The long-term outcomes of CIS patients in the Barcelona inception cohort: Looking back to recognize aggressive MS

Abstract

Objective: To explore the long-term outcomes of patients with clinically isolated syndromes from the Barcelona cohort. Methods: We selected patients with a follow-up longer than 10 years to (1) estimate the risks of multiple sclerosis (MS) and disability accumulation according to the baseline number of T2 lesions and to compare treated versus untreated patients and early versus delayed treatment, and (2) to study baseline features of patients with aggressive MS (Expanded Disability Status Scale (EDSS) ⩾6.0 at 10 years). Results: In all, 401 patients were included (mean follow-up of 14.4 (standard deviation of 2.9) years). A higher number of T2 lesions was associated with an earlier MS diagnosis and an earlier risk of irreversible disability. Early treatment was associated with a decreased risk of EDSS of 3.0: adjusted hazard ratio = 0.4, 95% confidence interval = (0.2, 0.7). Patients with aggressive MS differed in their baseline brain magnetic resonance images: The median (interquartile range) number of T2 lesions and contrastenhancing lesions (CEL) was 71 (28-95) versus 7 (1-19) and 3 (1-24) versus 0 (0-1), respectively. The cut-offs that better classified patients with aggressive MS were 20 for T2 lesions and 2 for CEL. Conclusion: Although MS natural history is changing, a high lesion load at onset is helpful to identify patients at risk of presenting an aggressive MS.

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

“…In both cohorts, approximately 5.0-6.0% of patients fulfilled this definition. 13,14 Their findings are described in the clinical and MRI subsections in the following.…”

“…The presence of a high T2 lesion load, >2 Gd + lesions, lesion topography, T1 black holes and early discernible atrophy are well recognized early predictors for disease progression. 13,[29][30][31][32][33][34][68][69][70] A study of over Table 2. Potential parameters associated with more aggressive disease course (any one or a combination of these characteristics may signal aggressive disease and all are deserving of further exploration and if possible, validation in the context of assessing severity of disease and poor prognosis).…”

“…High T2 lesion burden 13,29,30 ⩾20 T2 lesions at the time of disease onset 13 ⩾2 Gd+ lesions 10,31 ⩾2 Gd+ lesions at the time of disease onset 13 T1 black holes 29,32 Infratentorial lesions 30,33 Spinal cord lesion and/or atrophy 30,34,35 Early discernible atrophy 36 Cortical and deep grey matter atrophy 32,37,38 Smouldering lesions 39…”

“…• At onset -⩾2 Gd+ lesions 10 -High T2 lesion load 68,71 -Presence of spinal cord > infratentorial lesions 33,34,74 • During early follow-up -⩾2 new Gd+ lesions 30,71 -⩾1 new spinal cord lesions 30 -Atrophy measures, possibly spinal cord > brain; PBVC decrease below -0.817% in the first year 37,70,75,76 Combined factors ⩾20 lesions on T2-weighted images and ⩾2 Gd+ lesions at disease onset (18.9% risk) 13…”

Aggressive multiple sclerosis (2): Treatment

“…To the extent possible, paraclinical and clinical biomarkers may aid stratify the more severe cases of both relapsing and pMS phenotypes. As mentioned before, two studies have recently proposed EDSS ⩾ 6.0 at 10 years as a definition of aggressive MS, 8,9 but this proposal needs to be validated in other cohorts or registries. In addition, it is important to assess whether other biomarkers of aggressive disease (i.e.…”