Paramagnetic Rim Lesions Are Associated With Trans-Synaptic Degeneration of the Visual Pathway in Multiple Sclerosis

Area of Science:

• Neuroscience
• Ophthalmology
• Radiology

Background:

• Retrograde trans-synaptic degeneration (rTSD) is a known consequence of posterior visual pathway lesions in multiple sclerosis (MS).
• This degeneration manifests as hemi-macular ganglion cell-inner plexiform layer (GCIPL) thinning and contralateral visual field loss.
• Paramagnetic rim lesions (PRL) are a specific MRI finding in MS associated with active inflammation.

Purpose of the Study:

• To investigate the associations between rTSD, PRL, and longitudinal visual disability in people with MS (pwMS).
• To utilize a novel optical coherence tomography (OCT)-based biomarker for quantifying rTSD.
• To identify predictors of rTSD and its progression in pwMS.

Main Methods:

• Quantitative rTSD index developed using OCT to measure hemispheric GCIPL asymmetry.
• Generalized linear models used to identify MRI and clinical predictors of baseline rTSD.
• Mixed-effects linear regression models employed to assess longitudinal changes in rTSD.

Main Results:

• PwMS exhibited significantly higher rTSD compared to healthy and non-MS controls.
• PRL in the optic radiations (OR) was associated with increased rTSD and reduced hemifield sensitivity.
• Longitudinal rTSD progression correlated with worsening visual sensitivity and increased odds of Expanded Disability Status Scale score progression.

Conclusions:

• PRL in the OR, African American race, longer disease duration, and higher BMI are linked to rTSD in pwMS.
• Progressive rTSD is a significant predictor of worsening visual impairment and clinical disability in MS.
• The study highlights the clinical relevance of rTSD as a biomarker for MS progression.