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

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

Affiliations

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.

PMID: 25680984
DOI: 10.1177/1352458514568827

Multicenter Study

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

J Kuhle et al. Mult Scler. 2015 Jul.

. 2015 Jul;21(8):1013-24.

doi: 10.1177/1352458514568827. Epub 2015 Feb 13.

Authors

Affiliations

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.

PMID: 25680984
DOI: 10.1177/1352458514568827

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.

Keywords: Clinically definite multiple sclerosis (CDMS); Epstein-Barr nuclear antigen 1 (EBNA-1); clinically isolated syndrome (CIS); oligoclonal bands (OCBs); serum 25-hydroxyvitamin D3 (25-OH-D).

PubMed Disclaimer

Comment in

Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study.
Ciccarelli O, Toosy AT. Ciccarelli O, et al. Mult Scler. 2015 Jul;21(8):967-8. doi: 10.1177/1352458515588583. Epub 2015 Jun 3. Mult Scler. 2015. PMID: 26041796 No abstract available.

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- Atypon
Other Literature Sources
- The Lens - Patent Citations Database
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Comment in

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical