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Association of Spinal Cord Atrophy and Brain Paramagnetic Rim Lesions With Progression Independent of Relapse
Alessandro Cagol1, Pascal Benkert1, Lester Melie-Garcia1
1From Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, Faculty of Medicine (A. Cagol, L.M.-G., S.L., C.T., M.B., R.G., P.-J.L., M.W., E.R., E.-W.R., Ö.Y., L.K., C. Granziera), Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB) (A. Cagol, L.M.-G., C.T., M.B., R.G., P.-J.L., M.W., E.R.,O.Y., J.O., J.L., M.D.S., B.F.-B., T.D., D.L., L.K., J.K., C. Granziera), Department of Clinical Research (P.B., S.A.S.), Division of Radiological Physics, Department of Radiology (M.W.), and Division of Diagnostic and Interventional Neuroradiology, Clinic for Radiology and Nuclear Medicine (J.M.L.), University Hospital Basel, University of Basel, Switzerland; Translational Neuroradiology Section (C.T), National Institute of Neurological Disorders and Stroke, National Institutes of Health (NIH), Bethesda, MD; Medical Image Analysis Center (MIAC) and Quantitative Biomedical Imaging Group (qbig), Department of Biomedical Engineering (E.R., P.C.C.), University Basel; Departments of Neurology (S.M., J.V.) and Radiology (J.W.), Cantonal Hospital St. Gallen; Departments of Neurology (L.A., O.F.) and Radiology (L.R.), Cantonal Hospital Aarau; Departments of Neurology (G.D., C.Z., C.G.) and Neuroradiology (E.P.), Neurocenter of Southern Switzerland, Lugano; Departments of Neurology, Inselspital (A. Chan, A.S.), and Diagnostic and Interventional Neuroradiology, Inselspital (F.W.) Bern University Hospital and University of Bern; Departments of Clinical Neurosciences, Division of Neurology (C.P., R.A.D.P.), and Radiology (R.A.D.P.) Lausanne University Hospital and University of Lausanne; Department of Clinical Neurosciences, Division of Neurology (C.B., P.H.L.), and Radiology (M.I.V.) Geneva University Hospitals and Faculty of Medicine; Faculty of Biomedical Sciences (C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Institute of Experimental Neurology, Division of Neuroscience (M.A.); Vita-Salute San Raffaele University and Hospital, Milan, Italy.
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.
