Franziska Hopfner1, Rick C Helmich2. 1. Department of Neurology, University Hospital Schleswig-Holstein, Christian-Albrechts University Kiel, Germany. 2. Department of Neurology, Donders Centre for Medical Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands. Electronic address: Rick.Helmich@radboudumc.nl.
Abstract
INTRODUCTION: Essential tremor (ET) is characterized by bilateral upper limb action tremor. Here we review the pathophysiology (cerebral mechanisms) and etiology (genetic and environmental risk factors) of ET. METHODS: We reviewed the literature (until June 2017) by searching PubMed for relevant papers. RESULTS: The pathophysiology of ET involves oscillatory activity in the cortico-olivo-cerebello-thalamic circuit, evidenced by electrophysiological and metabolic imaging. Possible underlying mechanisms include GABA-ergic dysfunction, cerebellar neurodegeneration, olivary dysfunction, or a combination. Genetic studies have examined affected ET families (linkage studies and whole-exome sequencing studies). These studies revealed several chromosomal regions and genes associated with ET, but the findings have not been replicated across different ET families. Genetic studies also assessed the sporadic occurrence of ET using genome wide genotyping of single nucleotide polymorphisms (SNP's) and candidate gene studies. Several SNP's are associated with ET, and this has been replicated across different cohorts. Interestingly, some of the involved genes are linked to the cerebellum and inferior olive. Environmental studies point to an association between ET and beta-carboline alkaloids (such as harmane), which have been found in the cerebellum. CONCLUSION: Genetic and environmental risk factors may influence cerebellar and/or olivary function, resulting in abnormal cortico-olivo-cerebello-thalamic activity, and ultimately ET.
INTRODUCTION: Essential tremor (ET) is characterized by bilateral upper limb action tremor. Here we review the pathophysiology (cerebral mechanisms) and etiology (genetic and environmental risk factors) of ET. METHODS: We reviewed the literature (until June 2017) by searching PubMed for relevant papers. RESULTS: The pathophysiology of ET involves oscillatory activity in the cortico-olivo-cerebello-thalamic circuit, evidenced by electrophysiological and metabolic imaging. Possible underlying mechanisms include GABA-ergic dysfunction, cerebellar neurodegeneration, olivary dysfunction, or a combination. Genetic studies have examined affected ET families (linkage studies and whole-exome sequencing studies). These studies revealed several chromosomal regions and genes associated with ET, but the findings have not been replicated across different ET families. Genetic studies also assessed the sporadic occurrence of ET using genome wide genotyping of single nucleotide polymorphisms (SNP's) and candidate gene studies. Several SNP's are associated with ET, and this has been replicated across different cohorts. Interestingly, some of the involved genes are linked to the cerebellum and inferior olive. Environmental studies point to an association between ET and beta-carboline alkaloids (such as harmane), which have been found in the cerebellum. CONCLUSION: Genetic and environmental risk factors may influence cerebellar and/or olivary function, resulting in abnormal cortico-olivo-cerebello-thalamic activity, and ultimately ET.
Authors: Sheng-Han Kuo; Elan D Louis; Phyllis L Faust; Adrian Handforth; Su-Youne Chang; Billur Avlar; Eric J Lang; Ming-Kai Pan; Lauren N Miterko; Amanda M Brown; Roy V Sillitoe; Collin J Anderson; Stefan M Pulst; Martin J Gallagher; Kyle A Lyman; Dane M Chetkovich; Lorraine N Clark; Murni Tio; Eng-King Tan; Rodger J Elble Journal: Cerebellum Date: 2019-12 Impact factor: 3.847
Authors: Wai Yan Yau; Emer O'Connor; Zhongbo Chen; Jana Vandrovcova; Nicholas W Wood; Henry Houlden Journal: Brain Date: 2020-07-01 Impact factor: 13.501