Paediatric multiple sclerosis: a new era in diagnosis and treatment

Abstract

Multiple sclerosis is a chronic immune‐mediated demyelinating disease of the central nervous system. The diagnosis of multiple sclerosis in children, as in adults, requires evidence of dissemination of inflammatory activity in more than one location in the central nervous system (dissemination in space) and recurrent disease over time (dissemination in time). The identification of myelin oligodendrocyte glycoprotein antibodies (MOG‐Ab) and aquaporin‐A antibodies (AQP4‐Ab), and the subsequent discovery of their pathogenic mechanisms, have led to a shift in the classification of relapsing demyelinating syndromes. This is reflected in the 2017 revised criteria for the diagnosis of multiple sclerosis, which emphasizes the exclusion of multiple sclerosis mimics and aims to enable earlier diagnosis and thus treatment initiation. The long‐term efficacy of individual therapies initiated in children with multiple sclerosis is hard to evaluate, owing to the small numbers of patients who have the disease, the relatively high number of patients who switch therapy, and the need for long follow‐up studies. Nevertheless, an improvement in prognosis with a globally reduced annual relapse rate in children with multiple sclerosis is now observed compared with the pretreatment era, indicating a possible long‐term effect of therapies. Given the higher relapse rate in children compared with adults, and the impact multiple sclerosis has on cognition in the developing brain, there is a question whether rapid escalation or potent agents should be used in children, while the short‐ and long‐term safety profiles of these drugs are being established. With the results of the first randomized controlled trial of fingolimod versus interferon‐β1a in paediatric multiple sclerosis published in 2018 and several clinical trials underway, there is hope for further progress in the field of paediatric multiple sclerosis. What this paper adds Early and accurate diagnosis of multiple sclerosis is crucial. The discovery of antibody‐mediated demyelination has changed the diagnosis and management of relapsing demyelination syndromes. Traditional escalation therapy is being challenged by induction therapy.

Paediatric multiple sclerosis and antibody-associated demyelination: clinical, imaging, and biological considerations for diagnosis and care

“…Supplementary Figure 1 outlines the timeline, approved doses (largely approved for adults) and summarizes the presumed mechanisms of action for currently available disease modifying therapies (DMTs) for MS and AQP4-NMOSD. Several recent comprehensive reviews of therapeutic strategies are available for pediatric MS 70,71 and AQP4-NMOSD 37 , and while treatment reviews are not yet available for MOGAD, a recent international survey summarizes current considerations 64,72 .…”

Use of Disease-Modifying Therapies in Pediatric Relapsing-Remitting Multiple Sclerosis in the United Kingdom

“…6 The approach to treatment of relapsing-remitting multiple sclerosis (RRMS) is rapidly evolving, with 15 disease-modifying therapies (DMTs) currently licensed for adults, that target the immune system peripherally and reduce MS relapse risk. 7 These range from injectables (interferon-β and glatiramer acetate), with favorable side effect profiles but moderate clinical efficacy, to newer oral or infusion DMTs, associated with greater treatment efficacy, but a higher risk profile. 8 Current treatment strategies in pediatric MS are largely center specific and reliant on adult protocols; there is a clear need to balance the risk of undertreating children causing poor disease control and accrual of motor, visual, and cognitive disabilities or overtreating them, particularly with sequential immunotherapy, exposing the child to unnecessary toxic effects, which may include reduced fertility, malignancy risks, and premature immune senescence.…”

Cognitive Assessment and Rehabilitation for Pediatric-Onset Multiple Sclerosis: A Scoping Review

“…Cognitive issues in pediatric MS have become a research priority in this field, and more studies surrounding cognitive evaluation for these patients were published over the past decade. Although routine cognitive screening is recommended for pediatric MS [ 26 ], and cognition has been incorporated into disease activity measure and treatment consideration [ 5 , 27 , 28 ], the best assessment tools for pediatric MS remain to be determined. Findings yielded by commonly used tools were sometimes discrepant across studies.…”