Advancements in the Understanding of Chronic Lesion Expansion and Smouldering Inflammation in Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is characterised by complex interactions between inflammatory processes and neurodegenerative changes in the central nervous system. While significant advances have been made in understanding acute disease mechanisms, the pathophysiological processes driving progressive neurodegeneration remain poorly defined, particularly regarding the role of chronic inflammation and central brain structures such as the choroid plexus.

This thesis investigates the temporal and spatial evolution of chronic inflammatory processes in MS, with a specific focus on their relationship to progressive tissue injury. Through longitudinal analysis of advanced neuroimaging measures, the research characterises novel patterns of lesion progression and their association with choroid plexus changes. These investigations reveal previously unrecognised relationships between compartmentalised inflammation and neurodegeneration, suggesting new mechanisms underlying disease progression.

The findings presented advance our understanding of MS pathophysiology and provide new frameworks for monitoring disease progression in MS, particularly during progressive disease stages where current treatments demonstrate limited efficacy.