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(Stroke. 2009;40:1704.)
© 2009 American Heart Association, Inc.

Original Contributions

Results of the MRI Substudy of the Intravenous Magnesium Efficacy in Stroke Trial

Chelsea S. Kidwell, MD; Kennedy R. Lees, MD; Keith W. Muir, MD; Christopher Chen, MD; Stephen M. Davis, MD; Deidre A. De Silva, MD; Christopher J. Weir, PhD; Sidney Starkman, MD; Jeffry R. Alger, PhD; Jeffrey L. Saver, MD for the MR IMAGES Investigators

From Georgetown University (C.S.K., D.A.D.), Washington DC; University of California (C.S.K., S.S., J.R.A., J.L.S.), Los Angeles, Calif; Western Infirmary (K.R.L.), Faculty of Medicine, University of Glasgow, Scotland; Division of Clinical Neurosciences (K.W.M.), University of Glasgow, Scotland; National University of Singapore (C.C.), Singapore; National Medical Research Council (C.C., D.A.D.), Singapore; Royal Melbourne Hospital (D.M.D.), Victoria, Australia; University of Melbourne (S.M.D.), Australia; National Neuroscience Institute (D.A.D.), Singapore General Hospital campus, Singapore; Robertson Centre for Biostatistics (C.J.W.), University of Glasgow, Scotland.

Correspondence to Chelsea S. Kidwell, Building D, Suite 150, Georgetown University, 4000 Reservoir Road, NW, Washington DC, 20007. E-mail ck256{at}georgetown.edu

Background and Purpose— Although magnesium is neuroprotective in animal stroke models, no clinical benefit was confirmed in the Intravenous Magnesium Efficacy in Stroke (IMAGES) trial of acute stroke patients. The Magnetic Resonance in IMAGES (MR IMAGES) substudy investigated the effects of magnesium on the imaging surrogate outcome of infarct growth.

Methods— IMAGES trial patients in participating centers were randomized to receive either intravenous magnesium or placebo within 12 hours of stroke onset. Infarct growth was defined as volume difference between baseline diffusion-weighted imaging and day 90 fluid-attenuated inversion recovery image lesions. Patients who died were imputed the largest infarct growth observed.

Results— Among the 90 patients included in the primary analysis, there was no difference in infarct growth (median absolute growth, P=0.639; median percentage growth, P=0.616; proportion with any growth, P=0.212) between the 46 treated with magnesium and 44 with placebo. Infarct growth correlated with NIHSS score change from baseline to day 90. There was a trend showing baseline serum glucose correlated with infarct growth with magnesium treatment, but not in the placebo group. The mismatch frequency was reduced from 73% to 47% by increasing the mismatch threshold from >20% to >100% of core volume.

Conclusions— Infarct growth, confirmed here as a surrogate for clinical progression, was similar between magnesium and placebo treatment, paralleling the main IMAGES trial clinical outcomes. Glucose was a covariate for infarct growth with magnesium treatment. A more stringent mismatch threshold to define penumbra more appropriately would have excluded half of the patients in this 12-hour time window stroke study.

Key Words: diffusion-weighted imaging • glucose • magnesium • magnetic resonance imaging • surrogate endpoint