Guidetti, D., Juergenson, I. B., Iaffaldano, P., Ianniello, A., Iasevoli, L., Imperiale, D., Infante, M. T., Iodice, R., Iovino, A., Konrad, G., Landi, D., Lapucci, C., Lavorgna, L., L'Episcopo, M. R., Leva, S., Liberatore, G., Lo Re, M., Longoni, M., Lopiano, L., Lorefice, L., Lucchini, M., Lus, G., Maimone, D., Malentacchi, M., Mallucci, G., Malucchi, S., Mancinelli, C. R., Mancinelli, L., Manganotti, P., Maniscalco, G. T., Mantero, V., Marangoni, S., Marastoni, D., Marinelli, F., Marti, A., Boneschi Martinelli, F., Masserano, Z. F., Matta, F., Mendozzi, L., Meucci, G., Miante, S., Miele, G., Milano, E., Mirabella, M., Missione, R., Moccia, M., Moiola, L., Montepietra, S., Montibragadin, M., Montini, F., Motta, R., Nardone, R., Gabri Nicoletti, C., Nobile-Orazio, E., Nozzolillo, A., Onofrj, M., Orlandi, R., Palmieri, A., Paolicelli, D., Pasquali, L., Pasto, L., Pedrazzoli, E., Petracca, M., Petrone, A., Piantadosi, C., Pietroboni, A. M., Pinardi, F., Portaccio, E., Pozzato, M., Pozzilli, C., Prosperini, L., Protti, A., Ragonese, P., Rasia, S., Realmuto, S., Repice, A., Rigoni, E., Rilla, M. T., Rinaldi, F., Romano, C. M., Ronzoni, M., Rovaris, M., Ruscica, F., Sabattini, L., Salemi, G., Saraceno, L., Sartori, A., Sbragia, E., Scarano, G. I., Scarano, V., Sessa, M., Sgarito, C., Sibilia, G., Siciliano, G., Signori, A., Signoriello, E., Sinisi, L., Sireci, F., Sola, P., Solaro, C., Sotgiu, S., Sparaco, M., Stromillo, M. L., Strumia, S., Susani, E. L., Tabiadon, G., Teatini, F., Tomassini, V., Tonietti, S., Torri, V., Tortorella, C., Toscano, S., Totaro, R., Trotta, M., Turano, G., Ulivelli, M., Valentino, M., Vaula, G., Vecchio, D., Vercellino, M., Verrengia, E. P., Vianello, M., Virgilio, E., Vitetta, F., Vollaro, S., Zaffaroni, M., Zampolini, M., Zarbo, I. R., Zito, A., and Zuliani, L.
Subjects: Multiple Sclerosis, Anosmia, Clinical Sciences, neurological disorders, Neurodegenerative, Settore MED/26, demyelinating disease, COVID-19, demyelinating diseases, disease-modifying treatment, multiple sclerosis, Humans, neurological disorder, Aged, Neurology & Neurosurgery, SARS-CoV-2, Pain Research, Neurosciences, Brain Disorders, Settore MED/26 - NEUROLOGIA, Good Health and Well Being, Neurology, multiple sclerosi, Neurology (clinical), MuSC-19 Study Group, Ageusia, Human
Abstract: Background and purpose: Clinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID-19) have been thoroughly investigated, but a further analysis on main signs and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID-19 in MS patients and identify all factors associated with their manifestation. Method: Logistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number. Results: From March 2020 to November 2021, data were collected from 1354 MS patients with confirmed infection of COVID-19. Ageusia and anosmia was less frequent in older people (odds ratio [OR] 0.98; p=0.005) and more in smoker patients (OR 1.39; p=0.049). Smoke was also associated with an incremental number of symptoms (OR 1.24; p=0.031), substance abuse (drugs or alcohol), conjunctivitis and rash (OR 5.20; p=0.042) and the presence of at least one comorbidity with shortness of breath, tachycardia or chest pain (OR 1.24; p=0.008). Some disease-modifying therapies were associated with greater frequencies of certain COVID-19 symptoms (association between anti-CD20 therapies and increment in the number of concomitant symptoms: OR 1.29; p=0.05). Differences in frequencies between the three waves were found for flu-like symptoms (G1, p=0.024), joint or muscle pain (G2, p=0.013) and ageusia and anosmia (G5, p < 0.001). All cases should be referred to variants up to Delta. Conclusion: Several factors along with the choice of specific therapeutic approaches might have a different impact on the occurrence of some COVID-19 symptoms.
Published: 2022

19. Worldwide experience of homozygous familial hypercholesterolaemia:retrospective cohort study

Author: Tycho R Tromp, Merel L Hartgers, G Kees Hovingh, Antonio J Vallejo-Vaz, Kausik K Ray, Handrean Soran, Tomas Freiberger, Stefano Bertolini, Mariko Harada-Shiba, Dirk J Blom, Frederick J Raal, Marina Cuchel, Tycho R. Tromp, Merel L. Hartgers, G. Kees Hovingh, Antonio J. Vallejo-Vaz, Kausik K. Ray, Stefano A. Bertolini, Jing Pang, Gerald F. Watts, Susanne Greber-Platzer, Martin Mäser, Thomas M. Stulnig, Christoph F. Ebenbichler, Khalid Bin Thani, David Cassiman, Olivier S. Descamps, Daisy Rymen, Peter Witters, Raul D. Santos, Liam R. Brunham, Gordon A. Francis, Jacques Genest, Robert A. Hegele, Brooke A. Kennedy, Isabelle Ruel, Mark H. Sherman, Long Jiang, Luya Wang, Željko Reiner, Vladimir Blaha, Richard Ceska, Jana Dvorakova, Lubomir Dlouhy, Pavel Horak, Vladimir Soska, Lukas Tichy, Robin Urbanek, Helena Vaverkova, Michal Vrablik, Stanislav Zemek, Lukas Zlatohlavek, Sameh Emil, Tarek Naguib, Ashraf Reda, Sophie Béliard, Eric Bruckert, Antonio Gallo, Moses S. Elisaf, Genovefa Kolovou, Hofit Cohen, Ronen Durst, Eldad J. Dann, Avishay Elis, Osama Hussein, Eran Leitersdorf, Daniel Schurr, Nitika Setia, Ishwar C. Verma, Mohammed D. Alareedh, Mutaz Al-Khnifsawi, Ali F. Abdalsahib Al-Zamili, Sabah H. Rhadi, Foaad K. Shaghee, Marcello Arca, Maurizio Averna, Andrea Bartuli, Marco Bucci, Paola S. Buonuomo, Paolo Calabrò, Sebastiano Calandra, Manuela Casula, Alberico L. Catapano, Angelo B. Cefalù, Arrigo F.G. Cicero, Sergio D'Addato, Laura D'Erasmo, Alessia Di Costanzo, Tommaso Fasano, Marta Gazzotti, Antonina Giammanco, Gabriella Iannuzzo, Anastasia Ibba, Emanuele A. Negri, Andrea Pasta, Chiara Pavanello, Livia Pisciotta, Claudio Rabacchi, Carlo Ripoli, Tiziana Sampietro, Francesco Sbrana, Fulvio Sileo, Patrizia Suppressa, Patrizia Tarugi, Chiara Trenti, Maria G. Zenti, Mika Hori, Mahmoud H. Ayesh, Sami T. Azar, Fadi F. Bitar, Akl C. Fahed, Elie M. Moubarak, Georges Nemer, Hapizah M. Nawawi, Ramón Madriz, Roopa Mehta, Arjen J. Cupido, Joep C. Defesche, M. Doortje Reijman, Jeanine E. Roeters-van Lennep, Erik S.G. Stroes, Albert Wiegman, Linda Zuurbier, Khalid Al-Waili, Fouzia Sadiq, Krzysztof Chlebus, Mafalda Bourbon, Isabel M. Gaspar, Katarina S. Lalic, Marat V. Ezhov, Andrey V. Susekov, Urh Groselj, Min-Ji Charng, Weerapan Khovidhunkit, Melih Aktan, Bulent B. Altunkeser, Sinan Demircioglu, Melis Kose, Cumali Gokce, Osman Ilhan, Meral Kayikcioglu, Leyla G. Kaynar, Irfan Kuku, Erdal Kurtoglu, Harika Okutan, Osman I. Ozcebe, Zafer Pekkolay, Saim Sag, Osman Z. Salcioglu, Ahmet Temizhan, Mustafa Yenercag, Mehmet Yilmaz, Hamiyet Yilmaz Yasar, Olena Mitchenko, Alexander R.M. Lyons, Christophe A.T. Stevens, Julie A. Brothers, Lisa C. Hudgins, Christina Nguyen, Rano Alieva, Aleksandr Shek, Doan-Loi Do, Ngoc-Thanh Kim, Hong-An Le, Thanh-Tung Le, Mai-Ngoc T. Nguyen, Thanh-Huong Truong, Dirk J. Blom, Frederick J. Raal, VU University medical center, Tromp T.R., Hartgers M.L., Hovingh G.K., Vallejo-Vaz A.J., Ray K.K., Soran H., Freiberger T., Bertolini S., Harada-Shiba M., Blom D.J., Raal F.J., Cuchel M., Bertolini S.A., Pang J., Watts G.F., Greber-Platzer S., Maser M., Stulnig T.M., Ebenbichler C.F., Bin Thani K., Cassiman D., Descamps O.S., Rymen D., Witters P., Santos R.D., Brunham L.R., Francis G.A., Genest J., Hegele R.A., Kennedy B.A., Ruel I., Sherman M.H., Jiang L., Wang L., Reiner Z., Blaha V., Ceska R., Dvorakova J., Dlouhy L., Horak P., Soska V., Tichy L., Urbanek R., Vaverkova H., Vrablik M., Zemek S., Zlatohlavek L., Emil S., Naguib T., Reda A., Beliard S., Bruckert E., Gallo A., Elisaf M.S., Kolovou G., Cohen H., Durst R., Dann E.J., Elis A., Hussein O., Leitersdorf E., Schurr D., Setia N., Verma I.C., Alareedh M.D., Al-Khnifsawi M., Abdalsahib Al-Zamili A.F., Rhadi S.H., Shaghee F.K., Arca M., Averna M., Bartuli A., Bucci M., Buonuomo P.S., Calabro P., Calandra S., Casula M., Catapano A.L., Cefalu A.B., Cicero A.F.G., D'Addato S., D'Erasmo L., Di Costanzo A., Fasano T., Gazzotti M., Giammanco A., Iannuzzo G., Ibba A., Negri E.A., Pasta A., Pavanello C., Pisciotta L., Rabacchi C., Ripoli C., Sampietro T., Sbrana F., Sileo F., Suppressa P., Tarugi P., Trenti C., Zenti M.G., Hori M., Ayesh M.H., Azar S.T., Bitar F.F., Fahed A.C., Moubarak E.M., Nemer G., Nawawi H.M., Madriz R., Mehta R., Cupido A.J., Defesche J.C., Reijman M.D., Roeters-van Lennep J.E., Stroes E.S.G., Wiegman A., Zuurbier L., Al-Waili K., Sadiq F., Chlebus K., Bourbon M., Gaspar I.M., Lalic K.S., Ezhov M.V., Susekov A.V., Groselj U., Charng M.-J., Khovidhunkit W., Aktan M., Altunkeser B.B., Demircioglu S., Kose M., Gokce C., Ilhan O., Kayikcioglu M., Kaynar L.G., Kuku I., Kurtoglu E., Okutan H., Ozcebe O.I., Pekkolay Z., Sag S., Salcioglu O.Z., Temizhan A., Yenercag M., Yilmaz M., Yilmaz Yasar H., Mitchenko O., Lyons A.R.M., Stevens C.A.T., Brothers J.A., Hudgins L.C., Nguyen C., Alieva R., Shek A., Do D.-L., Kim N.-T., Le H.-A., Le T.-T., Nguyen M.-N.T., Truong T.-H., University of Amsterdam, University of Pennsylvania, European Atherosclerosis Society, Experimental Vascular Medicine, Graduate School, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, Human Genetics, Paediatric Metabolic Diseases, ACS - Diabetes & metabolism, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Heart failure & arrhythmias, R Tromp, Tycho, L Hartgers, Merel, Kees Hovingh, G, J Vallejo-Vaz, Antonio, K Ray, Kausik, Soran, Handrean, Freiberger, Toma, A Bertolini, Stefano, Harada-Shiba, Mariko, Pang, Jing, F Watts, Gerald, Greber-Platzer, Susanne, Mäser, Martin, M Stulnig, Thoma, F Ebenbichler, Christoph, Bin Thani, Khalid, Cassiman, David, S Descamps, Olivier, Rymen, Daisy, Witters, Peter, D Santos, Raul, R Brunham, Liam, A Francis, Gordon, Genest, Jacque, A Hegele, Robert, A Kennedy, Brooke, Ruel, Isabelle, H Sherman, Mark, Jiang, Long, Wang, Luya, Reiner, Željko, Blaha, Vladimir, Ceska, Richard, Dvorakova, Jana, Dlouhy, Lubomir, Horak, Pavel, Soska, Vladimir, Tichy, Luka, Urbanek, Robin, Vaverkova, Helena, Vrablik, Michal, Zemek, Stanislav, Zlatohlavek, Luka, Emil, Sameh, Naguib, Tarek, Reda, Ashraf, Béliard, Sophie, Bruckert, Eric, Gallo, Antonio, S Elisaf, Mose, Kolovou, Genovefa, Cohen, Hofit, Durst, Ronen, J Dann, Eldad, Elis, Avishay, Hussein, Osama, Leitersdorf, Eran, Schurr, Daniel, Setia, Nitika, C Verma, Ishwar, D Alareedh, Mohammed, Al-Khnifsawi, Mutaz, F Abdalsahib Al-Zamili, Ali, H Rhadi, Sabah, K Shaghee, Foaad, Arca, Marcello, Averna, Maurizio, Bartuli, Andrea, Bucci, Marco, S Buonuomo, Paola, Calabrò, Paolo, Calandra, Sebastiano, Casula, Manuela, L Catapano, Alberico, B Cefalù, Angelo, G Cicero, Arrigo F, D'Addato, Sergio, D'Erasmo, Laura, Di Costanzo, Alessia, Fasano, Tommaso, Gazzotti, Marta, Giammanco, Antonina, Iannuzzo, Gabriella, Ibba, Anastasia, A Negri, Emanuele, Pasta, Andrea, Pavanello, Chiara, Pisciotta, Livia, Rabacchi, Claudio, Ripoli, Carlo, Sampietro, Tiziana, Sbrana, Francesco, Sileo, Fulvio, Suppressa, Patrizia, Tarugi, Patrizia, Trenti, Chiara, G Zenti, Maria, Hori, Mika, H Ayesh, Mahmoud, T Azar, Sami, F Bitar, Fadi, C Fahed, Akl, M Moubarak, Elie, Nemer, George, M Nawawi, Hapizah, Madriz, Ramón, Mehta, Roopa, J Cupido, Arjen, C Defesche, Joep, Doortje Reijman, M, E Roeters-van Lennep, Jeanine, G Stroes, Erik S, Wiegman, Albert, Zuurbier, Linda, Al-Waili, Khalid, Sadiq, Fouzia, Chlebus, Krzysztof, Bourbon, Mafalda, M Gaspar, Isabel, S Lalic, Katarina, V Ezhov, Marat, V Susekov, Andrey, Groselj, Urh, Charng, Min-Ji, Khovidhunkit, Weerapan, Aktan, Melih, B Altunkeser, Bulent, Demircioglu, Sinan, Kose, Meli, Gokce, Cumali, Ilhan, Osman, Kayikcioglu, Meral, G Kaynar, Leyla, Kuku, Irfan, Kurtoglu, Erdal, Okutan, Harika, I Ozcebe, Osman, Pekkolay, Zafer, Sag, Saim, Z Salcioglu, Osman, Temizhan, Ahmet, Yenercag, Mustafa, Yilmaz, Mehmet, Yilmaz Yasar, Hamiyet, Mitchenko, Olena, M Lyons, Alexander R, T Stevens, Christophe A, A Brothers, Julie, C Hudgins, Lisa, Nguyen, Christina, Alieva, Rano, Shek, Aleksandr, Do, Doan-Loi, Kim, Ngoc-Thanh, Le, Hong-An, Le, Thanh-Tung, T Nguyen, Mai-Ngoc, Truong, Thanh-Huong, J Blom, Dirk, J Raal, Frederick, and Cuchel, Marina
Subjects: Adult, Male, Homozygous Familial Hypercholesterolemia, Adolescent, retrospective study, CHILDREN, Doenças Cardio e Cérebro-vasculares, Cohort Studies, Young Adult, Medicine, General & Internal, General & Internal Medicine, Cardiovascular Disease, Humans, Registries, LIPOPROTEIN-APHERESIS, Child, 11 Medical and Health Sciences, Retrospective Studies, Homozygous Familial Hypercholesterolaemia International Clinical Collaborators, Science & Technology, GUIDANCE, clinical characteristic, EVOLOCUMAB, Homozygous familial hypercholesterolemia, Worldwide, Therapies, Cardiovascular disease, General Medicine, CARE, OPEN-LABEL, EFFICACY, INSIGHTS, Child, Preschool, outcome, Female, genetic, Familial Hypercholesterolaemia, Life Sciences & Biomedicine
Abstract: [Background]: Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from small studies, mostly from high-income countries. The objective of this study was to assess the clinical and genetic characteristics, as well as the impact, of current practice on health outcomes of HoFH patients globally., [Methods]: The HoFH International Clinical Collaborators registry collected data on patients with a clinical, or genetic, or both, diagnosis of HoFH using a retrospective cohort study design. This trial is registered with ClinicalTrials.gov, NCT04815005., [Findings]: Overall, 751 patients from 38 countries were included, with 565 (75%) reporting biallelic pathogenic variants. The median age of diagnosis was 12∙0 years (IQR 5∙5–27∙0) years. Of the 751 patients, 389 (52%) were female and 362 (48%) were male. Race was reported for 527 patients; 338 (64%) patients were White, 121 (23%) were Asian, and 68 (13%) were Black or mixed race. The major manifestations of ASCVD or aortic stenosis were already present in 65 (9%) of patients at diagnosis of HoFH. Globally, pretreatment LDL cholesterol levels were 14∙7 mmol/L (IQR 11∙6–18∙4). Among patients with detailed therapeutic information, 491 (92%) of 534 received statins, 342 (64%) of 534 received ezetimibe, and 243 (39%) of 621 received lipoprotein apheresis. On-treatment LDL cholesterol levels were lower in high-income countries (3∙93 mmol/L, IQR 2∙6–5∙8) versus non-highincome countries (9∙3 mmol/L, 6∙7–12∙7), with greater use of three or more lipid-lowering therapies (LLT; highincome 66% vs non-high-income 24%) and consequently more patients attaining guideline-recommended LDL cholesterol goals (high-income 21% vs non-high-income 3%). A first major adverse cardiovascular event occurred a decade earlier in non-high-income countries, at a median age of 24∙5 years (IQR 17∙0–34∙5) versus 37∙0 years (29∙0–49∙0) in high-income countries (adjusted hazard ratio 1∙64, 95% CI 1∙13–2∙38)., [Interpretation]: Worldwide, patients with HoFH are diagnosed too late, undertreated, and at high premature ASCVD risk. Greater use of multi-LLT regimens is associated with lower LDL cholesterol levels and better outcomes. Significant global disparities exist in treatment regimens, control of LDL cholesterol levels, and cardiovascular event-free survival, which demands a critical re-evaluation of global health policy to reduce inequalities and improve outcomes for all patients with HoFH., Amsterdam University Medical Centers, Location Academic Medical Center; Perelman School of Medicine at the University of Pennsylvania; and European Atherosclerosis Society
Published: 2022

