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Anatomical and Neurochemical Changes in Minimal Hepatic Encephalopathy and their Neuropsychological Correlates

was significantly higher (p<0.0004), and its Ins/Cr lower (p<0.01), in patients than in healthy controls. The thalamus ratio correlated negatively with the basal ganglia’s Ins/Cr (r=-0.578, n=16, p=0.019). In the frontal gray matter, Ins/Cr was correlated negatively with the thalamus (r=-0.629, n=14, p=0.016) and corpus callosum ratios (r=-0.608, n=14, p=0.021), and NAA/Cr correlated negatively with the corpus callosum ratio (r=-0.497, n=19, p=0.031). The occipital white matter’s ratio of Cho/Cr correlated negatively with the corpus callosum ratio (r=-0.560, n=22, p=0.007). Ins/Cr in the occipital white matter correlated negatively with both the corpus callosum (r=-0.723, n=12, p=0.008) and thalamus (r=-0.770, n=12, p=0.003) ratios. In the frontal gray matter, the ratio of Ins/Cr correlated positively with the Speed of Processing score (r=0.540, n=14, p=0.046). Executive Function correlated positively with both Gln/Cr (r=0.599, n=14, p=0.024) and (Gln+Glu)/Cr (r=0.487, n=18, p=0.041). Motor Function correlated positively with Gln/Cr (r=0.667, n=14, p=0.009) and (Gln+Glu)/Cr (r=0.588, n=18, p=0.010). In the occipital white matter, Glu/Cr and [Gln+Glu]/Cr correlated positively with Motor Function (r=0.503, n=18, p=0.033 and r=0.678, n=20, p=0.001, respectively) and Executive Function (r=0.567, n=18, p=0.014 and r=0.585, n=20, p=0.007, respectively). Gln/Cr and [Gln+Glu]/Cr correlated negatively with the Speed of Processing score (r=-0.757, n=11, p=0.007 and r=-0.628, n=20, p=0.003, respectively) (Figure 2). Discussion Hyperintensity of the globus pallidus is found to be an indicator of HE. The observed reduction of Ins/Cr in the frontal gray matter and occipital white matter of patients with minimal HE is consistent with a proposed mechanism of HE pathogenesis: the heightened synthesis of glutamine by brain glutamate and excess blood ammonia in astrocytes followed by a compensatory loss of myo-inositol to maintain astrocyte volume homeostasis. 2 In all three brain regions examined, there were negative correlations between Ins/Cr and the MRI measurements of the globus pallidus signal intensity. These correlations suggest that the globus pallidus hyperintensity of minimal HE patients may serve as an indication of the severity of HE. Cho/Cr and NAA/Cr were correlated negatively with the globus pallidus signal intensity. The roles of these metabolites in HE are not yet known. Executive Function and Motor Function scores are high for poorly performing subjects, as these tests quantify the time required to perform various complex tasks. Impairments of HE patients’ motor functioning are linked to an excess of glutamine and total Gln+Glu in the frontal gray matter and an excess of glutamate and total Gln+Glu in the occipital white matter. Impairment of executive functioning corresponds to a surplus of glutamine and total Gln+Glu in the frontal gray matter, and an excess of glutamate and total Gln+Glu in the occipital white matter. Reduced speed of processing is associated with an excess of glutamine and total Gln+Glu in the occipital white matter.