MRI characteristics are predictive for CDMS in monofocal, but not in multifocal patients with a clinically isolated syndrome

Abstract

Background: To diagnose multiple sclerosis (MS), evidence for dissemination in space and time is required. There is no clear definition on how symptoms and signs of a patient indicate clinical dissemination in space. To provide a uniform approach on this subject, a clinical classification system was described recently differentiating patients with mono- and multifocal clinical presentation. Here we assess the predictive value of clinically defined dissemination in space at first presentation for time to clinically definite MS (CDMS).

Methods: Four hundred and sixty-eight patients with a first episode suggestive of MS were classified as clinically mono- or multifocal by two neurologists blinded to magnetic resonance imaging (MRI) results. These patients were part of the BENEFIT study in which 292 patients were randomized to interferon beta-1b (IFNB-1b) and 176 to placebo. By using Kaplan-Meier statistics the risk for CDMS was studied in mono- and multifocal patients of the placebo group, both with and without taking into account MRI measures of potential prognostic relevance.

Results: Time to CDMS was similar in monofocal and multifocal patients. In monofocal patients, the risk for CDMS over 2 years was significantly higher when >or= 9 T2 lesions or at least one Gd-enhancing lesion were present at the first event or 3 or 6 months after the first event. In patients with multifocal presentation, these MRI measures had no significant added value in predicting time to CDMS.

Conclusion: These data indicate that a carefully performed neurological assessment of symptoms and signs, combined with lesions on MRI, is important for defining the risk of conversion to CDMS.

Trial registration: The Benefit trial has been registered under NCT00185211 http://www.clinicaltrials.gov.

Figures

Figure 1

Time to CDMS in mono- vs multifocal placebo patients stratified by MRI findings at screening. Note the predictive value of baseline MRI findings in monofocal patients (left panels) and the absence of predictive value of MRI in multifocal patients (right panels). There was a significant interaction between mono-/multifocality and the presence of either ≥ 9 T2 hyperintense lesions (p = 0.042). CDMS: clinically definite MS.

Figure 2

Time to CDMS in mono- vs multifocal placebo patients stratified by MRI findings at month 3 and month 6. Note the significant predictive value of months 3 and 6 MRI findings in monofocal patients (left panels) and the absence of predictive value in multifocal patients (right panels). There was a significant interaction between mono-/multifocality and the presence of at least one Gd-enhancing lesion at month 3 (both p = 0.042). CDMS: clinically definite MS.