Effect of dimethyl fumarate on gray and white matter pathology in subjects with relapsing multiple sclerosis: a longitudinal study

Zivadinov, Robert; Hagemeier, Jesper; Bergsland, Niels; Weinstock‐Guttman, Bianca

doi:10.1111/ene.13562

Cited by 9 publications

(5 citation statements)

References 39 publications

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“…DMF showing lower average DTI metrics compared with injectables and fingolimod may be because the cohort was younger and had a shorter disease duration and shorter time since the last relapse. The positive effect of DMF on DTI metrics was also seen in another study 30 showing no change in DTI measures following 2-YFU DMF therapy, suggesting a neuroprotective role of DMF. Previous studies on the effect of DTI post fingolimod therapy exhibit varying results.…”

Section: Discussionmentioning

confidence: 53%

Stability of longitudinal DTI metrics in MS with treatment of injectables, fingolimod and dimethyl fumarate

et al. 2022

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Background and purpose Diffusion MRI (dMRI) is sensitive to microstructural changes in white matter of people with relapse-remitting multiple sclerosis (pw-RRMS) that lead to progressive disability. The role of diffusion in assessing the efficacy of different therapies requires more investigation. This study aimed to evaluate selected dMRI metrics in normal-appearing white matter and white matter-lesion in pw-RRMS and healthy controls longitudinally and compare the effect of therapies given. Material and methods Structural and dMRI scans were acquired from 78 pw-RRMS (29 injectables, 36 fingolimod, 13 dimethyl fumarate) and 43 HCs at baseline and 2-years follow-up. Changes in dMRI metrics and correlation with clinical parameters were evaluated. Results Differences were observed in most clinical parameters between pw-RRMS and HCs at both timepoints ( p ≤ 0.01). No significant differences in average changes over time were observed for any dMRI metric between treatment groups in either tissue type. Diffusion metrics in NAWM and WML correlated negatively with most cognitive domains, while FA correlated positively at baseline but only for NAWM at follow-up ( p ≤ 0.05). FA correlated negatively with disability in NAWM and WML over time, while MD and RD correlated positively only in NAWM. Conclusions This is the first DTI study comparing the effect of different treatments on dMRI parameters over time in a stable cohort of pw-RRMS. The results suggest that brain microstructural changes in a stable MS cohort are similar to HCs independent of the therapies used.

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Section: Discussionmentioning

confidence: 53%

Stability of longitudinal DTI metrics in MS with treatment of injectables, fingolimod and dimethyl fumarate

et al. 2022

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“…In a recent longitudinal observation, a relatively stable pattern in diffusion metrics was encountered in patients with relapsing-remitting MS which were administered dimethyl fumarate (DMF). In the same study, healthy controls showed a significantly greater rate of diffusion parameters increase in the thalamus and normal-appearing white matter, compared to the subjects with MS [145], cautiously (due to small sample sizes and lack of a placebo-controlled arm) suggesting a supplementary neuroprotective effect of DMF. Other studies reported a significant FA increase and radial diffusivity decrease in the corticospinal tract after initiation of fingolimod [146], or a stable pattern of diffusion parameters in the normal-appearing white matter for up to 48 months under natalizumab treatment [147].…”

Section: Main Textmentioning

confidence: 99%

Detecting neurodegenerative pathology in multiple sclerosis before irreversible brain tissue loss sets in

Schependom

Guldolf

D’hooghe

et al. 2019

Transl Neurodegener

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BackgroundMultiple sclerosis (MS) is a complex chronic inflammatory and degenerative disorder of the central nervous system. Accelerated brain volume loss, or also termed atrophy, is currently emerging as a popular imaging marker of neurodegeneration in affected patients, but, unfortunately, can only be reliably interpreted at the time when irreversible tissue damage likely has already occurred. Timing of treatment decisions based on brain atrophy may therefore be viewed as suboptimal.Main bodyThis Narrative Review focuses on alternative techniques with the potential of detecting neurodegenerative events in the brain of subjects with MS prior to the atrophic stage. First, metabolic and molecular imaging provide the opportunity to identify early subcellular changes associated with energy dysfunction, which is an assumed core mechanism of axonal degeneration in MS. Second, cerebral hypoperfusion has been observed throughout the entire clinical spectrum of the disorder but it remains an open question whether this serves as an alternative marker of reduced metabolic activity, or exists as an independent contributing process, mediated by endothelin-1 hyperexpression. Third, both metabolic and perfusion alterations may lead to repercussions at the level of network performance and structural connectivity, respectively assessable by functional and diffusion tensor imaging. Fourth and finally, elevated body fluid levels of neurofilaments are gaining interest as a biochemical mirror of axonal damage in a wide range of neurological conditions, with early rises in patients with MS appearing to be predictive of future brain atrophy.ConclusionsRecent findings from the fields of advanced neuroradiology and neurochemistry provide the promising prospect of demonstrating degenerative brain pathology in patients with MS before atrophy has installed. Although the overall level of evidence on the presented topic is still preliminary, this Review may pave the way for further longitudinal and multimodal studies exploring the relationships between the abovementioned measures, possibly leading to novel insights in early disease mechanisms and therapeutic intervention strategies.

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“…12 Notably, we also reported an effect on thalamic atrophy, according a possibile neuroprotective role of the drug, that is in line with the lack of microstructural changes over a 24-month follow-up observed in both normalappearing WM and thalamus. 34 Also, the evaluation of focal cortical damage by means of CLs, for which no data were so far available and which could represent a more useful and feasible tool in clinical practice, provided support on the efficacy of DMF on GM pathology.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Two years’ effect of dimethyl fumarate on focal and diffuse gray matter pathology in multiple sclerosis

Marastoni

Crescenzo²,

Pisani

et al. 2022

Mult Scler

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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.

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Effect of dimethyl fumarate on gray and white matter pathology in subjects with relapsing multiple sclerosis: a longitudinal study

Abstract: The lack of changes in diffusion tensor imaging metrics in patients with MS over 24 months possibly indicates a neuroprotective role of DMF. These findings provide additional evidence of the beneficial effect of DMF on MS-related pathology.

Cited by 9 publications

References 39 publications

Stability of longitudinal DTI metrics in MS with treatment of injectables, fingolimod and dimethyl fumarate

Stability of longitudinal DTI metrics in MS with treatment of injectables, fingolimod and dimethyl fumarate

Detecting neurodegenerative pathology in multiple sclerosis before irreversible brain tissue loss sets in

Two years’ effect of dimethyl fumarate on focal and diffuse gray matter pathology in multiple sclerosis

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