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Home , Essential tremor, Intention tremor, Movement disorder, Tremor

PROBLEM-ORIENTED DIAGNOSIS

Tremor SHARON SMAGA, M.D., Southern Illinois University School of Medicine, Carbondale, Illinois

Tremor, a rhythmic, involuntary, oscillatory movement of body parts, is the most com- mon . are classified as rest or action tremors. Rest tremor O A patient informa- occurs when the affected body part is completely supported against gravity. Action tion handout about , writ- tremors are produced by voluntary and are further divided into ten by the author of postural, isometric, or kinetic tremors. This article describes clinical signs and symp- this article, is provided toms of six tremor syndromes, including physiologic tremor, essential tremor, Parkin- on page 1553. son’s disease, toxic and -induced tremor, cerebellar tremor, and psychogenic tremor, and presents a detailed diagnostic approach to tremor. Although new tech- nologies such as positron emission tomography and single photon emission computed tomography are under investigation for possible use in diagnosing specific tremor syn- dromes, they have no widespread applicability or use at this time. The history and physical examination remain the most important diagnostic tools available to clini- cians in identifying and classifying tremor syndromes. (Am Fam Physician 2003;68: 1545-52,1553. Copyright© 2003 American Academy of Family Physicians.)

Members of various remor—a rhythmic, involun- into postural, isometric, or kinetic tremors. family practice depart- tary, oscillatory movement of Postural tremor occurs when the affected ments develop articles body parts1—is the most com- body part maintains position against gravity for “Problem-Oriented 2 Diagnosis.” This article mon movement disorder. The (e.g., extending arms in front of body). Iso- is one in a series coor- diagnosis is based on a careful metric tremor results from muscle contrac- dinated by the Depart- Tassessment of the history and physical exami- tion against stationary objects (e.g., squeezing ment of Family Medi- nation, although some tests, including the examiner’s fingers). Kinetic tremor, which cine at the Southern positron emission tomography (PET) and occurs with voluntary movement, is either Illinois University School of Medicine, single photon emission computed tomogra- simple kinetic tremor or . Springfield, Illinois. phy (SPECT), are being investigated as diag- Simple kinetic tremor is associated with Guest editor of the nostic aids.2-5 This article reviews the classifi- movement of extremities (e.g., pronation- series is John G. cation and causes of tremor and provides supination or flexion-extension wrist move- Bradley, M.D. evaluation guidelines. ments). Intention tremor occurs during visu- ally guided movement toward a target (e.g., Classification finger-to-nose or finger-to-finger testing), Tremors are classified as rest or action with significant amplitude fluctuation on tremors. Rest tremor occurs when the affected approaching the target2 (Table 1).1,6 body part is completely supported against grav- Although this classification helps in deter- ity (e.g., hands resting in the lap). Amplitude mining cause, the presentation of tremor syn- increases during mental (e.g., counting dromes varies. Other aspects of the history backwards) or with general movement (e.g., and physical examination should be consid- ) and diminishes with target-directed ered when evaluating patients with tremor. movement (e.g., finger-to-nose test).1,2,6 Action tremors are produced by voluntary Tremor Syndromes muscle contraction. They are further divided PHYSIOLOGIC TREMOR All normal persons exhibit physiologic tremor, a benign, high-frequency, low-ampli- All normal persons exhibit physiologic tremor, a benign, tude postural tremor. Usually invisible to the naked eye, it can be amplified by holding a high-frequency, low-amplitude postural tremor. piece of paper on the outstretched hand or pointing a laser at a distant screen.1,2

Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright© 2003 American Academy of Family Physicians. For the private, noncommercial use of one individual user of the Web site. All other rights reserved. kinetic component.1 It is the most common Essential tremor is the most common movement disorder in movement disorder worldwide; prevalence the world, ranging from 4.1 to 39.2 cases per 1,000 persons ranges from 4.1 to 39.2 cases per 1,000 per- sons, to as high as 50.5 per 1,000 in persons younger than 60 years. older than 60 years.8 These figures may underestimate the true prevalence, however, because up to 50 percent of persons with mild Enhanced physiologic tremor is a visible, essential tremor are unaware of it.9 Reports of high-frequency postural tremor that occurs in family history vary widely, with 21.7 percent the absence of neurologic disease and is of patients in one study9 and 62 percent in caused by medical conditions such as thyro- another study10 reporting a family history of toxicosis, , the use of certain tremor. , or withdrawal from or benzo- Essential tremor develops insidiously and diazepines. It is usually reversible once the progresses slowly, presenting as a postural, cause is corrected1,2 (Table 2).6,7 distal arm tremor in 95 percent of patients. Onset peaks bimodally in the teens and 50s. ESSENTIAL TREMOR The tremor may start in a single limb, but it Essential tremor is a visible postural tremor becomes bilateral over time, most often as a of hands and forearms that may include a flexion-extension movement of the wrist with

TABLE 1 Classification and Characteristics of Tremor

Type of tremor Frequency Amplitude Occurrence Examples

Rest tremor Low to medium High; decreases with Limb supported against Parkinson’s disease; drug-induced (3 to 6 Hz) target-directed gravity; muscles are not (neuroleptics; movement activated [Reglan]) Action tremor — — Any voluntary muscle contraction Postural tremor Medium to high Low; increases with Limb maintains position Physiologic tremor; essential (4 to 12 Hz) voluntary movement against gravity tremor; metabolic disturbance; drug or alcohol withdrawal Kinetic tremor Simple kinetic Variable (3 to Does not change with Simple movements of — 10 Hz) target-directed the limb movement Intention Low (< 5 Hz) Increases with target- Target-directed movement Cerebellar (, multiple directed movement sclerosis, tumor); drug-induced (, alcohol) Isometric tremor Medium Variable Muscle contraction against Holding a heavy object in stationary objects one hand Task-specific Variable (4 to Variable Occurs with specific action Handwriting tremor; musician’s tremor 10 Hz) tremor

Information from references 1 and 6.

1546 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 68, NUMBER 8 / OCTOBER 15, 2003 Tremor TABLE 2 Potential Effects of Drugs on Physiologic Tremor

May exacerbate physiologic tremor May reduce physiologic tremor Lithium Alcohol Beta- agonists (Ritalin) (albuterol [Proventil]) Pseudoephedrine Beta-adrenergic antagonists sulfate (Brethine) ( [Inderal]) (Tegretol) (Mysoline) Thyroid hormones (Prozac) Tricyclic (Haldol) Valproic acid (Depakene) Hypoglycemic agents

Information from references 6 and 7.

