Author Of 2 Presentations
P0620 - QSM detects greater rate of reduction in lesion magnetic susceptibility in patients treated with Dimethyl Fumarate over Glatiramer Acetate treatment (ID 1783)
Abstract
Background
Chronic active multiple sclerosis (MS) lesions, characterized by a hyperintense rim (rim+) on quantitative susceptibility mapping (QSM), have been shown to contain iron-enriched, activated microglia and macrophages. QSM is a potential biomarker to monitor treatments directed toward the CNS inflammation. Studies have suggested that dimethyl fumarate (DMF) may reduce the pro-inflammatory innate immune response in the CNS. A comparison to other disease modifying therapies (DMTs) is warranted to evaluate this potential benefit.
Objectives
To determine if dimethyl fumarate (DMF) reduces the iron load, as measured on QSM, in chronic active MS lesions at a greater rate than glatiramer acetate (GA) treatment.
Methods
Sixty-one patients (41 female, 20 male, mean age: 42.1 years +/- 10.9 and EDSS 0.82 +/- 1.2), were considered for this analysis. Fifty-six patients had relapsing-remitting MS and 5 had clinically-isolated syndrome; 37 patients were treated with DMF and 24 with GA. The two treatment groups had similar baseline clinical characteristics; however, DMF patients had less time on treatment as compared to GA (3.86 +/- 1.75 years vs 5.99 +/- 2.67 years, p<0.001). Patients had a QSM scan prior to treatment and a minimum of two on-treatment QSM MRIs. Lesions were classified as rim+ or rim- negative based upon a review of two independent reviewers. To compare longitudinal QSM change in the rim+ lesions among treatment groups, a linear mixed effects model was utilized.
Results
At baseline, patients treated with GA had more QSM rim+ lesions (9.4%) as compared to those starting DMF (4.5%), p=0.0004, however the number of patients having at least one rim+ lesion was similar (16 vs 18 patients) among the treatment groups. DMF patients with rim+ lesions had a longer disease duration as compared to rim+ GA patients (8.15 +/- 6.82 vs 3.55 +/- 4.85 years, p= 0.032). In the subset of patients with QSM rim+ lesions, there was a significantly larger decrease in susceptibility in rim+ lesions with DMF treatment as compared to GA, p< 0.0009. There was minimal reduction of susceptibility in rim- lesions, which was similar among treatment groups; all patients (p=0.92) and QSM rim+ only patients (p=0.11).
Conclusions
This study suggests that DMF reduces the iron load in rim+ MS lesions at a greater rate than GA. These results support QSM to evaluate the effectiveness of various DMTs on the CNS innate immune response in chronic active MS lesions.
P0802 - Differences in Regional Cortical Thickness and Subcortical Volumes Among Cognitively Impaired and Unimpaired Multiple Sclerosis Patients (ID 829)
Abstract
Background
The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) is a well-established neuropsychological battery to evaluate cognitive changes in patients with Multiple Sclerosis (MS). FreeSurfer has been used to assess neuroanatomical features, including cortical thickness and subcortical volume, as correlates of disease activity. The evaluation of cognitive performance, when combined with FreeSurfer analysis, may offer unique cross-sectional insight into the natural history of MS and the ways in which neurodegeneration interacts with cognition across different stages of disease.
Objectives
This study aims to take a cross-sectional view of a large MS patient cohort and study the relationship between cortical/subcortical measurements and cognitive function across various domains. Its objective is to compare the differences in cortical thickness and subcortical volume in subjects who are cognitively impaired and cognitively unimpaired.
Methods
163 patients with MS underwent both T1-weighted magnetic resonance imaging (MRI) and formal BICAMS testing within three months of one another. FreeSurfer was then used to analyze imaging data. BICAMS includes the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test (CVLT), and the Brief Visuospatial Memory Test (BVMT). Impairment was based upon published age-matched normative data. Patients had a mean disease duration of 10.5 +/- 7.3 years; mean Expanded Disability Status Scale (EDSS) of 1.3 +/- 1.6; mean age of 42.9 +/- 10.5 years. Multivariate regression analysis was used to compare cortical thickness and subcortical volume in impaired vs.unimpaired subjects.
