Defining the clinical course of multiple sclerosis: the 2013 revisions

Fred D Lublin¹, Stephen C Reingold¹, Jeffrey A Cohen¹, Gary R Cutter¹, Per Soelberg Sørensen¹, Alan J Thompson¹, Jerry S Wolinsky¹, Laura J Balcer¹, Brenda Banwell¹, Frederik Barkhof¹, Bruce Bebo Jr¹, Peter A Calabresi¹, Michel Clanet¹, Giancarlo Comi¹, Robert J Fox¹, Mark S Freedman¹, Andrew D Goodman¹, Matilde Inglese¹, Ludwig Kappos¹, Bernd C Kieseier¹, John A Lincoln¹, Catherine Lubetzki¹, Aaron E Miller¹, Xavier Montalban¹, Paul W O'Connor¹, John Petkau¹, Carlo Pozzilli¹, Richard A Rudick¹, Maria Pia Sormani¹, Olaf Stüve¹, Emmanuelle Waubant¹, Chris H Polman¹

Affiliations

Affiliation

¹ From the Corinne Goldsmith Dickenson Center for Multiple Sclerosis (F.D.L., A.E.M.), Icahn School of Medicine at Mount Sinai, New York, NY; Scientific and Clinical Review Associates, LLC (S.C.R.), Salisbury, CT; The Mellen Center for MS Treatment and Research (J.A.C., R.J.F., R.A.R.), Cleveland Clinic, OH; the Department of Biostatistics (G.R.C.), University of Alabama at Birmingham; the Danish Multiple Sclerosis Center (P.S.S.), Department of Neurology, Copenhagen University Hospital Rigshospitalet, Denmark; University College London Institute of Neurology (A.J.T.), UK; the Department of Neurology (J.S.W., J.A.L.), University of Texas Health Sciences Center, Houston; the Department of Neurology (L.J.B.), New York University Langone Medical Center, New York; the Division of Neurology (B. Banwell), The Children's Hospital of Philadelphia, PA; the Departments of Radiology and Nuclear Medicine (F.B.) and Neurology (C.H.P.), VU Medical Center, Amsterdam, the Netherlands; Research Programs Department (B. Bebo), National Multiple Sclerosis Society, New York, NY; the Department of Neurology (P.A.C.), The Johns Hopkins Hospital, Baltimore, MD; Fédération de Neurologie (M.C.), CHU Hôpital Purpan, Toulouse, France; the Department of Neurology (G.C.), Scientific Institute San Raffaele, University Vita-Salute San Raffaele, Milan, Italy; University of Ottawa and the Ottawa Hospital Research Institute (M.S.F.), Canada; the Department of Neurology (A.D.G.), University of Rochester Medical Center, NY; the Departments of Neurology, Radiology and Neuroscience (M.I.), Mount Sinai School of Medicine, New York, NY; the Department of Neurology (L.K.), University Hospital, Basel, Switzerland; the Department of Neurology (B.C.K.), Heinrich-Heine-University, Düsseldorf, Germany; the Department of Neurology (C.L.), Salpêtrière Hospital, UPMC, Paris, France; the Department of Neurology-Neuroimmunology (X.M.), Cemcat, Hospital Universitari Vall d'Hebron, Barcelona, Spain; the Division of

PMID: 24871874
PMCID: PMC4117366
DOI: 10.1212/WNL.0000000000000560

Defining the clinical course of multiple sclerosis: the 2013 revisions

Fred D Lublin et al. Neurology. 2014.

. 2014 Jul 15;83(3):278-86.

doi: 10.1212/WNL.0000000000000560. Epub 2014 May 28.

