It remains unknown which multiple sclerosis (MS) disease process is the main cause of progressive disability. Brain lesions have been thought to play a relatively minor role in progressive MS, in contrast to the relapsing-remitting forms of MS where lesions are the main cause of symptoms. However, brain biopsies from people with MS have shown substantial chronic activity in lesions, with ongoing inflammation and neurodegeneration.

During my fellowship, I implemented a new way to identify slowly expanding lesions (SELs) on brain magnetic resonance imaging (MRI), as a surrogate marker for the chronic lesion activity.

My project objective was to explore the relationship between SELs and clinical measures, in order to understand their contribution to disability in MS. I analysed 345 scans from a research trial in secondary-progressive MS and 150 scans from an international observational cohort of relapsing-remitting MS patients. SELs constitute up to ~36% of the total lesion volume, with a predominance in SPMS compared to RRMS, in line with findings from pathological studies. SELs demonstrated more structural damage compared to other lesion types, as measured by reductions of the magnetization transfer ratio (MTR, a marker of tissue integrity), and a greater volume of SELs correlated with higher percentage brain volume reduction (a marker of neurodegeneration). SELs were also independently associated with increasing physical and cognitive disability scores. We conclude that SELs are a new and clinically relevant MRI measure that may be of interest in future progressive MS treatment trials. 

Publications