Serum neurofilament light chain and optical coherence tomography measures in MS: A longitudinal study.
Tavazzi EFrom the Buffalo Neuroimaging Analysis Center (E.T., D.J., J.H., O.O., N.B., M.G.D., R.Z.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; IRCCS (N.B.), Fondazione Don Carlo Gnocchi, Milan, Italy; Neurologic Clinic and Policlinic (J.K., C.B., Z.M., N.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Pharmaceutical Sciences (M.R.), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; Novartis Pharma AG (D.T., H.K., D.L.), Basel, Switzerland; Jacobs MS Center (R.H.B.B., B.W.-G.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z.), University at Buffalo, State University of New York.
Jakimovski DFrom the Buffalo Neuroimaging Analysis Center (E.T., D.J., J.H., O.O., N.B., M.G.D., R.Z.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; IRCCS (N.B.), Fondazione Don Carlo Gnocchi, Milan, Italy; Neurologic Clinic and Policlinic (J.K., C.B., Z.M., N.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Pharmaceutical Sciences (M.R.), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; Novartis Pharma AG (D.T., H.K., D.L.), Basel, Switzerland; Jacobs MS Center (R.H.B.B., B.W.-G.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z.), University at Buffalo, State University of New York.
Kuhle JFrom the Buffalo Neuroimaging Analysis Center (E.T., D.J., J.H., O.O., N.B., M.G.D., R.Z.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; IRCCS (N.B.), Fondazione Don Carlo Gnocchi, Milan, Italy; Neurologic Clinic and Policlinic (J.K., C.B., Z.M., N.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Pharmaceutical Sciences (M.R.), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; Novartis Pharma AG (D.T., H.K., D.L.), Basel, Switzerland; Jacobs MS Center (R.H.B.B., B.W.-G.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z.), University at Buffalo, State University of New York.
Hagemeier JFrom the Buffalo Neuroimaging Analysis Center (E.T., D.J., J.H., O.O., N.B., M.G.D., R.Z.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; IRCCS (N.B.), Fondazione Don Carlo Gnocchi, Milan, Italy; Neurologic Clinic and Policlinic (J.K., C.B., Z.M., N.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Pharmaceutical Sciences (M.R.), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; Novartis Pharma AG (D.T., H.K., D.L.), Basel, Switzerland; Jacobs MS Center (R.H.B.B., B.W.-G.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z.), University at Buffalo, State University of New York.
Ozel OFrom the Buffalo Neuroimaging Analysis Center (E.T., D.J., J.H., O.O., N.B., M.G.D., R.Z.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; IRCCS (N.B.), Fondazione Don Carlo Gnocchi, Milan, Italy; Neurologic Clinic and Policlinic (J.K., C.B., Z.M., N.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Pharmaceutical Sciences (M.R.), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; Novartis Pharma AG (D.T., H.K., D.L.), Basel, Switzerland; Jacobs MS Center (R.H.B.B., B.W.-G.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z.), University at Buffalo, State University of New York.
Ramanathan MFrom the Buffalo Neuroimaging Analysis Center (E.T., D.J., J.H., O.O., N.B., M.G.D., R.Z.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; IRCCS (N.B.), Fondazione Don Carlo Gnocchi, Milan, Italy; Neurologic Clinic and Policlinic (J.K., C.B., Z.M., N.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Pharmaceutical Sciences (M.R.), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; Novartis Pharma AG (D.T., H.K., D.L.), Basel, Switzerland; Jacobs MS Center (R.H.B.B., B.W.-G.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z.), University at Buffalo, State University of New York.
Barro CFrom the Buffalo Neuroimaging Analysis Center (E.T., D.J., J.H., O.O., N.B., M.G.D., R.Z.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; IRCCS (N.B.), Fondazione Don Carlo Gnocchi, Milan, Italy; Neurologic Clinic and Policlinic (J.K., C.B., Z.M., N.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Pharmaceutical Sciences (M.R.), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; Novartis Pharma AG (D.T., H.K., D.L.), Basel, Switzerland; Jacobs MS Center (R.H.B.B., B.W.-G.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z.), University at Buffalo, State University of New York.
