title: Central nervous system dysfunction in primary biliary cirrhosis and its relationship to symptoms.
abstract: OBJECTIVE
  Primary biliary cirrhosis (PBC) is associated with fatigue, memory impairment, and sleep disturbances. These symptoms suggest the possibility of underlying central nervous system (CNS) dysfunction. During exercise, fatigue develops due to muscular processes (peripheral fatigue) and decreased neurological activation of the muscle (central fatigue). In this study we objectively quantify central and peripheral fatigue in PBC and investigate the integrity of cortical inhibitory and excitatory circuits. Finally, we determine the relationship of these indices to the symptoms of PBC.
  
  
  METHODS
  16 early-stage PBC patients, 8 post-liver transplant PBC patients, and 12 age-matched controls were studied at the Specialist PBC clinic and neuroscience research unit. In these patients, twitch interpolation was used to measure peripheral and central fatigue. Paired-pulse trans-cranial magnetic stimulation was used to assess intra-cortical inhibition (ICI) and facilitation (ICF).
  
  
  RESULTS
  PBC patients had a significantly lower central activation before fatiguing exercise (mean 86.6.8% (±12.75) vs. 95.2% (±7.4); p<0.05) and a greater response variability than controls. The decline in central activation during exercise and peripheral fatigue were normal. ICI was significantly reduced in PBC patients and daytime somnolence was greater in patients where net inhibition exceeded facilitation. Transplanted and non-transplanted patients had similar central activation, ICI, and ICF.
  
  
  CONCLUSIONS
  PBC patients have impaired central activation and abnormal ICI, suggesting CNS abnormalities beyond voluntary control. Transplanted and non-transplanted patients show similar abnormalities raising interesting questions about the mechanisms underpinning these changes and the permanence of neurological dysfunction in PBC. ICI and ICF and the balance between them are related to daytime somnolence (an important symptom in PBC).
authors.affiliation: Institute of Cellular Medicine, Newcastle University, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: McDonald
authors.forename: Julia
authors.initials: J
authors.lastname: Newton
authors.forename: H Ming
authors.initials: HM
authors.lastname: Lai
authors.forename: Stuart N
authors.initials: SN
authors.lastname: Baker
authors.forename: David E
authors.initials: DE
authors.lastname: Jones
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002490:Central Nervous System / Q000503:physiopathology*; D006970:Disorders of Excessive Somnolence / Q000209:etiology / Q000503:physiopathology; D005221:Fatigue / Q000209:etiology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000150:complications / Q000503:physiopathology* / Q000601:surgery; D016031:Liver Transplantation / Q000502:physiology; D008875:Middle Aged; D050781:Transcranial Magnetic Stimulation