Bimonthly cranial MRI activity following an isolated monosymptomatic demyelinating syndrome: potential outcome measures for future multiple sclerosis `prevention' trials

Abstract

Patients with characteristic white matter lesions on MR imaging are at increased risk for the subsequent development of clinically definite MS (CDMS) following an isolated, monosymptomatic demyelinating syndrome (IMDS). These MR positive first-onset patients are thus candidates for MS prevention trials. Seven consecutive patients with IMDS and two or more periventricular and/or oval lesions on MR imaging were enrolled into a prospective trial based on serial T2-weighted and enhanced MR imaging at two month intervals for 12-15 months. Forty-seven new enhancing lesions were detected with triple dose MR contrast compared to 31 lesions using the standard dose. Four of the seven patients accounted for 98% of all enhancing lesions in this study, while the remaining three patients showed little MRI or clinical disease activity. New T2 lesion counts correlated strongly with enhanced lesion counts (r=0.82-0.98). We detected 49 new T2-hyperintense (T2) lesions based on short-interval (2 monthly) follow-up, and 31 new T2-lesions comparing exit and entry examinations. These results suggest several potential MR-based strategies for evaluating first onset patients in a phase III MS prevention trial. Since these patients have a small average T2-lesion load, it is quite easy to visually detect new T2 lesions. As a result, at a bimonthly study interval, T2-weighted lesion analysis is an effective measure of cumulative disease activity, provided high-resolution T2-weighted imaging studies are acquired to quantitate new T2-lesions. Enhanced lesion activity remains an important measure of blood-brain-barrier breakdown and may predict short term MRI and clinical disease activity in IMDS patients.

Keywords

magnetic resonance imaging multiple sclerosis optic neuritis partial transverse myelitis brainstem syndrome contrast media

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