Author Of 3 Presentations
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 2 Presentations
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.