20. Exploring in vivo multiple sclerosis brain microstructural damage through T1w/T2w ratio: a multicentre study

Author: Monica Margoni, Elisabetta Pagani, Alessandro Meani, Loredana Storelli, Sarlota Mesaros, Jelena Drulovic, Frederik Barkhof, Hugo Vrenken, Eva Strijbis, Antonio Gallo, Alvino Bisecco, Deborah Pareto, Jaume Sastre-Garriga, Olga Ciccarelli, Marios Yiannakas, Jacqueline Palace, Paolo Preziosa, Maria A Rocca, Massimo Filippi, Margoni, Monica, Pagani, Elisabetta, Meani, Alessandro, Storelli, Loredana, Mesaros, Sarlota, Drulovic, Jelena, Barkhof, Frederik, Vrenken, Hugo, Strijbis, Eva, Gallo, Antonio, Bisecco, Alvino, Pareto, Deborah, Sastre-Garriga, Jaume, Ciccarelli, Olga, Yiannakas, Mario, Palace, Jacqueline, Preziosa, Paolo, Rocca, Maria A, Filippi, Massimo, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, and Amsterdam Neuroscience - Neuroinfection & -inflammation
Subjects: T1w/T2w-ratio, Brain, Multiple Sclerosis, Chronic Progressive, multiple sclerosis, Magnetic Resonance Imaging, White Matter, Psychiatry and Mental health, Cross-Sectional Studies, Brain Injuries, Humans, Surgery, Neurology (clinical), Retrospective Studies, MRI
Abstract: ObjectivesTo evaluate white matter and grey matter T1-weighted (w)/T2w ratio (T1w/T2w ratio) in healthy controls and patients with multiple sclerosis, and its association with clinical disability.MethodsIn this cross-sectional study, 270 healthy controls and 434 patients with multiple sclerosis were retrospectively selected from 7 European sites. T1w/T2w ratio was obtained from brain T2w and T1w scans after intensity calibration using eyes and temporal muscle.ResultsIn healthy controls, T1w/T2w ratio increased until 50–60 years both in white and grey matter. Compared with healthy controls, T1w/T2w ratio was significantly lower in white matter lesions of all multiple sclerosis phenotypes, and in normal-appearing white matter and cortex of patients with relapsing-remitting and secondary progressive multiple sclerosis (p≤0.026), but it was significantly higher in the striatum and pallidum of patients with relapsing-remitting, secondary progressive and primary progressive multiple sclerosis (p≤0.042). In relapse-onset multiple sclerosis, T1w/T2w ratio was significantly lower in white matter lesions and normal-appearing white matter already at Expanded Disability Status Scale (EDSS) ConclusionsT1w/T2w ratio may represent a clinically relevant marker sensitive to demyelination, neurodegeneration and iron accumulation occurring at the different multiple sclerosis phases.
Published: 2022

21. Humoral response and safety of the third booster dose of BNT162b2 mRNA COVID-19 vaccine in patients with multiple sclerosis treated with ocrelizumab or fingolimod

Author: Rocco Capuano, Manuela Altieri, Miriana Conte, Alvino Bisecco, Alessandro d’Ambrosio, Giovanna Donnarumma, Elena Grimaldi, Nicola Coppola, Nicola Medici, Massimiliano Galdiero, Gioacchino Tedeschi, Antonio Gallo, Capuano, Rocco, Altieri, Manuela, Conte, Miriana, Bisecco, Alvino, D'Ambrosio, Alessandro, Donnarumma, Giovanna, Grimaldi, Elena, Coppola, Nicola, Medici, Nicola, Galdiero, Massimiliano, Tedeschi, Gioacchino, and Gallo, Antonio
Subjects: Booster dose, Multiple Sclerosis, COVID-19 Vaccines, BNT162b2 mRNA vaccine, Fingolimod Hydrochloride, SARS-CoV-2, COVID-19 Vaccine, COVID-19, Fingolimod, Antibodies, Viral, Neurology, Immunoglobulin G, Multiple Sclerosi, Humans, Neurology (clinical), Ocrelizumab, RNA, Messenger, BNT162 Vaccine, Human
Abstract: Background The assessment of the safety and the humoral response to a third booster dose of the BNT162b2 mRNA COVID-19 vaccine is relevant in patients with Multiple Sclerosis (pwMS) treated with Ocrelizumab (OCR) or Fingolimod (FNG). Methods Serum samples were collected from Healthy controls (HCs) and pwMS treated with OCR or FNG at the following time-points: before the first of two vaccine doses (T0); 8 (T1), 16 (T2), 24 (T3) weeks after the first dose; within 8 weeks before (T0b) and after (T1b) the booster dose. IgG antibodies to SARS-CoV-2 trimeric spike protein (Anti-TSP IgG) were quantified and expressed as binding antibody units (BAU)/mL. Results 40 HCs, 28 pwMS on OCR and 19 on FNG were included. At T0b 12 (42.9%) pwMS on OCR and 6 (31.6%) on FNG were still positive while, at T1b 16 (57.14%) pwMS on OCR and 16 (84.2%) on FNG, passed the threshold of positivity. The increase of Anti-TSP IgG levels at T1b was higher for: (i) HCs with respect to OCR (p p = 0.032) groups; (ii) pwMS on FNG compared with pwMS on OCR (p Conclusions The third booster dose of BNT162b2 mRNA vaccine to OCR- and FNG-treated pwMS revives the humoral response, independently of any clinical variable, and manifests a good safety and tolerability profile.
Published: 2022

22. Differential association of cortical, subcortical and spinal cord damage with multiple sclerosis disability milestones: A multiparametric MRI study

Author: Chiara Zecca, Alvino Bisecco, Alessandro Meani, Paola Valsasina, Gioacchino Tedeschi, Antonio Gallo, Milagros Hidalgo de la Cruz, Maria A. Rocca, Claudio Gobbi, Massimo Filippi, Hidalgo de la Cruz, Milagro, Valsasina, Paola, Meani, Alessandro, Gallo, Antonio, Gobbi, Claudio, Bisecco, Alvino, Tedeschi, Gioacchino, Zecca, Chiara, A Rocca, Maria, Filippi, Massimo, and Rocca, Maria A
Subjects: Pathology, medicine.medical_specialty, Multiple Sclerosis, Cord, brain, volumetric MRI, Disease, Disability Evaluation, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, medicine, Humans, Gray Matter, Multiparametric Magnetic Resonance Imaging, 030304 developmental biology, 0303 health sciences, Disability, business.industry, Multiple sclerosis, cord, Brain, Multiparametric MRI, medicine.disease, Spinal cord, Magnetic Resonance Imaging, medicine.anatomical_structure, Spinal Cord, Neurology, Neurology (clinical), Atrophy, business, 030217 neurology & neurosurgery
Abstract: Background: In multiple sclerosis (MS), cortical, subcortical and infratentorial structural damage may have a differential contribution to clinical disability according to disease phases. Purpose: To determine the relative contributions of cortical, deep (D) grey matter (GM), cerebellar and cervical cord damage to MS disability milestones. Methods: Multi-centre 3T brain and cervical cord T2- and three-dimensional (3D) T1-weighted images were acquired from 198 MS patients (139 relapsing-remitting (RR) MS, 59 progressive (P) MS) and 67 healthy controls. Brain/cord lesion burden, cortical thickness (CTh), DGM and cerebellar volumetry and cord cross-sectional area (CSA) were quantified. Random forest analyses identified predictors of expanded disability status scale (EDSS) disability milestones (EDSS = 3.0, 4.0 and 6.0). Results: MS patients had widespread atrophy in all investigated compartments versus controls ( p-range: ⩽0.001–0.05). Informative determinants of EDSS = 3.0 were cord CSA, brain lesion volume, frontal CTh and thalamic and cerebellar atrophy (out-of-bag (OOB) accuracy = 0.84, p-range: ⩽0.001–0.05). EDSS = 4.0 was mainly predicted by cerebellar and cord atrophy, frontal and sensorimotor CTh and cord lesion number (OOB accuracy = 0.84, p-range: ⩽0.001–0.04). Cervical cord CSA ( p = 0.001) and cord lesion number ( p = 0.003) predicted EDSS = 6.0 (OOB accuracy = 0.77). Conclusion: Brain lesion burden, cortical and thalamic atrophy were the main determinants of EDSS = 3.0 and 4.0, while cord damage played a major contribution to EDSS = 6.0.
Published: 2022

23. Post-contrast MRI in multiple sclerosis: Towards a judicious use of gadolinium-based contrast agents

Author: Lucia, Gentili, Rocco, Capuano, Lorenzo, Gaetani, Andrea, Fiacca, Alvino, Bisecco, Alessandro, d'Ambrosio, Andrea, Mancini, Giorgio, Guercini, Gioacchino, Tedeschi, Lucilla, Parnetti, Antonio, Gallo, Massimiliano, Di Filippo, Gentili, Lucia, Capuano, Rocco, Gaetani, Lorenzo, Fiacca, Andrea, Bisecco, Alvino, D'Ambrosio, Alessandro, Mancini, Andrea, Guercini, Giorgio, Tedeschi, Gioacchino, Parnetti, Lucilla, Gallo, Antonio, and Di Filippo, Massimiliano
Subjects: Multiple sclerosis, Neurology, Humans, Brain, Contrast Media, Gadolinium, Neurology (clinical), Magnetic Resonance Imaging, MRI
Published: 2022

