Early Predictors of 9‐Year Disability in Pediatric Multiple Sclerosis

Abstract

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.

Spinal cord lesions and brain grey matter atrophy independently predict clinical worsening in definite multiple sclerosis: a 5-year, multicentre study

“…Availability of 3.0T scanners and improved spinal cord MRI acquisition allowed a better cord lesion detection, resulting in increased correlations with clinical measures 33. In line with this, recent studies reported a significant predictive role of cervical cord lesions on subsequent MS disease course 5 9…”

“…In definite MS, T2-weighted5–8 and T1-weighted6 9 10 MRI brain abnormalities have been associated with more severe disability at medium-term and long-term follow-up 5–10. Conversely, only a few studies found that spinal cord lesions predicted long-term disability 5 9 11…”

“…Longitudinal work has shown that, in patients with clinically isolated syndromes, the presence, number and topography of brain and spinal cord T2-hyperintense lesions relates to the conversion to clinically definite MS and disability accumulation over the long-term. [2][3][4] In definite MS, T2-weighted [5][6][7][8] and T1-weighted 6, 9, 10 MRI brain abnormalities have been associated with more severe disability at medium-and long-term follow-up. [5][6][7][8][9][10] Conversely, only a few studies found that spinal cord lesions predicted long-term disability.…”

Multiple Sclerosis in Children: Differential Diagnosis, Prognosis, and Disease-Modifying Treatment

“…Moreover, POMS patients with the first demyelinating attack affecting the brainstem have a significantly greater risk for future disability progression (up to 5 times) when compared with patients with lesions in other CNS locations [ 27 ]. In a recent 9-year follow-up study, early treatment with high-efficacy medication resulted in a significantly longer time to a new relapse [ 28 ]. The presence of cerebellar lesions at baseline and high-efficacy medications was also associated with a lower long-term annualized relapse rate (ARR), whereas presentation of transverse myelitis was associated with a higher ARR over the follow-up [ 28 ].…”

“…In a recent 9-year follow-up study, early treatment with high-efficacy medication resulted in a significantly longer time to a new relapse [ 28 ]. The presence of cerebellar lesions at baseline and high-efficacy medications was also associated with a lower long-term annualized relapse rate (ARR), whereas presentation of transverse myelitis was associated with a higher ARR over the follow-up [ 28 ]. In terms of long-term disability outcome, the occurrence of two new T2 hyperintensities and an EDSS increase within the first 2 years of the disease were able to predict 9-year disability worsening [ 28 ].…”