Serum neurofilament light chain levels are increased in patients with a clinically isolated syndrome

none99siBackground Neurofilament light chain (NfL) represents a promising biomarker for axonal injury. We present the first exploratory study on serum NfL in patients with a clinically isolated syndrome (CIS) and healthy controls. Methods We investigated serum NfL levels in 100 patients with CIS with a short conversion interval to clinically definite multiple sclerosis (MS) (fast converters (FC), median (IQR) conversion time: 110 days (79-139)); 98 patients with non-converting CIS (non-converters (NC), follow-up: 6.5 years (5.3-7.9)); and 92 healthy controls. Results NfL levels were higher in FC (24.1 pg/mL (13.5-51.8)) and NC (19.3 pg/mL (13.6-35.2)) than in healthy controls (7.9 pg/mL (5.6-17.2)) (OR=5.85; 95% CI 2.63 to 13.02; p=1.5×10-5 and OR=7.03; 95% CI 2.85 to 17.34; p=2.3×10-5, respectively). When grouping FC and NC, increased serum NfL concentration was also associated with increasing numbers of T2 hyperintense MRI lesions (OR=2.36; 95% CI 1.21 to 4.59; p=0.011), gadolinium-enhancing lesions (OR=2.69; 95% CI 1.13 to 6.41; p=0.026) and higher disability scores (OR=2.54; 95% CI 1.21 to 5.31; p=0.013) at CIS diagnosis. Conclusions If replicated in future studies, serum NfL may represent a reliable and easily accessible biomarker of early axonal damage in CIS and MS.restrictedDisanto G1, Adiutori R2, Dobson R2, Martinelli V3, Dalla Costa G3, Runia T4, Evdoshenko E5, Thouvenot E6, Trojano M7, Norgren N8, Teunissen C9, Kappos L10, Giovannoni G2, Kuhle J, Bianchi L, Topping J, Bestwick JP, Meier UC, , Lazareva N, Iaffaldano P, Direnzo V, Khademi M, Piehl F, Comabella M, Sombekke M, Killestein J, Hegen H, Rauch S, D'Alfonso S, Alvarez-Cermeño JC, Kleinová P, Horáková D, Roesler R, Lauda F, Llufriu S, Avsar T, Uygunoglu U, Altintas A, Saip S, Menge T, Rajda C, Bergamaschi R, Moll N, Khalil M, Marignier R, Dujmovic I, Larsson H, Malmestrom C, Scarpini E, Fenoglio C, Wergeland S, Laroni A, Annibali V, Romano S, Martínez AD, Carra A, Salvetti M, Uccelli A, Torkildsen Ø, Myhr KM, Galimberti D, Rejdak K, Lycke J, Frederiksen JL, Drulovic J, Confavreux C, Brassat D, Enzinger C, Fuchs S, Bosca I, Pelletier J, Picard C, Colombo E, Franciotta D, Derfuss T, Lindberg RL, Yaldizli Ö, Vécsei L, Kieseier BC, Hartung HP, Villoslada P, Siva A, Saiz A, Tumani H, Havrdová E, Villar LM, Leone M, Barizzone N, Deisenhammer F, Montalban X, Tintoré M, Olsson T, Lehmann S, Castelnovo G, Lapin S, Hintzen R, Furlan R, Comi G, Ramagopalan SV.Disanto, G1; Adiutori, R2; Dobson, R2; Martinelli, V3; Dalla Costa, G3; Runia, T4; Evdoshenko, E5; Thouvenot, E6; Trojano, M7; Norgren, N8; Teunissen, C9; Kappos, L10; Giovannoni, G2; Kuhle, J; Bianchi, L; Topping, J; Bestwick, Jp; Meier, Uc; Lazareva, N; Iaffaldano, P; Direnzo, V; Khademi, M; Piehl, F; Comabella, M; Sombekke, M; Killestein, J; Hegen, H; Rauch, S; D'Alfonso, S; Alvarez-Cermeño, Jc; Kleinová, P; Horáková, D; Roesler, R; Lauda, F; Llufriu, S; Avsar, T; Uygunoglu, U; Altintas, A; Saip, S; Menge, T; Rajda, C; Bergamaschi, R; Moll, N; Khalil, M; Marignier, R; Dujmovic, I; Larsson, H; Malmestrom, C; Scarpini, E; Fenoglio, C; Wergeland, S; Laroni, A; Annibali, V; Romano, S; Martínez, Ad; Carra, A; Salvetti, M; Uccelli, A; Torkildsen, Ø; Myhr, Km; Galimberti, D; Rejdak, K; Lycke, J; Frederiksen, Jl; Drulovic, J; Confavreux, C; Brassat, D; Enzinger, C; Fuchs, S; Bosca, I; Pelletier, J; Picard, C; Colombo, E; Franciotta, D; Derfuss, T; Lindberg, Rl; Yaldizli, Ö; Vécsei, L; Kieseier, Bc; Hartung, Hp; Villoslada, P; Siva, A; Saiz, A; Tumani, H; Havrdová, E; Villar, Lm; Leone, M; Barizzone, N; Deisenhammer, F; Montalban, X; Tintoré, M; Olsson, T; Lehmann, S; Castelnovo, G; Lapin, S; Hintzen, R; Furlan, R; Comi, G; Ramagopalan, Sv

Epstein-Barr-negative MS: a true phenomenon?

This work was supported by institutional funding and in part by the BMBF grant KKNMS (Competence Net Multiple Sclerosis) to H Tumani

Health-related quality of life in multiple sclerosis: Effects of natalizumab

Objective: To report the relationship between disease activity and health-related quality of life (HRQoL) in relapsing multiple sclerosis, and the impact of natalizumab. Methods: HRQoL data were available from 2,113 multiple sclerosis patients in natalizumab clinical studies. In the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) study, patients received natalizumab 300mg (n = 627) or placebo (n = 315); in the Safety and Efficacy of Natalizumab in Combination with Interferon Beta-1a in Patients with Relapsing Remitting Multiple Sclerosis (SENTINEL) study, patients received interferon beta-la (IFN-\u3b2-1a) plus natalizumab 300mg (n = 589), or IFN-\u3b2-1a plus placebo (n = 582). The Short Form-36 (SF-36) and a subject global assessment visual analog scale were administered at baseline and weeks 24, 52, and 104. Prespecified analyses included changes from baseline to week 104 in SF-36 and visual analog scale scores. Odds ratios for clinically meaningful improvement or worsening on the SF-36 Physical Component Summary (PCS) and Mental Component Summary were calculated. Results: Mean baseline SF-36 scores were significantly less than the general US population and correlated with Expanded Disability Status Scale scores, sustained disability progression, relapse number, and increased volume of brain magnetic resonance imaging lesions. Natalizumab significantly improved SF-36 PCS and Mental Component Summary scores at week 104 in AFFIRM. PCS changes were significantly improved by week 24 and at all subsequent time points. Natalizumab-treated patients in both studies were more likely to experience clinically important improvement and less likely to experience clinically important deterioration on the SF-36 PCS. The visual analog scale also showed significantly improved HRQoL with natalizumab. Interpretation: HRQoL was impaired in relapsing multiple sclerosis patients, correlated with severity of disease as measured by neurological ratings or magnetic resonance imaging, and improved significantly with natalizumab. \ua9 2007 American Neurological Association. Published by Wiley-Liss, Inc