Redefining the Multiple Sclerosis Severity Score (MSSS): The effect of sex and onset phenotype

Yuan Zhou, Suzi B. Claflin, Jim Stankovich, Ingrid van der Mei, Steve Simpson, Richard H. Roxburgh, Tomas Kalincik, Leigh Blizzard, Alessandra Lugaresi, Raed Alroughani, Seyed Aidin Sajedi, Helmut Butzkueven, Eugenio Pucci, Daniele L.A. Spitaleri, Franco Granella, Edgardo Cristiano, Bassem Yamout, Stella Hughes, Riadh Gouider, José Luis Sánchez MenoyoJavier Olascoaga, Chris McGuigan, Cameron Shaw, Allan G. Kermode, Krisztian Kasa, Talal Al-Harbi, Ayse Altintas, Guy Laureys, Yara Fragoso, Todd A. Hardy, Tunde Csepany, Carmen Adella Sirbu, Danny Decoo, Attila Sas, Jose C. Alvarez-Cermeño, Karim Kotkata, Jorge Millán-Pascual, Bruce V. Taylor

Research output: Contribution to journalArticlepeer-review


Background: The Multiple Sclerosis Severity Score (MSSS) is a widely used measure of the disability progression rate. However, the global MSSS may not be the best basis for comparison between all patient groups. Objective: We evaluated sex-specific and onset phenotype–specific MSSS matrices to determine if they were more effective than the global MSSS as a basis for comparison within these subsets. Methods: Using a large international dataset of multiple sclerosis (MS) patient records and the original MSSS algorithm, we constructed global, sex-specific and onset phenotype–specific MSSS matrices. We compared matrices using permutation analysis. Results: Our final dataset included 30,203 MS cases, with 28.9% males and 6.5% progressive-onset cases. Our global MSSS matrix did not differ from previously published data (p > 0.05). The progressive-onset-specific matrix differed significantly from the relapsing-onset-specific matrix (p < 0.001), with lower MSSS attributed to cases with the same Expanded Disability Status Score (EDSS) and disease duration. When evaluated with a simulation, using an onset-specific MSSS improved statistical power in mixed cohorts. There were no significant differences by sex. Conclusion: The differences in the disability accrual rate between progressive- and relapsing-onset MS have a significant effect on MSSS. An onset-specific MSSS should be used when comparing the rate of disability progression among progressive-onset cases and for mixed cohorts.

Original languageEnglish
JournalMultiple Sclerosis Journal
Publication statusE-pub ahead of print - Jan 1 2019


  • disability progression
  • Multiple sclerosis
  • Multiple Sclerosis Severity Score
  • onset phenotype

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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