Contributions
Abstract: 132
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: Multiple sclerosis (MS) is classified into phenotypes based on clinical history and MRI. It remains unclear, however, whether we can associate a signature of grey matter (GM) volume loss (rate and order of regions on the basis of their rate) to MS phenotypes or to patients with a more disabling disease course.
Aims: The aims of this study were to:
(1) investigate whether the rate and spatial distribution of cortical and deep GM volume loss discriminate among MS phenotypes, and
(2) explore the relationship between GM volume loss and changes in disability.
Methods: We included 820 subjects,retrospectively, who had longitudinal T1-weighted MRIs from
4 European MS centres: London (446 subjects), Amsterdam (212), Siena (134), and Rome (28). After quality-assurance, we included 2377 T1-weighted scans from a total of 155 healthy controls (HC) and 655 patients; 96 clinically isolated syndrome (CIS), 388 relapsing remitting MS (RRMS), 102 primary-progressive MS (PPMS), and 79 with secondary-progressive MS (SPMS). Average length of follow-up was 4.02 years. We used FSL,and GIF softwares for image analysis. We contoured visible white matter lesions on PD/T2-weighted scans. After coregistration with T1-weighted scans,we used these masks to fill the lesions. We segmented GM in an unbiased within-subject space, and calculated the volume of the deep GM, cortical GM and cerebellum. To compare rates of atrophy and associations with EDSS changes, we used 3-level mixed effects models to adjust for the effect of repeated measures, centres, age, total intracranial volume, gender, and their interactions with time.
Results: At baseline, all patient phenotypes showed a lower total GM volume than HCs (average in HC=492.9,CIS=473.2,RRMS=463.6,PPMS=461.2, and SPMS=444.2 ml,p< 0.001). During follow-up, progressive patients developed the fastest total GM, cortical GM and deep GM atrophy rate (total GM atrophy rate per year: HCs=0.8%, CIS=1%, RRMS=1.1%, SPMS=1.6%, and PPMS=1.5%).Rate of atrophy was fastest in deep GM, and slowest in cerebellum and occipital lobe, in all MS phenotypes (p< 0.01). In all MS patients together, the annual changes in deep GM were associated with EDSS changes (p=0.03), whilst changes in cortical GM were not.
Conclusion: All MS phenotypes show a similar regional order of GM atrophy over time,but the rate is the fastest in progressive MS and in the deep GM. The progressive volume loss of the deep GM is a stronger predictor of EDSS changes than cortical GM.
Disclosure:
Arman Eshaghi has received Fellowship from the MAGNIMS study group (www.magnims.eu). He has received McDonald Fellowship from Multiple Sclerosis International Federation (www.msif.org).
Frederik Barkhof acts as a consultant to Biogen-Idec, Janssen Alzheimer Immunotherapy, Bayer-Schering, Merck-Serono, Roche, Novartis, Genzyme, and Sanofi-aventis. He has received sponsorship from EU-H2020, NWO, SMSR, EU-FP7, TEVA, Novartis, and Toshiba. He is on the editorial board of Radiology, Brain, Neuroradiology, MSJ, Neurology.
Olga Ciccarelli is an Associate Editor of Neurology and serves as a consultant for GE Healthcare, Novartis, Roche, Biogen, Genzyme and Teva.
Declan Chard has received research support from the MS Society of Great Britain and Northern Ireland, and the National Institute for Health Research University College London Hospitals Biomedical Research Centre. He has received honoraria (paid to his employer) from Ismar Healthcare NV, Swiss MS Society, Excemed (previously Serono Symposia International Foundation), Merck, Bayer and Teva for faculty-led education work; Teva for advisory board work; meeting expenses from Merck, Teva, Novartis, the MS Trust and National MS Society; and has previously held stock in GlaxoSmithKline. He is a member of the MS Society of Great Britain and Northern Ireland"s Biomedical Grant Review Panel. He is a member of the Data Safety Monitoring Committee for the PROXIMUS study, which is funded by National Multiple Sclerosis Society and Novartis. Both of these roles are unpaid.
