Multiple sclerosis optic neuritis and trans-synaptic pathology on cortical thinning in people with multiple sclerosis

J Neurol. 2023 Aug;270(8):3758-3769. doi: 10.1007/s00415-023-11709-y. Epub 2023 Apr 17.


Background: The multi-order visual system represents an excellent testing site regarding the process of trans-synaptic degeneration. The presence and extent of global versus trans-synaptic neurodegeneration in people with multiple sclerosis (pwMS) is not clear.

Objective: To explore cross-sectional and longitudinal relationships between retinal, thalamic and cortical changes in pwMS with and without MS-related optic neuritis (pwMSON and pwoMSON) using MRI and optical coherence tomography (OCT).

Methods: 162 pwMS and 47 healthy controls (HCs) underwent OCT and brain MRI at baseline and 5.5-years follow-up. Peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell inner plexiform layer (mGCIPL) thicknesses were determined. Global volume measures of brain parenchymal volume (BPV)/percent brain volume change (PBVC), thalamic volume and T2-lesion volume (LV) were derived using standard analysis protocols. Regional cortical thickness was determined using FreeSurfer. Cross-sectional and longitudinal relationship between the retinal measures, thalamic volume and cortical thickness were assessed using age, BPV/PBVC and T2-LV adjusted correlations and regressions.

Results: After age, BPV and T2-LV adjustment, the thalamic volume explained additional variance in the thickness of pericalcarine (R2 increase of 0.066, standardized β = 0.299, p = 0.039) and lateral occipital (R2 increase of 0.024, standardized β = 0.299, p = 0.039) gyrii in pwMSON. In pwoMSON, the thalamic volume was a significant predictor only of control (frontal) regions of pars opercularis. There was no relationship between thalamic atrophy and cortical thinning over the follow-up in both pwMS with and without MSON. While numerically lower in the pwMSON group, the inter-eye difference was not able to predict the presence of MSON.

Conclusions: MSON can induce a measurable amount of trans-synaptic pathology on second-order cortical regions.

Keywords: Ganglion cell and inner plexiform layers; Magnetic resonance imaging; Multiple sclerosis; Multiple sclerosis optic neuritis; Optical coherence tomography; Retinal nerve fiber layer.

MeSH terms

  • Adult
  • Aged
  • Cerebral Cortical Thinning* / pathology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis* / complications
  • Multiple Sclerosis* / diagnostic imaging
  • Multiple Sclerosis* / pathology
  • Optic Neuritis* / complications
  • Optic Neuritis* / diagnostic imaging
  • Optic Neuritis* / pathology
  • Retina / diagnostic imaging
  • Retina / pathology
  • Retinal Ganglion Cells
  • Retrograde Degeneration*
  • Tomography, Optical Coherence