Bergsland NFrom the Buffalo Neuroimaging Analysis Center (E.T., D.J., J.H., O.O., N.B., M.G.D., R.Z.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; IRCCS (N.B.), Fondazione Don Carlo Gnocchi, Milan, Italy; Neurologic Clinic and Policlinic (J.K., C.B., Z.M., N.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Pharmaceutical Sciences (M.R.), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; Novartis Pharma AG (D.T., H.K., D.L.), Basel, Switzerland; Jacobs MS Center (R.H.B.B., B.W.-G.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z.), University at Buffalo, State University of New York.
Tomic DFrom the Buffalo Neuroimaging Analysis Center (E.T., D.J., J.H., O.O., N.B., M.G.D., R.Z.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; IRCCS (N.B.), Fondazione Don Carlo Gnocchi, Milan, Italy; Neurologic Clinic and Policlinic (J.K., C.B., Z.M., N.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Pharmaceutical Sciences (M.R.), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; Novartis Pharma AG (D.T., H.K., D.L.), Basel, Switzerland; Jacobs MS Center (R.H.B.B., B.W.-G.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z.), University at Buffalo, State University of New York.
Kropshofer HFrom the Buffalo Neuroimaging Analysis Center (E.T., D.J., J.H., O.O., N.B., M.G.D., R.Z.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; IRCCS (N.B.), Fondazione Don Carlo Gnocchi, Milan, Italy; Neurologic Clinic and Policlinic (J.K., C.B., Z.M., N.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Pharmaceutical Sciences (M.R.), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; Novartis Pharma AG (D.T., H.K., D.L.), Basel, Switzerland; Jacobs MS Center (R.H.B.B., B.W.-G.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z.), University at Buffalo, State University of New York.
Leppert DFrom the Buffalo Neuroimaging Analysis Center (E.T., D.J., J.H., O.O., N.B., M.G.D., R.Z.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; IRCCS (N.B.), Fondazione Don Carlo Gnocchi, Milan, Italy; Neurologic Clinic and Policlinic (J.K., C.B., Z.M., N.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Pharmaceutical Sciences (M.R.), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; Novartis Pharma AG (D.T., H.K., D.L.), Basel, Switzerland; Jacobs MS Center (R.H.B.B., B.W.-G.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z.), University at Buffalo, State University of New York.
Michalak ZFrom the Buffalo Neuroimaging Analysis Center (E.T., D.J., J.H., O.O., N.B., M.G.D., R.Z.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; IRCCS (N.B.), Fondazione Don Carlo Gnocchi, Milan, Italy; Neurologic Clinic and Policlinic (J.K., C.B., Z.M., N.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Pharmaceutical Sciences (M.R.), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; Novartis Pharma AG (D.T., H.K., D.L.), Basel, Switzerland; Jacobs MS Center (R.H.B.B., B.W.-G.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z.), University at Buffalo, State University of New York.
Lincoff NFrom the Buffalo Neuroimaging Analysis Center (E.T., D.J., J.H., O.O., N.B., M.G.D., R.Z.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; IRCCS (N.B.), Fondazione Don Carlo Gnocchi, Milan, Italy; Neurologic Clinic and Policlinic (J.K., C.B., Z.M., N.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Pharmaceutical Sciences (M.R.), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; Novartis Pharma AG (D.T., H.K., D.L.), Basel, Switzerland; Jacobs MS Center (R.H.B.B., B.W.-G.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z.), University at Buffalo, State University of New York.
