Association of Spinal Cord Atrophy and Brain Paramagnetic Rim Lesions With Progression Independent of Relapse Activity in People With MS
Alessandro Cagol, Pascal Benkert, Lester Melie‐García, Sabine Schaedelin, Selina Leber, Charidimos Tsagkas, Muhamed Baraković, Riccardo Galbusera, Po‐Jui Lu, Matthias Weigel, Esther Ruberte, Ernst‐Wilhelm Radue, Özgür Yaldizli, Johanna Oechtering, Johannes Lorscheider, Marcus D’Souza, Bettina Fischer‐Barnicol, Stefanie Müller, Lutz Achtnichts, Jochen Vehoff, Giulio Disanto, Oliver Findling, Andrew Chan, Anke Salmen, Caroline Pot, Claire Bridel, Chiara Zecca, Tobias Derfuss, Johanna Lieb, Luca Remonda, Franca Wagner, María Isabel Vargas, Renaud Du Pasquier, Patrice H. Lalive, Emanuele Pravatà, Johannes Weber, Philippe C. Cattin, Martina Absinta, Claudio Gobbi, David Leppert, Ludwig Kappos, Jens Kühle, Cristina Granziera
Abstract
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: ≤ 0.002). DISCUSSION: Our results show that PIRA is associated with both increased spinal cord atrophy and PRL burden, and this association is evident also in patients with RRMS. These findings further point to the need to develop targeted treatment strategies for PIRA to prevent irreversible neuroaxonal loss and optimize long-term outcomes of patients with MS.