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Brain atrophy and disability worsening in primary progressive multiple sclerosis: insights from the INFORMS study

OBJECTIVE: To investigate the relationship between brain volume and disability worsening over ≥3 years in the natural history of primary progressive multiple sclerosis using data from the placebo group of the INFORMS trial (n = 487; clinicaltrials.gov NCT00731692). METHODS: Magnetic resonance imagin...

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Autores principales: Miller, David H., Lublin, Fred D., Sormani, Maria Pia, Kappos, Ludwig, Yaldizli, Özgür, Freedman, Mark S., Cree, Bruce A. C., Weiner, Howard L., Lubetzki, Catherine, Hartung, Hans‐Peter, Montalban, Xavier, Uitdehaag, Bernard M. J., MacManus, David G., Yousry, Tarek A., Gandini Wheeler‐Kingshott, Claudia A. M., Li, Bingbing, Putzki, Norman, Merschhemke, Martin, Häring, Dieter A., Wolinsky, Jerry S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846448/
https://www.ncbi.nlm.nih.gov/pubmed/29560379
http://dx.doi.org/10.1002/acn3.534
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author Miller, David H.
Lublin, Fred D.
Sormani, Maria Pia
Kappos, Ludwig
Yaldizli, Özgür
Freedman, Mark S.
Cree, Bruce A. C.
Weiner, Howard L.
Lubetzki, Catherine
Hartung, Hans‐Peter
Montalban, Xavier
Uitdehaag, Bernard M. J.
MacManus, David G.
Yousry, Tarek A.
Gandini Wheeler‐Kingshott, Claudia A. M.
Li, Bingbing
Putzki, Norman
Merschhemke, Martin
Häring, Dieter A.
Wolinsky, Jerry S.
author_facet Miller, David H.
Lublin, Fred D.
Sormani, Maria Pia
Kappos, Ludwig
Yaldizli, Özgür
Freedman, Mark S.
Cree, Bruce A. C.
Weiner, Howard L.
Lubetzki, Catherine
Hartung, Hans‐Peter
Montalban, Xavier
Uitdehaag, Bernard M. J.
MacManus, David G.
Yousry, Tarek A.
Gandini Wheeler‐Kingshott, Claudia A. M.
Li, Bingbing
Putzki, Norman
Merschhemke, Martin
Häring, Dieter A.
Wolinsky, Jerry S.
author_sort Miller, David H.
collection PubMed
description OBJECTIVE: To investigate the relationship between brain volume and disability worsening over ≥3 years in the natural history of primary progressive multiple sclerosis using data from the placebo group of the INFORMS trial (n = 487; clinicaltrials.gov NCT00731692). METHODS: Magnetic resonance imaging scans were collected annually. Brain volume loss was determined using SIENA. Patients were stratified by baseline normalized brain volume after adjusting for demographic and disease‐burden covariates. RESULTS: Baseline normalized brain volume was predictive of disability worsening: Risk of 3‐month confirmed disability progression was reduced by 36% for high versus low baseline normalized brain volume (Cox's model hazard ratio 0.64, P = 0.0339; log‐rank test: P = 0.0297). Moreover, on‐study brain volume loss was significantly associated with disability worsening (P = 0.012) and was evident in patients with or without new lesions or relapses. Brain volume loss depended significantly on baseline T2 lesion volume (P < 0.0001). Despite low inflammatory activity at baseline (13% of patients had gadolinium‐enhancing lesions) and throughout the study (mean 0.5 new/enlarging T2 lesions and 172 mm(3) T2 lesion volume increase per year), baseline T2 lesion volume was substantial (mean 10 cm(3)). Lower normalized brain volume at baseline correlated with higher baseline T2 volume and older age (both P < 0.0001). INTERPRETATION: Baseline brain volume and the rate of ongoing brain atrophy are significantly associated with disability worsening in primary progressive multiple sclerosis. Brain volume loss is significantly related to baseline T2 lesion volume, but partially independent of new lesion activity, which might explain the limited efficacy of anti‐inflammatory treatment.
