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Research paper
The Kurtzke EDSS rank stability increases 4 years after the onset of multiple sclerosis: results from the MSBase Registry
  1. Stella Hughes1,2,3,
  2. Timothy Spelman1,
  3. Maria Trojano4,
  4. Alessandra Lugaresi5,
  5. Guillermo Izquierdo6,
  6. Francois Grand'Maison7,
  7. Pierre Duquette8,
  8. Marc Girard8,
  9. Pierre Grammond9,
  10. Celia Oreja-Guevara10,
  11. Raymond Hupperts11,
  12. Cavit Boz12,
  13. Roberto Bergamaschi13,
  14. Giorgio Giuliani14,
  15. Maria Edite Rio15,
  16. Jeannette Lechner-Scott16,
  17. Vincent van Pesch17,
  18. Gerardo Iuliano18,
  19. Marcela Fiol19,
  20. Freek Verheul20,
  21. Michael Barnett21,
  22. Mark Slee22,
  23. Joseph Herbert23,
  24. Ilya Kister23,
  25. Norbert Vella24,
  26. Fraser Moore25,
  27. Tatjana Petkovska-Boskova26,
  28. Vahid Shaygannejad27,
  29. Vilija Jokubaitis1,
  30. Gavin McDonnell2,
  31. Stanley Hawkins2,3,
  32. Frank Kee3,
  33. Orla Gray28,
  34. Helmut Butzkueven1,29,30 on behalf of the MSBase Study Group
  1. 1Department of Neurology, Royal Melbourne Hospital, Victoria, Australia
  2. 2Royal Victoria Hospital, Belfast, UK
  3. 3UKCRC Centre of Excellence for Public Health Research, Queen's University Belfast, Belfast, UK
  4. 4University of Bari, Bari, Italy
  5. 5MS Center, Department of Neuroscience and Imaging, University of ‘G. d'Annunzio’, Chieti, Italy
  6. 6Hospital Universitario, Sevilla, Spain
  7. 7Neuro Rive-Sud, Quebec, Canada
  8. 8Hopital Notre Dame, Montreal, Canada
  9. 9Hotel-Dieu de Levis, Quebec, Canada
  10. 10Hospital Universitario La Paz, IdiPAZ, Madrid, Spain
  11. 11Maaslandziekenhuis, Sittard, The Netherlands
  12. 12Karadeniz Technical University, Trabzon, Turkey
  13. 13Neurological Institute IRCCS Mondino, Pavia, Italy
  14. 14Ospedale di Macerata, Macerata, Italy
  15. 15Hospital S. Joao, Porto, Portugal
  16. 16John Hunter Hospital, New South Wales, Australia
  17. 17Cliniques Universitaires Saint Luc, Brussels, Belgium
  18. 18Ospedali Riuniti di Salerno, Salerno, Italy
  19. 19FLENI, Buenos Aires, Argentina
  20. 20Groen Hart Ziekenhuis, Gouda, The Netherlands
  21. 21Brain and Mind Research Institute, New South Wales, Australia
  22. 22Flinders Medical Centre, South Australia, Australia
  23. 23New York University Hospital for Joint Diseases, New York, USA
  24. 24Mater Dei Hospital, Msida, Malta
  25. 25Jewish General Hospital, Montreal, Canada
  26. 26Clinic of Neurology Clinical Center, Skopje, Macedonia
  27. 27Al-Zahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
  28. 28Craigavon Area Hospital, Portadown, UK
  29. 29Department of Medicine, The University of Melbourne, Victoria, Australia
  30. 30Department of Neurology, Box Hill Hospital, Monash University, Victoria, Australia
  1. Correspondence to Professor Helmut Butzkueven, MS Clinical and Research Unit, Department of Medicine, Royal Melbourne Hospital and University of Melbourne, Grattan St, Parkville, Victoria 3050, Australia; butz{at}


Background The Expanded Disability Status Scale (EDSS) is widely used to rate multiple sclerosis (MS) disability, but lack of disease duration information limits utility in assessing severity. EDSS ranking at specific disease durations was used to devise the MS Severity Score, which is gaining popularity for predicting outcomes. As this requires validation in longitudinal cohorts, we aimed to assess the utility of EDSS ranking as a predictor of 5-year outcome in the MSBase Registry.

Methods Rank stability of EDSS over time was examined in the MSBase Registry, a large multicentre MS cohort. Scores were ranked for 5-year intervals, and correlation of rank across intervals was assessed using Spearman's rank correlation. EDSS progression outcomes at 10 years were disaggregated by 5-year EDSS scores.

