A new study suggests identifying people with radiologically isolated syndrome who are at higher risk of developing clinical symptoms of multiple sclerosis is crucial for prognosis. It may also be important for guiding treatment decisions, such as determining which individuals may benefit most from early initiation of disease-modifying therapies or enrollment in clinical trials.

An international team of researchers set out to identify prognostic factors of radiologically isolated syndrome diagnosis linked to the development of MS symptoms. This cohort study was performed using samples collected between July 2004 and September 2022 and included 33 MS centers.

The study included 273 people with radiologically isolated syndrome with an average follow-up of five years. All people with radiologically isolated syndrome who met the 2017 McDonald criteria for dissemination in space with a sample collected near the diagnostic MRI were included. The data was analyzed from July 2024 to November 2024.

A total of 101 people with radiologically isolated syndrome developed MS symptoms. The presence of immunoglobulin G oligoclonal bands, immunoglobulin M OBs, and a Kappa free light chain index of 6.1 or more were linked to MS symptoms. High cerebrospinal fluid neurofilament light chain levels and high serum NfL Z-scores were also linked to an increased risk of MS symptoms. In contrast, high anti-CMV titers and high ultraviolet radiation exposure in the year before and the year after diagnosis reduced the risk of MS symptoms. For all these prognostic factors, the multivariable analysis yielded similar results. The combination of high serum NfL Z-scores and positive immunoglobulin G OBs conferred a five-year risk of clinical symptoms of 58.3 percent. This risk increased to 81.6 percent in people with radiologically isolated syndrome who were younger and positive for immunoglobulin M OBs.

The study illustrates the prognostic factors that significantly affect the risk of developing MS symptoms in people with radiologically isolated syndrome at diagnosis, thereby, enhancing the potential for tailored clinical interventions.

The findings were published in the journal JAMA Neurology.