title: Low visual cortex GABA levels in hepatic encephalopathy: links to blood ammonia, critical flicker frequency, and brain osmolytes.
abstract: The pathogenesis of hepatic encephalopathy (HE) is not fully understood yet. Hyperammonemia due to liver failure and subsequent disturbance of cerebral osmolytic balance is thought to play a pivotal role in the emergence of HE. The aim of this in-vivo MR spectroscopy study was to investigate the levels of γ-aminobutyric acid (GABA) and its correlations with clinical symptoms of HE, blood ammonia, critical flicker frequency, and osmolytic levels. Thirty patients with minimal HE or HE1 and 16 age-matched healthy controls underwent graduation of HE according to the West-Haven criteria and including the critical flicker frequency (CFF), neuropsychometric testing and blood testing. Edited proton magnetic resonance spectroscopy ((1)H MRS) was used to non-invasively measure the concentrations of GABA, glutamate (Glu), glutamine (Gln), and myo-inositol (mI) - all normalized to creatine (Cr) - in visual and sensorimotor cortex. GABA/Cr in the visual area was significantly decreased in mHE and HE1 patients and correlated both to the CFF (r = 0.401, P = 0.013) and blood ammonia levels (r = -0.434, P = 0.006). Visual GABA/Cr was also strongly linked to mI/Cr (r = 0.720, P < 0.001) and Gln/Cr (r = -0.699, P < 0.001). No group differences or correlations were found for GABA/Cr in the sensorimotor area. Hepatic encephalopathy is associated with a regional specific decrease of GABA levels in the visual cortex, while no changes were revealed for the sensorimotor cortex. Correlations of visual GABA/Cr with CFF, blood ammonia, and osmolytic regulators mI and Gln indicate that decreased visual GABA levels might contribute to HE symptoms, most likely as a consequence of hyperammonemia.
authors.affiliation: Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University Düsseldorf, Universitätsstr. 1, D-40225, Düsseldorf, Germany. georg.oeltzschner@med.uni-duesseldorf.de.|Medical Faculty, Department of Diagnostic and Interventional Radiology, University Düsseldorf, D-40225, Düsseldorf, Germany. georg.oeltzschner@med.uni-duesseldorf.de.
authors.forename: Georg
authors.initials: G
authors.lastname: Oeltzschner
authors.affiliation: Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University Düsseldorf, Universitätsstr. 1, D-40225, Düsseldorf, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Butz
authors.affiliation: Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University Düsseldorf, Universitätsstr. 1, D-40225, Düsseldorf, Germany.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Baumgarten
authors.affiliation: Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University Düsseldorf, Universitätsstr. 1, D-40225, Düsseldorf, Germany.
authors.forename: Nienke
authors.initials: N
authors.lastname: Hoogenboom
authors.affiliation: Medical Faculty, Department of Diagnostic and Interventional Radiology, University Düsseldorf, D-40225, Düsseldorf, Germany.
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Wittsack
authors.affiliation: Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University Düsseldorf, Universitätsstr. 1, D-40225, Düsseldorf, Germany.
authors.forename: Alfons
authors.initials: A
authors.lastname: Schnitzler
mesh_terms: D000641:Ammonia / Q000097:blood*; D001923:Brain Chemistry; D003401:Creatine / Q000378:metabolism; D005260:Female; D005425:Flicker Fusion; D005973:Glutamine / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000378:metabolism* / Q000523:psychology; D006801:Humans; D007294:Inositol / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009994:Osmolar Concentration; D014793:Visual Cortex / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005973:Glutamine; D007294:Inositol; D005680:gamma-Aminobutyric Acid; D000641:Ammonia; D003401:Creatine; D005998:Glycine
keywords: Ammonia; Critical flicker frequency; Hepatic encephalopathy; MEGA-PRESS; MR spectroscopy; γ-aminobutyric acid