Central Vein Sign Profile of Newly Developing Lesions in Multiple Sclerosis

Al‐Louzi, Omar; Letchuman, Vijay; Manukyan, Sargis; Beck, Erin; Roy, Snehashis; Ohayon, Joan; Pham, Dzung L.; Cortese, Irene; Sati, Pascal; Reich, Daniel S.

doi:10.1212/nxi.0000000000001120

Cited by 24 publications

(18 citation statements)

References 35 publications

(45 reference statements)

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“…Standardized CVS rating was performed on all lesions by a single rater (O.A.) masked to the clinical status of the cases, as described in detail previously, 20 and using a novel specialized workflow displaying each separate segmented lesion for rating while blinding the rater to all other lesions in the scan volume. The implementation details and code for the CVS rating workflow are publicly available: https://github.com/omarallouz/ CVS_rater.…”

Section: In Vivo Mrimentioning

confidence: 99%

Lesion size and shape in central vein sign assessment for multiple sclerosis diagnosis: An in vivo and postmortem MRI study

et al. 2022

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Background: The “central vein sign” (CVS), a linear hypointensity on T2*-weighted imaging corresponding to a central vein/venule, is associated with multiple sclerosis (MS) lesions. The effect of lesion-size exclusion criteria on MS diagnostic accuracy has not been extensively studied. Objective: Investigate the optimal lesion-size exclusion criteria for CVS use in MS diagnosis. Methods: Cross-sectional study of 163 MS and 51 non-MS, and radiological/histopathological correlation of 5 MS and 1 control autopsy cases. The effects of lesion-size exclusion on MS diagnosis using the CVS, and intralesional vein detection on histopathology were evaluated. Results: CVS+ lesions were larger compared to CVS− lesions, with effect modification by MS diagnosis (mean difference +7.7 mm3, p = 0.004). CVS percentage-based criteria with no lesion-size exclusion showed the highest diagnostic accuracy in differentiating MS cases. However, a simple count of three or more CVS+ lesions greater than 3.5 mm is highly accurate and can be rapidly implemented (sensitivity 93%; specificity 88%). On magnetic resonance imaging (MRI)-histopathological correlation, the CVS had high specificity for identifying intralesional veins (0/7 false positives). Conclusion: Lesion-size measures add important information when using CVS+ lesion counts for MS diagnosis. The CVS is a specific biomarker corresponding to intralesional veins on histopathology.

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Section: In Vivo Mrimentioning

confidence: 99%

Lesion size and shape in central vein sign assessment for multiple sclerosis diagnosis: An in vivo and postmortem MRI study

et al. 2022

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“… 4 , 5 MS lesions are associated with the presence of a “central vein sign” visible in MRI, suggesting that immune cells invade the brain though the veins. 3 , 6 However, the reason why veins are the main site of immune cell infiltration remain unclear.…”

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confidence: 99%

Single-Cell Transcriptomics Identifies Brain Endothelium Inflammatory Networks in Experimental Autoimmune Encephalomyelitis

Fournier

Tastet

Charabati

et al. 2023

Neurol Neuroimmunol Neuroinflamm

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Background and ObjectivesMultiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease characterized by infiltration of immune cells in multifocal areas of the CNS. The specific molecular processes allowing autoreactive immune cells to enter the CNS compartment through the blood-brain barrier remain elusive.MethodsUsing endothelial cell (EC) enrichment and single-cell RNA sequencing, we characterized the cells implicated in the neuroinflammatory processes in experimental autoimmune encephalomyelitis, an animal model of MS. Validations on human MS brain sections of the most differentially expressed genes in venous ECs were performed using immunohistochemistry and confocal microscopy.ResultsWe found an upregulation of genes associated with antigen presentation and interferon in most populations of CNS-resident cells, including ECs. Interestingly, instead of transcriptionally distinct profiles, a continuous gradient of gene expression separated the arteriovenous zonation of the brain vasculature. However, differential gene expression analysis presented more transcriptomic alterations on the venous side of the axis, suggesting a prominent role of venous ECs in neuroinflammation. Furthermore, analysis of ligand-receptor interactions identified important potential molecular communications between venous ECs and infiltrated immune populations. To confirm the relevance of our observation in the context of human disease, we validated the protein expression of the most upregulated genes (Ackr1andLcn2) in MS lesions.DiscussionIn this study, we provide a landscape of the cellular heterogeneity associated with neuroinflammation. We also present important molecular insights for further exploration of specific cell processes that promote infiltration of immune cells inside the brain of experimental autoimmune encephalomyelitis mice.

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“…[28][29][30] Most of these focal and disseminated demyelinating white matter lesions ("plaques") of the brain, brainstem, cerebellum, spinal cord, and optic nerve show a perivenous location which points to an association of the cerebral vasculature with lesion formation. [31][32][33] The so-called central vein sign is now considered an emerging imaging biomarker of MS, as it rarely occurs in relevant MS mimics. 34,35 In acute focal white matter lesions, axonal transection is a characteristic feature.…”

Section: Neuropathology and Diagnosis Of Msmentioning

confidence: 99%

Multiple sclerosis and circadian rhythms: Can diet act as a treatment?

2023

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Multiple sclerosis (MS) is an autoimmune inflammatory and neurodegenerative disease of the central nervous system (CNS) with increasing incidence and prevalence. MS is associated with inflammatory and metabolic disturbances that, as preliminary human and animal data suggest, might be mediated by disruption of circadian rhythmicity. Nutrition habits can influence the risk for MS, and dietary interventions may be effective in modulating MS disease course.Chronotherapeutic approaches such as time-restricted eating (TRE) may benefit people with MS by stabilizing the circadian clock and restoring immunological and metabolic rhythms, thus potentially counteracting disease progression. This review provides a summary of selected studies on dietary intervention in MS, circadian rhythms, and their disruption in MS, including clock gene variations, circadian hormones, and retino-hypothalamic tract changes. Furthermore, we present studies that reported diurnal variations in MS, which might result from circadian disruption. And lastly, we suggest how chrononutritive approaches like TRE might counteract MS disease activity.

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Central Vein Sign Profile of Newly Developing Lesions in Multiple Sclerosis

Cited by 24 publications

References 35 publications

Lesion size and shape in central vein sign assessment for multiple sclerosis diagnosis: An in vivo and postmortem MRI study

Lesion size and shape in central vein sign assessment for multiple sclerosis diagnosis: An in vivo and postmortem MRI study

Single-Cell Transcriptomics Identifies Brain Endothelium Inflammatory Networks in Experimental Autoimmune Encephalomyelitis

Multiple sclerosis and circadian rhythms: Can diet act as a treatment?

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