An MRI-defined Measure of Cerebral Lesion Severity to Assess Therapeutic Effects in Multiple Sclerosis

J Neurol. 2016 Mar;263(3):531-8. doi: 10.1007/s00415-015-8009-8. Epub 2016 Jan 11.

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.

Keywords: Brain atrophy; Composite scale; Glatiramer acetate; MRI; Multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atrophy
  • Cerebral Cortex / diagnostic imaging*
  • Disability Evaluation
  • Disease Progression
  • Female
  • Glatiramer Acetate / therapeutic use*
  • Humans
  • Image Processing, Computer-Assisted
  • Immunosuppressive Agents / therapeutic use*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis / diagnostic imaging*
  • Multiple Sclerosis / drug therapy*
  • Retrospective Studies
  • Severity of Illness Index

Substances

  • Immunosuppressive Agents
  • Glatiramer Acetate