Dataset Information

Slowly eroding lesions in multiple sclerosis.

ABSTRACT: BACKGROUND:At autopsy, 20%-40% of chronic multiple sclerosis (MS) lesions are labeled "slowly expanding" and feature myelin phagocytosis at the lesion edge. As pathological lesion classification relies on a single, terminal time point, the rate of lesion expansion cannot be directly measured. OBJECTIVE:To study long-term volume changes in individual MS lesions. METHODS:Volumes of individual lesions on proton density magnetic resonance imaging (MRI) acquired between 1992 and 2015 were measured in 22 individuals (one lesion per person). After correction for acquisition protocol, a mixed model evaluated lesion volume changes. RESULTS:The mean (standard deviation) lesion volume at baseline was 142 (82)?mL, falling to 74 (51)?mL after 16 (3)?years. All lesions shrank over time. Change in lesion volume did not correlate with change in supratentorial brain volume ( p?=?0.33). In simulations, the results could be explained by a process of slow radial expansion superimposed on substantially more rapid resorption of damaged tissue. CONCLUSION:We noted sustained radiological contraction of MS lesions, a surprising result given that fresh myelin breakdown products within chronic active lesions are observed relatively frequently at autopsy. Therefore, the primary pathological process in chronic lesions, even those described as "slowly expanding," is likely to be tissue loss.

SUBMITTER: Sethi V

PROVIDER: S-EPMC5182188 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Slowly eroding lesions in multiple sclerosis.

Sethi Varun V Nair Govind G Absinta Martina M Sati Pascal P Venkataraman Arun A Ohayon Joan J Wu Tianxia T Yang Kelly K Shea Colin C Dewey Blake E BE Cortese Irene Cm IC Reich Daniel S DS

Multiple sclerosis (Houndmills, Basingstoke, England) 20160711 3

<h4>Background</h4>At autopsy, 20%-40% of chronic multiple sclerosis (MS) lesions are labeled "slowly expanding" and feature myelin phagocytosis at the lesion edge. As pathological lesion classification relies on a single, terminal time point, the rate of lesion expansion cannot be directly measured.<h4>Objective</h4>To study long-term volume changes in individual MS lesions.<h4>Methods</h4>Volumes of individual lesions on proton density magnetic resonance imaging (MRI) acquired between 1992 and ...[more]

PMID: 27339071

Similar Datasets

Project description:Multiple sclerosis (MS) is a demyelinating disease of the central nervous system characterized by increased inflammation and immune responses, oxidative injury, mitochondrial dysfunction, and iron dyshomeostasis leading to demyelination and axonal damage. In MS, incomplete remyelination results in chronically demyelinated axons and degeneration coinciding with disability. This suggests a failure in the ability to remyelinate in MS, however, the precise underlying mechanisms remain unclear. We aimed to identify proteins whose expression was altered in chronic inactive white matter lesions and periplaque white matter in MS tissue to reveal potential pathogenic mechanisms. Laser capture microdissection coupled to proteomics was used to interrogate spatially preserved changes in formalin-fixed paraffin-embedded brain tissue from chronic MS individuals and controls with no apparent neurological complications. Histopathological maps guided the capture of inactive lesions, periplaque white matter, and cortex from chronic MS individuals along with corresponding white matter and cortex from control tissue. Label free quantitation by liquid chromatography tandem mass spectrometry was used to discover differentially expressed proteins between the various brain regions. In addition to confirming loss of several myelin-associated proteins known to be affected in MS, proteomics analysis of chronic inactive MS lesions revealed alterations in myelin assembly, metabolism, and cytoskeletal organization. Notably, a subset of proteins that were altered in MS white matter indicate altered lipid metabolism. Our findings highlight proteome changes in chronic inactive MS white matter lesions and periplaque white matter, which may be crucial for proper myelinogenesis, bioenergetics, focal adhesions, and cellular function. These findings highlight the importance and feasibility of spatial approaches such as laser capture microdissection-based proteomics analysis of pathologically distinct regions of MS brain tissue. Identification of spatially resolved changes in the proteome of MS brain tissue should aid in the understanding of pathophysiological mechanisms and the development of novel therapies.

Dataset Information

Slowly eroding lesions in multiple sclerosis.

Publications

Slowly eroding lesions in multiple sclerosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure