Leptomeningeal Contrast Enhancement Is Associated with Disability Progression and Grey Matter Atrophy in Multiple Sclerosis

Leptomeningeal contrast enhancement (LMCE) on magnetic resonance imaging (MRI) is a newly recognized possible biomarker in multiple sclerosis (MS), associated with MS progression and cortical atrophy. In this study, we aimed to assess the prevalence of LMCE foci and their impact on neurodegeneration and disability. Materials. 54 patients with MS were included in the study. LMCE were detected with a 3 Tesla scanner on postcontrast fluid-attenuated inversion-recovery (FLAIR) sequence. Expanded Disability Status Scale (EDSS) score, number of relapses during 5 years from MS onset, and number of contrast-enhancing lesions on T1 weighted MRI were counted. Results. LMCE was detected in 41% (22/54) of patients. LMCE-positive patients had longer disease duration (p=0,0098) and higher EDSS score (p=0,039), but not a higher relapse rate (p=0,091). No association of LMCE with higher frequency of contrast-enhancing lesions on T1-weighted images was detected (p=0,3842). Analysis of covariates, adjusted for age, sex, and disease duration, revealed a significant effect of LMCE on the cortex volume (p=0.043, F=2.529), the total grey matter volume (p=0.043, F=2.54), and total ventricular volume (p=0.039, F=2.605). Conclusions. LMCE was shown to be an independent and significant biomarker of grey matter atrophy and disability in MS.

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FP14-TU-03 The effect of disease duration on grey matter volume and cognitive performance in relapsing-remitting multiple sclerosis patients

Journal of the Neurological Sciences ◽

10.1016/s0022-510x(09)70337-5 ◽

2009 ◽

Vol 285 ◽

pp. S79 ◽

Cited By ~ 1

Author(s):

A.A. Achiron ◽

S. Tal ◽

D. Magalashvili ◽

A. Achiron

Keyword(s):

Multiple Sclerosis ◽

Cognitive Performance ◽

Grey Matter ◽

Disease Duration ◽

Grey Matter Volume ◽

Matter Volume ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis

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Cortical involvement determines impairment 30 years after a clinically isolated syndrome

Brain ◽

10.1093/brain/awab033 ◽

2021 ◽

Author(s):

Lukas Haider ◽

Ferran Prados ◽

Karen Chung ◽

Olivia Goodkin ◽

Baris Kanber ◽

...

Keyword(s):

Multiple Sclerosis ◽

Grey Matter ◽

Disease Duration ◽

Magnetization Transfer ◽

Clinically Isolated Syndrome ◽

Cervical Cord ◽

Grey Matter Volume ◽

Cortical Lesions ◽

Matter Volume

Abstract Many studies report an overlap of MRI and clinical findings between patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), which in part is reflective of inclusion of subjects with variable disease duration and short periods of follow-up. To overcome these limitations, we examined the differences between RRMS and SPMS and the relationship between MRI measures and clinical outcomes 30 years after first presentation with clinically isolated syndrome suggestive of multiple sclerosis. Sixty-three patients were studied 30 years after their initial presentation with a clinically isolated syndrome; only 14% received a disease modifying treatment at any time point. Twenty-seven patients developed RRMS, 15 SPMS and 21 experienced no further neurological events; these groups were comparable in terms of age and disease duration. Clinical assessment included the Expanded Disability Status Scale, 9-Hole Peg Test and Timed 25-Foot Walk and the Brief International Cognitive Assessment For Multiple Sclerosis. All subjects underwent a comprehensive MRI protocol at 3 T measuring brain white and grey matter (lesions, volumes and magnetization transfer ratio) and cervical cord involvement. Linear regression models were used to estimate age- and gender-adjusted group differences between clinical phenotypes after 30 years, and stepwise selection to determine associations between a large sets of MRI predictor variables and physical and cognitive outcome measures. At the 30-year follow-up, the greatest differences in MRI measures between SPMS and RRMS were the number of cortical lesions, which were higher in SPMS (the presence of cortical lesions had 100% sensitivity and 88% specificity), and grey matter volume, which was lower in SPMS. Across all subjects, cortical lesions, grey matter volume and cervical cord volume explained 60% of the variance of the Expanded Disability Status Scale; cortical lesions alone explained 43%. Grey matter volume, cortical lesions and gender explained 43% of the variance of Timed 25-Foot Walk. Reduced cortical magnetization transfer ratios emerged as the only significant explanatory variable for the symbol digit modality test and explained 52% of its variance. Cortical involvement, both in terms of lesions and atrophy, appears to be the main correlate of progressive disease and disability in a cohort of individuals with very long follow-up and homogeneous disease duration, indicating that this should be the target of therapeutic interventions.

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Progression of regional grey matter atrophy in multiple sclerosis

10.1101/190116 ◽

2017 ◽

Cited By ~ 1

Author(s):

Arman Eshaghi ◽

Razvan V. Marinescu ◽

Alexandra L. Young ◽

Nicholas C. Firth ◽

Ferran Prados ◽

...

Keyword(s):

Multiple Sclerosis ◽

Grey Matter ◽

Disease Duration ◽

Cingulate Cortex ◽

Posterior Cingulate Cortex ◽

Data Driven ◽

Healthy Controls ◽

Primary Progressive ◽

Grey Matter Atrophy ◽

Over Time

SummaryGrey matter atrophy is present from the earliest clinical stages of multiple sclerosis (MS), but the temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in MS, and its association with disability accumulation.In this longitudinal study, we included 1,417 subjects: 253 with clinically-isolated syndrome (CIS), 708 relapsing-remitting MS (RRMS), 128 secondary-progressive MS (SPMS), 125 primary-progressive MS (PPMS), and 203 healthy controls from 7 European centres. Subjects underwent repeated MRI scanning (total number of scans 3,604); the mean follow-up for patients was 2.41yrs (SD±1.97). Disability was scored using the Expanded Disability Status Scale (EDSS). We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template. We used an established data-driven event-based model (EBM) to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific EBM stage, based on the number of their atrophic regions. We used nested linear mixed-effects regression models to explore the associations between the rate of increase in the EBM stages over time, disease duration and annual rate of EDSS gain.The first regions to become atrophic in CIS and relapse-onset MS patients (RRMS and SPMS) were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. The sequence of atrophy in PPMS showed a similar involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset MS and late atrophy in PPMS. Patients with SPMS showed the highest EBM stages (highest number of atrophic regions, all p<0.001) at study entry. Rates of increase in EBM stages were significantly different from healthy controls in all MS phenotypes, except for CIS. The increase in the number of atrophic regions (EBM stage) was associated with disease duration in all patients. EBM stage was associated with disability accumulation in RRMS independent of disease duration (p<0.0001).This data-driven staging of atrophy progression in a large MS sample demonstrates that grey matter atrophy spreads to involve more regions over time. The sequence in which regions become atrophic is reasonably consistent across MS phenotypes. The spread of atrophy was associated with disease duration, and disability accumulation in RRMS.AbbreviationsMSmultiple sclerosisGMgrey matterFLAIRFluid Attenuated Inversion RecoveryPPMSprimary progressive multiple sclerosis; primary-progressive MS

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