Mechanisms and Pharmacotherapy for Ethanol-Responsive Movement Disorders.

Jingying Wu,Huidong Tang,Li Cao,Shengdi Chen

doi:10.3389/fneur.2020.00892

Abstract

Ethanol-responsive movement disorders are a group of movement disorders of which clinical manifestation could receive significant improvement after ethanol intake, including essential tremor, myoclonus-dystonia, and some other hyperkinesia. Emerging evidence supports that the sensitivity of these conditions to ethanol might be attributed to similar anatomical targets and pathophysiologic mechanisms. Cerebellum and cerebellum-related networks play a critical role in these diseases. Suppression of inhibitory neurotransmission and hyper-excitability of these regions are the key points for pathogenesis. GABA pathways, the main inhibitory system involved in these regions, were firstly linked to the pathogenesis of these diseases, and GABAA receptors and GABAB receptors play critical roles in ethanol responsiveness. Moreover, impairment of low-voltage-activated calcium channels, which were considered as a contributor to oscillation activity of the nervous system, also participates in the sensitivity of ethanol in relevant disease. Glutamate transporters and receptors that are closely associated with GABA pathways are the action sites for ethanol as well. Accordingly, alternative medicines aiming at these shared mechanisms appeared subsequently to mimic ethanol-like effects with less liability, and some of them have achieved positive effects on different diseases with well-tolerance. However, more clinical trials with a large sample and long-term follow-ups are needed for pragmatic use of these medicines, and further investigations on mechanisms will continue to deepen the understanding of these diseases and also accelerate the discovery of ideal treatment.

Highlights

Ethanol is known to have a significant influence on human bodies, especially on the nervous system [1]
In the aspects of neural networks involved in these diseases, though compelling evidence has supported the essential role of the cerebellum and circuits linked to the cerebellum, the unsolved question is whether these movement disorders are originated from the cerebellum, or are subsequently mediated by other structures within the shared anatomical networks, or are the result of disruption in connectivity between several brain structures
Ethanol-responsive movement disorders are a group of dyskinesia, of which clinical manifestation could receive significant improvement after consumption of ethanol

Summary

INTRODUCTION

Ethanol is known to have a significant influence on human bodies, especially on the nervous system [1]. With deeper understanding of the pathogenesis, corresponding medicines have emerged subsequently to mimic alcohol-like effects through the common pathways among ERMDs. In this review, we will elaborate reported diseases with ethanol responsiveness and analyze their shared anatomical networks, summarize the possible mechanisms underlying the treatment-like effects of ethanol, describe the main deficiencies of current ethanol therapy, and introduce progress on relevant medication that could substitute for ethanol to avoid some of its side effects. While the therapeutic effects vary among different diseases, shared anatomical networks in these diseases, especially cerebellum and neural circuits related to the cerebellum, suggest the possibility of common mechanisms underlying ethanol responsiveness. Evidence from most published studies indicates the critical role of the cerebellum in the pathophysiology of ERMDs. Essential tremor (ET), the most common movement disorder worldwide [2], is predominantly related to the cerebellum and is mainly linked to Purkinje cells, the main cerebellar output, and TABLE 1 | Effects of ethanol on reported ethanol-responsive movement disorders

LIMITATIONS

Findings

CONCLUSION