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

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.

In Vivo Proton Exchange Rate (kex) MRI for the Characterization of Multiple Sclerosis Lesions in Patients

“…Novel molecular and metabolic imaging methods may be useful to refine the identification of lesion subtype to assist in understanding disease, including the contribution of reactive oxygen species and other direct causes of tissue damage 5 . Better imaging strategies may enable prospective identification of aggressive disease to facilitate patient stratification into aggressive vs. conservative treatment plans 6 . Moreover, new noninvasive imaging biomarkers of neuroprotection and repair are needed to guide clinical decisions and allow evaluation of experimental therapeutics, particularly those directed toward regeneration in gadolinium‐negative lesions 7–10 …”

Aggressive multiple sclerosis (2): Treatment

“…A review of the pathology, demographic and clinical characteristics, and prognosis of aggressive MS, as well as the methods used to try to reach a consensus definition are presented in a companion article. 7 Prior to the workshop, specific treatments or groups of treatments were assigned to different participating MS specialists who conducted a relevant literature search on PubMed including but not limited to the terms: ‘treatment x’ AND ‘multiple sclerosis’ OR ‘MS’ AND ‘aggressive’ OR ‘highly active’. The search was performed up to March 2018 with no limits on language.…”

“…These patients may have frequent, severe relapses with incomplete recovery and are at risk of developing greater and permanent disability within a short time frame. 6 , 7 Although it was not possible to come to consensus about a definition of aggressive MS at the end of the workshop, we considered radiological, clinical and biological features that might be used to obtain such a consensus. Two recent papers proposed reaching an Expanded Disability Status Scale (EDSS) ⩾ 6.0 within 10 years of disease onset as aggressive MS (please refer to the companion paper 7 for a more detailed discussion).…”

“… 6 , 7 Although it was not possible to come to consensus about a definition of aggressive MS at the end of the workshop, we considered radiological, clinical and biological features that might be used to obtain such a consensus. Two recent papers proposed reaching an Expanded Disability Status Scale (EDSS) ⩾ 6.0 within 10 years of disease onset as aggressive MS (please refer to the companion paper 7 for a more detailed discussion). 8 , 9 These and several other definitions are based on relapse frequency or severity, lack of recovery, disability accrual or magnetic resonance imaging (MRI) lesions.…”

Monitoring the Redox Status in Multiple Sclerosis

“…Nearly 10% of MS patients suffer from steady deterioration of neurological functions without recovery, termed primary progressive MS (PPMS). As few as 5% of MS patients present progressive neurological deficits with acute attacks with or without recovery, termed progressive-relapsing MS (PRMS) [ 17 ]. However, PRMS is no longer considered a subtype of MS and is now grouped into PPMS with active disease of new symptoms or changes in the MRI scan [ 18 ].…”