Hepatic encephalopathy: A neurochemical, neuroanatomical, and neuropsychological study

Abstract

Hepatic encephalopathy (HE) is normally diagnosed by neuropsychological (NP) tests, which are not very specific and do not reveal the underlying pathology. Magnetic resonance imaging (MRI) and spectroscopy (MRS) of the brain offer alternative and possibly more specific markers for HE. These methods were applied in conjunction with NP testing in order to determine their usefulness in the identification of HE and to understand the pathogenesis of HE more clearly. MR imaging and spectroscopy examinations, in addition to a battery of 15 NP tests, were administered to investigate 31 patients awaiting liver transplantation and 23 healthy controls. MR image intensities from the globus pallidus region were calculated and normalized to those of the thalamus. Absolute concentrations and ratios with respect to creatine (Cr) of several metabolites were computed from MR spectra. The MR data were correlated with the results of NP tests. The patients showed impairment in NP tests of attention and visuospatial and verbal fluency. In T 1 -weighted MRI, the relative intensity of the globus pallidus with respect to that of the thalamus region was significantly elevated in patients and correlated (negatively) with three NP tests (Hooper, FAS, and Trails B). The absolute concentrations of myo-inositol (mI) and choline (Ch) were significantly reduced in three brain regions. In addition, the absolute concentrations of glutamine (Gln) and combined glutamate and glutamine (Glx) were increased in all three locations, with Gln increase being significant in all areas while that of Glx only in the occipital white matter. In summary, this study partially confirms a hypothesized mechanism of HE pathogenesis, an increased synthesis of glutamine by brain glutamate in astrocytes due to excessive blood ammonia, followed by a compensatory loss of myo-inositol to maintain astrocyte volume homeostasis. It also indicates that the hyperintensity observed in globus pallidus could be used as complementary to the NP test scores in evaluating the mental health of HE patients.PACS number: 87.61.Pk

Continuous veno-venous single-pass albumin hemodiafiltration in children with acute liver failure*

“…However, a reduction of HE score by 1 or 2 degrees before LTX in five out of our eight children due to SPAD is very similar to the results reported in patients with MARS treatment (8,23).Therefore, SPAD as well as MARS seem to be able to reduce substances associated with HE such as ammonium and glutamate as shown by our own data and by others (8,21,24,25). In adults suffering from ALF, a significant (p Ͻ .001) decrease in HE closely related to a decreased cerebral blood flow and falling serum ammonium levels during MARS has been reported (26,27).…”

“…The risk of edema increases to 25%-35% with progression to grade 3 and to 65%-75% (or more) in patients reaching grade 4 encephalopathy. A randomized trial in pigs with experimentally induced ALF reported an attenuated increase of intracerebral blood flow in the MARS treatment compared to the control group (p ϭ .005) (21). In two small uncontrolled series, a decrease in intracerebral blood flow in patients with ALF and chronic liver disease following treatment with MARS or SPAD in adults has been described (4,22).…”

Pathogenetic mechanisms of hepatic encephalopathy

“…In vivo 1H-MRS studies on the brain of patients with cirrhosis consistently show an increase of the glutamine/glutamate signal accompanied by a depletion of myo-inositol, which is indicative of a partially compensated glial oedema 13 15 22 – 25. The presence of a low-grade cerebral oedema in patients with cirrhosis and HE was confirmed by other magnetic resonance techniques, such as magnetisation transfer ratio measurements26 27 and the recently introduced T1 mapping with partial inversion recovery (TAPIR ), which allows quantitative water mapping in the human brain in vivo 28.…”

Threshold for toxicity from hyperammonemia in critically ill children

“…Ammonia has been shown to affect brain function, to modulate both excitatory and inhibitory neurotransmission, and to contribute to cerebral edema. The pathophysiology of disabling symptoms associated with hyperammonemia is not fully understood, but various mechanisms have been observed in patients and experimental models: higher ammonia permeability of the blood brain barrier leading to changes in cellular pH, alteration of response to neurotransmitters, astrocyte swelling through glutamine accumulation, mitochondrial dysfunction with changes in cerebral energy metabolism, and reduced ATP concentration [3,4]. Ammonia induces oxidative and nitrosative stress that lead to apoptosis.…”