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Published on: June 30, 2014
An MRI-defined measure of cerebral lesion severity to assess therapeutic effects in multiple sclerosis
Gloria Kim1, Shahamat Tauhid1, Sheena L Dupuy1
1Department of Neurology, Brigham and Women's Hospital, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Boston, MA, USA.
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.
Insights
The Magnetic Resonance Disease Severity Scale (MRDSS) shows promise in monitoring glatiramer acetate treatment for multiple sclerosis (MS). New MRI metrics, particularly T1/T2, may offer sensitive detection of treatment effects in MS patients.
Area of Science:
- Neurology
- Radiology
- Medical Imaging
Background:
- Relapsing-remitting multiple sclerosis (MS) requires effective treatment monitoring.
- Glatiramer acetate (GA) is a disease-modifying therapy for MS.
- Cerebral lesions and atrophy are key indicators of MS progression.
Purpose of the Study:
- To assess the sensitivity of the Magnetic Resonance Disease Severity Scale (MRDSS) for monitoring GA treatment in MS.
- To evaluate novel cerebral MRI metrics for tracking therapeutic response in MS.
Main Methods:
- Retrospective pilot study comparing GA patients (n=23) with no disease-modifying therapy (noDMT) (n=21) over 2 years.
- MRDSS calculated using T2 lesion volume (T2LV), T1/T2 ratio, and brain parenchymal fraction (BPF) z-scores.
- Statistical analysis included Wilcoxon rank sum and signed rank tests.
Main Results:
- GA group showed less progression than noDMT on T1/T2 (p=0.003) and MRDSS (p=0.01).
- No significant differences were observed between groups for BPF (p=0.59) and T2LV (p=0.40).
- GA patients worsened only on BPF, while noDMT patients worsened on BPF, T1/T2, and MRDSS.
Conclusions:
- MRDSS demonstrates potential for monitoring MS treatment response.
- The T1/T2 ratio, reflecting lesion destructive potential, may be particularly sensitive to GA treatment effects.
- Preliminary findings suggest utility of new MRI metrics for assessing MS therapeutic efficacy.
