Redefining the Multiple Sclerosis Severity Score (MSSS): The effect of sex and onset phenotype
Yuan Zhou 1, Suzi B Claflin 1, Jim Stankovich 2, Ingrid van der Mei 1, Steve Simpson Jr 3, Richard H Roxburgh 4, Tomas Kalincik 5, Leigh Blizzard 1, Alessandra Lugaresi 6, Raed Alroughani 7, Seyed Aidin Sajedi 8, Helmut Butzkueven 2, Eugenio Pucci 9, Daniele LA Spitaleri 10, Franco Granella 11, Edgardo Cristiano 12, Bassem Yamout 13, Stella Hughes 14, Riadh Gouider 15, José Luis Sánchez Menoyo 16, Javier Olascoaga 17, Chris McGuigan 18, Cameron Shaw 19, Allan G Kermode 20, Krisztian Kasa 21, Talal Al-Harbi 22, Ayse Altintas 23, Guy Laureys 24, Yara Fragoso 25, Todd A Hardy 26, Tunde Csepany 27, Carmen-Adella Sirbu 28, Danny Decoo 29, Attila Sas 30, Jose C Alvarez-Cermeño 31, Karim Kotkata 32, Jorge Millán-Pascual 33, Bruce V Taylor 1
Affiliations
Affiliations
- 1Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
- 2Department of Neuroscience, Monash University, Melbourne, VIC, Australia.
- 3Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia/Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia.
- 4Centre for Brain Research Neurogenetics Clinic, The University of Auckland, Auckland, New Zealand.
- 5CORe, Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia/Department of Neurology, The University of Melbourne, Melbourne, VIC, Australia.
- 6IRCCS Istituto delle Scienze Neurologiche di Bologna, UOSI Riabilitazione Sclerosi Multipla, Bologna, Italy/Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy.
- 7Amiri Hospital, Kuwait City, Kuwait.
- 8Neuroscience Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
- 9Generale Provinciale Macerata, Macerata, Italy.
- 10Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino, Italy.
- 11University of Parma, Parma, Italy.
- 12Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
- 13American University of Beirut Medical Center, Beirut, Lebanon.
- 14Craigavon Area Hospital, Craigavon, UK.
- 15Razi Hospital, Tunis, Tunisia.
- 16Hospital de Galdakao-Usansolo, Bizkaia, Spain.
- 17Hospital Donostia, Gipuzkoa, Spain.
- 18St. Vincent's University Hospital, Dublin, Ireland.
- 19Geelong Hospital, Geelong, VIC, Australia.
- 20Perron Institute for Neurological and Translational Sciences, Nedlands, WA, Australia.
- 21Jahn Ferenc Teaching Hospital, Budapest, Hungary.
- 22King Fahad Specialist Hospital-Dammam, Dammam, Saudi Arabia.
- 23Department of Neurology, School of Medicine, Koç University, Istanbul, Turkey.
- 24University Hospital Ghent, Gent, Belgium.
- 25Universidade Metropolitana de Santos, Santos, Brazil.
- 26University of Parma, Parma, Italy/Concord Repatriation General Hospital, Sydney, NSW, Australia.
- 27Department of Neurology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
- 28Central University Emergency Military Hospital, Bucharest, Romania.
- 29AZ Alma, Eeklo, Belgium.
- 30Borsod-Abaúj-Zemplén County Hospital, Miskolc, Hungary.
- 31Ramon y Cajal University Hospital, Madrid, Spain.
- 32Alexandria University Student Hospital, Alexandria, Egypt.
- 33Hospital Mancha Centro, Real, Spain.
Abstract
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.
Keywords: Multiple Sclerosis Severity Score; Multiple sclerosis; disability progression; onset phenotype.
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