Abstract
Essential tremor is clinically defined but there is increasing evidence that it is not a unique entity. Its pathophysiology has been studied with many methods but may also vary between subtypes. Neurophysiologically, there is strong evidence that a specific cerebello-thalamo-cortical loop is abnormally oscillating. The cause of its uncontrolled oscillation is not yet understood. The clear proof of a degenerative cause is still lacking and abnormal receptors or other causes of altered non-progressive functional disturbance cannot be excluded. Strong evidence supports the major involvement of the cerebellum and there is ample evidence that GABA is the main neurotransmitter involved in the pathophysiology in ET. Genetics have provided so far only a few rare subtypes which are due to specific mutations but there is no doubt that it is mostly a hereditary condition. There is evidence that the large subgroup of late onset tremor is a separate condition and this tremor is an independent risk factor for earlier mortality and comes with signs of premature aging (aging-related tremor). It will be important to improve phenotyping of patients in more detail possibly to include not only features of the tremor itself but also other clinical assessments like force measurements or cognitive testing. Based on these variables, we may be able to better understand the presumably different mechanisms underlying different variants of the disease.
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