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

Author: Marida Della Corte, Gioacchino Tedeschi, Antonio Gallo, Luigi Lavorgna, Sabrina Esposito, Maria Cropano, Simona Bonavita, Maddalena Sparaco, Gabriella Santangelo, Giuseppina Miele, Federica Garramone, Santangelo, Gabriella, Corte, Marida Della, Sparaco, Maddalena, Miele, Giuseppina, Garramone, Federica, Cropano, Maria, Esposito, Sabrina, Lavorgna, Luigi, Gallo, Antonio, Tedeschi, Gioacchino, and Bonavita, Simona
Subjects: Adult, Male, medicine.medical_specialty, Coping (psychology), Neurology, Physical disability, Neuropsychological Tests, Correlation, Disease activity, Coping strategie, 03 medical and health sciences, Social support, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Clinical activity, Adaptation, Psychological, medicine, Humans, Multiple sclerosi, Prospective Studies, 030212 general & internal medicine, Depression, business.industry, Multiple sclerosis, Cognition, General Medicine, Middle Aged, medicine.disease, Cognitive impairment, Disease Progression, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Relapses, Clinical psychology
Abstract: Few studies evaluated coping strategies in people with multiple sclerosis (pwMS) in relation to annualized relapse rate (ARR) and lesion load (LL). Overall, results might have been influenced by the inclusion of depressed patients. To investigate the coping strategies and their association to disease activity, we studied relapsing-remitting pwMS accurately selected to avoid the confounding effect of depression. Sixty-seven relapsing-remitting pwMS and 67 healthy subjects (HS) underwent to Coping Orientation to Problems Experienced (I-COPE) and Coping Inventory for Stressful Situation (CISS) and Beck Depression Inventory-II. Cognitive performances, ARR, physical disability and magnetic resonance imaging T2-LL were assessed for correlation with coping and depression scores. pwMS showed lower scores than HSs on social support and turning to religion subscales of I-COPE and on emotion dimension of CISS. In pwMS, higher ARR was related to higher positive attitude and lower score on the turning to religion subscale of I-COPE. The present study revealed a less employment of emotion-based coping strategies in pwMS. A scarce use of faith for support and a frequent adoption of a positive attitude were associated with an increase of MS activity in terms of ARR.
Published: 2019

25. 'Better explanations' in multiple sclerosis diagnostic workup

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

26. POLR3A variants in hereditary spastic paraparesis and ataxia: clinical, genetic, and neuroradiological findings in a cohort of Italian patients

Author: Ivana Ricca, Giovanna De Michele, Nicola Fini, Mario Cirillo, Antonio Federico, Maria Teresa Dotti, Alessandra Tessa, Mariarosa A. B. Melone, Fiorella Gurrieri, Alessandro Filla, Gabriella Silvestri, Ilaria Di Donato, Vittorio Riso, Filippo M. Santorelli, Federica Matrone, Alfonso Cerase, Gemma Natale, Antonio Gallo, Di Donato, Ilaria, Gallo, Antonio, Ricca, Ivana, Fini, Nicola, Silvestri, Gabriella, Gurrieri, Fiorella, Cirillo, Mario, Cerase, Alfonso, Natale, Gemma, Matrone, Federica, Riso, Vittorio, Melone, Mariarosa Anna Beatrice, Tessa, Alessandra, De Michele, Giovanna, Federico, Antonio, Filla, Alessandro, Teresa Dotti, Maria, and Maria Santorelli, Filippo
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, Ataxia, Hereditary spastic paraplegia, Dermatology, Spastic ataxia, Compound heterozygosity, 03 medical and health sciences, 0302 clinical medicine, medicine, Spastic, Missense mutation, Humans, Spinocerebellar Ataxias, Child, Cerebellar ataxia, business.industry, Genetic heterogeneity, Spastic Paraplegia, Hereditary, POLR3A, Leukodystrophy, RNA Polymerase III, General Medicine, medicine.disease, Settore MED/26 - NEUROLOGIA, Psychiatry and Mental health, Optic Atrophy, 030104 developmental biology, Phenotype, Mutation, Paraparesis, Spastic, Original Article, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Mutations in POLR3A are characterized by high phenotypic heterogeneity, with manifestations ranging from severe childhood-onset hypomyelinating leukodystrophic syndromes to milder and later-onset gait disorders with central hypomyelination, with or without additional non-neurological signs. Recently, a milder phenotype consisting of late-onset spastic ataxia without hypomyelinating leukodystrophy has been suggested to be specific to the intronic c.1909 + 22G > A mutation in POLR3A. Here, we present 10 patients from 8 unrelated families with POLR3A-related late-onset spastic ataxia, all harboring the c.1909 + 22G > A variant. Most of them showed an ataxic-spastic picture, two a “pure” cerebellar phenotype, and one a “pure” spastic presentation. The non-neurological findings typically associated with POLR3A mutations were absent in all the patients. The main findings on brain MRI were bilateral hyperintensity along the superior cerebellar peduncles on FLAIR sequences, observed in most of the patients, and cerebellar and/or spinal cord atrophy, found in half of the patients. Only one patient exhibited central hypomyelination. The POLR3A mutations present in this cohort were the c.1909 + 22G > A splice site variant found in compound heterozygosity with six additional variants (three missense, two nonsense, one splice) and, in one patient, with a novel large deletion involving exons 14–18. Interestingly, this patient had the most “complex” presentation among those observed in our cohort; it included some neurological and non-neurological features, such as seizures, neurosensory deafness, and lipomas, that have not previously been reported in association with late-onset POLR3A-related disorders, and therefore further expand the phenotype.
Published: 2021

27. Injectable Versus Oral First-Line Disease-Modifying Therapies: Results from the Italian MS Register

Author: Marco Onofrj, Giacomo Lus, Damiano Paolicelli, Matilde Inglese, Giorgia Teresa Maniscalco, Massimo Filippi, Emanuele D'Amico, M. Vianello, Simonetta Galgani, Vincenzo Brescia Morra, Francesco Patti, Antonio Gallo, Aurora Zanghì, Paolo Confalonieri, Giuseppe Salemi, Giovanna De Luca, Maria Trojano, Carlo Avolio, Maria Pia Amato, Eleonora Cocco, Marzia Romeo, D'Amico, E., Zanghi, A., Romeo, M., Cocco, E., Maniscalco, G. T., Brescia Morra, V., Paolicelli, D., De Luca, G., Galgani, S., Amato, M. P., Salemi, G., Inglese, M., Confalonieri, P. A., Lus, G., Avolio, C., Gallo, A., Vianello, M., Onofrj, M., Filippi, M., Trojano, M., Patti, F., D'Amico, Emanuele, Zanghì, Aurora, Romeo, Marzia, Cocco, Eleonora, Maniscalco, Giorgia Teresa, Brescia Morra, Vincenzo, Paolicelli, Damiano, De Luca, Giovanna, Galgani, Simonetta, Amato, Maria Pia, Salemi, Giuseppe, Inglese, Matilde, Confalonieri, Paolo Agostino, Lus, Giacomo, Avolio, Carlo, Gallo, Antonio, Vianello, Marika, Onofrj, Marco, Filippi, Massimo, Trojano, Maria, and Patti, Francesco
Subjects: Male, oral DMTs, oral DMT, Administration, Oral, Disease, Relapsing-Remitting, Cohort Studies, 0302 clinical medicine, Immunologic, injectable DMT, Pharmacology (medical), 030212 general & internal medicine, Registries, Subcutaneous, Middle Aged, Italy, EDSS score, injectable DMTs, Multiple sclerosis, real-world setting, Adjuvants, Immunologic, Adult, Female, Follow-Up Studies, Glatiramer Acetate, Humans, Immunologic Factors, Injections, Subcutaneous, Interferon-beta, Multiple Sclerosis, Relapsing-Remitting, Retrospective Studies, Administration, Cohort, Settore MED/26 - Neurologia, Original Article, Neurosurgery, Cohort study, Oral, medicine.medical_specialty, Lower risk, Injections, 03 medical and health sciences, Internal medicine, medicine, Multiple sclerosi, Adjuvants, Pharmacology, business.industry, medicine.disease, Discontinuation, Observational study, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: The current study aims to compare injectable and oral first-line disease-modifying therapies (DMTs) for time to first relapse, time to confirmed disability progression (CDP), and time to discontinuation using a cohort of relapsing remitting multiple sclerosis (RRMS) patients, with data extracted from the Italian MS Register. This multicenter, observational, retrospectively acquired, and propensity-adjusted cohort study utilized RRMS-naïve patients from the Italian MS Register who started either injectable or oral first-line DMTs between January 1, 2010, and December 31, 2017, to evaluate the impact on disability outcomes in patients. Enrolled patients were divided into two groups, namely the injectable group (IG) and the oral group (OG). Of a cohort of 11,416 patients, 4602 were enrolled (3919 in the IG and 683 in the OG). The IG had a higher rate of women (67.3% vs 63.4%, p p p p = 0.941), while a lower risk of DMT was found in the OG (HR = 0.72; CI 95% 0.58–0.88, p = 0.002) for the event time to discontinuation. Real-world data from the Italian MS Register suggests that first-line oral DMTs are associated with a lower risk of experiencing a new relapse and of therapy discontinuation compared to injectable DMTs.
Published: 2021

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

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

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

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

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

Author: Gianmarco Abbadessa, Carlo Avolio, Patrizia Sola, Franco Granella, Graziella Callari, Stefania Barone, Elisabetta Signoriello, Simona Bonavita, Francesco Patti, Aurora Zanghì, Maria Buccafusca, Valeria Di Francescantonio, Antonio Gallo, Rocco Capuano, Diana Ferraro, Roberta Lanzillo, Paola Valentino, Matteo Lucchini, Erica Curti, Giuseppe Pontillo, Massimiliano Mirabella, Emanuele D'Amico, Maria Petracca, Giacomo Lus, Zanghì, Aurora, Gallo, Antonio, Avolio, Carlo, Capuano, Rocco, Lucchini, Matteo, Petracca, Maria, Bonavita, Simona, Lanzillo, Roberta, Ferraro, Diana, Curti, Erica, Buccafusca, Maria, Callari, Graziella, Barone, Stefania, Pontillo, Giuseppe, Abbadessa, Gianmarco, Di Francescantonio, Valeria, Signoriello, Elisabetta, Lus, Giacomo, Sola, Patrizia, Granella, Franco, Valentino, Paola, Mirabella, Massimiliano, Patti, Francesco, D'Amico, Emanuele, Zanghi, A., Gallo, A., Avolio, C., Capuano, R., Lucchini, M., Petracca, M., Bonavita, S., Lanzillo, R., Ferraro, D., Curti, E., Buccafusca, M., Callari, G., Barone, S., Pontillo, G., Abbadessa, G., Di Francescantonio, V., Signoriello, E., Lus, G., Sola, P., Granella, F., Valentino, P., Mirabella, M., Patti, F., and D'Amico, E.
Subjects: 0301 basic medicine, Male, Immunosuppressive Agent, 0302 clinical medicine, Natalizumab, Immunologic Factor, Risk Factors, Retrospective Studie, Pharmacology (medical), Prospective Studies, Disease activity, Ocrelizumab, Drug Substitution, Progressive multifocal leukoencephalopathy, Leukoencephalopathy, Progressive Multifocal, Settore MED/26 - NEUROLOGIA, Original Article, Rituximab, Female, Immunosuppressive Agents, medicine.drug, Human, Adult, medicine.medical_specialty, Adolescent, Lower risk, Antibodies, Monoclonal, Humanized, Cladribine, Exit strategy, Follow-Up Studie, 03 medical and health sciences, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, Post-hoc analysis, medicine, Humans, Immunologic Factors, Retrospective Studies, Pharmacology, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Risk Factor, medicine.disease, Prospective Studie, 030104 developmental biology, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: The main aim of the study is to evaluate the efficacy and safety profile of ocrelizumab (OCR), rituximab (RTX), and cladribine (CLA), employed as natalizumab (NTZ) exit strategies in relapsing–remitting multiple sclerosis (RRMS) patients at high-risk for progressive multifocal leukoencephalopathy (PML). This is a multicentre, retrospective, real-world study on consecutive RRMS patients from eleven tertiary Italian MS centres, who switched from NTZ to OCR, RTX, and CLA from January 1st, 2019, to December 31st, 2019. The primary study outcomes were the annualized relapse rate (ARR) and magnetic resonance imaging (MRI) outcome. Treatment effects were estimated by the inverse probability treatment weighting (IPTW), based on propensity-score (PS) approach. Additional endpoint included confirmed disability progression (CDP) as measured by Expanded Disability Status Scale and adverse events (AEs). Patients satisfying predefined inclusion and exclusion criteria were 120; 64 switched to OCR, 36 to RTX, and 20 to CLA. Patients from the 3 groups did not show differences for baseline characteristics, also after post hoc analysis. The IPTW PS-adjusted models revealed that patients on OCR had a lower risk for ARR than patients on CLA (ExpBOCR0.485, CI 95% 0.264–0.893,p = 0.020). This result was confirmed also for 12-month MRI activity (ExpBOCR0.248 CI 95% 0.065–0.948,p = 0.042). No differences were found in other pairwise comparisons (OCR vs RTX and RTX vs CLA) for the investigated outcomes. AEs were similar among the 3 groups. Anti-CD20 drugs were revealed to be effective and safe options as NTZ exit strategies. All investigated DMTs showed a good safety profile.
Published: 2021

