Tremor

Tremor is an involuntary, rhythmic, oscillatory movement of one or more body parts. It is the most common movement disorder and is classified into resting tremor and action tremor (e.g., postural tremor, intention tremor). Resting tremor is typical in Parkinson disease and manifests as an asymmetrical tremor that occurs at rest. Postural tremor occurs when a position is held against gravity and includes essential, physiologic, and orthostatic tremor. Essential tremor is the most common pathologic tremor, usually involves the hands, is characteristically bilateral, and improves with alcohol consumption. Physiologic tremor is bilateral, most commonly involves the hands, and is enhanced with sympathetic stimulation (e.g., caffeine, anxiety). Orthostatic tremor is associated with standing and resolves when sitting or lying down. Intention tremor is a coarse hand tremor that is aggravated by goal-directed movement and is often caused by cerebellar lesions (e.g., due to strokes, trauma, multiple sclerosis). Various medications and toxins are associated with tremor, most commonly enhanced physiologic tremor. Diagnosis is typically clinical, but laboratory tests and imaging may be required to determine the underlying cause. Treatment is based on the type of tremor and the underlying condition.

By activation condition ^[5]

Resting tremor ^[1][6]

Resting tremor occurs in a body part that is not being voluntarily activated.

Action tremor ^[1][6]

Action tremor occurs with voluntary muscle contraction.

• Postural tremor: occurs when a body part is held against gravity
• Isometric tremor: occurs with static muscle contraction against resistance
• Kinetic tremor: occurs with any voluntary movement
  • Intention tremor: increases in amplitude as the body part nears the target
  • Task-specific tremor: occurs with specific tasks (e.g., writing)
  • Simple kinetic tremor: remains constant throughout the movement

By tremor characteristics

• Frequency ^[1][6]
  • Low (< 4 Hz)
  • Medium (4–7 Hz)
  • High (> 7 Hz)
• Amplitude: usually described as coarse (large amplitude) or fine (small amplitude) ^[7]

Conditions associated with tremor

Neurodegenerative diseases ^[3]

• Parkinson disease
• Corticobasal degeneration
• Multiple system atrophy
• Progressive supranuclear palsy

Focal lesions ^[3][6]

• Stroke or space-occupying lesion affecting the basal ganglia and/or cerebello-thalamo-cortical network
• Multiple sclerosis
• Posttraumatic

Hereditary conditions ^[3]

• Spinocerebellar ataxia
• Klinefelter syndrome
• Fragile X syndrome
• Leigh syndrome

Metabolic conditions ^[3]

• Wilson disease
• Hyperthyroidism
• Electrolyte disturbances (e.g., hypocalcemia, hyponatremia, hypomagnesemia)
• Hypoglycemia
• Hyperparathyroidism
• Vitamin B₁₂ deficiency

Neuropathies ^[3]

• Hereditary motor sensory neuropathy
• Acute inflammatory demyelinating polyradiculoneuropathy
• Chronic inflammatory demyelinating polyradiculoneuropathy
• Multifocal neuropathy

Medications associated with tremor ^[3][8][9]

• Sympathomimetics
• Hormones
  • Levothyroxine
  • Steroids: progesterone, corticosteroids
• Antiepileptics
• Dopamine antagonists
  • Antipsychotics
  • Metoclopramide
• Antidepressants
  • Selective serotonin reuptake inhibitors
  • Tricyclic antidepressants
• Chemotherapeutic agents
• Others: amiodarone, lithium, theophylline

Substances associated with tremor ^[3][9][10]

• Stimulant toxicity (e.g., caffeine, nicotine, cocaine)
• Substance withdrawal
  • Alcohol withdrawal
  • Benzodiazepine withdrawal
  • Marijuana withdrawal ^[11]
• Alcohol
• Toxins
  • Metal toxicity: mercury, lead, arsenic, manganese
  • Cyanide toxicity
  • Carbon monoxide toxicity
  • Organic solvent toxicity: toluene, lindane
  • Naphthalene

Approach ^[1][6][8]

Tremor is primarily a clinical diagnosis. Ancillary testing beyond routine laboratory studies is typically ordered by specialists.

• Obtain a medical history, focusing on tremor etiologies, e.g.:
  • Triggers and exposures (e.g., medications associated with tremor, substances associated with tremor)
  • Underlying conditions associated with tremor
• Perform a neurological examination, focusing on:
  • Typical features of common types of tremors
  • Activation condition
  • Associated features
• Order routine laboratory studies and consider additional testing based on clinical suspicion.

Laboratory studies ^[1][8]

• Routine studies
  • POC glucose
  • BMP
  • Thyroid function test
  • Liver chemistries
• Additional studies
  • Blood alcohol level
  • Ammonia
  • Magnesium
  • Diagnostics for Wilson disease
  • Drug levels, e.g., lithium, tacrolimus
  • Urine drug test

Imaging ^[1]

Imaging may be indicated to rule out secondary causes.

