Maxime Donadieu1, Yann Le Fur2, Adil Maarouf3, Soraya Gherib2, Ben Ridley2, Lauriane Pini2, Stanislas Rapacchi2, Sylviane Confort-Gouny2, Maxime Guye2, Lothar R Schad4, Andrew A Maudsley5, Jean Pelletier3, Bertrand Audoin3, Wafaa Zaaraoui2, Jean-Philippe Ranjeva2. 1. Aix-Marseille University, CNRS, CRMBM, APHM, Marseille, France/Timone University Hospital, CEMEREM, Marseille, France/Siemens Healthineers, Saint-Denis, France. 2. Aix-Marseille University, CNRS, CRMBM, APHM, Marseille, France/Timone University Hospital, CEMEREM, Marseille, France. 3. Aix-Marseille University, CNRS, CRMBM, APHM, Marseille, France/Timone University Hospital, CEMEREM, Marseille, France/APHM, Timone University Hospital, Department of Neurology, Marseille, FranceCNRS, CRMBM UMR 7339, Medical School of Marseille, Aix-Marseille University, Marseille, France/AP-HM, CHU Timone, Department of Imaging, CEMEREM, Marseille, France/AP-HM, CHU Timone, Pole de Neurosciences Cliniques, Department of Neurology, Marseille, France. 4. Computer Assisted Clinical Medicine, Mannheim University Hospital, Heidelberg University, Mannheim, Germany. 5. Department of Radiology, University of Miami School of Medicine, Miami, FL, USA.
Abstract
BACKGROUND: Increase of brain total sodium concentrations (TSC) is present in multiple sclerosis (MS), but its pathological involvement has not been assessed yet. OBJECTIVE: To determine in vivo the metabolic counterpart of brain sodium accumulation. MATERIALS/ METHODS: Whole brain 23Na-MR imaging and 3D-1H-EPSI data were collected in 21 relapsing-remitting multiple sclerosis (RRMS) patients and 20 volunteers. Metabolites and sodium levels were extracted from several regions of grey matter (GM), normal-appearing white matter (NAWM) and white matter (WM) T2 lesions. Metabolic and ionic levels expressed as Z-scores have been averaged over the different compartments and used to explain sodium accumulations through stepwise regression models. RESULTS: MS patients showed significant 23Na accumulations with lower choline and glutamate-glutamine (Glx) levels in GM; 23Na accumulations with lower N-acetyl aspartate (NAA), Glx levels and higher Myo-Inositol (m-Ins) in NAWM; and higher 23Na, m-Ins levels with lower NAA in WM T2 lesions. Regression models showed associations of TSC increase with reduced NAA in GM, NAWM and T2 lesions, as well as higher total-creatine, and smaller decrease of m-Ins in T2 lesions. GM Glx levels were associated with clinical scores. CONCLUSION: Increase of TSC in RRMS is mainly related to neuronal mitochondrial dysfunction while dysfunction of neuro-glial interactions within GM is linked to clinical scores.
BACKGROUND: Increase of brain total sodium concentrations (TSC) is present in multiple sclerosis (MS), but its pathological involvement has not been assessed yet. OBJECTIVE: To determine in vivo the metabolic counterpart of brain sodium accumulation. MATERIALS/ METHODS: Whole brain 23Na-MR imaging and 3D-1H-EPSI data were collected in 21 relapsing-remitting multiple sclerosis (RRMS) patients and 20 volunteers. Metabolites and sodium levels were extracted from several regions of grey matter (GM), normal-appearing white matter (NAWM) and white matter (WM) T2 lesions. Metabolic and ionic levels expressed as Z-scores have been averaged over the different compartments and used to explain sodium accumulations through stepwise regression models. RESULTS: MS patients showed significant 23Na accumulations with lower choline and glutamate-glutamine (Glx) levels in GM; 23Na accumulations with lower N-acetyl aspartate (NAA), Glx levels and higher Myo-Inositol (m-Ins) in NAWM; and higher 23Na, m-Ins levels with lower NAA in WM T2 lesions. Regression models showed associations of TSC increase with reduced NAA in GM, NAWM and T2 lesions, as well as higher total-creatine, and smaller decrease of m-Ins in T2 lesions. GM Glx levels were associated with clinical scores. CONCLUSION: Increase of TSC in RRMS is mainly related to neuronal mitochondrial dysfunction while dysfunction of neuro-glial interactions within GM is linked to clinical scores.