Alex Rovira serves on scientific advisory boards for Biogen Idec, Novartis, Genzyme, and OLEA Medical, has received speaker honoraria from Bayer, Genzyme, Sanofi-Aventis, Bracco, Merck-Serono, Teva Pharmaceutical Industries Ltd, OLEA Medical, Stendhal, Novartis and Biogen Idec, and has research agreements with Siemens AG.
Massimo Filippi is Editor-in-Chief of the Journal of Neurology; serves on scientific advisory boards for Teva Pharmaceutical Industries; has received compensation for consulting services and/or speaking activities from Biogen Idec, Excemed, Novartis, and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Teva Pharmaceutical Industries, Novartis, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, Cure PSP, Alzheimer´s Drug Discovery Foundation (ADDF), the Jacques and Gloria Gossweiler Foundation (Switzerland), and ARiSLA (Fondazione Italiana di Ricerca per la SLA).
Maria A Rocca received speakers honoraria from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis and Excemed and receives research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla.
David Miller has received honoraria from Genzyme , Teva, Novartis, and Biogen for educational lectures. He serves as a board member on Novartis, and Mitsubishi Pharma Europe. He has acted as consultant to Novartis,and Bayer Schering Pharma. He served on the editorial board of McAlpines Multiple Sclerosis, 4th edition. He has received royalties from Novartis and Biogen Idec. All payments are made to his employer.
Carmen Tur has received an ECTRIMS post-doctoral research fellowship in 2015. She has also received honoraria and support for travelling from Bayer-Schering, Teva, Merck-Serono and Serono Foundation, Biogen, Sanofi-Aventis, Novartis, and Ismar Healthcare.
Cyra Leurs has received a grant from the Dutch MS research Foundation.
Alan J Thompson received honoraria/support for travel for consultancy from Eisai, Excemed, MedDay, support for travel from the International Progressive MS Alliance and National MS Society (USA), and an honorarium from SAGE Publishers as Editor-in-Chief of MSJ.
Abstract: 132
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: Multiple sclerosis (MS) is classified into phenotypes based on clinical history and MRI. It remains unclear, however, whether we can associate a signature of grey matter (GM) volume loss (rate and order of regions on the basis of their rate) to MS phenotypes or to patients with a more disabling disease course.
Aims: The aims of this study were to:
(1) investigate whether the rate and spatial distribution of cortical and deep GM volume loss discriminate among MS phenotypes, and
(2) explore the relationship between GM volume loss and changes in disability.
Methods: We included 820 subjects,retrospectively, who had longitudinal T1-weighted MRIs from
4 European MS centres: London (446 subjects), Amsterdam (212), Siena (134), and Rome (28). After quality-assurance, we included 2377 T1-weighted scans from a total of 155 healthy controls (HC) and 655 patients; 96 clinically isolated syndrome (CIS), 388 relapsing remitting MS (RRMS), 102 primary-progressive MS (PPMS), and 79 with secondary-progressive MS (SPMS). Average length of follow-up was 4.02 years. We used FSL,and GIF softwares for image analysis. We contoured visible white matter lesions on PD/T2-weighted scans. After coregistration with T1-weighted scans,we used these masks to fill the lesions. We segmented GM in an unbiased within-subject space, and calculated the volume of the deep GM, cortical GM and cerebellum. To compare rates of atrophy and associations with EDSS changes, we used 3-level mixed effects models to adjust for the effect of repeated measures, centres, age, total intracranial volume, gender, and their interactions with time.
Results: At baseline, all patient phenotypes showed a lower total GM volume than HCs (average in HC=492.9,CIS=473.2,RRMS=463.6,PPMS=461.2, and SPMS=444.2 ml,p< 0.001). During follow-up, progressive patients developed the fastest total GM, cortical GM and deep GM atrophy rate (total GM atrophy rate per year: HCs=0.8%, CIS=1%, RRMS=1.1%, SPMS=1.6%, and PPMS=1.5%).Rate of atrophy was fastest in deep GM, and slowest in cerebellum and occipital lobe, in all MS phenotypes (p< 0.01). In all MS patients together, the annual changes in deep GM were associated with EDSS changes (p=0.03), whilst changes in cortical GM were not.
