About 1 in 10 cases of multiple sclerosis (MS) arise in childhood [1]. Children with MS experience high disease activity, characterised by frequent relapses and the accumulation of brain lesions [2]. Individuals with pediatric-onset MS (POMS) typically recover quickly from attacks but cognitive impairment can still emerge as early as the first year from disease onset [3, 4]. Early therapeutic intervention is effective on disease activity also in this population and might prevent loss of brain volume, cognitive impairment, and early disability [5].
Professor Yael Hacohen, from the University College London, tells us, “MS in pediatric population is very rare. In the UK, around 250 children live with MS. Children recover from attacks very quickly and with very little disability. This, along with the fact that MS is very rare in children, can sometimes lead to a delay in diagnosis. In the beginning, blurred vision, numbness can be dismissed by parents and family doctors, who may attribute these symptoms to anxiety about exams rather than relating them to MS. However, once they undergo a magnetic resonance, it becomes clear that they have MS. In fact, even with few symptoms, children can have multiple brain lesions. Most children have positive intrathecal oligoclonal bands, and it is quite atypical not to observe periventricular lesions in this age group. There is not much difference between MS onset in individuals under 12 and those over 12. However, the time between two relapses is typically shorter in the pediatric population.”
Progressive brain damage in children
Progressive processes are present also in children with MS. Slowly expanding lesions (SELs) have been observed in pediatric onset MS, but not in children with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) [6]. Professor Giulia Fadda, from the University of Ottawa, tells us, “In a recent study, we observed a total of 70 SELs in 16 children with MS, with a median age of 14.3 years, and only 1 SEL in 14 children with MOGAD. SELs seem to be a distinctive feature of pediatric MS compared to other demyelinating conditions.”
Paramagnetic rim lesions (PRL) are also common in children with MS. Researchers detected at least one paramagnetic rim lesion in 77% of children in a small cohort of 13 participants [7].
Cortical pathology – linked to progressive mechanisms in MS – has been observed in children [8]. “Cortical lesions have been detected in children with MS across multiple studies, especially when using ultrahigh field MRI of 7 TESLA”, Professor Fadda tells us, “Furthermore, it has been shown that children with MS have smaller brain and skull sizes compared to their healthy peers. The ongoing smoldering damage in the paediatric population with MS is also evident from the consistent divergence from the expected growth of the brain, and especially of the thalamus. In contrast, children with MOGAD do not show such a linear divergence. Instead, they experience more pronounced changes shortly after an attack, followed by less noticeable changes over time [9].”
Brain volume loss, affecting both grey and white matter, and increased ventricular volume is evident already at the time of first clinical presentation [10]. Multiple sclerosis disrupts the normal development of white matter in children and leads to a progressive loss of the integrity of the tissue [11].
Treatments for the paediatric population with MS
Early treatment of children with MS with highly effective therapies is associated with a substantial reduction in the risk of first relapse sustained over 5 years, as well as better tolerance compared to moderately effective therapies [5]. Notably, after 2 years, the likelihood of stopping the treatment can be much higher with moderately than highly effective therapies, primarily due to lack of efficacy and intolerance [5]. However, long-term studies on the safety of high-efficacy treatments are still needed [5]. Children respond well to extended-interval dosing of rituximab or ocrelizumab, administered every 18 months, with no disability worsening or development of new lesion [12].
At ECTRIMS 2024, Professor Yael Hacohen highlighted the importance of extended-interval dosing to prevent the reduction of immunoglobulin levels, which can be observed in about 22% of children [13]. This condition – known as hypogammaglobulinemia – is associated with higher risk of infections (see also Strategies to mitigate infection risks in MS therapies) [14]. Immunisation is crucial strategy to prevent infections in children with MS [15]. Ideally, vaccinations should be completed before starting immunosuppressive therapies [15]. The European consensus on vaccination in people with MS proposes the best vaccination strategies in terms of timing and precautions in children with and without disease-modifying treatments [15].
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Written by Stefania de Vito
Special thanks to Professor Yael Hacohen (University College London) and Professor Giulia Fadda (University of Ottawa) for their insights.
References
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