a frequency of 4 to 12 Hz. It may involve the tural reflexes are examined by the pull test: the head, appearing as a yes-yes or no-no head patient stands with arms hanging loosely at movement. Amplitude increases with stress, the sides; from behind, the examiner holds the fatigue, and certain such as cen- patient’s upper arms just under the shoulders tral , and may and gently pulls backward; if the patient increase with certain voluntary activities such begins to fall, postural instability is indicated12 as holding a fork or cup. Rest, beta blockers, (Table 3).16 primidone (Mysoline), and alcohol ingestion decrease the tremor.2,10,11 CEREBELLAR TREMOR Cerebellar tremor presents as a unilateral or PARKINSON’S DISEASE bilateral, low-frequency (less then 5 Hz) inten- Parkinson’s disease (PD) is 20 times less tion tremor caused by stroke, tumor, common than essential tremor.8 Nevertheless, or .2,17 It may include postural approximately 1 million Americans have PD.12 tremor.1 Classically, cerebellar produce Because specific treatment options are avail- able, accurate diagnosis is essential.2,6,12,13 Symptoms develop insidiously, often after TABLE 3 age 50, although early-onset disease may Comparison of Essential Tremor and Parkinson’s Disease appear in the 20s.13 Initial symptoms include resting tremor beginning distally in one arm Clinical features Parkinson’s disease Essential tremor at a 4- to 6-Hz frequency. Typically, the tremor Age at onset > 50 years Bimodal: teens and 50s is a flexion-extension elbow movement, a Gender Men more than women Men and women equal pronation-supination of the forearm, or a pill-rolling finger movement. It worsens with Family history > 25 percent > 90 percent stress and diminishes with voluntary move- Asymmetry Affects ipsilateral limbs Often symmetric ment. It may have postural or kinetic compo- at first nents.2,12 However, 10 to 20 percent of patients Character At rest Postural, kinetic have no tremor during the course of PD.2,14 Frequency 4 to 6 Hz 4 to 10 Hz Other signs of PD include rigidity, bradyki- Distribution Hands, legs Hands, head, voice nesia, and impaired postural reflexes. The Effect of alcohol Unaffected Reduced by alcohol physician may note cogwheel rigidity (i.e., on tremor ratchet-like resistance) during passive range of Associated findings Bradykinesia, rigidity, — motion while examining the extremities. postural instability Bradykinesia includes a slow, shuffling gait, decreased arm swing with walking, difficulty Adapted with permission from Jankovic J. Essential tremor: clinical characteris- rising from a seated position, and reduced . 2000;54(11 suppl 4):S24. facial animation (masked facies).12,13,15 Pos-

OCTOBER 15, 2003 / VOLUME 68, NUMBER 8 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1547 Drug-induced tremor commonly occurs after use of sympatho- TABLE 4 mimetics such as pseudoephedrine, bronchodilators, or theo- Common Causes of Drug-Induced Tremor phylline, and antidepressants such as tricyclics or fluoxetine. Postural tremor Amiodarone (Cordarone), amphetamines, beta- adrenergic agonists (albuterol [Proventil]), caffeine, kinetic tremor on the ipsilateral side of the calcitonin (Salmonine, Miacalcin), , cyclosporine (Sandimmune), (Intropin), body. Finger-to-nose, finger-to-finger, and lithium, procainamide (Pronestyl), steroids, heel-to-shin testing results in worsening tremor theophylline, thyroid hormones, tricyclic as the extremity approaches the target.2 Other antidepressants, valproic acid (Depakene) signs include abnormalities of gait, speech, and Intention tremor ocular movements; inability to perform rapid Alcohol (chronic), 6 alternating hand movements; and titubation, a Rest tremor postural tremor of the trunk and head.5 Metoclopramide (Reglan), neuroleptics (haloperidol [Haldol], trifluoperazine [Stelazine]) DRUG-INDUCED AND TOXIC TREMORS Drug-induced tremor may follow ingestion Adapted with permission from Deuschl G, Bain P, of certain drugs (Table 4)1;toxic tremors Brin M. Consensus statement of the Movement Dis- occur following intoxication. Tremors also are order Society on Tremor. Ad Hoc Scientific Commit- tee. Mov Disord 1998;13(suppl):13. present during withdrawal from certain drugs and alcohol.1 The most common drug-induced tremor is enhanced physiologic tremor following use of with serum concentration, lithium toxicity sympathomimetics such as pseudoephedrine, may cause permanent damage to the cerebel- bronchodilators, or theophylline, and antide- lum that precipitates postural and intention pressants such as tricyclics or fluoxetine tremors. Amiodarone (Cordarone) may cause (Prozac).1,7 This tremor also may accompany a dose-dependent reversible neurologic syn- withdrawal.2,7 Approximately drome consisting of postural tremor, , 25 percent of patients taking long-term val- and ; symptoms proic acid (Depakene) therapy exhibit postural develop in the first week of treatment and tremor three to 12 months after starting ther- improve following dosage reduction or dis- apy. Lowering the dosage decreases the tremor.2 continuation. One study2 failed to demon- Lithium can induce a fine postural tremor strate that moderate caffeine intake causes or of the hands (8 to 12 Hz). Directly correlated exacerbates tremor. Neuroleptic agents such as haloperidol (Haldol) or dopamine–recep- tor-blocking drugs like metoclopramide (Reglan) may induce parkinsonian tremor.7 The Author Acute alcohol intake temporarily reduces SHARON SMAGA, M.D., is associate professor in the Department of Family and Com- physiologic and essential tremors,2,16 while munity Medicine at Southern Illinois University School of Medicine in Carbondale, Ill. She received her medical degree from the University of Chicago and completed three alcohol withdrawal may cause postural years of residency training at Southern Illinois University School of Medicine, Carbon- tremor.18 Chronic may produce dale Family Practice Center, in Carbondale. She has a certificate of added qualification cerebellar tremor1,5 (Table 4).1 in geriatric medicine.

