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Hepatic Encephalopathy: A neurochemical, anatomical and psychological study
Abstract
Hepatic encephalopathy (HE) is normally diagnosed by neuropsychological tests, which are not very specific and do not reveal the underlying pathology. Magnetic resonance imaging (MRI) and spectroscopy (MRS) of the brain offer alternate and possibly more specific markers for HE. These methods were applied in conjunction with neuropsychological (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 neuropsychological 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 neuropsychological tests.
The patients showed impairment in neuropsychological tests of attention, visuospatial and verbal fluency. In T1-weighted MRI, the relative intensity of the globus pallidus with respect to that of thalamus region was significantly elevated in patients and correlated (negatively) with three of 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 the three locations, with Gln increase being significant in all the 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 hepatic encephalopathy patients.
MR imaging and spectroscopy examinations, in addition to a battery of 15 neuropsychological 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 neuropsychological tests.
The patients showed impairment in neuropsychological tests of attention, visuospatial and verbal fluency. In T1-weighted MRI, the relative intensity of the globus pallidus with respect to that of thalamus region was significantly elevated in patients and correlated (negatively) with three of 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 the three locations, with Gln increase being significant in all the 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 hepatic encephalopathy patients.
Keywords
Cerebral metabolites, PRESS, glutamine/glutamate, myo-inositol, choline, hyperintensity and neuropsychology