MS optic neuritis-induced long-term structural changes within the visual pathway

Abstract

BackgroundThe visual pathway is commonly involved in multiple sclerosis (MS), even in its early stages, including clinical episodes of optic neuritis (ON). The long-term structural damage within the visual compartment in patients with ON, however, is yet to be elucidated.ObjectiveOur aim was to characterize visual system structure abnormalities using MRI along with optical coherence tomography (OCT) and pattern-reversal visual evoked potentials (VEPs) depending on a single history of ON.MethodsTwenty-eight patients with clinically definitive MS, either with a history of a single ON (HON) or without such history and normal VEP findings (NON), were included. OCT measures comprised OCT-derived peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell/inner plexiform layer (GCIPL) thickness. Cortical and global gray and white matter, thalamic, and T2 lesion volumes were assessed using structural MRI. Diffusion-weighted MRI-derived measures included fractional anisotropy (FA), mean (MD), radial (RD), and axial (AD) diffusivity within the optic radiation (OR).ResultsMean (SD) duration after ON was 8.3 (3.7) years. Compared with the NON group, HON patients showed significant RNFL (p = 0.01) and GCIPL thinning (p = 0.002). OR FA (p = 0.014), MD (p = 0.005), RD (p = 0.007), and AD (p = 0.004) were altered compared with NON. Global gray and white as well as other regional gray matter structures did not differ between the 2 groups.ConclusionA single history of ON induces long-term structural damage within the retina and OR suggestive of both retrograde and anterograde neuroaxonal degeneration.

Structure–Function Relationship of Retinal Ganglion Cells in Multiple Sclerosis

“…The changes in HON reported in the present and in previous studies might be related to retrograde degeneration of optic nerve axons and RGC bodies following a demyelinating event at the level of the optic nerve or even posterior to it [ 14 ]. In accordance, previous combined diffusion magnetic resonance imaging (MRI) and OCT studies reported retrograde, i.e., GCIPL/pRNFL, as well as anterograde, i.e., optic radiation, transsynaptic degeneration [ 23 ] and associated brain volume reduction [ 24 ].…”

Retinal thinning and brain atrophy in early MS and CIS

“…Optical coherence tomography can qualitatively and quantitatively measure changes of ganglion cell‐inner plexiform layer (GCIPL) around fovea and of unmyelinated optic nerve fiber layer (RNFL) in the papilla 5,6 . Optical coherence tomography has been validated as a sensitive and reliable tool to quantify inflammation, axonal loss and neurodegeneration in MS 7,8 and is increasingly used to monitor first‐order neurons of the afferent visual pathway in the retina 9,10 …”

Understanding neurodegenerative changes of the afferent visual pathway in MS

“…2 So far, researchers have not succeeded in untangling these effects. In addition, the study of Pawlitzki et al 4 does not shed light on this enigma: the frequency of lesions in the optic radiation is lower in the non-ON group, and the extent of ON-independent visual pathway damage in this cohort could not be evaluated because the study did not include healthy controls.…”

“…Interestingly, the thickness of the primary visual cortex was neither associated with optic radiation DTI parameters nor with RNFL and GCIPL thinning. 4 DTI and retinal atrophy have emerged as important outcome measures in clinical MS research. 1 However, to widely implement OCT and DTI for the individual monitoring of disease progression and treatment response, we still lack important pathologic and technical considerations.…”

“…3 DTI facilitates the reconstruction and analysis of white matter tracts and can thereby reveal microstructural changes of the optic radiation as the most frequently affected white matter pathway in MS. 2 Although fractional anisotropy (FA) is considered as a marker of microstructural integrity, higher radial diffusivity (RD) can be caused by demyelination and axial diffusivity (AD) changes are suggested to be associated with axonal damage. 2 In this issue of Neurology ® Neuroimmunology & Neuroinflammation, Pawlitzki et al 4…”