Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study. (July 2015)

• Record Type: Journal Article
• Authors: Kuhle, J; Disanto, G; Dobson, R; Adiutori, R; Bianchi, L; Topping, J; Bestwick, JP; Meier, U-C; Marta, M; Costa, G Dalla; Runia, T; Evdoshenko, E; Lazareva, N; Thouvenot, E; Iaffaldano, P; Direnzo, V; Khademi, M; Piehl, F; Comabella, M; Sombekke, M; Killestein, J; Hegen, H; Rauch, S; D'Alfonso, S; Alvarez-Cermeño, JC; Kleinová, P; Horáková, D; Roesler, R; Lauda, F; Llufriu, S; Avsar, T; Uygunoglu, U; Altintas, A; Saip, S; Menge, T; Rajda, C; Bergamaschi, R; Moll, N; Khalil, M; Marignier, R; Dujmovic, I; Larsson, H; Malmestrom, C; Scarpini, E; Fenoglio, C; Wergeland, S; Laroni, A; Annibali, V; Romano, S; Martínez, AD; Carra, A; Salvetti, M; Uccelli, A; Torkildsen, Ø; Myhr, KM; Galimberti, D; Rejdak, K; Lycke, J; Frederiksen, JL; Drulovic, J; Confavreux, C; Brassat, D; Enzinger, C; Fuchs, S; Bosca, I; Pelletier, J; Picard, C; Colombo, E; Franciotta, D; Derfuss, T; Lindberg, RLP; Yaldizli, Ö; Vécsei, L; Kieseier, BC; Hartung, HP; Villoslada, P; Siva, A; Saiz, A; Tumani, H; Havrdová, E; Villar, LM; Leone, M; Barizzone, N; Deisenhammer, F; Teunissen, C; Montalban, X; Tintoré, M; Olsson, T; Trojano, M; Lehmann, S; Castelnovo, G; Lapin, S; Hintzen, R; Kappos, L; Furlan, R; Martinelli, V; Comi, G; Ramagopalan, SV; Giovannoni, G;
• Is Part Of: Multiple sclerosis. Volume 21:Number 8(2015)
• Page Start: 1013
• Page End: 1024
• Publication Date: 2015-07
• Subjects: Clinically definite multiple sclerosis (CDMS) -- clinically isolated syndrome (CIS) -- Epstein-Barr nuclear antigen 1 (EBNA-1) -- oligoclonal bands (OCBs) -- serum 25-hydroxyvitamin D3 (25-OH-D); Central nervous system -- Diseases -- Periodicals; Myelin sheath -- Diseases -- Periodicals; Inflammation -- Periodicals; Multiple sclerosis -- Periodicals; Central Nervous System Diseases -- Periodicals; Demyelinating Diseases -- Periodicals; Inflammation -- Periodicals; Multiple Sclerosis -- Periodicals; Système nerveux central -- Maladies -- Périodiques; Gaine de myéline -- Maladies -- Périodiques; Inflammation (Pathologie) -- Périodiques; Sclérose en plaques -- Périodiques; Electronic journals; 616.834005
• DOI: 10.1177/1352458514568827
• Languages: English
• ISSNs: 1352-4585

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.