GABA-ergic tone hypothesis in hepatic encephalopathy - Revisited

Stefan Jun Groiss; Markus Butz; Thomas J Baumgarten; Nur-Deniz Füllenbach; Dieter Häussinger; Alfons Schnitzler

doi:10.1016/j.clinph.2019.03.011

GABA-ergic tone hypothesis in hepatic encephalopathy - Revisited

Clin Neurophysiol. 2019 Jun;130(6):911-916. doi: 10.1016/j.clinph.2019.03.011. Epub 2019 Mar 30.

Authors

Stefan Jun Groiss¹, Markus Butz², Thomas J Baumgarten², Nur-Deniz Füllenbach³, Dieter Häussinger³, Alfons Schnitzler⁴

Affiliations

¹ Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany. Electronic address: groiss-js@umin.net.
² Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
³ Department of Gastroenterology, Hepatology and Infectiology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
⁴ Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.

PMID: 30981176
DOI: 10.1016/j.clinph.2019.03.011

Abstract

Objective: The GABA hypothesis of hepatic encephalopathy (HE) proposes an increased cerebral GABA-ergic tone in HE but has not been investigated in vivo in HE-patients yet. Cortical GABA-ergic and glutamatergic neurotransmission in HE-patients were evaluated using transcranial magnetic stimulation.

Methods: Twenty-one patients with HE grade 1 and 2 and age matched controls participated in the study. GABA-ergic (short- and long-interval intracortical inhibition (SICI and LICI)) and glutamatergic (intracortical and short-interval intracortical facilitation (ICF and SICF)) excitability of the primary motor cortex (M1) and global corticospinal excitability (motor threshold, motor evoked potential recruitment curve (MEP-RC) were compared between the groups. SICI and ICF were correlated to the critical flicker frequency (CFF) as measure for disease severity.

Results: In HE-patients, the slope of MEP-RC was significantly shallower compared to healthy controls. SICI was significantly reduced in patients with HE grade 2 compared to healthy controls. In HE-patients, SICI and ICF was significantly correlated to CFF.

Conclusion: Although global corticospinal excitability was reduced in HE-patients, GABA-ergic inhibition was reduced in M1 depending on HE severity. Moreover CFF related alteration of GABAergic and glutamatergic neurotransmission in patients with HE could support the notion of a severity dependent alteration of cortical excitability.

Significance: The decrease of cortical GABA-ergic tone challenges the classical GABA hypothesis in HE.

Keywords: Cortical excitability; GABA; Hepatic encephalopathy; TMS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Electromyography / methods*
Female
GABAergic Neurons / physiology*
Hepatic Encephalopathy / diagnosis*
Hepatic Encephalopathy / physiopathology*
Humans
Male
Middle Aged
Motor Cortex / physiology*
Transcranial Magnetic Stimulation / methods*