Cerebellar inhibition in hepatic encephalopathy

Abstract Objective Previous animal work reported that hyperammonemia leads to opposing changes of GABAergic neurotransmission in terms of increase in the cerebellum and decrease in the cerebral cortex. In this study, we investigate GABAergic tone in the cerebellum in patients with hepatic encephalopathy (HE) at different stages of the disease and its relation to critical flicker frequency (CFF) and ataxia. Methods Cerebellar inhibition using transcranial magnetic stimulation was investigated in 15 patients with different stages of HE and 15 healthy controls. All patients were assessed using CFF and the score for assessment and rating of ataxia (SARA). Results Decreased cerebellar inhibition (CBI) was observed in manifest HE at interstimulus interval from 5 to 7 ms. However, the degree of CBI at 7 ms correlated significantly with disease severity measured with SARA and with CFF by trend. Conclusion Reduced CBI in HE patients indicates affection of the cerebellar efferent pathway. The disease severity dependent increase of CBI magnitude supports the notion of disease stage dependent increase of GABAergic neurotransmission in Purkinje cells. Significance The results support previous animal experiments showing increase of GABA-ergic neurotransmission in the cerebellum and decrease in the motor cortex in HE.