Cortical involvement determines impairment 30 years after a clinically isolated syndrome

Many studies report an overlap of MRI and clinical findings between patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), which in part is reflective of inclusion of subjects with variable disease duration and short periods of follow-up. To...

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Autores: Haider, Lukas, Prados Carrasco, Ferran, Chung, Karen, Goodkin, Olivia, Kanber, Baris, Sudre, Carole, Yiannakas, Marios, Samson, Rebecca, Mangesius, Stephanie, Thompson, Alan, Gandini Wheeler-Kingshott, Claudia A.M., Ciccarelli, Olga, Chard, Declan, Barkhof, Frederik
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universitat Oberta de Catalunya (UOC)
Repositorio:O2, repositorio institucional de la UOC
OAI Identifier:oai:openaccess.uoc.edu:10609/147533
Acceso en línea:https://hdl.handle.net/10609/147533
http://hdl.handle.net/10609/147533
Access Level:acceso abierto
Palabra clave:multiple sclerosis
clinically isolated syndrome
atrophy
magnetic resonance imaging
cortex
esclerosis múltiple
síndrome clínicament aïllada
atrofia
imatge de ressonància magnètica
escorça
síndrome clínicamente aislado
imagen de resonancia magnética
corteza
esclerosi múltiple
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repository_id_str
spelling Cortical involvement determines impairment 30 years after a clinically isolated syndromeHaider, LukasPrados Carrasco, FerranChung, KarenGoodkin, OliviaKanber, BarisSudre, CaroleYiannakas, MariosSamson, RebeccaMangesius, StephanieThompson, AlanGandini Wheeler-Kingshott, Claudia A.M.Ciccarelli, OlgaChard, DeclanBarkhof, Frederikmultiple sclerosisclinically isolated syndromeatrophymagnetic resonance imagingcortexesclerosis múltiplesíndrome clínicament aïlladaatrofiaimatge de ressonància magnèticaescorçaesclerosis múltiplesíndrome clínicamente aisladoatrofiaimagen de resonancia magnéticacortezamultiple sclerosisesclerosi múltipleesclerosis múltipleMany studies report an overlap of MRI and clinical findings between patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), which in part is reflective of inclusion of subjects with variable disease duration and short periods of follow-up. To overcome these limitations, we examined the differences between RRMS and SPMS and the relationship between MRI measures and clinical outcomes 30 years after first presentation with clinically isolated syndrome suggestive of multiple sclerosis. Sixty-three patients were studied 30 years after their initial presentation with a clinically isolated syndrome; only 14% received a disease modifying treatment at any time point. Twenty-seven patients developed RRMS, 15 SPMS and 21 experienced no further neurological events; these groups were comparable in terms of age and disease duration. Clinical assessment included the Expanded Disability Status Scale, 9-Hole Peg Test and Timed 25-Foot Walk and the Brief International Cognitive Assessment For Multiple Sclerosis. All subjects underwent a comprehensive MRI protocol at 3 T measuring brain white and grey matter (lesions, volumes and magnetization transfer ratio) and cervical cord involvement. Linear regression models were used to estimate age- and gender-adjusted group differences between clinical phenotypes after 30 years, and stepwise selection to determine associations between a large sets of MRI predictor variables and physical and cognitive outcome measures. At the 30-year follow-up, the greatest differences in MRI measures between SPMS and RRMS were the number of cortical lesions, which were higher in SPMS (the presence of cortical lesions had 100% sensitivity and 88% specificity), and grey matter volume, which was lower in SPMS. Across all subjects, cortical lesions, grey matter volume and cervical cord volume explained 60% of the variance of the Expanded Disability Status Scale; cortical lesions alone explained 43%. Grey matter volume, cortical lesions and gender explained 43% of the variance of Timed 25-Foot Walk. Reduced cortical magnetization transfer ratios emerged as the only significant explanatory variable for the symbol digit modality test and explained 52% of its variance. Cortical involvement, both in terms of lesions and atrophy, appears to be the main correlate of progressive disease and disability in a cohort of individuals with very long follow-up and homogeneous disease duration, indicating that this should be the target of therapeutic interventions.Oxford University Press (OUP)University College London (UCL)Medical University of ViennaUniversitat Oberta de Catalunya (UOC)King’s College LondonMedical University of InnsbruckUniversity of PaviaIRCCS Mondino FoundationVU University Medical Centre202320232021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/10609/147533http://hdl.handle.net/10609/147533reponame:O2, repositorio institucional de la UOCinstname:Universitat Oberta de Catalunya (UOC)InglésBrain, 2021, 144(5)Brain;144https://doi.org/10.1093/brain/awab033info:eu-repo/grantAgreement/MSSociety//CC BY 4.0https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:openaccess.uoc.edu:10609/1475332026-05-28T12:42:01Z
dc.title.none.fl_str_mv Cortical involvement determines impairment 30 years after a clinically isolated syndrome
title Cortical involvement determines impairment 30 years after a clinically isolated syndrome
spellingShingle Cortical involvement determines impairment 30 years after a clinically isolated syndrome
Haider, Lukas
multiple sclerosis
clinically isolated syndrome
atrophy
magnetic resonance imaging
cortex
esclerosis múltiple
síndrome clínicament aïllada
atrofia
imatge de ressonància magnètica
escorça
esclerosis múltiple
síndrome clínicamente aislado
atrofia
imagen de resonancia magnética
corteza
multiple sclerosis
esclerosi múltiple
esclerosis múltiple
title_short Cortical involvement determines impairment 30 years after a clinically isolated syndrome
title_full Cortical involvement determines impairment 30 years after a clinically isolated syndrome
title_fullStr Cortical involvement determines impairment 30 years after a clinically isolated syndrome
title_full_unstemmed Cortical involvement determines impairment 30 years after a clinically isolated syndrome
title_sort Cortical involvement determines impairment 30 years after a clinically isolated syndrome
dc.creator.none.fl_str_mv Haider, Lukas
Prados Carrasco, Ferran
Chung, Karen
Goodkin, Olivia
Kanber, Baris
Sudre, Carole
Yiannakas, Marios
Samson, Rebecca
Mangesius, Stephanie
Thompson, Alan
Gandini Wheeler-Kingshott, Claudia A.M.
