A brain with a smoldering ring of fire burning in the middle.

What Are Smoldering Lesions?

The progression of MS can be varied from person to person. Some individuals may experience rapid progression and significant disability, while others may progress slower and experience fewer symptoms. The underlying reasons for these differences are not well understood. However, a study published earlier this year points toward a specific type of brain lesion that might contribute to more aggressive progression.

What are smoldering lesions?

Researchers at the National Institute of Health (NIH) used high-powered brain scanners to detect the presence of rimmed spots within the brain. These rimmed spots, also called smoldering lesions, have dark boundaries around them that are visible on these scans. Typically, the autoimmune response related to MS can create lesions, or spots, in the brain. These lesions can be used in diagnosing MS and monitoring its progression or response to treatment. High-powered MRI images have allowed scientists to find these rimmed lesions and distinguish them from non-rimmed lesions.

Differences between rimmed and non-rimmed lesions

Lesions that are non-rimmed (non-smoldering lesions) can shrink or completely go away over time. However, these newly identified rimmed lesions are different. The rimmed lesions often remain their normal size or expand. They are thought to represent chronic, active inflammation that is “smoldering”, or consistent, in nature. This type of inflammation can be especially damaging to the brain.

What does the research say?

The researchers created a study to find out if rimmed lesions were associated with severe forms of MS. In order to find out more, they studied high-powered brain scans from 192 people with MS. Each person was allowed to remain on their current treatment plan during the study. Overall, 56 percent of participants had at least 1 rimmed lesion. About 34 percent had 1 to 3 smoldering lesions and 22 percent had more than 4 of these lesions. Roughly 44 percent of participants had no smoldering lesions, meaning they had only rimless lesions.

More rimmed lesions were associated with more progressive MS

The researchers compared the number of lesions to the clinical symptoms of each person. Those with 4 or more rimmed lesions were 1.6 times more likely to have progressive MS than those with no rimmed lesions. Additionally, those same people were more likely to have earlier cognitive or motor disabilities. Those with 4 or more smoldering lesions also had less white matter and smaller basal ganglia overall, both of which are important communication-related components of the brain. These results suggest that the higher the number of rimmed lesions a person has, the more likely they are to have severe, progressive MS.

Active sites of chronic inflammation

The researchers also used a 3D printer to compare the rimmed lesions found on the high-powered scans to autopsy (post-death) tissue samples from a person with MS. This allowed the scientists to get a better idea of what the smoldering lesions actually look like inside the brain. They found that the expanding, rimmed lesions had all of the classic inflammatory signs under the microscope. The rimmed lesions seemed to be active sites of chronic inflammation causing significant damage in the brain.

What does this mean for MS?

While much more research is needed to understand the role rimmed lesions may play in the progression of MS, and to better understand who is at risk for them, these results suggest that smoldering lesions may be associated with more severe forms of the condition. Detecting rimmed lesions may help predict progression and determine who is at risk for more severe forms of MS. These lesions may also provide a new marker to test and monitor treatment options for progressive MS. Although the scientists in the study used a specific, high-powered MRI machine, they released guidelines on how to reprogram existing machines to better detect smoldering lesions. This may make detecting these spots more feasible across many different healthcare settings.

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