Smouldering disease in paediatric-onset multiple sclerosis.

Abstract

Smouldering disease in multiple sclerosis (MS) refers to chronic central nervous system processes that occur beyond acute inflammation, driving long-term disability. Although current therapies effectively reduce relapse rates and MRI lesions, many individuals experience progression independent of relapse activity. While clinical progression is uncommon during childhood or adolescence, growing evidence suggests that subclinical progressive disease biology is already active even in this young age group, warranting early intervention to preserve function. Conventional MRI, while critical for diagnosis, lacks sensitivity for subtle damage. Advanced MRI techniques, including detection of chronic active lesions, global and focal brain damage, hold promise for early identification. Fluid biomarkers, such as neurofilament light chain and glial fibrillary acidic protein, provide non-invasive measures of neuroaxonal injury and ongoing chronic inflammation. This review summarises the role of MRI and fluid biomarkers in detecting smouldering disease in paediatric-onset MS and their application in supporting therapeutic decision-making.