Researchers discovered that the early use of disease-modifying therapy (DMT) in patients with radiologically isolated syndrome (RIS) may reduce the impact of established risk factors on clinically evident disease, according to a study published in Multiple Sclerosis and Related Disorders. In high-risk patients, this also lowers the risk of conversion to clinically definite central nervous system (CNS) demyelinating disease. 

An urgent question in medicine today is how to identify when multiple sclerosis (MS) begins to develop, so that treatment can be started as soon as possible. RIS represents one of the earliest possible signs of MS.

Certain risk factors predispose someone with RIS to develop clinically definite CNS demyelinating disease. Among the most cited risk factors are: being male, having spinal cord lesions, and being younger than 37 years old. The researchers in this study set out to investigate the impact of established risk factors on the conversion from RIS to clinically definite disease. 

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Researchers searched the medical records of patients at their institution in Boston, Massachusetts, who had a diagnosis of RIS by their treating neurologist. The period covered was from January 2005 to April 2020. In total, 89 patients were recruited, with a median age of 41 years. In accessing their medical records, researchers specifically looked at demographics, clinical outcomes, and treatment. For each person, they calculated the length of “time to first clinical event representing a demyelinating disease attack or last follow up without clinically definite disease.”  

Of the patients recruited for this study, 76% were female, 45% had spinal cord lesions, and 8% had a family history of MS. Two-thirds of them had never smoked and 40% had a BMI over 30 kg/m2. Sixteen patients (18%) were observed to have developed clinically definite disease during follow-up, with the median follow-up period being 3.8 years and the median time to first event being 3.4 years. The median Expanded Disability Status Scale (EDSS) score was 1.25 out of a possible maximum of 4.

Out of the 89 patients recruited, 84 had longitudinal brain imaging, with 42 (50%) displaying new demyelinating lesions. The study found that the 3 most commonly cited risk factors (being male, having spinal cord lesions, and being below 37 years old) were not statistically significant, suggesting that that the early use of disease-modifying therapy (DMT) in patients with RIS may reduce the impact of established risk factors on clinically evident disease.

Twenty-six patients were started on a DMT for MS; dimethyl fumarate was used in 6 patients, glatiramer acetate in 7, and the rest were put on second-line DMT. The cohort of patients who were started on DMT had a statistically significantly higher number of established risk factors for conversion to clinically definite disease, compared to the cohort who were not. Most patients were started on DMT due to the discovery of MRI changes that indicated new demyelinating disease (n=16). 


George IC, Rice DR, Chibnik LB, Mateen FJ. Radiologically isolated syndrome: a single-center, retrospective cohort study. Mult Scler Relat Disord. Published online August 2, 2021. doi:10.1016/j.msard.2021.103183