Christian Cordano1, Bardia Nourbakhsh2, Hao H Yiu2, Nico Papinutto2, Eduardo Caverzasi2, Ahmed Abdelhak2, Frederike C Oertel2, Alexandra Beaudry-Richard2, Adam Santaniello2, Simone Sacco2, Daniel J Bennett2, Apraham Gomez2, Christina J Sigurdson2, Stephen L Hauser2, Roberta Magliozzi2, Bruce A C Cree2, Roland G Henry2, Ari J Green2. 1. From the Department of Neurology (C.C., N.P., E.C., A.A., F.C.O., A.B.-R., A.S., S.S., D.J.B., A.G., S.L.H., B.A.C.C., R.G.H., A.J.G.), UCSF Weill Institute for Neurosciences, University of California, San Francisco; Department of Neurology (B.N.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Biology (H.H.Y.), University of Maryland, College Park; Department of Pathology (C.J.S.), University of California, San Diego, La Jolla; and Department of Neurosciences (R.M.), Biomedicine and Movement Sciences, University of Verona, Italy. christian.cordano@ucsf.edu. 2. From the Department of Neurology (C.C., N.P., E.C., A.A., F.C.O., A.B.-R., A.S., S.S., D.J.B., A.G., S.L.H., B.A.C.C., R.G.H., A.J.G.), UCSF Weill Institute for Neurosciences, University of California, San Francisco; Department of Neurology (B.N.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Biology (H.H.Y.), University of Maryland, College Park; Department of Pathology (C.J.S.), University of California, San Diego, La Jolla; and Department of Neurosciences (R.M.), Biomedicine and Movement Sciences, University of Verona, Italy.
Abstract
BACKGROUND AND OBJECTIVES: The timing of neurodegeneration in multiple sclerosis (MS) remains unclear. It is critical to understand the dynamics of neuroaxonal loss if we hope to prevent or forestall permanent disability in MS. We therefore used a deeply phenotyped longitudinal cohort to assess and compare rates of neurodegeneration in retina and brain throughout the MS disease course. METHODS: We analyzed 597 patients with MS who underwent longitudinal optical coherence tomography imaging annually for 4.5 ± 2.4 years and 432 patients who underwent longitudinal MRI scans for 10 ± 3.4 years, quantifying macular ganglion cell-inner plexiform layer (GCIPL) volume and cortical gray matter (CGM) volume. The association between the slope of decline in the anatomical structure and the age of entry in the cohort (categorized by the MRI cohort's age quartiles) was assessed by hierarchical linear models. RESULTS: The rate of CGM volume loss declined with increasing age of study entry (1.3% per year atrophy for the age of entry in the cohort younger than 35 years; 1.1% for older than 35 years and younger than 41; 0.97% for older than 41 years and younger than 49; 0.9% for older than 49 years) while the rate of GCIPL thinning was highest in patients in the youngest quartile, fell by more than 50% in the following age quartile, and then stabilized (0.7% per year thinning for the age of entry in the cohort younger than 35 years; 0.29% for age older than 35 and younger than 41 years; 0.34% for older than 41 and younger than 49 years; 0.33% for age older than 49 years). DISCUSSION: An age-dependent reduction in retinal and cortical volume loss rates during relapsing-remitting MS suggests deceleration in neurodegeneration in the earlier period of disease and further indicates that the period of greatest adaptive immune-mediated inflammatory activity is also the period with the greatest neuroaxonal loss.
BACKGROUND AND OBJECTIVES: The timing of neurodegeneration in multiple sclerosis (MS) remains unclear. It is critical to understand the dynamics of neuroaxonal loss if we hope to prevent or forestall permanent disability in MS. We therefore used a deeply phenotyped longitudinal cohort to assess and compare rates of neurodegeneration in retina and brain throughout the MS disease course. METHODS: We analyzed 597 patients with MS who underwent longitudinal optical coherence tomography imaging annually for 4.5 ± 2.4 years and 432 patients who underwent longitudinal MRI scans for 10 ± 3.4 years, quantifying macular ganglion cell-inner plexiform layer (GCIPL) volume and cortical gray matter (CGM) volume. The association between the slope of decline in the anatomical structure and the age of entry in the cohort (categorized by the MRI cohort's age quartiles) was assessed by hierarchical linear models. RESULTS: The rate of CGM volume loss declined with increasing age of study entry (1.3% per year atrophy for the age of entry in the cohort younger than 35 years; 1.1% for older than 35 years and younger than 41; 0.97% for older than 41 years and younger than 49; 0.9% for older than 49 years) while the rate of GCIPL thinning was highest in patients in the youngest quartile, fell by more than 50% in the following age quartile, and then stabilized (0.7% per year thinning for the age of entry in the cohort younger than 35 years; 0.29% for age older than 35 and younger than 41 years; 0.34% for older than 41 and younger than 49 years; 0.33% for age older than 49 years). DISCUSSION: An age-dependent reduction in retinal and cortical volume loss rates during relapsing-remitting MS suggests deceleration in neurodegeneration in the earlier period of disease and further indicates that the period of greatest adaptive immune-mediated inflammatory activity is also the period with the greatest neuroaxonal loss.
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