Author Of 4 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.
P0516 - BDNF Val66Met polymorphism effect on hippocampal subfields in multiple sclerosis patients (ID 1688)
Abstract
Background
Brain-derived neurotrophic factor (BDNF) can promote neuronal growth and repair, playing a key role in synaptic plasticity, especially in the hippocampus. The BDNF Val66Met polymorphism was shown to strongly affect BDNF function, but its role in modulating gray matter damage in multiple sclerosis (MS) patients is still not clear.
Objectives
Considering BDNF relevance on hippocampal function, we aimed to explore the effect of BDNF Val66Met polymorphism on the atrophy of hippocampal subfields and its role in cognitive functioning in MS patients.
Methods
Using a 3T scanner, we obtained dual-echo and 3DT1-weighted sequences from 50 MS patients and 15 healthy controls (HC). MS patients also underwent genotype analysis of BDNF and an extensive neuropsychological evaluation. Hippocampal subfields were segmented by using Freesurfer 7.0.1 software. Multiple linear regression models adjusted for age, sex and disease duration were used for between-group comparisons and analysis of associations.
Results
The BDNF Val66Met polymorphism was found in 22 MS patients (44%). Compared to HC, MS patients had reduced volumes of: bilateral hippocampus-amygdala transition area (HATA); left cornus ammonis (CA)1, CA3 and granule cell layer of dentate gyrus (GCL-DG); and right fimbria and presubiculum. BDNF Val66Met polymorphism carriers compared to wild-type (Val66Val) MS patients had higher volume of left hippocampal CA1, CA3, CA4, GCL-DG, molecular layer of subiculum and HATA; and of right hippocampal tail, fissure and presubiculum. In MS patients, higher volume in left CA3 and in right presubiculum correlated with better performance in semantic fluency, while higher volume in left GCL-DG correlated with better visuo-spatial memory performance.
Conclusions
The BNDF Val66Met polymorphism has a protective role in MS patients against both hippocampal atrophy and cognitive deterioration. BDNF genotype may be a potential biomarker for predicting cognitive prognosis, and an interesting target to study for neuroprotective strategies.
P0604 - Mild Gray Matter Atrophy in Patients with Longstanding Multiple Sclerosis and Favorable Clinical Course (ID 1263)
Abstract
Background
Understanding whether multiple sclerosis (MS) can have a favorable course is still challenging. However, a small group of patients who are not disabled after many years of disease can be identified. The mechanisms responsible for this ‘benign’ clinical course remain unclear, likely due to the lack of long-term studies.
Objectives
To assess brain damage in multiple sclerosis patients with no or minimal disability after a longstanding clinical course.
Methods
We compared 13 patients with long-term benign clinical course (LT-BMS, age >55 years, disease duration >30 years, Expanded Disability Status Scale [EDSS] <3.0) and 27 non-benign MS (non-BMS) patients (age >55 years, EDSS >3.0). MRI scans were retrospectively assessed (mean follow-up: 11 years, mean scan per patient: 3). Comparisons of brain volumes (BV) and total T2-lesion volume (LV) changes between the two groups were performed using a mixed effect model. Lesion probability maps (LPMs) of both groups were compared using a nonparametric permutation test.
Results
Patients with LT-BMS showed less over-time decrease in global BV (p=0.02) and grey matter (GM) volume (p<0.001) than non-BMS. Lower atrophy was seen in LT-BMS with no or mild cognitive impairment. By contrast, there was no over-time difference between patient groups in T2-LV accumulation and lesion frequency across brain.
Conclusions
Global brain and GM atrophy changes were mild in this unique patient group with long-standing and no or minimal physical and cognitive disability. These results support the relevant role of GM atrophy in characterizing MS patients who may have favorable long-term disease evolution.