The University of Sydney, Royal Prince Alfred Hospital

Author Of 1 Presentation

Observational Studies Poster Presentation

P0874 - Fingolimod therapy in real world relapsing MS patients: Cognition, quantitative MRI and deep gray matter quantitative susceptibility mapping (ID 1238)



Limited data is available regarding the effect of disease modifying therapies on cognitive decline and brain volume change in real world multiple sclerosis (MS) patients. Novel deep gray matter (DGM) quantitative susceptibility mapping (QSM) techniques have not been extensively studied in MS.


To assess cognitive performance, magnetic resonance imaging (MRI) brain volumetrics and deep gray matter QSM at baseline, 6 months, 12 months and 24 months in a real world relapsing MS patient cohort treated with fingolimod, referenced to age- and sex-matched healthy controls (HCs).


Relapsing MS patients from 2 centers (Sydney, Australia and Buffalo, United States of America) were recruited to this observational, prospective study following the decision by their treating neurologist to commence fingolimod therapy. Neurological assessment (Expanded Disability Status Scale (EDSS)), cognitive testing (Minimal Assessment of Cognitive Function (MACFIMS)), and 3 tesla (3T) MRI brain acquisition occurred at baseline, 6 months, 12 months and 24 months. Matched HCs were recruited prospectively from both centers and were followed longitudinally at the same time points.


The relapsing MS (n = 50) and HC (n = 41) cohorts were well matched for age and sex. With fingolimod treatment, clinical relapse rates and MRI lesion activity were significantly reduced, and the EDSS remained stable, in the relapsing MS patient group. Baseline DGM volumes, but not whole brain volumes, were significantly lower in the patient cohort compared to the HC cohort (p < 0.05). Longitudinal DGM volume changes were not significantly different between the groups. Between the baseline and 24 month time points the percentage whole brain atrophy, as measured using Structural Image Evaluation using Normalisation of Atrophy (SIENA), was higher in the patient group (mean: -1.25%) compared with the HC group (mean: -0.44%) (p = 0.006). Baseline thalamus QSM was significantly lower, and the baseline caudate and pallidus QSM were significantly higher, in the MS patient group (p < 0.05). Longitudinal DGM QSM changes were not significantly different between groups. Baseline cognitive performance was worse in the MS group (p < 0.05), but longitudinal cognitive stability/improvement was not significantly different between the two groups.


This real world prospective observational study suggests that fingolimod reduced clinical relapses and MRI lesion activity, and stabilized cognitive performance in the relapsing MS patient cohort. DGM volume and DGM QSM change rates were comparable between the fingolimod treated relapsing MS patients and the age- and sex-matched healthy controls. Whole brain atrophy between baseline and 24 months was greater in the fingolimod treated MS patients compared with HCs, but the differences were not significant for other epochs; further subgroup analysis is underway to explore this finding.