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

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 س¹, 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.

 

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.