Diagnosis and Treatment of Common Forms of Tremor

Andreas Puschmann, M.D.; Zbigniew K. Wszolek, M.D.

Disclosures

Semin Neurol. 2011;31(1):65-77. 

In This Article

General Approach to an Outpatient with Tremor

Tremor Phenomenology, Terminology, and Classification

Assessment of a patient with tremor starts with the characterization of the tremor phenomenology, which narrows down the differential diagnosis and often can establish a diagnosis. Tremors can be classified according to various parameters (Table 1). The most important parameter for tremor evaluation is describing when the tremor occurs in relation to movements or position of the affected body part, distinguishing between tremor at rest (rest or resting tremor) and action tremor. This distinction helps in grouping tremors according to their pathophysiology and etiology, which in turn is highly relevant for choosing the most promising treatment option.

Tremor at rest denotes a tremor in a body part that is not voluntarily moved or maintained in a certain position against gravity, and typically occurs in Parkinson's disease (PD). The other main tremor type, action tremor, includes all tremor manifestations in body parts that are not at rest, and comprises postural tremor and kinetic tremor (Table 2). In most cases, action tremor can be easily distinguished from tremor at rest. However, patients with PD may display a tremor that reoccurs when arms are maintained stretched out for some seconds (reemerging tremor). From a physiologic standpoint, this can be considered a tremor at rest, as the body part has been held motionless in this position for a period of time. Thus, tremor that reemerges after a short period should not be classified as true postural tremor.

Other tremor characteristics are the location or distribution in the different body parts, the tremor frequency, the presence of exacerbating or alleviating factors, and the presence of other neurologic signs or symptoms (Table 1). These characteristics are rarely specific for a certain cause of tremor. For example, essential tremor may or may not improve after alcohol ingestion, but also other types of tremor may improve with alcohol.[15]

Tremor Frequency The frequency of a tremor can be approximated by observation with the naked eye, and more accurately measured with surface electromyography. The most often encountered tremors have frequencies between 4 and 12 Hz.[1] Tremor in PD usually has a slower frequency of between 3 and 5 Hz, and essential tremor and enhanced physiologic tremor range from 5 to 10 Hz. However, although there may be general differences in average tremor frequency among different types of tremors, the frequencies overlap considerably between different disorders. Thus, the exact determination of tremor frequency rarely adds decisive new information when the cause of a tremor in an individual patient is uncertain. Exceptions are unusually fast or slow tremor frequencies, which may help to establish a correct diagnosis. Tremor frequencies below 4 Hz occur in PD, cerebellar disease, Holmes' tremor (midbrain tremor), drug-induced or palatal tremors.[1] Primary orthostatic tremor has a high frequency of 12 to 18 Hz.[1] On the other hand, the clinical appearances of these syndromes are often characteristic enough for an accurate diagnosis without measuring tremor frequency.

Tremor Terminology The nomenclature of tremors is not standardized and sometimes confusing, and some terms may have different meanings. Strictly speaking, the term "intention tremor" only denotes rhythmic, oscillatory movements. However, the term is also sometimes used to describe more irregular, ataxic movements. Both represent a disturbance in the fine-tuning of goal-directed movements and point toward the cerebellum or its inflow- and outflow tracts. Similarly, the expression "dystonic tremor" usually stands for arrhythmic (i.e., the intervals between the movements are not equal) and/or irregular (i.e., amplitudes vary from one movement to the next) movements that are thus, not "tremor" according to its definition. However, both intention tremor and dystonic tremor are included in this review, as they are important differential diagnoses along with "true" tremors, and are commonly referred to as "tremors." We prefer the term "intention tremor" to "cerebellar tremor," as other types of tremor also involve the cerebellum (see below). Patients may display several types of tremor and it can be challenging to separate the single components. A general rule is to name the predominant tremor after the position in which the largest amplitude occurs. A diagnostic problem may arise when action tremor persists at rest. If an action tremor persists with the same amplitude during rest, by convention the tremor is considered an action tremor.[1]

Interview and Clinical Examination of Patients with Tremor

When assessing a patient with tremor, the type of tremor (Table 2) is characterized and other manifestations of a possible underlying neurologic disorder are actively sought. A thorough neurologic examination of a patient presenting with tremor includes the following:

Tremor at rest may be seen when observing the patient with the affected body part neither voluntarily activated nor supported against gravity. It can become more pronounced when the patient is concentrating on other tasks, e.g., when walking or during a conversation. Postural tremor that was not seen in other parts of the examination can become visible when the patient holds the upper extremities in an outstretched position with the hands supine, prone, and in the wing position (i.e., with the index fingers pointing at each other in front of the thorax but not touching). Irregular hand or finger movements in these positions are not tremor. Sudden loss of muscle tone with a sudden drop of a finger or hand, succeeded by a corrective movement back to the initial position, indicates negative myoclonus. Intention tremor is characterized by overshooting movements of increasing amplitude when approaching a goal. It can be elicited in goal-directed activities, such as finger-to-nose, heel-to-shin, and toe-to-finger movements. Observing a patient while drawing (e.g., Archimedes spirals) or writing is often helpful: Action tremor is increased during writing or drawing, and a task-specific tremor may become obvious. In PD, there usually is no tremor during writing, but other signs can be seen, such as increasing micrographia and slow movements. Pouring water from one cup into another shows the degree of disability due to kinetic tremor in a practical situation.

