Contribution of different relapse phenotypes to disability in multiple sclerosis

Tamasine Stewart, Tim Spelman, Eva Havrdova, Dana Horakova, Maria Trojano, Guillermo Izquierdo, Pierre Pascal Duquette, Marc Girard, Alexandre Prat, Alessandra Lugaresi, Francois Grand'Maison, Pierre Grammond, Patrizia Sola, Vahid Shaygannejad, Raymond Hupperts, Raed A Alroughani, Celia Oreja-Guevara, Eugenio Pucci, Cavit Boz, Jeannette Lechner-ScottRoberto Bergamaschi, Vincent Van Pesch, Gerardo Iuliano, Cristina Ramo, Bruce V Taylor, Mark Slee, Daniele La Spitaleri, Franco Granella, Freek Verheul, Pamela A McCombe, Suzanne J Hodgkinson, Maria Pia Amato, Steve Vucic, Orla M Gray, Edgardo Cristiano, Michael Barnett, Jose Luis Sanchez-Menoyo, Erik Van Munster, Maria Laura Saladino, Javier Olascoaga, Julie Prevost, Norma H Deri, Cameron Shaw, Bhim Singhal, Fraser G A Moore, Csilla Rozsa, Neil Shuey, Olga Skibina, Ilya Kister, Tatjana Petkovska-Boskova, Radek Ampapa, Allan Kermode, Helmut Butzkueven, Vilija Jokubaitis, Tomas Kalincik

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31 Citations (Scopus)


Objective: This study evaluated the effect of relapse phenotype on disability accumulation in multiple sclerosis. Methods: Analysis of prospectively collected data was conducted in 19,504 patients with relapse-onset multiple sclerosis and minimum 1-year prospective follow-up from the MSBase cohort study. Multivariable linear regression models assessed associations between relapse incidence, phenotype and changes in disability (quantified with Expanded Disability Status Scale and its Functional System scores). Sensitivity analyses were conducted. Results: In 34,858 relapses recorded during 136,462 patient-years (median follow-up 5.9 years), higher relapse incidence was associated with greater disability accumulation (β = 0.16, p < 0.001). Relapses of all phenotypes promoted disability accumulation, with the most pronounced increase associated with pyramidal (β = 0.27 (0.25-0.29)), cerebellar (β = 0.35 (0.30-0.39)) and bowel/bladder (β = 0.42 (0.35-0.49)) phenotypes (mean (95% confidence interval)). Higher incidence of each relapse phenotype was associated with an increase in disability in the corresponding neurological domain, as well as anatomically related domains. Conclusion: Relapses are associated with accumulation of neurological disability. Relapses in pyramidal, cerebellar and bowel/bladder systems have the greatest association with disability change. Therefore, prevention of these relapses is an important objective of disease-modifying therapy. The differential impact of relapse phenotypes on disability outcomes could influence management of treatment failure in multiple sclerosis.

Original languageEnglish
Pages (from-to)266-276
Number of pages11
JournalMultiple Sclerosis Journal
Issue number2
Publication statusPublished - 1 Feb 2017


  • cohort studies
  • multiple sclerosis
  • observational study
  • outcome research
  • Prognosis
  • relapse phenotype

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