title: Quantifying risk of early relapse in patients with first demyelinating events: Prediction in clinical practice.
abstract: BACKGROUND
  Characteristics at clinically isolated syndrome (CIS) examination assist in identification of patient at highest risk of early second attack and could benefit the most from early disease-modifying drugs (DMDs).
  
  
  OBJECTIVE
  To examine determinants of second attack and validate a prognostic nomogram for individualised risk assessment of clinical conversion.
  
  
  METHODS
  Patients with CIS were prospectively followed up in the MSBase Incident Study. Predictors of clinical conversion were analysed using Cox proportional hazards regression. Prognostic nomograms were derived to calculate conversion probability and validated using concordance indices.
  
  
  RESULTS
  A total of 3296 patients from 50 clinics in 22 countries were followed up for a median (inter-quartile range (IQR)) of 1.92 years (0.90, 3.71). In all, 1953 (59.3%) patients recorded a second attack. Higher Expanded Disability Status Scale (EDSS) at baseline, first symptom location, oligoclonal bands and various brain and spinal magnetic resonance imaging (MRI) metrics were all predictors of conversion. Conversely, older age and DMD exposure post-CIS were associated with reduced rates. Prognostic nomograms demonstrated high concordance between estimated and observed conversion probabilities.
  
  
  CONCLUSIONS
  This multinational study shows that age at CIS onset, DMD exposure, EDSS, multiple brain and spinal MRI criteria and oligoclonal bands are associated with shorter time to relapse. Nomogram assessment may be useful in clinical practice for estimating future clinical conversion.
authors.affiliation: Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia.
authors.forename: Tim
authors.initials: T
authors.lastname: Spelman
authors.affiliation: Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia.|Department of Neurophysiologie, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Meyniel
authors.affiliation: Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Juan Ignacio
authors.initials: JI
authors.lastname: Rojas
authors.affiliation: MS Center, Department of Neuroscience and Imaging, University 'G. d'Annunzio', Chieti, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lugaresi
authors.affiliation: Hospital Universitario Virgen Macarena, Sevilla, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Izquierdo
authors.affiliation: Neuro Rive-Sud, Hôpital Charles LeMoyne, Greenfield Park, QC, Canada.
authors.forename: Francois
authors.initials: F
authors.lastname: Grand'Maison
authors.affiliation: Karadeniz Technical University, Trabzon, Turkey.
authors.forename: Cavit
authors.initials: C
authors.lastname: Boz
authors.affiliation: Amiri Hospital, Kuwait City, Kuwait.
authors.forename: Raed
authors.initials: R
authors.lastname: Alroughani
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, General University Hospital and Charles University in Prague, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, General University Hospital and Charles University in Prague, Prague, Czech Republic.
authors.forename: Dana
authors.initials: D
authors.lastname: Horakova
authors.affiliation: Ospedali Riuniti di Salerno, Salerno, Italy.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Iuliano
authors.affiliation: Hôpital Notre-Dame, Montreal, QC, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Duquette
authors.affiliation: Ondokuz Mayis University, Samsun, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Terzi
authors.affiliation: Centre de réadaptation en déficience physique Chaudière-Appalaches, Levis, QC, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Grammond
authors.affiliation: Maaslandziekenhuis, Sittard, The Netherlands.
authors.forename: Raymond
authors.initials: R
authors.lastname: Hupperts
authors.affiliation: John Hunter Hospital, Newcastle, NSW, Australia.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Lechner-Scott
authors.affiliation: Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Oreja-Guevara
authors.affiliation: Neurology Unit, ASUR Marche - AV3, Macerata, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Pucci
authors.affiliation: Groene Hart Ziekenhuis, Gouda, The Netherlands.
authors.forename: Freek
authors.initials: F
authors.lastname: Verheul
authors.affiliation: Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia, Buenos Aires, Argentina.
authors.forename: Marcela
authors.initials: M
authors.lastname: Fiol
authors.affiliation: Cliniques Universitaires Saint-Luc, Brussels, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Van Pesch
authors.affiliation: Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Edgardo
authors.initials: E
authors.lastname: Cristiano
authors.affiliation: Kommunehospitalet, Aarhus, Denmark.
authors.forename: Thor
authors.initials: T
authors.lastname: Petersen
authors.affiliation: Jewish General Hospital, Montreal, QC, Canada.
authors.forename: Fraser
authors.initials: F
authors.lastname: Moore
authors.affiliation: Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia.
authors.forename: Tomas
authors.initials: T
authors.lastname: Kalincik
authors.affiliation: Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia.
authors.forename: Vilija
authors.initials: V
authors.lastname: Jokubaitis
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Trojano
authors.affiliation: Department of Neurology, Box Hill hospital, Monash University, Box Hill, VIC, Australia.
authors.forename: Helmut
authors.initials: H
authors.lastname: Butzkueven
mesh_terms: D000328:Adult; D017668:Age of Onset; D003711:Demyelinating Diseases / Q000188:drug therapy / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology; D049451:Nomograms; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D012307:Risk Factors
chemical_list: D007166:Immunosuppressive Agents
keywords: CIS; CSF; MRI; MS; Nomogram; clinically definite multiple sclerosis; clinically isolated syndrome; disease-modifying drugs; second attack