Results Correlation coefficients for EDSS rank over 5-year intervals increased with MS duration: years 1–6=0.55, years 4–9=0.74, years 7–12=0.80 and years 10–15=0.83. EDSS progression risk at 10 years after onset was highly dependent on EDSS at 5 years; one-point progression risk was greater for EDSS score of >2 than ≤2. Two-point progression was uncommon for EDSS score of <2 and more common at EDSS score of 4.

Conclusions EDSS rank stability increases with disease duration, probably due to reduced relapses and less random variation in later disease. After 4 years duration, EDSS rank was highly predictive of EDSS rank 5 years later. Risk of progression by 10 years was highly dependent on EDSS score at 5 years duration. We confirm the utility of EDSS ranking to predict 5-year outcome in individuals 4 years after disease onset.

  • Multiple sclerosis
  • Multiple Sclerosis Severity Score (MSSS)
  • Expanded Disability Status Scale (EDSS)
  • predicting MS severity
  • EDSS ranking
  • neurochemistry
  • neuroepidemiology
  • neurovirology
  • neurogenetics
  • neuroimmunology
  • Guillain–Barre syndrome
  • myelopathy
  • neurourology
  • blood–brain barrier
  • CSF
  • EMG
  • parkinson's disease
  • pet
  • functional imaging
  • polymyositis
  • clinical neurology
  • interferon
  • image analysis

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  • To see the members of the MSBase Study group see end of article.

  • OG and HB contributed equally to this work.

  • Collaborators From University Hospital Nijmegen, The Netherlands, Dr Cees Zwanikken; From the University of Bari, Italy, Dr Damiano Paolicelli, Dr Guglielmo Lucchese and Dr Pietro Iaffaldano; From University of ‘G. d'Annunzio’, Chieti, Italy, Dr Giovanna De Luca, Dr Valeria Di Tommaso, Dr Daniela Travaglini, Dr Erika Pietrolongo, Dr Maria di Ioia and Dr Deborah Farina; From the Royal Melbourne Hospital, Australia, Dr Mark Marriott, Dr Trevor Kilpatrick, Dr John King, Dr Anneke Van der Walt, Ms Michelle Rutherford and Mrs Mary Tanner; From Kommunehospitalet, Aarhus C, Denmark, Dr Thor Petersen; From Ospedale di Macerata, Macerata, Italy, Dr Elisabetta Cartechini and Eugenio Pucci; From John Hunter Hospital, New South Wales, Australia, Dr David William and Dr Lisa Dark; From FLENI, Buenos Aires, Argentina, Dr Jorge Correale and Dr Celica Ysrraelit; From Francicus Ziekenhuis, The Netherlands, Ms Leontien Den Braber-Moerland; From Hospital Italiano, Buenos Aires, Argentina, Dr Edgardo Cristiano; From Multiple Sclerosis Centre Kamillus-Klinik, Asbach, Germany, Dr Dieter Poehlau; From INEBA, Buenos Aires, Argentina, Dr Maria Laura Saladino; From Hospital Fernandez, Buenos Aires, Argentina, Dr Norma Deri, Dr Gonzalo Jaacks, Dr Maria Fernanda Páez, Dr Daniel Muñoz and Dr Alfredo Laffue; From Instituta de Neurologica de Curibita, Curibita, Brazil, Dr Walter Oleschko Arruda; From Assaf Harofeh Medical Center, Beer-Yaakov, Israel, Dr Shlomo Flechter; From St Vincents Hospital, Victoria, Australia, Dr Mark Paine; From Centro Internacional de Restauracion Neurologica, Havana, Cuba, Dr Jose Antonio Cabrera-Gomez; From Consultorio Privado, Buenos Aires, Argentina, Dr Aldo Savino; From Mater Dei Hospital, Msida, Malta, Dr Malcolm Vella; From Geelong Hospital, Victoria, Australia, Dr Cameron Shaw; From Hospital de Especialidades. Centro Medico Nacional Siglo XXI, Mexico, Dr Eli Skromne; From HIGA Gral, San Martin La Plata, Argentina, Dr Vetere Santiago; From Instituto de Neurociencias Cordoba, Argentina, Dr Elisabeth Bacile.

  • Funding This study was funded by the MSBase Foundation, a not-for-profit organisation. The MSBase Foundation receives financial support from Merck Serono, Biogen Idec, Novartis Pharma, Bayer Schering and Sanofi Aventis.

  • Correction notice This article has been corrected since it was published Online First. Some of the author affiliations were incorrect and these have now been rectified.

