Association of Spinal Cord Atrophy and Brain Paramagnetic Rim Lesions With Progression Independent of Relapse Activity in People With MS.

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:

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 measurements of the cervical cord, whole brain, and cerebral cortex significantly predicted time to PIRA (all p ≤ 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.

• Authors: Alessandro Cagol, Pascal Benkert, Lester Melie-Garcia, Sabine A Schaedelin, Selina Leber, Charidimos Tsagkas, Muhamed Barakovic, 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 M Lieb, Luca Remonda, Franca Wagner, Maria Isabel Vargas, Renaud A Du Pasquier, Patrice H Lalive, Emanuele Pravatà, Johannes Weber, Philippe C Cattin, Martina Absinta, Claudio Gobbi, David Leppert, Ludwig Kappos, Jens Kuhle, Cristina Granziera
• Journal: Neurology (Neurology) Vol. 102 Issue 1 Pg. e207768 (Jan 09 2024) ISSN: 1526-632X [Electronic] United States
• PMID: 38165377 (Publication Type: Journal Article)

Topics

• Humans
• Female
• Child
• Male
• Cohort Studies
• Cross-Sectional Studies
• Brain (diagnostic imaging)
• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive (diagnostic imaging)
• Chronic Disease