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

Author: Sormani, Maria P., Nicola De Rossi, Irene, Schiavetti, Luca, Carmisciano, Cinzia, Cordioli, Lucia, Moiola, Marta, Radaelli, Paolo, Immovilli, Marco, Capobianco, Maria, Trojano, Paola, Zaratin, Gioacchino, Tedeschi, Giancarlo, Comi, Battaglia, Mario A., Francesco, Patti, Marco, Salvetti, Agostino, Nozzolillo, Alessandra, Bellacosa, Alessandra, Protti, Alessia Di Sapio, Alessio, Signori, Alfredo, Petrone, Alvino, Bisecco, Aniello, Iovino, Anna, Dutto, Anna Maria Repice, Antonella, Conte, Antonio, Bertolotto, Antonio, Bosco, Antonio, Gallo, Antonio, Zito, Arianna, Sartori, Bruno, Giometto, Carla, Tortorella, Carlo, Antozzi, Carlo, Pozzilli, Chiara Rosa Mancinelli, Chiara, Zanetta, Christian, Cordano, Cinzia, Scandellari, Clara, Guaschino, Claudio, Gasperini, Claudio, Solaro, Cristina, Fioretti, Daiana, Bezzini, Damiano, Marastoni, Damiano, Paolicelli, Domizia, Vecchio, Doriana, Landi, Elisabetta, Bucciantini, Elisabetta, Pedrazzoli, Elisabetta, Signoriello, Elvira, Sbragia, Emanuela Laura Susani, Erica, Curti, Eva, Milano, Fabiana, Marinelli, Federico, Camilli, Filippo Martinelli Boneschi, Flora, Govone, Francesca, Bovis, Francesca, Calabria, Francesca, Caleri, Francesca, Rinaldi, Francesca, Vitetta, Francesco, Corea, Francesco, Crescenzo, Francesco, Teatini, Giulietta, Tabiadon, Franco, Granella, Giacomo, Boffa, Giacomo, Lus, Giampaolo, Brichetto, Giorgia Teresa Maniscalco, Giovanna, Borriello, Giovanna De Luca, Giovanna, Konrad, Giovanna, Vaula, Girolama Alessandra Marfia, Giulia, Mallucci, Giuseppe, Liberatore, Giuseppe, Salemi, Giuseppina, Miele, Grazia, Sibilia, Ilaria, Pesci, Laura, Brambilla, Leonardo, Lopiano, Leonardo, Sinisi, Pasquali, Livia, Lorenzo, Saraceno, Luca, Chiveri, Luca, Mancinelli, Grimaldi, Luigi M. E., Luisa Maria Caniatti, Marco Della Cava, Marco, Onofrj, Marco, Rovaris, Marco, Vercellino, Margherita Monti Bragadin, Maria, Buccafusca, Maria Chiara Buscarinu, Maria Grazia Celani, Maria Grazia Grasso, Maria Laura Stromillo, Maria, Petracca, Maria Pia Amato, Maria Pia Sormani, Maria Rita L'Episcopo, Maria, Sessa, Maria Teresa Ferrò, Maria Vittoria Ercolani, Mariangela, Bianco, Marianna Lo Re, Marika, Vianello, Marinella, Clerico, Mario Alberto Battaglia, Mario di Napoli, Marta, Ponzano, Marta Zaffira Conti, Massimiliano, Calabrese, Massimiliano, Mirabella, Massimo, Filippi, Matilde, Inglese, Matteo, Lucchini, Matteo, Pozzato, Maura Chiara Danni, Mauro, Zaffaroni, Mauro, Zampolini, Michela, Ponzio, Milena De Riz, Nicola De Stefano, Paola, Cavalla, Paola De Mitri, Paola, Grossi, Paolo, Confalonieri, Paolo, Gallo, Paolo, Ragonese, Patrizia, Sola, Pietro, Annovazzi, Pietro, Iaffaldano, Raffaele, Nardone, Raffaella, Cerqua, Raffaella, Clerici, Roberta, Lanzillo, Roberta, Motta, Roberto, Balgera, Roberto, Bergamaschi, Rocco, Totaro, Rosa, Iodice, Ruggero, Capra, Sabrina, Marangoni, Sabrina, Realmuto, Salvatore, Cottone, Sara, Montepietra, Sarah, Rasia, Sebastiano, Arena, Sebastiano, Bucello, Silvia, Banfi, Simona, Bonavita, Simona, Malucchi, Simone, Tonietti, Stefano, Vollaro, Susanna, Cordera, Umberto, Aguglia, Valentina Torri Clerici, Valeria, Barcella, Valeria, Bergamaschi, Vincenzo Brescia Morra, Vincenzo, Dattola, and Vittorio Mantero, Sormani, M. P., De Rossi, N., Schiavetti, I., Carmisciano, L., Cordioli, C., Moiola, L., Radaelli, M., Immovilli, P., Capobianco, M., Trojano, M., Zaratin, P., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., P Sormani, Maria, De Rossi, Nicola, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Moiola, Lucia, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, Trojano, Maria, Zaratin, Paola, Tedeschi, Gioacchino, Comi, Giancarlo, A Battaglia, Mario, Patti, Francesco, Salvetti, Marco, Nozzolillo, Agostino, Bellacosa, Alessandra, Protti, Alessandra, Di Sapio, Alessia, Signori, Alessio, Petrone, Alfredo, Bisecco, Alvino, Iovino, Aniello, Dutto, Anna, Maria Repice, Anna, Conte, Antonella, Bertolotto, Antonio, Bosco, Antonio, Gallo, Antonio, Zito, Antonio, Sartori, Arianna, Giometto, Bruno, Tortorella, Carla, Antozzi, Carlo, Pozzilli, Carlo, Rosa Mancinelli, Chiara, Zanetta, Chiara, Cordano, Christian, Scandellari, Cinzia, Guaschino, Clara, Gasperini, Claudio, Solaro, Claudio, Fioretti, Cristina, Bezzini, Daiana, Marastoni, Damiano, Paolicelli, Damiano, Vecchio, Domizia, Landi, Doriana, Bucciantini, Elisabetta, Pedrazzoli, Elisabetta, Signoriello, Elisabetta, Sbragia, Elvira, Laura Susani, Emanuela, Curti, Erica, Milano, Eva, Marinelli, Fabiana, Camilli, Federico, Martinelli Boneschi, Filippo, Govone, Flora, Bovis, Francesca, Calabria, Francesca, Caleri, Francesca, Rinaldi, Francesca, Vitetta, Francesca, Corea, Francesco, Crescenzo, Francesco, Teatini, Francesco, Tabiadon, Giulietta, Granella, Franco, Boffa, Giacomo, Lus, Giacomo, Brichetto, Giampaolo, Teresa Maniscalco, Giorgia, Borriello, Giovanna, De Luca, Giovanna, Konrad, Giovanna, Vaula, Giovanna, Alessandra Marfia, Girolama, Mallucci, Giulia, Liberatore, Giuseppe, Salemi, Giuseppe, Miele, Giuseppina, Sibilia, Grazia, Pesci, Ilaria, Brambilla, Laura, Lopiano, Leonardo, Sinisi, Leonardo, Pasquali, Livia, Saraceno, Lorenzo, Chiveri, Luca, Mancinelli, Luca, E Grimaldi, Luigi M, Maria Caniatti, Luisa, Della Cava, Marco, Onofrj, Marco, Rovaris, Marco, Vercellino, Marco, Monti Bragadin, Margherita, Buccafusca, Maria, Chiara Buscarinu, Maria, Grazia Celani, Maria, Grazia Grasso, Maria, Laura Stromillo, Maria, Petracca, Maria, Pia Amato, Maria, Pia Sormani, Maria, Rita L'Episcopo, Maria, Sessa, Maria, Teresa Ferrò, Maria, Vittoria Ercolani, Maria, Bianco, Mariangela, Lo Re, Marianna, Vianello, Marika, Clerico, Marinella, Alberto Battaglia, Mario, di Napoli, Mario, Ponzano, Marta, Zaffira Conti, Marta, Calabrese, Massimiliano, Mirabella, Massimiliano, Filippi, Massimo, Inglese, Matilde, Lucchini, Matteo, Pozzato, Matteo, Chiara Danni, Maura, Zaffaroni, Mauro, Zampolini, Mauro, Ponzio, Michela, De Riz, Milena, De Stefano, Nicola, Cavalla, Paola, De Mitri, Paola, Grossi, Paola, Confalonieri, Paolo, Gallo, Paolo, Ragonese, Paolo, Sola, Patrizia, Annovazzi, Pietro, Iaffaldano, Pietro, Nardone, Raffaele, Cerqua, Raffaella, Clerici, Raffaella, Lanzillo, Roberta, Motta, Roberta, Balgera, Roberto, Bergamaschi, Roberto, Totaro, Rocco, Iodice, Rosa, Capra, Ruggero, Marangoni, Sabrina, Realmuto, Sabrina, Cottone, Salvatore, Montepietra, Sara, Rasia, Sarah, Arena, Sebastiano, Bucello, Sebastiano, Banfi, Silvia, Bonavita, Simona, Malucchi, Simona, Tonietti, Simone, Vollaro, Stefano, Cordera, Susanna, Aguglia, Umberto, Torri Clerici, Valentina, Barcella, Valeria, Bergamaschi, Valeria, Brescia Morra, Vincenzo, Dattola, Vincenzo, Mantero, Vittorio, Mp, Sormani, N, De Rossi, I, Schiavetti, L, Carmisciano, C, Cordioli, L, Moiola, M, Radaelli, P, Immovilli, M, Capobianco, M, Trojano, P, Zaratin, G, Tedeschi, G, Comi, Ma, Battaglia, F, Patti, M, Salvetti, Study Group Agostino Nozzolillo, Musc-19, Grimaldi, Luigi M. E., Vittorio Mantero, And, Nozzolillo, A., Bellacosa, A., Protti, A., Di Sapio, A., Signori, A., Petrone, A., Bisecco, A., Iovino, A., Dutto, A., Repice, A. M., Conte, A., Bertolotto, A., Bosco, A., Gallo, A., Zito, A., Sartori, A., Giometto, B., Tortorella, C., Antozzi, C., Pozzilli, C., Mancinelli, C. R., Zanetta, C., Cordano, C., Scandellari, C., Guaschino, C., Gasperini, C., Solaro, C., Fioretti, C., Bezzini, D., Marastoni, D., Paolicelli, D., Vecchio, D., Landi, D., Bucciantini, E., Pedrazzoli, E., Signoriello, E., Sbragia, E., Susani, E. L., Curti, E., Milano, E., Marinelli, F., Camilli, F., Boneschi, F. M., Govone, F., Bovis, F., Calabria, F., Caleri, F., Rinaldi, F., Vitetta, F., Corea, F., Crescenzo, F., Teatini, F., Tabiadon, G., Granella, F., Boffa, G., Lus, G., Brichetto, G., Maniscalco, G. T., Borriello, G., De Luca, G., Konrad, G., Vaula, G., Marfia, G. A., Mallucci, G., Liberatore, G., Salemi, G., Miele, G., Sibilia, G., Pesci, I., Brambilla, L., Lopiano, L., Sinisi, L., Pasquali, L., Saraceno, L., Chiveri, L., Mancinelli, L., Grimaldi, L. M. E., Caniatti, L. M., Cava, M. D., Onofrj, M., Rovaris, M., Vercellino, M., Bragadin, M. M., Buccafusca, M., Buscarinu, M. C., Celani, M. G., Grasso, M. G., Stromillo, M. L., Petracca, M., Amato, M. P., L'Episcopo, M. R., Sessa, M., Ferro, M. T., Ercolani, M. V., Bianco, M., Re, M. L., Vianello, M., Clerico, M., di Napoli, M., Ponzano, M., Conti, M. Z., Calabrese, M., Mirabella, M., Filippi, M., Inglese, M., Lucchini, M., Pozzato, M., Danni, M. C., Zaffaroni, M., Zampolini, M., Ponzio, M., De Riz, M., De Stefano, N., Cavalla, P., De Mitri, P., Grossi, P., Confalonieri, P., Gallo, P., Ragonese, P., Sola, P., Annovazzi, P., Iaffaldano, P., Nardone, R., Cerqua, R., Clerici, R., Lanzillo, R., Motta, R., Balgera, R., Bergamaschi, R., Totaro, R., Iodice, R., Capra, R., Marangoni, S., Realmuto, S., Cottone, S., Montepietra, S., Rasia, S., Arena, S., Bucello, S., Banfi, S., Bonavita, S., Malucchi, S., Tonietti, S., Vollaro, S., Cordera, S., Aguglia, U., Clerici, V. T., Barcella, V., Bergamaschi, V., Morra, V. B., Dattola, V., Mantero, V., Sormani M.P., De Rossi N., Schiavetti I., Carmisciano L., Cordioli C., Moiola L., Radaelli M., Immovilli P., Capobianco M., Trojano M., Zaratin P., Tedeschi G., Comi G., Battaglia M.A., Patti F., Salvetti M., Nozzolillo A., Bellacosa A., Protti A., Di Sapio A., Signori A., Petrone A., Bisecco A., Iovino A., Dutto A., Repice A.M., Conte A., Bertolotto A., Bosco A., Gallo A., Zito A., Sartori A., Giometto B., Tortorella C., Antozzi C., Pozzilli C., Mancinelli C.R., Zanetta C., Cordano C., Scandellari C., Guaschino C., Gasperini C., Solaro C., Fioretti C., Bezzini D., Marastoni D., Paolicelli D., Vecchio D., Landi D., Bucciantini E., Pedrazzoli E., Signoriello E., Sbragia E., Susani E.L., Curti E., Milano E., Marinelli F., Camilli F., Boneschi F.M., Govone F., Bovis F., Calabria F., Caleri F., Rinaldi F., Vitetta F., Corea F., Crescenzo F., Teatini F., Tabiadon G., Granella F., Boffa G., Lus G., Brichetto G., Maniscalco G.T., Borriello G., De Luca G., Konrad G., Vaula G., Marfia G.A., Mallucci G., Liberatore G., Salemi G., Miele G., Sibilia G., Pesci I., Brambilla L., Lopiano L., Sinisi L., Pasquali L., Saraceno L., Chiveri L., Mancinelli L., Grimaldi L.M.E., Caniatti L.M., Cava M.D., Onofrj M., Rovaris M., Vercellino M., Bragadin M.M., Buccafusca M., Buscarinu M.C., Celani M.G., Grasso M.G., Stromillo M.L., Petracca M., Amato M.P., L'Episcopo M.R., Sessa M., Ferro M.T., Ercolani M.V., Bianco M., Re M.L., Vianello M., Clerico M., di Napoli M., Ponzano M., Conti M.Z., Calabrese M., Mirabella M., Filippi M., Inglese M., Lucchini M., Pozzato M., Danni M.C., Zaffaroni M., Zampolini M., Ponzio M., De Riz M., De Stefano N., Cavalla P., De Mitri P., Grossi P., Confalonieri P., Gallo P., Ragonese P., Sola P., Annovazzi P., Iaffaldano P., Nardone R., Cerqua R., Clerici R., Lanzillo R., Motta R., Balgera R., Bergamaschi R., Totaro R., Iodice R., Capra R., Marangoni S., Realmuto S., Cottone S., Montepietra S., Rasia S., Arena S., Bucello S., Banfi S., Bonavita S., Malucchi S., Tonietti S., Vollaro S., Cordera S., Aguglia U., Clerici V.T., Barcella V., Bergamaschi V., Morra V.B., Dattola V., and Mantero V.
Subjects: Male, 0301 basic medicine, Dimethyl Fumarate, Neurodegenerative, multiple sclerosis, coronavirus, pneumonia, Severity of Illness Index, law.invention, Immunosuppressive Agent, Immunologic Factor, 0302 clinical medicine, Natalizumab, law, Monoclonal, Multiple Sclerosi, 80 and over, Lung, Humanized, Research Articles, Aged, 80 and over, Middle Aged, Intensive care unit, Hospitalization, Settore MED/26 - NEUROLOGIA, Intensive Care Units, Neurology, Methylprednisolone, Neurological, Pneumonia & Influenza, Interferon, Female, Immunosuppressive Agents, Research Article, Human, medicine.drug, Adult, medicine.medical_specialty, Musc-19 Study Group, Multiple Sclerosis, Adolescent, Clinical Sciences, Intensive Care Unit, Clinical Neurology, Settore MED/26, Antibodies, Monoclonal, Humanized, Autoimmune Disease, Antibodies, Young Adult, 03 medical and health sciences, Clinical Research, Internal medicine, Severity of illness, medicine, Humans, Immunologic Factors, Mortality, Aged, COVID-19, Fingolimod Hydrochloride, Interferons, SARS-CoV-2, Neurology & Neurosurgery, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Neurosciences, Pneumonia, Odds ratio, medicine.disease, Brain Disorders, Good Health and Well Being, 030104 developmental biology, Ocrelizumab, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18–4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (
Published: 2021

