Results of a study published in JAMA Neurology showed key prognostic biomarkers that predict which individuals with radiologically isolated syndrome (RIS) are at highest risk of developing clinical symptoms of multiple sclerosis (MS). Biomarkers including oligoclonal bands (OBs), elevated κ free light chain index, and neurofilament light chain (NfL) levels were strongly associated with the development of MS symptoms. These results may help guide decisions regarding early intervention with disease-modifying therapies (DMTs) or clinical trial enrollment in people with RIS.

The multicenter cohort study included 273 people with RIS (pwRIS) who met the 2017 McDonald criteria for dissemination in space, with a median follow-up of 5 years. Researchers collected samples between July 2004 and September 2022 across 33 MS centers from study participants near the time of their diagnostic MRI testing. Data was analyzed using univariable and multivariable Cox proportional hazards models, adjusting for age, sex, and post-diagnosis treatment. The primary outcome was the development of clinical MS symptoms.

Key findings include:

  • 37% of participants (n=101) developed MS symptoms.
  • The presence of immunoglobulin G OBs (hazard ratio [HR] 5.09; 95% CI, 2.36 to 10.97; P<.001) and immunoglobulin M OBs (HR 2.58; 95% CI, 1.61 to 4.14; P<.001), and κ free light chain index ≥6.1 (HR 2.79; 95% CI, 1.37 to 5.67; P=.005) were associated with MS symptoms.
  • High cerebrospinal fluid NfL levels (HR, 1.31; 95% CI, 1.18 to 1.45; P<.001) and high serum NfL z scores (HR, 1.42; 95% CI, 1.16 to 1.72; P=.005) were associated with an increased risk of MS symptoms.
  • High anti-cytomegalovirus titers (HR, 0.59; 95% CI, 0.38 to 0.93; P=.02) and high ultraviolet radiation exposure in the year before (HR, 0.52; 95% CI, 0.37 to 0.74; P<.001) and the year after (HR, 0.54, 95% CI, 0.38 to 0.75; P<.001) diagnosis were associated with a reduced risk of MS symptoms.

Source: Fissolo N, Schaedelin S, Villar LM, et al. Prognostic factors for multiple sclerosis symptoms in radiologically isolated syndrome. JAMA Neurol. 2025;82(7):722–733. doi:10.1001/jamaneurol.2025.1481