title: Increased total sodium concentration in gray matter better explains cognition than atrophy in MS.
abstract: OBJECTIVE
  To investigate whether brain total sodium accumulation assessed by23Na MRI is associated with cognitive deficit in relapsing-remitting multiple sclerosis (RRMS).
  
  
  METHODS
  Eighty-nine participants were enrolled in the study (58 patients with RRMS with a disease duration ≤10 years and 31 matched healthy controls). Patients were classified as cognitively impaired if they failed at least 2 tasks on the Brief Repeatable Battery. MRI was performed at 3T using23Na MRI to obtain total sodium concentration (TSC) in the different brain compartments (lesions, normal-appearing white matter [NAWM], gray matter [GM]) and1H- magnetization-prepared rapid gradient echo to assess GM atrophy (GM fraction).
  
  
  RESULTS
  The mean disease duration was 3.1 years and the median Expanded Disability Status Scale score was 1 (range 0-4.5). Thirty-seven patients were classified as cognitively preserved and 21 as cognitively impaired. TSC was increased in GM and NAWM in cognitively impaired patients compared to cognitively preserved patients and healthy controls. Voxel-wise analysis demonstrated that sodium accumulation was mainly located in the neocortex in cognitively impaired patients. Regression analysis evidenced than the 2 best independent predictors of cognitive impairment were GM TSC and age. Receiver operating characteristic analyses demonstrated that sensitivity and specificity of the GM TSC to classify patients according to their cognitive status were 76% and 71%, respectively.
  
