title: 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.
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Gloria
authors.initials: G
authors.lastname: Kim
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Shahamat
authors.initials: S
authors.lastname: Tauhid
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Sheena L
authors.initials: SL
authors.lastname: Dupuy
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Subhash
authors.initials: S
authors.lastname: Tummala
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Fariha
authors.initials: F
authors.lastname: Khalid
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Healy
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Boston, MA, USA. rbakshi@post.harvard.edu.|Department of Radiology, Brigham and Women's Hospital, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Boston, MA, USA. rbakshi@post.harvard.edu.|Laboratory for Neuroimaging Research, One Brookline Place, Brookline, MA, 02445, USA. rbakshi@post.harvard.edu.
authors.forename: Rohit
authors.identifier: http://orcid.org/0000-0001-8601-5534
authors.initials: R
authors.lastname: Bakshi
mesh_terms: D000328:Adult; D001284:Atrophy; D002540:Cerebral Cortex / Q000000981:diagnostic imaging*; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D000068717:Glatiramer Acetate / Q000627:therapeutic use*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D007166:Immunosuppressive Agents; D000068717:Glatiramer Acetate
keywords: Brain atrophy; Composite scale; Glatiramer acetate; MRI; Multiple sclerosis