[P03.071] Natalizumab (Tysabri) Promotes Remyelination in Patients with Multiple Sclerosis. A Voxel-Wise Magnetization Transfer Imaging Case-Control Study

Robert Zivadinov, Michael G. Dwyer, Niels Bergsland, Sara Hussein, Jennifer Cox, Jacqueline Durfee, Navdeep Nayyar, David Hojnacki, Komal Hashmi, Mari Heininen-Brown, Lynn Choufeh, Ellen Carl, Bianca Weinstock-Guttman, Buffalo, NY

OBJECTIVE: To define the effect of natalizumab monotherapy on a voxel-wise (VW) basis using magnetization transfer ratio (MTR) dynamic mapping of lesions and normal appearing brain tissue (NABT) in relapsing multiple sclerosis (MS), including relapsing- remitting (RRMS) and relapsing secondary progressive (RSPMS) patients. BACKGROUND: VWMTR method reveals focal demyelination and remyelination in-vivo and can be a powerful instrument to monitor disease activity and effectiveness of therapeutic interventions in patients with MS. DESIGN/METHODS: 41 RRMS and 21 RSPMS patients who started natalizumab monotherapy, and 22 age- and sex-matched normal controls (NC) were enrolled and followed for 12 months with 1.5T MRI and clinical examinations. Mean age was 44.2 years, mean disease duration 14.5 years and mean EDSS 4.0. For each subject, baseline and follow-up MTR volume maps were placed in a common halfway-space. The resulting VW subtraction map was then enhanced via threshold-free cluster enhancement (TFCE) algorithm, and a significance threshold was determined based on subject-specific Monte Carlo simulation. Supra-threshold volumes (95^th percentile) were quantified for both areas of increasing (remyelinating) and decreasing (demyelinating) MTR voxels. RESULTS: The increasing NABT VWMTR was significantly higher in natalizumab treated MS patients than in NC (3299.3 vs 2801.1mm³, p<0.001), whereas there was no significant difference in decreasing VWMTR (7132.3 vs 1909.9 mm³) over the follow-up between the 2 groups. RRMS patients showed higher increasing (4844.7 vs 517.4 mm³) and lower decreasing (5632.5 vs 9832 mm³) NABT VWMTR then the RSPMS. The decreasing VWMTR of T2-lesion volume (LV), T1-LV and Gadolinium LV was not significantly higher than the increasing one in both RR and RSPMS groups. The T2-LV, T1-LV and Gd-LV significantly improved over follow-up (p<0.003). The EDSS remained stable. CONCLUSIONS/RELEVANCE: Natalizumab promoted remyelination and stabilized demyelination both in lesions and NABT. The VWMTR method is a robust technique for quantifying remyelination effect of DMT. Supported by: This study was funded by a grant from Biogen Idec.
Category - MS and Related Diseases - Clinical Science

Tuesday, April 28, 2009 4:00 PM

Poster Session III: Multiple Sclerosis: Imaging (4:00 PM-7:00 PM)