• Head CT or MRI for suspected:
  • Stroke
  • Space-occupying lesion
  • Multiple sclerosis
  • Traumatic lesions
• DaTSCAN: to differentiate Parkinson disease from other diagnoses (e.g., essential tremor)

Advanced studies ^[3][8]

Specialists may request advance studies when the diagnosis is uncertain.

• Electromyography
• CSF analysis

Parkinson disease

• Epidemiology
  • Onset typically ≥ 60 years ^[6]
  • Most common cause of resting tremor ^[1]
• Pathophysiology: caused by a dysfunction of the basal ganglia, especially substantia nigra
• Clinical features ^[12][13]
  • Typically, asymmetric resting tremor of the extremities (especially apparent in the hands); at a frequency of 4–6 Hz
  • Hand motion resembling pill-rolling
  • Decreases with target-directed movement
  • Usually unilateral; may progress to bilateral tremors
  • Often associated with rigidity, bradykinesia, and postural instability (see “Parkinsonism”)
• Diagnosis: See “Diagnostics in Parkinson disease.”
• Management: See “Management of Parkinson disease.”

“Rest in the park”: The most common cause of resting tremor is Parkinson disease. ^[1]

Tremor that is apparent at rest but does not decrease with target-directed movement is unlikely to be due to parkinsonism. ^[1]

Other causes

• Drug-induced parkinsonism (e.g., typical antipsychotics, metoclopramide) ^[14]
• Parkinson-plus syndromes (e.g., progressive supranuclear palsy)
• Severe essential tremor ^[1]

Essential tremor ^[2][3][6]

• Definition
  • Isolated bilateral upper limb action tremor in the absence of other neurological signs, e.g., dystonia, ataxia, or parkinsonism
  • May be accompanied by tremor of the head, neck, voice, and/or lower limbs
  • Formal diagnosis requires symptoms to be present for ≥ 3 years.
• Epidemiology
  • Most common pathologic form of tremor ^[1]
  • Bimodal distribution: adolescence or early adulthood and adults aged > 60 years (most common in older adults) ^[6]
• Etiology: positive family history in up to 70% of patients ; may be sporadic ^[15]
• Clinical features
  • Localization: hands (most common), head ("yes-yes” or "no-no” motion), voice
  • Bilateral postural tremor with a frequency between 6–12 Hz
    • Slowly progressive
    • Worse with voluntary movement, stress or anxiety, fatigue, and caffeine
    • Improves with alcohol consumption
  • May be accompanied by intention tremor and/or resting tremor
• Diagnosis
  • Clinical diagnosis
  • See “Diagnostics for tremor.”
• Treatment ^[2][16][17]
  • First-line medications
    • Propranolol ^[17]
    • Primidone (off-label) ^[17]
  • Alternative medications (if propranolol and primidone are ineffective or contraindicated)
    • Other beta blockers (e.g., atenolol, metoprolol)
    • Other anticonvulsants; (e.g., topiramate, gabapentin)
    • Benzodiazepines (e.g., alprazolam, clonazepam)
  • Drug-resistant essential tremor
    • Deep brain stimulation (DBS)
    • Thalamotomy

Consider essential tremor in patients with chronic bilateral hand tremor who have a positive family history and are otherwise neurologically intact.

Physiologic tremor ^[1][5][9]

All individuals have physiologic tremor, but it is generally not symptomatic or visible. Enhanced physiologic tremor occurs when reversible conditions (e.g., stress, fatigue) magnify physiologic tremor.

Enhanced physiologic tremor ^[1][5][9]

• Epidemiology: may occur at any age
• Etiology: usually caused by increased sympathetic stimulation, e.g.,
  • Stress, exercise, fatigue
  • Medications (e.g., albuterol, levothyroxine)
  • Substance use (e.g., sympathomimetic drugs)
  • Substance withdrawal syndromes (e.g., alcohol withdrawal)
  • Medical conditions (e.g., hyperthyroidism, pheochromocytoma, hypoglycemia) ^[8][10]
• Clinical features: usually a fine bilateral postural tremor in the hands and fingers (8–12 Hz)
• Diagnosis
  • Clinical diagnosis
  • See “Diagnostics for tremor.”
• Treatment
  • Reversible once the underlying cause is treated
  • Propranolol may be considered under specialist guidance.

Orthostatic tremor ^[5][18][19]

• Epidemiology ^[19]
  • Rare
  • ♀ > ♂
  • Onset ∼ 60 years
• Etiology: unknown
• Clinical features:
  • Occurs upon standing and resolves when sitting or lying down
  • Tremor occurs primarily in the legs but may involve other body parts, e.g., hands. ^[20]
  • May be associated with falls and postural instability
• Diagnosis
  • Clinical diagnosis
  • Electromyography shows 13–18 Hz tremor in the patient's legs while standing
  • See “Diagnostics for tremor.”
• Treatment
  • Tailored to symptoms (e.g., physical aids, physical therapy, occupational therapy)
  • Consider clonazepam or gabapentin ^[20]

