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Multimodal Analysis of the Visual Pathways in Friedreich's Ataxia Reveals Novel Biomarkers |
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| Authors: | Gilbert Thomas-Black MBBS PhD Daniel R. Altmann PhD Harry Crook MSc Nita Solanky PhD Ferran Prados Carrasco PhD Marco Battiston PhD Francesco Grussu PhD Marios C. Yiannakas PhD Baris Kanber PhD Jasleen K. Jolly PhD Jon Brett BSc Susan M. Downes MB ChB MD Marni Moran MA Ping K. Chan PhD Emmanuel Adewunmi BSc Claudia A.M. Gandini Wheeler-Kingshott PhD Andrea H. Németh MBBS DPhil Richard Festenstein MBBS PhD Fion Bremner MBBS PhD Paola Giunti MD PhD |
| Affiliation: | 1. The Ataxia Centre, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK;2. Medical Statistics Department, London School of Hygiene and Tropical Medicine, London, UK;3. Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, University College London (UCL) Queen Square Institute of Neurology, Faculty of Brain Sciences, UCL, London, UK Department of Medical Physics and Biomedical Engineering, Centre for Medical Image Computing, UCL, London, UK e-Health Centre, Open University of Catalonia, Barcelona, Spain;4. Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, University College London (UCL) Queen Square Institute of Neurology, Faculty of Brain Sciences, UCL, London, UK;5. Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, University College London (UCL) Queen Square Institute of Neurology, Faculty of Brain Sciences, UCL, London, UK Centre for Medical Image Computing, Department of Computer Science, University College London, London, UK Radiomics Group, Vall d'Hebron Institute of Oncology, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain;6. Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, University College London (UCL) Queen Square Institute of Neurology, Faculty of Brain Sciences, UCL, London, UK Department of Medical Physics and Biomedical Engineering, Centre for Medical Image Computing, UCL, London, UK;7. Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK Vision and Eye Research Institute, Anglia Ruskin University, Cambridge, UK;8. Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK;9. NIHR Clinical Research Network, Oxford University Hospitals NHS Foundation Trust, Oxford, UK;10. Gene Control Mechanisms and Disease Group, Department of Medicine, Division of Brain Sciences and MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London, UK;11. Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, University College London (UCL) Queen Square Institute of Neurology, Faculty of Brain Sciences, UCL, London, UK Brain MRI 3T Research Center, IRCCS Mondino Foundation, Pavia, Italy Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy;12. NIHR Clinical Research Network, Oxford University Hospitals NHS Foundation Trust, Oxford, UK Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK;13. National Hospital for Neurology and Neurosurgery, University College London Hospitals Foundation NHS Trust, London, UK |
| Abstract: | BackgroundOptic neuropathy is a near ubiquitous feature of Friedreich's ataxia (FRDA). Previous studies have examined varying aspects of the anterior and posterior visual pathways but none so far have comprehensively evaluated the heterogeneity of degeneration across different areas of the retina, changes to the macula layers and combined these with volumetric MRI studies of the visual cortex and frataxin level.MethodsWe investigated 62 genetically confirmed FRDA patients using an integrated approach as part of an observational cohort study. We included measurement of frataxin protein levels, clinical evaluation of visual and neurological function, optical coherence tomography to determine retinal nerve fibre layer thickness and macular layer volume and volumetric brain MRI.ResultsWe demonstrate that frataxin level correlates with peripapillary retinal nerve fibre layer thickness and that retinal sectors differ in their degree of degeneration. We also shown that retinal nerve fibre layer is thinner in FRDA patients than controls and that this thinning is influenced by the AAO and GAA1. Furthermore we show that the ganglion cell and inner plexiform layers are affected in FRDA. Our MRI data indicate that there are borderline correlations between retinal layers and areas of the cortex involved in visual processing.ConclusionOur study demonstrates the uneven distribution of the axonopathy in the retinal nerve fibre layer and highlight the relative sparing of the papillomacular bundle and temporal sectors. We show that thinning of the retinal nerve fibre layer is associated with frataxin levels, supporting the use the two biomarkers in future clinical trials design. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. |
| Keywords: | Friedreich's ataxia biomarkers frataxin OCT MRI |