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Cranio-caudal patterns of cervical cord atrophy progression in MS according to disease phenotype and clinical worsening: a multicenter study
ECTRIMS Online Library. Rocca M. Oct 12, 2018; 232021
Dr. Maria Assunta Rocca
Dr. Maria Assunta Rocca
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Abstract: 268

Type: Scientific Session

Abstract Category: Pathology and pathogenesis of MS - MRI and PET

Background: In MS, it is still unclear how early cord atrophy starts to develop and whether a differential involvement of cord levels occurs at different stages of the disease. Aim of this study was to characterize the regional evolution of cervical cord atrophy over time in MS patients from a multicentre dataset acquired at 9 European sites.
Methods: Baseline and one-year 3D T1-weighted cervical cord scans and clinical evaluation were obtained from 179 HC, 35 clinically isolated syndromes (CIS), 57 early (disease duration< 5 years) and 187 late (disease duration>5 years) relapsing-remitting (RR), 99 secondary progressive (SP) and 42 primary progressive (PP) MS patients. At follow-up, MS patients were classified as clinically stable or worsened according to their EDSS change. Normalized cross-sectional area (CSAn) and regional whole-cervical curves of atrophy were obtained with an active surface method. Linear random effect and B-spline models investigated regional patterns of cord atrophy in different phenotypes and in clinically worsened vs stable MS.
Results: Baseline CSAn was lower in MS patients vs HC (p< 0.001). CSAn did not differ between HC and CIS (p=0.9) nor between early RRMS and CIS patients (p=0.7), while late RRMS showed significant cord atrophy vs early RRMS (p=0.02). PPMS and SPMS patients were both characterized by a severe CSAn decrease (p< 0.001). At a regional level, atrophy was mainly located between C1 and C5 in RRMS vs CIS, while an involvement of C5/C6 was found in SPMS vs PPMS patients. During the follow-up, cord CSAn decreased in all MS groups (p< 0.001), except CIS. The highest rate of cord atrophy was found in early RRMS (CSAn change=-1.66%) and in clinically worsened MS patients (CSAn change=-2.01%). The regional analysis of cord atrophy distribution showed that worsened MS patients had a more widespread involvement of cord segments (between C3 and C6) than clinically stable MS patients (between C4 and C5).
Conclusions: Significant and distributed cord atrophy is a feature of progressive MS, suggesting that neurodegenerative processes leading to irreversible tissue loss have a cumulative effect over time. The study of early RRMS patients allowed to detect a cranio-caudal gradient of cord atrophy distribution and progression which may improve the understanding of the factors responsible for cord neurodegeneration. The rate of cord atrophy progression and its spatial extension are both clinically relevant.
Disclosure: MA 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.
P Valsasina, A Meani, H Kearney, L Matthews, and P Eisele have nothing to disclose.
Claudio Gobbi, Chiara 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.
Alex Rovira serves on scientific advisory boards for Novartis, Sanofi-Genzyme, Icometrix, SyntheticMR, and OLEA Medical, and has received speaker honoraria from Bayer, Sanofi-Genzyme, 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 specialised 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.
A Gass has received honoraria for lecturing, travel expenses for attending meetings, and financial support for research from Novartis, Biogen, Merck Serono, Sanofi-Genzyme, Roche.
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, Biogen-IDEC, 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 (IMDI-NWO), 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).

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