32. Association of Gray Matter Atrophy Patterns With Clinical Phenotype and Progression in Multiple Sclerosis

Author: Maria A, Rocca, Paola, Valsasina, Alessandro, Meani, Claudio, Gobbi, Chiara, Zecca, Alex, Rovira, Jaume, Sastre-Garriga, Hugh, Kearney, Olga, Ciccarelli, Lucy, Matthews, Jacqueline, Palace, Antonio, Gallo, Alvino, Bisecco, Carsten, Lukas, Barbara, Bellenberg, Frederik, Barkhof, Hugo, Vrenken, Paolo, Preziosa, Massimo, Filippi, Tarek, Yousry, Rocca, M. A., Valsasina, P., Meani, A., Gobbi, C., Zecca, C., Rovira, A., Sastre-Garriga, J., Kearney, H., Ciccarelli, O., Matthews, L., Palace, J., Gallo, A., Bisecco, A., Lukas, C., Bellenberg, B., Barkhof, F., Vrenken, H., Preziosa, P., Filippi, M., Anatomy and neurosciences, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Neuroinfection & -inflammation, Rocca, Maria A, Valsasina, Paola, Meani, Alessandro, Gobbi, Claudio, Zecca, Chiara, Rovira, Alex, Sastre-Garriga, Jaume, Kearney, Hugh, Ciccarelli, Olga, Matthews, Lucy, Palace, Jacqueline, Gallo, Antonio, Bisecco, Alvino, Lukas, Carsten, Bellenberg, Barbara, Barkhof, Frederik, Vrenken, Hugo, Preziosa, Paolo, and Filippi, Massimo
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Internal medicine, medicine, Humans, In patient, Gray Matter, Clinical phenotype, Clinically isolated syndrome, business.industry, Multiple sclerosis, Area under the curve, Brain, Odds ratio, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 030104 developmental biology, Phenotype, Brain size, Disease Progression, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: ObjectivesGay matter (GM) involvement is clinically relevant in multiple sclerosis (MS). Using source-based morphometry (SBM), we characterized GM atrophy and its 1-year evolution across different MS phenotypes.MethodsClinical and MRI data were obtained at 8 European sites from 170 healthy controls (HCs) and 398 patients with MS (34 with clinically isolated syndrome [CIS], 226 with relapsing-remitting MS [RRMS], 95 with secondary progressive MS [SPMS], and 43 with primary progressive MS [PPMS]). Fifty-seven HCs and 144 with MS underwent 1-year follow-up. Baseline GM loss, atrophy progression, and correlations with disability and 1-year clinical worsening were assessed.ResultsSBM identified 26 cerebellar, subcortical, sensory, motor, and cognitive GM components. GM atrophy was found in patients with MS vs HCs in almost all components (p range R2 = 0.65) with baseline lower normalized brain volume (β = −0.13, p = 0.001), greater sensorimotor GM atrophy (β = −0.12, p = 0.002), and longer disease duration (β = 0.09, p = 0.04). Baseline normalized GM volume (odds ratio 0.98, p = 0.008) and cerebellar GM atrophy (odds ratio 0.40, p = 0.01) independently predicted clinical worsening (area under the curve 0.83).ConclusionGM atrophy differed across disease phenotypes and progressed at 1 year in MS. In addition to global atrophy measures, sensorimotor and cerebellar GM atrophy explained baseline disability and clinical worsening.
Published: 2020

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

Author: D'Amico E., Zanghi A., Sciandra M., Lanzillo R., Callari G., Cortese A., Lus G., Lucchini M., Buccafusca M., Bonavita S., Gallo A., Curti E., Gajofatto A., Signoriello E., Bisecco A., Gobbin F., Ferro M. T., Ferrazzano G., Sparaco M., Valentino P., Mirabella M., Granella F., Bresciamorra V., Grimaldi L. M. E., Patti F., Borriello G., Grossi P., Carotenuto A., Siena E., Tsantes E., Giugno A., Abbadessa G. M., Chisari C. G., D'Amico, Emanuele, Zanghì, Aurora, Sciandra, Mariangela, Lanzillo, Roberta, Callari, Graziella, Cortese, Antonio, Lus, Giacomo, Lucchini, Matteo, Buccafusca, Maria, Bonavita, Simona, Gallo, Antonio, Curti, Erica, Gajofatto, Alberto, Signoriello, Elisabetta, Bisecco, Alvino, Gobbin, Francesca, Ferrò, Maria Teresa, Ferrazzano, Gina, Sparaco, Maddalena, Valentino, Paola, Mirabella, Massimiliano, Granella, Franco, Brescia Morra, Vincenzo, Grimaldi, Luigi Maria Edoardo, Patti, Francesco, D'Amico, E., Zanghi, A., Sciandra, M., Lanzillo, R., Callari, G., Cortese, A., Lus, G., Lucchini, M., Buccafusca, M., Bonavita, S., Gallo, A., Curti, E., Gajofatto, A., Signoriello, E., Bisecco, A., Gobbin, F., Ferro, M. T., Ferrazzano, G., Sparaco, M., Valentino, P., Mirabella, M., Granella, F., Bresciamorra, V., Grimaldi, L. M. E., Patti, F., Borriello, G., Grossi, P., Carotenuto, A., Siena, E., Tsantes, E., Giugno, A., Abbadessa, G. M., and Chisari, C. G.
Subjects: Adult, Data Analysis, Male, medicine.medical_specialty, Neurology, Efficacy, Toluidines, Dimethyl Fumarate, Hydroxybutyrates, Relapsing-Remitting, Multiple sclerosis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, Teriflunomide, Nitriles, medicine, Humans, Multiple sclerosi, 030212 general & internal medicine, Neuroradiology, Dimethyl fumarate, Proportional hazards model, business.industry, Safety, Female, Italy, Middle Aged, Crotonates, Immunosuppressive Agents, medicine.disease, Settore MED/26 - NEUROLOGIA, Event data, chemistry, Cohort, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Background: The introduction of oral disease-modifying therapies (DMTs) for relapsing–remitting multiple sclerosis (RRMS) changed algorithms of RRMS treatment. Objectives: To compare the effectiveness of treatment with dimethyl fumarate (DMF) and teriflunomide (TRF) in a large multicentre Italian cohort of RRMS patients. Materials and Methods: Patients with RRMS who received treatment with DMF and TRF between January 1st, 2012 and December 31st, 2018 from twelve MS centers were identified. The events investigated were “time-to-first-relapse”, “time-to-Magnetic-Resonance-Imaging (MRI)-activity” and “time-to-disability-progression”. Results: 1445 patients were enrolled (1039 on DMF, 406 on TRF) and followed for a median of 34months. Patients on TRF were older (43.5 ± 8.6 vs 38.8 ± 9.2years), with a predominance of men and higher level of disability (p < 0.001 for all). Patients on DMF had a higher number of relapses and radiological activity (p 38DMF = 3.83, CI = 1.11 to 13.23, p = 0.033). Both DMTs controlled similarly MRI activity and disability progression. Conclusions: Patients on DMF had higher relapse-free survival time than TRF group after the first 38 months ontherapy.
Published: 2020

34. 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

35. Clinically relevant cranio-caudal patterns of cervical cord atrophy evolution in MS

Author: Maria A, Rocca, Paola, Valsasina, Alessandro, Meani, Claudio, Gobbi, Chiara, Zecca, Àlex, Rovira, Xavier, Montalban, Hugh, Kearney, Olga, Ciccarelli, Lucy, Matthews, Jacqueline, Palace, Antonio, Gallo, Alvino, Bisecco, Achim, Gass, Philipp, Eisele, Carsten, Lukas, Barbara, Bellenberg, Frederik, Barkhof, Hugo, Vrenken, Paolo, Preziosa, Giancarlo, Comi, Massimo, Filippi, Tarek, Yousry, Amsterdam Neuroscience - Neuroinfection & -inflammation, Radiology and nuclear medicine, Rocca, Maria A, Valsasina, Paola, Meani, Alessandro, Gobbi, Claudio, Zecca, Chiara, Rovira, Àlex, Montalban, Xavier, Kearney, Hugh, Ciccarelli, Olga, Matthews, Lucy, Palace, Jacqueline, Gallo, Antonio, Bisecco, Alvino, Gass, Achim, Eisele, Philipp, Lukas, Carsten, Bellenberg, Barbara, Barkhof, Frederik, Vrenken, Hugo, Preziosa, Paolo, Comi, Giancarlo, Filippi, Massimo, Rocca, M. A., Valsasina, P., Meani, A., Gobbi, C., Zecca, C., Rovira, A., Montalban, X., Kearney, H., Ciccarelli, O., Matthews, L., Palace, J., Gallo, A., Bisecco, A., Gass, A., Eisele, P., Lukas, C., Bellenberg, B., Barkhof, F., Vrenken, H., Preziosa, P., Comi, G., and Filippi, M.
Subjects: Adult, Male, medicine.medical_specialty, Cord, Multiple Sclerosis, Adolescent, Primary Progressive Multiple Sclerosis, Cervical cord, Gastroenterology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Atrophy, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, medicine, Humans, In patient, 030212 general & internal medicine, Longitudinal Studies, Aged, business.industry, Multiple sclerosis, Middle Aged, Multiple Sclerosis, Chronic Progressive, medicine.disease, Magnetic Resonance Imaging, Spinal Cord, Cervical Vertebrae, Disease Progression, Secondary progressive multiple sclerosis, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Demyelinating Diseases
Abstract: ObjectiveTo characterize the distribution and regional evolution of cervical cord atrophy in patients with multiple sclerosis (MS) in a multicenter dataset.MethodsMRI and clinical evaluations were acquired from 179 controls and 435 patients (35 clinically isolated syndromes [CIS], 259 relapsing-remitting multiple sclerosis [RRMS], 99 secondary progressive multiple sclerosis [SPMS], and 42 primary progressive multiple sclerosis [PPMS]). Sixty-nine controls and 178 patients underwent a 1-year MRI and clinical follow-up. Patients were classified as clinically stable/worsened according to their disability change. Longitudinal changes of cord atrophy were investigated with linear mixed-effect models. Sample size calculations were performed using age-, sex- and site-adjusted annualized percentage normalized cord cross-sectional area (CSAn) changes.ResultsBaseline CSAn was lower in patients with MS vs controls (p < 0.001), but not different between controls and patients with CIS or between patients with early RRMS (disease duration ≤5 years) and patients with CIS. Patients with late RRMS (disease duration >5 years) showed significant cord atrophy vs patients with early RRMS (p = 0.02). Patients with progressive MS had decreased CSAn (p < 0.001) vs patients with RRMS. Atrophy was located between C1/C2 and C5 in patients with RRMS vs patients with CIS, and widespread along the cord in patients with progressive MS vs patients with RRMS, with an additional C5/C6 involvement in patients with SPMS vs patients with PPMS. At follow-up, CSAn decreased in all phenotypes (p < 0.001), except CIS. Cord atrophy rates were highest in patients with early RRMS and clinically worsened patients, who had a more widespread cord involvement than stable patients. The sample size per arm required to detect a 50% treatment effect was 118 for patients with early RRMS.ConclusionsCord atrophy increased in MS during 1 year, except for CIS. Faster atrophy contributed to explain clinical worsening.
Published: 2019

36. Improved assessment of longitudinal spinal cord atrophy in multiple sclerosis using a registration-based approach: Relevance for clinical studies

Author: Antonio Gallo, Mark A. Horsfield, Massimo Filippi, Claudio Gobbi, Alessandro Meani, Paola Valsasina, Maria A. Rocca, Valsasina, Paola, Horsfield, Mark A, Meani, Alessandro, Gobbi, Claudio, Gallo, Antonio, Rocca, Maria A, Filippi, Massimo, Valsasina, P., Horsfield, M. A., Meani, A., Gobbi, C., Gallo, A., Rocca, M. A., and Filippi, M.
Subjects: medicine.medical_specialty, Cord, Multiple Sclerosis, multiple sclerosis, Atrophy, Physical medicine and rehabilitation, Interquartile range, registration, Linear regression, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Relevance (information retrieval), Retrospective Studies, Spinal cord atrophy, business.industry, Multiple sclerosis, spinal cord, Reproducibility of Results, medicine.disease, Magnetic Resonance Imaging, Standard error, Spinal Cord, Neurology, Sample size determination, multiple sclerosi, Cohort, Neurology (clinical), Nuclear medicine, volumetric measurement, business
Abstract: Reliable measurements of cervical cord atrophy progression may be useful for monitoring neurodegeneration in multiple sclerosis (MS). Background: Reliable measurements of cervical cord atrophy progression may be useful for monitoring neurodegeneration in multiple sclerosis (MS). Purpose: To compare a new, registration-based (Reg) method with two existing methods (active surface [AS] and propagation segmentation [PropSeg]) to measure cord atrophy changes over time in MS. Study Type: Retrospective. Subjects: Cohort I: Eight healthy controls (HC) and 28 MS patients enrolled at a single institution, and cohort II: 25 HC and 63 MS patients enrolled at three European sites. Field Strength/Sequence: 3D T1-weighted gradient echo sequence, acquired at 1.5 T (cohort I) and 3.0 T (cohort II). Assessment: Percentage cord area changes (PCACs) between baseline and follow-up (cohort I: 2.34 years [interquartile range = 2.00–2.55 years], cohort II: 1.05 years [interquartile range = 1.01–1.18 years]) were evaluated for all subjects using Reg, AS, and PropSeg. Reg included an accurate registration of baseline and follow-up straightened cord images, followed by AS-based optimized cord segmentation. A subset of studies was analyzed twice by two observers. Statistical Tests: Linear regression models were used to estimate annualized PCAC, and effect sizes expressed as the ratio between the estimated differences and HC error term (P < 0.05). Reproducibility was assessed by linear mixed-effect models. Annualized PCACs were used for sample size calculations (significance: α = 0.05, power: 1 − β = 0.80). Results: Annualized PCACs and related standard errors (SEs) were lower with Reg than with other methods: PCAC in MS patients at 1.5 T was −1.12% (SE = 0.22) with Reg, −1.32% (SE = 0.30) with AS, and −1.40% (SE = 0.33) with PropSeg, while at 3.0 T PCAC was −0.83% (SE = 0.25) with Reg, −0.92% (SE = 0.32) with AS, and −1.18 (SE = 0.53) with PropSeg. This was reflected in larger effect sizes and lower sample sizes. Intra- and inter-observer agreement range was 0.72–0.91 with AS, and it was >0.96 with Reg. Data Conclusion: The results support the use of the registration method to measure cervical cord atrophy progression in future MS clinical studies. Level of Evidence: 3. Technical Efficacy Stage: 2.
Published: 2021

37. Validity and reproducibility of the Italian version of the patient determined disease steps scale in people with multiple sclerosis

