Different white matter lesion characteristics correlate with distinct grey matter abnormalities on magnetic resonance imaging in secondary progressive multiple sclerosis

Furby, J; Hayton, Tom; Altmann, Daniel R.; Brenner, Robert; Chataway, Jeremy; Smith, Kenneth J.; Miller, D. H.; Kapoor, Raju

doi:10.1177/1352458509103176

Cited by 13 publications

(4 citation statements)

References 37 publications

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“…Clues that GM atrophy may mostly be based on neuronal and glial damage come from a post mortem study, 27 in which strict regional associations between cortical demyelination and atrophy were not found. Relations between GM atrophy and T2 lesion volume have been reported previously, 3,28 and in our study T2 lesion volume was an independent predictor of NGMV. Although this finding may be an argument for the hypothesis that GM damage results from damage to WM tracts, an equally likely possibility is that GM atrophy and T2 lesion volume occur independently but mirror the general disease process in certain phases of the disease.…”

Section: Discussionsupporting

confidence: 87%

Grey matter volume in a large cohort of MS patients: relation to MRI parameters and disability

et al. 2011

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Section: Discussionsupporting

confidence: 87%

Grey matter volume in a large cohort of MS patients: relation to MRI parameters and disability

et al. 2011

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“…An alternative possibility is that damage to myelin and axons in active and mixed activeinactive WMLs could trigger retrograde degeneration propagating backwards towards cortical neurons, resulting in demyelination and neurodegeneration giving rise to GMLs. Consistent with the idea that WMLs may drive the formation of GMLs, several cross-sectional MRI studies have reported significant correlations between the total grey matter volume and the total white matter volume in T1-and T2-weighted lesions (51)(52)(53)(54). Moreover, several longitudinal MRI studies have shown an association between the volume of white matter lesions and the loss of GM volume (55), ventricular enlargement (56) and upstream GM atrophy of the visual cortex (57).…”

Section: Discussionmentioning

confidence: 74%

Accumulation of meningeal lymphocytes correlates with white matter lesion activity in progressive multiple sclerosis

Ahmed¹,

Fransen²,

Touil³

et al. 2022

JCI Insight

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Subpial cortical demyelination is an important component of multiple sclerosis (MS) pathology contributing to disease progression, yet mechanism(s) underlying its development remain unclear.Compartmentalized inflammation involving the meninges may drive this type of injury. Given recent findings identifying substantial white matter (WM) lesion activity in patients with progressive MS, elucidating whether and how WM lesional activity relates to meningeal inflammation and subpial cortical injury is of interest. Using post-mortem formalin-fixed paraffinembedded tissue blocks (range, 5-72 blocks; median, 30 blocks) for each of 27 progressive MS patients, we assessed the relationship between meningeal inflammation, the extent of subpial cortical demyelination, and the state of subcortical WM lesional activity. Meningeal accumulations of T cells and B cells, but not myeloid cells, were spatially adjacent to subpial cortical lesions and greater immune-cell accumulation was associated with higher subpial lesion numbers. Patients with a higher extent of meningeal inflammation harboured a greater proportion of active and mixed (active-inactive) WM lesions, and an overall lower proportion of inactive and remyelinated WM lesions. Our findings support the involvement of meningeal lymphocytes in subpial cortical injury, and also point to a potential link between inflammatory subpial cortical demyelination and pathological mechanisms occurring in the subcortical white matter.

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“…A correlation between white matter lesion load and thalamic atrophy was found in patients with clinically isolated syndrome 23 and early relapsing remitting multiple sclerosis (RRMS) 24 . More generally, the assumption that white matter lesions and grey matter atrophy are linked is supported by several cross-sectional MRI studies showing significant correlations between the total grey matter volume and the total volume of white matter T1-and T2-weighted lesions [25][26][27][28] . Even when a more sensitive regional analysis was performed, a correlation between regional cortical grey matter loss and white matter lesion volume in the corresponding or adjacent lobes in progressive multiple sclerosis patients was observed 29 , although the location and extent of grey matter lesions were not studied.…”

Section: Evidence That Links Grey and White Matter Damagementioning

confidence: 92%

Exploring the origins of grey matter damage in multiple sclerosis

et al. 2015

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Multiple sclerosis is characterized at the gross pathological level by the presence of widespread focal demyelinating lesions of the myelin-rich white matter. However, it is becoming clear that grey matter is not spared, even during the earliest phases of the disease. Furthermore, grey matter damage may have an important role both in physical and cognitive disability. Grey matter pathology involves both inflammatory and neurodegenerative mechanisms, but the relationship between the two is unclear. Histological, immunological and neuroimaging studies have provided new insight in this rapidly expanding field, and form the basis of the most recent hypotheses on the pathogenesis of grey matter damage. DOI: https://doi.org/10.1038/nrn3900Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-111099 Accepted Version Originally published at: Calabrese, Massimiliano; Magliozzi, Roberta; Ciccarelli, Olga; Geurts, Jeroen J G; Reynolds, Richard; Martin, Roland (2015). Exploring the origins of grey matter damage in multiple sclerosis. Nature Reviews Neuroscience, 16 (3) AbstractMultiple sclerosis is characterised at the gross pathological level by the presence of widespread focal demyelinating lesions of the myelin-rich white matter. However, in recent years it has become clear that grey matter is not spared, even during the earliest phases of the disease. Furthermore, grey matter damage has been suggested to have an important role both in physical and cognitive disability. Grey matter pathology involves both inflammatory and neurodegenerative mechanisms, but the relationship between the two is unclear. This review will summarize and highlight important histological, immunological, and neuroimaging results from this rapidly expanding field and will address the most recent hypotheses on the pathogenesis of grey matter damage.

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Different white matter lesion characteristics correlate with distinct grey matter abnormalities on magnetic resonance imaging in secondary progressive multiple sclerosis

Cited by 13 publications

References 37 publications

Grey matter volume in a large cohort of MS patients: relation to MRI parameters and disability

Grey matter volume in a large cohort of MS patients: relation to MRI parameters and disability

Accumulation of meningeal lymphocytes correlates with white matter lesion activity in progressive multiple sclerosis

Exploring the origins of grey matter damage in multiple sclerosis

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