An MRI-defined measure of cerebral lesion severity to assess therapeutic effects in multiple sclerosis

Abstract

Assess the sensitivity of the Magnetic Resonance Disease Severity Scale (MRDSS), based on cerebral lesions and atrophy, for treatment monitoring of glatiramer acetate (GA) in relapsing-remitting multiple sclerosis (MS). This retrospective non-randomized pilot study included patients who started daily GA [n = 23, age (median, range) 41 (26.2, 53.1) years, Expanded Disability Status Scale (EDSS) score 1.0 (0, 3.5)], or received no disease-modifying therapy (noDMT) [n = 21, age 44.8 (28.2, 55.4), EDSS 0 (0, 2.5)] for 2 years. MRDSS was the sum of z-scores (normalized to a reference sample) of T2 hyperintense lesion volume (T2LV), the ratio of T1 hypointense LV to T2LV (T1/T2), and brain parenchymal fraction (BPF) multiplied by negative 1. The two groups were compared by Wilcoxon rank sum tests; within group change was assessed by Wilcoxon signed rank tests. Glatiramer acetate subjects had less progression than noDMT on T1/T2 [(median z-score change (range), 0 (−1.07, 1.20) vs. 0.41 (−0.30, 2.51), p = 0.003)] and MRDSS [0.01 (−1.33, 1.28) vs. 0.46 (−1.57, 2.46), p = 0.01]; however, not on BPF [0.12 (−0.18, 0.58) vs. 0.10 (−1.47,0.50), p = 0.59] and T2LV [−0.03 (−0.90, 0.57) vs. 0.01 (−1.69, 0.34), p = 0.40]. While GA subjects worsened only on BPF [0.12 (−0.18, 0.58), p = 0.001], noDMT worsened on BPF [0.10 (−1.47, 0.50), p = 0.002], T1/T2 [0.41 (−0.30, 2.51), p = 0.0002], and MRDSS [0.46 (−1.57, 2.46), p = 0.0006]. These preliminary findings show the potential of two new cerebral MRI metrics to track MS therapeutic response. The T1/T2, an index of the destructive potential of lesions, may provide particular sensitivity to treatment effects.

Association Between Serum MicroRNAs and Magnetic Resonance Imaging Measures of Multiple Sclerosis Severity

“…This observation is consistent with the notion that T2 lesions are nonspecific for the nature and severity of tissue injury, but the development of lesional T1 hypointensity 9 has a higher clinical relevance. This would explain why a T1:T2 lesion index shows more utility than T2LV in tracking therapeutic effects and providing clinical relevance in MS. 11,89 …”

“…40 As an index of the destructive potential of the lesions, we calculated the intrapatient ratio of T1LV to T2LV (T1:T2) based on its unique and valuable role in previous studies. 11,41,42 …”

“…9 Persisting T1 hypointense lesions (black holes) specifically indicate irreversible tissue destruction. 10 The total burden of such lesions and the proportion of T2 lesions showing T1 hypointensity 11 provide a better indication of physical disability, 12 quality of life, 13 and unemployment. 14 …”

Identification of multiple sclerosis patients at highest risk of cognitive impairment using an integrated brain magnetic resonance imaging assessment approach

“…In addition, deep grey matter (GM) atrophy may represent a stronger and more specific MRI correlate of CI compared to whole brain atrophy [6,28,31]. The aim was to investigate conventional MRI volumetric markers such as lesion volume and BPF that are currently the most available and established correlates of disease burden in MS [13][14][15][16][17].…”

Brain MRI Predicts Worsening Multiple Sclerosis Disability over 5 Years in the SUMMIT Study

“…Brain MRI is commonly used as a surrogate to monitor the underlying multiple sclerosis (MS) disease process . This includes the detection of lesions and atrophy, both of which are associated with physical disability, cognitive impairment, risk of disease progression, and response to disease‐modifying therapy . In prospectively designed multicenter MS therapeutic trials, MRI is commonly employed as a supportive outcome measure .…”