title: Contribution of different relapse phenotypes to disability in multiple sclerosis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia.
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authors.affiliation: Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia/Department of Neurology, Melbourne Brain Centre at Royal Melbourne Hospital, Parkville, VIC, Australia.
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authors.lastname: Spelman
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, General University Hospital and Charles University in Prague, Prague, Czech Republic.
authors.forename: Eva
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authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, General University Hospital and Charles University in Prague, Prague, Czech Republic.
authors.forename: Dana
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authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy.
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authors.affiliation: Hôpital Notre Dame, CHUM and Université de Montréal, Montreal, QC, Canada.
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authors.affiliation: Hôpital Notre Dame, CHUM and Université de Montréal, Montreal, QC, Canada.
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authors.affiliation: MS Centre, Department of Neuroscience, Imaging and Clinical Sciences, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy.
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authors.affiliation: Neurology Unit, Department of Neuroscience, Nuovo Ospedale Civile S. Agostino-Estense, Modena, Italy.
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authors.affiliation: Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
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authors.forename: Jeannette
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authors.forename: Vincent
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authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
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authors.affiliation: Flinders University and Medical Centre, Adelaide, SA, Australia.
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authors.affiliation: AORN San Giuseppe Moscati, Avellino, Italy.
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authors.lastname: Spitaleri
authors.affiliation: University of Parma, Parma, Italy.
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authors.affiliation: Groene Hart Ziekenhuis, Gouda, The Netherlands.
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authors.affiliation: Centre for Clinical Research, The University of Queensland Australia, Brisbane, QLD, Australia.
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authors.affiliation: Departments of Nephrology and Neurology, Liverpool Hospital, Liverpool, NSW, Australia.
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authors.affiliation: Section of Neurosciences, NEUROFARBA, University of Florence, Florence, Italy.
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authors.affiliation: Westmead Hospital, Sydney, NSW, Australia.
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authors.affiliation: Craigavon Area Hospital, Portadown, UK.
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authors.affiliation: Brain and Mind Centre, Camperdown, NSW, Australia.
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authors.affiliation: Department of Neurology, Hospital de Galdakao-Usansolo, Galdakao, Spain.
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authors.lastname: Skibina
authors.affiliation: Department of Neurology, NYU School of Medicine, New York, NY, USA.
authors.forename: Ilya
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authors.affiliation: Clinical Neurology Clinical Center, Skopje, Macedonia.
authors.forename: Tatjana
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authors.lastname: Petkovska-Boskova
authors.affiliation: Nemocnice Jihlava, Jihlava, Czech Republic.
authors.forename: Radek
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authors.affiliation: Western Australian Neuroscience Research Institute, The University of Western Australia, Perth, WA, Australia/Institute of Immunology and Infectious Diseases, Murdoch University, Perth, WA, Australia.
authors.forename: Allan
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authors.lastname: Kermode
authors.affiliation: Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia/Department of Neurology, Melbourne Brain Centre at Royal Melbourne Hospital, Parkville, VIC, Australia/Department of Neurology, Box Hill Hospital, Monash University, Melbourne, VIC, Australia.
authors.forename: Helmut
authors.initials: H
authors.lastname: Butzkueven
authors.affiliation: Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia/Department of Neurology, Melbourne Brain Centre at Royal Melbourne Hospital, Parkville, VIC, Australia.
authors.forename: Vilija
authors.initials: V
authors.lastname: Jokubaitis
authors.affiliation: Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia/Department of Neurology, Melbourne Brain Centre at Royal Melbourne Hospital, Parkville, VIC, Australia.
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mesh_terms: D000328:Adult; D002908:Chronic Disease; D004185:Disability Evaluation; D006233:Persons with Disabilities / Q000706:statistics & numerical data*; D018450:Disease Progression; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000503:physiopathology; D011446:Prospective Studies; D012008:Recurrence
chemical_list: D016899:Interferon-beta
keywords: Prognosis; cohort studies; multiple sclerosis; observational study; outcome research; relapse phenotype