Smoldering spots in the brain may signal severe multiple sclerosis

National Institutes of Health (NIH) researchers peered inside the brains of hundreds of multiple sclerosis 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.

NIH researchers found that dark rimmed spots representing ongoing, “smoldering” inflammation, may be a hallmark of more disabling forms of multiple sclerosis. Photo: Reich lab/NIH/NINDS

“We found that it is possible to use brain scans to detect which patients are highly susceptible to the more aggressive forms of multiple sclerosis. The more chronic active lesions a patient has the greater the chances they will experience this type of MS,” said Daniel S. Reich, M.D., Ph.D., senior investigator at the NIH’s National Institute of Neurological Disorders and Stroke. “We hope these results will help test the effectiveness of new therapies for this form of MS and reduce the suffering patients experience.”

Affecting more than 2 million people worldwide, multiple sclerosis 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.

Doctors 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.

The team 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.

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 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.

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 results support the idea that chronic active lesions are very damaging to the brain. It 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. (National Institutes of Health)

YOU MAY ALSO LIKE

Eosinophilic esophagitis may be due to missing protein

Scientists have discovered that the absence of a specific protein in cells lining the esophagus may cause inflammation and tissue damage in people with eosinophilic esophagitis.

A healthy lifestyle cuts stroke risk, irrespective of genetic risk

People at high genetic risk of stroke can still reduce their chance of having a stroke by sticking to a healthy lifestyle, in particular stopping smoking and not being overweight.

Connectome map more than doubles human cortex’s known regions

Researchers have mapped 180 distinct areas in our brain’s outer mantle, or cortex – more than twice the number previously known.

Preschoolers benefit from peanut allergy therapy

Researchers tested peanut oral immunotherapy in preschool-aged children with a newly diagnosed peanut allergy. After the treatment, most children could eat peanut-containing foods without an allergic reaction.

Study links irregular sleep patterns to metabolic disorders

A new study has found that not sticking to a regular bedtime and wakeup schedule — and getting different amounts of sleep each night — can put a person at higher risk for obesity, high cholesterol, hypertension, high blood sugar and other metabolic disorders.

Researchers have found a link between allergen in red meat and heart disease

A team of researchers says it has linked sensitivity to an allergen in red meat to the buildup of plaque in the arteries of the heart.