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 will be 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. Patients will 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 will be obtained at
baseline and week 25. 7-tesla scans will be obtained at baseline and at weeks 13 and 25.
Participants with one or more centripetal/rim-enhancing lesions at the baseline scan will be
randomized and followed. Clinical evaluation and blood testing will be 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 2010 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)