Dataset Information

A pilot, longitudinal, 24-week study to evaluate the effect of interferon beta-1a subcutaneous on changes in susceptibility-weighted imaging-filtered phase assessment of lesions and subcortical deep-gray matter in relapsing-remitting multiple sclerosis.

ABSTRACT:

Background

Studies have shown a relationship between increased iron content and clinical progression, cognitive impairment, and brain atrophy in patients with multiple sclerosis. Altered phase, as determined by susceptibility-weighted imaging (SWI), can potentially capture iron content changes.

Objective

The objective of this study was to investigate phase changes in white matter (WM) lesions and subcortical deep-gray matter (SDGM) of patients with relapsing-remitting (RR) MS treated with interferon beta-1a administered subcutaneously versus untreated healthy controls (HCs).

Methods

We conducted a 24-week, nonrandomized, open-label pilot study of 23 patients with RRMS receiving interferon beta-1a administered subcutaneously and 15 HCs. Patients were imaged on a 3T scanner at baseline, 12, and 24 weeks; changes in phase behavior in WM lesions and regional SDGM [mean phase of low-phase voxels (MP-LPV)], and in SDGM volumes, were measured. Between- and within-group changes were tested using nonparametric statistics adjusted for multiple comparisons.

Results

The number (p = 0.003) and volume (p < 0.001) of phase WM lesions both significantly decreased among RRMS patients over 24 weeks. At baseline, MP-LPV was lower (suggestive of greater iron content) in total SDGM among RRMS patients versus HCs (p = 0.002). Week 24 MP-LPV changes from baseline were not significantly different between groups in total SDGM or any region except the putamen (-0.0025 radians in RRMS patients versus 0.0035 radians in HCs; p = 0.041).

Conclusions

Over 24 weeks, phase lesions were reduced significantly in the RRMS group. These preliminary results suggest that SWI-filtered phase may become a useful tool for monitoring RRMS disease activity.

SUBMITTER: Zivadinov R

PROVIDER: S-EPMC4356661 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Publications

A pilot, longitudinal, 24-week study to evaluate the effect of interferon beta-1a subcutaneous on changes in susceptibility-weighted imaging-filtered phase assessment of lesions and subcortical deep-gray matter in relapsing-remitting multiple sclerosis.

Zivadinov Robert R Dwyer Michael M Markovic-Plese Silva S Hayward Brooke B Bergsland Niels N Heininen-Brown Mari M Carl Ellen E Kennedy Cheryl C Dangond Fernando F Weinstock-Guttman Bianca B

Therapeutic advances in neurological disorders 20150301 2

<h4>Background</h4>Studies have shown a relationship between increased iron content and clinical progression, cognitive impairment, and brain atrophy in patients with multiple sclerosis. Altered phase, as determined by susceptibility-weighted imaging (SWI), can potentially capture iron content changes.<h4>Objective</h4>The objective of this study was to investigate phase changes in white matter (WM) lesions and subcortical deep-gray matter (SDGM) of patients with relapsing-remitting (RR) MS trea ...[more]

PMID: 25941537

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Project description:One of our new major finding among the genes that contributes to MS susceptibility is ICSBP1. The so called disease modifying therapies like interferon-beta (IFN-β), possibly acting on the peripheral T-cells, reduce the disease activity and the clinical progression, with a MRI-detectable effect in preventing lesion burden and cerebral atrophy development in RR-MS. It suggests a critical role of peripheral blood mononuclear cells (PBMCs) immune response and modulation in developing inflammation in the brain. We tested the hypothesis that the genetic effect of the susceptible allele ICSBP1 can impact the gene expression profile of molecules belonging to the interferon pathway. We therefore interrogated the PBMC for changes in gene expression profile. We correlate those changes with the minor allele frequency for ICSBP1, performing independent quantitative trait analysis for each treatment category. Expression Quantitative Trait Loci Association with a p value < 0.05 have been used in follow up analysis. The regression coefficient of the Quantitative trait association represents the degree of correlation between the gene expression for each interrogated target gene and the minor allele frequency of the SNP for our gene of interest. This coefficient has been used as input in the subsequent Gene Set Enrichment Analysis performed in a pre-ranked approach. The resulting GSEA-SNP method rests on the assumption that SNPs underlying a disease phenotype might affect genes constituting a signaling pathway or genes with a common regulation. Therefore, GSEA-SNP can facilitate the identification of pathways or of underlying biological mechanisms. We used microarrays to capture gene expression profile of untreated subjects and of subjects under disease modyfing treatment (Interferon Beta and Glatiramer Acetate), in order to correlate gene expression and genotype data and in order to identify sets of genes specifically regulated in the different treatment categories.

Dataset Information

A pilot, longitudinal, 24-week study to evaluate the effect of interferon beta-1a subcutaneous on changes in susceptibility-weighted imaging-filtered phase assessment of lesions and subcortical deep-gray matter in relapsing-remitting multiple sclerosis.

Background

Objective

Methods

Results

Conclusions

Publications

A pilot, longitudinal, 24-week study to evaluate the effect of interferon beta-1a subcutaneous on changes in susceptibility-weighted imaging-filtered phase assessment of lesions and subcortical deep-gray matter in relapsing-remitting multiple sclerosis.

Similar Datasets

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