tremors

Tremors are involuntary, rhythmic, alternating, or oscillatory movements of interrelated muscle groups. They typically involve the hands, head, facial structures, vocal cords, trunk, or legs. Tremors can be characterized by

Frequency of oscillation (rapid or slow)

Amplitude of movement (fine or coarse)

Movements or postures that evoke them (eg, rest, action, certain positions)

Pathophysiology

Tremors are considered a movement disorder. Movement is controlled by interaction of the corticospinal (pyramidal) tracts, basal ganglia, and cerebellum. The basal ganglia consist of the caudate nucleus, putamen, globus pallidus, and substantia nigra, which together form the extrapyramidal system.

Most neural lesions that cause movement disorders occur in the extrapyramidal system; thus, movement disorders are also called extrapyramidal disorders. Neural dysfunction or lesions responsible for tremor may result from injury, ischemic or metabolic insult, or a neurodegenerative disorder. Sometimes tremor is an inherited condition (eg, essential tremor).

Classification: Tremor is classified primarily based on when it occurs:

Resting tremors are maximal at rest and decrease with activity; they occur at a frequency of 3 to 6 cycles/sec (Hz).

Postural tremors are maximal when a limb is maintained in a fixed position against gravity (eg, holding the arms out); they occur at a frequency of 5 to 18 Hz.

Intention tremors are maximal during movement toward a target, as in finger-to-nose testing; they occur at a frequency of 3 to 10 Hz.

Tremor can also be classified based on whether it is within the range of normal (physiologic tremor), a primary disorder (essential tremor, Parkinson’s disease), or a pathologic sign of CNS injury (eg, poststroke).

Etiology

Physiologic tremor: Physiologic tremor is the most common cause of tremor in otherwise healthy people; it is present normally but usually causes such small movements that it is noticeable only when enhanced by certain drugs or conditions (eg, anxiety; stress; fatigue; thyrotoxicosis; use of caffeine, phosphodiesterase inhibitors, ß-adrenergic agonists, or corticosteroids).

Nonphysiologic tremor: There are many causes (see Table 5: Movement and Cerebellar Disorders: Some Causes of Tremor), but the most common are

Essential tremor

Parkinson’s disease

Cerebral or cerebellar injury (eg, from a stroke or multiple sclerosis)

Hereditary disorders involving the cerebellum (eg, spinocerebellar ataxia)

Table 5

Some Causes of Tremor

Cause
Suggestive Findings
Diagnostic Approach

Postural tremor

Alcohol or drug withdrawal
Agitation and fine tremor starting 24–72 h after the last use of alcohol or benzodiazepines

Sometimes hypertension, tachycardia, or fever, especially in hospitalized patients
Clinical evaluation

Drug-induced (see Table 6: Movement and Cerebellar Disorders: Some Drug Causes of Tremor by Type)
History of drug use
Clinical response to stopping the drug

Endocrinologic, metabolic, and toxic abnormalities:

Anoxic encephalopathy

Heavy metal poisoning

Hepatic encephalopathy

Hyperparathyroidism

Hyperthyroidism

Hypoglycemia

Pheochromocytoma

Uremic encephalopathy
Tremor plus altered level of consciousness (suggesting encephalopathy) and an obvious underlying disorder (eg, renal or hepatic failure)

Exophthalmos, hyperreflexia, tachycardia, and heat intolerance (suggesting hyperthyroidism)

Extreme, refractory hypertension (suggesting pheochromocytoma)
TSH level

24-h urine collection to check for metanephrines, ammonia level, BUN, glucose level, Ca and PTH levels

Heavy metal testing

Essential tremor
Progressively persistent coarse or fine, slow (4–8 Hz) tremor, usually symmetric and affecting both upper extremities and sometimes the head and voice, particularly in patients with a family history of tremor
Clinical evaluation

Physiologic tremor
Fine, rapid (8–13 Hz) tremor that occurs in otherwise healthy people and may be enhanced by certain drugs or conditions (see above)

Usually, suppression of tremor with low doses of alcohol and other sedatives
Clinical evaluation

Resting tremor

Drug-induced parkinsonism

(see Table 6: Movement and Cerebellar Disorders: Some Drug Causes of Tremor by Type)
History of drug use
Clinical response to stopping the drug

Parkinson’s disease
Low-frequency (4–5 Hz) alternating tremor, often of the thumb against the index finger (pill rolling) but sometimes also the chin or a leg

Usually accompanied by other symptoms, such as micrographia, bradykinesia (slow movement), cogwheel rigidity, and shuffling gait

Often no family history of Parkinson’s tremor and no reduction in movement after alcohol consumption
Specific clinical criteria

Good response to empiric trial of dopaminergic therapy

Progressive supranuclear palsy
Tremor (sometimes coarse or jerky) in middle-aged patients with supranuclear (primarily vertical) gaze dysfunction, extrapyramidal symptoms, and cognitive dysfunction
Specific clinical criteria

Intention tremor

Cerebellar lesions:

