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              <p>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 &lt; 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p &lt; 0.001; &gt;9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p &lt; 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p &lt; 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.</p>
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            <address>
              <addrLine>P.O. Box 6573/14 Badaro, Museum, Beirut</addrLine>
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          <orgName type="acronym">UNIMI</orgName>
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            <address>
              <addrLine>Via Festa del Perdono 7 - 20122 Milano</addrLine>
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            <address>
              <addrLine>BP 53 - 38041 Grenoble Cedex 9</addrLine>
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              <addrLine>46 avenue Félix Viallet 38031 Grenoble Cedex 1</addrLine>
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          <orgName>University of Pisa [Italy] = Università di Pisa [Italia] = Université de Pise [Italie]</orgName>
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          <orgName type="acronym">INSA Lyon</orgName>
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              <addrLine>20 Avenue Albert Einstein, 69621 Villeurbanne cedex</addrLine>
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          <orgName type="acronym">UJM</orgName>
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          <orgName>Aix Marseille Université</orgName>
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            <address>
              <addrLine>Aix-Marseille UniversitéJardins du Pharo58 Boulevard Charles Livon13284 Marseille cedex 7</addrLine>
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          <desc>
            <address>
              <addrLine>20 Avenue du Stade de France 93218 La Plaine Saint Denis</addrLine>
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            <ref type="url">https://www.dondusang.net</ref>
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          <orgName>University of Szeged [Szeged]</orgName>
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            <address>
              <addrLine>13 Dugonics square H-6720 Szeged</addrLine>
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            <ref type="url">http://www.u-szeged.hu/english/</ref>
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            <ref type="url">http://fr.ap-hm.fr/nos-hopitaux/hopital-nord</ref>
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          <date type="start">1965-01-01</date>
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            <address>
              <addrLine>Umeå University901 87 Umeå, Sweden</addrLine>
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            <ref type="url">http://www.umu.se/english</ref>
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            <address>
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