title: Fatigue and primary biliary cirrhosis: association of globus pallidus magnetisation transfer ratio measurements with fatigue severity and blood manganese levels.
abstract: OBJECTIVE
  Fatigue is the commonest symptom in primary biliary cirrhosis (PBC), affecting individuals at all stages of disease. The pathogenesis of fatigue in PBC is unknown although rat models suggest a central nervous system (CNS) cause. We examined the hypothesis that a CNS abnormality related to cholestasis, rather than cirrhosis per se, underlies this symptom.
  
  
  METHODS
  Fourteen patients with precirrhotic PBC (stage I-II disease), four patients with stage III-IV PBC, and 11 healthy women were studied using cerebral magnetisation contrast imaging and proton magnetic resonance spectroscopy (MRS).
  
  
  RESULTS
  The globus pallidus magnetisation transfer ratio (MTR), a quantifiable tissue characteristic that may be abnormal in the presence of normal magnetic resonance imaging, was significantly reduced in precirrhotic PBC patients compared with healthy controls. These measurements correlated with blood manganese levels and were more abnormal in the more fatigued subjects. There were no differences in MRS measurements between the three study groups, suggesting that the abnormal MTR was not related to hepatic encephalopathy.
  
  
  CONCLUSIONS
  This study suggests that impairments in liver function in PBC may adversely affect the brain long before the development of cirrhosis and hepatic encephalopathy, possibly as a result of altered manganese homeostasis within the CNS.
authors.affiliation: Liver Unit, Faculty of Medicine, St Mary's Hospital Campus, Imperial College London, London, UK. d.forton@imperial.ac.uk
authors.forename: D M
authors.initials: DM
authors.lastname: Forton
authors.forename: N
authors.initials: N
authors.lastname: Patel
authors.forename: M
authors.initials: M
authors.lastname: Prince
authors.forename: A
authors.initials: A
authors.lastname: Oatridge
authors.forename: G
authors.initials: G
authors.lastname: Hamilton
authors.forename: J
authors.initials: J
authors.lastname: Goldblatt
authors.forename: J M
authors.initials: JM
authors.lastname: Allsop
authors.forename: J V
authors.initials: JV
authors.lastname: Hajnal
authors.forename: H C
authors.initials: HC
authors.lastname: Thomas
authors.forename: M
authors.initials: M
authors.lastname: Bassendine
authors.forename: D E J
authors.initials: DE
authors.lastname: Jones
authors.forename: S D
authors.initials: SD
authors.lastname: Taylor-Robinson
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology; D002908:Chronic Disease; D005221:Fatigue / Q000097:blood / Q000209:etiology* / Q000473:pathology; D005260:Female; D005917:Globus Pallidus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000150:complications* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008345:Manganese / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged
chemical_list: D008345:Manganese