Patient outcomes influenced by reduced lymphocyte counts after dimethyl fumarate initiation

Objective: To examine the temporal profile of absolute and lymphocyte subset data from dimethyl fumarate (DMF) start and relationships to disease behavior. Methods: A retrospective study performed on patients with an existing diagnosis of MS and a history of DMF exposure from a single MS center. Demographic, laboratory, and corresponding clinical relapse and MRI data were recorded from baseline and in 3-4-month intervals after treatment initiation extending to 3 years. The Spearman rank coefficient and mixed-effects models were used to assess longitudinal correlations between cell counts and measures of disease activity. Results: A total of 292 patients with MS (228 women; median age at DMF initiation: 40.6 years, range: 16.1-66.7 years) were identified. An increased risk of disease activity was associated with higher absolute lymphocyte count (ALC) values at 3 months (p = 0.001, OR: 1.82) and at 6 months (p = 0.032, hazard ratio: 1.73). A reduced risk of disease evolution in patients with lower ALC values < 1,200 cells/L compared with midtier (1,210-1,800 cells/L) and the highest tertile (>1,810 cells/L) was observed (p = 0.01). Conclusions: Reductions in ALC values at months 3 and 6 after treatment initiation appear to be associated with improved clinical and radiologic outcomes. These data alone may help to provide a better understanding of both the safety and efficacy of DMF

Three-Dimensional Shape and Surface Features Distinguish Multiple Sclerosis Lesions from Nonspecific White Matter Disease

BACKGROUND AND PURPOSE: There remains a need to further refine the ability of clinicians to differentiate multiple sclerosis (MS) from other disease etiologies. Here, we illustrate the value of 3-dimensional (3D) geometric shape and surface lesion characteristics between disease states. METHODS: Standardized 3-Tesla 3D brain magnetic resonance imaging studies were performed on enrolled MS and nonspecific white matter (NSWM) patients. Focal supratentorial lesions were identified, reconstructed using maximum intensity projection, manually segmented, and 3D printed. Printed 3D models were randomly evaluated by three blinded raters for selected shape and surface characteristics. Regression models adjusting for age, disease duration, and individual patient effects were applied to assess lesion characteristics between patient groups. Patient-level and latent class analyses between groups were performed. RESULTS: A total of 1,001 supratentorial lesions were analyzed (710 MS; 291 NSWM) from 30 patients (19 with confirmed MS [11 female; median age = 33.6 years, range: 26.9-54.5], median disease duration = 2.2 years [.4-19.4]), 11 with verified nonspecific white matter (NSWM) disease without MS (11 female; median age = 55.0 years, range: 27.9-66.2). Lesions originating from MS in comparison to NSWM patients demonstrated a higher percentage of asymmetry (75.9% vs. 43%; OR: 4.39 [2.37-8.12]; P < .001), complex surface morphologies (65.9% vs. 27.8%; OR: 2.3 [1.74-3.05]; P < .001), and were multilobular (11.0% vs. .3%, P < .001), and elongated (12.8% vs. 2.4%, P < .001) in shape. Spatially, these traits were of higher frequency within the juxtacortical, deep white matter, and periventricular regions. CONCLUSION: Three-dimensional lesion data may provide new biologic insights related to injury along with offering another approach for determining the origin of lesion types