Aided by a high-powered brain scanner and a 3D printer, researchers peered inside the brains of hundreds of MS patients and found that dark rimmed spots representing ongoing, "smoldering" inflammation, called chronic active lesions, may be a hallmark of more aggressive and disabling forms of the disease.

While some lesions heal, completely or partially, other lesions remain and rimmed ones appear to actively expand, or "smolder," for many years. Until recently, researchers did not fully understand the role chronic active lesions play in the disease, in part, because it was difficult to find the ones that remain chronically inflamed.

Researchers at NIH's National Institute of Neurological Disorders and Stroke scanned the brains of 192 MS patients who had entered a trial at the NIH's Clinical Center. They found that, regardless of the treatment they were receiving, 56 percent of the patients had at least one rimmed lesion. Further analysis showed that 44 percent of patients had only rimless lesions; 34 percent had one to three rimmed lesions; and 22 percent had four or more rimmed lesions.

They then compared the brain scans to the neurological examinations the patients received upon enrollment. Patients 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 developed motor and cognitive disabilities at a younger age than the patients who had no rimmed lesions. When the researchers analyzed key parts of the patients' brains, they found that patients who had four or more rimmed lesions had less white matter and smaller basal ganglia than those who had no rimmed lesions.

The team then analyzed a subset of patients whose brains had been scanned once every year for 10 years or longer. Their results suggested that, while the rimless lesions generally shrank, the rimmed lesions either grew or stayed the same size and were particularly damaged.

Finally, the team used a 3D printer to compare the spots they had seen on scans to the lesions they observed in brain tissue samples autopsied from a patient who had passed away during the trial. They found that all expanding rimmed spots seen on the scans had the telltale features of chronic active lesions when examined under a microscope.

The researchers said results support the idea that chronic active lesions are very damaging to the brain and the need to attack these lesions as early as possible. The fact that these lesions are present in patients who are receiving anti-inflammatory drugs that quiet the body's immune system also suggests that the field of MS research may want to focus on new treatments that target the brain's unique immune system – especially a type of brain cell called microglia.

The paper was published in JAMA Neurology.