Subcortical but Not Cortical Gray Matter Atrophy Predicts Disability Progression over 5 Years in Patients with Early Relapsing-Remitting Multiple Sclerosis (P03.063)

Objective: Investigate the association between long-term subcortical deep gray matter (SDGM) and cortical volume changes and disability progression in early relapsing-remitting multiple sclerosis (RRMS). Background Pathological changes in gray matter are thought to have an important role in MS disease progression. However, no long-term clinical studies of SDGM and cortical changes have been reported in early RRMS. Design/Methods: One hundred eighty RRMS patients who participated in the Avonex-Steroid-Azathioprine study were assessed yearly for clinical and magnetic resonance imaging outcomes over 5 years. Healthy controls (n=48) were also assessed yearly over 2 years. MS patients were divided into those with and without sustained disability progression (SDP), defined as a ≥1.0-point increase in Expanded Disability Status Scale score lasting for ≥12 weeks at any time over the 5-year study period. Results: Of the 180 patients, 90 patients experienced SDP and 90 had stable disease after 5 years. At baseline, SDP patients were older and had longer disease duration, greater T2 lesion volume, and smaller SDGM and cortical volumes ( P ≤0.014). At 2 years, significant differences were seen in T2 and lateral ventricle volumes as well as whole brain, total SDGM, putamen, thalamus, nucleus accumbens, and amygdala volumes across the 2 RRMS groups and healthy controls; SDP patients had larger percentage changes in these same measures except for nucleus accumbens and amygdala when compared with stable MS patients at 2 years. At 5 years, SDP patients had greater percentage change decreases in volumes of whole brain, total SDGM, putamen, and thalamus and a greater increase in lateral ventricle volume than patients with stable disease ( P ≤0.02). No differences in cortical, white matter, or T2 lesion volumes were observed between patients with and without SDP at 5 years. Conclusions: SDP in early RRMS is associated with SDGM atrophy progression, especially in the putamen and thalamus, but not with cortical atrophy. Supported by: Biogen Idec Inc. and Czech Ministry of Education, Research Program MSM 0021620849. Disclosure: Dr. Zivadinov has received personal compensation for activities with Teva Neuroscience, Biogen Idec, EMD Serono, and Questcor Pharmaceuticals as a speaker and/or consultant. Dr. Zivadinov has received research support from Biogen Idec, Teva Neuroscience, Genzyme Corporation, Bracco, Questcor Pharmaceuticals and EMD Serono. Dr. Bergsland has nothing to disclose. Dr. Dolezal has received personal compensation for activities with Merck Serono, Biogen Idec, and Novartis as a consultant. Dr. Hussein has nothing to disclose. Dr. Seidl has received research support from Biogen Idec. Dr. Dwyer has nothing to disclose. Dr. Vaneckova has nothing to disclose. Dr. Krasensky has received research support from Biogen Idec. Dr. Potts has received personal compensation for activities with Biogen Idec. Dr. Havrodova has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, Genzyme Corporation, GlaxoSmithKline, Inc., Novartis, Merck, Sanofi-Aventis Pharmaceuticals, Serono, Inc., and Teva as consultant, speaker and/or advisory board participant. Dr. Horakova has received personal compensation for activities with Biogen Idec as a speaker.Dr. Horakova has received research support from Biogen Idec.