Early Predictors of 9-Year Disability in Pediatric Multiple Sclerosis

Ermelinda De Meo, Raffaello Bonacchi, Lucia Moiola, Bruno Colombo, Francesca Sangalli, Chiara Zanetta, Maria Pia Amato, Vittorio Martinelli, Maria Assunta Rocca, Massimo Filippi
Annals of Neurology 2021, 89 (5): 1011-1022

OBJECTIVE: The purpose of this study was to assess early predictors of 9-year disability in pediatric patients with multiple sclerosis.

METHODS: Clinical and magnetic resonance imaging (MRI) assessments of 123 pediatric patients with multiple sclerosis were obtained at disease onset and after 1 and 2 years. A 9-year clinical follow-up was also performed. Cox proportional hazard and multivariable regression models were used to assess independent predictors of time to first relapse and 9-year outcomes.

RESULTS: Time to first relapse was predicted by optic nerve lesions (hazard ratio [HR] = 2.10, p = 0.02) and high-efficacy treatment exposure (HR = 0.31, p = 0.005). Predictors of annualized relapse rate were: at baseline, presence of cerebellar (β = -0.15, p < 0.001), cervical cord lesions (β = 0.16, p = 0.003), and high-efficacy treatment exposure (β = -0.14, p = 0.01); considering also 1-year variables, number of relapses (β = 0.14, p = 0.002), and the previous baseline predictors; considering 2-year variables, time to first relapse (2-year: β = -0.12, p = 0.01) entered, whereas high-efficacy treatment exposure exited the model. Predictors of 9-year disability worsening were: at baseline, presence of optic nerve lesions (odds ratio [OR] = 6.45, p = 0.01); considering 1-year and 2-year variables, Expanded Disability Status Scale (EDSS) changes (1-year: OR = 26.05, p < 0.001; 2-year: OR = 16.38, p = 0.02), and ≥ 2 new T2-lesions in 2 years (2-year: OR = 4.91, p = 0.02). Predictors of higher 9-year EDSS score were: at baseline, EDSS score (β = 0.58, p < 0.001), presence of brainstem lesions (β = 0.31, p = 0.04), and number of cervical cord lesions (β = 0.22, p = 0.05); considering 1-year and 2-year variables, EDSS changes (1-year: β = 0.79, p < 0.001; 2-year: β = 0.55, p < 0.001), and ≥ 2 new T2-lesions (1-year: β = 0.28, p = 0.03; 2-year: β = 0.35, p = 0.01).

INTERPRETATION: A complete baseline MRI assessment and an accurate clinical and MRI monitoring during the first 2 years of disease contribute to predict 9-year prognosis in pediatric patients with multiple sclerosis. ANN NEUROL 2021;89:1011-1022.

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