[1-C-13] glucose MRS in chronic hepatic encephalopathy in man

[1-C-13]-labeled glucose was infused intravenously in a single dose of 0.2 g/kg body weight over 15 min in six patients with chronic hepatic encephalo pathy, and three controls. Serial C-13 MR spectra of the brain were acquire d. Patients exhibited the following characteristics relative to normal cont rols: 1) Cerebral glutamine concentration was increased (12.6 +/- 3.8 vs. 6 .5 +/- 1.9 mmol/kg, P < 0.006) and glutamate was reduced (8.2 +/- 1.0 vs. 9 .9 +/- 0.6 mmol/kg, P < 0.02). 2) C-13 incorporation into glutamate C, and C, positions was reduced in patients (80 min after start of infusion C,: 0. 43 +/- 0.09 vs. 0.84 +/- 0.15 mmol/kg, P < 0.001; C-2: 0.20 +/- 0.03 vs. 0. 45 +/- 0.07 mmol/kg, P < 0.0001). 3) C-13 incorporation into bicarbonate wa s delayed (90 +/- 21 vs. 40 +/- 10 min, P < 0.003), and the time interval b etween detection of glutamate C, and C, labeling was longer in patients (22 +/- 8 vs. 12 +/- 3 min, P < 0.03). 4) Glutamate C, turnover time was reduc ed in chronic hepatic encephalopathy (17.1 +/- 6.8 vs. 49.6 +/- 8.7 min, P < 0.0002). 5) C-13 accumulation into glutamine C, relative to its substrate glutamate C, increased progressively with the severity of clinical symptom s (r = 0.96, P < 0.01). These data indicate disturbed neurotransmitter glut amate/glutamine cycling and reduced glucose oxidation in chronic hepatic en cephalopathy. [1-C-13] glucose MRS provides novel insights into disease pro gression and the pathophysiology of chronic hepatic encephalopathy. (C) 200 1 Wiley-Liss, Inc.