Paired associative stimulation demonstrates alterations in motor cortical synaptic plasticity in patients with hepatic encephalopathy

Petyo Nikolov; Thomas J. Baumgarten; Shady Safwat Hassan; Nur-Deniz Füllenbach; Gerald Kircheis; Dieter Häussinger; Markus Jördens; Markus Butz; Alfons Schnitzler; Stefan J. Groiss

doi:10.1016/j.clinph.2021.07.019

arXiv · 2205.02465

Paired associative stimulation demonstrates alterations in motor cortical synaptic plasticity in patients with hepatic encephalopathy

Petyo Nikolov·Thomas J. Baumgarten·Shady Safwat Hassan·Nur-Deniz Füllenbach·Gerald Kircheis·Dieter Häussinger·Markus Jördens·Markus Butz·Alfons Schnitzler·Stefan J. Groiss

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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. Conclusion: 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.

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Petyo Nikolov, Thomas J. Baumgarten, Shady Safwat Hassan, Nur-Deniz Füllenbach, Gerald Kircheis, Dieter Häussinger, Markus Jördens, Markus Butz, Alfons Schnitzler, Stefan J. Groiss. 2022-05-06. Paired associative stimulation demonstrates alterations in motor cortical synaptic plasticity in patients with hepatic encephalopathy. https://doi.org/10.1016/j.clinph.2021.07.019

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