Associations between cortical lesions, optic nerve damage, and disability at the onset of multiple sclerosis: insights into neurodegenerative processes

Kyriakoula Varmpompiti; Geoffrey Chow; Michael Foster; Srikirti Kodali; Ferran Prados; Marios C Yiannakas; Baris Kanber; Ailbhe Burke; Lola Ogunbowale; Indran Davagnanam; Ahmed T Toosy; Sara Collorone

doi:10.1016/j.msard.2023.105413

Associations between cortical lesions, optic nerve damage, and disability at the onset of multiple sclerosis: insights into neurodegenerative processes

Mult Scler Relat Disord. 2024 Mar:83:105413. doi: 10.1016/j.msard.2023.105413. Epub 2023 Dec 26.

Authors

Affiliations

¹ NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
² Centre for Medical Image Computing (CMIC), Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
³ NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK; Centre for Medical Image Computing (CMIC), Department of Medical Physics and Biomedical Engineering, University College London, London, UK; eHealth Center, Universitat Oberta de Catalunya, Barcelona, Spain.
⁴ NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK; Centre for Medical Image Computing (CMIC), Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
⁵ Moorfields Eye Hospital, City Road, London, UK.
⁶ Department of Brain Repair and Rehabilitation, University College London Institute of Neurology, Faculty of Brain Sciences, UCL, London, UK.
⁷ NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK. Electronic address: s.collorone@ucl.ac.uk.

PMID: 38215633
DOI: 10.1016/j.msard.2023.105413

Abstract

Background: Multiple sclerosis cortical lesions are areas of demyelination and neuroaxonal loss. Retinal layer thickness, measured with optical coherence tomography (OCT), is an emerging biomarker of neuroaxonal loss. Studies have reported correlations between cortical lesions and retinal layer thinning in established multiple sclerosis, suggesting a shared pathophysiological process. Here, we assessed the correlation between cortical lesions and OCT metrics at the onset of multiple sclerosis, examining, for the first time, associations with physical or cognitive disability.

Objective: To examine the relationship between cortical lesions, optic nerve and retinal layer thicknesses, and physical and cognitive disability at the first demyelinating event.

Methods: Thirty-nine patients and 22 controls underwent 3T-MRI, optical coherence tomography, and clinical tests. We identified cortical lesions on phase-sensitive inversion recovery sequences, including occipital cortex lesions. We measured the estimated total intracranial volume and the white matter lesion volume. OCT metrics included peripapillary retinal nerve fibre layer (pRNFL), ganglion cell and inner plexiform layer (GCIPL) and inner nuclear layer (INL) thicknesses.

Results: Higher total cortical and leukocortical lesion volumes correlated with thinner pRNFL (B = -0.0005, 95 % CI -0.0008 to -0.0001, p = 0.01; B = -0.0005, 95 % CI -0.0008 to -0.0001, p = 0.01, respectively). Leukocortical lesion number correlated with colour vision deficits (B = 0.58, 95 %CI 0.039 to 1,11, p = 0.036). Thinner GCIPL correlated with a higher Expanded Disability Status Scale (B = -0.06, 95 % CI -1.1 to -0.008, p = 0.026). MS diagnosis (n = 18) correlated with higher cortical and leukocortical lesion numbers (p = 0.004 and p = 0.003), thinner GCIPL (p = 0.029) and INL (p = 0.041).

Conclusion: The association between cortical lesions and axonal damage in the optic nerve reinforces the role of neurodegenerative processes in MS pathogenesis at onset.

Keywords: Clinically isolated syndrome; Cortical lesions; MRI; Multiple sclerosis; Optical coherence tomography; Retinal atrophy.

MeSH terms

Humans
Multiple Sclerosis* / complications
Multiple Sclerosis* / diagnostic imaging
Optic Nerve / pathology
Retina / pathology
Retinal Degeneration* / etiology
Retinal Ganglion Cells / pathology
Tomography, Optical Coherence

Grants and funding

MR/S026088/1/MRC_/Medical Research Council/United Kingdom