Pediatric Cardiology for Practitioners

Abstract

<h3>Background and Objectives:</h3> The timing of neurodegeneration in MS remains unclear. It is critical to understand the dynamics of neuroaxonal loss if we hope to prevent or forestall permanent disability in MS. We therefore used a deeply phenotyped longitudinal cohort to assess and compare rates of neurodegeneration in retina and brain throughout the MS disease course. <h3>Methods:</h3> We analyzed 597 MS patients who underwent longitudinal OCT imaging annually for 4.5±2.4 years and 432 patients who underwent longitudinal MRI scans for 10±3.4 yrs, quantifying macular ganglion-cell–inner plexiform layer (GCIPL) volume and cortical gray matter (CGM) volume. To evaluate the rate of loss, linear mixed-effects modeling with subject-specific intercepts and slopes were fitted using restricted maximum likelihood estimation. The association between the slope of decline in the anatomical structure and the age of entry in the cohort (categorized by the MRI cohort’s age quartiles) was assessed by linear regression models. <h3>Results:</h3> The rate of CGM volume loss declined with increasing age of study entry (1.3%/year atrophy for the age of entry in the cohort &lt;35 years; 1.1% for age &gt;35 years and &lt;41; 0.97% for age &gt;41 years and &lt;49; 0.9% for age &gt;49 years) while the rate of GCIPL thinning was highest in patients in the youngest quartile, fell by more than 50% in the following age quartile, and then stabilized (0.7%/year thinning for the age of entry in the cohort &lt;35 years; 0.29% for age &gt;35 years and &lt;41; 0.34% for age &gt;41 years and &lt;49; 0.33% for age &gt;49 years). <h3>Conclusions:</h3> An age-dependent reduction in retinal and cortical volume loss rates during RRMS suggests deceleration in neurodegeneration in the earlier period of disease and further indicates that the period of greatest adaptive-immune-mediated inflammatory activity is also the period with the greatest neuroaxonal loss.