Patterns of grey matter atrophy in patients with MS: a multivariate analysis using source-based morphometry
ECTRIMS Online Library. Valsasina P. 09/11/19; 278875; P515
Paola Valsasina
Paola Valsasina
Contributions
Abstract

Abstract: P515

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Neurodegeneration

P. Valsasina1, A. Meani1, C. Gobbi2, C. Zecca2, A. Rovira3, X. Montalban4, H. Kearney5, O. Ciccarelli5, L. Matthews6, J. Palace6, A. Gallo7, A. Bisecco7, C. Lukas8, B. Bellenberg8, F. Barkhof9,10, H. Vrenken9, P. Preziosa1,11, M.A. Rocca1,11, M. Filippi1,11, for the MAGNIMS Study Group

1Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, 2Department of Neurology, Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano, Switzerland, 3Section of Neuroradiology and MRI Unit, Department of Radiology, 4Department of Neurology/Neuroimmunology, Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain, 5NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, 6Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, 7Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, and MRI-Center 'SUN-FISM', University of Campania 'Luigi Vanvitelli', Naples, Italy, 8Department of Radiology and Nuclear Medicine, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany, 9Department of Radiology and Nuclear Medicine, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands, 10Institutes of Neurology and Healthcare Engineering, University College London, London, United Kingdom, 11Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy

Introduction: Grey matter (GM) pathology is a crucial component of multiple sclerosis (MS). Source-based morphometry (SBM) is a multivariate technique, able to decompose GM maps into co-varying patterns of GM density.
Aims: In this study, we characterized atrophy of such GM patterns across different stages of MS, and its evolution over one-year of follow-up, by analyzing a large, multicentre dataset acquired at 8 European sites.
Methods: MRI and clinical evaluations were acquired from 171 healthy controls (HC) and 399 MS patients (34 clinically isolated syndromes [CIS], 227 relapsing-remitting [RR], 95 secondary progressive [SP] and 43 primary progressive [PP] MS). Fifty-four HC and 146 MS patients underwent a one-year MRI and clinical follow-up. Baseline GM loss and longitudinal changes of GM atrophy were investigated using generalized linear mixed-effect models.
Results: SBM identified 32 relevant GM components, which were assigned to the following networks: cerebellar (5 components), subcortical (3), hippocampal (2), sensorimotor (4), visual (3), temporal (2), default-mode (4), fronto-parietal (4), executive control (3) and salience (2) networks. Compared with HC, MS patients showed significant GM atrophy in all subcortical, cerebellar, sensory and motor components, and in most of default-mode, hippocampal, frontoparietal, executive and salience components (p=range < 0.001-0.02). Compared to HC, CIS patients showed GM atrophy circumscribed to one subcortical, one sensorimotor and one salience component, while RRMS patients exhibited widespread GM atrophy involving most of relevant GM components. PPMS patients showed a pattern of GM atrophy vs HC that was mainly located in cerebellar, subcortical, sensorimotor and visual regions. The same components showed additional GM atrophy in SPMS vs RRMS. At one-year, circumscribed GM atrophy progression vs baseline was detected in HC in one sensorimotor, one default-mode and one fronto-parietal component (p=range 0.005-0.01). Conversely, GM atrophy significantly progressed over time in MS patients in 10 components, mainly located in subcortical, cerebellar, sensorimotor, temporal, fronto-parietal and default-mode regions (p=range 0.001-0.04).
Conclusions: Patterns of GM atrophy detected by SBM highlighted a differential involvement of brain regions across different stages of the disease. Cortical and subcortical GM atrophy progressed significantly in MS patients over one year of follow-up.
Disclosure: P. Valsasina received speakers' honoraria from ExceMed.
A. Meani, H. Kearney and L. Matthews have nothing to disclose.
C. Gobbi and C. Zecca: The Department of Neurology, Regional Hospital Lugano (EOC), Lugano, Switzerland receives financial support from Teva, Merck Serono, Biogen, Genzyme, Roche, Celgene, Bayer and Novartis.
A. Rovira serves on scientific advisory boards for Novartis, Sanofi-Genzyme, Icometrix, SyntheticMR, and OLEA Medical, and has received speaker honoraria from Bayer, SanofiGenzyme, Bracco, Merck-Serono, Teva Pharmaceutical Industries Ltd, Novartis, Roche and Biogen Idec.
X. Montalban has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Actelion, Bayer, Biogen, Celgene, Hoffmann-La Roche, Merck, Novartis, Oryzon Genomics, Sanofi-Genzyme and Teva Pharmaceutical.
O. Ciccarelli receives research grants from the MS Society of Great Britain & Northern Ireland, Engineering and Physical Sciences Research Council (EPSCR), University College London/University College London Hospitals NHS Foundation Trust (UCL/UCLH), National Institute for Health Research (NIHR) Biomedical Research Centre (BRC), Wellcome Trust, EUH2020, Spinal Cord Research Foundation and Rosetrees Trust. Professor Ciccarelli serves as a consultant for Novartis, Teva & Roche. Professor Ciccarelli receives an honorarium from the AAN as Associate Editor of Neurology and serves on the Editorial Board of Multiple Sclerosis Journal. Professor Ciccarelli does not have any patents, royalties, stocks or shares.
J. Palace is partly funded by highly specialiszed services to run a national congenital myasthenia service and a neuromyelitis service. She has received support for scientific meetings and honorariums for advisory work from Merck Serono, Biogen Idec, Novartis, Teva, Chugai Pharma and Bayer Schering, Alexion, Roche, Genzyme, MedImmune, EuroImmun, MedDay, Abide and ARGENX, and grants from Merck Serono, Novartis, Biogen Idec, Teva, Abide and Bayer Schering. Her hospital trust received funds for her role as clinical lead for the RSS, and she has received grants from the MS society and Guthie Jackson Foundation for research studies.
A. Gallo received speaker and consulting fees from Biogen, Sanofi-Genzyme, Merck Serono and Teva.
A. Bisecco received speakers honoraria and/or compensation for consulting service from Biogen, Merck, Genzyme and Actelion.
C. Lukas received a research grant by the German Federal Ministry for Education and Research, BMBF, German Competence Network Multiple Sclerosis (KKNMS), grant no.01GI1601I, has received consulting and speaker´s honoraria from Biogen Idec, Bayer Schering, Daiichi Sanykyo, Merck Serono, Novartis, Sanofi, Genzyme and TEVA.
B. Bellenberg received financial support by the German Federal Ministry for Education and Research, BMBF, German Competence Network Multiple Sclerosis (KKNMS), grant no.01GI1601I.
F. Barkhof has received consultance and speaker honoraria from Bayer-Schering Pharma, BiogenIDEC, TEVA, Merck-Serono, Novartis, Roche, Jansen Research, Genzyme-Sanofi, IXICO Ltd., GeNeuro and Apitope Ltd. He is a honorary board member for the Journals: Brain, Eur. Radiology, Neurology, Multiple Sclerosis Journal, and Radiology. His institution has received grants by AMYPAD (IMI), EuroPOND (H2020), UK MS Society, Dutch MS Society, PICTURE (IMDINWO), NIHR UCLH Biomedical Research Centre (BRC), ECTRIMS-MAGNIMS.
H. Vrenken has received research grants from Novartis, MerckSerono and Teva, and consulting fees from MerckSerono; all funds were paid directly to his institution.
P. Preziosa received speakers honoraria from Biogen Idec, Novartis and ExceMED. G Comi has received consulting fees for participating on advisory boards from Novartis, Teva Pharmaceutical Ind. Ltd, Sanofi, Genzyme, Merck Serono, Bayer, Actelion and honorarium for speaking activities for Novartis, Teva Pharmaceutical Ind. Ltd, Sanofi, Genzyme, Merck Serono, Bayer, Biogen, ExceMED. M Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).
M.A. Rocca received speakers honoraria from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono, and Roche and receives research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla.
M. Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Abstract: P515

