Fingolimod effect on gray matter, thalamus, and white matter in patients with multiple sclerosis

Neurology ◽  
2018 ◽  
Vol 90 (15) ◽  
pp. e1324-e1332 ◽  
Author(s):  
Laura Gaetano ◽  
Dieter A. Häring ◽  
Ernst-Wilhelm Radue ◽  
Nicole Mueller-Lenke ◽  
Avinash Thakur ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Gray Matter ◽  
Brain Volume ◽  
Percentage Change ◽  
Phase Iii ◽  
Volume Loss ◽  
Image Evaluation ◽  
Long Term Outcome ◽  
Structural Image

ObjectiveTo study the effect of fingolimod on deep gray matter (dGM), thalamus, cortical GM (cGM), white matter (WM), and ventricular volume (VV) in patients with relapsing-remitting multiple sclerosis (RRMS).MethodsData were pooled from 2 phase III studies. A total of 2,064 of 2,355 (88%) contributed to the analysis: fingolimod 0.5 mg n = 783, fingolimod 1.25 mg n = 799, or placebo n = 773. Percentage change from baseline in dGM and thalamic volumes was evaluated with FMRIB’s Integrated Registration & Segmentation Tool; WM, cGM, and VV were evaluated with structural image evaluation using normalization of atrophy cross-sectional version (SIENAX) at months 12 and 24.ResultsAt baseline, compound brain volume (brain volume in the z block [BVz] = cGM + dGM + WM) correlated with SIENAX-normalized brain volume (r = 0.938, p < 0.001); percentage change from baseline in BVz over 2 years correlated with structural image evaluation using normalization of atrophy percentage brain volume change (r = 0.713, p < 0.001). For placebo, volume reductions were most pronounced in cGM, and relative changes from baseline were strongest in dGM. Over 24 months, there were significant reductions with fingolimod vs placebo for dGM (0.5 mg −14.5%, p = 0.017; 1.25 mg −26.6%, p < 0.01) and thalamus (0.5 mg −26.1%, p = 0.006; 1.25 mg −49.7%, p < 0.001). Reduction of cGM volume loss was not significant. Significantly less WM loss and VV enlargement were seen with fingolimod vs placebo (all p < 0.001). A high T2 lesion volume at baseline predicted on-study cGM, dGM, and thalamic volume loss (p < 0.0001) but not WM loss. Patients taking placebo with high dGM (hazard ratio [HR] 0.54, p = 0.0323) or thalamic (HR 0.58, p = 0.0663) volume at baseline were less likely to show future disability worsening.ConclusionsFingolimod significantly reduced dGM volume loss (including thalamus) vs placebo in patients with RRMS. Reducing dGM and thalamic volume loss might improve long-term outcome.

scholarly journals Thalamic Injury and Cognition in Multiple Sclerosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Moein Amin ◽  
Daniel Ontaneda
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Gray Matter ◽  
Diffusion Tensor ◽  
Clinical Manifestations ◽  
White Matter Injury ◽  
Volume Loss ◽  
Thalamic Nuclei ◽  
Dorsomedial Nucleus ◽  
Deep Gray Matter

Multiple sclerosis (MS) produces demyelination and degeneration in both gray and white matter. Both cortical and deep gray matter injury is observed during the course of MS. Among deep gray matter structures, the thalamus has received special attention, as it undergoes volume loss in different MS subtypes and is involved in the earliest form of the disease, radiologically isolated syndrome. The thalamus plays an important role as an information relay center, and involvement of the thalamus in MS has been associated with a variety of clinical manifestations in MS, including fatigue, movement disorders, pain, and cognitive impairment (CI). Similar to thalamic volume loss, CI is seen from the earliest stages of MS and is potentially one of the most debilitating manifestations of the disease. The thalamus, particularly the dorsomedial nucleus as part of the basolateral limbic circuit and anterior thalamic nuclei through connections with the prefrontal cortex, has been shown to be involved in CI. Specifically, several cognitive performance measures such as processing speed and memory correlate with thalamic volume. Thalamic atrophy is one of the most important predictors of CI in MS, and both thalamic volume, diffusion tensor imaging measures, and functional activation correlate with the degree of CI in MS. Although the exact mechanism of thalamic atrophy is not well-understood, it is hypothesized to be secondary to degeneration following white matter injury resulting in secondary neurodegeneration and neuronal loss. The thalamus may represent an ideal biomarker for studies aiming to test neuroprotective or restorative therapies aimed at cognition.

