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

Introduction: Hepatic encephalopathy (HE) is a potentially reversible brain dysfunction as result of 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 intra-stimulus interval of 25ms (PAS25), a non-invasive transcranial magnetic stimulation (TMS) protocol, to study synaptic plasticity of the motor cortex in patients with manifest HE. Materials and methods: Twenty HE-patients and twenty-three healthy controls were enrolled in the study. Motor evoked potential (MEP) amplitudes were used as measure for cortical excitability. Time course of MEP amplitude changes after PAS25 were compared between the groups. Results: MEP-amplitudes significantly increased after PAS25 in the control group indicating PAS25-induced synaptic plasticity in healthy subjects. On the other hand, MEP-amplitudes within the HE-group did not change and were significantly lower than in the control group, indicating no plasticity induction. Discussion: The reduced synaptic plasticity in HE might represent a valuable link between pathological changes on the molecular level and early clinical symptoms of the disease. The reduced plasticity may be caused by disturbances in the glutamatergic neurotransmission, due to ammonia overload. Conclusion: Our study shows a reduced synaptic plasticity over the primary motor cortex in HE. Further research is needed to determine the relation between altered plasticity and both motor and non-motor symptoms of the disease.