Clinical correlations of brain lesion distribution in multiple sclerosis

AbstractTo identify markers in the CSF of multiple sclerosis (MS) subtypes, we used a two-step proteomic approach: (i) Discovery proteomics compared 169 pooled CSF from MS subtypes and inflammatory/degenerative CNS diseases (NMO spectrum and Alzheimer disease) and healthy controls. (ii) Next, 299 proteins selected by comprehensive statistics were quantified in 170 individual CSF samples. (iii) Genes of the identified proteins were also screened among transcripts in 73 MS brain lesions compared to 25 control brains. F-test based feature selection resulted in 8 proteins differentiating the MS subtypes, and secondary progressive (SP)MS was the most different also from controls. Genes of 7 out these 8 proteins were present in MS brain lesions: GOLM was significantly differentially expressed in active, chronic active, inactive and remyelinating lesions, FRZB in active and chronic active lesions, and SELENBP1 in inactive lesions. Volcano maps of normalized proteins in the different disease groups also indicated the highest amount of altered proteins in SPMS. Apolipoprotein C-I, apolipoprotein A-II, augurin, receptor-type tyrosine-protein phosphatase gamma, and trypsin-1 were upregulated in the CSF of MS subtypes compared to controls. This CSF profile and associated brain lesion spectrum highlight non-inflammatory mechanisms in differentiating CNS diseases and MS subtypes and the uniqueness of SPMS.

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Multiple Sclerosis Atlas: A Molecular Map of Brain Lesion Stages in Progressive Multiple Sclerosis

Network and Systems Medicine ◽

10.1089/nsm.2020.0006 ◽

2020 ◽

Vol 3 (1) ◽

pp. 122-129

Author(s):

Tobias Frisch ◽

Maria L. Elkjaer ◽

Richard Reynolds ◽

Tanja Maria Michel ◽

Tim Kacprowski ◽

...

Keyword(s):

Multiple Sclerosis ◽

Brain Lesion ◽

Progressive Multiple Sclerosis ◽

Molecular Map

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Brain lesion location and clinical status 20 years after a diagnosis of clinically isolated syndrome suggestive of multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458511420269 ◽

2011 ◽

Vol 18 (3) ◽

pp. 322-328 ◽

Cited By ~ 23

Author(s):

CM Dalton ◽

B Bodini ◽

RS Samson ◽

M Battaglini ◽

LK Fisniku ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spatial Distribution ◽

Brain Lesion ◽

Multiple Linear Regression Model ◽

Clinically Isolated Syndrome ◽

Optic Radiation ◽

Lesion Location ◽

T2 Lesions ◽

Significant Difference ◽

T1 And T2

Background/Objectives: The objective of this study was to investigate associations between the spatial distribution of brain lesions and clinical outcomes in a cohort of people followed up 20 years after presentation with a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). Methods: Brain lesion probability maps (LPMs) of T1 and T2 lesions were generated from 74 people who underwent magnetic resonance imaging (MRI) and clinical assessment a mean of 19.9 years following a CIS. One-tailed t-test statistics were used to compare LPMs between the following groups: clinically definite (CD) MS and those who remained with CIS, with an abnormal MRI; people with MS and an Expanded Disability Status Scale (EDSS) ≤3 and >3; people with relapsing–remitting (RR) and secondary progressive (SP) MS. The probability of each voxel being lesional was analysed adjusting for age and gender using a multiple linear regression model. Results: People with CDMS were significantly more likely than those with CIS and abnormal scan 20 years after onset to have T1 and T2 lesions in the corona radiata, optic radiation, and splenium of the corpus callosum (periventricularly) and T2 lesions in the right fronto-occipital fasciculus. People with MS EDSS >3, compared with those with EDSS ≤3, were more likely to have optic radiation and left internal capsule T2 lesions. No significant difference in lesion distribution was noted between RRMS and SPMS. Conclusion: This work demonstrates that lesion location characteristics are associated with CDMS and disability after long-term follow-up following a CIS. The lack of lesion spatial distribution differences between RRMS and SPMS suggests focal pathology affects similar regions in both subgroups.

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Molecular Network Analysis of Multiple Sclerosis Brain Lesion Proteome

Japanese Journal of Clinical Immunology ◽

10.2177/jsci.33.182 ◽

2010 ◽

Vol 33 (4) ◽

pp. 182-188

Author(s):

Jun-ichi SATOH

Keyword(s):

Multiple Sclerosis ◽

Network Analysis ◽

Brain Lesion ◽

Molecular Network

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Activated suppressor cell function in multiple sclerosis — clinical correlations☆

Journal of Neuroimmunology ◽

10.1016/0165-5728(88)90123-3 ◽

1988 ◽

Vol 17 (4) ◽

pp. 323-330 ◽

Cited By ~ 21

Author(s):

J ANTEL ◽

M BROWN ◽

M NICHOLAS ◽

M BLAIN ◽

A NORONHA ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cell Function ◽

Suppressor Cell ◽

Clinical Correlations

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Relevance of hypointense brain MRI lesions for long-term worsening of clinical disability in relapsing multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458513494490 ◽

2013 ◽

Vol 20 (2) ◽

pp. 214-219 ◽

Cited By ~ 25

Author(s):

Antonio Giorgio ◽

Maria Laura Stromillo ◽

Maria Letizia Bartolozzi ◽

Francesca Rossi ◽

Marco Battaglini ◽

...

Keyword(s):

Multiple Sclerosis ◽

Brain Mri ◽

Univariate Analysis ◽

Brain Lesion ◽

Brain Magnetic Resonance Imaging ◽

Stepwise Multiple Regression ◽

Lesion Volume ◽

Magnetic Resonance Imaging Mri ◽

Relapsing Remitting Multiple Sclerosis

Background: The accrual of brain focal pathology is considered a good substrate of disability in relapsing–remitting multiple sclerosis (RRMS). However, knowledge on long-term lesion evolution and its relationship with disability progression is poor. Objective: The objective of this paper is to evaluate in RRMS the long-term clinical relevance of brain lesion evolution. Methods: In 58 RRMS patients we acquired, using the same scanner and protocol, brain magnetic resonance imaging (MRI) at baseline and 10±0.5 years later. MRI data were correlated with disability changes as measured by the Expanded Disability Status Scale (EDSS). Results: The annualized 10-year lesion volume (LV) growth was +0.25±0.5 cm3 (+6.7±8.7%) for T2-weighted (T2-W) lesions and +0.20±0.31 cm3 (+11.5±12.3%) for T1-weighted (T1-W) lesions. The univariate analysis showed moderate correlations between baseline MRI measures and EDSS at 10 years ( p < 0.001). Also, 10-year EDSS worsening correlated with LV growth and the number of new/enlarging lesions measured over the same period ( p < 0.005). In the stepwise multiple regression analysis, EDSS worsening over 10 years was best correlated with the combination of baseline T1-W lesion count and increasing T1-W LV ( R = 0.61, p < 0.001). Conclusion: In RRMS patients, long-term brain lesion accrual is associated with worsening in clinical disability. This is particularly true for hypointense, destructive lesions.

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