Contributions
Abstract: P1750
Type: Poster Sessions
Abstract Category: N/A
Background: The association between serum neurofilament light chain levels (sNfL) and cortical pathology in patients with multiple sclerosis (MS) was not previously investigated.
Objective: To identify the role of sNfL in development of cortical pathology, as measured by cortical atrophy and leptomeningeal contrast-enhancement (LM CE) in clinically isolated syndrome (CIS) and MS patients, as compared to healthy individuals (HI).
Materials and methods: The study included 127 MS patients, 20 clinically isolated syndrome (CIS) patients and 52 HI. The MS cohort was composed of 85 relapsing-remitting MS (RR) and 42 progressive (PMS) patients. At baseline and 5 years follow-up, all participants underwent standardized 3T MRI and serum sampling. The evolution of brain atrophy, and accumulation of lesion volumes (LVs) was measured. LMCE was assessed using subtraction imaging between 3D-FLAIR pre- and post-contrast sequences. sNfL levels were measured by Simoa assay in pg/ml. Multiple linear regression analyses using age- and sex-adjusted sNfL levels were performed.
Results: MS patients had higher baseline sNfL levels compared to HI (25.8 vs. 18.4, p=0.016), whereas there were no differences between CIS patients and HI (21.1 vs.18.4, p=0.489). PMS patients had significantly higher change of sNfL over 5 years, compared to RRMS (+7.6 vs. -0.6, p=0.049). In MS/CIS patients, higher baseline sNfL predicted higher percentage brain volume change (p< 0.001), percentage cortical volume change (PCVC) (p=0.001), absolute accumulation in gadolinium LV (p< 0.001), T2-LV (p=0.002), T1-LV (p=0.032) and enlargement of lateral ventricles (p=0.014) over 5 years. Higher absolute change in sNfL over 5 years was significantly associated with higher absolute accumulation in gadolinium LV (p< 0.001) and PCVC (p=0.017) in RRMS patients, and with T2-LV accumulation in HI (p=0.034). No significant association between LMCE and sNfL was detected over 5 years.
Conclusion: Higher sNfL levels are associated with cortical pathology and accumulation of LVs in MS/CIS patients over 5 years.
Disclosure: This study was in part funded by Novartis Pharma AG, Basel, Switzerland.
Robert Zivadinov received personal compensation from EMD Serono, Genzyme-Sanofi, Claret Medical, Celgene and Novartis for speaking and consultant fees. He received financial support for research activities from Genzyme-Sanofi, Novartis, Celgene, Claret Medical, Intekrin-Coherus, Protembis and Qunitiles/IMS.
Dejan Jakimovski, Jesper Hagemeier, Niels Bergsland and Zuzanna Michalak have nothing to disclose.
Murali Ramanathan received research funding or consulting fees from EMD Serono, Biogen Idec, Pfizer Inc, the National Multiple Sclerosis Society, the Department of Defense, Jog for the Jake Foundation, the National Institutes of Health and National Science Foundation. He received compensation for serving as an Editor from the American Association of Pharmaceutical Scientists.
Christian Barro received conference travel grant from Teva and Novartis
Michael G. Dwyer has received consultant fees from Claret Medical and EMD Serono.
Davorka Tomic, Harald Kropshofer and David Leppert are employees of Novartis Pharma AG, Basel, Switzerland.
Ralph RH. Benedict received personal compensation from Neurocog Trials, Genentech, Roche, Takeda, Abbvie, Novartis, Sanofi and EMD Serono for speaking and consultant fees. He received financial support for research activities from Genzyme, Biogen, Mallinckrodt.
Bianca Weinstock- Guttman received honoraria as a speaker and as a consultant for Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme&Sanofi, Novartis and Acorda. Dr Weinstock-Guttman received research funds from Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme&Sanofi, Novartis, Acorda.
Jens Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva.
Abstract: P1750
Type: Poster Sessions
Abstract Category: N/A
Background: The association between serum neurofilament light chain levels (sNfL) and cortical pathology in patients with multiple sclerosis (MS) was not previously investigated.
Objective: To identify the role of sNfL in development of cortical pathology, as measured by cortical atrophy and leptomeningeal contrast-enhancement (LM CE) in clinically isolated syndrome (CIS) and MS patients, as compared to healthy individuals (HI).
Materials and methods: The study included 127 MS patients, 20 clinically isolated syndrome (CIS) patients and 52 HI. The MS cohort was composed of 85 relapsing-remitting MS (RR) and 42 progressive (PMS) patients. At baseline and 5 years follow-up, all participants underwent standardized 3T MRI and serum sampling. The evolution of brain atrophy, and accumulation of lesion volumes (LVs) was measured. LMCE was assessed using subtraction imaging between 3D-FLAIR pre- and post-contrast sequences. sNfL levels were measured by Simoa assay in pg/ml. Multiple linear regression analyses using age- and sex-adjusted sNfL levels were performed.
Results: MS patients had higher baseline sNfL levels compared to HI (25.8 vs. 18.4, p=0.016), whereas there were no differences between CIS patients and HI (21.1 vs.18.4, p=0.489). PMS patients had significantly higher change of sNfL over 5 years, compared to RRMS (+7.6 vs. -0.6, p=0.049). In MS/CIS patients, higher baseline sNfL predicted higher percentage brain volume change (p< 0.001), percentage cortical volume change (PCVC) (p=0.001), absolute accumulation in gadolinium LV (p< 0.001), T2-LV (p=0.002), T1-LV (p=0.032) and enlargement of lateral ventricles (p=0.014) over 5 years. Higher absolute change in sNfL over 5 years was significantly associated with higher absolute accumulation in gadolinium LV (p< 0.001) and PCVC (p=0.017) in RRMS patients, and with T2-LV accumulation in HI (p=0.034). No significant association between LMCE and sNfL was detected over 5 years.
Conclusion: Higher sNfL levels are associated with cortical pathology and accumulation of LVs in MS/CIS patients over 5 years.
Disclosure: This study was in part funded by Novartis Pharma AG, Basel, Switzerland.
Robert Zivadinov received personal compensation from EMD Serono, Genzyme-Sanofi, Claret Medical, Celgene and Novartis for speaking and consultant fees. He received financial support for research activities from Genzyme-Sanofi, Novartis, Celgene, Claret Medical, Intekrin-Coherus, Protembis and Qunitiles/IMS.
Dejan Jakimovski, Jesper Hagemeier, Niels Bergsland and Zuzanna Michalak have nothing to disclose.
Murali Ramanathan received research funding or consulting fees from EMD Serono, Biogen Idec, Pfizer Inc, the National Multiple Sclerosis Society, the Department of Defense, Jog for the Jake Foundation, the National Institutes of Health and National Science Foundation. He received compensation for serving as an Editor from the American Association of Pharmaceutical Scientists.
Christian Barro received conference travel grant from Teva and Novartis
Michael G. Dwyer has received consultant fees from Claret Medical and EMD Serono.
Davorka Tomic, Harald Kropshofer and David Leppert are employees of Novartis Pharma AG, Basel, Switzerland.
Ralph RH. Benedict received personal compensation from Neurocog Trials, Genentech, Roche, Takeda, Abbvie, Novartis, Sanofi and EMD Serono for speaking and consultant fees. He received financial support for research activities from Genzyme, Biogen, Mallinckrodt.
Bianca Weinstock- Guttman received honoraria as a speaker and as a consultant for Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme&Sanofi, Novartis and Acorda. Dr Weinstock-Guttman received research funds from Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme&Sanofi, Novartis, Acorda.
Jens Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva.