MRI reveals smouldering MS lesions


30 October 2019

The study in brief

A team of researchers have recently developed a new MRI technique which makes it possible to visualise a type of MS lesion called smouldering, or chronic active, lesions which have a dark rim and grow slowly for many years. They used this technique to follow the evolution of smouldering lesions from 192 people with MS over a six year period.

More than half of the participants had at least one smouldering lesion, regardless of type of MS, or whether they had previously or were currently taking a disease modifying drug.

44% had no smouldering lesions, 34% had 1 to 3, 22% had 4 or more. Those with 4 or more smouldering lesions were more likely to have developed cognitive and mobility problems at an earlier age, had lower brain volume and were more likely to have MS that had become progressive, when compared to people with no smouldering lesions.

In a subset of people who had yearly MRI scans for 10 years or longer, rimless lesions shrank over time, but chronic active lesions remained the same size or expanded. Smouldering lesions showed MRI features typical of on-going tissue destruction.

The researchers conclude that smouldering lesions are common in MS and are associated with a more aggressive course of MS, cause tissue damage and occur even in people taking effective disease modifying drugs.

In addition to learning more about the biological processes which lead to increased disability, the ability to visualise smouldering lesions provides a new tool for assessing potential treatments, particularly those being developed for progressive MS.

The study in more detail

Background

An MS lesion is an area of damage or scarring (sclerosis) in the brain or spinal cord. Lesions are caused by inflammation that results from the immune system attacking the myelin sheath around nerves.

While some MS lesions heal, completely or partially, other lesions remain, have a dark rim and appear to actively expand for many years.  These persistent lesions have been given various names including rim lesions, chronic active lesions or smouldering lesions. 

New MRI techniques have recently made it possible to visualise chronic active lesions.  This study used these techniques to see how the lesions change over time and begin to understand how they are linked with different types and stages of MS.

How this study was carried out

A team of researchers in the States has developed a new MRI procedure which allows them to visualise chronic active MS lesions.  Using this technique, they followed the evolution of lesions from the high-powered MRI scans of 192 people with MS over a six year period, from 2012 to 2018.  They also looked at how the lesions were linked to disability and brain volume change.

What was found?

Overall, more than half of the participants (56%) had at least one chronic active lesion, regardless of type of MS, or whether they had previously or were currently taking a disease modifying drug. 

44% had no chronic active lesions, 34% had 1 to 3, 22% had 4 or more. Those with 4 or more chronic lesions were more likely to have developed cognitive and walking problems at an earlier age, had lower brain volume and were more likely to have MS that had become progressive, when compared to people without chronic active lesions.

In a subset of people who had yearly MRI scans for 10 years of longer, rimless lesions shrank over time, but chronic active lesions remained the same size or expanded by approximately 2.2% each year.  

Chronic active lesions showed MRI features typical of on-going tissue destruction. One participant who passed away during the course of the study donated brain tissue to the study; all of the 10 rim lesions that had expanded showed tissue changes typical of chronic active inflammation.

What does it mean?

The researchers conclude that chronic active lesions are common in MS and are associated with a more aggressive course of MS, cause tissue damage and occur even in people taking effective disease modifying drugs. 

This type of lesion has been recognised for some years, but only in tissues from brains donated after death.  As a result, researchers do not fully understand the role these lesions play in MS.  This new technique will allow researchers to track the development of the lesions over time.  In addition to learning more about the biological processes which lead to increased disability, the ability to visualise smouldering lesions provides a new tool for assessing potential treatments, particularly those that are being developed for progressive MS.

The research team has shared a program that will enable other investigators to detect smouldering lesions with less powerful MRI scanners that are more commonly used in clinics to encourage their incorporation in research and future clinical trials. They also are continuing to study the role of chronic active lesions in people with MS.

Absinta M, et al.
Association of chronic active multiple sclerosis lesions with disability in vivo.
JAMA Neurology 2019 Aug 12. [Epub ahead of print].

Find out more about smouldering lesions

The distinctive dark rim around chronic active lesions is caused by microglia. Microglia are mobile cells that roam the central nervous system cleaning up damaged cells and pathogens. In MS and other conditions, they can be activated by inflammation, and become overactive. This may be how lesions get started.

Microglia may be particularly important for understanding the progressive forms of MS. It is thought that they may be nibbling away at the edges of lesions, enlarging them and causing disability accumulation. 

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