Genetic Correlations of Brain Lesion Distribution in Multiple Sclerosis: An Exploratory Study

Sombekke, Madeleine H.; Vellinga, M.M.; Uitdehaag, Bernard M. J.; Barkhof, Frederik; Polman, Chris H.; Arteta, David; Tejedor, Diego; Martínez, Antonio; Crusius, J. Bart A.; Peña, A. S.; Geurts, Jeroen J. G.; Vrenken, Hugo

doi:10.3174/ajnr.a2352

Cited by 10 publications

(5 citation statements)

References 49 publications

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“…A recent larger study with 126 people with RRMS and 42 with SPMS has found that phenotypes associated with a higher total brain lesion volume were also associated with an increased local lesion probability. 26 This study has a number of limitations that are worth noting. First, including lesion load as a covariate in the model yielded no areas of significance.…”

Section: Discussionmentioning

confidence: 96%

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

Dalton¹,

Bodini²,

Samson³

et al. 2011

Mult Scler

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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

Dalton¹,

Bodini²,

Samson³

et al. 2011

Mult Scler

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“…In all analyses, age and sex were used as covariates. In addition, since it is not clear whether the total brain LV can be relevant to lesion frequency assessment [23], [25], [26], all analyses were repeated adding T2-LV as a covariate. Values of T2-LV were log-transformed in order to obtain a normal distribution.…”

Section: Methodsmentioning

confidence: 99%

Relevance of Brain Lesion Location to Cognition in Relapsing Multiple Sclerosis

et al. 2012

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ObjectiveTo assess the relationship between cognition and brain white matter (WM) lesion distribution and frequency in patients with relapsing-remitting multiple sclerosis (RR MS).MethodsMRI-based T2 lesion probability map (LPM) was used to assess the relevance of brain lesion location for cognitive impairment in a group of 142 consecutive patients with RRMS. Significance of voxelwise analyses was p<0.05, cluster-corrected for multiple comparisons. The Rao Brief Repeatable Battery was administered at the time of brain MRI to categorize the MS population into cognitively preserved (CP) and cognitively impaired (CI).ResultsOut of 142 RRMS, 106 were classified as CP and 36 as CI. Although the CI group had greater WM lesion volume than the CP group (p = 0.001), T2 lesions tended to be less widespread across the WM. The peak of lesion frequency was almost twice higher in CI (61% in the forceps major) than in CP patients (37% in the posterior corona radiata). The voxelwise analysis confirmed that lesion frequency was higher in CI than in CP patients with significant bilateral clusters in the forceps major and in the splenium of the corpus callosum (p<0.05, corrected). Low scores of the Symbol Digit Modalities Test correlated with higher lesion frequency in these WM regions.ConclusionsOverall these results suggest that in MS patients, areas relevant for cognition lie mostly in the commissural fiber tracts. This supports the notion of a functional (multiple) disconnection between grey matter structures, secondary to damage located in specific WM areas, as one of the most important mechanisms leading to cognitive impairment in MS.

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“…Meta-analyses have revealed that monitoring CNS damage using MRI is a poor predictor of disease progression in MS, likely because variation in the resulting damage (shape, location, size) obscures its consequence [ 51 , 52 ]. Clinically, MRI quantification of lesion load weakly correlates with immune responses (0.1 < ρ < 0.6) [ 53 , 54 ] and future disability (0.1 < ρ < 0.5) [ 55 , 56 ].…”

Section: Discussionmentioning

confidence: 99%

CEST MRI and MALDI imaging reveal metabolic alterations in the cervical lymph nodes of EAE mice

Thomas

Yang

Smith

et al. 2022

J Neuroinflammation

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Background Multiple sclerosis (MS) is a neurodegenerative disease, wherein aberrant immune cells target myelin-ensheathed nerves. Conventional magnetic resonance imaging (MRI) can be performed to monitor damage to the central nervous system that results from previous inflammation; however, these imaging biomarkers are not necessarily indicative of active, progressive stages of the disease. The immune cells responsible for MS are first activated and sensitized to myelin in lymph nodes (LNs). Here, we present a new strategy for monitoring active disease activity in MS, chemical exchange saturation transfer (CEST) MRI of LNs. Methods and results We studied the potential utility of conventional (T2-weighted) and CEST MRI to monitor changes in these LNs during disease progression in an experimental autoimmune encephalomyelitis (EAE) model. We found CEST signal changes corresponded temporally with disease activity. CEST signals at the 3.2 ppm frequency during the active stage of EAE correlated significantly with the cellular (flow cytometry) and metabolic (mass spectrometry imaging) composition of the LNs, as well as immune cell infiltration into brain and spinal cord tissue. Correlating primary metabolites as identified by matrix-assisted laser desorption/ionization (MALDI) imaging included alanine, lactate, leucine, malate, and phenylalanine. Conclusions Taken together, we demonstrate the utility of CEST MRI signal changes in superficial cervical LNs as a complementary imaging biomarker for monitoring disease activity in MS. CEST MRI biomarkers corresponded to disease activity, correlated with immune activation (surface markers, antigen-stimulated proliferation), and correlated with LN metabolite levels.

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Genetic Correlations of Brain Lesion Distribution in Multiple Sclerosis: An Exploratory Study

Cited by 10 publications

References 49 publications

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

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

Relevance of Brain Lesion Location to Cognition in Relapsing Multiple Sclerosis

CEST MRI and MALDI imaging reveal metabolic alterations in the cervical lymph nodes of EAE mice

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