New severity metric allows longitudinal comparability of sufferers with MS

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

Current severity measurements for multiple sclerosis (MS) are largely in cross-section, making comparison between patients difficult. Although the ARMSS and MS Severity Score (MSSS) make it possible to rank a patient’s Extended Disability Status Scale (EDSS) by years since the onset or age of the disease, the study researchers looked for a measurement that was more comprehensive and less sensitive to the disease Follow-up time is.

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

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

They also predicted the heaviest nARMSS quartile at 10 years of follow-up, using both the MSSS and EDSS values ​​at 2 and 4 years. The means of nARMSS and EDSS were compared for patients in nARMSS quartiles.

The nARMSS quartiles of the Swedish cohort were compared with the first Symbol Digit Modalities Test (SDMT) and with the first physical and psychological results of the MS Impact Scale 29 (MSIS-29) at each point in time during the follow-up examination.

The range of nARMSS for all subjects had a median of 1.17 points across all patient visits, compared to a median of 3.24 for the underlying ARMSS that was recorded. The inter-area ratio was 0.36 or about a two-thirds reduction in instability.

EDSS was more accurate than nARMSS at 2 and 4 years in predicting whether SPMS had been achieved after 10 years of follow-up.

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

EDSS, MSIS-29 physical and psychological scores, and MS cases in the severest nARMSS quartile had lower first SDMT scores compared to the lowest nARMSS quartile.

An under-analysis of nARMSS for those with and without missing SDMT found that the mean nARMSS was significantly different for all quartiles, with the fourth quarter having the largest increase in nARMSS between non-missing and missing data, leading study researchers to believe that more severe disability likely in the fourth quarter is underreported and that interquartile range differences could increase with more complete data.

The limitations of the nARMSS include its construction from EDSS measurements and the subsequent tendency towards mobility.

The study’s researchers concluded: “The nARMSS provides a reliable, generalizable, and easily measurable metric that enables a longitudinal comparison of disease progression between individuals.”

Disclosure: Some authors of the study stated that they were part of the industry. For a full list of the authors’ information, see the original reference.


Manouchehrinia A, Kingwell E, Zhu F, Tremlett H, Hillert J, Ramanujam R. Mult Scler. Published online January 25, 2021. doi: 10.1177 / 1352458520988632

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