Contributions
Abstract: P1741
Type: Poster Sessions
Abstract Category: N/A
Background: Both lower cross-sectional deep gray matter (DGM) volume and higher longitudinal DGM atrophy have been demonstrated as main drivers of disability worsening in multiple sclerosis (MS) patients. Similarly, serum neurofilament light chain (sNfL) levels have been associated with MS disability, disease-modifying treatment response, and with MRI-derived MS pathology.
Objective: To determine the associations between sNfL and MRI-derived cross-sectional and longitudinal DGM volumes over a period of 5 years.
Materials and methods: The study included 52 healthy controls (HCs), 127 MS patients, and 20 clinically isolated syndrome (CIS) patients. Over the follow-up, 13 CIS patients converted to MS. The MS cohort was composed of 85 relapsing-remitting MS (RRMS) and 42 progressive MS (PMS) patients. At both visits, all participants underwent standardized 3T MRI and blood sampling. The cross-sectional and longitudinal DGM volumes were derived using the FIRST software, whereas 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 when compared to HCs (25.8 vs. 18.4, p=0.016), whereas there were no differences between CIS patients and HC (21.1 vs.18.4, p=0.489). There was a trend for higher sNfL in PMS compared to RRMS patients (30.4 vs 23.5, p=0.055). Baseline CIS/MS sNfL levels were significantly associated with the cross-sectional volume of both total DGM (p=0.004), and of individual nuclei volumes including hippocampus (p=0.001) thalamus (p=0.006), caudate (p=0.019) and putamen (p=0.035). Equivalently, the baseline sNfL levels were significantly associated with 5-year longitudinal volume change of total DGM volume (p< 0.001), putamen (p=0.001) and thalamus (p=0.012). Within the HC population, the baseline sNfL levels were only associated with hippocampal volume change over 5 years (p=0.003).
Conclusion: Higher sNfL levels are associated with lower cross-sectional volume and higher prospective DGM atrophy in MS patients.
Disclosure: This study was in part funded by Novartis Pharma AG, Basel, Switzerland.
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.
Dejan Jakimovski, Jesper Hagemeier, Niels Bergsland and Zuzanna Michalak have nothing to disclose.
Christian Barro received conference travel grant from Teva and Novartis
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.
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.
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, Claret Medical, Intekrin-Coherus, Protembis and Qunitiles/IMS.
Abstract: P1741
Type: Poster Sessions
Abstract Category: N/A
Background: Both lower cross-sectional deep gray matter (DGM) volume and higher longitudinal DGM atrophy have been demonstrated as main drivers of disability worsening in multiple sclerosis (MS) patients. Similarly, serum neurofilament light chain (sNfL) levels have been associated with MS disability, disease-modifying treatment response, and with MRI-derived MS pathology.
Objective: To determine the associations between sNfL and MRI-derived cross-sectional and longitudinal DGM volumes over a period of 5 years.
Materials and methods: The study included 52 healthy controls (HCs), 127 MS patients, and 20 clinically isolated syndrome (CIS) patients. Over the follow-up, 13 CIS patients converted to MS. The MS cohort was composed of 85 relapsing-remitting MS (RRMS) and 42 progressive MS (PMS) patients. At both visits, all participants underwent standardized 3T MRI and blood sampling. The cross-sectional and longitudinal DGM volumes were derived using the FIRST software, whereas 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 when compared to HCs (25.8 vs. 18.4, p=0.016), whereas there were no differences between CIS patients and HC (21.1 vs.18.4, p=0.489). There was a trend for higher sNfL in PMS compared to RRMS patients (30.4 vs 23.5, p=0.055). Baseline CIS/MS sNfL levels were significantly associated with the cross-sectional volume of both total DGM (p=0.004), and of individual nuclei volumes including hippocampus (p=0.001) thalamus (p=0.006), caudate (p=0.019) and putamen (p=0.035). Equivalently, the baseline sNfL levels were significantly associated with 5-year longitudinal volume change of total DGM volume (p< 0.001), putamen (p=0.001) and thalamus (p=0.012). Within the HC population, the baseline sNfL levels were only associated with hippocampal volume change over 5 years (p=0.003).
Conclusion: Higher sNfL levels are associated with lower cross-sectional volume and higher prospective DGM atrophy in MS patients.
Disclosure: This study was in part funded by Novartis Pharma AG, Basel, Switzerland.
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.
Dejan Jakimovski, Jesper Hagemeier, Niels Bergsland and Zuzanna Michalak have nothing to disclose.
Christian Barro received conference travel grant from Teva and Novartis
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.
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.
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, Claret Medical, Intekrin-Coherus, Protembis and Qunitiles/IMS.