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 a 1000 mg/day or oral prednisone at 1250mg/day) or to no treatment. Design. This is a multi-site study with Johns Hopkins University. Some analysis of identifiable data will be conducted at Johns Hopkins University JHU under a reliance agreement. Patients will not be consented to the study or participate in study interventions/procedures at JHU. 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.
- INCLUSION CRITERIA: - Multiple sclerosis, as defined by the 2017 Revised McDonald Criteria; - Age 25 or older; - Ability to provide informed consent; - Able to participate in study procedures and provide high-quality clinical research and imaging data, based on limited artifacts on prior MRI scans and, when possible to determine; - Presence of a gadolinium enhancing lesion on the screening (3T or 7T) brain MRI that demonstrates either centripetal/rim enhancement or a phase rim, or both; - Simultaneously participates in another screening or natural history protocol within the NINDS Neuroimmunology Clinic at the time of study entry. - Willing to use birth control if able to conceive a child EXCLUSION CRITERIA: - Medical contraindications for MRI (e.g., any non organic implant or other device such as a cardiac pacemaker or infusion pump or other metallic implants, objects, or body piercings that are not MRIcompatible or cannot be removed); - Psychological contraindications for MRI (e.g., claustrophobia), to be assessed at the time the medical history is collected; - Treatment with systemic steroids in previous 30 days (non-systemic administration of steroids, such as topical or local injection, is acceptable); - Experiencing new neurological symptoms, with onset in previous 2 weeks, attributable to MS relapse; - Pregnancy or current breastfeeding; - Screening labs demonstrating estimated glomerular filtration rate <60 mL/min; - Known hypersensitivity to gadolinium-based contrast agents; - Medical contraindications to corticosteroid administration (e.g., diabetes, gastric ulcer)