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Updated: Jun 19, 2025
Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla
Published on: February 19, 2021
Smouldering-Associated Worsening in Multiple Sclerosis: An International Consensus Statement on Definition, Biology,
Antonio Scalfari1, Anthony Traboulsee2, Jiwon Oh3
1Center of Neuroscience, Department of Medicine, Charing Cross Hospital, Imperial College, London, UK.
Abstract:
Despite therapeutic suppression of relapses, multiple sclerosis (MS) patients often experience subtle deterioration, which extends beyond the definition of "progression independent of relapsing activity." We propose the concept of smouldering-associated-worsening (SAW), encompassing physical and cognitive symptoms, resulting from smouldering pathological processes, which remain unmet therapeutic targets. We provide a consensus-based framework of possible pathological substrates and manifestations of smouldering MS, and we discuss clinical, radiological, and serum/cerebrospinal fluid biomarkers for potentially monitoring SAW. Finally, we share considerations for optimizing disease surveillance and implications for clinical trials to promote the integration of smouldering MS into routine practice and future research efforts. ANN NEUROL 2024;96:826-845.
Insights
Multiple sclerosis patients face subtle worsening despite relapse treatment. We introduce smouldering-associated worsening (SAW), driven by persistent pathology, and propose biomarkers for monitoring this condition.
Area of Science:
- Neurology
- Neuroimmunology
- Pathology
Background:
- Multiple sclerosis (MS) patients often experience gradual deterioration beyond relapse activity.
- Current treatments primarily target relapses, leaving underlying smoldering pathology unaddressed.
Purpose of the Study:
- Introduce the concept of smouldering-associated worsening (SAW) in MS.
- Define pathological substrates and clinical/radiological manifestations of smoldering MS.
- Discuss biomarkers for monitoring SAW and implications for clinical practice.
Main Methods:
- Consensus-based framework development.
- Review of clinical, radiological, and fluid biomarkers.
- Analysis of disease surveillance and clinical trial considerations.
Main Results:
- Smouldering MS involves persistent pathological processes contributing to physical and cognitive decline.
- SAW represents a distinct clinical entity beyond progression independent of relapse activity.
- Potential biomarkers identified for monitoring smouldering MS activity.
Conclusions:
- SAW is a critical, unmet therapeutic challenge in multiple sclerosis.
- Integrating SAW into routine practice and research is essential for improved patient outcomes.
- Further research and clinical trials are needed to target smouldering pathology.
