Normal cortical regional cerebral blood flow justifies the normal neuropsychological performance in patients with cholestatic liver disease
Article first published online: 14 MAR 2007
Psychiatry and Clinical Neurosciences
Volume 61, Issue 2, pages 209–210, April 2007
How to Cite
SENZOLO, M., PIZZOLATO, G., DAM, M., STURNIOLO, G. C. and BURRA, P. (2007), Normal cortical regional cerebral blood flow justifies the normal neuropsychological performance in patients with cholestatic liver disease. Psychiatry and Clinical Neurosciences, 61: 209–210. doi: 10.1111/j.1440-1819.2007.01645.x
- Issue published online: 14 MAR 2007
- Article first published online: 14 MAR 2007
- Received 4 October 2006; accepted 15 October 2006.
Sorell et al. have recently reported their results on neuropsychological deficits in patients with different etiologies of liver disease evaluated for liver transplantation.1 Not surprisingly, they found that patients with alcoholic liver disease perform worse when compared to other etiologies, moreover, they found that patients with cholestatic liver disease, irrespectively to the severity of liver disease assessed by Model for Endstage Liver Disease score, have less cerebral function impairment.
However, no hypothesis is formulated for the last finding and the authors feel that there are some comments and considerations to make about the Sorell et al. paper.
First, it would be important to know the period of abstinence from alcohol abuse in patients in the alcoholic group. Neuropsychological tests and cerebral blood flow and metabolism have been reported to be impaired in abstinent alcoholic patients up to 10 years after withdrawal of alcohol.2 The present authors have described residual frontal cerebral blood metabolism defects seen by positron emission tomography 1 year after successful liver transplantation in patients with pre-existing alcoholic liver disease.3 Cerebral atrophy should have been excluded by a cerebral computed tomography scan, because a direct correlation between cerebral atrophy and neuropsychological impairment have also been demonstrated.4
The newest finding of the Sorell et al. paper is the better performance of cholestatic group which needs some discussion. This result is in keeping with the article from Floreani et al., but in the latter, a correlation with hepatic fibrosis is given, suggesting that the severity of hepatic function impairment is essential in these groups of patients for developing subclinical hepatic encephalopathy.5
The present authors have recently described that patients with biopsy proven primary biliary cirrhosis or primary sclerosing cholangitis, irrespectively from the severity of liver disease, even when assessed by Child-Pugh score, did show a cerebral cortical regional blood flow not significantly different from controls and better than viral or alcoholic cirrhotic patients, however, there was a significant decrease in regional cortical blood flow in subcortical regions compared to quantified by single positron emission tomography with 99mTc-hexamethylpropylene-amine-oxime (Fig. 1).
The only pathophysiological mechanism the present authors could hypothesize was that cholestasis can reduce the permeability of the blood brain barrier, due to an alteration of the cholesterol content in the membrane, as shown by one paper on rats.6 Therefore, this could lead to a different transport and metabolism of ammonia with consequent less neuronal and astrocyte damage in those areas.
The demonstrated hypoperfusion of the caudatus, thalamus and cerebellum which was not different from the other etiologies, could be a consequence of a selective toxicity of bilirubin towards the subcortical regions, even though this should not happen in adults because of the complete blood brain barrier.
The pathogenetic role of cholestasis in the development of cognitive function alterations in patients with liver disease needs further studies. New imaging techniques, such as the new functional positron emission tomography, could be important tools to investigate and characterize this phenomenon.