Background: The Canadian Prospective Cohort Study to Understand Progression in People Living with MS (CanProCo) aims to better understand disease progression in multiple sclerosis (MS) by evaluating targeted groups of people with different MS sub-types, followed over 5 years. Enrolment started in April 2019, and recruitment is on-going.
Objectives: In this preliminary study, we examined advanced MRI measures in the spinal cord (SC) to evaluate relationships between SC atrophy and demyelination in different MS subtypes.
Methods: Data from one representative CanProCo site with the most balanced recruitment of different MS subtypes were utilized, which included 8 subjects with primary progressive MS (PPMS), 33 with relapsing-remitting MS (RRMS), 12 with radiologically isolated syndrome (RIS), and 9 healthy controls (HC). Imaging protocols followed recommendations from the Generic Acquisition, Database and Analysis Protocol for Quantitative MRI of the SC (https://spine-generic.readthedocs.io/). Using Spinal Cord Toolbox, we segmented and extracted measurements of cross-sectional area at C2 (CSA), mean C2-C5 white matter volume (WMV), and mean C2-C5 white matter magnetization transfer ratio (MTR). Groups were compared with an ANOVA, and linear regressions were performed between MRI metrics across all groups.
Results: The PPMS cohort had the lowest CSA [71.6±6.4mm2]. RRMS, RIS and HC had mean CSAs of 74.4±9.6, 76.0±6.6, 75.2±5.3 mm2, respectively. The PPMS cohort also had the lowest WMV [2923.9± 389.8 mm3], while the RRMS, RIS and HC groups had 3091.0±468.8, 3102.9±235.5, 3141.0±332.3 mm3, respectively. Finally, the PPMS cohort had the lowest MTR [45.6±1.7 percent units (pu)], while the RRMS, RIS and HC had 45.3±2.0, 46.1±1.4, 47.0±1.1 pu, respectively. Mean MTR was significantly different between groups (p=0.02) with PPMS lower than HC (p<0.0001) or RIS (p=0.05), and RRMS lower than HC (p=0.02). There were correlations between CSA and WMV (r=0.62 (p<0.0001)), WMV and MTR (r=0.47 (p<0.0001)), and CSA and MTR (r=0.27 (p=0.03)). Conclusions: In this preliminary analysis, PPMS showed the most atrophy and myelin loss compared to HC. RIS subjects had larger SC CSA than HC, possibly due to the presence of more acute edematous lesions. White matter MTR was correlated with volumetrics, particularly WMV, supporting that SC atrophy is in part driven by loss of myelin. Future work will include evaluating how these measurements change over time, in relation to clinical disability progression.