Association of regional gray matter volume loss and progression of white matter lesions in multiple sclerosis — A longitudinal voxel-based morphometry study

NeuroImage ◽  
2009 ◽  
Vol 45 (1) ◽  
pp. 60-67 ◽  
Author(s):  
Kerstin Bendfeldt ◽  
Pascal Kuster ◽  
Stefan Traud ◽  
Hanspeter Egger ◽  
Sebastian Winklhofer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Gray Matter ◽  
Gray Matter Volume ◽  
White Matter Lesions ◽  
Volume Loss ◽  
Voxel Based Morphometry ◽  
Matter Volume

Childhood multiple sclerosis is associated with reduced brain volumes at first clinical presentation and brain growth failure

2019 ◽  
Vol 25 (7) ◽  
pp. 927-936 ◽  
Author(s):  
Frederik Bartels ◽  
Katharina Nobis ◽  
Graham Cooper ◽  
Eva Wendel ◽  
Robert Cleaveland ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Clinical Presentation ◽  
Brain Volume ◽  
Volume Loss ◽  
Brain Growth ◽  
Whole Brain ◽  
Brain Volumes ◽  
Brain Volume Loss

Background: Paediatric multiple sclerosis (pedMS) patients at a single site were shown to have reduced brain volumes and failure of age-expected brain growth compared to healthy controls. However, the precise time of onset of brain volume loss remains unclear. Objective: To longitudinally study brain volumes in a multi-centre European cohort at first presentation and after 2 years. Methods: Brain volumes of high-resolution magnetic resonance imaging (MRI) data from 37 pedMS patients at first presentation prior to steroid therapy and at 2-year follow-up ( n = 21) were compared to matched longitudinal MRI data from the NIH Paediatric MRI Data Repository. Results: Patients showed significantly reduced whole brain, grey and white matter and increased ventricular volumes at initial presentation and at follow-up compared to controls. Over 2 years, patients exhibited significant reduction of whole brain and white matter volumes, accompanied by increased ventricular volume. Brain volume loss at follow-up correlated with a higher number of infratentorial lesions, relapses and an increased Expanded Disability Status Scale (EDSS) score. Conclusions: In pedMS patients, brain volume loss is present already at first clinical presentation and accelerated over 2 years. Increased disease activity is associated with more severe brain volume loss. MRI brain volume change might serve as an outcome parameter in future prospective pedMS studies.

Brain Volume Loss During the First Year of Interferon-Beta Treatment in Multiple Sclerosis: Baseline Inflammation and Regional Brain Volume Dynamics

2016 ◽  
Vol 26 (5) ◽  
pp. 532-538 ◽  
Author(s):  
Angela Vidal-Jordana ◽  
Jaume Sastre-Garriga ◽  
Francisco Pérez-Miralles ◽  
Deborah Pareto ◽  
Jordi Rio ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Interferon Beta ◽  
Brain Volume ◽  
First Year ◽  
Volume Loss ◽  
Brain Volume Loss ◽  
Regional Brain ◽  
Regional Brain Volume

Association of Age at Onset With Gray Matter Volume and White Matter Microstructural Abnormalities in People With Multiple Sclerosis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012869
Author(s):  
Raffaello Bonacchi ◽  
Alessandro Meani ◽  
Elisabetta Pagani ◽  
Olga Marchesi ◽  
Andrea Falini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Gray Matter ◽  
Linear Models ◽  
Gray Matter Volume ◽  
Age At Onset ◽  
Healthy Controls ◽  
Compensatory Mechanisms ◽  
Cross Sectional ◽  
Matter Volume

