ECTRIMS 2025 | The clinical relevance of PRLs and SELs as MRI biomarkers in MS

So paramagnetic lesions and slowly expanding lesions are basically two different approaches that we can use to detect the presence of chronic active lesions in patients with multiple sclerosis. We know from the pathology that chronic active lesions are a specific subset of MS lesions characterized by chronic smoldering inflammatory activity, which is also associated with neurodegeneration of the tissues surrounding the lesions. And therefore, these lesions are considered to be extremely important drivers of disability progression and disease progression in patients with multiple sclerosis. And this motivates the need to develop biomarkers that are able to detect these lesions in people. And paramagnetic rim lesions are one of these biomarkers that we can use. So we can exploit this accumulation of iron-laden macrophages and microglia at the lesion border to detect in people the presence of chronic active lesions, while slowly expanding lesions are another biomarker that we can use, which basically reflects the presence of lesions that do exhibit a progressive concentric expansion in terms of volume over time. So this change in the volume is the means that we use to detect the presence, in this case, of chronic active lesions. So these are two different biomarkers that are based on magnetic resonance imaging. Then we can also use potentially positron emission tomography. And this is the third big chapter to detect the presence of chronic active lesions in people. So regarding paramagnetic rim lesions, paramagnetic rim lesions are becoming more and more relevant in the field of multiple sclerosis and potentially also in the management of patients with multiple sclerosis as they have been recently introduced in the new revision of the McDonald criteria as one of the paraclinical tools that can support in specific situations the diagnosis. Of course, the presence and the detection of paramagnetic rim lesions is not necessary and is not strictly mandatory for supporting the diagnosis, but in some specific situations can support and can help the process of making the diagnosis. And this is due to the fact that multiple studies have actually shown that paramagnetic rim lesions are a characteristic, are a specific finding that is highly typical of multiple sclerosis and typically not detected in other conditions that can mimic multiple sclerosis, both from the clinical point of view and the radiological point of view. There is one only important exception, which is Susac syndrome. We still have a few cases of this condition investigated using susceptibility-based MRI sequences where there was reported a relatively high presence of lesions that actually resembled paramagnetic rim lesions. But with this exception, in general, in other conditions that mimic multiple sclerosis, we typically don’t see paramagnetic rim lesions. And even more importantly, it has been shown in some studies that paramagnetic rim lesions in patients with clinically isolated syndrome are predictive of a conversion to clinically definite multiple sclerosis. And this has basically motivated the introduction of paramagnetic rim lesions in the new revision of the McDonald criteria. But of course, paramagnetic rim lesions are not only useful for the diagnosis, as we mentioned before, they are also useful for the prognosis as they reflect chronic compartmentalized inflammation within the central nervous system. And indeed, they are considered potential correlates and potential drivers of disability accumulation. Importantly, some studies have recently shown, including our study, that the burden of paramagnetic rim lesion is associated with the risk of disease progression, including progression that occurs independently of relapse activity, therefore potentially highlighting paramagnetic rim lesions and chronic active lesions as correlates and drivers of non-relapsing disease progression. And similar for slowly expanding lesions, studies have shown that this accumulation and the presence of lesions that enlarge over time is associated with an increased risk of more severe disease trajectories. Therefore, making these biomarkers potentially useful for stratifying patients as potential prognostic biomarkers and also potentially in the future as biomarkers useful to monitor treatment effects.

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