Materials and methods

We studied 12 men with chronic alcoholism (mean age 56 (SD 7)) and 12 age matched healthy men who did not drink alcohol (mean age 57 (SD 6)). All subjects gave their informed consent. The patients fulfilled the DSM-IV criteria of alcohol dependence5 and did not have any other relevant diseases (head trauma, depression, seizures, neurological complications of chronic alcoholism) or any significant abnormality on head CT and blood tests (hepatic function and standard blood biochemistry and haematology tests). No patients had Wernicke-Korsakoff syndrome and their average score for the mini mental state examination6 was 25. Mean height was 165 cm, mean weight 62.3 kg, and mean blood pressure 138/88 mm Hg in the chronic alcoholic group and these variables were not significantly different from the healthy control group. Any medications which may have affected cerebral blood flow or cerebral metabolism (including benzodiazepines) were discontinued two weeks before the study of cerebral blood flow. All patients drank alcohol the night before the cerebral blood flow examination but on the day of examination they did not drink alcohol until after the examination, which was performed in the afternoon.

Cerebral blood flow was measured by the stable xenon CT method.7 8 The mathematical modelling of Meyer et al 9 and the procedure of Fatouros et al 10 were used to generate parametric maps. The basal ganglia section and the lateral ventricle section parallel to the orbitomeatal line were selected as the regions of interest. The subjects inhaled room air followed by a mixture of 30% xenon and 50% oxygen for three minutes. Serial scanning was performed, once before xenon inhalation, three times in the wash in process, and five times in the wash out process of five minutes. The serial scanning programme consisted of 18 scans with nine serial scans on each section. The xenon concentration in the end tidal expired gas was continuously recorded by the thermoconductivity method. We used the xenon delivery and analysis system AZ-7000 model, Anzai Sogyo, Tokyo, Japan and CT equipment from PreSage, Yokogawa Medical Systems, Tokyo, Japan. Values for regional cerebral blood flow were obtained with the procedure of Kawamuraet al.11 Xenon CT examinations were performed before and 20 minutes after intravenous injection of 17 mg/kg acetazolamide.

Statistical analysis of the cerebral blood flows was performed by Mann-Whitney U test.

Results

The figure shows xenon CT examination before and after intravenous injection of acetazolamide. The table shows the mean (SD) of the blood flows. Blood flows in the cerebral cortex, thalamus, and putamen were significantly lower in the chronic alcoholic group than in the healthy control group. The absolute changes and the increased rates of blood flows did not show any significant differences between the two groups.

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Xenon CT before and after intravenous injection of acetazolamide. (A) a patient with chronic alcoholism, (B) a healthy control. Before injection of acetazolamide, the blood flows in the cerebral cortex, thalamus, and putamen were lower in (A) than in (B). Cerebrovascular response to acetazolamide was high in both (A) and (B).

Discussion

Cerebral blood flow has been reported to be decreased in patients with chronic alcoholism1-4 but only one study used the xenon CT method.12 The main advantage of this method is that it provides relatively high resolution and quantitative information on regional cerebral blood flow coupled with anatomy by CT.8 Hata et al 12 reported that local cerebral blood flows were reduced throughout all grey matter in patients with chronic alcoholism without Wernicke-Korsakoff syndrome. However, the present study showed that the blood flow in the cerebral cortex, thalamus, and putamen were reduced but that in the caudate nucleus was normal. The normal blood flow in the caudate nucleus may be due to the few patients studied so far.

The mechanism of decreased cerebral blood flow in patients with chronic alcoholism has not yet been elucidated2 13-15 although it is thought to be due to decreased cerebral metabolism.2 15 Because the effects of chronic alcoholism on metabolism are not uniformly distributed in the present study, the result cannot be explained by the possibility that the patients with chronic alcoholism are more sensitive to the anaesthetic effects of xenon. The present study showed that the cerebrovascular response to acetazolamide was normal in such patients. Acetazolamide is considered to dilate the cerebral arterioles by inhibiting the carbonic anhydrase in the red blood cells and increasing carbon dioxide in the arterioles.16 Although the possible influence of early withdrawal effects on cerebral blood flow cannot be excluded, the result of the present study suggests that the reduced blood flow is not due to vascular problems such as arteriosclerosis in patients with chronic alcoholism.