No abstract

Three-dimensional lesion data may provide new biologic insights related to injury along with offering another approach for determining the origin of lesion types.

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/μL compared with midtier (1,210–1,800 cells/μL) and the highest tertile (>1,810 cells/μL) 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.

The accurate recognition of multiple sclerosis (MS) lesions is challenged by the high sensitivity and imperfect specificity of MRI. To examine whether longitudinal changes in volume, surface area, 3-dimensional (3D) displacement (i.e. change in lesion position), and 3D deformation (i.e. change in lesion shape) could inform on the origin of supratentorial brain lesions, we prospectively enrolled 23 patients with MS and 11 patients with small vessel disease (SVD) and performed standardized 3-T 3D brain MRI studies. Bayesian linear mixed effects regression models were constructed to evaluate associations between changes in lesion morphology and disease state. A total of 248 MS and 157 SVD lesions were studied. Individual MS lesions demonstrated significant decreases in volume < 3.75mm3 (p = 0.04), greater shifts in 3D displacement by 23.4% with increasing duration between MRI time points (p = 0.007), and greater transitions to a more non-spherical shape (p < 0.0001). If 62.2% of lesions within a given MRI study had a calculated theoretical radius > 2.49 based on deviation from a perfect 3D sphere, a 92.7% in-sample and 91.2% out-of-sample accuracy was identified for the diagnosis of MS. Longitudinal 3D shape evolution and displacement characteristics may improve lesion classification, adding to MRI techniques aimed at improving lesion specificity.