Authors

Affiliation

¹ From the Corinne Goldsmith Dickenson Center for Multiple Sclerosis (F.D.L., A.E.M.), Icahn School of Medicine at Mount Sinai, New York, NY; Scientific and Clinical Review Associates, LLC (S.C.R.), Salisbury, CT; The Mellen Center for MS Treatment and Research (J.A.C., R.J.F., R.A.R.), Cleveland Clinic, OH; the Department of Biostatistics (G.R.C.), University of Alabama at Birmingham; the Danish Multiple Sclerosis Center (P.S.S.), Department of Neurology, Copenhagen University Hospital Rigshospitalet, Denmark; University College London Institute of Neurology (A.J.T.), UK; the Department of Neurology (J.S.W., J.A.L.), University of Texas Health Sciences Center, Houston; the Department of Neurology (L.J.B.), New York University Langone Medical Center, New York; the Division of Neurology (B. Banwell), The Children's Hospital of Philadelphia, PA; the Departments of Radiology and Nuclear Medicine (F.B.) and Neurology (C.H.P.), VU Medical Center, Amsterdam, the Netherlands; Research Programs Department (B. Bebo), National Multiple Sclerosis Society, New York, NY; the Department of Neurology (P.A.C.), The Johns Hopkins Hospital, Baltimore, MD; Fédération de Neurologie (M.C.), CHU Hôpital Purpan, Toulouse, France; the Department of Neurology (G.C.), Scientific Institute San Raffaele, University Vita-Salute San Raffaele, Milan, Italy; University of Ottawa and the Ottawa Hospital Research Institute (M.S.F.), Canada; the Department of Neurology (A.D.G.), University of Rochester Medical Center, NY; the Departments of Neurology, Radiology and Neuroscience (M.I.), Mount Sinai School of Medicine, New York, NY; the Department of Neurology (L.K.), University Hospital, Basel, Switzerland; the Department of Neurology (B.C.K.), Heinrich-Heine-University, Düsseldorf, Germany; the Department of Neurology (C.L.), Salpêtrière Hospital, UPMC, Paris, France; the Department of Neurology-Neuroimmunology (X.M.), Cemcat, Hospital Universitari Vall d'Hebron, Barcelona, Spain; the Division of

PMID: 24871874
PMCID: PMC4117366
DOI: 10.1212/WNL.0000000000000560

Abstract

Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined.

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Figures

**Figure 1. The 1996 vs 2013 multiple sclerosis phenotype descriptions for relapsing disease**
*Activity determined by clinical relapses and/or MRI activity (contrast-enhancing lesions; new or unequivocally enlarging T2 lesions assessed at least annually); if assessments are not available, activity is “indeterminate.” **CIS, if subsequently clinically active and fulfilling current multiple sclerosis (MS) diagnostic criteria, becomes relapsing-remitting MS (RRMS).

**Figure 2. The 1996 vs 2013 multiple sclerosis phenotype descriptions for progressive disease**
*Activity determined by clinical relapses assessed at least annually and/or MRI activity (contrast-enhancing lesions; new and unequivocally enlarging T2 lesions). **Progression measured by clinical evaluation, assessed at least annually. If assessments are not available, activity and progression are “indeterminate.” MS = multiple sclerosis; PP = primary progressive; PR = progressive relapsing; SP = secondary progressive.

See this image and copyright information in PMC

Comment in

Active and progressive: a new duality of MS classification.
Cross AH, Wingerchuk DM, Weinshenker BG. Cross AH, et al. Neurology. 2014 Jul 15;83(3):206-7. doi: 10.1212/WNL.0000000000000601. Epub 2014 Jun 13. Neurology. 2014. PMID: 24928117 No abstract available.
Defining the clinical course of multiple sclerosis: the 2013 revisions.
Jacques FH. Jacques FH. Neurology. 2015 Mar 3;84(9):963. doi: 10.1212/01.wnl.0000462309.76486.c5. Neurology. 2015. PMID: 25732366 No abstract available.
Author response.
Lublin FD. Lublin FD. Neurology. 2015 Mar 3;84(9):963. Neurology. 2015. PMID: 25905117 No abstract available.

References

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1. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011;69:292–302 - PMC - PubMed
1. Miller D, Barkhof F, Montalban X, Thompson A, Filippi M. Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis. Lancet Neurol 2005;4:281–288 - PubMed
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1. O'Riordan JI, Thompson AJ, Kingsley DP, et al. The prognostic value of brain MRI in clinically isolated syndromes of the CNS: a 10-year follow-up. Brain 1998;121:495–503 - PubMed

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Defining the clinical course of multiple sclerosis: the 2013 revisions

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Defining the clinical course of multiple sclerosis: the 2013 revisions

Authors

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Abstract

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References

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LinkOut - more resources

Full Text Sources

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Medical