Aetiology

Initial consideration should be given as to whether the tremor is a rest or action tremor, as their aetiologies differ. Some patients have both rest and action tremors. In such cases, a tremor that lessens with movement or maintenance of posture is likely to be primarily a rest tremor, whereas a tremor that worsens with movement is more likely to be primarily an action tremor.

Rest tremor

Rest tremors may fluctuate in amplitude but are typically 3 to 6 Hz in frequency. They are most commonly caused by Parkinson's disease (PD) or other parkinsonian syndromes.

PD

  • Progressive neurodegenerative disorder characterised by the presence of 2 of the 3 classic motor features (rest tremor, bradykinesia, and rigidity) and a sustained response to dopaminergic therapy.[2]

Dementia with Lewy bodies

  • Characterised by dementia and parkinsonism beginning within 1 year of each other.[3]

  • Symptoms include visual hallucinations and fluctuating cognition.

Multiple system atrophy (MSA)

  • Characterised by various combinations of parkinsonism, cerebellar dysfunction, and dysautonomia (i.e., severe orthostatic hypotension, atonic bladder, gastroparesis).

  • May resemble PD but is often associated with other signs, such as early falls, severely affected speech, and noisy breathing or gasping. Should be considered in patients with rapidly progressive parkinsonism that is unresponsive to levodopa.[4] 

  • Categorised as either MSA-P (with predominant parkinsonian features) or MSA-C (with predominant cerebellar features), depending on which features predominate.[4]

Progressive supra-nuclear palsy

  • Uncommon parkinsonian syndrome that may resemble PD early in its course but is associated with other signs, such as early falls, postural instability, growling voice, dystonic facies, and gunslinger gait. Absence of a response to levodopa helps to differentiate progressive supra-nuclear palsy from PD.[5]

  • Diagnosis made clinically when patients develop vertical supra-nuclear gaze palsy.[5]

Toxin-induced parkinsonism

  • May result from exposure to carbon disulfide, carbon monoxide, cyanide, manganese, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), herbicides, or organic solvents.

Action tremor

Action tremors are more common than rest tremors. They include postural, kinetic, isometric, or task-specific tremors. There are many aetiologies, the most common of which are listed below.

Enhanced physiological tremor

  • Physiological tremor occurs in all healthy people but can be enhanced by intake of stimulants (e.g., caffeine) and other drugs; withdrawal from other drugs or alcohol; certain medical conditions (e.g., elevated thyroid hormone levels, low glucose level, phaeochromocytoma); and stress and fatigue. Any cause of increased adrenaline secretion may enhance physiological tremor.

  • Occurs in the absence of a neurological disease and is a high-frequency postural and kinetic tremor that occurs in arms, legs, and voice, but not the head.

Essential tremor (ET) or ET plus

  • Action tremor of both hands (typically 4-12 Hz), with or without head and/or voice involvement, should be classified as ET in the absence of other neurological signs.[6]

  • While ET is usually characterised by postural and/or kinetic tremor, resting tremor has occasionally been reported. In one study of 64 patients with ET, 12 (19%) had a tremor at rest and a more long-standing and severe disease than those without resting tremor.[7][8]

  • Tremors characteristic for ET that also present with subtle neurological signs of uncertain significance (impaired tandem gait, questionable dystonic posturing, memory impairment) should be classified as ET plus.[9]

  • One of the most common movement disorders worldwide, and usually familial.[10][11]

  • Alcohol may lead to transient suppression of tremor in some patients.[6][12]

Cerebellar tremor (multiple sclerosis, trauma, stroke)

  • Can result from any lesion affecting cerebellar pathways, including connections to brainstem and thalamus.

  • May be accompanied by ataxia.

Fragile X tremor ataxia syndrome (FXTAS)

  • A movement disorder characterised by late-onset tremor and/or ataxia with cognitive involvement (e.g., decline in memory and/or executive function), neuropathy, parkinsonian symptoms, and psychiatric disorders (e.g., depression or anxiety).[13][14]

  • Caused by a premutation in the FMR1 gene on the X chromosome. Up to 75% of male carriers eventually develop symptoms of FXTAS, but only 20% of female carriers develop symptoms. Female carriers may have premature ovarian failure.[13][14]

Orthostatic tremor

  • Rare, high-frequency leg tremor (usually 16 Hz, range 13-18 Hz) that occurs on standing, usually after a brief delay, and provokes an unsteady feeling.

  • Resolves with sitting or walking.

Primary writing tremor

  • Uncommon, task-specific tremor that occurs only with writing and no other activities involving the hands.

Neuropathic tremor

  • Can occur with any type of neuropathy, but most commonly with hereditary motor and sensory neuropathy type I and chronic inflammatory demyelinating polyneuropathy.

  • Uncommon and most often a postural hand tremor.

Mixed rest and action tremor

Some tremors present with mixed rest and action tremor components.

Drug-induced tremor

  • Rest tremor: dopamine receptor blockers such as neuroleptics, atypical antipsychotics, anti-nausea agents (metoclopramide, prochlorperazine, promethazine), and calcium-channel blockers (flunarizine, cinnarizine) or dopamine depletors (tetrabenazine).

  • Action tremor: antidepressants (serotonin-reuptake inhibitors, tricyclics, monoamine oxidase inhibitors), mood stabilisers (lithium), antiepileptic drugs (valproic acid), cardiac drugs (amiodarone), immunosuppressants (ciclosporin, tacrolimus, corticosteroids), asthma drugs (salbutamol, theophylline), and stimulants (amphetamines).

Dystonic tremor

  • Tremor occurring in a body part affected by dystonia.[9]

  • Often irregular with a jerky, directional quality.

  • May be very sensitive to task-specific or positional factors e.g., may disappear at a specific position ('null point').

  • Most commonly affects the head and upper neck, though may affect limbs.

  • Patients with dystonic tremor may use a sensory trick (geste antagoniste) to relieve or diminish the tremor.

Tremor secondary to Wilson's disease

  • Disorder of copper metabolism that usually affects children and younger adults.

  • Copper deposits in the brain can cause tremor (rest and action) or any other involuntary movement, especially in the setting of dysarthria, dystonia, or gait disturbance.

Functional (psychogenic) tremor

  • Generally of sudden onset and presenting with rest tremor, action tremor, or both.

  • Varying frequency and amplitudes, and decreases on distraction.

Holmes' tremor (rubral tremor, mid-brain tremor)

  • Characterised by the combination of rest, postural, and intention tremor involving proximal and distal upper extremities, and often other cerebellar signs.

  • Slow frequency (2-5 Hz) and is more irregular than other tremors.

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