Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study-Reference-Cited by-同舟云学术

Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study

Published:2015-02-13 Issue:8 Volume:21 Page:1013-1024
ISSN:1352-4585
Container-title:Multiple Sclerosis Journal
language:en
Short-container-title:Mult Scler

Author:

Kuhle J¹,Disanto G²,Dobson R²,Adiutori R²,Bianchi L²,Topping J²,Bestwick JP³,Meier U-C²,Marta M²,Costa G Dalla⁴,Runia T⁵,Evdoshenko E⁶,Lazareva N⁶,Thouvenot E⁷,Iaffaldano P⁸,Direnzo V⁸,Khademi M⁹,Piehl F⁹,Comabella M¹⁰,Sombekke M¹¹,Killestein J¹¹,Hegen H¹²,Rauch S¹³,D’Alfonso S¹⁴,Alvarez-Cermeño JC¹⁵,Kleinová P¹⁶,Horáková D¹⁶,Roesler R¹⁷,Lauda F¹⁷,Llufriu S¹⁸,Avsar T¹⁹,Uygunoglu U²⁰,Altintas A²⁰,Saip S²⁰,Menge T²¹,Rajda C²²,Bergamaschi R²³,Moll N²⁴,Khalil M²⁵,Marignier R²⁶,Dujmovic I²⁷,Larsson H²⁸,Malmestrom C²⁹,Scarpini E³⁰,Fenoglio C³⁰,Wergeland S³¹,Laroni A³²,Annibali V³³,Romano S³³,Martínez AD³⁴,Carra A³⁴,Salvetti M³³,Uccelli A³²,Torkildsen Ø³¹,Myhr KM³²,Galimberti D³⁰,Rejdak K³⁵,Lycke J²⁹,Frederiksen JL³⁶,Drulovic J²⁷,Confavreux C²⁶,Brassat D³⁷,Enzinger C²⁵,Fuchs S²⁵,Bosca I³⁸,Pelletier J²⁴,Picard C²⁴,Colombo E²³,Franciotta D²³,Derfuss T³⁹,Lindberg RLP³⁹,Yaldizli Ö³⁹,Vécsei L²²,Kieseier BC²¹,Hartung HP²¹,Villoslada P¹⁸,Siva A²⁰,Saiz A¹⁸,Tumani H¹⁷,Havrdová E¹⁶,Villar LM¹⁵,Leone M⁴⁰,Barizzone N¹⁴,Deisenhammer F¹²,Teunissen C¹¹,Montalban X¹⁰,Tintoré M¹⁰,Olsson T⁹,Trojano M⁸,Lehmann S⁷,Castelnovo G⁷,Lapin S⁶,Hintzen R⁵,Kappos L³⁹,Furlan R⁴,Martinelli V⁴,Comi G⁴,Ramagopalan SV⁴¹,Giovannoni G²

Affiliation:

1. 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

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

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

4. Department of Neurology and INSPE, Vita-Salute San Raffaele University, Scientific Institute San Raffaele, Italy

5. Department of Neurology, Erasmus MC University Medical Center, The Netherlands

6. Centre of Multiple Sclerosis, City Clinical Hospital#31, Russia

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

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

9. Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Sweden

10. Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Institut de Receca Vall d’Hebron (VHIR), Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Spain

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

12. Department of Neurology, Innsbruck Medical University, Austria

13. Department of Radiology, Innsbruck Medical University, Austria

14. Department of Health Sciences and IRCAD, Eastern Piedmont University, Italy

15. Department of Neurology and Immunology, Hospital Ramón y Cajal, Spain

16. Department of Neurology, Charles University in Prague, Czech Republic

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

18. Center for Neuroimmunology and Department of Neurology. Institut d’investigacions Biomèdiques August Pi Sunyer (IDIBAPS) – Hospital Clinic of Barcelona, Spain

19. Dr Orhan Öcalgiray Molecular Biology-Biotechnology and Genetics Research Centre, Istanbul Technical University, Turkey

20. Department of Neurology, Istanbul University, Turkey

21. Department of Neurology, Medical Faculty, Heinrich-Heine-University, Germany

22. Department of Neurology, University of Szeged, Hungary

23. C. Mondino National Neurological Institute, Italy

24. 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

25. Department of Neurology, Medical University of Graz, Austria

26. Department of Neurology, Université de Lyon, Université Claude Bernard-Lyon 1, France

27. Clinic of Neurology, Belgrade University School of Medicine, Serbia

28. Unit of Functional Imaging, Glostrup Hospital, University of Copenhagen, Denmark

29. Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sweden

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

31. KG Jebsen Centre for MS-Research, Department of Clinical Medicine, Haukeland University Hospital, University of Bergen, Norway

32. Department of Neurology, University of Genoa, Italy

33. Centre for Experimental Neurological Therapies, S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University, Italy

34. Department of Neurology of Hospital Británico of Buenos Aires, Argentina

35. Department of Neurology, Medical University of Lublin, Poland

36. Department of Neurology, Glostrup Hospital, University of Copenhagen, Denmark

37. Department of Neurology, University of Toulouse, France

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

39. Departments of Neurology and Biomedicine, University Hospital Basel, University of Basel, Switzerland

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

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

Abstract

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.

Publisher

SAGE Publications

Subject

Clinical Neurology,Neurology

Link

http://journals.sagepub.com/doi/pdf/10.1177/1352458514568827

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