Athina Papadopoulou1, Laura Gaetano2, Armanda Pfister2, Anna Altermatt2, Charidimos Tsagkas2, Felix Morency2, Alexander U Brandt2, Martin Hardmeier2, Mallar M Chakravarty2, Maxime Descoteaux2, Ludwig Kappos2, Till Sprenger2, Stefano Magon2. 1. From the Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedical Engineering (A. Papadopoulou, L.G., A. Pfister, C.T., M.H., L.K., T.S., S.M.), and Translational Imaging in Neurology (ThINK) Basel, Department of Medicine and Biomedical Engineering (A. Papadopoulou, L.G., A.A., C.T., S.M.), University Hospital Basel and University of Basel, Switzerland; NeuroCure Clinical Research Center (NCRC) (A. Papadopoulou, A.U.B.), and Experimental and Clinical Research Center (A. Papadopoulou, A.U.B.), Max Delbrück Center for Molecular Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; Medical Image Analysis Center (MIAC) (L.G., A.A., C.T., S.M.), Basel, Switzerland; Imeka Solutions (F.M.), Sherbrooke, Canada; Department of Neurology (A.U.B.), University of California Irvine; Cerebral Imaging Centre (M.M.C.), Douglas Mental Health University Institute; Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal; University of Sherbrooke (M.D.), Canada; and Department of Neurology (T.S.), DKD Helios Klinik Wiesbaden, Germany. The present address for L.G. is F. Hoffmann-La Roche, Basel, Switzerland. athina.papadopoulou@usb.ch. 2. From the Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedical Engineering (A. Papadopoulou, L.G., A. Pfister, C.T., M.H., L.K., T.S., S.M.), and Translational Imaging in Neurology (ThINK) Basel, Department of Medicine and Biomedical Engineering (A. Papadopoulou, L.G., A.A., C.T., S.M.), University Hospital Basel and University of Basel, Switzerland; NeuroCure Clinical Research Center (NCRC) (A. Papadopoulou, A.U.B.), and Experimental and Clinical Research Center (A. Papadopoulou, A.U.B.), Max Delbrück Center for Molecular Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; Medical Image Analysis Center (MIAC) (L.G., A.A., C.T., S.M.), Basel, Switzerland; Imeka Solutions (F.M.), Sherbrooke, Canada; Department of Neurology (A.U.B.), University of California Irvine; Cerebral Imaging Centre (M.M.C.), Douglas Mental Health University Institute; Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal; University of Sherbrooke (M.D.), Canada; and Department of Neurology (T.S.), DKD Helios Klinik Wiesbaden, Germany. The present address for L.G. is F. Hoffmann-La Roche, Basel, Switzerland.
Abstract
OBJECTIVE: To study if the thalamic lateral geniculate nucleus (LGN) is affected in multiple sclerosis (MS) due to anterograde degeneration from optic neuritis (ON) or retrograde degeneration from optic radiation (OR) pathology, and if this is relevant for visual function. METHODS: In this cross-sectional study, LGN volume of 34 patients with relapsing-remitting MS and 33 matched healthy controls (HC) was assessed on MRI using atlas-based automated segmentation (MAGeT). ON history, thickness of the ganglion cell-inner plexiform layer (GC-IPL), OR lesion volume, and fractional anisotropy (FA) of normal-appearing OR (NAOR-FA) were assessed as measures of afferent visual pathway damage. Visual function was tested, including low-contrast letter acuity (LCLA) and Hardy-Rand-Rittler (HRR) plates for color vision. RESULTS: LGN volume was reduced in patients vs HC (165.5 ± 45.5 vs 191.4 ± 47.7 mm3, B = -25.89, SE = 5.83, p < 0.001). It was associated with GC-IPL thickness (B = 0.95, SE = 0.33, p = 0.006) and correlated with OR lesion volume (Spearman ρ = -0.53, p = 0.001), and these relationships remained after adjustment for normalized brain volume. There was no association between NAOR-FA and LGN volume (B = -133.28, SE = 88.47, p = 0.137). LGN volume was not associated with LCLA (B = 5.5 × 10-5, SE = 0.03, p = 0.998), but it correlated with HRR color vision (ρ = 0.39, p = 0.032). CONCLUSIONS: LGN volume loss in MS indicates structural damage with potential functional relevance. Our results suggest both anterograde degeneration from the retina and retrograde degeneration from the OR lesions as underlying causes. LGN volume is a promising marker reflecting damage of the visual pathway in MS, with the advantage of individual measurement per patient on conventional MRI.
OBJECTIVE: To study if the thalamic lateral geniculate nucleus (LGN) is affected in multiple sclerosis (MS) due to anterograde degeneration from optic neuritis (ON) or retrograde degeneration from optic radiation (OR) pathology, and if this is relevant for visual function. METHODS: In this cross-sectional study, LGN volume of 34 patients with relapsing-remitting MS and 33 matched healthy controls (HC) was assessed on MRI using atlas-based automated segmentation (MAGeT). ON history, thickness of the ganglion cell-inner plexiform layer (GC-IPL), OR lesion volume, and fractional anisotropy (FA) of normal-appearing OR (NAOR-FA) were assessed as measures of afferent visual pathway damage. Visual function was tested, including low-contrast letter acuity (LCLA) and Hardy-Rand-Rittler (HRR) plates for color vision. RESULTS: LGN volume was reduced in patients vs HC (165.5 ± 45.5 vs 191.4 ± 47.7 mm3, B = -25.89, SE = 5.83, p < 0.001). It was associated with GC-IPL thickness (B = 0.95, SE = 0.33, p = 0.006) and correlated with OR lesion volume (Spearman ρ = -0.53, p = 0.001), and these relationships remained after adjustment for normalized brain volume. There was no association between NAOR-FA and LGN volume (B = -133.28, SE = 88.47, p = 0.137). LGN volume was not associated with LCLA (B = 5.5 × 10-5, SE = 0.03, p = 0.998), but it correlated with HRR color vision (ρ = 0.39, p = 0.032). CONCLUSIONS: LGN volume loss in MS indicates structural damage with potential functional relevance. Our results suggest both anterograde degeneration from the retina and retrograde degeneration from the OR lesions as underlying causes. LGN volume is a promising marker reflecting damage of the visual pathway in MS, with the advantage of individual measurement per patient on conventional MRI.
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