Author: Sabrina Esposito, Alvino Bisecco, Maddalena Sparaco, Antonio Gallo, Luigi Lavorgna, Robert W. Motl, Simona Bonavita, Gioacchino Tedeschi, Lavorgna, Luigi, Sparaco, Maddalena, Esposito, Sabrina, Motl, Robert W., Gallo, Antonio, Bisecco, Alvino, Tedeschi, Gioacchino, and Bonavita, Simona
Subjects: Adult, Male, medicine.medical_specialty, Validation study, Multiple Sclerosis, Walking, Disability Evaluation, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Humans, Medicine, Patient Reported Outcome Measures, 030212 general & internal medicine, Reproducibility, business.industry, Multiple sclerosis, Reproducibility of Results, General Medicine, Middle Aged, Translating, medicine.disease, Neurology, DISEASE STEPS, Scale (social sciences), Exercise Test, Physical therapy, Regression Analysis, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Published: 2017

38. Fatigue in multiple sclerosis: The contribution of resting-state functional connectivity reorganization

Author: Renato Docimo, Alessandro d’Ambrosio, Antonio Gallo, Giuseppina Caiazzo, Leonardo Sinisi, Mario Cirillo, Simona Bonavita, Alvino Bisecco, Gioacchino Tedeschi, Federica Di Nardo, Rocco Capuano, Fabrizio Esposito, Bisecco, Alvino, Nardo, Federica Di, Docimo, Renato, Caiazzo, Giuseppina, D'Ambrosio, Alessandro, Bonavita, Simona, Capuano, Rocco, Sinisi, Leonardo, Cirillo, Mario, Esposito, Fabrizio, Tedeschi, Gioacchino, and Gallo, Antonio
Subjects: Adult, Male, 0301 basic medicine, Multiple Sclerosis, Rest, sensorimotor network, Gyrus Cinguli, default mode network, 03 medical and health sciences, 0302 clinical medicine, Neural Pathways, Image Processing, Computer-Assisted, medicine, Humans, Multiple sclerosi, resting state, Fatigue, Default mode network, Brain Mapping, fatigue, functional magnetic resonance imaging, Multiple sclerosis, Neurology, Neurology (clinical), Resting state fMRI, medicine.diagnostic_test, business.industry, Functional connectivity, medicine.disease, Magnetic Resonance Imaging, 030104 developmental biology, Relapsing remitting, Sensorimotor network, Female, Nerve Net, Functional magnetic resonance imaging, business, Neuroscience, 030217 neurology & neurosurgery
Abstract: Objectives: To investigate resting-state functional connectivity (RS-FC) of the default-mode network (DMN) and of sensorimotor network (SMN) network in relapsing remitting (RR) multiple sclerosis (MS) patients with fatigue (F) and without fatigue(NF). Methods: In all, 59 RRMS patients and 29 healthy controls (HC) underwent magnetic resonance imaging (MRI) protocol including resting-state fMRI (RS-fMRI). Functional connectivity of the DMN and SMN was evaluated by independent component analysis (ICA). A linear regression analysis was performed to explore whether fatigue was mainly driven by changes observed in the DMN or in the SMN. Regional gray matter atrophy was assessed by voxel-based morphometry (VBM). Results: Compared to HC, F-MS patients showed a stronger RS-FC in the posterior cingulate cortex (PCC) and a reduced RS-FC in the anterior cingulated cortex (ACC) of the DMN. F-MS patients, compared to NF-MS patients, revealed (1) an increased RS-FC in the PCC and a reduced RS-FC in the ACC of the DMN and (2) an increased RS-FC in the primary motor cortex and in the supplementary motor cortex of the SMN. The regression analysis suggested that fatigue is mainly driven by RS-FC changes of the DMN. Conclusions: Fatigue in RRMS is mainly associated to a functional rearrangement of non-motor RS networks.
Published: 2017

39. The role of diet in multiple sclerosis: A review

Author: Sabrina Esposito, Maddalena Sparaco, Antonio Gallo, Gioacchino Tedeschi, Simona Bonavita, Esposito, Sabrina, Bonavita, Simona, Sparaco, Maddalena, Gallo, Antonio, and Tedeschi, Gioacchino
Subjects: Complementary Therapies, Leptin, Lipopolysaccharides, 0301 basic medicine, Medicine (miscellaneous), Disease, Gut flora, Recommended Dietary Allowances, Bioinformatics, Antioxidants, 0302 clinical medicine, Risk Factors, Micronutrients, Vitamin D, Randomized Controlled Trials as Topic, Nutrition and Dietetics, biology, General Neuroscience, Fatty Acids, General Medicine, Nutritional assessment, Dietary recommendation, Body Composition, Fatty Acids, Unsaturated, Nutrients in multiple sclerosi, Multiple Sclerosis, Nutritional Status, Gut microbiota, 03 medical and health sciences, medicine, Genetic predisposition, Vitamin D and neurology, Animals, Humans, Multiple sclerosi, Obesity, Inflammation, business.industry, Multiple sclerosis, Malnutrition, medicine.disease, biology.organism_classification, Diet, Disease Models, Animal, 030104 developmental biology, Immunology, Dysbiosis, Osteoporosis, business, 030217 neurology & neurosurgery
Abstract: Multiple sclerosis (MS) is a multifactorial, inflammatory, and neurodegenerative disease of the central nervous system, where environmental factors interact with genetic susceptibility. The role of diet on MS has not been comprehensively elucidated; therefore, through an extensive search of relevant literature, this review reports the most significant evidence regarding nutrition as a possible co-factor influencing the inflammatory cascade by acting on both its molecular pathways and gut microbiota. Since nutritional status and dietary habits in MS patients have not been extensively reported, the lack of a scientific-based consensus on dietary recommendation in MS could encourage many patients to experiment alternative dietetic regimens, increasing the risk of malnutrition. This work investigates the health implications of an unbalanced diet in MS, and collects recent findings on nutrients of great interest among MS patients and physicians. The aim of this review is to elucidate the role of an accurate nutritional counseling in MS to move toward a multidisciplinary management of the disease and to encourage future studies demonstrating the role of a healthy diet on the onset and course of MS.
Published: 2017

40. Cognitive reserve and neuropsychological performance in multiple sclerosis: A meta-analysis

Author: Manuela Altieri, Gabriella Santangelo, Antonio Gallo, Christian Enzinger, Luigi Trojano, Santangelo, Gabriella, Altieri, Manuela, Enzinger, Christian, Gallo, Antonio, and Trojano, Luigi
Subjects: Funnel plot, medicine.medical_specialty, Multiple Sclerosis, Cognitive decline, Cognitive reserve, PsycINFO, Audiology, Neuropsychological Tests, 050105 experimental psychology, Cognition, Memory, medicine, Verbal fluency test, Humans, 0501 psychology and cognitive sciences, Attention, Meta-analysi, Multiple sclerosi, 05 social sciences, Neuropsychology, Cognitive impairment, Neuropsychology and Physiological Psychology, Meta-analysis, Verbal memory, Psychology
Abstract: Objective Cognitive dysfunction is frequent in multiple sclerosis (MS), and its relationship with cognitive reserve (CR) has been investigated in several studies with conflicting results. In this meta-analysis, we here sought to determine the relationship between CR and cognition in MS patients and to ascertain whether demographic or clinical variables could moderate the above-mentioned relationship. Method We searched three electronic databases for studies assessing the relationship between CR and performance in 6 cognitive domains or processes (verbal and spatial memory, attention, processing speed, verbal fluency, inhibitory control). The initial literature search yielded 1,452 articles; 245 full-texts were evaluated, and 18 studies were entered into the meta-analysis. Mean weighted effect sizes (ES) were calculated using Hedges' g. Sensitivity analyses and examinations of funnel plots served to reduce heterogeneity. Results A total number of 1,903 MS patients were included, analyzing each aspect of cognition separately. ES for the relationship between CR and cognition were significant (except for verbal fluency) and moderate. After applying specific techniques to reduce heterogeneity, the verbal fluency ES became significant. Metaregression analysis revealed that older age and female sex increased the ES for attention and verbal memory outcomes. Conclusions High levels of CR were associated with better cognitive task performance in verbal and spatial memory, attention, processing speed, verbal fluency, and inhibitory control. The results indirectly emphasize the value of early cognitive assessments of cognitive status and CR levels to enable timely initiation of cognitive interventions to increase CR in MS in patients with low levels of CR. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Published: 2019

41. Dilated perivascular spaces and fatigue: is there a link? Magnetic resonance retrospective 3Tesla study

Author: Antonella Paccone, Mario Cirillo, Antonio Gallo, Gioacchino Tedeschi, Sossio Cirillo, Giuseppina Caiazzo, Angela Sardaro, Rosaria Sacco, Maddalena Sparaco, Alberto Negro, Luigi Lavorgna, Renata Conforti, Conforti, Renata, Cirillo, Mario, Sardaro, Angela, Caiazzo, Giuseppina, Negro, Alberto, Paccone, Antonella, Sacco, Rosaria, Sparaco, Maddalena, Gallo, Antonio, Lavorgna, Luigi, Tedeschi, Gioacchino, and Cirillo, Sossio
Subjects: Adult, Male, medicine.medical_specialty, Pathology, Multiple Sclerosis, Neurology, Statistics as Topic, Comorbidity, Fluid-attenuated inversion recovery, Sensitivity and Specificity, 030218 nuclear medicine & medical imaging, Correlation, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Risk Factors, Prevalence, medicine, Humans, Radiology, Nuclear Medicine and imaging, Fatigue, Neuroradiology, Cerebral atrophy, Brain Diseases, medicine.diagnostic_test, business.industry, Multiple sclerosis, Reproducibility of Results, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, Multiple sclerosis (MS), Dilated perivascular spaces, Dilated perivascular spaces (dPS), Causality, Fatigue (F), Italy, Pia Mater, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, Nuclear medicine, business, 030217 neurology & neurosurgery, Dilatation, Pathologic, Dilated Virchow-Robin spaces (dVRS)
Abstract: Fatigue (F) is a common, inexplicable, and disabling symptom in multiple sclerosis (MS) patients. The purpose of this study was to evaluate a possible correlation between fatigue and morpho-volumetric features and site of dilated perivascular spaces (dPS), visible on 3T magnetic resonance (MR) in fatigued multiple sclerosis patients (FMS). We studied 82 relapsing remitting (RR) FMS patients and 43 HC, matched for age, sex, and education. F was assessed by the Fatigue Severity Scale (FSS). To evaluate a possible correlation between degree of F and characteristics of dPS, patients were divided in two groups: more (mFMS) (FSS ≥ 5; n = 30) and less fatigued (lFMS) (FSS ≥ 4; n = 52), compared to a matched healthy control (HC) subject group. The MR study was performed with 3T scanner by SpinEcho T1, Fast-SpinEcho DP-T2, FLAIR, and 3D FSPGR T1 sequences. dPS volumes were measured with Medical Image Processing Analysis and Visualization (MIPAV); Global Cerebral Atrophy (GCA), expressed as Brain Parenchymal Fraction (BPF), was assessed by FSL SIENAX. The t test showed significantly increased dPS number (p = 0.021) in FMS patients (mFMS p = 0.0024 and lFMS p = 0.033) compared to HC. Pearson correlation revealed a significant correlation between dPS number and FSS (r = 0.208 p = 0.051). Furthermore, the chi-squared test confirms the intragroup (HC, mFMS, lFMS) differences about dPS location (p = 0.01) and size (p = 0.0001). Our study confirms that PS in MS patients presents with different volumetric and site characteristics as compared to HC; moreover, F severity significantly correlates with dPS number, site, and size.
Published: 2016

42. The management of multiple sclerosis by reference centers in south of Italy: a 2011 survey on health demands and needs in Campania region

Author: Daniele Spitaleri, Emilio Lombardi, Walter Di Iorio, Roberta Lanzillo, Mario Alberto Battaglia, Anna Pia Spadera, F. Romano, Giuseppe Orefice, Antonio Gallo, Pasquale Vivo, Francesco Di Nardo, Darko Nedovic, Vincenzo Busillo, Giorgia Teresa Maniscalco, Chiara De Waure, Walter Mazzucco, Walter Ricciardi, Leonardo Sinisi, Maria Petracca, de Waure, Chiara, Di Nardo, Francesco, Mazzucco, Walter, Nedovic, Darko, Battaglia, Mario Alberto, Busillo, Vincenzo, Di Iorio, Walter, Gallo, Antonio, Lanzillo, Roberta, Lombardi, Emilio, Maniscalco, Giorgia Teresa, Orefice, Giuseppe, Petracca, Maria, Romano, Felice, Sinisi, Leonardo, Spadera, Anna Pia, Spitaleri, Daniele, Vivo, Pasquale, Ricciardi, Walter, de Waure, C, Di Nardo, F, Mazzucco, W, Nedovic, D, Battaglia, Ma, Busillo, V, Di Iorio, W, Lanzillo, R, Lombardi, E, Maniscalco, Gt, Orefice, G, Petracca, M, Romano, F, Sinisi, L, Spadera, Ap, Spitaleri, D, Vivo, P, and Ricciardi, W.
Subjects: Adult, Male, medicine.medical_specialty, Pediatrics, Multiple Sclerosis, Cross-sectional study, Neurological examination, Dermatology, Disease management, Health services needs and demand, Multiple sclerosis, Cross-Sectional Studies, Female, Humans, Italy, Surveys and Questionnaires, Needs Assessment, 2708, Neurology (clinical), Psychiatry and Mental Health, 03 medical and health sciences, 0302 clinical medicine, medicine, Multiple sclerosi, 030212 general & internal medicine, Disease management (health), Glatiramer acetate, Settore MED/42 - IGIENE GENERALE E APPLICATA, Neuroradiology, Expanded Disability Status Scale, medicine.diagnostic_test, business.industry, General Medicine, Management of multiple sclerosis, medicine.disease, Psychiatry and Mental health, Physical therapy, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: This cross-sectional study has investigated the diagnostic and therapeutic management of patients suffering from multiple sclerosis (MS) in the Campania Region (Italy). A survey involving all the reference centers for MS in Campania Region was conducted from March to August 2011. Centers responded to a web-administered questionnaire on management and clinical characteristics of MS patients. In the study period, 3263 patients (mean age 37 years, 66 % females) accessed the centers. Patients received a first diagnosis of MS in 161 cases (4.9 %). About 37 % of the subjects without a previous diagnosis came to the centers on their own initiative. All patients underwent a complete neurological examination and expanded disability status scale. The other most common investigations were magnetic resonance imaging (44.0 %) and evoked potentials (22.1 %). The number of treated patients was 2797 (87.1 %). The most used drugs were interferon β and glatiramer acetate. The time between diagnosis and initiation of therapy exceeded 6 months in 32 % of cases. Second-line drugs were under-used: 16 % of patients who might benefit from them show high clinical and radiological disease activity despite treatment with immunomodulant drugs. The MS care management of the surveyed centers showed consistent margins for improvement in 2011. Even though these data do not represent the current situation, they can be used to monitor improvements in MS care.
Published: 2015

