TY - JOUR

T1 - Conversion from clinically isolated syndrome to multiple sclerosis

T2 - A large multicentre study

AU - Kuhle, J

AU - Disanto, G

AU - Dobson, R

AU - Adiutori, R

AU - Bianchi, L

AU - Topping, J

AU - Bestwick, J P

AU - Meier, U-C

AU - Marta, M

AU - Dalla Costa, G

AU - Runia, T

AU - Evdoshenko, E

AU - Lazareva, N

AU - Thouvenot, E

AU - Iaffaldano, P

AU - Direnzo, V

AU - Khademi, M

AU - Piehl, F

AU - Comabella, M

AU - Sombekke, M

AU - Killestein, J

AU - Hegen, H

AU - Rauch, S

AU - D'Alfonso, S

AU - Alvarez-Cermeño, J C

AU - Kleinová, P

AU - Horáková, D

AU - Roesler, R

AU - Lauda, F

AU - Llufriu, S

AU - Avsar, T

AU - Uygunoglu, U

AU - Altintas, A

AU - Saip, S

AU - Menge, T

AU - Rajda, C

AU - Bergamaschi, R

AU - Moll, N

AU - Khalil, M

AU - Marignier, R

AU - Dujmovic, I

AU - Larsson, H

AU - Malmestrom, C

AU - Scarpini, E

AU - Fenoglio, C

AU - Wergeland, S

AU - Laroni, A

AU - Annibali, V

AU - Romano, S

AU - Martínez, A D

AU - Carra, A

AU - Salvetti, M

AU - Uccelli, A

AU - Torkildsen, Ø

AU - Myhr, K M

AU - Galimberti, D

AU - Rejdak, K

AU - Lycke, J

AU - Fredriksen, Jette Lautrup

AU - Drulovic, J

AU - Confavreux, C

AU - Brassat, D

AU - Enzinger, C

AU - Fuchs, S

AU - Bosca, I

AU - Pelletier, J

AU - Picard, C

AU - Colombo, E

AU - Franciotta, D

AU - Derfuss, T

AU - Lindberg, Rlp

AU - Yaldizli, Ö

AU - Vécsei, L

AU - Kieseier, B C

AU - Hartung, H P

AU - Villoslada, P

AU - Siva, A

AU - Saiz, A

AU - Tumani, H

AU - Havrdová, E

AU - Villar, L M

AU - Leone, M

AU - Barizzone, N

AU - Deisenhammer, F

AU - Teunissen, C

AU - Montalban, X

AU - Tintoré, M

AU - Olsson, T

AU - Trojano, M

AU - Lehmann, S

AU - Castelnovo, G

AU - Lapin, S

AU - Hintzen, R

AU - Kappos, L

AU - Furlan, R

AU - Martinelli, V

AU - Comi, G

AU - Ramagopalan, S V

AU - Giovannoni, G

N1 - © The Author(s), 2015.

PY - 2015/7

Y1 - 2015/7

N2 - 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.

AB - 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.

KW - Adult

KW - Cohort Studies

KW - Disease Progression

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Immunoglobulin G

KW - Magnetic Resonance Imaging

KW - Male

KW - Multiple Sclerosis

KW - Nuclear Proteins

KW - Oligoclonal Bands

KW - Predictive Value of Tests

KW - Prognosis

KW - Risk Assessment

KW - Survival Analysis

KW - Vitamin D

U2 - 10.1177/1352458514568827

DO - 10.1177/1352458514568827

M3 - Journal article

C2 - 25680984

VL - 21

SP - 1013

EP - 1024

JO - Multiple Sclerosis Journal

JF - Multiple Sclerosis Journal

SN - 1352-4585

IS - 8

ER -