Clinical and histopathological findings hint at regional differences in the brain's sensitivity to metabolic changes in cirrhosis. The aim of the present study was to examine regional differences in cerebral ammonia metabolism in patients with cirrhosis and grade 0-to-I hepatic encephalopathy (HE). 13 N-ammonia, 15 O-water positron emission tomography (PET) and magnetic resonance imaging (MRI) were performed. Quantitative values of cerebral blood flow (CBF) and the initial cerebral ammonia uptake rate (K1) were derived for several regions of interest from images of the desired parameters after interactive coregistration with the patients' MRI-studies. CBF (mL/mL/min), K1 (mL/mL/min), and the ammonia extraction fraction (K1/CBF) showed marked regional variance with the highest levels in the thalamus, the lenticular nucleus, and the cerebellum. In conclusion, the regional differences in cerebral ammonia uptake correspond to the distribution of histopathological changes in the brain of patients with cirrhosis as well as clinical features of HE, characterized by signs of basal ganglia and cerebellar dysfunction with corresponding signs of functional impairment, especially of the frontal cortex and cingulate gyrus. (HEPATOLOGY 2004;40: 73-79.) H epatic encephalopathy (HE) is characterized by distinct clinical findings: patients display motor disturbances even at the lower grades of HE. Patients' faces are without expression, their movements are very slow, and muscle tone may be rigid. In some patients, body position is similar to Parkinson's disease, and posture reflexes are abnormal. Several patients present with tremor or asterixis. 1 With regard to cognition, deficits in attention, visual perception, visuospatial orientation, and visual construction predominate. 2,3 Thus, clinical and neuropsychological findings hint at a special sensitivity of distinct cerebral regions for toxic substances active in HE. Recent 18 F-fluorodeoxyglucose PET studies of cerebral glu-cose metabolism in patients with cirrhosis and minimal encephalopathy support this assumption. It has been shown that in such patients with HE, glucose utilization is decreased in the cingulum and frontal and parieto-occipital cortex and increased in the basal ganglia, cerebellum, and temporomesial structures, compared to healthy controls and patients with cirrhosis and no HE. [4][5][6] The mechanisms responsible for these differences are unknown. Regional differences in ammonia metabolism could be one possible cause.
Ammonia is regarded as playing a major role in the pathophysiology of HE. Recent studies have shown that hyperammonemia affects GABAergic and glutamatergic neurotransmission and induces astrocytic swelling, considered to be major pathophysiological mechanisms in the development of HE. [7][8][9] The aim of the present study was to analyze cerebral ammonia metabolism in patients with cirrhosis, examining regional differences and their relationship to the grade of encephalopathy and the grade of liver dysfunction.
The results of this study have been presented, in part, in abstract form. 10
Patients and Methods
Twenty patients (5 female), ages 32 to 74 (mean age, 50 Ϯ 12 [SD]) with biopsy-proven liver cirrhosis under-