Abstract Details

We aim to demonstrate a quantifiable reduction in intensity in rim+ lesions on QSM when comparing chronic active lesions at the time of initiation and one year post-treatment with ocrelizumab.

Chronic active multiple sclerosis (MS) lesions are characterized by an iron-laden rim of pro-inflammatory microglia and macrophages. Quantitative susceptibility mapping (QSM) allows for accurate quantification of iron deposition in the brain, and identifies chronic active lesions with a hyperintense rim. Ocrelizumab is a monoclonal antibody that depletes CD20+ B cells in the periphery and has a therapeutic benefit in both relapsing remitting and primary progressive MS. However, its impact on CNS inflammation in MS has yet to be fully determined.

Patients starting treatment with ocrelizumab who had MRI sequences at initiation of and at 12 months post-ocrelizumab showing lesions with a hyperintense rim on QSM (rim+) were included and were referenced to adjacent normal appearing white matter. Change in susceptibility values on QSM pre and post treatment was evaluated in both rim+ and rim- lesions.

Twelve patients (10 RRMS, 1 PPMS, 1 SPMS) with mean EDSS 3.33 +/- 1.89 were selected. Twenty-nine lesions (17%) were rim+ and the remaining 140 were solidly hyperintense or isointense on QSM.  Susceptibility in rim+ (6.04 ppb) lesions was significantly higher that rim- (-16.73 ppb) lesions, p=<0.0001. During the year prior to treatment, susceptibility was stable for rim+ (1.49 +/- 11.08, p=0.47) with a slight increase in rim- (1.8, p=0.038) lesions. After one year of treatment, susceptibility decreased in both rim+ (-6.67, +/- 9.9, p=0.0011) rim- (-5.546 +/-16.46, p=0.0001) lesions. Reduction was greater in rim+ lesions, but did not reach significance, p=0.88. 

In this preliminary analysis, we demonstrate a potential treatment effect of ocrelizumab on chronic active lesions. Although limited by sample size, we plan to expand this analysis to establish the potential therapeutic benefit.