Increased availability of central benzodiazepine receptors in patients with chronic hepatic encephalopathy and alcohol related cirrhosis

被引:40
作者
Jalan, R
Turjanski, N
Taylor-Robinson, SD
Koepp, MJ
Richardson, MP
Wilson, JA
Bell, JD
Brooks, DJ
机构
[1] Hammersmith Hosp, Robert Steiner MR Unit, Imperial Coll, Sch Med,MRC,Clin Sci Ctr, London W12 0NN, England
[2] Hammersmith Hosp, MRC, Cyclotron Unit, London W12 0NN, England
基金
英国医学研究理事会;
关键词
benzodiazepine receptors; chronic hepatic encephalopathy; C-11-flumazenil; in vivo proton magnetic resonance spectroscopy; positron emission tomography;
D O I
10.1136/gut.46.4.546
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/aims-To measure cerebral benzodiazepine receptor binding using C-11-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 C-11-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-acetyl-aspartate, and creatine resonances. Results-The mean volume of distribution of C-11-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.
引用
收藏
页码:546 / 552
页数:7
相关论文
共 43 条
[1]   MECHANISM OF THE EXCESSIVE SEDATIVE RESPONSE OF CIRRHOTICS TO BENZODIAZEPINES - MODEL EXPERIMENTS WITH TRIAZOLAM [J].
BAKTI, G ;
FISCH, HU ;
KARLAGANIS, G ;
MINDER, C ;
BIRCHER, J .
HEPATOLOGY, 1987, 7 (04) :629-638
[2]   ELEVATED BRAIN CONCENTRATIONS OF 1,4-BENZODIAZEPINES IN FULMINANT HEPATIC-FAILURE [J].
BASILE, AS ;
HUGHES, RD ;
HARRISON, PM ;
MURATA, Y ;
PANNELL, L ;
JONES, EA ;
WILLIAMS, R ;
SKOLNICK, P .
NEW ENGLAND JOURNAL OF MEDICINE, 1991, 325 (07) :473-478
[3]   BRAIN CONCENTRATIONS OF BENZODIAZEPINES ARE ELEVATED IN AN ANIMAL-MODEL OF HEPATIC-ENCEPHALOPATHY [J].
BASILE, AS ;
PANNELL, L ;
JAOUNI, T ;
GAMMAL, SH ;
FALES, HM ;
JONES, EA ;
SKOLNICK, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (14) :5263-5267
[4]  
BASILE AS, 1991, PHARMACOL REV, V43, P27
[5]   AMMONIA - KEY FACTOR IN THE PATHOGENESIS OF HEPATIC-ENCEPHALOPATHY [J].
BUTTERWORTH, RF ;
GIGUERE, JF ;
MICHAUD, J ;
LAVOIE, J ;
LAYRARGUES, GP .
NEUROCHEMICAL PATHOLOGY, 1987, 6 (1-2) :1-12
[6]  
BUTTERWORTH RF, 1997, ADV HEPATIC ENCEPHAL, P167
[7]   WHAT THE CLINICIAN CAN LEARN FROM MR GLUTAMINE GLUTAMATE ASSAYS [J].
CHAMULEAU, RAFM ;
BOSMAN, DK ;
BOVEE, WMMJ ;
LUYTEN, PR ;
DENHOLLANDER, JA .
NMR IN BIOMEDICINE, 1991, 4 (02) :103-108
[8]  
CONN HO, 1977, GASTROENTEROLOGY, V72, P573
[9]  
CONN HO, 1992, THERAPY IN LIVER DISEASES, P277
[10]   SPECTRAL-ANALYSIS OF DYNAMIC PET STUDIES [J].
CUNNINGHAM, VJ ;
JONES, T .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1993, 13 (01) :15-23