Effect of Corticosteroids on Inflammation at the Edge of Acute Multiple Sclerosis Plaques

Objectives: The primary aim of this pilot study is to assess the effects of short-term, high-dose corticosteroid administration on the 12-week evolution of multiple sclerosis lesions with centripetal enhancement pattern on magnetic resonance imaging (MRI), in particular with respect to the development of a hypointense rim on 7-tesla phase images. In our prior work, the phase rim has been associated with persistent deleterious inflammation with poor repair and ongoing neurodegeneration within lesions. Study population: Up to 30 multiple sclerosis patients with asymptomatic contrast-enhancing lesions will be enrolled. Patients are randomly assigned to either 3 days of corticosteroids (intravenous methylprednisolone at 1000 mg/day or oral prednisone at 1250 mg/day) or to no treatment. Design: This is a single-site study.Patients undergo serial brain MRIs with gadolinium-based contrast agent on both 3- and 7-tesla scanners over an approximate 25-week period. 3-tesla scans are obtained at baseline and week 25. 7-tesla scans are obtained at baseline and at weeks 13 and 25. Participants with one or more centripetal/rim-enhancing lesions at the baseline scan are randomized and followed. Clinical evaluation and blood testing are performed at baseline and weeks 13 and 25. Outcome measures: The primary outcome measure is the presence or absence, on the week-13 7-tesla scan, of a hypointense phase rim in each of the lesions followed over time. Secondary outcome measures include the presence or absence of a hypointense phase rim at week 25, as well as the lesion volume and intralesional median R1 relaxation rate at weeks 13 and 25. From 3-tesla scans, we will measure the change in normalized intralesional proton density-weighted and T1-weighted signal, as well as the R1 relaxation rate, between baseline and week 25. We will also assess for the presence or absence of a hypointense phase at 3T. Additional exploratory outcome measures, including clinical and immunological assessments, will also be collected.