  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.
