Increased Serum Neurofilament Light and Thin Ganglion Cell-Inner Plexiform Layer Are Additive Risk Factors for Disease Activity in Early Multiple Sclerosis

Ting-Yi Lin; Viktoriya Vitkova; Susanna Asseyer; Ivette Martorell Serra; Seyedamirhosein Motamedi; Claudia Chien; Marc Ditzhaus; Athina Papadopoulou; Pascal Benkert; Jens Kuhle; Judith Bellmann-Strobl; Klemens Ruprecht; Friedemann Paul; Alexander U Brandt; Hanna G Zimmermann

doi:10.1212/NXI.0000000000001051

Increased Serum Neurofilament Light and Thin Ganglion Cell-Inner Plexiform Layer Are Additive Risk Factors for Disease Activity in Early Multiple Sclerosis

Neurol Neuroimmunol Neuroinflamm. 2021 Aug 4;8(5):e1051. doi: 10.1212/NXI.0000000000001051. Print 2021 Sep.

Authors

Affiliations

¹ From the Experimental and Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; NeuroCure Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Psychiatry and Psychotherapy (C.C.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Statistics (M.D.), TU Dortmund University, Germany; Neurology Clinic and Policlinic (A.P., J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (K.R., F.P.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; and Department of Neurology (A.U.B.), University of California, Irvine.
² From the Experimental and Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; NeuroCure Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Psychiatry and Psychotherapy (C.C.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Statistics (M.D.), TU Dortmund University, Germany; Neurology Clinic and Policlinic (A.P., J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (K.R., F.P.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; and Department of Neurology (A.U.B.), University of California, Irvine. hanna.zimmermann@charite.de.

Abstract

Objective: To investigate the association of combined serum neurofilament light chain (sNfL) and retinal optical coherence tomography (OCT) measurements with future disease activity in patients with early multiple sclerosis (MS).

Methods: We analyzed sNfL by single molecule array technology and performed OCT measurements in a prospective cohort of 78 patients with clinically isolated syndrome and early relapsing-remitting MS with a median (interquartile range) follow-up of 23.9 (23.3-24.7) months. Patients were grouped into those with abnormal or normal sNfL levels, defined as sNfL ≥/<80th percentile of age-corrected reference values. Likewise, patients were grouped by a median split into those with thin or thick ganglion cell and inner plexiform layer (GCIP), peripapillary retinal nerve fiber layer, and inner nuclear layer in nonoptic neuritis eyes. Outcome parameters were violation of no evidence of disease activity (NEDA-3) criteria or its components.

Results: Patients with abnormal baseline sNfL had a higher risk of violating NEDA-3 (hazard ratio [HR] 2.28, 95% CI 1.27-4.09, p = 0.006) and developing a new brain lesion (HR 2.47, 95% CI 1.30-4.69, p = 0.006), but not for a new relapse (HR 2.21, 95% CI 0.97-5.03, p = 0.058). Patients with both abnormal sNfL and thin GCIP had an even higher risk for NEDA-3 violation (HR 3.61, 95% CI 1.77-7.36, p = 4.2e^-4), new brain lesion (HR 3.19, 95% CI 1.51-6.76, p = 0.002), and new relapse (HR 5.38, 95% CI 1.61-17.98, p = 0.006) than patients with abnormal sNfL alone.

Conclusions: In patients with early MS, the presence of both abnormal sNfL and thin GCIP is a stronger risk factor for future disease activity than the presence of each parameter alone.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Female
Humans
Male
Multiple Sclerosis / blood*
Multiple Sclerosis / diagnostic imaging*
Multiple Sclerosis / pathology
Neurofilament Proteins / blood*
Retinal Ganglion Cells / pathology
Risk Factors
Tomography, Optical Coherence
Young Adult

Substances

Neurofilament Proteins
neurofilament protein L