Abscess

Friedreich’s ataxia

Hemorrhage

Multiple sclerosis

Spinocerebellar degeneration

Stroke

Tumor
Low-frequency (< 4 Hz) tremor that usually occurs unilaterally with ataxia, dysmetria, dysdiadochokinesia, and dysarthria

In some patients, family history of the disorder (eg, Friedreich's ataxia)
MRI of the brain

Drug-induced (see Table 6: Movement and Cerebellar Disorders: Some Drug Causes of Tremor by Type)
History of drug use
Clinical response to stopping the drug

Complex tremors

Holmes' tremor (midbrain, red nucleus, rubral, or thalamic tremor)
Irregular, low-frequency (< 4.5 Hz) tremor predominantly of proximal limbs

Combination of rest, postural, and intention tremors due to midbrain lesions (eg, due to stroke or multiple sclerosis) near the red nucleus

Sometimes signs of ataxia and weakness
MRI of the brain

Neuropathic tremor:

Chronic relapsing polyneuropathy

Guillain-Barré syndrome

Diabetes

IgM neuropathy
Variable tremor type and frequency, usually postural and intention tremor in the affected extremities

Other signs of peripheral neuropathy
Electromyography

Psychogenic tremor
Abrupt onset and/or spontaneous remission of complex mixed-type tremor with changing characteristics

Increased by attention and lessened by distraction of patient
Clinical evaluation

Wilson's disease
Variable type tremor (usually in the proximal arm) in children or young adults, often with signs of hepatic failure, rigidity, clumsy gait, dysarthria, inappropriate grinning, drooling, and neuropsychiatric signs
24-h urine collection to measure copper level; serum ceruloplasmin

Slit-lamp examination
PTH = parathyroid hormone; TSH = thyroid-stimulating hormone.

Drugs can cause or aggravate different types of tremor (see Table 6: Movement and Cerebellar Disorders: Some Drug Causes of Tremor by Type). Low doses of some sedatives (eg, alcohol) may relieve some tremors (eg, essential and physiologic tremor); higher doses may cause or exacerbate tremor.
Table 6

Some Drug Causes of Tremor by Type

Drug
Postural Tremor
Resting Tremor (Drug-Induced Parkinsonism)
Intention Tremor

Amiodarone

*

Amitriptyline

*

Amphotericin-B

β-Agonists (inhaled)*

Caffeine*

Calcitonin

Cimetidine

Cocaine*

Cyclosporine

*

Cytarabine

Epinephrine

Ethanol*


Haloperidol

*

Ifosfamide

Interferon-alfa

Lithium

*


MDMA (Ecstasy)

Medroxyprogesterone


Metoclopramide

*

Mexiletine

Nicotine

*

Procainamide

Reserpine


SSRIs*

Tacrolimus

Tamoxifen

Theophylline

*

Thioridazine

*

Thyroxine*

Valproate

*

Vidarabine


*More common cause of tremor.
MDMA = methylenedioxymethamphetamine.

Data from Morgan JC, Sethi KD: Drug-induced tremors. The Lancet Neurology 4:866–876, 2005.

Evaluation

Because the diagnosis of tremor is largely clinical, a meticulous history and physical examination are essential.

History: History of present illness should cover acuity of onset (eg, gradual, abrupt), age at onset, body parts affected, provoking factors (eg, movement, rest, standing), and alleviating or exacerbating factors (eg, alcohol, caffeine, stress, anxiety). If onset is abrupt, patients should be asked about potential triggering events (eg, recent trauma, use of a new drug).

Review of systems should seek symptoms of causative disorders, including double vision (multiple sclerosis), recent onset of motor weakness or dysarthria (stroke), headaches and fevers (brain abscess or tumor), muscle rigidity and slow movement (Parkinson's disease), weight loss and heat intolerance (hyperthyroidism), sensory deficits (peripheral neuropathy), and agitation and hallucinations (alcohol withdrawal).

Past medical history should cover conditions associated with tremor (see Table 5: Movement and Cerebellar Disorders: Some Causes of Tremor). Family history should include questions about tremor in 1st-degree relatives. The drug profile should be reviewed for causative drugs (see Table 6: Movement and Cerebellar Disorders: Some Drug Causes of Tremor by Type), and patients should be asked specifically about caffeine intake and alcohol and recreational drug use (particularly recent discontinuation).

Physical examination: Vital signs should be reviewed for tachycardia, hypertension, or fever. General examination should note any cachexia, psychomotor agitation, and presence or absence of facial expressions. The thyroid should be palpated for nodules or thyromegaly, and any signs of exophthalmus or lid lag should be noted.

Focused examination of the tremor should note distribution and frequency of the tremor while the affected body parts are at rest and fully supported (eg, in the patient's lap), while the patient assumes certain postures (eg, holding the arms outstretched), and while the patient is walking or doing tasks with the affected body part. The examiner should note whether the tremor changes during mental distraction tasks (eg, serial subtraction of 7 from 100). The quality of the voice should be observed while the patient sustains a long note.

A complete and extensive neurologic examination is mandatory and should include cranial nerve evaluation, motor and sensory function testing, gait testing, assessment of deep tendon reflexes, and evaluation of cerebellar maneuvers (eg, finger-to-nose, shin-to-heel, rapid alternating hand movements). The examiner should test muscles for rigidity by moving the limbs through their range of motion.

