Essential tremor: Choosing the right management plan for your patient
ABSTRACTEssential tremor is a common neurologic problem seen widely at all levels of patient care. It should be differentiated from secondary causes of tremor and Parkinson disease. It can be managed with commonly used drugs. However, severe, resistant, or atypical cases should be referred to a specialist for evaluation and the possible use of botulinum toxin or deep brain stimulation.
KEY POINTS
- In addition to motor dysfunction, the tremor can also have a significant psychological impact on the patient, especially since it usually gets worse in social situations.
- Essential tremor is a clinical diagnosis. After a thorough review of the medical history and medication exposures, laboratory and imaging tests may be ordered to rule out a secondary cause.
- The two first-line agents in drug therapy for essential tremor are the nonselective beta-blocker propranolol (Inderal) and the antiepileptic primidone (Mysoline). They can be used alone or in combination.
- Botulinum toxin injection and deep brain stimulation are reserved for resistant tremor or for patients who do not tolerate drug therapy.
Secondary causes of postural-kinetic tremor
Enhanced physiologic tremor. A very mild postural tremor is present in almost all people and is considered “physiologic” since it has almost no clinical significance. This type of tremor is often invisible, but when “enhanced,” it can be visually demonstrated by placing a piece of paper over the stretched hands and watching the ripple from the paper.
Certain conditions can aggravate this physiologic tremor and can make it symptomatic. Common causes include anxiety, sleep deprivation, hypoglycemia, hyperthyroidism, pheochromocytoma, serotonin syndrome, and carcinoid syndrome.
Metabolic tremor. Hyperammonemia can cause tremor in patients with hepatic encephalopathy, and uremia can cause tremor in patients with renal failure. These metabolic conditions classically result in “flappy” tremor (asterixis), a special form of postural tremor characterized by jerking movements with high amplitude. It is best seen when the patient stretches out the arms and extends the wrists as if trying to stop traffic. But even though it may look like tremor, asterixis is thought to be a form of “negative” myoclonus.
Drug-related tremor. Postural-kinetic tremor can be induced by drugs, including lithium (Lithobid), valproate (Depakote), amiodarone (Cordarone), central nervous system stimulants, beta agonists (including inhalers), and some antidepressants. Tremor can also occur with alcohol or sedative withdrawal.
Psychogenic tremor. Tremor can be seen as part of a somatoform disorder commonly referred to as conversion disorder or conversion reaction. Psychogenic tremor is characterized by acute onset, commonly following a psychosocial stressor; it is often atypical, variable in frequency, amplitude, and body-part involvement, and it can readily be interrupted on examination by distracting the patient.
Neurologic disorders. The postural and kinetic elements of essential tremor may also be seen in the following neurologic conditions:
- Holmes (rubral) tremor, a combination of resting, postural, kinetic, and intentional tremor of low frequency and high amplitude. It usually has a proximal component and is often unilateral. It commonly is due to a lesion that involves the brainstem, eg, red nucleus, inferior olive, cerebellum, or thalamus. Common causes include stroke, prolonged hypoxia, and head trauma (including closed-head trauma with negative imaging). This type of tremor is usually associated with ataxia.14
- Dystonic tremor is predominantly postural and is associated with abnormal dystonic posturing of the affected body part, commonly the head, hands, or feet. Unlike the rhythmic oscillations of essential tremor, dystonic tremor is often irregular in rhythm.
- Multiple sclerosis can present with a combination of postural, kinetic, and intentional tremor. Patients usually have a clear history of recurrent neurologic deficits and show a combination of pyramidal, cerebellar, and sensory signs on examination consistent with multiple sclerosis.15
- Neuropathic tremor is seen in a small proportion of patients with peripheral neuropathy, especially demyelinating neuropathy.16 The tremor is usually posturalkinetic and is associated with signs of neuropathy, such as a glove-and-stocking pattern of hypoesthesia, reduced reflexes, and sensory ataxia (including intentional tremor when the eyes are closed).
- Posttraumatic tremor can occur after severe or even mild head trauma, especially in children. It is commonly rubral, but other types have been reported, including a presentation resembling essential tremor.17
- Monosymptomatic or isolated tremor. A number of conditions related to essential tremor with location-specific or task-specific tremor have been described. These rare conditions historically have been classified as “possible essential tremor” or “essential tremor variants” but are now considered separate entities. These include task-specific tremor (eg, writing tremor), isolated head tremor, isolated voice tremor, and orthostatic tremor (tremor in the legs and trunk upon standing in place, but not when sitting or walking).18,19
DIAGNOSIS IS CLINICAL
Essential tremor is a clinical diagnosis. After a thorough review of the medical history and medication exposures, laboratory and imaging tests may be ordered to rule out a secondary cause. A complete metabolic panel, including blood glucose and thyroid-stimulating hormone levels, is usually sufficient. Brain imaging or other imaging is ordered for patients with an atypical presentation.
TREATMENT IS SYMPTOMATIC
Treatment of essential tremor is symptomatic. Several drugs of different pharmacologic classes can reduce the severity of the tremor and improve function.
Choosing the appropriate treatment depends on the type of tremor and the presence of associated conditions. The response to treatment and the development of side effects guide further adjustments. The following is a brief description of the available antitremor agents.
FIRST-LINE AGENTS
Propranolol
Propranolol (Inderal), a nonselective beta blocker, is the most widely used antitremor drug and the only agent approved by the US Food and Drug Administration for essential tremor. It should be started at a low dose and titrated upward gradually. The usual starting dose is 10 mg three times daily. The average effective dose is 120 mg daily. The dose can be increased up to 320 mg if needed and tolerated.
Sustained-release preparations are equally effective and are given as a single daily dose to improve compliance.20
Propranolol improves tremor in 50% to 70% of patients with essential tremor and achieves an average tremor reduction of 50% to 60%.1,21–25 Side effects include bronchoconstriction, bradycardia, hypotension, depression, impotence, fatigue, and gastrointestinal disturbances.
Other beta-blockers, such as nadolol (Corgard) and timolol, are also effective against tremor but are less potent than propranolol.26,27 The selective beta-1-blocker metoprolol (Lopressor) may be effective and has fewer noncardiac side effects than propranolol.28 It can be used in patients who discontinue propranolol because of adverse effects. Atenolol (Tenormin) and pindolol (Visken) have little or no effect on tremor.29
A good candidate for propranolol therapy in essential tremor is:
- A patient with no known contraindication to propranolol
- A patient with hypertension, coronary heart disease, or tachyarrhythmia
- A patient with anxiety or social phobia.
Absolute contraindications to propranolol are:
- Moderate to severe bronchial asthma
- Significant bradycardia or heart block
- Symptomatic hypotension
- End-stage heart failure
- Concurrent use of a calcium channel blocker.
Relative contraindications are:
- Wheezing (eg, chronic obstructive pulmonary disease)
- Depression
- Diabetes mellitus in a patient more prone to hypoglycemia (propranolol masks the warning signs of hypoglycemia)
- Reduced sexual potency in a male patient.
