Norwegian Multiple Sclerosis Competence Centre and Research Group
Conversion from CIS to MS

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

Researchers at the Kristian Gerhard Jebsen Centre for MS Research have contributed to an international multicentre study recently published in Multiple Sclerosis Journal.

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


Kuhle J1, Disanto G2, Dobson R2, Adiutori R2, Bianchi L2, Topping J2, Bestwick J3, Meier UC2, Marta M2, Costa GD4, Runia T5, Evdoshenko E6, Lazareva N6, Thouvenot E7, Iaffaldano P8, Direnzo V8, Khademi M9, Piehl F9, Comabella M10, Sombekke M11, Killestein J11, Hegen H12, Rauch S13, D'Alfonso S14, Alvarez-Cermeño J15, Kleinová P16, Horáková D16, Roesler R17, Lauda F17, Llufriu S18, Avsar T19, Uygunoglu U20, Altintas A20, Saip S20, Menge T21, Rajda C22, Bergamaschi R23, Moll N24, Khalil M25, Marignier R26, Dujmovic I27, Larsson H28, Malmestrom C29, Scarpini E30, Fenoglio C30, Wergeland S31, Laroni A32, Annibali V33, Romano S33, Martínez A34, Carra A34, Salvetti M33, Uccelli A32, Torkildsen Ø31, Myhr K32, Galimberti D30, Rejdak K35, Lycke J29, Frederiksen J36, Drulovic J27, Confavreux C26, Brassat D37, Enzinger C25, Fuchs S25, Bosca I38, Pelletier J24, Picard C24, Colombo E23, Franciotta D23, Derfuss T39, Lindberg R39, Yaldizli Ö39, Vécsei L22, Kieseier B21, Hartung H21, Villoslada P18, Siva A20, Saiz A18, Tumani H17, Havrdová E16, Villar L15, Leone M40, Barizzone N14, Deisenhammer F12, Teunissen C11, Montalban X10, Tintoré M10, Olsson T9, Trojano M8, Lehmann S7, Castelnovo G7, Lapin S6, Hintzen R5, Kappos L39, Furlan R4, Martinelli V4, Comi G4, Ramagopalan S41, Giovannoni G42.




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.