| Contributors: |
Cagol, A.; Benkert, P.; Melie-Garcia, L.; Schaedelin, S. A.; Leber, S.; Tsagkas, C.; Barakovic, M.; Galbusera, R.; Lu, P. -J.; Weigel, M.; Ruberte, E.; Radue, E. -W.; Yaldizli, O.; Oechtering, J.; Lorscheider, J.; D'Souza, M.; Fischer-Barnicol, B.; Muller, S.; Achtnichts, L.; Vehoff, J.; Disanto, G.; Findling, O.; Chan, A.; Salmen, A.; Pot, C.; Bridel, C.; Zecca, C.; Derfuss, T.; Lieb, J. M.; Remonda, L.; Wagner, F.; Vargas, M. I.; Du Pasquier, R. A.; Lalive, P. H.; Pravata', E.; Weber, J.; Cattin, P. C.; Absinta, M.; Gobbi, C.; Leppert, D.; Kappos, L.; Kuhle, J.; Granziera, C. |
| Description: |
Background and Objectives: Progression independent of relapse activity (PIRA) is a crucial determinant of overall disability accumulation in multiple sclerosis (MS). Accelerated brain atrophy has been shown in patients experiencing PIRA. In this study, we assessed the relation between PIRA and neurodegenerative processes reflected by (1) longitudinal spinal cord atrophy and (2) brain paramagnetic rim lesions (PRLs). Besides, the same relationship was investigated in progressive MS (PMS). Last, we explored the value of cross-sectional brain and spinal cord volumetric measurements in predicting PIRA. Methods: From an ongoing multicentric cohort study, we selected patients with MS with (1) availability of a susceptibility-based MRI scan and (2) regular clinical and conventional MRI follow-up in the 4 years before the susceptibility-based MRI. Comparisons in spinal cord atrophy rates (explored with linear mixed-effect models) and PRL count (explored with negative binomial regression models) were performed between: (1) relapsing-remitting (RRMS) and PMS phenotypes and (2) patients experiencing PIRA and patients without confirmed disability accumulation (CDA) during follow-up (both considering the entire cohort and the subgroup of patients with RRMS). Associations between baseline MRI volumetric measurements and time to PIRA were explored with multivariable Cox regression analyses. Results: In total, 445 patients with MS (64.9% female; mean [SD] age at baseline 45.0 [11.4] years; 11.2% with PMS) were enrolled. Compared with patients with RRMS, those with PMS had accelerated cervical cord atrophy (mean difference in annual percentage volume change [MD-APC] -1.41; p = 0.004) and higher PRL load (incidence rate ratio [IRR] 1.93; p = 0.005). Increased spinal cord atrophy (MD-APC -1.39; p = 0.0008) and PRL burden (IRR 1.95; p = 0.0008) were measured in patients with PIRA compared with patients without CDA; such differences were also confirmed when restricting the analysis to patients with RRMS. Baseline volumetric ... |