Elsevier

Journal of Hepatology

Volume 35, Issue 5, November 2001, Pages 598-604
Journal of Hepatology

The development of low-grade cerebral edema in cirrhosis is supported by the evolution of 1H-magnetic resonance abnormalities after liver transplantation

https://doi.org/10.1016/S0168-8278(01)00181-7Get rights and content

Abstract

Background/Aims: Liver failure may cause brain edema through an increase in brain glutamine. However, usually standard neuroimaging techniques do not detect brain edema in cirrhosis. We assessed magnetization transfer ratio and 1H-magnetic resonance (MR) spectroscopy before and after liver transplantation to investigate changes in brain water content in cirrhosis.

Methods: Non-alcoholic cirrhotics without overt hepatic encephalopathy (n=24) underwent 1H-MR of the brain and neuropsychological tests. 1H-MR results were compared with those of healthy controls (n=10). In a subgroup of patients (n=11), the study was repeated after liver transplantation.

Results: Cirrhotic patients showed a decrease in magnetization transfer ratio (31.5±3.1 vs. 37.1±1.1, P<0.01) and an increase in glutamine/glutamate signal (2.22±0.47 vs. 1.46±0.26, P<0.01). The increase in glutamine/glutamate signal was correlated to the decrease in magnetization transfer ratio and to neuropsychological function. Following liver transplantation, there was a progressive normalization of magnetization transfer ratio, glutamine/glutamate signal and neuropsychological function. Accordingly, correlations between these variables were lost after liver transplantation.

Conclusions: Cirrhotic patients show reversible changes in magnetization transfer ratio that are compatible with the development of low-grade cerebral edema. Minimal hepatic encephalopathy and low-grade cerebral edema appear to be the consequences of the metabolism of ammonia in the brain.

Introduction

Brain edema is a well-documented complication of fulminant hepatic failure, that leads to intracranial hypertension in an important number of patients [1], and that may be secondary to an increase in brain glutamine [2]. While cirrhotic patients show high levels of brain glutamine, in this circumstance intracranial hypertension is seldom seen [3]. The observation of changes in brain organic osmolytes in chronic liver failure raises the possibility that cirrhotic patients develop cerebral edema that is of low-grade because of the activation of compensatory mechanisms [4]. Low-grade cerebral edema may not be detected by standard neuroimaging techniques. Magnetization transfer imaging provides a new type of tissue contrast – based on the transfer of magnetization between free protons in water and bound protons associated with macromolecules – that can be quantified through the calculation of the magnetization transfer ratio (MTR) [5]. The increase in the amount of free water that takes place in brain edema will cause a decrease in MTR, as has been shown in clinical and experimental studies [5], [6], [7].

We undertook a prospective study to investigate the relationship between brain water content assessed by MTR, brain organic osmolytes assessed by 1H-magnetic resonance (MR) spectroscopy and minimal hepatic encephalopathy (MHE) assessed by neuropsychological tests. We investigated the same patients after liver transplantation, because this procedure offers a good paradigm to understand the relationship between MHE and the abnormalities found by 1H-MR. The study was designed to exclude the confounding effects of alcohol on brain function [8].

Section snippets

Characteristics of subjects

We studied a consecutive series of 24 non-alcoholic cirrhotic patients that were clinically stable, while they were being evaluated for liver transplantation (Table 1). Subjects with a history of drug abuse, those affected by neurological or psychiatric diseases and individuals receiving medications known to have significant effects on the central nervous system were excluded. All patients underwent laboratory analysis (fasting state, 08:00 h), neuropsychological tests (after breakfast, 10:00

Baseline study

The magnetization transfer study of parietal white matter showed a decrease of MTR in cirrhosis (Fig. 1). The results of MTR in frontal white matter were similar and closely correlated to those found in parietal white matter (32.1±3.3 vs. 31.5±3.1, r=0.88). 1H-MR spectroscopy in parietal white matter of cirrhotic patients showed an increase in Glx/Cr (2.22±0.47 vs. 1.46±0.26, P<0.01), a decrease in mIns/Cr (0.27±0.16 vs. 0.64±0.10, P<0.01) and a decrease in Cho/Cr (0.68±0.11 vs. 0.81±0.11; P

Discussion

The present study shows a decrease in magnetization transfer ratio in the brain of cirrhotic patients that is reversible after liver transplantation. In addition, cirrhotic patients show a reversible increase in Glx/Cr that correlates with the decrease in magnetization transfer ratio and with neuropsychological function.

The results of this study support the interpretation of the development of low-grade cerebral edema in cirrhosis [21]. We observed a decrease in MTR without signs of brain edema

Acknowledgements

The study was supported by Fondo de Investigaciones Sanitarias (FIS 98/231).

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