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spelling pubmed-58464482018-03-20 Brain atrophy and disability worsening in primary progressive multiple sclerosis: insights from the INFORMS study Miller, David H. Lublin, Fred D. Sormani, Maria Pia Kappos, Ludwig Yaldizli, Özgür Freedman, Mark S. Cree, Bruce A. C. Weiner, Howard L. Lubetzki, Catherine Hartung, Hans‐Peter Montalban, Xavier Uitdehaag, Bernard M. J. MacManus, David G. Yousry, Tarek A. Gandini Wheeler‐Kingshott, Claudia A. M. Li, Bingbing Putzki, Norman Merschhemke, Martin Häring, Dieter A. Wolinsky, Jerry S. Ann Clin Transl Neurol Research Articles OBJECTIVE: To investigate the relationship between brain volume and disability worsening over ≥3 years in the natural history of primary progressive multiple sclerosis using data from the placebo group of the INFORMS trial (n = 487; clinicaltrials.gov NCT00731692). METHODS: Magnetic resonance imaging scans were collected annually. Brain volume loss was determined using SIENA. Patients were stratified by baseline normalized brain volume after adjusting for demographic and disease‐burden covariates. RESULTS: Baseline normalized brain volume was predictive of disability worsening: Risk of 3‐month confirmed disability progression was reduced by 36% for high versus low baseline normalized brain volume (Cox's model hazard ratio 0.64, P = 0.0339; log‐rank test: P = 0.0297). Moreover, on‐study brain volume loss was significantly associated with disability worsening (P = 0.012) and was evident in patients with or without new lesions or relapses. Brain volume loss depended significantly on baseline T2 lesion volume (P < 0.0001). Despite low inflammatory activity at baseline (13% of patients had gadolinium‐enhancing lesions) and throughout the study (mean 0.5 new/enlarging T2 lesions and 172 mm(3) T2 lesion volume increase per year), baseline T2 lesion volume was substantial (mean 10 cm(3)). Lower normalized brain volume at baseline correlated with higher baseline T2 volume and older age (both P < 0.0001). INTERPRETATION: Baseline brain volume and the rate of ongoing brain atrophy are significantly associated with disability worsening in primary progressive multiple sclerosis. Brain volume loss is significantly related to baseline T2 lesion volume, but partially independent of new lesion activity, which might explain the limited efficacy of anti‐inflammatory treatment. John Wiley and Sons Inc. 2018-01-30 /pmc/articles/PMC5846448/ /pubmed/29560379 http://dx.doi.org/10.1002/acn3.534 Text en © 2018 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Miller, David H.
Lublin, Fred D.
Sormani, Maria Pia
Kappos, Ludwig
Yaldizli, Özgür
Freedman, Mark S.
Cree, Bruce A. C.
Weiner, Howard L.
Lubetzki, Catherine
Hartung, Hans‐Peter
Montalban, Xavier
Uitdehaag, Bernard M. J.
MacManus, David G.
Yousry, Tarek A.
Gandini Wheeler‐Kingshott, Claudia A. M.
Li, Bingbing
Putzki, Norman
Merschhemke, Martin
Häring, Dieter A.
Wolinsky, Jerry S.
Brain atrophy and disability worsening in primary progressive multiple sclerosis: insights from the INFORMS study
title Brain atrophy and disability worsening in primary progressive multiple sclerosis: insights from the INFORMS study
title_full Brain atrophy and disability worsening in primary progressive multiple sclerosis: insights from the INFORMS study
title_fullStr Brain atrophy and disability worsening in primary progressive multiple sclerosis: insights from the INFORMS study
title_full_unstemmed Brain atrophy and disability worsening in primary progressive multiple sclerosis: insights from the INFORMS study
title_short Brain atrophy and disability worsening in primary progressive multiple sclerosis: insights from the INFORMS study
title_sort brain atrophy and disability worsening in primary progressive multiple sclerosis: insights from the informs study
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846448/
https://www.ncbi.nlm.nih.gov/pubmed/29560379
http://dx.doi.org/10.1002/acn3.534
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