The landscape of paediatric multiple sclerosis (MS) is rapidly evolving. In her presentation titled ‘Pediatric MS – Current treatment strategies and future directions’ at the MS State of the Art Symposium, Prof. Dr Brenda Banwell from the University of Pennsylvania discussed the clinical features and diagnostic criteria used to identify MS in children and what the future directions in terms of therapies in paediatric MS were.1
About 70% of children with an acute demyelinating syndrome will have a single event, whereas 30% will have the first attack of a chronic illness.2 Prof. Banwell discussed the results from her study which showed that the features most strongly associated with confirming an MS diagnosis were the presence of a so-called black hole at first attack, lesions perpendicular to the long axis of the corpus callosum (Dawson’s fingers), contrast enhancing lesions and periventricular lesions. The McDonald criteria used in the diagnosis on MS appear to apply in the paediatric population as well.2,3 Further investigations were performed in understanding what might help confirm an MS diagnosis, based on the first attack. At least one ventricular lesion and one black hole were strong indicators. The presence of both conveyed an 80 percent probability that the child was manifesting with multiple sclerosis, based on the MRI of the first attack.2
Brain changes in paediatric MS
The progression of MS in the paediatric population varies quite strongly from its adult counterpart. Prof. Banwell presented the case study of a 12-year-old who displayed considerable loss of brain volume over a span of two years, which in adults could take a decade or more.1 MS is thought of as a disease driven by perivenular inflammation, leading to focal lesions with loss of myelin and subsequently, a loss of axonal neuronal integrity. However, Prof. Banwell challenged this view and proposed that, at least in a sizeable proportion of the MS population, it is not a consequence of the inflammation, but of tissue injury driven by (as yet) unknown factors, which then leads to the focal pathology that incites an inflammatory response. The importance of thinking of neuroprotection as early as possible, because of the strong effect that MS has on brain health, becomes particularly significant in this context. The inner skull volume in a paediatric MS patient was already below normal at the time of the first attack, raising the possibility that the subclinical phase possibly started years before.4
Therapies for the paediatric population
Previously, first line therapies like interferon or glatiramer acetate were initially used in the treatment of paediatric MS. Patients would switch back and forth if needed, and higher potency therapies were used only if these failed, i.e., if there was evidence of ongoing relapses and new disease.1 However recent studies have indicated that patients using highly effective therapies have better outcomes. The results of the PARADIGMS study showed an 82 percent reduction in relapses in the fingolimod group, compared to interferon beta 1A. All the imaging metrics were met, so the patients had fewer new lesions and were less likely to acquire gadolinium enhancing lesions. In addition to this, the rate of brain volume loss over the course of the almost two-year study was considerably less in the patients provided fingolimod versus interferon.5
MS therapies are changing with increasing access to highly effective therapies. As opposed to an ‘escalate when treatment fails’ approach, paediatric MS care is now switching to a ‘treat quickly and effectively’ paradigm. Early and effective therapy holds great promise in trying to mitigate against physical disability, and to improve cognitive outcomes and quality of life.
Read more MS State of the Art Symposium 2022 coverage by following this link.
- Banwell, B. Pediatric MS – Current treatment strategies and future directions. Presented at MS State of the Art Symposium, 31 January 2022.
- Fadda G et al. Lancet Child Adolesc Health 2018; 2(3):191–204.
- Thompspn AJ et al. Lancet 2018 ; 17(2) :162–173
- Longoni G et al. Brain 2017;140 :1300–1315
- Chitnis T et al. N Engl J Med 2018;379 :1017–1027