#ECTRIMS2022 – 2 Brain Lesion Types Linked to Greater Disability

Recently diagnosed multiple sclerosis (MS) patients with two forms of chronic active brain lesions — slowly expanding lesions (SELs) and paramagnetic rim lesions (PRLs) — on their MRI scans experience greater disability progression than those with SELs only, a small study suggests.

Also, the slowly expanding lesions are more common among patients than the other type, suggesting they reflect different aspects of chronic neuroinflammatory activity in MS, the researchers noted.

The results were shared in an oral presentation at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held Oct. 26–28 both virtually and in Amsterdam, the Netherlands.

The presentation, titled “Relationship between paramagnetic rim lesions and slowly expanding lesions in people with multiple sclerosis,” was given by Alberto Calvi, MD, PhD, of the Queen Square Multiple Sclerosis Centre at the University College London’s Institute of Neurology, U.K.

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MS is caused by abnormal inflammatory and immune attacks that damage myelin, the fatty sheath around nerve fibers that helps them send electric signals. This leads to demyelination, or myelin loss, in the brain and spinal cord, and these areas of inflammation and demyelination are visible on MRI scans as lesions.

On MRI, chronic active lesions are characterized by regions of demyelination and nerve cell loss that are surrounded by a “rim” of iron-laden immune cells, like microglia and macrophages.

These lesions can be identified via different types of MRI techniques: slowly expanding lesions can be observed in T1/T2-weighted volumetric MRI and paramagnetic rim lesions in susceptibility-weighted imaging.

Both lesion types are associated with clinical worsening and have been used as synonyms of each other, but they have not been studied in combination.

In combination, [slowly expanding lesions] and [paramagnetic rim lesions] might have an adverse impact on MS severity

Now, Calvi and colleagues in the U.K., Spain, and the Netherlands assessed potential associations between the two lesion types in people recently diagnosed with MS, and whether these lesions, alone or in combination, could predict disability worsening.

The researchers retrospectively analyzed demographic, clinical, and MRI data from 61 patients (42 women and 19 men) with a median age of 34.4 years. At first assessment, most patients (90.1%) were diagnosed with relapsing-remitting MS, while six had clinically isolated syndrome. Their median disease duration was 4.8 months, and they had mild disability.

Participants underwent three MRI scans: at first evaluation, after a median of 9.6 months (range was 4.8 months to 6.4 years), and after a median of 3.2 years (range of 8.4 months to 8.3 years). 

Results showed that 616 (41.3%) of the 1,492 lesions analyzed were classified as SELs and 80 (5.4%) as PRLs.

“SELs are more numerous than PRLs in relapse-onset MS, suggesting they represent separate aspects of chronic inflammatory activity,” the researchers wrote.

Out of a median of 20 lesions per patient, five were SELs and one was PRL, and higher counts of SELs were significantly associated with more PRLs, Calvi noted. Also, a significantly greater proportion of PRLs coincided with SELs than with non-SELs (7% vs. 4%).

Most patients (92%) had one SEL or more, and more than half (56%) had at least one PRL. About half (51%) had both, while 41% had at least one SEL, but no PRL.

Patients with both types show significantly faster MS progression

Patients with both types showed the highest lesion burden. In addition, a higher number of PRLs was significantly associated with more and larger SELs, while higher SEL volumes were significantly linked to greater brain shrinkage.

The team then looked at potential links between these markers and disease progression, which was assessed with the expanded disability status scale scores. Higher scores indicate worse disability and greater increases over time reflect faster progression.

After adjusting for potential influencing factors such as age, sex, lesion counts at first assessment, disease duration, relapses, and treatment status at last assessment, faster disease progression was predicted independently by “a higher SEL count and the presence of PRLs,” Calvi said.

Patients with both lesion types progressed significantly faster than those with SELs only and those with neither type.

“In combination, SELs and PRLs might have an adverse impact on MS severity,” the researchers concluded.

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These findings highlight that SELs are common, even in recently diagnosed MS patients, and that a combination of both lesion types are also found in about half of these patients, Calvi noted.

“This combination might also imply higher lesion load and higher risk of disability [worsening], Calvi said, which needs to be explored in the future.

Future studies are needed to integrate these “MRI markers of chronic [disease] activity to predict prognostically disability outcomes and look better at how they can explain treatment response,” Calvi added.

Note: The Multiple Sclerosis News Today team is providing in-depth coverage of the ECTRIMS Forum 2022 Oct. 26–28. Go here to see the latest stories from the conference.