Author Of 2 Presentations
LB1208 - Linking structural and functional brain alterations in relapsing-remitting MS (ID 2063)
Abstract
Background
MRI studies have consistently shown structural and functional alterations in the brain of patients with MS. However, pathogenic mechanisms of MS are “multidimensional”, reflecting complex events and thus requiring multivariate analysis methods. A complementary knowledge of such events and their clinical relevance is currently lacking in MS.
Objectives
To investigate “hidden” covarying structural-functional pathogenic patterns in MS patients compared to normal controls (NC).
Methods
We applied linked independent component analysis, a type of fusion approach, to images of grey matter (GM) density, fractional anisotropy (FA) and resting-state functional MRI. We assessed 100 relapsing-remitting MS patients (age: 39.7±10.5 years, 60 female, disease duration: 9.4±6.9 years; median EDSS=1.5, cognitive impairment [CI]: 30%) and 43 demographically-matched NC.
Results
Out of 20 linked structural-functional patterns across study population, only one showed significant group difference, with a loading coefficient across MRI modalities lower in MS than NC (-0.29±1.05 vs 0.69±0.34, corrected-p <0.004), which was already present at very early disease stage and was particularly low in the MS subgroups with larger white matter (WM) lesion volume (LV, >3.5 cm3), higher EDSS (>1.5), CI occurrence and longer disease duration (>5 years). The contribution of each modality to the significant linked covarying pattern was 41% for GM density, 42% for WM FA and 17% for network-functional connectivity (FC). The contribution of FC increased in the MS group with increasing LV, EDSS, CI and disease duration.
Conclusions
These findings suggest that in MS patients with mild disability common pathogenic mechanisms are characterized by a prevalent structural damage equally affecting WM and GM and, to a lesser degree, by concurrent widespread alteration of short-range FC. Such mechanism is already present since the early MS stage and becomes more pronounced with increasing focal pathology and disease severity.
LB1272 - Distinct co-varying functional-structural patterns in multiple sclerosis for physical disability and cognitive impairment (ID 2171)
Abstract
Background
There is still a need to bridge the gap in linking structural and functional alterations in order to evaluate their relative contribution and location towards clinical picture of patients with MS.
Objectives
To identify how distinct covarying structural-functional patterns are able to explain clinical measures of physical disability and cognitive impairment in MS.
Methods
We applied linked independent component analysis (ICA), a type of fusion approach, to images of grey matter (GM) density, fractional anisotropy (FA) and resting-state functional MRI in patients with relapsing-remitting MS (age: 39.7±10.5 years, 60 female, disease duration: 9.4±6.9 years; median EDSS=1.5, cognitive impairment [CI]: 30%). Loading coefficients across the three MRI modalities of linked ICA were used in multiple stepwise linear regression models for EDSS, CI and Rao Battery test scores, adjusted for age and sex.
Results
Higher EDSS was explained (R2adj=0.46, p<0.001) by a linked covarying pattern of structural damage (40%), including lower GM density (30%) and WM FA (10%) and of altered network-FC (60%). CI was explained (R2adj=0.56, p<0.001) by a linked covarying pattern of structural damage (26%), including lower GM density (18%) WM FA (8%) and especially of altered network-FC (74%). Among the different cognitive domains, attention and processing speed, as measured by symbol digit modalities test (SDMT), was best explained (R2adj =0.62, p<0.001) by a pattern mostly driven by altered network-FC (70%) and including, to a lesser extent, structural damage (30%), with equal contribution from lower GM density and lower WM FA.
Conclusions
The highest contribution of altered network-FC with respect to structural damage in explaining physical disability and cognitive impairment of our MS group with mild disability points out the relevance at this early disease stage of mechanisms of cortical plasticity, which however may undergo exhaustion and downregulation in the more advanced stages of disease.
Presenter Of 1 Presentation
LB1208 - Linking structural and functional brain alterations in relapsing-remitting MS (ID 2063)
Abstract
Background
MRI studies have consistently shown structural and functional alterations in the brain of patients with MS. However, pathogenic mechanisms of MS are “multidimensional”, reflecting complex events and thus requiring multivariate analysis methods. A complementary knowledge of such events and their clinical relevance is currently lacking in MS.
Objectives
To investigate “hidden” covarying structural-functional pathogenic patterns in MS patients compared to normal controls (NC).
Methods
We applied linked independent component analysis, a type of fusion approach, to images of grey matter (GM) density, fractional anisotropy (FA) and resting-state functional MRI. We assessed 100 relapsing-remitting MS patients (age: 39.7±10.5 years, 60 female, disease duration: 9.4±6.9 years; median EDSS=1.5, cognitive impairment [CI]: 30%) and 43 demographically-matched NC.
Results
Out of 20 linked structural-functional patterns across study population, only one showed significant group difference, with a loading coefficient across MRI modalities lower in MS than NC (-0.29±1.05 vs 0.69±0.34, corrected-p <0.004), which was already present at very early disease stage and was particularly low in the MS subgroups with larger white matter (WM) lesion volume (LV, >3.5 cm3), higher EDSS (>1.5), CI occurrence and longer disease duration (>5 years). The contribution of each modality to the significant linked covarying pattern was 41% for GM density, 42% for WM FA and 17% for network-functional connectivity (FC). The contribution of FC increased in the MS group with increasing LV, EDSS, CI and disease duration.
Conclusions
These findings suggest that in MS patients with mild disability common pathogenic mechanisms are characterized by a prevalent structural damage equally affecting WM and GM and, to a lesser degree, by concurrent widespread alteration of short-range FC. Such mechanism is already present since the early MS stage and becomes more pronounced with increasing focal pathology and disease severity.