Abstract
Cerebral edema is the common pathogenic mechanism for cognitive impairment in minimal hepatic encephalopathy. Whether complete reversibility of brain edema, cognitive deficits, and their associated imaging can be achieved after liver transplantation remains an open question. To characterize white matter integrity before and after liver transplantation in patients with minimal hepatic encephalopathy, multiple diffusivity indices acquired via diffusion tensor imaging was applied. Twenty-eight patients and thirty age- and sex-matched healthy volunteers were included. Multiple diffusivity indices were obtained from diffusion tensor images, including mean diffusivity, fractional anisotropy, axial diffusivity and radial diffusivity. The assessment was repeated 6–12 month after transplantation. Differences in white matter integrity between groups, as well as longitudinal changes, were evaluated using tract-based spatial statistical analysis. Correlation analyses were performed to identify first scan before transplantation and interval changes among the neuropsychiatric tests, clinical laboratory tests, and diffusion tensor imaging indices. After transplantation, decreased water diffusivity without fractional anisotropy change indicating reversible cerebral edema was found in the left anterior cingulate, claustrum, postcentral gyrus, and right corpus callosum. However, a progressive decrease in fractional anisotropy and an increase in radial diffusivity suggesting demyelination were noted in temporal lobe. Improved pre-transplantation albumin levels and interval changes were associated with better recoveries of diffusion tensor imaging indices. Improvements in interval diffusion tensor imaging indices in the right postcentral gyrus were correlated with visuospatial function score correction. In conclusion, longitudinal voxel-wise analysis of multiple diffusion tensor imaging indices demonstrated different white matter changes in minimal hepatic encephalopathy patients. Transplantation improved extracellular cerebral edema and the results of associated cognition tests. However, white matter demyelination may advance in temporal lobe.
Highlights
Hepatic encephalopathy (HE) is frequently associated with a wide range of neuropsychiatric abnormalities in liver cirrhosis, and has been classified as a continuum from minimal HE (MHE) to different grades of overt HE. [1] It is believed that cerebral edema is the common pathogenic mechanism for cognitive impairment in MHE and overt HE. [2,3] patients with MHE present as essentially normal, such patients perform abnormally on psychometric tests and have an increased risk of motor vehicle accidents
We found a worse performance of visuospatial function (Letter-number search, p = 0.01; Block design, p = 0.04) and the Cognitive Ability Screening Instrument (CASI) global performance score (p = 0.02) but was not survived with correcting for multiple comparisons (FDR,0.05)
After Liver transplantation (LT), we found that improvement of albumin(baseline-followup) levels were significantly positively associated with recovery of Drad (r = 0.76, p,0.001) and mean diffusivity (MD)(baseline-followup) (r = 0.63, p = 0.001) values in right anterior cingulate (Figure 3)
Summary
Hepatic encephalopathy (HE) is frequently associated with a wide range of neuropsychiatric abnormalities in liver cirrhosis, and has been classified as a continuum from minimal HE (MHE) to different grades of overt HE. [1] It is believed that cerebral edema is the common pathogenic mechanism for cognitive impairment in MHE and overt HE. [2,3] patients with MHE present as essentially normal, such patients perform abnormally on psychometric tests and have an increased risk of motor vehicle accidents. [1] It is believed that cerebral edema is the common pathogenic mechanism for cognitive impairment in MHE and overt HE. [5] whether complete reversibility of brain edema, cognitive deficits, and their associated imaging can be achieved remains an open question. The MHE patients can experience persistent cognitive deficits after LT. [8] it is common for cirrhotic patients to experience acute liver failure or overt HE accompanied by irreversible cytotoxic cerebral edema. [12] The widely used DTI indices, FA and MD, are associated with cognitive impairment in MHE patients before LT. [8,13] there are no reports of longitudinal neuro-imaging studies investigating changes in WM in MHE patients before and after LT through the use of multiple diffusion indices.
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