MS progression involves complex mechanisms that contribute to increasing disability over time. Through extensive longitudinal studies spanning over a decade, our research has revealed that the expansion of existing brain lesions plays a crucial role in this process. The findings presented here are based on long-term data collected as part of the Mechanisms of Axonal Degeneration in Multiple Sclerosis (MADMS) study, which has provided unprecedented insights into how MS lesions evolve over time.

The Dominant Role of Lesion Expansion

1. Our investigations have revealed that chronic lesion expansion represents the largest contributor to overall lesion burden in treated MS. In our longitudinal studies, we found that expansion of existing lesions accounts for ~70% of the total increase in brain lesion volume, with new lesion formation contributing the remainder. This finding challenges the traditional focus on new lesion formation as the primary marker of disease activity.
2. We discovered that expansion in chronic lesion volume is a key driver of disease progression, as measured by both radiological and clinical biomarkers.
3. Our recent research has revealed that lesion expansion follows remarkably consistent patterns within individual patients while varying significantly between different patients.          
4. We demonstrated that when present, the rate of lesion expansion remains relatively constant within individual patients over periods of up to 7 years. This consistency suggests that expansion is driven by patient-specific factors rather than random inflammatory events.

Clinical Implications and Future Directions

These findings have significant implications for both clinical practice and research. The strong link between lesion expansion and disease progression suggests that treatments targeting chronic inflammation and lesion expansion might be particularly important for preventing long-term disability. Additionally, the patient-specific nature of lesion expansion patterns points toward the potential for more personalized treatment approaches based on individual expansion characteristics.