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Magnetic Resonance Imaging Predictors of Conversion to Multiple Sclerosis in the BENEFIT Study
Bastiaan Moraal, MD;
Christoph Pohl, MD;
Bernard M. J. Uitdehaag, MD, PhD;
Chris H. Polman, MD, PhD;
Gilles Edan, MD;
Mark S. Freedman, MD;
Hans-Peter Hartung, MD;
Ludwig Kappos, MD;
David H. Miller, MD;
Xavier Montalban, MD;
Vivian Lanius, PhD;
Rupert Sandbrink, MD, PhD;
Frederik Barkhof, MD, PhD
Arch Neurol. 2009;66(11):1345-1352.
Background Several studies have confirmed the predictive value of baseline and follow-up magnetic resonance (MR) imaging variables for conversion to clinically definite multiple sclerosis (CDMS), depending on the population, follow-up duration, and treatment intervention. However, the timing of follow-up imaging and the effect of treatment intervention on the predictive value of baseline MR imaging variables require further elucidation.
Objectives To assess the prognostic value of baseline MR imaging variables for conversion to CDMS over 3 years and whether this was affected by treatment intervention and (2) to assess the increased risk for conversion posed by dissemination in time on follow-up MR imaging.
Design Cohort study.
Setting Multicenter randomized clinical trial.
Patients Four hundred sixty-eight patients with a clinically isolated syndrome who had an initial clinical demyelinating event within the past 60 days who received early treatment (3 years of interferon beta-1b) or delayed treatment (placebo first, followed by  1 year of interferon beta-1b).
Intervention Magnetic resonance imaging.
Main Outcome Measure Time to CDMS.
Results The overall conversion rate to CDMS was 42%. Barkhof criteria with the strongest prognostic value were the presence at baseline of at least 9 T2-weighted lesions (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.15-2.33; P = .006) and at least 3 periventricular lesions (1.66; 1.14-2.41; P = .009). No specific advantage was noted in using a fixed cutoff of at least 3 Barkhof criteria (HR, 1.31; 95% CI, 0.95-1.79; P = .10). The prognostic value of all MR imaging criteria was unaffected by treatment intervention (P .20 for all). Dissemination in time resulted in increased risk for CDMS only in patients without dissemination in space at baseline and was most informative at the 9-month MR imaging (HR, 2.72; 95% CI, 1.26-5.87; P = .01).
Conclusions The modified Barkhof criteria showed moderate predictive value for conversion to CDMS, although all patients had received interferon beta-1b therapy for at least 1 year. The predictive value was unaffected by treatment intervention. Follow-up MR imaging was most informative after 9 months in patients without dissemination in space at baseline.
Author Affiliations: Departments of Diagnostic Radiology (Drs Moraal and Barkhof), Clinical Epidemiology and Biostatistics (Dr Uitdehaag), and Neurology (Drs Uitdehaag and Polman), Multiple Sclerosis Center Amsterdam, Vrije University Medical Center, Amsterdam, the Netherlands; Bayer Schering Pharma AG, Berlin (Drs Pohl, Lanius, and Sandbrink), Department of Neurology, University Hospital of Bonn, Bonn (Dr Pohl), and Heinrich-Heine University, Düsseldorf (Drs Hartung and Sandbrink), Germany; Department of Neurology, Centre Hospitalier Universitaire, Rennes, France (Dr Edan); Multiple Sclerosis Research Unit, The Ottawa Hospital, Ottawa, Ontario, Canada (Dr Freedman); Departments of Neurology and Neurosurgery, University Hospital Basel, Basel, Switzerland (Dr Kappos); Institute of Neurology, University College London, London, England (Dr Miller); and Unit of Clinica Neuroimmunology, Hospital Vall d’Hebron, Barcelona, Spain (Dr Montalban).
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