Results
31, 15 and 38 patients were found to be impaired on SDMT, CVLT, and BVMT testing, respectively. Significant differences were found in multiple subcortical regions among impaired and unimpaired on SDMT (Thalamus; p=0.01) and BVMT (Left/Right Accumbens; p=0.001, p=0.02; Caudate; p=<0.001; Left Cerebellum; p=0.02; Left/Right Hippocampus; p=0.004, p=0.02; Left Pallidum; p=0.01; Left/Right Putamen; p=0.02, p=0.004; Right Amygdala; p=0.02; Right Thalamus; p=0.004). Impairment on SDMT was associated with differences in caudal anterior cingulate cortex (p= 0.001) and entorhinal cortex (p=0.003) and BVMT impairment was associated with thinning in temporal lobe regions (Right Bank of Superior Temporal Lobe; p=0.008; Right Fusiform; p=0.02). SDMT, CVLT, BVMT were all associated with differences in various occipital lobe regions. No significant differences were found when looking at the four anatomic lobes in their entirety.
Conclusions
Our results show associations between impaired performance on certain neuropsychological tests and regional cortical thinning and subcortical volume loss in what is the largest known cohort to date. These findings could shed light on unique and overlapping neuroanatomical substrates underlying different cognitive processes in MS.
Presenter Of 1 Presentation
P0620 - QSM detects greater rate of reduction in lesion magnetic susceptibility in patients treated with Dimethyl Fumarate over Glatiramer Acetate treatment (ID 1783)
Abstract
Background
Chronic active multiple sclerosis (MS) lesions, characterized by a hyperintense rim (rim+) on quantitative susceptibility mapping (QSM), have been shown to contain iron-enriched, activated microglia and macrophages. QSM is a potential biomarker to monitor treatments directed toward the CNS inflammation. Studies have suggested that dimethyl fumarate (DMF) may reduce the pro-inflammatory innate immune response in the CNS. A comparison to other disease modifying therapies (DMTs) is warranted to evaluate this potential benefit.
Objectives
To determine if dimethyl fumarate (DMF) reduces the iron load, as measured on QSM, in chronic active MS lesions at a greater rate than glatiramer acetate (GA) treatment.
Methods
Sixty-one patients (41 female, 20 male, mean age: 42.1 years +/- 10.9 and EDSS 0.82 +/- 1.2), were considered for this analysis. Fifty-six patients had relapsing-remitting MS and 5 had clinically-isolated syndrome; 37 patients were treated with DMF and 24 with GA. The two treatment groups had similar baseline clinical characteristics; however, DMF patients had less time on treatment as compared to GA (3.86 +/- 1.75 years vs 5.99 +/- 2.67 years, p<0.001). Patients had a QSM scan prior to treatment and a minimum of two on-treatment QSM MRIs. Lesions were classified as rim+ or rim- negative based upon a review of two independent reviewers. To compare longitudinal QSM change in the rim+ lesions among treatment groups, a linear mixed effects model was utilized.
Results
At baseline, patients treated with GA had more QSM rim+ lesions (9.4%) as compared to those starting DMF (4.5%), p=0.0004, however the number of patients having at least one rim+ lesion was similar (16 vs 18 patients) among the treatment groups. DMF patients with rim+ lesions had a longer disease duration as compared to rim+ GA patients (8.15 +/- 6.82 vs 3.55 +/- 4.85 years, p= 0.032). In the subset of patients with QSM rim+ lesions, there was a significantly larger decrease in susceptibility in rim+ lesions with DMF treatment as compared to GA, p< 0.0009. There was minimal reduction of susceptibility in rim- lesions, which was similar among treatment groups; all patients (p=0.92) and QSM rim+ only patients (p=0.11).
Conclusions
This study suggests that DMF reduces the iron load in rim+ MS lesions at a greater rate than GA. These results support QSM to evaluate the effectiveness of various DMTs on the CNS innate immune response in chronic active MS lesions.