  
  CONCLUSIONS
  This study provides 2 main findings. (1) In RRMS, total sodium accumulation in the GM is better associated with cognitive impairment than GM atrophy; and (2) total sodium accumulation in patients with cognitive impairment is mainly located in the neocortex.
authors.affiliation: From CNRS (A.M., B.A., F.P., S.G., A.R., E.S., S.C.-G., M.G., J.P., J.-P.R., W.Z.), CRMBM UMR 7339, Aix-Marseille Université, Marseille; Service de Neurologie (A.M.), Centre Hospitalier Universitaire de Reims, Université de Reims Champagne Ardennes; Service de Neurologie (A.M., B.A., A.R., J.P.) and CEMEREM (M.G., A.M.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Marseille, France; and Computer Assisted Clinical Medicine (L.S.), Heidelberg University, Mannheim, Germany. adil.maarouf@ap-hm.fr.
authors.forename: Adil
authors.initials: A
authors.lastname: Maarouf
authors.affiliation: From CNRS (A.M., B.A., F.P., S.G., A.R., E.S., S.C.-G., M.G., J.P., J.-P.R., W.Z.), CRMBM UMR 7339, Aix-Marseille Université, Marseille; Service de Neurologie (A.M.), Centre Hospitalier Universitaire de Reims, Université de Reims Champagne Ardennes; Service de Neurologie (A.M., B.A., A.R., J.P.) and CEMEREM (M.G., A.M.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Marseille, France; and Computer Assisted Clinical Medicine (L.S.), Heidelberg University, Mannheim, Germany.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Audoin
authors.affiliation: From CNRS (A.M., B.A., F.P., S.G., A.R., E.S., S.C.-G., M.G., J.P., J.-P.R., W.Z.), CRMBM UMR 7339, Aix-Marseille Université, Marseille; Service de Neurologie (A.M.), Centre Hospitalier Universitaire de Reims, Université de Reims Champagne Ardennes; Service de Neurologie (A.M., B.A., A.R., J.P.) and CEMEREM (M.G., A.M.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Marseille, France; and Computer Assisted Clinical Medicine (L.S.), Heidelberg University, Mannheim, Germany.
authors.forename: Fanelly
authors.initials: F
authors.lastname: Pariollaud
authors.affiliation: From CNRS (A.M., B.A., F.P., S.G., A.R., E.S., S.C.-G., M.G., J.P., J.-P.R., W.Z.), CRMBM UMR 7339, Aix-Marseille Université, Marseille; Service de Neurologie (A.M.), Centre Hospitalier Universitaire de Reims, Université de Reims Champagne Ardennes; Service de Neurologie (A.M., B.A., A.R., J.P.) and CEMEREM (M.G., A.M.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Marseille, France; and Computer Assisted Clinical Medicine (L.S.), Heidelberg University, Mannheim, Germany.
authors.forename: Soraya
authors.initials: S
authors.lastname: Gherib
authors.affiliation: From CNRS (A.M., B.A., F.P., S.G., A.R., E.S., S.C.-G., M.G., J.P., J.-P.R., W.Z.), CRMBM UMR 7339, Aix-Marseille Université, Marseille; Service de Neurologie (A.M.), Centre Hospitalier Universitaire de Reims, Université de Reims Champagne Ardennes; Service de Neurologie (A.M., B.A., A.R., J.P.) and CEMEREM (M.G., A.M.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Marseille, France; and Computer Assisted Clinical Medicine (L.S.), Heidelberg University, Mannheim, Germany.
authors.forename: Audrey
authors.initials: A
authors.lastname: Rico
authors.affiliation: From CNRS (A.M., B.A., F.P., S.G., A.R., E.S., S.C.-G., M.G., J.P., J.-P.R., W.Z.), CRMBM UMR 7339, Aix-Marseille Université, Marseille; Service de Neurologie (A.M.), Centre Hospitalier Universitaire de Reims, Université de Reims Champagne Ardennes; Service de Neurologie (A.M., B.A., A.R., J.P.) and CEMEREM (M.G., A.M.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Marseille, France; and Computer Assisted Clinical Medicine (L.S.), Heidelberg University, Mannheim, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Soulier
authors.affiliation: From CNRS (A.M., B.A., F.P., S.G., A.R., E.S., S.C.-G., M.G., J.P., J.-P.R., W.Z.), CRMBM UMR 7339, Aix-Marseille Université, Marseille; Service de Neurologie (A.M.), Centre Hospitalier Universitaire de Reims, Université de Reims Champagne Ardennes; Service de Neurologie (A.M., B.A., A.R., J.P.) and CEMEREM (M.G., A.M.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Marseille, France; and Computer Assisted Clinical Medicine (L.S.), Heidelberg University, Mannheim, Germany.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Confort-Gouny
authors.affiliation: From CNRS (A.M., B.A., F.P., S.G., A.R., E.S., S.C.-G., M.G., J.P., J.-P.R., W.Z.), CRMBM UMR 7339, Aix-Marseille Université, Marseille; Service de Neurologie (A.M.), Centre Hospitalier Universitaire de Reims, Université de Reims Champagne Ardennes; Service de Neurologie (A.M., B.A., A.R., J.P.) and CEMEREM (M.G., A.M.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Marseille, France; and Computer Assisted Clinical Medicine (L.S.), Heidelberg University, Mannheim, Germany.
authors.forename: Maxime
authors.initials: M
authors.lastname: Guye
authors.affiliation: From CNRS (A.M., B.A., F.P., S.G., A.R., E.S., S.C.-G., M.G., J.P., J.-P.R., W.Z.), CRMBM UMR 7339, Aix-Marseille Université, Marseille; Service de Neurologie (A.M.), Centre Hospitalier Universitaire de Reims, Université de Reims Champagne Ardennes; Service de Neurologie (A.M., B.A., A.R., J.P.) and CEMEREM (M.G., A.M.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Marseille, France; and Computer Assisted Clinical Medicine (L.S.), Heidelberg University, Mannheim, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Schad
authors.affiliation: From CNRS (A.M., B.A., F.P., S.G., A.R., E.S., S.C.-G., M.G., J.P., J.-P.R., W.Z.), CRMBM UMR 7339, Aix-Marseille Université, Marseille; Service de Neurologie (A.M.), Centre Hospitalier Universitaire de Reims, Université de Reims Champagne Ardennes; Service de Neurologie (A.M., B.A., A.R., J.P.) and CEMEREM (M.G., A.M.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Marseille, France; and Computer Assisted Clinical Medicine (L.S.), Heidelberg University, Mannheim, Germany.
authors.forename: Jean
authors.initials: J
authors.lastname: Pelletier
authors.affiliation: From CNRS (A.M., B.A., F.P., S.G., A.R., E.S., S.C.-G., M.G., J.P., J.-P.R., W.Z.), CRMBM UMR 7339, Aix-Marseille Université, Marseille; Service de Neurologie (A.M.), Centre Hospitalier Universitaire de Reims, Université de Reims Champagne Ardennes; Service de Neurologie (A.M., B.A., A.R., J.P.) and CEMEREM (M.G., A.M.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Marseille, France; and Computer Assisted Clinical Medicine (L.S.), Heidelberg University, Mannheim, Germany.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Ranjeva
authors.affiliation: From CNRS (A.M., B.A., F.P., S.G., A.R., E.S., S.C.-G., M.G., J.P., J.-P.R., W.Z.), CRMBM UMR 7339, Aix-Marseille Université, Marseille; Service de Neurologie (A.M.), Centre Hospitalier Universitaire de Reims, Université de Reims Champagne Ardennes; Service de Neurologie (A.M., B.A., A.R., J.P.) and CEMEREM (M.G., A.M.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Marseille, France; and Computer Assisted Clinical Medicine (L.S.), Heidelberg University, Mannheim, Germany.
authors.forename: Wafaa
authors.initials: W
authors.lastname: Zaaraoui
mesh_terms: D000328:Adult; D001284:Atrophy / Q000209:etiology / Q000473:pathology; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000209:etiology*; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications* / Q000000981:diagnostic imaging; D009483:Neuropsychological Tests; D012964:Sodium / Q000378:metabolism*; D018709:Statistics, Nonparametric; D014316:Tritium / Q000378:metabolism
chemical_list: D014316:Tritium; D012964:Sodium