Correlations between magnetic resonance spectroscopy alterations and cerebral ammonia and glucose metabolism in cirrhotic patients with and without hepatic encephalopathy

Abstract

Background: Hepatic encephalopathy is considered to be mainly caused by increased ammonia metabolism of the brain. If this hypothesis is true, cerebral glucose utilisation, which is considered to represent brain function, should be closely related to cerebral ammonia metabolism. The aim of the present study was to analyse whether cerebral ammonia and glucose metabolism in cirrhotic patients with early grades of hepatic encephalopathy are as closely related as could be expected from current hypotheses on hepatic encephalopathy. Methods:13 N-ammonia and 18 F-fluorodesoxyglucose positron emission tomography, magnetic resonance imaging and magnetic resonance spectroscopy (MRS) were performed in 21 cirrhotic patients with grade 0-1 hepatic encephalopathy. Quantitative values of cerebral ammonia uptake and retention rate and glucose utilisation were derived for several regions of interest and were correlated with the MRS data of the basal ganglia, white matter and frontal cortex. Results: A significant correlation between plasma ammonia levels and cerebral ammonia metabolism, respectively, and MRS alterations could be shown only for white matter. In contrast, MRS alterations in all three regions studied were significantly correlated with the glucose utilisation of several brain regions. Cerebral ammonia and glucose metabolism were not correlated. Conclusion: Increase of cerebral ammonia metabolism is an important but not exclusive causal factor for the development of hepatic encephalopathy.

Quantitative multivoxel 1H MR spectroscopy of the brain in children with acute liver failure

“…Our study contrasts with a previous study of cirrhotic patients reporting hepatic encephalopathy changes in MR spectra in white matter only [8]. In the latter study the spectra in grey matter regions such as basal ganglia and frontal cortex were prone to artifacts; however, this was not the case in the present study.…”

“…All MRI/MRS examinations were performed with informed consent, and blood samples were collected on the same day. The missing values for blood lactate (patients 2, 3,6,7,8) and ammonia (patients 6,7,8) in Table 2 reflect lack of clinically indication for having these determined on the day of MRS. Patients 1-3 did not survive ALF or liver transplantation, due to failing liver grafts and abstinence from retransplantation because of progressive circulatory insufficiency with multi-organ failure, ongoing adenovirus infection with circulatory insufficiency and/or ongoing systemic yeast infection.…”

“…Moreover, the interpretations were based on the assumption that results obtained in one small volume were representative of the brain as a whole. In a recent MRS study of cirrhotic patients with hepatic encephalopathy, changes in MR spectra could be shown only for white matter [8]. Much earlier, regional variations in the obtained MRS metabolite ratios had already been pointed out, suggesting that spectral information from more than one voxel would be useful in the evaluation of patients with hepatic encephalopathy [9].…”

“…MRI of the latter patients was indicated to investigate the presence of intracranial hypertension (patient 4 second time), intracranial lesions in syndrome of Alagille (patients 6,8), structural defects as the cause of headaches (patient 7) or ischemic lesions after an epileptic episode (patient 9). Patients 2-5 were diagnosed with ALF, illustrated by a vitamin K-resistant coagulation abnormality (an international normalized ratio INR ≥1.5) [10] and any degree of mental alteration (encephalopathy) at the time of MRS.…”

Brain edema in acute liver failure and chronic liver disease: Similarities and differences

“…This suggests a direct link between hyperammonemia, brain ammonia and ICP (possibly brain edema). In CLD, HE patients often present elevated arterial ammonia concentrations; however, in contrast with ALF, the correlation between ammonia and severity of HE remains controversial , Kundra et al, 2005, Nicolao et al, 2003, Ong et al, 2003and Weissenborn et al, 2007. This infers other factors may be implicated in the pathogenesis of HE.…”