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Neurodegeneration

P. Valsasina1, A. Meani1, C. Gobbi2, C. Zecca2, A. Rovira3, X. Montalban4, H. Kearney5, O. Ciccarelli5, L. Matthews6, J. Palace6, A. Gallo7, A. Bisecco7, C. Lukas8, B. Bellenberg8, F. Barkhof9,10, H. Vrenken9, P. Preziosa1,11, M.A. Rocca1,11, M. Filippi1,11, for the MAGNIMS Study Group

1Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, 2Department of Neurology, Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano, Switzerland, 3Section of Neuroradiology and MRI Unit, Department of Radiology, 4Department of Neurology/Neuroimmunology, Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain, 5NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, 6Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, 7Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, and MRI-Center 'SUN-FISM', University of Campania 'Luigi Vanvitelli', Naples, Italy, 8Department of Radiology and Nuclear Medicine, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany, 9Department of Radiology and Nuclear Medicine, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands, 10Institutes of Neurology and Healthcare Engineering, University College London, London, United Kingdom, 11Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy

Introduction: Grey matter (GM) pathology is a crucial component of multiple sclerosis (MS). Source-based morphometry (SBM) is a multivariate technique, able to decompose GM maps into co-varying patterns of GM density.
Aims: In this study, we characterized atrophy of such GM patterns across different stages of MS, and its evolution over one-year of follow-up, by analyzing a large, multicentre dataset acquired at 8 European sites.
Methods: MRI and clinical evaluations were acquired from 171 healthy controls (HC) and 399 MS patients (34 clinically isolated syndromes [CIS], 227 relapsing-remitting [RR], 95 secondary progressive [SP] and 43 primary progressive [PP] MS). Fifty-four HC and 146 MS patients underwent a one-year MRI and clinical follow-up. Baseline GM loss and longitudinal changes of GM atrophy were investigated using generalized linear mixed-effect models.
Results: SBM identified 32 relevant GM components, which were assigned to the following networks: cerebellar (5 components), subcortical (3), hippocampal (2), sensorimotor (4), visual (3), temporal (2), default-mode (4), fronto-parietal (4), executive control (3) and salience (2) networks. Compared with HC, MS patients showed significant GM atrophy in all subcortical, cerebellar, sensory and motor components, and in most of default-mode, hippocampal, frontoparietal, executive and salience components (p=range < 0.001-0.02). Compared to HC, CIS patients showed GM atrophy circumscribed to one subcortical, one sensorimotor and one salience component, while RRMS patients exhibited widespread GM atrophy involving most of relevant GM components. PPMS patients showed a pattern of GM atrophy vs HC that was mainly located in cerebellar, subcortical, sensorimotor and visual regions. The same components showed additional GM atrophy in SPMS vs RRMS. At one-year, circumscribed GM atrophy progression vs baseline was detected in HC in one sensorimotor, one default-mode and one fronto-parietal component (p=range 0.005-0.01). Conversely, GM atrophy significantly progressed over time in MS patients in 10 components, mainly located in subcortical, cerebellar, sensorimotor, temporal, fronto-parietal and default-mode regions (p=range 0.001-0.04).
Conclusions: Patterns of GM atrophy detected by SBM highlighted a differential involvement of brain regions across different stages of the disease. Cortical and subcortical GM atrophy progressed significantly in MS patients over one year of follow-up.
Disclosure: P. Valsasina received speakers' honoraria from ExceMed.
A. Meani, H. Kearney and L. Matthews have nothing to disclose.
C. Gobbi and C. Zecca: The Department of Neurology, Regional Hospital Lugano (EOC), Lugano, Switzerland receives financial support from Teva, Merck Serono, Biogen, Genzyme, Roche, Celgene, Bayer and Novartis.
