New Severity Metric Enables Longitudinal Comparison of Patients With MS

Researchers tested the normalized age-related MS severity score they developed with both a Canadian cohort and a Swedish cohort.

Normalized age-related multiple sclerosis severity (nARMSS) scores can reliably summarize a patient’s disease course, according to study results published in Multiple Sclerosis Journal.

Current severity measurements for multiple sclerosis (MS) are largely cross-sectional, which makes comparison between patients harder. Although the ARMSS and the MS severity score (MSSS) enable a patient’s expanded disability status scale (EDSS) to be ranked by years since disease onset or age, study researchers sought a measurement that would be more comprehensive and less sensitive to follow-up time.

They developed the nARMSS, which is the deviation of individual age-related MS severity (ARMSS) scores from the expected value, integrated over the corresponding time period, and tested its performance in the study with two cohorts of patients with MS: 14,160 patients from a Swedish MS registry and 5989 from Canada.

To determine if nARMSS early in follow-up (at 2 and 4 years) could predict nARMSS for a patient through 10 years of follow-up, the study researchers used the closest chronological EDSS (ranging from 0.5 to 3 for 2 years and from 2 to 5 years for 4 years). They calculated the area under the curve (AUC) of the receiver operating characteristic (ROC) using the curve of sensitivity and specificity to determine the strength of the association.

They also predicted the most severe nARMSS quartile through 10 years of follow-up using both the MSSS and EDSS values at 2 and 4 years. The mean values of nARMSS and EDSS were compared for patients in nARMSS quartiles.

The Swedish cohort’s nARMSS quartiles were also compared with the first Symbol Digit Modalities Test (SDMT) at any point during follow-up, and with the first-ever MS impact scale-29 (MSIS-29) physical and psychological scores.

The range of nARMSS for all individuals had a median of 1.17 points over all patient visits, compared with a median range of 3.24 for the underlying ARMSS recorded. The ratio between ranges was 0.36, respectively, or a reduction in instability of about two-thirds.

EDSS held more accuracy than nARMSS at 2 and 4 years in predicting whether SPMS had been reached after 10 years of follow-up.

Similar AUC-ROC curves were calculated in the Canadian cohort for nARMSS at 2 and 4 years to predict the most severe quartile in up to 10 years of follow-up. All variables in predicting SPMS in the Canadian cohort showed slight increases compared with the Swedish cohort.

EDSS, MSIS-29 physical and psychological scores, and MS cases in the most severe nARMSS quartile had lower first SDMT scores when compared with the lowest nARMSS quartile.

A subanalysis of nARMSS for those with and without missing SDMT indicated that mean nARMSS was significantly different for all quartiles, with Q4 showing the largest increase in nARMSS between nonmissing and missing data, leading the study researchers to believe that more severe disability in Q4 is likely under-reported and that interquartile differences might increase with more complete data.

Limitations of the nARMSS include its construction from EDSS measurements and subsequent bias toward mobility.

Study researchers concluded, “The nARMSS provides a reliable, generalizable and easily measurable metric which makes longitudinal comparison of disease course between individuals feasible.”

Disclosure: Some study authors declared affiliations with the industry. Please see the original reference for a full list of authors’ disclosures.


Manouchehrinia A, Kingwell E, Zhu F, Tremlett H, Hillert J, Ramanujam R. A multiple sclerosis disease progression measure based on cumulative disability. Mult Scler. Published online January 25, 2021. doi:10.1177/1352458520988632