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. 2020 Jun 12;26(9):1352458520925369.
doi: 10.1177/1352458520925369. Online ahead of print.

Aggressive multiple sclerosis (1): Towards a definition of the phenotype

Ellen Iacobaeus  1 , Georgina Arrambide  2 , Maria Pia Amato  3 , Tobias Derfuss  4 , Sandra Vukusic  5 , Bernhard Hemmer  6 , Mar Tintore  2 , Lou Brundin  1 ; 2018 ECTRIMS Focused Workshop Group
Collaborators, Affiliations

Aggressive multiple sclerosis (1): Towards a definition of the phenotype

Ellen Iacobaeus et al. Mult Scler. .

Abstract

While the major phenotypes of multiple sclerosis (MS) and relapsing-remitting, primary and secondary progressive MS have been well characterized, a subgroup of patients with an active, aggressive disease course and rapid disability accumulation remains difficult to define and there is no consensus about their management and treatment. The current lack of an accepted definition and treatment guidelines for aggressive MS triggered a 2018 focused workshop of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) on aggressive MS. The aim of the workshop was to discuss approaches on how to describe and define the disease phenotype and its treatments. Unfortunately, it was not possible to come to consensus on a definition because of unavailable data correlating severe disease with imaging and molecular biomarkers. However, the workshop highlighted the need for future research needed to define this disease subtype while also focusing on its treatment and management. Here, we review previous attempts to define aggressive MS and present characteristics that might, with additional research, eventually help characterize it. A companion paper summarizes data regarding treatment and management.

Keywords: Aggressive; disability; highly active; multiple sclerosis; observational studies; relapsing/remitting.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: E.I. has honoraria for advisory boards or lecturing for Sanofi Genzyme and Merck outside the submitted work. G.A. has received compensation for consulting services or participation in advisory boards from Sanofi, Merck and Roche; research support from Novartis; travel expenses for scientific meetings from Novartis, Roche and Stendhal; and speaking honoraria from Sanofi and Merck. M.P.A. has received research grants and personal fees as a speaker and member of advisory boards by Biogen, Sanofi Genzyme, Merck Serono, Novartis, Roche and Teva, outside the submitted work. T.D. reports grants from Novartis and Biogen. Dr Derfuss’ institution received financial support from Novartis, Biogen, Roche, Merck Serono, Celgene, Sanofi Genzyme, MedDay, GeNeuro, Mitsubishi Pharma and Actelion for his activities as steering committee or advisory board member or consultant. S.V. has received grants, personal fees and non-financial support from Biogen, Celgene, Geneuro, Genzyme, Medday, Merck Serono, Novartis, Roche, Sanofi and Teva, outside the submitted work. B.H. has served on scientific advisory boards for Novartis and as DMSC member for AllergyCare and TG therapeutics; he or his institution have received speaker honoraria from Desitin; holds part of two patents; one for the detection of antibodies against KIR4.1 in a subpopulation of MS patients and one for genetic determinants of neutralizing antibodies to interferon. M.T. has received compensation for consulting services and speaking honoraria from Almirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Merck Serono, Novartis, Roche, Sanofi-Aventis and Teva Pharmaceuticals. M.T. is co-editor of Multiple Sclerosis Journal ETC. L.B. has received honoraria for advisory boards for Biogen, Sanofi-Genzyme, Novartis and Teva and has received lecturing fees from Biogen, Novartis, Teva and Sanofi-Genzyme outside the submitted work.

Figures

Figure 1.
Figure 1.
Typical characteristics of aggressive MS on conventional MRI: (a)–(c) T2-FLAIR transverse sequences showing multiple nodular, confluent lesions predominantly affecting the periventricular and callosal topographies (see arrows) in a 33-year-old male patient with a first demyelinating attack. (d)–(f) T1 transverse sequences in the same patient after gadolinium administration show multiple nodular and ring-enhancing lesions. (g) (T2-FLAIR transverse sequence) and (h) (T2 sagittal sequence of the cervical spinal cord) show multiple infratentorial and spinal cord lesions in a 24-year-old female patient with relapsing–remitting multiple sclerosis, several of which showed contrast enhancement despite treatment with (i) and (j) fingolimod.
See this image and copyright information in PMC

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