Objective:To investigate whether age at onset influences brain gray matter volume (GMV) and white matter (WM) microstructural abnormalities in adult multiple sclerosis (MS) patients, given its influence on clinical phenotype and disease course.Method:In this hypothesis-driven cross-sectional study, we enrolled 67 pediatric-onset MS (POMS) patients and 143 sex- and disease duration (DD)-matched randomly-selected adult-onset MS (AOMS) patients, together with 208 healthy controls. All subjects underwent neurological evaluation and 3T MRI acquisition. MRI variables were standardized based on healthy controls, to remove effects of age and sex. Associations with DD in POMS and AOMS patients were studied with linear models. Time to reach clinical and MRI milestones was assessed with product-limit approach.Results:At DD=1 year, GMV and WM fractional anisotropy (FA) were abnormal in AOMS but not in POMS patients. Significant interaction of age at onset (POMS vs AOMS) into the association with DD was found for GMV and WM FA. The crossing point of regression lines in POMS and AOMS patients was at 20 years of DD for GMV and 14 for WM FA. For POMS and AOMS patients, median DD was 29 and 19 years to reach Expanded Disability Status Scale=3 (p<0.001), 31 and 26 years to reach abnormal Paced Auditory Serial Addition Task-3 (p=0.01), 24 and 18 years to reach abnormal GMV (p=0.04), and 19 and 17 years to reach abnormal WM FA (p=0.36).Conclusions:Younger patients are initially resilient to MS-related damage. Then, compensatory mechanisms start failing with loss of WM integrity, followed by GM atrophy and finally disability.

NODDI microstructural abnormalities in normal-appearing gray matter and white matter contribute to cognitive impairment in multiple sclerosis

2021 ◽  
Vol 429 ◽  
pp. 118088
Author(s):  
Paolo Preziosa ◽  
Lorenzo Conti ◽  
Elisabetta Pagani ◽  
Olga Marchesi ◽  
Maria Rocca ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
White Matter ◽  
Gray Matter

scholarly journals Learning ability correlates with brain atrophy and disability progression in RRMS

2018 ◽  
Vol 90 (1) ◽  
pp. 38-43 ◽  
Author(s):  
Maria Pia Sormani ◽  
Nicola De Stefano ◽  
Gavin Giovannoni ◽  
Dawn Langdon ◽  
Daniela Piani-Meier ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Volume ◽  
Practice Effect ◽  
Wilcoxon Test ◽  
Learning Ability ◽  
Lesion Volume ◽  
Volume Loss ◽  
Disability Progression ◽  
Brain Volume Loss ◽  
Quartile Group

ObjectiveTo assess the prognostic value of practice effect on Paced Auditory Serial Addition Test (PASAT) in multiple sclerosis.MethodsWe compared screening (day −14) and baseline (day 0) PASAT scores of 1009 patients from the FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS) trial. We grouped patients into high and low learners if their PASAT score change was above or below the median change in their screening PASAT quartile group. We used Wilcoxon test to compare baseline disease characteristics between high and low learners, and multiple regression models to assess the respective impact of learning ability, baseline normalised brain volume and treatment on brain volume loss and 6-month confirmed disability progression over 2 years.ResultsThe mean PASAT score at screening was 45.38, increasing on average by 3.18 from day −14 to day 0. High learners were younger (p=0.003), had lower Expanded Disability Status Scale score (p=0.031), higher brain volume (p<0.001) and lower T2 lesion volume (p=0.009) at baseline. Learning status was not significantly associated with disability progression (HR=0.953, p=0.779), when adjusting for baseline normalised brain volume, screening PASAT score and treatment arm. However, the effect of fingolimod on disability progression was more pronounced in high learners (HR=0.396, p<0.001) than in low learners (HR=0.798, p=0.351; p for interaction=0.05). Brain volume loss at month 24 tended to be higher in low learners (0.17%, p=0.058), after adjusting for the same covariates.ConclusionsShort-term practice effects on PASAT are related to brain volume, disease severity and age and have clinically meaningful prognostic implications. High learners benefited more from fingolimod treatment.

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