September 9, 2019Neurology
Affecting more than 2 million people worldwide, multiple sclerosis (MS) is a disease for which there is no cure. The disease starts when the immune system attacks myelin, a protective coating that forms around nerve cells in a person's brain and spinal cord, to produce a variety of initial symptoms, including blurred or double vision, problems with muscle strength, balance and coordination, and abnormal sensations. Treatment with anti-inflammatory medications designed to quiet the immune system has helped some patients fully or partially recover. Nevertheless, a significant subset of patients will eventually suffer from a longer lasting, progressive form of the disease, which can cause further problems including paralysis, loss of bladder control and problems with attention, thinking, and memory.
Clinicians often use magnetic resonance imaging (MRI) to diagnose patients as the immune system's attack produces lesions that appear as spots on scans of patients' brains. While some of the lesions heal, completely or partially, other lesions remain and rimmed ones appear to actively expand, or smolder, for many years. Nevertheless, 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.
According to an article published in JAMA Neurology (12 August 2019), aided by a high-powered brain scanner and a 3D printer, when the authors peered inside the brains of hundreds of multiple sclerosis patients, they 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.
Starting in 2013, the authors showed that by using a high-powered, 7-tesla MRI scanner, it was possible to accurately identify damaging, chronic active lesions by their darkened outer rims, in agreement with previous studies. The authors noted that figuring out how to spot chronic active lesions was a big step and could not have been done without the high-powered MRI scanner provided by the NIH. To do this, the team scanned the brains of 192 multiple sclerosis patients who had entered a trial at the NIH's Clinical Center. Results showed that, regardless of the treatment they were receiving, 56% of the patients had at least one rimmed lesion. Further analysis showed that 44% of patients had only rimless lesions; 34% had one to three rimmed lesions; and 22% had four or more rimmed lesions.
The authors 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 authors 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.
According to the authors, the results support the idea that chronic active lesions are very damaging to the brain, and it is important 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 NIH is actively seeking patients who want to participate in studies like these.
In a previous article, the authors openly shared instructions for programming lower powered MRI scanners, found at most clinics, to detect rimmed chronic active lesions. They hope researchers around the world will use the instructions to develop and monitor better diagnostic and therapeutic strategies for MS patients.