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Two years' effect of dimethyl fumarate on focal and diffuse gray matter pathology in multiple sclerosis
Damiano Marastoni1, Francesco Crescenzo2, Anna I Pisani1
1Regional Multiple Sclerosis Center, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Background:
Data on the effect of dimethyl fumarate (DMF) on focal and diffuse gray matter (GM) damage, a relevant pathological substrate of multiple sclerosis (MS)-related disability are lacking.
Objective:
To evaluate the DMF effect on cortical lesions (CLs) accumulation and global and regional GM atrophy in subjects with relapsing-remitting MS.
Methods:
A total of 148 patients (mean age 38.1 ± 9.7 years) treated with DMF ended a 2-year longitudinal study. All underwent regular Expanded Disability Status Scale (EDSS assessment), and at least two 3T-magnetic resonance imaging (MRI) at 3 and 24 months after DMF initiation. CLs and changes in global and regional atrophy of several brain regions were compared with 47 untreated age and sex-matched patients.
Results:
DMF-treated patients showed lower CLs accumulation (median 0[0-3] vs 2[0-7], p < 0.001) with respect to controls. Global cortical thickness (p < 0.001) and regional thickness and volume were lower in treated group (cerebellum, hippocampus, caudate, and putamen: p < 0.001; thalamus p = 0.03). Lower relapse rate (14% vs 40%, p < 0.001), EDSS change (0.2 ± 0.4 vs 0.4 ± 0.9, p < 0.001), and new WM lesions (median 0[0-5] vs 2[0-6], p < 0.001) were reported. No severe adverse drug reactions occurred.
Conclusions:
Beyond the well-known effect on disease activity, these results provide evidence of the effect of DMF through reduced progression of focal and diffuse GM damage.
Insights
Dimethyl fumarate (DMF) reduces gray matter damage and cortical lesion accumulation in relapsing-remitting multiple sclerosis (MS) patients. This study shows DMF
Area of Science:
- Neuroscience
- Immunology
- Radiology
Background:
- Data on dimethyl fumarate (DMF) effects on gray matter (GM) damage in multiple sclerosis (MS) are limited.
- GM damage is a key factor in MS-related disability.
Purpose of the Study:
- To assess DMF's impact on cortical lesion (CL) accumulation.
- To evaluate DMF's effect on global and regional GM atrophy in relapsing-remitting MS (RRMS) patients.
Main Methods:
- A 2-year longitudinal study of 148 RRMS patients treated with DMF.
- Regular Expanded Disability Status Scale (EDSS) assessments and 3T-MRI scans at 3 and 24 months.
- Comparison of CLs and GM atrophy with 47 untreated controls.
Main Results:
- DMF-treated patients had significantly lower CL accumulation (p < 0.001).
- Reduced global cortical thickness and regional atrophy in cerebellum, hippocampus, caudate, putamen, and thalamus (p < 0.001).
- Lower relapse rates (14% vs 40%), reduced EDSS change, and fewer new white matter lesions were observed.
Conclusions:
- Dimethyl fumarate treatment is associated with reduced focal and diffuse gray matter damage progression in MS.
- DMF demonstrates efficacy beyond controlling disease activity, by mitigating neurodegenerative processes.
