Neocortical volume decrease in relapsing–remitting MS patients with mild cognitive impairment

Amato, Maria Pia; Bartolozzi, Maria Letizia; Zipoli, Valentina; Portaccio, Emilio; Mortilla, M.; Guidi, Leonello; Siracusa, G.; Sorbi, Sandro; Federico, Antonio; Stefano, Nicola De

doi:10.1212/01.wnl.0000129544.79539.d5

Cited by 296 publications

(223 citation statements)

References 39 publications

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“…In addition, GM histological abnormalities increase in MS over time [8], which might account for the significant increase of the FD in the transition from FAMS to RRMS. The topography of GM damage in MS drives the appearance of functional deficits [31,32]. We speculate that this might explain why in our study an overall measurement of GM damage such as FD does not correlate with disability, which depends on the topography of the brain damage (i.e.…”

Section: Discussionmentioning

confidence: 70%

Fractal dimension analysis of grey matter in multiple sclerosis

Esteban

Sepulcre

Miras

et al. 2009

Journal of the Neurological Sciences

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The fractal dimension (FD) is a quantitative parameter that characterizes the morphometric variability of a complex object. Among other applications, FD has been used to identify abnormalities of the human brain in conventional magnetic resonance imaging (MRI), including white matter abnormalities in patients with Multiple Sclerosis (MS). Extensive grey matter (GM) pathology has been recently identified in MS and it appears to be a key factor in long-term disability. The aim of the present work was to assess whether FD measurement of GM in T1 MRI sequences can identify GM abnormalities in patients with MS in the early phase of the disease. A voxel-based morphometry approach optimized for MS was used to obtain the segmented brain, where we later calculated the three-dimensional FD of the GM in MS patients and healthy controls. We found that patients with MS had a significant increase in the FD of the GM compared to controls. Such differences were present even in patients with short disease durations, including patients with first attacks of MS. In addition, the FD of the GM correlated with T1 and T2 lesion load, but not with GM atrophy or disability. The FD abnormalities of the GM here detected differed from the previously published FD of the white matter in MS, suggesting that different pathological processes were taking place in each structure. These results indicate that GM morphology is abnormal in patients with MS and that this alteration appears early in the course of the disease.

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Section: Discussionmentioning

confidence: 70%

Fractal dimension analysis of grey matter in multiple sclerosis

Esteban

Sepulcre

Miras

et al. 2009

Journal of the Neurological Sciences

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“…[40][41][42] Our findings suggesting the importance of cortical lesions with regard to CVLT-II are in line with previous studies showing associations between gray matter atrophy and verbal learning. 43,44 The absence of a significant correlation between cortical lesions and other cognitive tests (BVMT-R, COWAT, JLO, and D-KEFS) may be related to their lower sensitivity in showing associations with distributed multiple lesions [39][40][41]45 ; however, regional cortical lesions were not assessed in our study. Other factors may have contributed to our failure to find significant correlations across the spectrum of cognitive domains commonly affected in MS: The small sample size and the high proportion of patients with RRMS compared with SPMS may have limited the severity of the deficits observed.…”

Section: Discussionmentioning

confidence: 80%

Identification and Clinical Impact of Multiple Sclerosis Cortical Lesions as Assessed by Routine 3T MR Imaging

Mike¹,

Glanz²,

Hildenbrand³

et al. 2011

AJNR Am J Neuroradiol

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“…This is not surprising as several pathological (Kutzelnigg et al., 2005; Peterson, Bo, Mork, Chang, & Trapp, 2001) and MRI (Calabrese, Atzori, et al., 2007; Calabrese, De Stefano, et al., 2007; De Stefano et al., 2003) studies have shown that the cerebral cortex is profoundly affected in MS. Indeed, cortical atrophy has been proposed as one of the major underlying substrates of cognitive impairment in MS (Amato et al., 2004; Benedict et al., 2004; Tekok‐Kilic et al., 2007). Which regions within the cerebral cortex undergo atrophy and align with impairments in which cognitive domains is only beginning to be investigated (Wen et al., 2015).…”

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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Neocortical volume decrease in relapsing–remitting MS patients with mild cognitive impairment

Cited by 296 publications

References 39 publications

Fractal dimension analysis of grey matter in multiple sclerosis

Fractal dimension analysis of grey matter in multiple sclerosis

Identification and Clinical Impact of Multiple Sclerosis Cortical Lesions as Assessed by Routine 3T MR Imaging

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

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