Global loss of myelin water over 5 years in multiple sclerosis normal-appearing white matter

2017 ◽  
Vol 24 (12) ◽  
pp. 1557-1568 ◽  
Author(s):  
Irene M Vavasour ◽  
Sophie C Huijskens ◽  
David KB Li ◽  
Anthony L Traboulsee ◽  
Burkhard Mädler ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Geometric Mean ◽  
Peak Height ◽  
Cross Sectional ◽  
Longitudinal Changes ◽  
Water Fraction ◽  
Normal Appearing White Matter ◽  
Long Term Follow Up ◽  
Long Time

Background: Reduced myelin water fraction (MWF, a marker for myelin), increased geometric mean T2 (ieGMT2, reflecting intra/extracellular water properties), and increased T1 (related to total water content) have been observed in cross-sectional studies of multiple sclerosis (MS) normal-appearing white matter (NAWM). Objective: To assess longitudinal changes of magnetic resonance (MR) measures in relapsing-remitting MS (RRMS) brain NAWM. Methods: A total of 11 subjects with RRMS and 4 controls were scanned on a 3T MRI at baseline and long-term follow-up (LTFU; 3.2–5.8 years) with a 32-echo T2 relaxation and an inversion recovery T1 sequence. For every voxel, MWF, ieGMT2, and T1 were obtained. Mean, peak height, and peak location from NAWM mask-based histograms were determined. Results: In MS subjects, NAWM MWF mean decreased by 8% ( p = 0.0016). No longitudinal changes were measured in T1 or ieGMT2. There was no relationship between change in any MR metric and change in EDSS. Control white matter showed no differences over time in any metric. Conclusion: The decreases we observed in MWF suggest that changes in myelin integrity and loss of myelin may be occurring diffusely and over long time periods in the MS brain. The timescale of these changes indicates that chronic, progressive myelin damage is an evolving process occurring over many years.

scholarly journals Restriction spectrum imaging of white matter and its relation to neurological disability in multiple sclerosis

2018 ◽  
Vol 25 (5) ◽  
pp. 687-698 ◽  
Author(s):  
Piotr Sowa ◽  
Hanne F Harbo ◽  
Nathan S White ◽  
Elisabeth G Celius ◽  
Hauke Bartsch ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Fractional Anisotropy ◽  
Free Water ◽  
White Matter Lesions ◽  
Neurological Disability ◽  
Water Fraction ◽  
Neurite Density ◽  
Normal Appearing White Matter ◽  
Spectrum Imaging

Background: Restriction spectrum imaging (RSI) is a recently introduced magnetic resonance imaging diffusion technique. The utility of RSI in multiple sclerosis (MS) is unknown. Objective: To investigate the association between RSI-derived parameters and neurological disability in MS. Methods: Seventy-seven relapsing–remitting MS patients were scanned with RSI on a 3-T scanner. RSI-derived parameters: fast and slow apparent diffusion coefficient (sADC), fractional anisotropy, restricted fractional anisotropy, neurite density (ND), cellularity, extracellular water fraction, and free water fraction, were obtained in white matter lesions (WML) and normal appearing white matter (NAWM). Patients were divided into three groups according to their expanded disability status scale (EDSS): with minimal, low, and substantial disability (<2.5, 2.5–3, and >3, respectively). Group comparisons and correlation analyses were performed. Results: All tested RSI-derived parameters differed between WML and NAWM ( p < 0.001 for all pairwise comparisons). The sADC in WML showed largest difference across disability subgroups (analysis of variance (ANOVA): F = 5.1, η2 = 0.12, p = 0.008). ND in NAWM showed strongest correlation with disability (ϱ = –0.39, p < 0.001). Conclusion: The strongest correlation with EDSS of ND obtained in NAWM indicates that processes outside lesions are important for disability in MS. Our study suggests that RSI-derived parameters may help understand the “clinico-radiological paradox” and improve disease monitoring in MS.

