Younger Age, Certain Lesions Linked to Higher MS Risk for RIS Patients

Among people with nervous system damage indicative of multiple sclerosis (MS), but who don’t yet have the disease — a condition known as radiologically isolated syndrome or RIS — the risk of progressing to full-fledged MS is higher for those who are younger, have spinal cord lesions, and have actively inflamed lesions, a new study suggests.

“This study found that age younger than age 37 years, spinal cord involvement, and [inflamed] lesions on index MRI scan were associated with earlier clinical disease,” the researchers wrote.

These findings may help in furthering the diagnosis and treatment of MS in the future, according to the researchers.

“Given recent scientific advancements, RIS may be well-positioned to serve as a new focal point in our scientific efforts to more accurately and at an earlier stage recognize, guide, and possibly treat to optimize care,” they wrote.

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July 14, 2020 News by Marisa Wexler, MS

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The study, “Risk Factors and Time to Clinical Symptoms of Multiple Sclerosis Among Patients With Radiologically Isolated Syndrome,” was published in JAMA Network Open.

In some cases, MRI scans will reveal that a person has damage in the nervous system that is similar to what happens in MS — even though the individual doesn’t have any symptoms of the neurodegenerative disease. This condition is called radiologically isolated syndrome, or RIS.

A number of people with RIS will go on to develop MS symptoms. However, little is understood about what factors control the risk of conversion from RIS to MS.

Now, a team led by scientists in France conducted an analysis of 354 people with RIS who were followed for at least two years. The RIS patients ranged in age from 10 to 80, and about three-quarters were women. Reasons for the initial MRI that led to the RIS diagnosis included headache and problems with the ears, nose, throat, or eyes.

Over two years, 49 patients (13.8%) progressed from RIS to MS. The researchers performed statistical analyses to search for factors associated with an increased risk of this conversion.

The results showed that an age younger than 37 was associated with a roughly fourfold increase in the risk of conversion to MS. Lesions in the spinal cord were associated with a fivefold increased risk of MS, while gadolinium-enhancing lesions — which indicate areas of active inflammation — were linked with a twofold increased risk of conversion to MS.

Further analyses showed that the risk of conversion to MS after two years was about 11.3% in people with none of these risk factors. By contrast, the probability of converting to MS was 14.5% for people with one risk factor, 27.9% for those with two risk factors, and 90.9% for patients with all three risk factors.

An open area of uncertainty is whether giving MS therapies to people with RIS may reduce the risk of conversion. Two clinical trials are investigating this: one called ARISE (NCT02739542), testing Tecfidera (dimethyl fumarate), and a second dubbed TERIS (NCT03122652) that is assessing Aubagio (teriflunomide).

To support the design of further clinical trials, the researchers estimated how many people with RIS would need to be included in a clinical trial in order to see a statistically significant treatment effect over two years. Based on rates of conversion to MS in their dataset, the team calculated that a total of 160 individuals with RIS would be sufficient for a two-year trial with two arms (e.g., treatment and placebo).

The team noted that fewer patients would be needed if the patients included in trials were at higher risk of conversion to MS — specifically, those younger than 37, with spinal cord and/or gadolinium-enhancing lesions. An estimated 30 participants with all three risk factors would be sufficient to identify a significant treatment effect in a two-year trial, the researchers said.

These results “may be essential in guiding future study designs,” the researchers concluded, noting that the incidence of RIS worldwide is expected to increase in coming years.

“With the widespread use of MRI technology and expansion of access throughout the world, an increase in the recognition of individuals with abnormal MRI results suggesting incidental [MS-like damage] is anticipated,” they wrote.

The overarching goal of this research is to ultimately improve treatment for people with RIS.

“Although some informative clinical markers of disease course are available, the individual prognosis in RIS remains uncertain, leading to difficulties in counseling newly diagnosed patients,” the investigators wrote.

“Given that the search for novel biomarkers associated with future disease activity remains highly active, readily available data appear meaningful in predicting outcomes at an early phase of demyelinating disease,” they concluded.