A. Rovira serves on scientific advisory boards for Novartis, Sanofi-Genzyme, Icometrix, SyntheticMR, and OLEA Medical, and has received speaker honoraria from Bayer, SanofiGenzyme, Bracco, Merck-Serono, Teva Pharmaceutical Industries Ltd, Novartis, Roche and Biogen Idec.
X. Montalban has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Actelion, Bayer, Biogen, Celgene, Hoffmann-La Roche, Merck, Novartis, Oryzon Genomics, Sanofi-Genzyme and Teva Pharmaceutical.
O. Ciccarelli receives research grants from the MS Society of Great Britain & Northern Ireland, Engineering and Physical Sciences Research Council (EPSCR), University College London/University College London Hospitals NHS Foundation Trust (UCL/UCLH), National Institute for Health Research (NIHR) Biomedical Research Centre (BRC), Wellcome Trust, EUH2020, Spinal Cord Research Foundation and Rosetrees Trust. Professor Ciccarelli serves as a consultant for Novartis, Teva & Roche. Professor Ciccarelli receives an honorarium from the AAN as Associate Editor of Neurology and serves on the Editorial Board of Multiple Sclerosis Journal. Professor Ciccarelli does not have any patents, royalties, stocks or shares.
J. Palace is partly funded by highly specialiszed services to run a national congenital myasthenia service and a neuromyelitis service. She has received support for scientific meetings and honorariums for advisory work from Merck Serono, Biogen Idec, Novartis, Teva, Chugai Pharma and Bayer Schering, Alexion, Roche, Genzyme, MedImmune, EuroImmun, MedDay, Abide and ARGENX, and grants from Merck Serono, Novartis, Biogen Idec, Teva, Abide and Bayer Schering. Her hospital trust received funds for her role as clinical lead for the RSS, and she has received grants from the MS society and Guthie Jackson Foundation for research studies.
A. Gallo received speaker and consulting fees from Biogen, Sanofi-Genzyme, Merck Serono and Teva.
A. Bisecco received speakers honoraria and/or compensation for consulting service from Biogen, Merck, Genzyme and Actelion.
C. Lukas received a research grant by the German Federal Ministry for Education and Research, BMBF, German Competence Network Multiple Sclerosis (KKNMS), grant no.01GI1601I, has received consulting and speaker´s honoraria from Biogen Idec, Bayer Schering, Daiichi Sanykyo, Merck Serono, Novartis, Sanofi, Genzyme and TEVA.
B. Bellenberg received financial support by the German Federal Ministry for Education and Research, BMBF, German Competence Network Multiple Sclerosis (KKNMS), grant no.01GI1601I.
F. Barkhof has received consultance and speaker honoraria from Bayer-Schering Pharma, BiogenIDEC, TEVA, Merck-Serono, Novartis, Roche, Jansen Research, Genzyme-Sanofi, IXICO Ltd., GeNeuro and Apitope Ltd. He is a honorary board member for the Journals: Brain, Eur. Radiology, Neurology, Multiple Sclerosis Journal, and Radiology. His institution has received grants by AMYPAD (IMI), EuroPOND (H2020), UK MS Society, Dutch MS Society, PICTURE (IMDINWO), NIHR UCLH Biomedical Research Centre (BRC), ECTRIMS-MAGNIMS.
H. Vrenken has received research grants from Novartis, MerckSerono and Teva, and consulting fees from MerckSerono; all funds were paid directly to his institution.
P. Preziosa received speakers honoraria from Biogen Idec, Novartis and ExceMED. G Comi has received consulting fees for participating on advisory boards from Novartis, Teva Pharmaceutical Ind. Ltd, Sanofi, Genzyme, Merck Serono, Bayer, Actelion and honorarium for speaking activities for Novartis, Teva Pharmaceutical Ind. Ltd, Sanofi, Genzyme, Merck Serono, Bayer, Biogen, ExceMED. M Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).
M.A. Rocca received speakers honoraria from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono, and Roche and receives research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla.
M. Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

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