43. Does cognitive reserve play any role in multiple sclerosis? A meta-analytic study

Author: Manuela Altieri, Gabriella Santangelo, Antonio Gallo, Luigi Trojano, Santangelo, Gabriella, Altieri, Manuela, Gallo, Antonio, and Trojano, Luigi
Subjects: Physical disability, Multiple Sclerosis, 03 medical and health sciences, 0302 clinical medicine, Cognitive Reserve, Verbal fluency test, Medicine, Humans, Meta-analysi, Multiple sclerosi, 030212 general & internal medicine, Cognitive skill, Cognitive reserve, Expanded Disability Status Scale, business.industry, Verbal Behavior, Cognitive flexibility, Brain, Cognition, General Medicine, Moderation, Neurology, EDSS, Neurology (clinical), business, Cognition Disorders, 030217 neurology & neurosurgery, MRI, Clinical psychology
Abstract: Background: Inconsistent evidence is available about the possibility that cognitive reserve (CR) moderates the impact of disease progression, evaluated by MRI biomarkers (lesion load, white matter or gray matter volumes) or clinical proxies of physical disability (i.e. the Expanded Disability Status Scale, EDSS) on cognition in Multiple Sclerosis (MS). A meta-analytic study with a meta-regression approach was performed to investigate the possible role of CR as moderator of the impact of brain damage and physical disability on cognition. Methods: Two literature searches were performed to retrieve all studies that investigated the relationship between MRI biomarkers and cognition, or the relationship between physical disability and cognition. Data about CR proxies (education, vocabulary knowledge, CR questionnaires) were also collected. We performed several meta-analyses with random effect models (Hedges’ g), and a moderator analysis with a meta-regression approach (with CR entered as a numerical moderator). A p value of < 0.05 was set for statistical significance. Results: We found a significant impact of lesion load and gray matter abnormalities on most cognitive domains. Meta-regression showed that CR significantly moderated the relationship between brain damage and verbal fluency. Moreover, we found a significant impact of physical disability on cognitive functioning, but CR did not mitigate the relationship between EDSS and cognitive performance. Conclusion: The present findings limit the protective role of CR against the impact of the brain damage to selected aspects of cognition (those related to lexical access and cognitive flexibility) in MS. These findings reinforce the need for longitudinal studies exploring the moderator effect of CR over the course of MS.
Published: 2018

44. No evidence of disease activity (NEDA-3) and disability improvement after alemtuzumab treatment for multiple sclerosis: a 36-month real-world study

Author: Prosperini, L, Annovazzi, P, Boffa, L, Buscarinu, Mc, Gallo, A, Matta, M, Moiola, L, Musu, L, Perini, P, Avolio, C, Barcella, V, Bianco, A, Farina, D, Ferraro, E, Pontecorvo, S, Granella, F, Grimaldi, Lme, Laroni, A, Lus, G, Patti, F, Pucci, E, Pasca, M, Sarchielli, P, Ghezzi, A, Zaffaroni, M, Baroncini, D, Buttari, F, Centonze, D, Fornasiero, A, Salvetti, M, Docimo, R, Signoriello, E, Tedeschi, G, Bertolotto, A, Capobianco, M, Comi, G, Cocco, E, Gallo, P, Puthenparampil, M, Grasso, R, Di Francescantonio, V, Rottoli, Mr, Mirabella, M, Lugaresi, A, De Luca, G, Di Ioia, M, Di Tommaso, V, Mancinelli, L, Di Battista, G, Francia, A, Ruggieri, S, Pozzilli, C, Curti, E, Tsantes, E, Palmeri, B, Lapucci, C, Mancardi, Gl, Uccelli, A, Chisari, C, D'Amico, E, Cartechini, E, Repice, Am, Magnani, E, Massaccesi, L, Calabresi, P, Di Filippo, M, Di Gregorio, M, Italian Alemtuzumab Study, Group., Prosperini, Luca, Annovazzi, Pietro, Boffa, Laura, Buscarinu, Maria Chiara, Gallo, Antonio, Matta, Manuela, Moiola, Lucia, Musu, Luigina, Perini, Paola, Avolio, Carlo, Barcella, Valeria, Bianco, Assunta, Farina, Deborah, Ferraro, Elisabetta, Pontecorvo, Simona, Granella, Franco, Grimaldi, Luigi M E, Laroni, Alice, Lus, Giacomo, Patti, Francesco, Pucci, Eugenio, Pasca, Matteo, and Sarchielli, Paola
Subjects: Adult, Male, medicine.medical_specialty, Neurology, Outcome measurement, Relapsing-Remitting, Follow-Up Studie, Multiple sclerosis, 03 medical and health sciences, Immunologic Factor, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Alemtuzumab, Multiple sclerosis, Outcome measurement, Retrospective Studie, Alemtuzumab, Internal medicine, Medicine, Humans, Immunologic Factors, Multiple sclerosi, 030212 general & internal medicine, Female, Follow-Up Studies, Magnetic Resonance Imaging, Retrospective Studies, Treatment Outcome, Neurology (clinical), Expanded Disability Status Scale, medicine.diagnostic_test, business.industry, Retrospective cohort study, Magnetic resonance imaging, Odds ratio, medicine.disease, alemtuzumab, multiple sclerosis, outcome measurement, neurology, Clinical trial, Settore MED/26 - NEUROLOGIA, business, 030217 neurology & neurosurgery, Human, medicine.drug
Abstract: In this retrospective, multicenter, real-world study we collected clinical and magnetic resonance imaging (MRI) data of all patients (n = 40) with relapsing-remitting multiple sclerosis (RRMS) treated with alemtuzumab according to a "free-of-charge" protocol available before the drug marketing approval in Italy. Almost all (39/40) started alemtuzumab after discontinuing multiple disease-modifying treatments (DMTs) because of either lack of response or safety concerns. We considered the proportion of alemtuzumab-treated patients who had no evidence of disease activity (NEDA-3) and disability improvement over a 36-month follow-up period. NEDA-3 was defined as absence of relapses, disability worsening, and MRI activity. Disability improvement was defined as a sustained reduction of ≥ 1-point in Expanded Disability Status Scale (EDSS) score. At follow-up, 18 (45%) patients achieved NEDA-3, 30 (75%) were relapse-free, 33 (82.5%) were EDSS worsening-free, and 25 (62.5%) were MRI activity-free. Eleven (27.5%) patients had a sustained disability improvement. We found no predictor for the NEDA-3 status, while the interaction of higher EDSS score by higher number of pre-alemtuzumab relapses was associated with a greater chance of disability improvement (odds ratio 1.10, p = 0.049). Our study provides real-world evidence that alemtuzumab can promote clinical and MRI disease remission, as well as disability improvement, in a significant proportion of patients with RRMS despite prior multiple DMT failures. The drug safety profile was consistent with data available from clinical trials.
Published: 2018

45. A multicentRE observational analysiS of PErsistenCe to Treatment in the new multiple sclerosis era: the RESPECT study

Author: Massimiliano Calabrese, Eleonora Cocco, Roberta Fantozzi, Viviana Nociti, Antonio Gallo, Laura Boffa, Alice Laroni, Claudio Solaro, Valentina Torri Clerici, Giancarlo Coghe, Simona Malucchi, Massimiliano Di Filippo, Valentina Tomassini, Marcello Moccia, Pietro Annovazzi, Federica Pinardi, Carla Tortorella, Paola Cavalla, Ilaria Pesci, Luca Prosperini, Giorgia Teresa Maniscalco, Alberto Gajofatto, Claudio Gasperini, Roberta Lanzillo, Fabio Buttari, Paolo Ragonese, Marta Radaelli, Maria Chiara Buscarinu, Lanzillo, Roberta, Prosperini, Luca, Gasperini, Claudio, Moccia, Marcello, Fantozzi, Roberta, Tortorella, Carla, Nociti, Viviana, Annovazzi, Pietro, Cavalla, Paola, Radaelli, Marta, Malucchi, Simona, Clerici, Valentina Torri, Boffa, Laura, Buttari, Fabio, Ragonese, Paolo, Maniscalco, Giorgia Teresa, Di Filippo, Massimiliano, Buscarinu, Maria Chiara, Pinardi, Federica, Gallo, Antonio, Coghe, Giancarlo, Pesci, Ilaria, Laroni, Alice, Gajofatto, Alberto, Calabrese, Massimiliano, Tomassini, Valentina, Cocco, Eleonora, Solaro, Claudio, Lanzillo R., Prosperini L., Gasperini C., Moccia M., Fantozzi R., Tortorella C., Nociti V., Annovazzi P., Cavalla P., Radaelli M., Malucchi S., Clerici V.T., Boffa L., Buttari F., Ragonese P., Maniscalco G.T., Di Filippo M., Buscarinu M.C., Pinardi F., Gallo A., Coghe G., Pesci I., Laroni A., Gajofatto A., Calabrese M., Tomassini V., Cocco E., and Solaro C.
Subjects: Male, Injection, Time Factors, Patient Dropout, disease-modifying therapies, multiple sclerosis, outcome measurement, persistence to treatment, quality of life, Administration, Oral, Self Administration, Sex Factor, Kaplan-Meier Estimate, Relapsing-Remitting, Immunologic Factor, 0302 clinical medicine, Quality of life, Retrospective Studie, Risk Factors, Medicine, 030212 general & internal medicine, Disease-modifying therapie, Disease-modifying therapies, Multiple sclerosis, Outcome measurement, Persistence to treatment, Quality of life, Administration, Oral, Adult, Female, Follow-Up Studies, Humans, Immunologic Factors, Injections, Kaplan-Meier Estimate,Male, Multiple Sclerosis, Relapsing-Remitting, Patient Dropouts, Prognosis, Proportional Hazards Models, Retrospective Studies, Risk Factors, Self Administration, Sex Factors, Time Factors, Hazard ratio, Prognosis, Neurology, Tolerability, Administration, Settore MED/26 - Neurologia, Female, Human, Oral, Adult, medicine.medical_specialty, Patient Dropouts, Time Factor, Prognosi, Follow-Up Studie, Injections, 03 medical and health sciences, Route of administration, Multiple Sclerosis, Relapsing-Remitting, Sex Factors, Internal medicine, Humans, Immunologic Factors, Multiple sclerosi, Adverse effect, Proportional Hazards Models, Retrospective Studies, business.industry, Proportional hazards model, Risk Factor, Retrospective cohort study, Discontinuation, Disease-modifying therapies, Multiple sclerosis, Outcome measurement, Persistence to treatment, Follow-Up Studies, Proportional Hazards Model, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: In this independent, multicenter, retrospective study, we investigated the short-term persistence to treatment with first-line self-injectable or oral disease-modifying treatments (DMTs) in patients with relapsing–remitting multiple sclerosis. Data of patients regularly attending 21 Italian MS Centres who started a self-injectable or an oral DMT in 2015 were collected to: (1) estimate the proportion of patients discontinuing the treatment; (3) explore reasons for discontinuation; (3) identify baseline predictors of treatment discontinuation over a follow-up period of 12months. We analyzed data of 1832 consecutive patients (1289 women, 543 men); 374 (20.4%) of them discontinued the prescribed DMT after a median time of 6 months (range 3days to 11.5months) due to poor tolerability (n = 163; 43.6%), disease activity (n = 95; 25.4%), adverse events (n = 64; 17.1%), convenience (i.e. availability of new drug formulations) and pregnancy planning (n = 21; 1.1%). Although the proportion of discontinuers was higher with self-injectable (n = 107; 22.9%) than with oral DMT (n = 215; 16.4%), the Cox regression model revealed no significant between-group difference (p = 0.12). Female sex [hazard ratio (HR) = 1.39, p = 0.01] and previous exposure to ≥ 3 DMTs (HR = 1.71, p = 0.009) were two independent risk factors for treatment discontinuation, regardless of prescribed DMTs. Our study confirms that persistence to treatment represents a clinical challenge, irrespective of the route of administration.
Published: 2018

46. Attention and processing speed performance in multiple sclerosis is mostly related to thalamic volume

Author: Rosaria Sacco, Alessandro d’Ambrosio, Renato Docimo, Antonio Gallo, Svetlana Stamenova, Mario Cirillo, Sabrina Esposito, Giuseppina Caiazzo, Simona Bonavita, Gioacchino Tedeschi, Alvino Bisecco, Fabrizio Esposito, Bisecco, Alvino, Stamenova, Svetlana, Caiazzo, Giuseppina, Dâ€™Ambrosio, Alessandro, Sacco, Rosaria, Docimo, Renato, Esposito, Sabrina, Cirillo, Mario, Esposito, Fabrizio, Bonavita, Simona, Tedeschi, Gioacchino, and Gallo, Antonio
Subjects: Male, 0301 basic medicine, Cerebellum, Neuropsychological Tests, Audiology, Behavioral Neuroscience, Mental Processes, 0302 clinical medicine, Thalamus, Nuclear Medicine and Imaging, Attention, Gray matter, Magnetic resonance imaging, Multiple sclerosis, Processing speed, Radiology, Nuclear Medicine and Imaging, Neurology, Neurology (clinical), Cognitive Neuroscience, Psychiatry and Mental Health, Cellular and Molecular Neuroscience, Cognitive impairment, Putamen, Organ Size, medicine.anatomical_structure, Female, Psychology, Radiology, Adult, medicine.medical_specialty, 03 medical and health sciences, Imaging, Three-Dimensional, Multiple Sclerosis, Relapsing-Remitting, Atrophy, medicine, Humans, Multiple sclerosi, Radiology, Nuclear Medicine and imaging, Thalamu, Voxel-based morphometry, medicine.disease, 030104 developmental biology, Linear Models, FMRIB Software Library, Neuroscience, 030217 neurology & neurosurgery
Abstract: Cognitive impairment (CI), mainly involving attention and processing speed (A-PS), is a common and disabling symptom in multiple sclerosis (MS). Symbol Digit Modalities Test (SDMT) is one of the more sensitive and reliable tests to assess A-PS deficits in MS. Structural MRI correlates of A-PS in MS still need to be clarified. This study aimed to investigate, in a large group of MS patients, the relationship between regional gray matter (GM) atrophy and SDMT performance. 125 relapsing remitting MS patients and 52 healthy controls (HC) underwent a 3 TâMRI protocol including high-resolution 3DâT1 imaging. All subjects underwent a neurological evaluation and SDMT. A Voxel Based Morphometry analysis was performed to assess: 1) correlations between regional GM volume and SDMT performance in MS patients; 2) regional differences in GM volume between MS patients and HC. Thalamic, putamen and cerebellar volumes were also calculated using FIRST tool from the FMRIB Software Library. A linear regression analysis was performed to assess the contribution of each one of these structures to A-PS performance. A significant negative correlation was found between regional GM volume and SDMT score at the level of the thalamus, cerebellum, putamen, and occipital cortex in MS patients. Thalamus, cerebellum and putamen also showed significant GM atrophy in MS patients compared to HC. Thalamic atrophy is also an independent and additional contributor to A-PS deficits in MS patients. These findings support the role of thalamus as the most relevant GM structure subtending A-PS performance in MS, as measured by SDMT.
Published: 2018

