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Smouldering disease in paediatric-onset multiple sclerosis.

Massimo Filippi1, Monica Margoni2, Brenda Banwell3

  • 1Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy; Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Ebiomedicine
|September 12, 2025
PubMed
Summary

Smouldering disease in paediatric multiple sclerosis (MS) shows early subclinical activity. Advanced MRI and fluid biomarkers can detect this chronic damage, guiding early intervention to preserve function.

Keywords:
Chronic active lesionsConfirmed disability accrualFluid biomarkersGrey matterMRINeurofilamentsPaediatric-onset multiple sclerosisProgression independent of relapse activityRepairSmouldering diseaseSpinal cordTreatment

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Area of Science:

  • Neurology
  • Neuroimmunology
  • Radiology

Background:

  • Smouldering disease in multiple sclerosis (MS) involves chronic central nervous system processes contributing to long-term disability.
  • While current MS therapies manage acute inflammation and lesions, many patients experience progression unrelated to relapses.
  • Subclinical smouldering disease biology is active even in paediatric-onset MS, necessitating early intervention.

Purpose of the Study:

  • To review the role of MRI and fluid biomarkers in detecting smouldering disease in paediatric-onset MS.
  • To discuss the application of these detection methods in therapeutic decision-making for young MS patients.

Main Methods:

  • Review of advanced Magnetic Resonance Imaging (MRI) techniques for detecting chronic active lesions and subtle brain damage.
  • Analysis of fluid biomarkers, including neurofilament light chain and glial fibrillary acidic protein, as indicators of neuroaxonal injury and inflammation.

Main Results:

  • Conventional MRI has limitations in detecting subtle, smouldering damage in MS.
  • Advanced MRI techniques offer improved sensitivity for identifying chronic active lesions and overall brain damage.
  • Fluid biomarkers provide non-invasive measures of ongoing neuroaxonal damage and inflammation.

Conclusions:

  • Advanced MRI and fluid biomarkers are crucial for detecting subclinical smouldering disease in paediatric MS.
  • Early identification of smouldering disease is essential for timely therapeutic intervention to preserve neurological function.
  • These tools can support informed therapeutic decisions in managing paediatric-onset MS.