ObjectiveTo assess the ability of baseline MRI characteristics to predict the early development of clinically definite MS (CDMS) and combined CDMS/MRI outcomes in 190 patients with a positive MRI at the time of their first demyelinating event. Methods Based on individual and sets of baseline MRI characteristics, the authors evaluated the percentage of patients meeting outcomes of CDMS and various combined CDMS/MRI outcomes by 18 months. They also optimized a cutpoint for dichotomizing each baseline MRI characteristic and evaluated these variables using logistic regression to determine which MRI characteristics best predicted CDMS by 18 months. Results The presence of two or more gadolinium-enhancing lesions better predicted the development of CDMS and combined CDMS/MRI outcomes by 18 months than any other individual MRI characteristic or set of MRI characteristics. Among patients with two or more gadolinium-enhancing lesions, 52% developed CDMS compared with 24% of patients with fewer than two lesions. For those meeting the criteria of Barkhof et al., 32% of patients developed CDMS compared with 16% of those not meeting these criteria. Irrespective of individual or sets of criteria, however, the majority of patients developed either CDMS or demonstrated disease activity on brain MRI by 18 months. Conclusions For patients with positive MRI at the time of their initial neurologic event, both gadolinium-enhancing lesions and the Barkhof criteria are predictors for development of CDMS over a short interval. However, these results, based on a combined CDMS/MRI outcome, suggest that the majority of these patients are already in the earliest stages of MS, regardless of whether any further MRI criteria are met.

We evaluated 190 patients in the placebo group of the CHAMPS trial in order to assess factors associated with short-term clinical and brain magnetic resonance imaging (MRI) outcomes in patients with a first clinical demyelinating event involving the optic nerve, spinal cord, or brainstem/cerebellum, and subclinical demyelination on brain MRI. The two study outcomes were 1) development of clinically definite multiple sclerosis (CDMS) and 2) development of CDMS or two or more new or enlarging brain MRI T2 lesions. The presence of godolinium (Gd)-enhancing lesions on the baseline scan was the only MRI characteristic associated with a higher risk of both the clinical and combined outcomes (p=0.003 and <0.001, respectively). The only demographic or clinical characteristic associated with an increased risk of these outcomes was younger age (p<0.001 for both outcomes). The lowest risk subgroups we could define had a 30% risk of CDMS and a 65% risk of the combined clinical/MRI outcome. Our results indicate that all patients presenting with a first demyelinating event who also have brain MRI evidence of subclinical demyelination have at least a moderate risk of short-term disease activity. This finding provides support for initiating disease-modifying therapy at the time of the first demyelinating event in patients meeting the CHAMPS enrollment criteria.

PURPOSE: To evaluate the effect of treatment with interferon beta -1a (Avonex) initiated at the time of a first episode of optic neuritis in patients at high risk for multiple sclerosis (MS). DESIGN: Randomized clinical trial METHODS: Prospective. SETTING: Fifty clinical centers throughout the US and Canada. STUDY POPULATION: After the onset of a first episode of optic neuritis treated with intravenous and oral corticosteroids, 192 patients with brain magnetic resonance imaging (MRI) evidence of subclinical demyelination were randomly assigned to receive weekly intramuscular injections of 30 mug interferon beta -1a or placebo. MAIN OUTCOME MEASURE: The study outcomes were the development of clinically definite MS within 3 years of follow,up and brain MRI changes at 6, 12, and 18 months. RESULTS: The rates of clinically definite MS and of a combined MS/MRI outcome were lower in the interferon beta -1a group than in the placebo group (adjusted rate ratios 0.58, 95% confidence interval 0.34 to 1.00; and 0.50, 95% confidence interval 0.34 to 0.73, respectively). Compared with the placebo group, on the 18,month brain MRI the interferon beta -1a group had a smaller change from baseline in T2 lesion volume (P = .02), fewer new or enlarging T2 lesions (P < .001), and a lower frequency of Gd-enhancing lesions (P < .001). CONCLUSION: The clinical and brain MRI results of this trial support initiating interferon beta -1a treatment at the time of a first episode of optic neuritis occurring in patients at high risk for MS based on the presence of subclinical brain MRI lesions. (C) 2001 by Elsevier Science Inc. All rights reserved.