Contributions
Abstract: P1116
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Serum levels of neurofilament light chains (sNfL) in multiple sclerosis (MS) patients are associated with white matter lesion (WML) load and brain atrophy. Still, the relationship between sNfL and cortical lesion (CL) load has yet to be established.
Objectives: To assess the relationship between sNfL and cortical lesion load in a cohort of early RRMS patients.
Methods: 3T MRI and blood sampling was performed in 31 patients with early relapsing-remitting MS (34.8±10.2 years, 19 women/12 men, disease duration < 6 years). Fifteen of those patients also underwent 7T cerebellum MRI to achieve higher spatial resolution for the detection of cerebellar CL. Serum NfL levels were measured using an electrochemiluminescence-based immunoassay. CL segmentation and characterization (i.e. lesion type I,II,III) were performed by consensus by two experts in (i) brain 3T DIR, FLAIR and MP2RAGE images (1x1x1.2mm3) and (ii) cerebellum 7T MP2RAGE images (0.58 mm3 isotropic). A 3T CL union mask was created by merging the masks obtained manually on 3D DIR, FLAIR and MP2RAGE. Spearman's correlations were performed between sNfL in patients and the number/volume of (i) cerebral CL/WML and (ii) cerebellar CL/WML. False discovery rate correction was applied to account for multiple comparisons. Two univariate general linear models (GLM) were also performed to assess the relative contribution of cerebral/cerebellar CL and WML to sNfL variations. Results were bootstrapped with a case resampling rate of 1000.
Results: Serum NfL levels in MS patients correlated with total cerebral CL number/volume (Rho=0.4, p=0.03/p=0.01, corr-p < 0.05) to a similar extent than with cerebral WM lesion count/volume (Rho=0.4/0.5, p=0.01, corr-p < 0.05). Also, sNfL correlated with CL-type I number/volume (Rho=0.4, p=0.02, corr-p < 0.05) but not with CL-type II.
Besides, sNfL levels were related to cerebellar CL-type I number/volume (Rho=0.5, p=0.04, corr-p < 0.05) but not to cerebellar WML. GLM analysis showed that (i) cerebral WML volume was highly related to sNfL levels (p< 0001) whereas cerebral CL number showed a much weaker relationship (p= 0.05); and that (ii) cerebellar CL number/volume were strongly associated to sNfL levels but cerebellar WML number/volume were not.
Conclusions: In early RRMS patients, cerebral CL showed a much weaker association with sNfL levels than WML; however, cerebellar CL were strongly associated with sNfL measures whereas WM lesion load was not.
Disclosure:
- PJL has nothing to disclose.
- MJF has nothing to disclose.
- ÖY´s institution University Hospital Basel received grants from ECTRIMS/MAGNIMS, University of Basel, Pro Patient Stiftung University Hospital Basel, Free Academy Basel, Swiss Multiple Sclerosis Society and advisory board fees from Sanofi Genzyme and Novartis Poland exclusively used for support of research and educational activities.
- LK´s institution (University Hospital Basel) received and used exclusively for research support: steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Celgene/Receptos, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Sanofi, Santhera, Siemens, Teva, UCB, Xenoport; speaker fees from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi, Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva; grants from Bayer HealthCare, Biogen, F. Hoffmann-La Roche Ltd, Merck, Novartis, the European Union, the Roche Research Foundations, the Swiss Multiple Sclerosis Society, the Swiss National Research Foundation.
- CB has nothing to disclose.
- 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.
- CG has nothing to disclose.
Abstract: P1116
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Serum levels of neurofilament light chains (sNfL) in multiple sclerosis (MS) patients are associated with white matter lesion (WML) load and brain atrophy. Still, the relationship between sNfL and cortical lesion (CL) load has yet to be established.
Objectives: To assess the relationship between sNfL and cortical lesion load in a cohort of early RRMS patients.
Methods: 3T MRI and blood sampling was performed in 31 patients with early relapsing-remitting MS (34.8±10.2 years, 19 women/12 men, disease duration < 6 years). Fifteen of those patients also underwent 7T cerebellum MRI to achieve higher spatial resolution for the detection of cerebellar CL. Serum NfL levels were measured using an electrochemiluminescence-based immunoassay. CL segmentation and characterization (i.e. lesion type I,II,III) were performed by consensus by two experts in (i) brain 3T DIR, FLAIR and MP2RAGE images (1x1x1.2mm3) and (ii) cerebellum 7T MP2RAGE images (0.58 mm3 isotropic). A 3T CL union mask was created by merging the masks obtained manually on 3D DIR, FLAIR and MP2RAGE. Spearman's correlations were performed between sNfL in patients and the number/volume of (i) cerebral CL/WML and (ii) cerebellar CL/WML. False discovery rate correction was applied to account for multiple comparisons. Two univariate general linear models (GLM) were also performed to assess the relative contribution of cerebral/cerebellar CL and WML to sNfL variations. Results were bootstrapped with a case resampling rate of 1000.
Results: Serum NfL levels in MS patients correlated with total cerebral CL number/volume (Rho=0.4, p=0.03/p=0.01, corr-p < 0.05) to a similar extent than with cerebral WM lesion count/volume (Rho=0.4/0.5, p=0.01, corr-p < 0.05). Also, sNfL correlated with CL-type I number/volume (Rho=0.4, p=0.02, corr-p < 0.05) but not with CL-type II.
Besides, sNfL levels were related to cerebellar CL-type I number/volume (Rho=0.5, p=0.04, corr-p < 0.05) but not to cerebellar WML. GLM analysis showed that (i) cerebral WML volume was highly related to sNfL levels (p< 0001) whereas cerebral CL number showed a much weaker relationship (p= 0.05); and that (ii) cerebellar CL number/volume were strongly associated to sNfL levels but cerebellar WML number/volume were not.
Conclusions: In early RRMS patients, cerebral CL showed a much weaker association with sNfL levels than WML; however, cerebellar CL were strongly associated with sNfL measures whereas WM lesion load was not.
Disclosure:
- PJL has nothing to disclose.
- MJF has nothing to disclose.
- ÖY´s institution University Hospital Basel received grants from ECTRIMS/MAGNIMS, University of Basel, Pro Patient Stiftung University Hospital Basel, Free Academy Basel, Swiss Multiple Sclerosis Society and advisory board fees from Sanofi Genzyme and Novartis Poland exclusively used for support of research and educational activities.
- LK´s institution (University Hospital Basel) received and used exclusively for research support: steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Celgene/Receptos, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Sanofi, Santhera, Siemens, Teva, UCB, Xenoport; speaker fees from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi, Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva; grants from Bayer HealthCare, Biogen, F. Hoffmann-La Roche Ltd, Merck, Novartis, the European Union, the Roche Research Foundations, the Swiss Multiple Sclerosis Society, the Swiss National Research Foundation.
- CB has nothing to disclose.
- 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.
- CG has nothing to disclose.