BACKGROUND AND OBJECTIVE: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. METHODS: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. RESULTS: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. CONCLUSIONS: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.

Blizard Institute Queen Mary University of London Barts and The London School of Medicine and Dentistry UK

Blizard Institute Queen Mary University of London Barts and The London School of Medicine and Dentistry UK Departments of Neurology and Biomedicine University Hospital Basel University of Basel Switzerland

C Mondino National Neurological Institute Italy

Center for Neuroimmunology and Department of Neurology Institut d'investigacions Biomèdiques August Pi Sunyer Hospital Clinic of Barcelona Spain

Centre for Experimental Neurological Therapies S Andrea Hospital site Department of Neuroscience Mental Health and Sensory Organs Faculty of Medicine and Psychology Sapienza University Italy

Centre of Multiple Sclerosis City Clinical Hospital 31 Russia

Clinic of Neurology Belgrade University School of Medicine Serbia

Department of Basic Medical Sciences Neuroscience and Sense Organs University of Bari Italy

Department of Health Sciences and IRCAD Eastern Piedmont University Italy

Department of Neurology and Immunology Hospital Ramón y Cajal Spain

Department of Neurology and INSPE Vita Salute San Raffaele University Scientific Institute San Raffaele Italy

Department of Neurology Charles University Prague Czech Republic

Department of Neurology CSF Laboratory and MS Outpatient Unit University of Ulm Germany

Department of Neurology Erasmus MC University Medical Center The Netherlands

Department of Neurology Glostrup Hospital University of Copenhagen Denmark

Department of Neurology Innsbruck Medical University Austria

Department of Neurology Istanbul University Turkey

Department of Neurology Medical Faculty Heinrich Heine University Germany

Department of Neurology Medical University of Graz Austria

Department of Neurology Medical University of Lublin Poland

Department of Neurology of Hospital Británico of Buenos Aires Argentina

Department of Neurology Université de Lyon Université Claude Bernard Lyon 1 France

Department of Neurology University of Genoa Italy

Department of Neurology University of Szeged Hungary

Department of Neurology University of Toulouse France

Department of Physiology Anatomy and Genetics and Medical Research Council Functional Genomics Unit University of Oxford UK

Department of Radiology Innsbruck Medical University Austria

Departments of Neurology and Biomedicine University Hospital Basel University of Basel Switzerland

Departments of Neurology and Clinical Chemistry MS Center Neurocampus Amsterdam VU University Medical Centre Amsterdam The Netherlands and BioMS eu network

Dr Orhan Öcalgiray Molecular Biology Biotechnology and Genetics Research Centre Istanbul Technical University Turkey

Institut de Génomique Fonctionelle CNRS UMR5203 INSERM U661 Université Montpellier 1 Université Montpellier France and Hôpital Carémeau France

Institute of Neuroscience and Physiology The Sahlgrenska Academy University of Gothenburg Sweden

KG Jebsen Centre for MS Research Department of Clinical Medicine Haukeland University Hospital University of Bergen Norway

MS Centre SCDU Neurology Head and Neck Department AOU Maggiore della Carità Italy

MS Unit Neurology Department La Fe University and Polytechnic Hospital Instituto de investigación Sanitaria La Fe Spain

Neuroimmunology Unit Department of Clinical Neuroscience Karolinska Institutet Sweden

Neurology Unit Dept of Pathophysiology and Transplantation University of Milan Fondazione Cà Granda IRCCS Policlinico

Pôle de Neurosciences Cliniques Service de Neurologie Centre de Résonance Magnétique Biologique et Médicale Centre Hospitalier Universitaire Timone Laboratoire d'histocompatibilité Etablissement Français du Sang Alpes Méditerrannée Aix Marseille Université France

Servei de Neurologia Neuroimmunologia Centre d'Esclerosi Múltiple de Catalunya Hospital Universitari Vall d'Hebron Universitat Autònoma de Barcelona Spain

Unit of Functional Imaging Glostrup Hospital University of Copenhagen Denmark

Wolfson Institute of Preventive Medicine Queen Mary University of London Barts and the London School for Medicine and Dentistry UK

Mult Scler. 2015 Jul;21(8):967-8. doi: 10.1177/1352458515588583. PubMed

Citace poskytuje Crossref.org

Drug Treatment of Clinically Isolated Syndrome

Current status of biomarker research in neurology