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- W4297990738 abstract "Abstract Hepatic encephalopathy (HE) is a common neurological manifestation of liver cirrhosis. Clinical symptoms range from subtle attention deficits and motor disturbance to stupor and hepatic coma in the most severe cases. HE pathophysiology is characterized by an increase of ammonia in the brain due to impaired clearance in the cirrhotic liver. This results in disturbed glutamate-glutamine homeostasis as ammonia is increasingly metabolized by glutamine synthetase. Ammonia accumulation furthermore causes increased oxidative stress and disrupts neurotransmitter balance, including the GABAergic and glutamatergic systems. Clinical symptoms in the motor domain suggest that the cerebello-thalamo-cortical system plays a key role in HE. The aim of this study is to investigate metabolic abnormalities in the cerebello-thalamo-cortical system of HE patients using GABA-edited MRS. The study also investigates links between metabolite levels, disease severity, critical flicker frequency (CFF), motor performance scores, and blood ammonia levels. GABA-edited MRS was performed in 35 participants (16 controls, 19 patients (3 minimal HE, 16 HE)) on a clinical 3T MRI system. MRS voxels were placed in the right cerebellum, left thalamus, and left motor cortex. GABA+ levels were estimated from the GABA-edited difference spectra using Gaussian fitting with the Gannet software. Levels of other metabolites of interest (glutamine, glutamate, myo-inositol, glutathione, total choline, total NAA, and total creatine) were assessed using linear-combination modeling in LCModel. Creatine- and water-referenced levels were reported to minimize biases of both reference standards. Group differences in metabolite levels and associations with clinical metrics were tested. Modeling uncertainty estimates of metabolite levels (Cramer-Rao Lower Bounds) were included as statistical weighting factors. GABA+ levels were significantly increased in the cerebellum of patients with HE. GABA+ levels in the motor cortex were significantly decreased in HE patients, and correlated with the CFF (r = 0.73; p < .05) and motor performance scores (r = −0.65; p < .05). Well-established HE-typical metabolite patterns (increased glutamine, decreased myo-inositol and total choline) were confirmed in all three regions. These alterations were closely linked to clinical metrics. Increased glutathione levels were found in the thalamus and motor cortex. Explorative analysis indicated increased aspartate levels in all three regions and decreased scyllo-inositol levels in the motor cortex. In summary, our findings provide further evidence for alterations in the GABAergic system in the cerebellum and motor cortex in HE. These changes were accompanied by characteristic patterns of osmolytes and oxidative stress markers in the cerebello-thalamo-cortical system. These metabolic disturbances are a likely contributor to HE motor symptoms in HE. Graphical Abstract In patients with hepatic encephalopathy, GABA+ levels in the cerebello-thalamo-cortical loop are significantly increased in the cerebellum and significantly decreased in the motor cortex. GABA+ levels in the motor cortex strongly correlate with critical flicker frequency (CFF) and motor performance score (pegboard test tPEG), but not blood ammonia levels (NH 3 ). Highlights Motor deficits in HE may originate from the cerebello-thalamo-cortical system Altered GABAergic neurotransmission plays a critical role in the pathophysiology of HE J-difference GABA-edited MRS can be used to study in vivo GABA+ levels Cerebellar and motor cortical GABA+ levels were significantly altered in HE GABA+ levels in the motor cortex strongly correlated with clinical metrics" @default.
- W4297990738 created "2022-10-01" @default.
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- W4297990738 date "2022-09-29" @default.
- W4297990738 modified "2023-09-29" @default.
- W4297990738 title "J-difference GABA-edited MRS reveals altered cerebello-thalamo-cortical metabolism in patients with hepatic encephalopathy" @default.
- W4297990738 cites W108170107 @default.
- W4297990738 cites W1523695827 @default.
- W4297990738 cites W1639707408 @default.
- W4297990738 cites W1730237872 @default.
- W4297990738 cites W1901260206 @default.
- W4297990738 cites W1931807871 @default.
- W4297990738 cites W1957708244 @default.
- W4297990738 cites W1964200150 @default.
- W4297990738 cites W1967018010 @default.
- W4297990738 cites W1970718497 @default.
- W4297990738 cites W1975340444 @default.
- W4297990738 cites W1978592341 @default.
- W4297990738 cites W1981729261 @default.
- W4297990738 cites W1982049192 @default.
- W4297990738 cites W1982524572 @default.
- W4297990738 cites W1989947032 @default.
- W4297990738 cites W1991817028 @default.
- W4297990738 cites W1994958750 @default.
- W4297990738 cites W1995653322 @default.
- W4297990738 cites W1998615413 @default.
- W4297990738 cites W2000055901 @default.
- W4297990738 cites W2003822852 @default.
- W4297990738 cites W2006710432 @default.
- W4297990738 cites W2015777146 @default.
- W4297990738 cites W2018406010 @default.
- W4297990738 cites W2022850604 @default.
- W4297990738 cites W2029648184 @default.
- W4297990738 cites W2030219424 @default.
- W4297990738 cites W2030825382 @default.
- W4297990738 cites W2030833898 @default.
- W4297990738 cites W2032116345 @default.
- W4297990738 cites W2034359651 @default.
- W4297990738 cites W2035173503 @default.
- W4297990738 cites W2039560063 @default.
- W4297990738 cites W2039816076 @default.
- W4297990738 cites W2046010008 @default.
- W4297990738 cites W2061405560 @default.
- W4297990738 cites W2071640821 @default.
- W4297990738 cites W2083651237 @default.
- W4297990738 cites W2083754290 @default.
- W4297990738 cites W2084314432 @default.
- W4297990738 cites W2084678830 @default.
- W4297990738 cites W2086172331 @default.
- W4297990738 cites W2086172755 @default.
- W4297990738 cites W2092488871 @default.
- W4297990738 cites W2093037844 @default.
- W4297990738 cites W2093298383 @default.
- W4297990738 cites W2096665338 @default.
- W4297990738 cites W2096756730 @default.
- W4297990738 cites W2102407355 @default.
- W4297990738 cites W2104408320 @default.
- W4297990738 cites W2109582716 @default.
- W4297990738 cites W2117377303 @default.
- W4297990738 cites W2118395640 @default.
- W4297990738 cites W2130933952 @default.
- W4297990738 cites W2133002620 @default.
- W4297990738 cites W2138478614 @default.
- W4297990738 cites W2149909643 @default.
- W4297990738 cites W2158142306 @default.
- W4297990738 cites W2160453061 @default.
- W4297990738 cites W2167639183 @default.
- W4297990738 cites W2168529864 @default.
- W4297990738 cites W2169232412 @default.
- W4297990738 cites W2172524037 @default.
- W4297990738 cites W2178688050 @default.
- W4297990738 cites W2274382726 @default.
- W4297990738 cites W2279193171 @default.
- W4297990738 cites W2398736642 @default.
- W4297990738 cites W2418711796 @default.
- W4297990738 cites W2513117972 @default.
- W4297990738 cites W2582523445 @default.
- W4297990738 cites W2607428310 @default.
- W4297990738 cites W2859737781 @default.
- W4297990738 cites W2888688605 @default.
- W4297990738 cites W2895280550 @default.
- W4297990738 cites W2916317438 @default.
- W4297990738 cites W2918790514 @default.
- W4297990738 cites W2922109364 @default.
- W4297990738 cites W2932841619 @default.
- W4297990738 cites W2934888266 @default.
- W4297990738 cites W2977209294 @default.
- W4297990738 cites W2979308267 @default.
- W4297990738 cites W2999274113 @default.
- W4297990738 cites W3034834420 @default.
- W4297990738 cites W3037198595 @default.