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Metabolic Brain Disease

, Volume 30, Issue 6, pp 1429–1438 | Cite as

Low visual cortex GABA levels in hepatic encephalopathy: links to blood ammonia, critical flicker frequency, and brain osmolytes

  • Georg OeltzschnerEmail author
  • Markus Butz
  • Thomas J. Baumgarten
  • Nienke Hoogenboom
  • Hans-Jörg Wittsack
  • Alfons Schnitzler
Original Article

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 (1H 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.

Keywords

Hepatic encephalopathy MR spectroscopy γ-aminobutyric acid Ammonia Critical flicker frequency MEGA-PRESS 

Abbreviations

HE

hepatic encephalopathy

CFF

critical flicker frequency

MRS

magnetic resonance spectroscopy

GABA

γ-aminobutyric acid

Glu

glutamate

Gln

glutamine

mI

myo-inositol

Cr

creatine

MEGA-PRESS

Mescher-Garwood point resolved spectroscopy

TR

repetition time

TE

echo time

FoV

field of view

CRLB

Cramér-Rao lower bounds

MM

macromolecules

GM

gray matter

WM

white matter

CSF

cerebrospinal fluid

MEG

magnetoencephalography

Notes

Acknowledgments

The authors would like to express their thanks to Dr. James Murdoch (Toshiba Medical Research Institute USA) for the LCModel basis set and useful discussion on spectral evaluation, Nur-Deniz Füllenbach and Dr. Gerald Kircheis (Department of Gastroenterology, Hepatology and Infectiology, University Hospital Düsseldorf) for help with patient recruitment and psychometric grading, and Erika Rädisch (Department of Diagnostic and Interventional Radiology, University Hospital Düsseldorf) for support with MR measurements.

Funding

This work was supported by the Sonderforschungsbereich (SFB) 974 of the Deutsche Forschungsgemeinschaft (DFG).

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Georg Oeltzschner
    • 1
    • 2
    Email author
  • Markus Butz
    • 1
  • Thomas J. Baumgarten
    • 1
  • Nienke Hoogenboom
    • 1
  • Hans-Jörg Wittsack
    • 2
  • Alfons Schnitzler
    • 1
  1. 1.Institute of Clinical Neuroscience and Medical Psychology, Medical FacultyHeinrich Heine University DüsseldorfDüsseldorfGermany
  2. 2.Medical Faculty, Department of Diagnostic and Interventional RadiologyUniversity DüsseldorfDüsseldorfGermany

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