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Central nervous system dysfunction in primary biliary cirrhosis and its relationship to symptoms

Lookup NU author(s): Dr Claire McDonald, Emerita Professor Julia Newton, Professor Stuart BakerORCiD, Professor David Jones


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Background 82 Aims 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 ultra-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% (+/- 74) 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) (C) 2010 European Association for the Study of the Liver Published by Elsevier B V All rights reserved

Publication metadata

Author(s): McDonald C, Newton J, Lai HM, Baker SN, Jones DE

Publication type: Article

Publication status: Published

Journal: Journal of Hepatology

Year: 2010

Volume: 53

Issue: 6

Pages: 1095-1100

Print publication date: 11/08/2010

ISSN (print): 0168-8278

ISSN (electronic): 1600-0641

Publisher: Elsevier BV


DOI: 10.1016/j.jhep.2010.05.036


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Funder referenceFunder name
G0500020Medical Research Council