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

J Kuhle , G Disanto , R Dobson , R Adiutori , L Bianchi (1) , J Topping (2) , Jp Bestwick , U-C Meier (3) , M Marta , G Dalla Costa (4) , T Runia , E Evdoshenko , N Lazareva , Eric Thouvenot (5, 6, 7) , P Iaffaldano , V Direnzo , M Khademi , F Piehl , M Comabella , M Sombekke , J Killestein , H Hegen , S Rauch (8) , S d'Alfonso (9) , Jc Alvarez-Cermeño , P Kleinová , D Horáková , R Roesler (10) , F Lauda , S Llufriu (11, 12) , T Avsar , U Uygunoglu , A Altintas (13) , S Saip , T Menge , C Rajda , R Bergamaschi , N Moll (14) , M Khalil (15) , R Marignier , I Dujmovic , H Larsson (16) , C Malmestrom , E Scarpini (17) , C Fenoglio , S Wergeland , A Laroni , V Annibali , S Romano (18) , Ad Martínez (19) , A Carra (20) , M Salvetti (21) , A Uccelli (22) , Ø Torkildsen , Km Myhr (23) , D Galimberti , K Rejdak , J Lycke , Jl Frederiksen (24) , J Drulovic , C Confavreux (25) , David Brassat , C Enzinger , S Fuchs (26) , I Bosca , Christophe Picard (27, 28) , E Colombo , D Franciotta (29) , T Derfuss , Rlp Lindberg , Ö Yaldizli , L Vécsei (30) , Bc Kieseier , Hp Hartung (31) , P Villoslada (32) , A Siva , A Saiz (33) , H Tumani (34) , E Havrdová (32) , Lm Villar , M Leone (35) , N Barizzone (36) , F Deisenhammer , C Teunissen , X Montalban (37) , M Tintoré , T Olsson (38) , M Trojano , S Lehmann (39, 5) , Giovanni Castelnovo , S Lapin , R Hintzen , L Kappos (40) , R Furlan , V Martinelli (41) , G Comi (42) , Sv Ramagopalan (43) , G Giovannoni (44)

1 DAM - Direction des Applications Militaires
2 NOC - National Oceanography Centre
3 Department of Anatomy and Structural Biology Albert Einstein College of Medicine
4 Department of public health
5 Cellules souches normales et cancéreuses
6 PSNREC - Neuropsychiatrie : recherche épidémiologique et clinique
7 IGF - Institut de Génomique Fonctionnelle
8 Water Environment Technology
9 Department of Neurology, A.O.U. Maggiore della Carità, and IRCAD, Novara
10 IGB - Leibniz-Institut für Gewässerökologie und Binnenfischerei
11 Department of Neurology
12 Center for Neuroimmunology, Service of Neurology
13 UEB - Université européenne de Bretagne - European University of Brittany
14 IMS - Laboratoire de l'intégration, du matériau au système
15 Azm Center for Biotechnology Research
16 FOI
17 Centro Dino Ferrari [Milano]
18 IRMP-Louvain
19 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
20 TIMC-IMAG - Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525
21 DIA - Dipartimento Ingegneria Aerospaziale "Lucio Lazzarino"
22 International Centre for Hydrology "Dino Tonini" and Dipartimento IMAGE
23 Dept. of Neurology, University Hospital Rigshospitalet
24 UC Berkeley - University of California [Berkeley]
25 CREATIS - Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé
26 Department of Immunology
27 ADES - Anthropologie bio-culturelle, Droit, Ethique et Santé
28 EFS - Alpes-Méditerranée - Etablissement Français du Sang - Alpes-Méditerranée
29 UNIPV - Università degli Studi di Pavia = University of Pavia
30 Department of Neurology, Albert Szent-Gyorgyi Clinical Centre
31 Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf]
32 CRMBM - Centre de résonance magnétique biologique et médicale
33 Department of Neurology
34 University of Ulm, Department of Neurology
35 Service Anesthésie et Réanimation [Hôpital Nord - APHM]
36 University of Eastern Piedmont, Department of Medical Sciences, IRCAD, Novara
37 Vall d'Hebron University Hospital [Barcelona]
38 Department of Public Health and Clinical Medicine
39 IRB - Institut de recherche en biothérapie
40 Felix Splatter Hospital [Bâle]
41 Laboratory of Molecular Virology
42 Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute,
43 AOPP - Department of Atmospheric, Oceanic and Planetary Physics [Oxford]
44 Blizard Institute of Cell and Molecular Science

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. 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. 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. 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.

Mots clés: clinic study; sclerosis

Domaines: Anthropologie biologique

J Kuhle, G Disanto, R Dobson, R Adiutori, L Bianchi, et al.. Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study.. Multiple Sclerosis Journal, 2015, pp.2015 Feb 13. ⟨10.1177/1352458514568827⟩. ⟨hal-01139819⟩