J Kuhle1, G Disanto2, R Dobson2, R Adiutori2, L Bianchi2, J Topping2, J P Bestwick3, U-C Meier2, M Marta2, G Dalla Costa4, T Runia5, E Evdoshenko6, N Lazareva6, E Thouvenot7, P Iaffaldano8, V Direnzo8, M Khademi9, F Piehl9, M Comabella10, M Sombekke11, J Killestein11, H Hegen12, S Rauch13, S D'Alfonso14, J C Alvarez-Cermeño15, P Kleinová16, D Horáková16, R Roesler17, F Lauda17, S Llufriu18, T Avsar19, U Uygunoglu20, A Altintas20, S Saip20, T Menge21, C Rajda22, R Bergamaschi23, N Moll24, M Khalil25, R Marignier26, I Dujmovic27, H Larsson28, C Malmestrom29, E Scarpini30, C Fenoglio30, S Wergeland31, A Laroni32, V Annibali33, S Romano33, A D Martínez34, A Carra34, M Salvetti33, A Uccelli32, Ø Torkildsen31, K M Myhr32, D Galimberti30, K Rejdak35, J Lycke29, J L Frederiksen36, J Drulovic27, C Confavreux26, D Brassat37, C Enzinger25, S Fuchs25, I Bosca38, J Pelletier24, C Picard24, E Colombo23, D Franciotta23, T Derfuss39, Rlp Lindberg39, Ö Yaldizli39, L Vécsei22, B C Kieseier21, H P Hartung21, P Villoslada18, A Siva20, A Saiz18, H Tumani17, E Havrdová16, L M Villar15, M Leone40, N Barizzone14, F Deisenhammer12, C Teunissen11, X Montalban10, M Tintoré10, T Olsson9, M Trojano8, S Lehmann7, G Castelnovo7, S Lapin6, R Hintzen5, L Kappos39, R Furlan4, V Martinelli4, G Comi4, S V Ramagopalan41, G Giovannoni42. 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. 42. Blizard Institute, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, UK g.giovannoni@qmul.ac.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.
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.
Authors: Simon Gamraoui; Guillaume Mathey; Marc Debouverie; Catherine Malaplate; René Anxionnat; Francis Guillemin; Jonathan Epstein Journal: J Neurol Date: 2019-02-01 Impact factor: 4.849
Authors: Lorenzo Gaetani; Luca Prosperini; Andrea Mancini; Paolo Eusebi; Maria Chiara Cerri; Carlo Pozzilli; Paolo Calabresi; Paola Sarchielli; Massimiliano Di Filippo Journal: J Neurol Date: 2018-09-08 Impact factor: 4.849
Authors: Steffen Halbgebauer; André Huss; Mathias Buttmann; Petra Steinacker; Patrick Oeckl; Isabel Brecht; Andreas Weishaupt; Hayrettin Tumani; Markus Otto Journal: J Neurol Date: 2016-03-19 Impact factor: 4.849