Causes of Essential Tremor
Essential tremor is a progressive neurological disorder whose exact cause remains unknown, but current evidence points to a combination of genetic predisposition and possible environmental factors, with the cerebellum and cerebellar system now recognized as the primary site of pathology. 1
Genetic Factors
- Genetic factors are believed to be the primary contributor to essential tremor onset, with three gene loci identified: ETM1 on chromosome 3q13, ETM2 on 2p24.1, and a locus on 6p23. 2
- A Ser9Gly variant in the dopamine D3 receptor gene on chromosome 3q13 has been suggested as a risk factor for developing the condition. 2
- The disorder appears to follow a multifactorial genetic pattern, though specific causative mutations have not yet been definitively identified. 3
- Family history is a strong risk factor, as essential tremor demonstrates clear familial clustering patterns. 2
Neuroanatomical and Pathophysiological Mechanisms
- Recent research increasingly places the seat of the disease in the cerebellum and cerebellar system, with a host of neurodegenerative changes identified within the cerebellum, indicating this progressive disorder is likely degenerative in nature. 1
- The pathophysiology involves a central oscillator at the olive-cerebellar-thalamic-cortical-spinal level, which acts as the primary generator of essential tremor and is modulated by a peripheral component. 3
- The tremor results from interaction between increased central excitability and peripheral regulation, which reinforces the central overactivity. 3
- The monoaminergic system (catecholaminergic and serotoninergic pathways), beta-2 muscular adrenoreceptors, and body structure may influence the pathogenic mechanism. 3
Environmental and Toxic Factors
- Environmental agents have been proposed to play a role, though specific toxic exposures have not been definitively established. 2
- The etiology remains unknown despite extensive investigation into potential environmental triggers. 4
Clinical Heterogeneity
- Essential tremor demonstrates significant clinical, etiologic, and pathologic heterogeneity, with growing support for the notion that it may not be a single disease but rather a family of diseases whose central defining feature is kinetic tremor of the arms. 1
- This heterogeneity suggests multiple potential causative pathways may lead to the same clinical presentation. 1
Important Caveats
- Essential tremor itself appears to be a risk factor for other degenerative diseases such as Alzheimer's disease and Parkinson's disease, suggesting shared or overlapping pathogenic mechanisms. 1
- The disorder is chronic and progressive, with no current treatments that can slow its progression or cure the condition. 5
- While numerous drugs can aggravate essential tremor, and alcohol consumption may temporarily alleviate it, these observations have not led to clear etiologic insights. 4