title: Electroencephalogram variability in patients with cirrhosis associates with the presence and severity of hepatic encephalopathy.
abstract: The outputs of physiological systems fluctuate in a complex manner even under resting conditions. Decreased variability or increased regularity of these outputs is documented in several disease states. Changes are observed in the spatial and temporal configuration of the electroencephalogram (EEG) in patients with hepatic encephalopathy (HE), but there is no information on the variability of the EEG signal in this condition. The aim of this study was to measure and characterize EEG variability in patients with cirrhosis and to determine its relationship to neuropsychiatric status.
  
  
  
  Eyes-closed, awake EEGs were obtained from 226 patients with cirrhosis, classified, using clinical and psychometric criteria, as neuropsychiatrically unimpaired (n=127) or as having minimal (n=21) or overt (n=78) HE, and from a reference population of 137 healthy controls. Analysis of EEG signal variability was undertaken using continuous wavelet transform and sample entropy.
  
  
  
  EEG variability was reduced in the patients with cirrhosis compared with the reference population (coefficient of variation: 21.2% [19.3-23.4] vs. 22.4% [20.8-24.5]; p<0.001). A significant association was observed between EEG variability and neuropsychiatric status; thus, variability was increased in the patients with minimal HE compared with their neuropsychiatrically unimpaired counterparts (sample entropy: 0.98 [0.87-1.14] vs. 0.83 [0.75-0.95]; p=0.02), and compared with the patients with overt HE (sample entropy: 0.98 [0.87-1.14] vs. 0.82 [0.71-1.01]; p=0.01).
  
  
  
  Variability of the EEG is associated with both the presence and severity of HE. This novel finding may provide new insights into the pathophysiology of HE and provide a means for monitoring patients over time.
  
  
  
  Decreased variability or increased regularity of physiological systems is documented in several disease states. Variability of the electroencephalogram was found to be associated with both the presence and severity of brain dysfunction in patients with chronic liver disease.
authors.affiliation: Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Denmark. Electronic address: sso@mech-sense.com.
authors.forename: Søren Schou
authors.initials: SS
authors.lastname: Olesen
authors.affiliation: Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Gram
authors.affiliation: Department of Neurophysiology, Royal Free Hospital, Royal Free London NHS Foundation Trust, Hampstead, London, UK.
authors.forename: Clive Douglas
authors.initials: CD
authors.lastname: Jackson
authors.affiliation: UCL Institute for Liver and Digestive Health, Division of Medicine, Royal Free Campus, University College London, Hampstead, London, UK.
authors.forename: Edwin
authors.initials: E
authors.lastname: Halliday
authors.affiliation: Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Denmark.
authors.forename: Thomas Holm
authors.initials: TH
authors.lastname: Sandberg
authors.affiliation: Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Asbjørn Mohr
authors.initials: AM
authors.lastname: Drewes
authors.affiliation: UCL Institute for Liver and Digestive Health, Division of Medicine, Royal Free Campus, University College London, Hampstead, London, UK.
authors.forename: Marsha Yvonne
authors.initials: MY
authors.lastname: Morgan
mesh_terms: D004569:Electroencephalography; D006501:Hepatic Encephalopathy; D006801:Humans; D008103:Liver Cirrhosis; D011594:Psychometrics
keywords: Biological variability; Cirrhosis; Continuous wavelet transform; Electroencephalogram; Hepatic encephalopathy; Sample entropy; Spectral analysis