‘Smoldering’ spots: a hallmark for progressive multiple sclerosis?

Written by Sharon Salt, Editor

Researchers have indicated that dark-rimmed spots that represent ongoing, ‘smoldering’ inflammation (also referred to as chronic active lesions) may be a hallmark for more aggressive and disabling forms of multiple sclerosis (MS).

By using brain scans, the investigators were able to detect which patients were more susceptible to the aggressive forms of the disease. Daniel Reich (NIH National Institute of Neurological Disorders and Stroke, MD, USA), senior author of the study, stated that the more chronic active lesions a person has, the greater their chances are at experiencing this type of MS. The results have been published in JAMA Neurology.

In previous research, Reich and colleagues reported on the use of a high-powered MRI scanner that could accurately identify damaging, chronic active lesions by their darkened outer rims.

Martina Absinta (NIH National Institute of Neurological Disorders and Stroke), co-author of the study, explained that: “Figuring out how to spot chronic active lesions was a big step and we could not have done it without the high-powered MRI scanner provided by the NIH. It allowed us to then explore how MS lesions evolved and whether they played a role in progressive MS.”

Following on from this, the team conducted brain scans on 192 individuals with multiple sclerosis. They revealed that, regardless of the treatment being received, 56% of the participants had at least one rimmed lesion. Further analysis demonstrated that 44% of individuals had only rimless lesions, 34% had one to three rimmed lesions and 22% had four or more rimmed lesions.

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The brain scans were then compared to neurological examinations that the participants received upon enrollment. This revealed that participants who had four or more rimmed lesions were 1.6-times more likely to be diagnosed with progressive MS than those without rimmed lesions. Moreover, these patients were reported to develop motor and cognitive disabilities at a younger age compared with participants who had no rimmed lesions.

Additionally, individuals who had four or more rimmed lesions displayed less white matter in their brains and smaller basal ganglia in comparison with those who had no rimmed lesions.

The investigators subsequently analyzed a group of individuals whose brains had been scanned once a year for 10 years or longer. When examining the rimless regions, they revealed that these areas were normally observed to shrink. However, the rimmed lesions either grew or stayed the same size and were particularly damaged.

To finish, the team utilized a 3D printer to compare the spots identified on scans to the lesions observed in brain tissue samples from a patient who had passed away during the trial. When examined under a microscope, they revealed that all expanding rimmed spots observed on the scan included features of chronic active lesions.

Reich concluded that: “Our results support the idea that chronic active lesions are very damaging to the brain. We need to attack these lesions as early as possible.” He also stated that these lesions were present in people who were receiving anti-inflammatory drugs, which suggests that researchers may want to focus on new treatments that target the brain’s immune system, particularly microglia.

Sources: Absinta M, Sati P, Masuzzo F et al. Association of chronic active multiple sclerosis lesions with disability in vivo. JAMA Neurol. doi:10.1001/jamaneurol.2019.2399 (2019) (Epub ahead of print); www.ninds.nih.gov/News-Events/News-and-Press-Releases/Press-Releases/Smoldering-spots-brain-may-signal-severe-MS