Longitudinal Mixed-Effect Model Analysis Of The Association Between Global And Tissue Specific Brain Atrophy And Lesion Accumulation In Patients With CIS (P1.229)

Objectives: To investigate accumulation of new active lesions and lesion volume (LV) in respect to brain atrophy accumulation in patients with clinically isolated syndrome (CIS) over 2 years. Background: Brain atrophy has been shown to occur from clinical onset of multiple sclerosis. Materials and Methods: 216 CIS patients were recruited as part of an multi-center observational study of early interferon beta 1-a and were imaged on 1.5T MRI scanner at baseline, 6 months, 1 and 2 years. Longitudinal linear and quadratic mixed-effect models were performed. Evolution in percentage changes in whole brain and tissue-specific compartments (dependent variables) were compared respect to median accumulation in cumulative T2 lesions (<2, n=98; 蠅2, n=117), T2-LV (<-8.7%, n=102; 蠅-8.7%, n=102) and in cumulative contrast enhancing lesions (CEL), as the grouping (independent) variables. Reversed models, based on accumulation of cumulative T2 lesions, T2-LV and cumulative CEL (dependent variables) were compared respect to median percentage changes in whole brain and tissue-specific compartments (independent variables). All models were adjusted for age, gender, treatment-status, disease-duration, center and time until first recorded relapse. Results: CIS patients who developed 蠅2 T2 active lesions over the follow-up showed significantly higher decrease of whole brain, grey matter (GM) and cortical volumes and increase in lateral ventricle volume (all p<.05). Similar, yet stronger results were observed for reversed models with median percentage of brain volume changes as the grouping factor and accumulation of cumulative T2 lesion as the dependent variable: decreases in GM and cortical (p<.001) and thalamus (p=.016) volumes and increase in lateral ventricle volume (p<.001). No significance differences were found for mixed-effect models involving T2-LV or CEL. Conclusions: Lesion accumulation and brain volume changes are occurring simultaneously from the earliest phase of MS, although the rate of brain atrophy was better associated with accumulation of new T2 lesions then the reverse. This study was supported by the Czech Ministries of Education and Health [NT13237-4/2012, MSM 0021620849, PRVOUK-P26/LF1/4, RVO-VFN64165/2012] and Biogen Idec. Disclosure: Dr. Varosanec has nothing to disclose. Dr. Horakova has received personal compensation for activities with Biogen Idec, Novartis, Merck Serono, Teva Neuroscience, and Bayer Schering. Dr. Horakova has received research support from Biogen Idec. Dr. Hagemeier has nothing to disclose. Dr. Bergsland has nothing to disclose. Dr. Tyblova has received personal compensation for activities with Biogen Idec, Sanofi-Aventis Pharmaceuticals Inc., Teva Neuroscience, and Merck Serono. Dr. Tyblova has received research support from Biogen Idec. Dr. Seidl has received research support from Biogen Idec. Dr. Vaneckova has received research support from Biogen Idec. Dr. Krasensky has received research support from Biogen Idec. Dr. Dwyer has received personal compensation for activities with EMD Serono and Claret. Dr. Havrdova has received personal compensation for activities with Bayer Pharmaceuticals Corp., Biogen Idec, Genzyme Corp., Novartis, Serono Inc., and Teva Neuroscience. Dr. Havrdova has received research support from the Czech Ministries of Education and Health. Dr. Zivadinov has received personal compensation for activities with Teva, Biogen Idec, EMD Serono, Novartis, Claret and Sanofi-Genzyme. Dr. Zivadinov has received research support from Biogen Idec, Teva Pharmaceuticals, Sanofi-Genzyme, Novartis and EMD Serono.