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.

• INCLUSION CRITERIA:
• Multiple sclerosis, as defined by the 2017 Revised McDonald Criteria;
• Age 18 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 MRI-compatible 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, only if required per current NIH Clinical Center guidelines for kidney-function screening before gadolinium-based MRI contrast, 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)