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Increased availability of central benzodiazepine receptors in patients with chronic hepatic encephalopathy and alcohol related cirrhosis
  1. R Jalana,
  2. N Turjanskib,
  3. S D Taylor-Robinsona,
  4. M J Koeppb,
  5. M P Richardsonb,
  6. J A Wilsona,
  7. J D Bella,
  8. D J Brooksb
  1. aThe MR Unit, MRC Clinical Sciences Centre, Hammersmith Hospital, London, UK, bMRC Cyclotron Unit, Hammersmith Hospital
  1. Dr S D Taylor-Robinson, Robert Steiner MR Unit, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK

Abstract

BACKGROUND/AIMS To measure cerebral benzodiazepine receptor binding using 11C-flumazenil positron emission tomography in patients with stable chronic hepatic encephalopathy, who were also characterised by proton magnetic resonance spectroscopy.

METHODS Six abstinent patients of mean age 61 years with alcohol related cirrhosis and grade I–II hepatic encephalopathy and 11 matched healthy volunteers were studied. Each patient's encephalopathy was defined according to clinical, psychometric, electroencephalographic, and magnetic resonance spectroscopy criteria. Using positron emission tomography, the brain volume of distribution of 11C-flumazenil was obtained; this reflects benzodiazepine receptor availability. Proton magnetic resonance spectra were acquired at 1.5 T using a multivoxel technique; peak area ratios were calculated for choline, glutamine/glutamate, N-acetylaspartate, and creatine resonances.

RESULTS The mean volume of distribution of 11C-flumazenil was significantly higher in the cortex, cerebellum, and the basal ganglia in the patients compared with controls (p<0.001). In the patient group, the mean glutamine/glutamate to creatine ratio was significantly increased and the mean choline to creatine ratio was significantly decreased in all brain areas, compared with healthy volunteers. However, the N-acetylaspartate to creatine ratio was unchanged compared with controls.

CONCLUSIONS The spectroscopy results reflect the cerebral metabolic derangement associated with hepatic encephalopathy. Stable grade I–II chronic hepatic encephalopathy in alcohol related cirrhosis may be associated with increased cerebral benzodiazepine receptor availability. However, a direct effect of previous chronic exposure to alcohol cannot be excluded.

  • benzodiazepine receptors
  • chronic hepatic encephalopathy
  • 11C-flumazenil
  • in vivo proton magnetic resonance spectroscopy
  • positron emission tomography

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Footnotes

  • Abbreviations used in this paper:
    ARC
    alcohol related cirrhosis
    BGO
    bismuth germanate
    BzR
    benzodiazepine receptor
    Cho
    choline containing compounds
    cps
    cycles per second
    CNS
    central nervous system
    Cr
    creatine
    CSF
    cerebrospinal fluid
    CSI
    chemical shift imaging
    EEG
    electroencephalogram
    FMZ
    flumazenil
    GABA
    γ-aminobutyric acid
    Glx
    glutamine/glutamate
    HPLC
    high pressure liquid chromatography
    mcf
    mean cycle frequency
    MRS
    magnetic resonance spectroscopy
    NAA
    N-acetylaspartate
    NCT
    number connection test
    PET
    positron emission tomography
    ppm
    parts per million
    ROI
    region of interest
    TE
    echo time
    TR
    repetition time
    VD
    volume of distribution