MRI as a marker for disease heterogeneity in multiple sclerosis

Bielekova, Bibiana; Kadom, Nadja; Fisher, Elizabeth; Jeffries, Neal; Ohayon, Joan; Richert, Nancy; Howard, T.; Bash, C. N.; Frank, Joseph A.; Stone, Lael A.; Martin, Roland; Cutter, Gary; McFarland, H. F.

doi:10.1212/01.wnl.0000178984.30534.f9

Cited by 66 publications

(60 citation statements)

References 33 publications

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“…3 Recently, the heterogeneity of MS was also dissected in vivo using non-invasive magnetic resonance imaging (MRI) techniques combined with statistical remodeling. 4 Although in this study the MRI data could not be correlated with pathological data, the observed subgroups were clinically meaningful. The existence of heterogeneity in the brain of MS patients is proposed to reflect different pathogenic processes underlying MS: 3 an inflammation-mediated and an immune-independent demyelinating form, which both ultimately might drive brain tissue destruction.…”

Section: Introductionmentioning

confidence: 72%

A subtype of multiple sclerosis defined by an activated immune defense program

et al. 2006

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Given the heterogeneous nature of multiple sclerosis (MS), we applied DNA microarray technology to determine whether variability is reflected in peripheral blood (PB) cells. In this study, we studied whole-blood gene expression profiles of 29 patients with relapsing-remitting MS (RRMS) and 25 age-and sex-matched healthy controls. We used microarrays with a complexity of 43K cDNAs. The data were analyzed using sophisticated pathway-level analysis in order to provide insight into the deregulated peripheral immune response programs in MS. We found a remarkable elevated expression of a spectrum of genes known to be involved in immune defense in the PB of MS patients compared to healthy individuals. Cluster analysis revealed that the increased expression of these genes was characteristic for approximately half of the patients. In addition, the gene signature in this group of patients was comparable with a virus response program. We conclude that the transcriptional signature of the PB cells reflects the heterogeneity of MS and defines a sub-population of RRMS patients, who exhibit an activated immune defense program that resembles a virus response program, which is supportive for a link between viruses and MS.

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Section: Introductionmentioning

confidence: 72%

A subtype of multiple sclerosis defined by an activated immune defense program

et al. 2006

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“…An inverse relation between BPF and disability progression has repeatedly been demonstrated [11,12]. Further, MRI-based stratification by the amount of inflammatory lesions and the extent of both global and focal brain atrophy during consecutive, monthly MRI scans has been used to dissect disease heterogeneity in MS [13]. Interestingly, disease progression over time was most pronounced in the subgroup with both high inflammation and degenerative changes [13].…”

Section: Introductionmentioning

confidence: 98%

“…Further, MRI-based stratification by the amount of inflammatory lesions and the extent of both global and focal brain atrophy during consecutive, monthly MRI scans has been used to dissect disease heterogeneity in MS [13]. Interestingly, disease progression over time was most pronounced in the subgroup with both high inflammation and degenerative changes [13]. Assessing atrophy parameters employs three-dimensional MRI sequences and segmentation algorithms, that are, however, time consuming and not easily accessible in routine clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Loss of retinal nerve fibre layer axons indicates white but not grey matter damage in early multiple sclerosis

Young

Brandt

Petzold

et al. 2013

Euro J of Neurology

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BACKGROUND AND PURPOSE: Optical coherence tomography (OCT) has shown thinning of the retinal nerve fibre layer (RNFL) and total macular volume (TMV) in multiple sclerosis (MS) patients. Measures of retinal atrophy are associated with the brain parenchymal fraction (BPF) assessed by magnetic resonance imaging (MRI). However, in MS, data on the relation of OCT measures and grey and white matter volumes are contradictory. We performed a prospective cross-sectional study with a statistically pre-defined endpoint to test our hypothesis that OCT measures of neuro-axonal degeneration are related to global and partial brain atrophy in early forms of MS. METHODS AND RESULTS: Fortyfour patients with clinically isolated syndrome (n = 10) or relapsing-remitting MS (n = 34; mean disease duration = 3.2 years, median EDSS = 1.5) were enrolled in the study. Peripapillary-and volumetric OCT scans of the macula were performed using latest spectral-domain OCT technology. BPF as well as white and grey matter fractions (WMF/GMF) were assessed by 1.5 Tesla MRI scans. Generalized estimating equation models adjusted for age and linear regression statistics were used to assess the association between OCT and MRI measures. RNFL thickness, TMV and age were significantly associated with BPF. RNFL thickness and TMV independently predicted WMF (P = 0.003 and P = 0.032) but not GMF (P = 0.717 and P = 0.357) when corrected for age. In contrast, age was strongly associated with GMF (P < 0.001) but not WMF. CONCLUSION: Our study suggests that, in early MS, OCT measures of retinal atrophy are related to volumetric changes in the white but not grey matter compartment as assessed by MRI. It further substantiates the association of retinal thinning and brain tissue loss in MS. We performed a cross-sectional study with a statistically pre-defined endpoint to test our hypothesis that OCT measures of neuro-axonal degeneration are related to global and partial brain atrophy in early forms of MS.44 patients with clinically isolated syndrome (CIS, n=10) or relapsing remitting MS (RRMS, n=34) (mean disease duration=3.2 years, median EDSS=1.5) were enrolled in the study. Peripapillary-and volumetric OCT scans of the macula were performed using latest spectral-domain OCT technology. BPF as well as white and grey matter fractions (WMF/GMF) were assessed by 1.5 T MRI scans. Generalized estimating equation models (GEE) adjusted for age and linear regression statistics were used to assess the association between OCT and MRI measures.RNFL thickness, TMV and age were significantly associated with BPF. RNFL thickness, and TMV independently predicted WMF (p=0.003 and p=0.032) but not GMF (p=0.717 and p=0.357) when corrected for age. In contrast, age was strongly associated with GMF (p<0.001) but not WMF.

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“…4,12 In fact, signs of strong tissue destruction may occur during the course of MS despite low cumulative inflammatory activity. 13 The strong clinical relevance of brain volumetry in MS is supported by correlations between baseline brain volume and disability occurring 8 years later 14 and associations between early brain atrophy rates and clinical deterioration. 15 DWI detects alterations of microscopic diffusion processes in MS due to a variety of factors, including loss of myelin sheaths, loss of axonal membranes, neuronal apoptosis, and gliosis formation.…”

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confidence: 99%