Shady Safwat Hassan1, Thomas J Baumgarten2, Anwar M Ali3, Nur-Deniz Füllenbach4, Markus S Jördens4, Dieter Häussinger4, Markus Butz2, Alfons Schnitzler5, Stefan Jun Groiss6. 1. Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University Düsseldorf, Germany; Department of Neurology, Medical Faculty, Assiut University Hospital, Assiut, Egypt. 2. Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University Düsseldorf, Germany. 3. Department of Neurology, Medical Faculty, Assiut University Hospital, Assiut, Egypt. 4. Department of Gastroenterology, Hepatology and Infectiology, Medical Faculty, Heinrich Heine University Düsseldorf, Germany. 5. Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University Düsseldorf, Germany; Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Germany. 6. 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-js@umin.net.
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.
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.
Authors: Giuseppe Lanza; Francesco Fisicaro; Raffaele Dubbioso; Federico Ranieri; Andrei V Chistyakov; Mariagiovanna Cantone; Manuela Pennisi; Alfio Antonio Grasso; Rita Bella; Vincenzo Di Lazzaro Journal: Front Aging Neurosci Date: 2022-09-26 Impact factor: 5.702