Red flags: The following findings are of particular concern:

Abrupt onset

Onset in people 60)
All age groups

Family history
Usually negative
Positive in > 60% of patients

Alcohol
Not beneficial
Often beneficial

Tremor onset
Unilateral
Bilateral

Muscle tone
Cogwheel rigidity
Normal

Facial expression
Decreased
Normal

Gait
Decreased arm swing
Normal or mild imbalance

Tremor latency
Longer (8–9 sec)
Shorter (1–2 sec)

Gait is observed. Gait abnormalities suggest multiple sclerosis, stroke, Parkinson’s disease, or a cerebellar disorder. The gait is often normal in patients with essential tremor. It is characteristically narrow-based and shuffling in Parkinson’s disease and wide-based and ataxic in cerebellar disorders. The gait may have histrionic or inconsistent qualities in patients with psychogenic tremor.

Complex tremor that decreases with mental distraction or whose frequency entrains to a volitional tapping rhythm in an unaffected body part (maintaining 2 different volitional movement frequencies simultaneously in 2 different body parts is difficult) suggests a psychogenic tremor.

Testing: In most patients, history and physical examination are sufficient to identify the likely etiology. However, MRI or CT of the brain should be done if

Tremor onset is acute.

Progression is rapid.

Neurologic signs suggest stroke, a demyelinating disorder, or a structural lesion.

For certain patients (based on history and physical examination findings), thyroid-stimulating hormone (TSH) and thyroxine (T4) are measured to check for hyperthyroidism, Ca and parathyroid hormone are measured to check for hyperparathyroidism, and glucose testing is done to rule out hypoglycemia.

In patients with toxic encephalopathy, the underlying condition is usually readily apparent, but measurement of BUN and ammonia levels can help confirm the diagnosis. Measurement of free metanephrines in plasma is indicated in patients with unexplained refractory hypertension; serum ceruloplasmin and urinary copper levels should be measured in patients who are < 40 and have tremor and no family history of benign tremor.

Although electromyography (EMG) can differentiate true tremor from other movement disorders (eg, myoclonus, clonus, epilepsia partialis continua), it is rarely required. However, EMG may help establish peripheral neuropathy as a potential cause of tremor if a neuropathy is clinically suspected.

Treatment

Physiologic tremors: No treatment is necessary unless symptoms are bothersome.

Physiologic tremors enhanced by alcohol withdrawal or thyrotoxicosis respond to treatment of the underlying condition.

Oral benzodiazepines (eg, diazepam

2 to 10 mg, lorazepam

1 to 2 mg, oxazepam

10
to 30 mg) given tid or qid may be useful for people with tremor and chronic anxiety, but continuous use should be avoided. Propranolol

20 to 80 mg po qid (and other β-blockers) is
often effective for tremor enhanced by drugs or acute anxiety (eg, stage fright). Primidone

50 to 250 mg po tid may be tried if β-blockers are ineffective or poorly tolerated. For some patients, a small amount of alcohol is effective.

Essential tremors: Propranolol

20 to 80 mg po qid (or other β-blockers) is often effective, as
is primidone

50 to 250 mg po tid.

Cerebellar tremors: No effective drug is available; physical measures (eg, weighting the affected limbs or teaching patients to brace the proximal limb during activity) sometimes help.

Parkinsonian tremors: The underlying disorder is treated, usually with anticholinergic drugs or other antiparkinson drugs such as amantadine

, dopamine

agonists, and levodopa.

Disabling tremor: For patients with severe, disabling, drug-refractory essential tremor, surgical management with stereotactic thalamotomy or chronic thalamic deep brain stimulation may be done. Similarly, in Parkinson's disease, tremor substantially lessens after thalamic or subthalamic nucleus deep brain stimulation. Although these techniques are widely available, they should be used only after all drug treatment options have been tried.

Geriatrics Essentials

Many elderly patients attribute development of tremor to normal aging and may not seek medical attention. Although essential tremor is more prevalent among the elderly, a thorough history and physical examination are required to rule out other causes.

Comparatively lower doses of drugs may exacerbate tremor in the elderly, and adjusting doses of chronically used drugs (eg, amiodarone

, metoclopramide

, SSRIs, thyroxine) to
the lowest effective dose should be considered. Similarly, elderly patients are more vulnerable to adverse effects of drugs used to treat tremor (eg, anticholinergic drugs); thus, drugs should be used cautiously in the elderly, usually at lower dosages than are otherwise considered optimal.

Tremor can significantly affect functional ability in the elderly, particularly if they have other physical or cognitive impairments. Physical and occupational therapy can provide simple coping strategies, and assistive devices may help maintain quality of life.

Key Points

The most common causes of tremor include physiologic tremor, essential tremor, and Parkinson's disease.

Tremor can be classified as resting, postural, or intention.

History and physical examination can typically identify the etiology of tremor.

Abrupt onset of tremor or tremor in patients who are < 50 and do not have a family history of benign tremor requires prompt, in-depth evaluation.

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