title: Hypothalamic damage in multiple sclerosis correlates with disease activity, disability, depression, and fatigue.
abstract: OBJECTIVE
  Disturbances in the hypothalamo-pituitary axis are supposed to modulate activity of multiple sclerosis (MS). We hypothesised that the extent of HYP damage may determine severity of MS and may be associated with the disease evolution. We suggested fatigue and depression may depend on the degree of damage of the area.
  
  
  METHODS
  33 MS patients with relapsing-remitting and secondary progressive disease, and 24 age and sex-related healthy individuals (CON) underwent 1H-MR spectroscopy (1H-MRS) of the hypothalamus. Concentrations of glutamate + glutamin (Glx), cholin (Cho), myoinositol (mIns), N-acetyl aspartate (NAA) expressed as ratio with creatine (Cr) and NAA were correlated with markers of disease activity (RIO score), Multiple Sclerosis Severity Scale (MSSS), Depressive-Severity Status Scale and Simple Numerical Fatigue Scale.
  
  
  RESULTS
  Cho/Cr and NAA/Cr ratios were decreased and Glx/NAA ratio increased in MS patients vs CON. Glx/NAA, Glx/Cr, and mIns/NAA were significantly higher in active (RIO 1-2) vs non-active MS patients (RIO 0). Glx/NAA and Glx/Cr correlated with MSSS and fatigue score, and Glx/Cr with depressive score of MS patients. In CON, relationships between Glx/Cr and age, and Glx/NAA and fatigue score were inverse.
  
  
  CONCLUSIONS
  Our study provides the first evidence about significant hypothalamic alterations correlating with clinical outcomes of MS, using 1H-MRS. The combination of increased Glu or mIns with reduced NAA in HYP reflects whole-brain activity of MS. In addition, excess of Glu is linked to severe disease course, depressive mood and fatigue in MS patients, suggesting superiority of Glu over other metabolites in determining MS burden.
authors.affiliation: a Clinic of Neurology, Jessenius Faculty of Medicine in Martin , Comenius University Bratislava , Slovakia.
authors.forename: E
authors.initials: E
authors.lastname: Kantorová
authors.affiliation: b Clinic of Nuclear Medicine, Jessenius Faculty of Medicine in Martin , Comenius University Bratislava , Bratislava , Slovakia.
authors.forename: H
authors.initials: H
authors.lastname: Poláček
authors.affiliation: c BioMed Division of Neurosciences, Biomedical Center Martin, Jessenius Faculty of Medicine in Martin , Comenius University Bratislava , Bratislava , Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Bittšanský
authors.affiliation: c BioMed Division of Neurosciences, Biomedical Center Martin, Jessenius Faculty of Medicine in Martin , Comenius University Bratislava , Bratislava , Slovakia.
authors.forename: E
authors.initials: E
authors.lastname: Baranovičová
authors.affiliation: c BioMed Division of Neurosciences, Biomedical Center Martin, Jessenius Faculty of Medicine in Martin , Comenius University Bratislava , Bratislava , Slovakia.
authors.forename: P
authors.initials: P
authors.lastname: Hnilicová
authors.affiliation: d Department of Clinical Biochemistry, Jessenius Faculty of Medicine in Martin , Comenius University Bratislava , Bratislava , Slovakia.
authors.forename: D
authors.initials: D
authors.lastname: Čierny
authors.affiliation: a Clinic of Neurology, Jessenius Faculty of Medicine in Martin , Comenius University Bratislava , Slovakia.
authors.forename: Š
authors.initials: Š
authors.lastname: Sivák
authors.affiliation: a Clinic of Neurology, Jessenius Faculty of Medicine in Martin , Comenius University Bratislava , Slovakia.
authors.forename: V
authors.initials: V
authors.lastname: Nosáľ
authors.affiliation: e Clinic of Radiodiagnostics, Jessenius Faculty of Medicine in Martin , Comenius University Bratislava , Bratislava , Slovakia.
authors.forename: K
authors.initials: K
authors.lastname: Zeleňák
authors.affiliation: a Clinic of Neurology, Jessenius Faculty of Medicine in Martin , Comenius University Bratislava , Slovakia.
authors.forename: E
authors.initials: E
authors.lastname: Kurča
mesh_terms: D000328:Adult; D000375:Aging / Q000378:metabolism; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D016022:Case-Control Studies; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D003430:Cross-Sectional Studies; D003863:Depression / Q000000981:diagnostic imaging / Q000378:metabolism*; D004185:Disability Evaluation; D005221:Fatigue / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000000981:diagnostic imaging / Q000378:metabolism*; D007294:Inositol / Q000378:metabolism; D008297:Male; D020528:Multiple Sclerosis, Chronic Progressive / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology; D066244:Proton Magnetic Resonance Spectroscopy; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index
chemical_list: D001224:Aspartic Acid; D018698:Glutamic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline
keywords: MR spectroscopy; Multiple sclerosis; RIO score; depression; disability; fatigue; glutamate toxicity; hypothalamus