Author Of 5 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.
P0231 - Reduced grey matter atrophy in patients with relapsing multiple sclerosis treated with cladribine tablets (ID 951)
Abstract
Background
It is increasingly understood that grey matter (GM) atrophy is associated with disability progression and cognitive decline in patients with multiple sclerosis (MS). Previously, we demonstrated that treatment with cladribine tablets 3.5 mg/kg bodyweight (CT3.5; cumulative dose over 2 years) in the CLARITY study (NCT00213135) decreased brain atrophy compared with placebo, which was closely associated with a lower risk of disability progression [De Stefano et al. MSJ 2018].
Objectives
Post hoc evaluation of GM and white matter (WM) volume changes in patients with relapsing MS randomized to CT3.5 or placebo in the CLARITY study.
Methods
Images from pre-gadolinium T1-weighted magnetic resonance imaging scans of patients randomized to CT3.5 or placebo for 2 years in CLARITY were evaluated using SIENA-XL software. Images from 0–6 months (CT3.5, n=267; placebo, n=265) were analyzed independently of images from 6–24 months (CT3.5, n=184; placebo, n=186) to account for the potential effects of pseudoatrophy. Annualized mean changes in percentage of GM volume (PGMV) or WM volume (PWMV) between CT3.5 and placebo for 0–6 and 6–24 months were compared using a variance model.
Results
CT3.5 reduced GM and WM volume vs placebo in the first 6 months, consistent with pseudoatrophy [PGMV change: CT3.5 -0.53 vs placebo -0.25 (p=0.045); PWMV change: CT3.5 -0.49 vs placebo -0.34 (p=0.137)]. Brain volume loss from 6–24 months was reduced in patients randomized to CT3.5 with the difference between CT3.5 and placebo significant for GM [PGMV change: CT3.5 -0.90 vs placebo -1.27 (p=0.026); PWMV change: CT3.5-0.32 vs placebo -0.40 (p=0.52)].
Conclusions
Volume loss reduction in WM and, particularly, in GM was noted from 6-24 months in CT3.5-treated patients vs placebo, after a period of pseudoatrophy (0-6 months). Such findings suggest that CT3.5 significantly reduces brain atrophy predominantly in the GM, an effect that may contribute to lower risk of disability progression.
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.
P0708 - Differential MRI biomarkers between MOGAD, AQP4-NMOSD and RRMS: a MAGNIMS multicenter study (ID 1335)
Abstract
Background
Clinical and imaging features of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) may overlap with those of aquaporin 4-neuromyelitis optica spectrum disorder (AQP4-NMOSD) and relapsing remitting multiple sclerosis (RRMS). There is an unmet need for MRI biomarkers which reflect biological mechanisms involved in MOGAD and can help in the differential diagnosis.
Objectives
We aim to identify imaging features able to differentiate between non-acute MOG-antibody disease, AQP4-NMOSD and RRMS.
Methods
In this ongoing retrospective, cross-sectional MAGNIMS study, we analyzed data collected from 8 centers. All subjects (n=352) had brain and cervical cord 3T MRI. Quantification of MRI biomarkers included brain white matter lesions (WMLs), cortical lesions (CL), brain parenchymal fraction (BPF), white matter fraction (WMF), cortical and deep grey matter fractions (GMF) and cross-sectional cervical cord area (CSA) at C1-C2. Linear regression models were used to compare MRI measures between groups, corrected for age, sex, and centre. Statistical significance was considered when p was <0.05.
Results
91 patients with MOGAD (50F, mean age: 41yrs [±15]), 85 with AQP4-NMOSD (68F, 49yrs [±14]), 90 with RRMS (56F, 41yrs [±11]) and 87 healthy controls (HCs) (54F, 36yrs [±11.6]) were collected. The most common phenotypes at onset were optic neuritis and transverse myelitis in MOGAD (93%) and AQP4-NMOSD (87%). WMLs were detected in 57% MOGAD, 79% AQP4-NMOSD, all RRMS (100%) patients, and in 15% HCs. The mean lesion load and number of lesions were higher in RRMS than both MOGAD (p=0.007, p<0.001) and AQP4-NMOSD (p=0.001, p<0.001). At least one CL was seen in 8% patients with MOGAD (total n=8), 10% patients with AQP4-NMOSD (n=7), and in 69% patients with RRMS (n=150). All patient groups showed lower BPF than HCs, with lower WMF in MOGAD and RRMS than HCs (all p<0.01). Between groups, deep GMF was lower in RRMS than MOGAD (p<0.001) and AQP4-NMOSD (p=0.001). CSA was reduced in all disease groups when compared to HCs (all p<0.01) and lower in AQP4-NMOSD than RRMS (p=0.01).
Conclusions
This ongoing study indicates that MOGAD and AQP4-NMOSD share similar MRI features, and no specific MRI biomarker can distinguish between them. Patients with AQP4-NMOSD showed greater spinal cord atrophy than RRMS, and RRMS patients had a higher number of cortical lesions, and greater deep GM atrophy than AQP4-NMOSD and MOGAD. The next step is to investigate whether lesion distribution differs between the two antibody-mediated disease.
Presenter Of 1 Presentation
P0231 - Reduced grey matter atrophy in patients with relapsing multiple sclerosis treated with cladribine tablets (ID 951)
Abstract
Background
It is increasingly understood that grey matter (GM) atrophy is associated with disability progression and cognitive decline in patients with multiple sclerosis (MS). Previously, we demonstrated that treatment with cladribine tablets 3.5 mg/kg bodyweight (CT3.5; cumulative dose over 2 years) in the CLARITY study (NCT00213135) decreased brain atrophy compared with placebo, which was closely associated with a lower risk of disability progression [De Stefano et al. MSJ 2018].
Objectives
Post hoc evaluation of GM and white matter (WM) volume changes in patients with relapsing MS randomized to CT3.5 or placebo in the CLARITY study.
Methods
Images from pre-gadolinium T1-weighted magnetic resonance imaging scans of patients randomized to CT3.5 or placebo for 2 years in CLARITY were evaluated using SIENA-XL software. Images from 0–6 months (CT3.5, n=267; placebo, n=265) were analyzed independently of images from 6–24 months (CT3.5, n=184; placebo, n=186) to account for the potential effects of pseudoatrophy. Annualized mean changes in percentage of GM volume (PGMV) or WM volume (PWMV) between CT3.5 and placebo for 0–6 and 6–24 months were compared using a variance model.
Results
CT3.5 reduced GM and WM volume vs placebo in the first 6 months, consistent with pseudoatrophy [PGMV change: CT3.5 -0.53 vs placebo -0.25 (p=0.045); PWMV change: CT3.5 -0.49 vs placebo -0.34 (p=0.137)]. Brain volume loss from 6–24 months was reduced in patients randomized to CT3.5 with the difference between CT3.5 and placebo significant for GM [PGMV change: CT3.5 -0.90 vs placebo -1.27 (p=0.026); PWMV change: CT3.5-0.32 vs placebo -0.40 (p=0.52)].
Conclusions
Volume loss reduction in WM and, particularly, in GM was noted from 6-24 months in CT3.5-treated patients vs placebo, after a period of pseudoatrophy (0-6 months). Such findings suggest that CT3.5 significantly reduces brain atrophy predominantly in the GM, an effect that may contribute to lower risk of disability progression.