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Early predictors of disability in paediatric multiple sclerosis: evidence from a multi-national registry
Sifat Sharmin1, Charles B Malpas1,2, Izanne Roos1,2
1CORe, Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.
Insights
Later onset, higher disability, and specific symptoms in the first year predict faster disability worsening in pediatric multiple sclerosis (MS). Higher-efficacy disease-modifying therapies (DMTs) slow this progression.
Area of Science:
- Neurology
- Pediatric Neurology
- Multiple Sclerosis Research
Background:
- Early identification of disability progression markers is crucial for personalized therapy in pediatric multiple sclerosis (MS).
- Understanding predictors of rapid worsening is essential for timely intervention in children with MS.
Purpose of the Study:
- To identify early predictors of rapid disability accrual in patients with pediatric-onset MS.
- To analyze factors influencing disability worsening in young MS patients.
Main Methods:
- Utilized the global MSBase registry to identify patients with MS onset before age 18.
- Examined clinico-demographic factors including age at onset, initial disability, relapse frequency, and early neurological symptoms as predictors of MS Severity Score (MSSS).
- Employed a Bayesian log-normal generalized linear mixed model, adjusting for higher-efficacy disease-modifying therapy (DMT) use.
Main Results:
- Older age at onset, higher Expanded Disability Status Scale (EDSS) scores, and the presence of pyramidal, visual, or cerebellar symptoms within the first year were associated with increased MSSS.
- Each 24% increase in time on higher-efficacy DMTs was linked to a 4% reduction in MSSS.
- The study included 672 patients (70% female) with a median age of 16 years at symptom onset.
Conclusions:
- Later onset of MS in childhood, greater initial disability, and specific neurological symptoms in the first year are significant predictors of disability worsening.
- Consistent treatment with higher-efficacy DMTs is associated with a slower rate of disability progression in pediatric MS.
- These findings support tailored treatment strategies for children diagnosed with MS.
Background:
Early recognition of markers of faster disability worsening in paediatric-onset multiple sclerosis (MS) is a key requisite of personalised therapy for children with MS at the earliest possible time.
Objective:
To identify early predictors of rapid disability accrual in patients with paediatric-onset MS.
Methods:
Using the global MSBase registry, we identified patients who were <18 years old at the onset of MS symptoms. The clinico-demographic characteristics examined as predictors of future MS Severity Score (MSSS) included sex, age at symptom onset, absence of disability at the initial assessment, maximum Expanded Disability Status Scale (EDSS) score, relapse frequency and presence of brainstem, pyramidal, visual or cerebellar symptoms in the first year. A Bayesian log-normal generalised linear mixed model adjusted for cumulative proportion of time on higher-efficacy disease-modifying therapies (DMTs) was used to analyse the data.
Results:
672 patients (70% female) contributing 9357 visits were included. The median age at symptom onset was 16 (quartiles 15-17) years. Older age at symptom onset (exp(β)=1.10 (95% CI 1.04 to 1.17)), higher EDSS score (1.22 (1.12 to 1.34)) and pyramidal (1.31 (1.11 to 1.55)), visual (1.25 (1.10 to 1.44)) or cerebellar (1.18 (1.01 to 1.38)) symptoms in the first year were associated with higher MSSS. MSSS was reduced by 4% for every 24% increase in the proportion of time on higher-efficacy DMTs (0.96 (0.93 to 0.99)).
Conclusions:
A relatively later onset of MS in childhood, higher disability and pyramidal, visual or cerebellar symptoms during the first year predicted significant worsening in disability in patients with paediatric-onset MS. Persistent treatment with higher-efficacy DMTs was associated with a reduced rate of disability worsening.
