Early Clinical and MRI Predictors of Time to Second Attack and Disability in Children with Acute Demyelinating Syndromes: Findings from a Prospective National Cohort Study (S54.007)

BACKGROUND: Early predictors of outcome in children with multiple sclerosis (MS) have implications for clinical care and for identifying eligible children for clinical trials. OBJECTIVE: To determine clinical and MRI predictors of disability and time to second attack at onset in children with MS. METHOD: Children younger than 16 years of age with an acute demyelinating syndrome (ADS) were enrolled at 23 sites into a national prospective study. Standardized clinical and MRI data were acquired at onset, 3, 6, and 12 months and annually after onset for 9 years. Children were diagnosed with MS according to McDonald criteria. Age at ADS onset, gender, date of second attack, Expanded Disability Status Scale (EDSS) score at most recent visit, and relapse count were extracted from the database. Baseline and serial MRI scans were evaluated using a standardized scoring tool. Clinical and MRI parameters that predict time to second attack and EDSS score were evaluated using Cox proportional hazards and linear regression models. RESULTS: Of 302 eligible children, 74 (26%) have been diagnosed with MS (mean observation: 3.9±2.2 years, range: 0.04-8.1 years; 26 (65%) female). Mean annualized relapse rate was 0.9±1.0 (mean total relapses: 2.0± 1.0). The presence of 蠅1 persisting T1-hypointense lesion and 蠅1 periventricular lesion at onset predicted time to second attack (HR 2.8, 95% confidence interval 1.1-7.1). EDSS score at most recent visit was not associated with relapse count in the first 1 or 2 years after onset, but was correlated with total relapses (r=0.34, p=0.001), and to an even greater degree for those children followed 蠅4 years (r=0.44, p=0.001). EDSS was associated with new T2 lesion count over the first year following ADS (r=0.38, p=0.04). CONCLUSION: Specific MRI parameters present at onset are associated with time to second attack and disability in children with MS. Study Supported by: Canadian Multiple Sclerosis Scientific Research Foundation Disclosure: Dr. Verhey has received research support from the Canadian Institutes of Health, and the Multiple Sclerosis Society of Canada. Dr. Marrie has received research support from the Canadian Institutes of Health Research, Multiple Sclerosis Society of Canada, Consortium of MS Centers, and Sanofi-Aventis Pharmaceuticals, Inc. Dr. Bar-Or has received personal compensation for activities with Amplimmune, Aventis, Bayhill Therapeutics, Berlex/Bayer, Biogen Idec, BioMS, Diogenix, Eli Lilly & Company, EMD Serono, Genentech, Inc., Genzyme, GlaxoSmithKline, Inc., Guthy-Jackson/GGF, Medimmune, Mitsubishi Pharma, Novartis, Ono Pharma, Receptos, Roche, Sanofi-Aventis Pharmaceuticals, Inc., Teva Neuroscience, and Wyeth Pharmaceuticals. Dr. Bar-Or has received research support from Amplimmune, EMD Serono, and Novartis. Dr. Sadovnick has received personal compensation for activities with Biogen Idec, Merck Serono, Teva Neuroscience, and Bayer Pharmaceuticals Corp. Dr. Shroff has nothing to disclose. Dr. Arnold has received personal compensation for activities with Acorda Therapeutics, Bayer Pharmaceuticals Corporation, Biogen Idec, Coronado Biosciences, EMD Serono, Genentech Inc., Genzyme Corporation, GlaxoSmithKline Inc., MedImmune, NeuroRx Research. Dr. Arnold has received research support from Bayer Pharmaceuticals Corporation. Dr. Banwell has received personal compensation in an editorial capacity for Multiple Sclerosis and Related Disorders. Dr. Banwell9s institution has received research support from the Multiple Sclerosis Society of Canada, the Canadian Multiple Sclerosis Scientific Research Foundation, and Canadian Institute of Health Research.