Dwyer MGFrom the Buffalo Neuroimaging Analysis Center (E.T., D.J., J.H., O.O., N.B., M.G.D., R.Z.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; IRCCS (N.B.), Fondazione Don Carlo Gnocchi, Milan, Italy; Neurologic Clinic and Policlinic (J.K., C.B., Z.M., N.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Pharmaceutical Sciences (M.R.), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; Novartis Pharma AG (D.T., H.K., D.L.), Basel, Switzerland; Jacobs MS Center (R.H.B.B., B.W.-G.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z.), University at Buffalo, State University of New York.
Benedict RHBFrom the Buffalo Neuroimaging Analysis Center (E.T., D.J., J.H., O.O., N.B., M.G.D., R.Z.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; IRCCS (N.B.), Fondazione Don Carlo Gnocchi, Milan, Italy; Neurologic Clinic and Policlinic (J.K., C.B., Z.M., N.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Pharmaceutical Sciences (M.R.), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; Novartis Pharma AG (D.T., H.K., D.L.), Basel, Switzerland; Jacobs MS Center (R.H.B.B., B.W.-G.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z.), University at Buffalo, State University of New York.
Weinstock-Guttman BFrom the Buffalo Neuroimaging Analysis Center (E.T., D.J., J.H., O.O., N.B., M.G.D., R.Z.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; IRCCS (N.B.), Fondazione Don Carlo Gnocchi, Milan, Italy; Neurologic Clinic and Policlinic (J.K., C.B., Z.M., N.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Pharmaceutical Sciences (M.R.), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; Novartis Pharma AG (D.T., H.K., D.L.), Basel, Switzerland; Jacobs MS Center (R.H.B.B., B.W.-G.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z.), University at Buffalo, State University of New York.
Zivadinov RFrom the Buffalo Neuroimaging Analysis Center (E.T., D.J., J.H., O.O., N.B., M.G.D., R.Z.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; IRCCS (N.B.), Fondazione Don Carlo Gnocchi, Milan, Italy; Neurologic Clinic and Policlinic (J.K., C.B., Z.M., N.L.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Pharmaceutical Sciences (M.R.), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York; Novartis Pharma AG (D.T., H.K., D.L.), Basel, Switzerland; Jacobs MS Center (R.H.B.B., B.W.-G.), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, and Center for Biomedical Imaging at Clinical Translational Science Institute (R.Z.), University at Buffalo, State University of New York. rzivadinov@bnac.net.
English
OBJECTIVE To study the association between serum neurofilament light chain (sNfL) and multiple optical coherence tomography (OCT) measures in patients with MS and healthy controls (HCs).
METHODS In this prospective study, 110 patients with MS were recruited, together with 52 age- and sex-matched HCs. Clinical evaluation and spectral domain OCT and sNfL were obtained at baseline and after 5.5 years of follow-up. Nested linear mixed models were used to assess differences between MS vs HC and associations between sNfL and OCT measures. Partial correlation coefficients are reported, and p values were adjusted for the false discovery rate.
RESULTS At baseline, peripapillary retinal nerve fiber layer thickness (pRNFLT) and macular ganglion cell and inner plexiform layer thickness (mGCIP) were significantly lower in MS than HC both in MS-associated optic neuritis (MSON) (p = 0.007, p = 0.001) and nonaffected MSON (n-MSON) eyes (p = 0.003, p = 0.018), along with total macular volume (TMV) in n-MSON eyes (p = 0.011). At follow-up, MS showed significantly lower pRNFLT, mGCIP, and TMV both in MSON and n-MSON eyes (p < 0.001) compared with HC. In MS n-MSON eyes, sNfL was significantly associated with baseline pRNFLT and mGCIP (q = 0.019). No significant associations were found in MSON eyes.
CONCLUSIONS This study confirms the ability of sNfL to detect neurodegeneration in MS and advocates for the inclusion of sNfL and OCT measures in clinical trials.
CLASSIFICATION OF EVIDENCE This study provides Class III evidence that sNfL levels were associated with MS neurodegeneration measured by OCT.