Background/Purpose: Inflammation in the meninges is increasingly recognized as a critical component of the underlying pathophysiology of multiple sclerosis (MS). Histopathologic data suggests direct links between meningeal inflammation and both local and distant cortical demyelination and axonal loss. Neuroimaging studies of leptomeningeal enhancement (LME), a possible surrogate of meningeal inflammation, show a relationship between LME and cortical atrophy, although findings relating LME to cortical lesions (CLs) have been more inconsistent. In this study, we aimed to evaluate the interrelationship between LME, CLs, and more distant neuronal atrophy through evaluation of retinal thickness by optical coherence tomography (OCT).
Methods: Forty participants with MS underwent whole brain 7T imaging on a Philips Achieva scanner with a volume transmit/32 channel receive head coil and optical coherence tomography on a Heidelberg Engineering Spectralis spectral domain OCT scanner at baseline, along with annual follow up OCT images. 7T scans involved pre- and post-contrast acquisition of magnetization prepared 2 rapid acquisition gradient echo (MP2RAGE) sequences acquired at 0.7 mm x 0.688 mm x 0.68 mm resolution and a magnetization prepared fluid attenuated inversion recovery (MPFLAIR) image at 0.7mm3 isotropic resolution. MRI images were reviewed for LME and CLs and processed for segmented volumes. OCT images underwent segmentation for individual retinal layers. MRI and OCT data were evaluated using correlation testing and mixed models regression, adjusted for age, sex, treatment status, and optic neuritis history.
Results: The cohort consisted of 26 (65%) females and were mostly of the relapsing-remitting phenotype (30/40 (75%). Thirty-two (80%) subjects had at least one focus of LME and all had CLs on 7T MRI. Baseline ganglion cell/inner plexiform (GCIP) layer and average macular thickness (AMT) correlated with normalized CL volume (r = -0.45, p = 0.006 and r = -0.34, p = 0.049 respectively). Macular RNFL (mRNFL) and GCIP thickness and AMT were -4.60 (-7.85, -1.35) μm, -8.12 (-14.16, -2.08) μm, and 15.073 (-28.61, -1.54) μm thinner, respectively, if LME was present (p = 0.006, 0.009, and 0.030, respectively). In subjects in whom spread/fill-sulcal pattern LME was present at baseline, mRNFL thickness declined -0.84 (-1.61, -0.07) μm/year faster (p = 0.033) and OPL thickness declined -1.23 (-2.33, -0.13) μm/year faster (p = 0.029).
Conclusion: This study provides support for a relationship between MRI findings of cortical pathology and LME and thinning of retinal layers as measured by OCT. These associations suggest meningeal inflammation may be a common link resulting in widespread demyelination, neuronal loss, and axonal degeneration throughout the CNS and the retina.