47. Default mode network changes in multiple sclerosis: a link between depression and cognitive impairment?

Author: Luigi Lavorgna, Fabrizio Esposito, Alvino Bisecco, Rosaria Sacco, Renato Docimo, Antonio Gallo, Mario Cirillo, Simona Bonavita, Gioacchino Tedeschi, Sabrina Esposito, Alessandro d’Ambrosio, Daniele Corbo, M. Della Corte, Bonavita, Simona, Sacco, R., Esposito, S., D'Ambrosio, Alessandro, Della Corte, M., Corbo, D., Docimo, R., Gallo, Antonio, Lavorgna, L., Cirillo, Mario, Bisecco, Alvino, Esposito, F., and Tedeschi, Gioacchino
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Posterior parietal cortex, Neuropsychological Tests, Gyrus Cinguli, Resting state f-MRI, 03 medical and health sciences, Executive Function, 0302 clinical medicine, Cortex (anatomy), Internal medicine, medicine, Humans, Multiple sclerosi, Cognitive Dysfunction, Anterior cingulate cortex, Default mode network, Brain Mapping, Depressive Disorder, medicine.diagnostic_test, business.industry, Depression, Multiple sclerosis, Medicine (all), Neuropsychology, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 030104 developmental biology, medicine.anatomical_structure, Cognitive impairment, Neurology, Posterior cingulate, cognitive impairment, default mode network, depression, multiple sclerosis, resting state f-MRI, Neurology (clinical), Cardiology, Female, Atrophy, Nerve Net, business, Functional magnetic resonance imaging, Neuroscience, 030217 neurology & neurosurgery
Abstract: Background and purpose In multiple sclerosis (MS), depression is a common disorder whose pathophysiology is still debated. To gain insights into the pathophysiology of depression in MS, resting-state (RS) functional connectivity (FC) changes of the default mode network (DMN), salience network (SN) and executive control network (ECN) were assessed in a group of depressed MS (D-MS) patients and in appropriately matched control groups. Methods Sixteen D-MS patients, 17 non-depressed MS (ND-MS) patients, 17 non-depressed healthy controls and 15 depressed subjects (D-S), age, sex and education matched, cognitively preserved and non-fatigued, were enrolled. All participants underwent a neuropsychological evaluation and RS functional magnetic resonance imaging study. Results Comparing D-MS patients with D-S, within the DMN, a significant RS-FC suppression was found in the posterior cingulate cortex (PCC); comparing D-MS with ND-MS, FC was significantly increased in the anterior cingulate cortex and significantly reduced in the PCC. Within the SN increased FC in the right supramarginal gyrus and right middle frontal gyrus was found in D-MS patients compared to D-S and to ND-MS; within the ECN increased FC in the right inferior parietal cortex was found in D-MS patients compared to ND-MS patients. Conclusions In cognitively preserved D-MS patients, FC derangement occurs in the SN, ECN and DMN. In the latter, changes occurring both in the anterior cingulate cortex and PCC suggest that depression in MS may be linked to MS itself and, in particular, to a peculiar pattern of network abnormalities favored by MS pathology through disconnection mechanisms. Reduced FC in the PCC, similar to MS patients with cognitive impairment, suggests a functional link between depression and cognitive impairment in MS.
Published: 2017

48. Structural MRI correlates of cognitive impairment in patients with multiple sclerosis: A Multicenter Study

Author: M Atzori, Massimiliano Copetti, Gianna C Riccitelli, Franz Fazekas, Nicola De Stefano, Maria Laura Stromillo, Deborah Pareto, Massimo Filippi, Elisabetta Pagani, Frederik Barkhof, María Jesús Arévalo, Alvino Bisecco, Antonio Gallo, Hanneke E. Hulst, Tarek A. Yousry, Christian Enzinger, Paolo Preziosa, Maria A. Rocca, Preziosa, Paolo, Rocca, Maria A., Pagani, Elisabetta, Stromillo, Maria Laura, Enzinger, Christian, Gallo, Antonio, Hulst, Hanneke E., Atzori, Matteo, Pareto, Deborah, Riccitelli, Gianna C., Copetti, Massimiliano, De Stefano, Nicola, Fazekas, Franz, Bisecco, Alvino, Barkhof, Frederik, Yousry, Tarek A., Arévalo, Maria J., Filippi, Massimo, Anatomy and neurosciences, Amsterdam Neuroscience - Neuroinfection & -inflammation, Radiology and nuclear medicine, Preziosa, P, Rocca, Ma, Pagani, E, Stromillo, Ml, Enzinger, C, Gallo, A, Hulst, He, Atzori, M, Pareto, D, Riccitelli, Gc, Copetti, M, De Stefano, N, Fazekas, F, Bisecco, A, Barkhof, F, Yousry, Ta, Arévalo, Mj, and Filippi, M
Subjects: Adult, Male, Pathology, medicine.medical_specialty, Neurology, Multiple Sclerosis, Audiology, Neuropsychological Tests, Diffusion tensor MRI, 030218 nuclear medicine & medical imaging, White matter, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Nuclear Medicine and Imaging, medicine, Cognitive impairment, Multicenter, Multiple sclerosis, Voxel-wise analysis, Cognitive Dysfunction, Female, Humans, Middle Aged, Magnetic Resonance Imaging, Neurology (clinical), Anatomy, Radiology, Nuclear Medicine and Imaging, Radiological and Ultrasound Technology, Radiology, Nuclear Medicine and imaging, Neuropsychological assessment, Research Articles, medicine.diagnostic_test, Magnetic resonance imaging, Cognition, medicine.disease, medicine.anatomical_structure, multiple sclerosi, Psychology, Radiology, 030217 neurology & neurosurgery, Diffusion MRI, voxel-wise analysis
Abstract: In a multicenter setting, we applied voxel‐based methods to different structural MR imaging modalities to define the relative contributions of focal lesions, normal‐appearing white matter (NAWM), and gray matter (GM) damage and their regional distribution to cognitive deficits as well as impairment of specific cognitive domains in multiple sclerosis (MS) patients. Approval of the institutional review boards was obtained, together with written informed consent from all participants. Standardized neuropsychological assessment and conventional, diffusion tensor and volumetric brain MRI sequences were collected from 61 relapsing‐remitting MS patients and 61 healthy controls (HC) from seven centers. Patients with ≥2 abnormal tests were considered cognitively impaired (CI). The distribution of focal lesions, GM and WM atrophy, and microstructural WM damage were assessed using voxel‐wise approaches. A random forest analysis identified the best imaging predictors of global cognitive impairment and deficits of specific cognitive domains. Twenty‐three (38%) MS patients were CI. Compared with cognitively preserved (CP), CI MS patients had GM atrophy of the left thalamus, right hippocampus and parietal regions. They also showed atrophy of several WM tracts, mainly located in posterior brain regions and widespread WM diffusivity abnormalities. WM diffusivity abnormalities in cognitive‐relevant WM tracts followed by atrophy of cognitive‐relevant GM regions explained global cognitive impairment. Variable patterns of NAWM and GM damage were associated with deficits in selected cognitive domains. Structural, multiparametric, voxel‐wise MRI approaches are feasible in a multicenter setting. The combination of different imaging modalities is needed to assess and monitor cognitive impairment in MS. Hum Brain Mapp 37:1627‐1644, 2016. © 2016 Wiley Periodicals, Inc.
Published: 2016

49. Assessing response to interferon-β in a multicenter dataset of patients with MS

Author: Sormani, Mp, Gasperini, C, Romeo, M, Rio, J, Calabrese, M, Cocco, E, Enzingher, C, Fazekas, F, Filippi, M, Gallo, A, Kappos, L, Marrosu, Mg, Martinelli, V, Prosperini, Luca, Rocca, Ma, Rovira, A, Sprenger, T, Stromillo, Ml, Tedeschi, G, Tintorè, M, Tortorella, C, Trojano, M, Montalban, X, Pozzilli, Carlo, Comi, G, De Stefano, N, MAGNIMS study group, Sormani, Maria Pia, Gasperini, Claudio, Romeo, Marzia, Rio, Jordi, Calabrese, Massimiliano, Cocco, Eleonora, Enzingher, Christian, Fazekas, Franz, Filippi, Massimo, Gallo, Antonio, Kappos, Ludwig, Marrosu, Maria Giovanna, Martinelli, Vittorio, Prosperini, Luca, Rocca, Maria Assunta, Rovira, Alex, Sprenger, Till, Stromillo, Maria Laura, Tedeschi, Gioacchino, Tintorè, Mar, Tortorella, Carla, Trojano, Maria, Montalban, Xavier, Pozzilli, Carlo, Comi, Giancarlo, De Stefano, Nicola, Sormani, Mp, Gasperini, C, Romeo, M, Rio, J, Calabrese, M, Cocco, E, Enzingher, C, Fazekas, F, Gallo, A, Kappos, L, Marrosu, Mg, Martinelli, V, Prosperini, L, Rocca, Ma, Rovira, A, Sprenger, T, Stromillo, Ml, Tedeschi, G, Tintorè, M, Tortorella, C, Trojano, M, Montalban, X, Pozzilli, C, and De Stefano, N.
Subjects: Time Factors, multiple sclerosis, interferon-β therapy, Magnetic Resonance Imaging, assessment, follow-up, risk of treatment failure, Expanded Disability Status Scale, relapse, worsening, Datasets as Topic, Kaplan-Meier Estimate, Relapsing-Remitting, Disability Evaluation, 0302 clinical medicine, Adolescent, Adult, Aged, Child, Europe, Follow-Up Studies, Humans, Immunologic Factors, Interferon-beta, Middle Aged, Multiple Sclerosis, Relapsing-Remitting, Retrospective Studies, Risk, Treatment Failure, Young Adult, Neurology (clinical), 030212 general & internal medicine, Young adult, medicine.diagnostic_test, Hazard ratio, medicine.medical_specialty, 03 medical and health sciences, Internal medicine, medicine, Proportional hazards model, business.industry, Multiple sclerosis, Magnetic resonance imaging, Retrospective cohort study, medicine.disease, Confidence interval, multiple-sclerosis patients, treatment optimization, clinical-practice, ifn-beta, mri, recommendations, predictors, score, business, 030217 neurology & neurosurgery
Abstract: To provide new insights into the role of markers of response to interferon-β therapy in multiple sclerosis (MS) in a multicenter setting, focusing on the relevance of MRI lesions in combination with clinical variables.A large multicenter clinical dataset was collected within the Magnetic Resonance Imaging in MS (MAGNIMS) network. This included a large cohort of patients with relapsing-remitting MS on interferon-β treatment, MRI and clinical assessments during the first year of treatment, and clinical follow-up of at least 2 additional years. Heterogeneity among centers was assessed before pooling the data. The association of 1-year MRI or clinical relapses with the risk of treatment failure (defined as Expanded Disability Status Scale [EDSS] worsening or treatment switch for inefficacy) and of EDSS worsening alone was evaluated using multivariate Cox models.A pooled dataset of 1,280 patients with relapsing-remitting MS from 9 MAGNIMS centers was analyzed. The risk of failure had a relevant increase with 1 relapse (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.39-2.44, p0.001) and ≥3 new T2 lesions (HR 1.55, 95% CI 0.92-2.60, p = 0.09). In patients without relapses and less than 3 new T2 lesions, the 3-year risk of failure and EDSS worsening were 17% and 15%; in patients with 1 relapse or ≥3 new T2 lesions, the risks were 27% and 22%; in patients with both conditions or more than 1 relapse, the risks were 48% (p0.001) and 29% (p0.001).Substantial MRI activity, particularly if in combination with clinical relapses, during the first year of treatment with interferon-β indicates significant risk of treatment failure and EDSS worsening in the short term.
Published: 2016

50. Fatigue in multiple sclerosis: The contribution of occult white matter damage

Author: Renato Docimo, Giuseppina Caiazzo, Alvino Bisecco, Simona Bonavita, Antonio Gallo, Mario Cirillo, Elisabetta Pagani, Fabrizio Esposito, Rosaria Sacco, Gioacchino Tedeschi, Massimo Filippi, Alessandro d’Ambrosio, Bisecco, A, Caiazzo, G, D’Ambrosio, A, Sacco, R, Bonavita, S, Docimo, R, Cirillo, M, Pagani, E, Filippi, Massimo, Esposito, F, Tedeschi, G, Gallo, A., Bisecco, Alvino, Giuseppina, Caiazzo, D'Ambrosio, Alessandro, Rosaria, Sacco, Bonavita, Simona, Renato, Docimo, Cirillo, Mario, Elisabetta, Pagani, Massimo, Filippi, Esposito, Fabrizio, Tedeschi, Gioacchino, and Gallo, Antonio
Subjects: Adult, Male, Pathology, medicine.medical_specialty, diffusion tensor imaging, fatigue, magnetic resonance imaging, Multiple sclerosis, normal appearing white matter, tract-based spatial statistics, Neurology, Neurology (clinical), Tract based spatial statistics, behavioral disciplines and activities, 030218 nuclear medicine & medical imaging, White matter, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, medicine, Fatigue Severity Scale, Humans, Multiple sclerosi, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Middle Aged, medicine.disease, Occult, White Matter, medicine.anatomical_structure, nervous system, Correlation analysis, Female, Psychology, Nuclear medicine, business, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: Background: A functional cortico-subcortical disconnection has been recognized in fatigued multiple sclerosis (MS) patients. Normal appearing white matter (NAWM) damage might contribute to the abovementioned disconnectivity. Objectives: To assess the relationship between fatigue and microstructural NAWM damage in relapsing-remitting (RR) MS. Methods: Sixty RRMS patients and 29 healthy controls (HC) underwent a magnetic resonance imaging (MRI) protocol including diffusion tensor imaging (DTI). Patients with a mean Fatigue Severity Scale (FSS) score ⩾ 4 were considered fatigued (fatigued MS (F-MS)). Tract-based spatial statistics were applied for voxel-wise analysis of DTI indices. A correlation analysis was performed between FSS score and DTI indices in the entire MS group. Results: Thirty MS patients were F-MS. Compared to HC, F-MS patients showed a more extensive NAWM damage than not fatigued MS (NF-MS) patients, with additional damage in the following tracts: frontal and occipital juxtacortical fibers, external capsule, uncinate fasciculus, forceps minor, superior longitudinal fasciculus, cingulum, and pons. No differences were found between F-MS and NF-MS patients. Fatigue severity correlated to DTI abnormalities of corona radiata, cingulum, corpus callosum, forceps minor, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, thalamus and anterior thalamic radiation, cerebral peduncle, and midbrain. Conclusions: Fatigue is associated to a widespread microstructural NAWM damage, particularly in associative tracts connected to frontal lobes.
Published: 2016

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