Causes of Tremors
Tremors are primarily caused by damage to cerebello-thalamo-cortical pathways, basal ganglia dysfunction, or disruption of the dentato-rubro-olivary pathway (Guillain-Mollaret triangle), which leads to abnormal firing patterns in motor neurons controlling affected muscles. 1
Pathophysiological Mechanisms
Tremors develop through several distinct pathophysiological mechanisms:
Neurological Circuit Dysfunction
- Cerebello-thalamo-cortical pathway damage - produces action tremors that worsen with movement 1
- Basal ganglia dysfunction - causes parkinsonian tremors that predominate at rest and improve with voluntary movement 1
- Dentato-rubro-olivary pathway damage - particularly associated with Holmes' tremor 1
Specific Neurological Disorders
- Parkinson's disease - most common cause of resting tremor due to dopaminergic neuron loss in the substantia nigra 2
- Multiple systems atrophy and progressive supranuclear palsy - cause tremors through disruption of basal ganglia circuits 2, 1
- Cerebellar disorders - lead to intention tremors that worsen as the patient approaches a target 1
Types of Tremors Based on Presentation
Action Tremors
- Postural tremors - occur when maintaining a position against gravity
- Kinetic tremors - appear during voluntary movement
- Intention tremors - worsen as the patient approaches a target 3
Resting Tremors
- Occur when the affected body part is completely supported against gravity and not actively moving
- Typically seen in Parkinson's disease 3, 4
Common Causes by Tremor Type
Action Tremor Predominant Disorders
- Essential tremor
- Enhanced physiologic tremor
- Drug-induced tremor
- Dystonic tremor
- Primary writing tremor
- Orthostatic tremor
- Cerebellar tremor 3
Resting Tremor Predominant Disorders
- Parkinson's disease (most common)
- Atypical parkinsonian syndromes
- Drug-induced parkinsonism 4
Metabolic and Toxic Causes
Metabolic Disorders
- Wilson's disease - copper metabolism disorder causing "wing-beating" tremor 1
- Hepatic encephalopathy - hand tremor is a common early symptom due to hyperextension of the wrist as fingers spread apart 2
- Thyroid dysfunction - can cause enhanced physiologic tremor 1
Drug and Toxin-Induced Tremors
- Common medications: amiodarone, SSRIs/SNRIs, amitriptyline, lithium, valproate, β-adrenoceptor agonists, dopamine receptor antagonists, VMAT2 inhibitors 5
- Substances of abuse: alcohol, cocaine 5
- Risk factors: polypharmacy, male gender, older age, high doses, immediate-release preparations, toxic drug levels 5
Clinical Pearls and Pitfalls
- Asterixis or "flapping tremor" is not actually a tremor but a negative myoclonus consisting of loss of postural tone, often seen in early to middle stages of hepatic encephalopathy 2
- Tremors may not be fully reversible in some conditions, particularly after repeated episodes of hepatic encephalopathy 2
- Drug-induced tremors typically resolve when the offending medication is discontinued, but may persist in some cases (tardive tremor) 5
- Unilateral, task-specific, or position-dependent tremors with sudden onset may suggest dystonic or functional (psychogenic) tremor rather than the more common causes 5
Understanding the specific cause of tremor is crucial for establishing prognosis and selecting appropriate treatment, as emphasized by multiple clinical guidelines 1, 3, 6.