Conclusion: All MS phenotypes show a similar regional order of GM atrophy over time,but the rate is the fastest in progressive MS and in the deep GM. The progressive volume loss of the deep GM is a stronger predictor of EDSS changes than cortical GM.
Disclosure:
Arman Eshaghi has received Fellowship from the MAGNIMS study group (www.magnims.eu). He has received McDonald Fellowship from Multiple Sclerosis International Federation (www.msif.org).
Frederik Barkhof acts as a consultant to Biogen-Idec, Janssen Alzheimer Immunotherapy, Bayer-Schering, Merck-Serono, Roche, Novartis, Genzyme, and Sanofi-aventis. He has received sponsorship from EU-H2020, NWO, SMSR, EU-FP7, TEVA, Novartis, and Toshiba. He is on the editorial board of Radiology, Brain, Neuroradiology, MSJ, Neurology.
Olga Ciccarelli is an Associate Editor of Neurology and serves as a consultant for GE Healthcare, Novartis, Roche, Biogen, Genzyme and Teva.
Declan Chard has received research support from the MS Society of Great Britain and Northern Ireland, and the National Institute for Health Research University College London Hospitals Biomedical Research Centre. He has received honoraria (paid to his employer) from Ismar Healthcare NV, Swiss MS Society, Excemed (previously Serono Symposia International Foundation), Merck, Bayer and Teva for faculty-led education work; Teva for advisory board work; meeting expenses from Merck, Teva, Novartis, the MS Trust and National MS Society; and has previously held stock in GlaxoSmithKline. He is a member of the MS Society of Great Britain and Northern Ireland"s Biomedical Grant Review Panel. He is a member of the Data Safety Monitoring Committee for the PROXIMUS study, which is funded by National Multiple Sclerosis Society and Novartis. Both of these roles are unpaid.
Alex Rovira serves on scientific advisory boards for Biogen Idec, Novartis, Genzyme, and OLEA Medical, has received speaker honoraria from Bayer, Genzyme, Sanofi-Aventis, Bracco, Merck-Serono, Teva Pharmaceutical Industries Ltd, OLEA Medical, Stendhal, Novartis and Biogen Idec, and has research agreements with Siemens AG.
Massimo Filippi is Editor-in-Chief of the Journal of Neurology; serves on scientific advisory boards for Teva Pharmaceutical Industries; has received compensation for consulting services and/or speaking activities from Biogen Idec, Excemed, Novartis, and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Teva Pharmaceutical Industries, Novartis, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, Cure PSP, Alzheimer´s Drug Discovery Foundation (ADDF), the Jacques and Gloria Gossweiler Foundation (Switzerland), and ARiSLA (Fondazione Italiana di Ricerca per la SLA).
Maria A Rocca received speakers honoraria from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis and Excemed and receives research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla.
David Miller has received honoraria from Genzyme , Teva, Novartis, and Biogen for educational lectures. He serves as a board member on Novartis, and Mitsubishi Pharma Europe. He has acted as consultant to Novartis,and Bayer Schering Pharma. He served on the editorial board of McAlpines Multiple Sclerosis, 4th edition. He has received royalties from Novartis and Biogen Idec. All payments are made to his employer.
Carmen Tur has received an ECTRIMS post-doctoral research fellowship in 2015. She has also received honoraria and support for travelling from Bayer-Schering, Teva, Merck-Serono and Serono Foundation, Biogen, Sanofi-Aventis, Novartis, and Ismar Healthcare.
Cyra Leurs has received a grant from the Dutch MS research Foundation.
Alan J Thompson received honoraria/support for travel for consultancy from Eisai, Excemed, MedDay, support for travel from the International Progressive MS Alliance and National MS Society (USA), and an honorarium from SAGE Publishers as Editor-in-Chief of MSJ.