Spatiotemporal distribution of white matter lesions in relapsing–remitting and secondary progressive multiple sclerosis

2012 ◽  
Vol 18 (11) ◽  
pp. 1577-1584 ◽  
Author(s):  
Lukas Filli ◽  
Louis Hofstetter ◽  
Pascal Kuster ◽  
Stefan Traud ◽  
Nicole Mueller-Lenke ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Disease Progression ◽  
Spatiotemporal Distribution ◽  
Centrum Semiovale ◽  
Cross Sectional ◽  
Secondary Progressive ◽  
Lateral Ventricles ◽  
Relapsing Remitting ◽  
T1 And T2

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. MS lesions show a typical distribution pattern and primarily affect the white matter (WM) in the periventricular zone and in the centrum semiovale. Objective: To track lesion development during disease progression, we compared the spatiotemporal distribution patterns of lesions in relapsing–remitting MS (RRMS) and secondary progressive MS (SPMS). Methods: We used T1 and T2 weighted MR images of 209 RRMS and 62 SPMS patients acquired on two different 1.5 Tesla MR scanners in two clinical centers followed up for 25 (± 1.7) months. Both cross-sectional and longitudinal differences in lesion distribution between RRMS and SPMS patients were analyzed with lesion probability maps (LPMs) and permutation-based inference. Results: MS lesions clustered around the lateral ventricles and in the centrum semiovale. Cross-sectionally, compared to RRMS patients, the SPMS patients showed a significantly higher regional probability of T1 hypointense lesions ( p≤0.03) in the callosal body, the corticospinal tract, and other tracts adjacent to the lateral ventricles, but not of T2 lesions (peak probabilities were RRMS: T1 9%, T2 18%; SPMS: T1 21%, T2 27%). No longitudinal changes of regional T1 and T2 lesion volumes between baseline and follow-up scan were found. Conclusion: The results suggest a particular vulnerability to neurodegeneration during disease progression in a number of WM tracts.

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 discloses early changes in the normal appearing white matter in paediatric multiple sclerosis

2021 ◽  
Vol 429 ◽  
pp. 118881
Author(s):  
Monica Margoni ◽  
Umberto Villani ◽  
Silvia Franciotta ◽  
Martina Rubin ◽  
Margherita Nosadini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Normal Appearing White Matter ◽  
Paediatric Multiple Sclerosis

scholarly journals A higher proportion of ermin-immunopositive oligodendrocytes in areas of remyelination

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256155
Author(s):  
Intakhar Ahmad ◽  
Stig Wergeland ◽  
Eystein Oveland ◽  
Lars Bø
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Corpus Callosum ◽  
Mouse Model ◽  
Grey Matter ◽  
Early Stage ◽  
Relative Proportion ◽  
Normal Appearing White Matter ◽  
The Brain

Incomplete remyelination is frequent in multiple sclerosis (MS)-lesions, but there is no established marker for recent remyelination. We investigated the role of the oligodendrocyte/myelin protein ermin in de- and remyelination in the cuprizone (CPZ) mouse model, and in MS. The density of ermin+ oligodendrocytes in the brain was significantly decreased after one week of CPZ exposure (p < 0.02). The relative proportion of ermin+ cells compared to cells positive for the late-stage oligodendrocyte marker Nogo-A increased at the onset of remyelination in the corpus callosum (p < 0.02). The density of ermin-positive cells increased in the corpus callosum during the CPZ-phase of extensive remyelination (p < 0.0001). In MS, the density of ermin+ cells was higher in remyelinated lesion areas compared to non-remyelinated areas both in white- (p < 0.0001) and grey matter (p < 0.0001) and compared to normal-appearing white matter (p < 0.001). Ermin immunopositive cells in MS-lesions were not immunopositive for the early-stage oligodendrocyte markers O4 and O1, but a subpopulation was immunopositive for Nogo-A. The data suggest a relatively higher proportion of ermin immunopositivity in oligodendrocytes compared to Nogo-A indicates recent or ongoing remyelination.

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