Altered motor cortical plasticity in patients with hepatic encephalopathy: A paired associative stimulation study

Petyo Nikolov; Thomas J Baumgarten; Shady S Hassan; Sarah N Meissner; Nur-Deniz Füllenbach; Gerald Kircheis; Dieter Häussinger; Markus S Jördens; Markus Butz; Alfons Schnitzler; Stefan J Groiss

doi:10.1016/j.clinph.2021.07.019

Altered motor cortical plasticity in patients with hepatic encephalopathy: A paired associative stimulation study

Clin Neurophysiol. 2021 Oct;132(10):2332-2341. doi: 10.1016/j.clinph.2021.07.019. Epub 2021 Aug 13.

Authors

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.
² Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany; Neuroscience Institute, New York University School of Medicine, New York, USA.
³ Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany; Department of Neurology, Medical Faculty, Assiut University Hospital, Assiut, Egypt.
⁴ Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany; Department of Health Sciences and Technology, ETH Zürich, Switzerland.
⁵ Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
⁶ Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
⁷ 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@uni-duesseldorf.de.

PMID: 34454259
DOI: 10.1016/j.clinph.2021.07.019

Abstract

Objective: Hepatic encephalopathy (HE) is a potentially reversible brain dysfunction caused by liver failure. Altered synaptic plasticity is supposed to play a major role in the pathophysiology of HE. Here, we used paired associative stimulation with an inter-stimulus interval of 25 ms (PAS25), a transcranial magnetic stimulation (TMS) protocol, to test synaptic plasticity of the motor cortex in patients with manifest HE.

Methods: 23 HE-patients and 23 healthy controls were enrolled in the study. Motor evoked potential (MEP) amplitudes were assessed as measure for cortical excitability. Time courses of MEP amplitude changes after the PAS25 intervention were compared between both groups.

Results: MEP-amplitudes increased after PAS25 in the control group, indicating PAS25-induced synaptic plasticity in healthy controls, as expected. In contrast, MEP-amplitudes within the HE group did not change and were lower than in the control group, indicating no induction of plasticity.

Conclusions: Our study revealed reduced synaptic plasticity of the primary motor cortex in HE.

Significance: Reduced synaptic plasticity in HE provides a link between pathological changes on the molecular level and early clinical symptoms of the disease. This decrease may be caused by disturbances in the glutamatergic neurotransmission due to the known hyperammonemia in HE patients.

Keywords: Critical flicker frequency; Hepatic encephalopathy; Motor evoked potential; Paired associative stimulation; Synaptic plasticity; Transcranial magnetic stimulation.

Publication types

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

MeSH terms

Aged
Evoked Potentials, Motor / physiology*
Female
Hepatic Encephalopathy / diagnosis
Hepatic Encephalopathy / physiopathology*
Hepatic Encephalopathy / therapy
Humans
Male
Middle Aged
Motor Cortex / physiology*
Neuronal Plasticity / physiology*
Paired-Associate Learning / physiology*
Transcranial Magnetic Stimulation / methods*