Understanding Smoldering Disease in MS Beyond Focal Inflammatory Activity: Antonio Scalfari, MD, PhD

WATCH TIME: 4 minutes

“Smoldering disease activity goes beyond relapses and focal inflammatory lesions, affecting cognitive, psychiatric, and other non-motor functions, thus requiring a broader diagnostic approach.”

Recent studies showed that progression independent of relapse activity (PIRA) begins in the early relapsing–remitting phase of multiple sclerosis (MS), suggesting that the disease is driven by a biological continuum with intertwined pathological mechanisms from disease onset. However, research also reveals that PIRA, which is primarily assessed through motor performance scales, often misses subtle symptoms in other clinical areas. These clinical insights point to a paradigm shift in understanding the central nervous system mechanisms that contribute to MS worsening.

Researchers suggest that the gradual buildup of disability in MS is fueled by smoldering pathological processes, which remains an unmet therapeutic target. Recently published in Annals of Neurology, a group of experts proposed the concept of smoldering-associated-worsening (SAW), encompassing physical and cognitive symptoms of the disease.¹ The experts provided a consensus-based framework of smoldering MS and discussed biomarkers for potentially monitoring SAW. In addition, the experts shared considerations for promoting the integration of smoldering MS into the clinical practice and research in the future.

One of the experts that contributed to the published consensus paper, lead author Antonio Scalfari, MD, PhD, a consultant neurologist at Imperial College Healthcare Trust and Northwest London Healthcare Trust, recently sat down with NeurologyLive^® to discuss how the concept of smoldering disease expands the understanding of MS progression. Scalfari, who also serves as an honorary senior clinical lecturer at Imperial College London, talked about why the traditional focus was on motor impairment limiting when diagnosing disease worsening in MS in reference to the consensus paper. Furthermore, he spoke about the potential benefits of recognizing non-motor symptoms like cognitive decline and depression in MS management.

REFERENCES
1. Scalfari A, Traboulsee A, Oh J, et al. Smouldering-Associated Worsening in Multiple Sclerosis: An International Consensus Statement on Definition, Biology, Clinical Implications, and Future Directions. Ann Neurol. Published online July 25, 2024. doi:10.1002/ana.27034