Baseline cerebellar volume as short-term predictor of clinical disability in Multiple Sclerosis: MRI Findings from the CombiRx trial (S6.005)

Objective: To investigate whether cerebellar volume is a predictor of short-term disability in patients with relapsing-remitting multiple sclerosis (RRMS). Background: The cerebellum is a predilection site of demyelination in MS and cerebellar atrophy is a strong contributor of clinical impairment. Cerebellar volume loss over one-year has been reported as predictor of disease worsening in progressive MS patients. However, the predictive role of baseline cerebellar volume as short-term predictor of disability has never been tested in a large group of MS patients. Design/Methods: MRI data from the first 100 of 1,008 RRMS patients who participated in the multi-center, randomized, phase III CombiRx Trial were analyzed. All patients were under immuno-modulatory treatment with either glatiramer acetate (n=26), interferon β-1a (n=24) or glatiramer acetate+interferon β-1a (n=50). On the baseline MRI scans, whole brain T2 and Gd-enhancing lesion number where obtained using MRIAP, while grey matter fraction (GMF) and cerebellar volume were measured using SPM12. Clinical measures included the Multiple Sclerosis Functional Composite (MSFC), evaluated at baseline and 6 month follow-up evaluations. A hierarchical multiple linear regression analysis was performed to assess the relationship among baseline T2 hyperintense and Gd-enhancing lesion number, GMF, cerebellar GM volume and clinical disability at baseline and follow-up, adjusted for age, gender and disease duration. Results: The regression model including T2 and Gd-enhancing lesion number, GMF and cerebellar GM volume, significantly correlated with the clinical impairment at baseline (R 2 =0.20, p=0.001), and predicted subsequent impairment at 6 months (R 2 =0.25, p Conclusions: These preliminary results suggest that cerebellar volume is an independent predictor of short-term clinical disability in MS patients as measured by MSFC. The study is ongoing and results from the entire trial population will be presented. Study Supported by: TheCombiRx trial was supported by NINDS/NIH grant # U01 NS045719. Disclosure: Dr. Petracca has nothing to disclose. Dr. Cocozza has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi Genzyme. Dr. Freeman has nothing to disclose. Dr. Kangarlu has nothing to disclose. Dr. Droby has nothing to disclose. Dr. Krieger has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with acorda, bayer, biogen, emd serono, genentech, genzyme, mallinckrodt, medday, novartis, teva, and tg therapeutics . Dr. Cutter has nothing to disclose. Dr. Wolinsky has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with has served on advisory boards and data monitoring or steering committees, has held consulting agreements or has received speaker honoraria from AbbVie, Alkermes, Biogen, Bionest, Clene Nanomedicine, EMD Serono, Forward Pharma, MedDay, Pharmaceuticals, Nov. Dr. Wolinsky has received royalty, license fees, or contractual rights payments from royalties for monoclonal antibodies out-licensed to Chemicon International through UTHealth. Dr. Lublin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting and advisory boards: Bayer HealthCare Pharmaceuticals; Biogen Idec; EMD Serono; Novartis; Teva; Actelion; Sanofi/Genzyme; Acorda; F. Hoffmann-La Roche/Genentech; MedImmune; Receptos/Celgene; Forward Pharma; Akros; TG Therapeutics; Abbvie; Rege. Dr. Lublin has received personal compensation in an editorial capacity for Co-Chief Editor of Multiple Sclerosis and Related Disorders. Dr. Lublin has received research support from Research funding from: Biogen Idec; Novartis Pharmaceuticals Corp; Teva Neuroscience, Inc.; Genzyme; Sanofi; Celgene; Transparency Life Sciences; NIH; NMSS. Dr. Inglese has nothing to disclose.