The Effect of Dimethyl Fumarate on Cerebral Gray Matter Atrophy in Multiple Sclerosis

被引:21
作者
Dupuy S.L. [1 ]
Tauhid S. [1 ]
Hurwitz S. [2 ]
Chu R. [1 ]
Yousuf F. [1 ]
Bakshi R. [3 ]
机构
[1] Department of Neurology, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA
[2] Department of Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA
[3] Departments of Neurology and Radiology, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA
关键词
Cerebral gray matter atrophy; Dimethyl fumarate; Multiple sclerosis;
D O I
10.1007/s40120-016-0054-4
中图分类号
学科分类号
摘要
Introduction: The objective of this pilot study was to compare cerebral gray matter (GM) atrophy over 1 year in patients starting dimethyl fumarate (DMF) for multiple sclerosis (MS) to that of patients on no disease-modifying treatment (noDMT). DMF is an established therapy for relapsing–remitting (RR) MS. Methods: We retrospectively analyzed 20 patients with RRMS at the start of DMF [age (mean ± SD) 46.1 ± 10.2 years, Expanded Disability Status Scale (EDSS) score 1.1 ± 1.2, timed 25-foot walk (T25FW) 4.6 ± 0.8 s] and eight patients on noDMT (age 42.5 ± 6.6 years, EDSS 1.7 ± 1.1, T25FW 4.4 ± 0.6 s). Baseline and 1-year 3D T1-weighted 3T MRI was processed with automated pipelines (SIENA, FSL-FIRST) to assess percentage whole brain volume change (PBVC) and deep GM (DGM) atrophy. Group differences were assessed by analysis of covariance, with time between MRI scans as a covariate. Results: Over 1 year, the DMF group showed a lower rate of whole brain atrophy than the noDMT group (PBVC: −0.37 ± 0.49% vs. −1.04 ± 0.67%, p = 0.005). The DMF group also had less change in putamen volume (−0.06 ± 0.22 vs. −0.32 ± 0.28 ml, p = 0.02). There were no significant on-study differences between groups in caudate, globus pallidus, thalamus, total DGM volume, T2 lesion volume, EDSS, or T25FW (all p > 0.20). Conclusions: These results suggest a treatment effect of DMF on GM atrophy appearing at 1 year after starting therapy. However, due to the retrospective study design and sample size, these findings should be considered preliminary, and require confirmation in future investigations. Funding: Biogen. © 2016, The Author(s).
引用
收藏
页码:215 / 229
页数:14
相关论文
共 75 条
[1]  
Bakshi R., Dandamudi V.S., Neema M., De C., Bermel R.A., Measurement of brain and spinal cord atrophy by magnetic resonance imaging as a tool to monitor multiple sclerosis, J Neuroimaging, 15, pp. 30S-45S, (2005)
[2]  
Filippi M., Wolinsky J.S., Comi G., CORAL Study Group. Effects of oral glatiramer acetate on clinical and MRI-monitored disease activity in patients with relapsing multiple sclerosis: a multicentre, double-blind, randomised, placebo-controlled study, Lancet Neurol, 5, pp. 213-220, (2006)
[3]  
Filippi M., Rocca M.A., Arnold D.L., Et al., EFNS guidelines on the use of neuroimaging in the management of multiple sclerosis, Eur J Neurol, 13, pp. 313-325, (2006)
[4]  
Zivadinov R., Bakshi R., Role of MRI in multiple sclerosis I: inflammation and lesions, Front Biosci, 9, pp. 665-683, (2004)
[5]  
Filippi M., Preziosa P., Rocca M.A., Magnetic resonance outcome measures in multiple sclerosis trials: time to rethink?, Curr Opin Neurol, 27, pp. 290-299, (2014)
[6]  
Rudick R.A., Fisher E., Lee J.C., Simon J., Jacobs L., Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Multiple Sclerosis Collaborative Research Group, Neurology, 53, pp. 1698-1704, (1999)
[7]  
Sharma J., Sanfilipo M.P., Benedict R.H., Weinstock-Guttman B., Munschauer F.E., Bakshi R., Whole-brain atrophy in multiple sclerosis measured by automated versus semiautomated MR imaging segmentation, AJNR Am J Neuroradiol, 25, pp. 985-996, (2004)
[8]  
Bakshi R., Yeste A., Patel B., Et al., Serum lipid antibodies are associated with cerebral tissue damage in multiple sclerosis, Neurol Neuroimmunol Neuroinflamm, 3, (2016)
[9]  
Chu R., Hurwitz S., Tauhid S., Bakshi R., Deep gray matter segmentation from 1.5T vs. 3T MRI in normal controls and patients with multiple sclerosis meeting of the American Academy of Neurology, Vancouver, Canada, Neurology, 86, P4, (2016)
[10]  
Chu R., Tauhid S., Glanz B., Et al., Whole brain volume measured from 1.5T versus 3T MRI in healthy subjects and patients with multiple sclerosis, J Neuroimaging, 26, pp. 62-67, (2016)