Important clues about an underlying neurologic disorder in patients presenting with a tremor can be found during the examination of the cranial nerves, speech, gait, balance, and muscle tone. Eye movement abnormalities may suggest cerebellar disease, and Kayser-Fleischer rings are specific for impaired copper homeostasis, although their absence does not exclude Wilson's disease. Torticollis, blepharospasm, or orofacial twitching may indicate dystonia. These signs can be very mild, in which case the patient may not be aware of any disturbance. Several movement disorders affect the fine-tuned movements of the tongue, where possible abnormal findings include fasciculations or slowness of tongue movements. Slow and irregular speech with increased separation of syllables or explosive sounds may indicate cerebellar dysarthria. Dystonia can manifest as spasmodic dysphonia, with effortful, jerky, strained sounds in the adductor type of spasmodic dysphonia, or a breathy, whispering voice with sudden breaks in the abductor type of spasmodic dysphonia. Typical parkinsonian or cerebellar gait may be noted, and muscular rigidity in combination with a tremor at rest is typical for PD, whereas spasticity may develop in multiple sclerosis.

As with other movement disorder symptoms, the severity of a patient's tremor may wax and wane considerably over time, and is influenced by the patient's emotional state. Although the opposite may be true, generally action tremors will be more severe during an office visit (which usually is accompanied by some uneasiness or anxiety), and tremors at rest will become less obvious or not visible at all. Thus, observations made during a short office visit may be misleading, and information from the patient (or proxy) is important.

Identifying Drugs and Toxins that May Cause Tremor

The list of medications and toxins that can cause tremor is long. A comprehensive history must include all medications that a patient is taking, as well as possible exposure to toxins. Table 3 summarizes the most common medications and toxins that cause tremor. If in doubt, reports of the given drug inducing and/or exacerbating tremor should be sought. For most of these medications, tremor is a dose-dependent side effect and will disappear as the dose is decreased or the medication discontinued. In a patient who is treated with lithium or valproate sodium and who develops tremor, the serum concentrations of these substances should be determined. Some individuals may consume coffee, tea, or other stimulants in unusually high amounts, which can be a sufficient explanation for pronounced tremors. Hyperthyroidism and hypoglycemia may also cause tremor.

Ancillary Testing in the Assessment of Tremor Patients

In the outpatient setting, the clinical features and neurologic examination findings are the most important assessment tools in evaluating patients with tremor. Extensive laboratory testing is usually not necessary. For routine evaluation, thyroid function tests are performed in most or all patients with tremor to exclude hyperthyroidism. In patients under 55 years, serum and urine tests for Wilson's disease may be indicated. Serum ceruloplasmin as well as serum and urine copper levels can exclude Wilson's disease with reasonable sensitivity, but when they give ambiguous or negative results and a clinical suspicion of Wilson's disease remains, other test methods need to be considered.[16–18] Further studies are warranted in individual patients where a rare cause of the tremor is suspected, but these will rarely be used in the initial workup of a tremor outpatient.

Nonpharmacologic Treatment

Various nonpharmacologic treatment options for tremor are available, most of which are not specific for a tremor of a certain etiology. Coping strategies form an integral part in the care of a tremor patient. Simple advice may sometimes be helpful, such as avoiding the use of a computer mouse or laser pointer, which magnify tremor movements, in situations where this is embarrassing. The patient can be encouraged to inform others openly about his or her propensity to tremors and about their benign nature. Some patients may seek medical advice because of concerns that the tremor may be the first sign of a severe disorder such as PD, amyotrophic lateral sclerosis, or a brain tumor. Such patients may not need medical treatment, but feel comfortable after reassurance that their tremor does not herald a more severe disorder. Counseling should include stressing the benign natural course of a particular tremor when appropriate. Agents that are suspected to cause or worsen a tremor should be removed whenever possible. Nonpharmacologic symptomatic treatment options include the use of larger utensil handles or wrist weights, or occupational assessments and advice.[19,20] Positive effects of biofeedback, acupuncture, and whole body sound wave vibration therapy on tremor have been reported.[21–23]

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