Gray and white matter volume changes in early RRMS

Tiberio, M.; Chard, Declan; Altmann, Daniel R.; Davies, G.; Griffin, Colette; Rashid, Waqar; Sastre‐Garriga, Jaume; Thompson, Alan J.; Miller, David H.

doi:10.1212/01.wnl.0000154526.22878.30

Cited by 159 publications

(191 citation statements)

References 57 publications

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“…When brain atrophy was studied in early RRMS patients, for example, both grey and white matter atrophy were observed, but the correlation between the two was only moderate 43 . A 2-year follow-up of these patients revealed that fluctuations in inflammatory white matter lesions were related to volume changes in white matter rather than to grey matter loss 44 . Voxel-based morphometry and tract-based spatial statistical analyses were applied to assess regional grey matter and white matter damage in 36 RRMS and 25 sex-and agematched controls.…”

Section: Evidence For Independent Grey Matter Damagementioning

confidence: 88%

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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Section: Evidence For Independent Grey Matter Damagementioning

confidence: 88%

Exploring the origins of grey matter damage in multiple sclerosis

et al. 2015

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“…However, neuroimaging studies revealed microglia activation with minimal inflammatory cell infiltrates in proximity of cortical axonal transections [19]; this gray matter abnormality occurs surprisingly early and correlates much better with permanent disability, demonstrating that microglia activation in gray matter correlates with neuron loss and MS onset ( [37,51,201,230]). …”

Section: The Eae Animal Modelmentioning

confidence: 99%

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

Vegeto

Benedusi

Maggi

2008

Frontiers in Neuroendocrinology

271

206

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a b s t r a c tRecent studies highlight the prominent role played by estrogens in protecting the central nervous system (CNS) against the noxious consequences of a chronic inflammatory reaction. The neurodegenerative process of several CNS diseases, including Multiple Sclerosis, Alzheimer's and Parkinson's Diseases, is associated with the activation of microglia cells, which drive the resident inflammatory response. Chronically stimulated during neurodegeneration, microglia cells are thought to provide detrimental effects on surrounding neurons. The inhibitory activity of estrogens on neuroinflammation and specifically on microglia might thus be considered as a beneficial therapeutic opportunity for delaying the onset or progression of neurodegenerative diseases; in addition, understanding the peculiar activity of this female hormone on inflammatory signalling pathways will possibly lead to the development of selected anti-inflammatory molecules. This review summarises the evidence for the involvement of microglia in neuroinflammation and the anti-inflammatory activity played by estrogens specifically in microglia.

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“…Some studies have reported no significant, or conflicting, effects of DMTs on brain atrophy (Bermel & Bakshi, 2006; Calabrese et al., 2012; Lublin et al., 2016; Tiberio et al., 2005). Others have reported statistically significant slowing of brain atrophy, but only after 24 months or more (Cohen et al., 2012; Coles et al., 2012; Kappos et al., 2010; Mattioli, Stampatori, Bellomi, Scarpazza, & Capra, 2015; Miller et al., 2007; Rinaldi et al., 2012).…”

Section: Introductionmentioning

confidence: 99%

Estriol‐mediated neuroprotection in multiple sclerosis localized by voxel‐based morphometry

et al. 2018

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IntroductionProgressive gray matter (GM) atrophy is a hallmark of multiple sclerosis (MS). Cognitive impairment has been observed in 40%–70% of MS patients and has been linked to GM atrophy. In a phase 2 trial of estriol treatment in women with relapsing–remitting MS (RRMS), higher estriol levels correlated with greater improvement on the paced auditory serial addition test (PASAT) and imaging revealed sparing of localized GM in estriol‐treated compared to placebo‐treated patients. To better understand the significance of this GM sparing, the current study explored the relationships between the GM sparing and traditional MRI measures and clinical outcomes.MethodsSixty‐two estriol‐ and forty‐nine placebo‐treated RRMS patients underwent clinical evaluations and brain MRI. Voxel‐based morphometry (VBM) was used to evaluate voxelwise GM sparing from high‐resolution T1‐weighted scans.ResultsA region of treatment‐induced sparing (TIS) was defined as the areas where GM was spared in estriol‐ as compared to placebo‐treated groups, localized primarily within the frontal and parietal cortices. We observed that TIS volume was directly correlated with improvement on the PASAT. Next, a longitudinal cognitive disability‐specific atlas (DSA) was defined by correlating voxelwise GM volumes with PASAT scores, that is, areas where less GM correlated with less improvement in PASAT scores. Finally, overlap between the TIS and the longitudinal cognitive DSA revealed a specific region of cortical GM that was preserved in estriol‐treated subjects that was associated with better performance on the PASAT.ConclusionsDiscovery of this region of overlap was biology driven, not based on an a priori structure of interest. It included the medial frontal cortex, an area previously implicated in problem solving and attention. These findings indicate that localized GM sparing during estriol treatment was associated with improvement in cognitive testing, suggesting a clinically relevant, disability‐specific biomarker for clinical trials of candidate neuroprotective treatments in MS.

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Gray and white matter volume changes in early RRMS

Cited by 159 publications

References 57 publications

Exploring the origins of grey matter damage in multiple sclerosis

Exploring the origins of grey matter damage in multiple sclerosis

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

Estriol‐mediated neuroprotection in multiple sclerosis localized by voxel‐based morphometry

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