MRI and serum NfL/GFAP predictors of cognitive and clinical decline in newly diagnosed relapsing remitting multiple sclerosis patients: a 3-year follow-up study.

Resumen

Introduction: Neuroimaging biomarkers frequently used in relapsing-remitting multiple sclerosis (RRMS) are helpful for diagnosis and outcome prediction, but the relative significance of imaging compared to serological markers as predictors of cognitive and clinical functioning in newly diagnosed MS patients is still debatedObjectives/Aims: To understand longitudinal changes of global or regional grey matter (GM) volume, cortical thickness (CT), neuropsychiatric symptoms, serum levels of neurodegeneration and astrocytic activation as well as their role in predicting the short-term cognitive and clinical decline in recently diagnosed RRMS patients.Methods: We longitudinally evaluated 35 RRMS patients and 22 healthy controls (HC), followed-up for 2.97+0.27 years. Participants simultaneously underwent a magnetic resonance imaging (MRI) study, a full clinical and neuropsychological assessment, and blood sampling to obtain neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) serum levels using single molecule array. Stepwise multiple regression modeling was used to examine the prognostic value of these measures as indicators of cognitive and clinical decline.Results: At 3-year follow-up, 49% of patients developed significant deterioration in cognitive function and were categorized as cognitively-declining (CD) RRMS. While cognitively-stable (CS) RRMS did not exhibited significant GM volume loss or cortical thinning at baseline compared to HC, CD subgroup displayed accelerated changes in GM volume loss and CT mainly affecting thalamus and temporal, parietal and frontal cortical regions. Interestingly, while global CT and mood symptoms as well as thalamus and caudal middle frontal GM volumes at baseline predicted cognitive functioning at follow-up, short-term clinical disability was predicted by baseline global CT and GFAP levels. Conclusion: Serum biomarkers did not clearly distinguish RRMS patients from HC. However, global and regional cortical thinning, thalamic GM atrophy, astrocytic activation, and mood status could represent distinctive MS hallmarks to track progression of cognitive and clinical decline in newly diagnosed patients with MS. Disclosure of interest: A.J. Cruz-Gómez, Jaime F. GómezRamirez, and F. Sanmartino were supported by 2 postdoctoral fellowships from the Department of Health (grants: PI-0025-2017 and PI-0034-2019). L Forero received speaker fees and travel support from Biogen, Merck Serono, Novartis, Sanofi, Teva, and Roche. E Lozano-Soto was supported by a research contract form the Andalusian General Secretariat of Universities, Research and Technology (grant: ProyExcel-01041). F. CanoCano was supported by the INiBICA through a predoctoral fellowship. R. Gutierrez-Cortés was supported by a training grant from European Social Fund within the framework of the Youth Employment Operational Program (POEJ). A. del Marco had nothing to disclose. R. Rashid-López received speaker fees and travel support from Teva, AbbVie, Zambon, BIAL, and Italfarmaco. J. Paz-Esposito had nothing to disclose. C. GarcíaGuijo received travel support from Biogen, Merck Serono, Novartis, Sanofi, Teva, and Roche. R. Espinosa-Rosso received speaker fees and travel support from Teva, AbbVie, Zambon, BIAL, Italfarmaco, Biogen, Merck Serono, Novartis, Sanofi, and Roche. J.J. González-Rosa was supported by the University of Cadiz and a tenure-track “Ramon y Cajal” research fellowship/grant (RYC-2015-18467).