  • Competing interests SHu has received unrestricted educational grants from Bayer Schering Australia, Biogen Idec, Merck Serono and Sanofi Aventis. MT received honoraria for consultancy and/or speaking from Biogen Idec, Sanofi-Aventis, Merck Serono and Bayer Schering and research grants from Merck Serono, Biogen Idec and Novartis Pharma. AL is a Biogen Dompe, Merck Serono and Bayer Schering advisory board member. She receives travel grants and honoraria from Bayer Schering, Biogen Dompe, Merck Serono, Novartis, Sanofi Aventis and Teva and research grants from Bayer Schering, Biogen Dompe, Merck Serono, Novartis and Sanofi Aventis. She is a member of the steering committee of a trial sponsored by Merck Serono and is the Italian coordinator of a Biogen-Dompé study. She has also received travel and research grants from the Associazione Italiana Sclerosi Multipla and is a consultant of ‘Fondazione Cesare Serono’. GIz has received honoraria for consultation from Biogen Idec, Merck Serono, Teva, Bayer, Novartis and Sanofi Aventis. FG is a Novartis advisory board member and receives Speakers Bureau from Teva and research grants from Genzyme, Novartis, BiogenIdec, Teva, ONO, UBC and EMD Serono. PD reports participating in advisory boards for TEVA, EMD Serono, Biogen Idec, Novartis and Bayer Schering. He also receives research grants from Biogen Idec, CIHR and the MS Society of Canada. MG reports participating in advisory boards for Teva Neuroscience and Biogen Idec. He has received travel grants from Biogen Idec and EMD Serono as well as honoraria for speaking engagements from Teva Neurosciences, Biogen Idec, EMD Serono and Novartis Pharma. PG has received research grants from Sanofi-Avantis and Biogen-Idec. PG has also received honoraria for advisory councils and teaching programs with Novartis Pharma, Teva Neuroscience, EMD Serono, Biogen Idec and Bayer. CO-G has received honoraria as consultant in scientific advisory boards by Biogen-Idec, Bayer-Schering, Merck-Serono, Teva and Novartis and has also participated in clinical trials and other research projects promoted by Biogen-Idec, GSK, Teva and Novartis. RH has received honoraria for consultancy for Biogen Idec, reports participating in an advisory board for Merck Serono and has received grants from Biogen Idec and Merck Serono. RB has received research grants from Bayer-Schering, Biogen Dompè, Novartis, Sanofi Aventis and Merck Serono; honoraria for speaking from Bayer-Schering, Sanofi Aventis and Merck Serono; grants to cover travel expenses from Bayer-Schering, Biogen Dompè, Sanofi Aventis, Merck Serono and Novartis. MER has received payment for lectures from Serono Symposia International. JL-S institution receives non-directed funding as well as honoraria for presentations and membership on advisory boards from Sanofi Aventis, Biogen Idec, Bayer Health Care, Merck Serono and Novartis Australia. VvP serves on an advisory board for Biogen Idec. He has received travel grants from Biogen Idec, Bayer Schering, Sanofi Aventis, Merck Serono and Novartis Pharma and speaking honoraria from Biogen Idec. MF received conference travel support from Merck Serono. FV has received honoraria as a member of an advisory board for Merck Serono. MB has received research support and/or honoraria from Bayer Schering, Biogen Idec, Merck Serono, Novartis Pharma, Sanofi Aventis and Teva. MS reports participating in advisory boards for Sanofi Aventis, Merck Serono, Biogen Idec, Novartis Pharma and Bayer Schering. JH receives honoraria from Teva, Bayer, Merck Serono and Biogen Idec. IK has received grants from the National MS Society and Bayer. NV receives honoraria from Novartis Pharma and conference travel support from Biogen Idec, Eisai, GSK, Novartis and Bayer Schering. FM has participated in MS clinical trials sponsored by EMD Serono and Bayer and has received honorarium from Teva and Bayer for consultancy, EMD Serono for organisation of a teaching course and Serono for speaking. He has also received conference support from Serono, Teva and Biogen. SHa has received an unrestricted educational grant and travel grants from Merck Serono. OG has received unrestricted educational grants from Merck Serono and Biogen Idec. HB has served on scientific advisory boards for Biogen Idec, Novartis and Sanofi-Aventis and has received conference travel support from Novartis, Biogen Idec and Sanofi Aventis. He serves on steering committees for trials conducted by Merck Serono, Biogen Idec and Novartis. HB has received research support from Merck Serono, Novartis and Biogen Idec in his capacity as honorary chair of the MSBase Foundation. He is on the editorial board of Multiple Sclerosis International. He is the recipient of a National Health and Medical Research Council (NHMRC) Career Development Award (628856), NHMRC Project Grants (566513, 628799, 1009757), NHMRC Centre of Excellence Award (1001216), an Australian Research Council Linkage Grant (LP110100473) RG and a National MS Society (USA) Project Grant (RG3850A3/1). TS, CB, GG, GIu, TP-B, VS, VJ, GM and FK report no disclosures.

  • Ethics approval Relevant ethics approvals or waivers were obtained at each participating site.

  • Provenance and peer review Not commissioned; externally peer reviewed.