• Etiology ^[1][4][9]
  • Cerebellar stroke, tumor, or trauma
  • Drug-induced: alcohol, lithium
  • Multiple sclerosis
  • Wilson disease ^[18]
  • Other causes of cerebellar dysfunction (e.g., acute cerebellitis)
• Clinical features ^[6][8]
  • Coarse hand tremor
  • Slow tremor with a frequency of < 5 Hz
  • Worse with goal-directed movement
  • Other cerebellar signs
• Diagnosis
  • Clinical diagnosis
  • Additional diagnostics based on suspected cause, e.g.:
    • Diagnosis of stroke (e.g., CT, MRI)
    • Diagnosis of multiple sclerosis
    • Diagnosis of Wilson disease
    • Lithium poisoning
  • See “Diagnostics for tremor.”
• Treatment ^[1]
  • Treatment of the underlying cause
  • Deep brain stimulation
  • Supportive measures (e.g., occupational therapy, physical therapy)

Various medications and substances are associated with tremor, e.g., enhanced physiologic tremor due to sympathetic activation or resting tremor due to dopamine receptor antagonism. ^[1][8][9]

• Etiology
  • See “Medications associated with tremor.”
  • See “Substances associated with tremor.”
• Clinical features: variable; most commonly enhanced physiologic tremor ^[6]
• Diagnostics
  • Review of medication and toxin exposure
  • See “Diagnostics for tremor.”
• Treatment: based on the underlying cause
  • Reduction or removal of offending agent
  • Management of stimulant intoxication
  • Treatment of alcohol withdrawal, benzodiazepine withdrawal, or cannabis withdrawal
  • For treatment of toxin-induced symptoms, see also “Metal toxicity” and “Poisoning.”

Flapping tremor (asterixis) ^[21]

• Etiology
  • Metabolic encephalopathies
    • Hepatic encephalopathy (most common)
    • Respiratory failure and hypercapnia
    • Renal failure and uremia
    • Cardiac failure
    • Electrolyte abnormalities: hypokalemia, hypomagnesemia
    • Hypoglycemia
  • Lesions in the thalamus (e.g., ischemic stroke, hemorrhage, space-occupying lesion)
  • Wilson disease
  • Drug-induced (e.g., phenytoin, benzodiazepines, barbiturates)
  • Infections (e.g., cerebral malaria)
• Clinical features
  • Irregular, high-amplitude oscillations when arms are extended and wrists are dorsiflexed
  • Caused by negative myoclonus: short loss of postural muscle tone followed by a compensatory corrective movement
  • Features of the underlying cause, e.g.:
    • Signs of hepatic encephalopathy
    • Signs of Wilson disease
    • Signs of stroke
• Diagnosis
  • Clinical diagnosis
  • Additional diagnostics based on suspected cause, e.g.:
    • Diagnosis of hepatic encephalopathy
    • Diagnosis of Wilson disease
    • Diagnosis of stroke
  • See “Diagnostics for tremor.”
• Treatment: based on the underlying cause, e.g.,
  • See “Treatment of hepatic encephalopathy.”
  • See “Treatment of Wilson disease.”
  • See “Renal replacement therapy.”

Functional tremor ^[1][3][8]

• Etiology: : a common feature of conversion disorder; may occur in other psychiatric disorders (e.g., anxiety disorders, factitious disorder, depression)
• Clinical features
  • Complex resting, postural, and/or action tremor
  • Sudden onset
  • Worsens under direct observation and diminishes with distraction
  • Variability in the amplitude, frequency, or distribution of the movement over time
  • Other clinical features of conversion disorder
• Diagnosis: clinical diagnosis; usually made by a specialist ^[3][22]
  • Entrainment test
    • The patient performs a voluntary movement (e.g., tapping) with an unaffected limb and at a set rhythm that is different from the frequency of the tremor.
    • Positive test: The tremor of the affected limb aligns with the frequency of the voluntary movement.
  • See “Diagnostics for tremor.”
  • See “Diagnostics” in “Conversion disorder.”
• Treatment
  • Multidisciplinary care that may include cognitive behavioral therapy and pharmacotherapy (e.g., antidepressants)
  • See “Management” in “Conversion disorder.”
  • See “Approach to patients with suspected somatic symptom and related disorders.”

Other types of tremor

• Dystonic tremor: focal postural and/or kinetic tremor that occurs in muscles with preexisting dystonia ^[18]
• Holmes tremor ^[3]
  • Low-frequency, large-amplitude tremor that is present at rest and worsens when performing an action or maintaining certain postures.
  • Causes: stroke, traumatic brain injury, multiple sclerosis, intracranial hypertension, CNS infections
• Cerebellar tremor
• Wing-beating tremor

Other types of involuntary movement and hyperkinetic movement disorders include: ^[6][23]

• Seizure
• Dystonia
• Chorea
• Dyskinesia, tardive dyskinesia
• Clonus, myoclonus
• Akathisia
• Tics
• Ballismus

The differential diagnoses listed here are not exhaustive.