title: Hypoperfusion of the thalamus is associated with disability in relapsing remitting multiple sclerosis.
abstract: BACKGROUND
  While gray matter (GM) perfusion abnormalities have been evidenced in multiple sclerosis (MS) patients, the relationships with disability still remain unclear. Considering that atrophy is known to impact on perfusion, we aimed to assess perfusion abnormalities in GM of MS patients, outside atrophic regions and investigate relationships with disability.
  
  
  METHODS
  Brain perfusion of 23 relapsing remitting MS patients and 16 matched healthy subjects were assessed at 3T using the pseudo-continuous arterial spin labeling magnetic resonance imaging technique. In order to locate potential GM perfusion abnormalities in regions spared by atrophy, we combined voxelwise comparisons of GM cerebral blood flow (CBF) maps (cortex and deep GM) (P<0.005, FWE-corrected) and voxel-based-morphometry analysis (P<0.005, FDR-corrected) to exclude atrophic regions. Disability was assessed using the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite score (MSFC).
  
  
  RESULTS
  In patients, significant GM hypoperfusion outside atrophic regions was depicted only in bilateral thalami. No other cluster was found to be hypoperfused compared to controls. Perfusion of thalami was correlated to MSFC (P=0.011, rho=0.523). A trend of correlation was found between perfusion of thalami and EDSS (P=0.061, rho=-0.396).
  
  
  CONCLUSIONS
  In relapsing remitting MS, perfusion abnormalities in thalamic regions contribute to disability. These findings suggest that functional impairments of thalami, representing a major brain hub, may disturb various cerebral functions even before structural damage.
authors.affiliation: Aix-Marseille University, CNRS, CRMBM UMR 7339, 13005, Marseille, France; Aix-Marseille University, AP-HM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, 13005, Marseille, France. Electronic address: emilie.doche@ap-hm.fr.
authors.forename: Emilie
authors.initials: E
authors.lastname: Doche
authors.affiliation: Aix-Marseille University, CNRS, CRMBM UMR 7339, 13005, Marseille, France.
authors.forename: Angèle
authors.initials: A
authors.lastname: Lecocq
authors.affiliation: Aix-Marseille University, CNRS, CRMBM UMR 7339, 13005, Marseille, France; Aix-Marseille University, AP-HM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, 13005, Marseille, France; Aix-Marseille University, AP-HM, Hôpital de la Timone, Pôle d'Imagerie Médicale, CEMEREM, 13005, Marseille, France.
authors.forename: Adil
authors.initials: A
authors.lastname: Maarouf
authors.affiliation: Aix-Marseille University, CNRS, CRMBM UMR 7339, 13005, Marseille, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Duhamel
authors.affiliation: Aix-Marseille University, CNRS, CRMBM UMR 7339, 13005, Marseille, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Soulier
authors.affiliation: Aix-Marseille University, CNRS, CRMBM UMR 7339, 13005, Marseille, France.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Confort-Gouny
authors.affiliation: Aix-Marseille University, CNRS, CRMBM UMR 7339, 13005, Marseille, France; Aix-Marseille University, AP-HM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, 13005, Marseille, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Rico
authors.affiliation: Aix-Marseille University, CNRS, CRMBM UMR 7339, 13005, Marseille, France; Aix-Marseille University, AP-HM, Hôpital de la Timone, Pôle d'Imagerie Médicale, CEMEREM, 13005, Marseille, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Guye
authors.affiliation: Aix-Marseille University, CNRS, CRMBM UMR 7339, 13005, Marseille, France; Aix-Marseille University, AP-HM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, 13005, Marseille, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Audoin
authors.affiliation: Aix-Marseille University, CNRS, CRMBM UMR 7339, 13005, Marseille, France; Aix-Marseille University, AP-HM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, 13005, Marseille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Pelletier
authors.affiliation: Aix-Marseille University, CNRS, CRMBM UMR 7339, 13005, Marseille, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Ranjeva
authors.affiliation: Aix-Marseille University, CNRS, CRMBM UMR 7339, 13005, Marseille, France.
authors.forename: Wafaa
authors.initials: W
authors.lastname: Zaaraoui
mesh_terms: D000328:Adult; D001284:Atrophy / Q000000981:diagnostic imaging; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology; D004185:Disability Evaluation; D005260:Female; D066128:Gray Matter; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000000981:diagnostic imaging* / Q000473:pathology*; D012720:Severity of Illness Index; D013113:Spin Labels; D013788:Thalamus / Q000098:blood supply* / Q000000981:diagnostic imaging* / Q000473:pathology*
chemical_list: D013113:Spin Labels
keywords: Atrophy; Disability; Multiple sclerosis; Perfusion; Pseudo-continuous arterial spin labeling; Thalamus