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

J. Kuhle, G. Disanto, R. Dobson, R. Adiutori, L. Bianchi, J. Topping, J. P. Bestwick, U. C. Meier, M. Marta, G. Dalla Costa, T. Runia, E. Evdoshenko, N. Lazareva, E. Thouvenot, P. Iaffaldano, V. Direnzo, M. Khademi, F. Piehl, M. Comabella, M. SombekkeJ. Killestein, H. Hegen, S. Rauch, S. Dalfonso, J. C. Alvarez-Cermeño, P. Kleinová, D. Horáková, R. Roesler, F. Lauda, S. Llufriu, T. Avsar, U. Uygunoglu, A. Altintas, S. Saip, T. Menge, C. Rajda, R. Bergamaschi, N. Moll, M. Khalil, R. Marignier, I. Dujmovic, H. Larsson, C. Malmestrom, E. Scarpini, C. Fenoglio, S. Wergeland, A. Laroni, V. Annibali, S. Romano, A. D. Martínez, A. Carra, M. Salvetti, A. Uccelli, Torkildsen, K. M. Myhr, D. Galimberti, K. Rejdak, J. Lycke, J. L. Frederiksen, J. Drulovic, C. Confavreux, D. Brassat, C. Enzinger, S. Fuchs, I. Bosca, J. Pelletier, C. Picard, E. Colombo, D. Franciotta, T. Derfuss, R. L.P. Lindberg, Yaldizli, L. Vécsei, B. C. Kieseier, H. P. Hartung, P. Villoslada, A. Siva, A. Saiz, H. Tumani, E. Havrdová, L. M. Villar, M. Leone, N. Barizzone, F. Deisenhammer, C. Teunissen, X. Montalban, M. Tintoré, T. Olsson, M. Trojano, S. Lehmann, G. Castelnovo, S. Lapin, R. Hintzen, L. Kappos, R. Furlan, V. Martinelli, G. Comi, S. V. Ramagopalan, G. Giovannoni

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150 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1013-1024
JournalMultiple Sclerosis
Volume21
Issue number8
DOIs
Publication statusPublished - 1 Jan 2015

Keywords

  • 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)

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