Ciccarelli, Olga
Chard, Declan
Barkhof, Frederik
author Haider, Lukas
author_facet Haider, Lukas
Prados Carrasco, Ferran
Chung, Karen
Goodkin, Olivia
Kanber, Baris
Sudre, Carole
Yiannakas, Marios
Samson, Rebecca
Mangesius, Stephanie
Thompson, Alan
Gandini Wheeler-Kingshott, Claudia A.M.
Ciccarelli, Olga
Chard, Declan
Barkhof, Frederik
author_role author
author2 Prados Carrasco, Ferran
Chung, Karen
Goodkin, Olivia
Kanber, Baris
Sudre, Carole
Yiannakas, Marios
Samson, Rebecca
Mangesius, Stephanie
Thompson, Alan
Gandini Wheeler-Kingshott, Claudia A.M.
Ciccarelli, Olga
Chard, Declan
Barkhof, Frederik
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv University College London (UCL)
Medical University of Vienna
Universitat Oberta de Catalunya (UOC)
King’s College London
Medical University of Innsbruck
University of Pavia
IRCCS Mondino Foundation
VU University Medical Centre
dc.subject.none.fl_str_mv multiple sclerosis
clinically isolated syndrome
atrophy
magnetic resonance imaging
cortex
esclerosis múltiple
síndrome clínicament aïllada
atrofia
imatge de ressonància magnètica
escorça
esclerosis múltiple
síndrome clínicamente aislado
atrofia
imagen de resonancia magnética
corteza
multiple sclerosis
esclerosi múltiple
esclerosis múltiple
topic multiple sclerosis
clinically isolated syndrome
atrophy
magnetic resonance imaging
cortex
esclerosis múltiple
síndrome clínicament aïllada
atrofia
imatge de ressonància magnètica
escorça
esclerosis múltiple
síndrome clínicamente aislado
atrofia
imagen de resonancia magnética
corteza
multiple sclerosis
esclerosi múltiple
esclerosis múltiple
description Many studies report an overlap of MRI and clinical findings between patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), which in part is reflective of inclusion of subjects with variable disease duration and short periods of follow-up. To overcome these limitations, we examined the differences between RRMS and SPMS and the relationship between MRI measures and clinical outcomes 30 years after first presentation with clinically isolated syndrome suggestive of multiple sclerosis. Sixty-three patients were studied 30 years after their initial presentation with a clinically isolated syndrome; only 14% received a disease modifying treatment at any time point. Twenty-seven patients developed RRMS, 15 SPMS and 21 experienced no further neurological events; these groups were comparable in terms of age and disease duration. Clinical assessment included the Expanded Disability Status Scale, 9-Hole Peg Test and Timed 25-Foot Walk and the Brief International Cognitive Assessment For Multiple Sclerosis. All subjects underwent a comprehensive MRI protocol at 3 T measuring brain white and grey matter (lesions, volumes and magnetization transfer ratio) and cervical cord involvement. Linear regression models were used to estimate age- and gender-adjusted group differences between clinical phenotypes after 30 years, and stepwise selection to determine associations between a large sets of MRI predictor variables and physical and cognitive outcome measures. At the 30-year follow-up, the greatest differences in MRI measures between SPMS and RRMS were the number of cortical lesions, which were higher in SPMS (the presence of cortical lesions had 100% sensitivity and 88% specificity), and grey matter volume, which was lower in SPMS. Across all subjects, cortical lesions, grey matter volume and cervical cord volume explained 60% of the variance of the Expanded Disability Status Scale; cortical lesions alone explained 43%. Grey matter volume, cortical lesions and gender explained 43% of the variance of Timed 25-Foot Walk. Reduced cortical magnetization transfer ratios emerged as the only significant explanatory variable for the symbol digit modality test and explained 52% of its variance. Cortical involvement, both in terms of lesions and atrophy, appears to be the main correlate of progressive disease and disability in a cohort of individuals with very long follow-up and homogeneous disease duration, indicating that this should be the target of therapeutic interventions.
publishDate 2021
dc.date.none.fl_str_mv 2021
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/10609/147533
http://hdl.handle.net/10609/147533
url https://hdl.handle.net/10609/147533
http://hdl.handle.net/10609/147533
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Brain, 2021, 144(5)
Brain;144
https://doi.org/10.1093/brain/awab033
info:eu-repo/grantAgreement/MSSociety//
dc.rights.none.fl_str_mv CC BY 4.0
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv CC BY 4.0
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press (OUP)
publisher.none.fl_str_mv Oxford University Press (OUP)
dc.source.none.fl_str_mv reponame:O2, repositorio institucional de la UOC
instname:Universitat Oberta de Catalunya (UOC)
instname_str Universitat Oberta de Catalunya (UOC)
reponame_str O2, repositorio institucional de la UOC
collection O2, repositorio institucional de la UOC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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