Address correspondence to Sharon Smaga, M.D., Southern Illinois University School of PSYCHOGENIC TREMOR Medicine, Department of Family and Community Medicine, SIU Family Practice Center, 305 West Jackson, Suite 200, Carbondale, IL 62901 (e-mail: [email protected]). Psychogenic tremor presents as a variable Reprints are not available from the author. tremor that may decrease or disappear when

1548 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 68, NUMBER 8 / OCTOBER 15, 2003 Tremor

not under direct observation, or with psy- occasionally presenting during childhood chotherapy or placebo. The patient is asked to include essential, enhanced physiologic, and tap a with the limb contralateral to the primary writing tremors, and tremor follow- tremulous limb: if the tremor decreases or ing severe head .20 shifts to the frequency of the tapping (i.e., A rare but important cause of tremor in the entrainment), psychogenic tremor is sus- young is Wilson’s disease, an inborn error of pected.19 Co-activation of antagonistic mus- copper metabolism that can be fatal if left cles of the tremulous limb may be detected untreated. Symptoms begin between 11 and clinically or electrophysiologically.19 25 years of age, although they may present as early as 4 years of age. Tremor may be of the UNCOMMON TREMOR SYNDROMES intention type or, more commonly, a wing- AND TREMORS IN CHILDREN beating movement when the arm is abducted Less common tremors include primary at the shoulder. Other signs are findings writing and other task-specific tremors17; related to liver dysfunction and ring-shaped tremor secondary to peripheral neuropathies; copper pigmentation in the cornea, called and primary orthostatic tremor.1,2 Tremors Kayser-Fleischer rings21 (Table 5).3

TABLE 5 Clinical and Diagnostic Features of Tremor Syndromes

Tremor syndrome Clinical features Diagnostic tests

Enhanced physiologic Postural tremor: absence of neurologic disease Chemistry profile (glucose, liver function tests); tremor thyroid function tests; review of medications Essential tremor Postural tremor: affects arms and head; increases No specific test; rule out other problems with with stress, fatigue, and stimulants; increases with general chemistry profile, CBC, and thyroid voluntary activities; decreases with alcohol; function tests. responds to , primidone (Mysoline) Parkinson’s disease Resting tremor: increases with stress, decreases with No testing needed for typical presentation; voluntary movement of limb, responds to MRI for atypical presentations; consider PET or dopaminergic agents; bradykinesia, rigidity, SPECT scanning, if available. impaired postural reflexes Cerebellar tremor Intention tremor (same side of body as the lesion); CT scan or MRI; examination abnormal heel-to-shin testing, rapid alternating for IgG gamma globulins (if multiple sclerosis is hand movements; gait abnormalities; suspected); screen for alcohol abuse (if suspected); (speech problems); check lithium level if lithium toxicity is suspected. Psychogenic tremor Variable (resting, postural, or intention): increases Electrophysiologic testing under direct observation, decreases with distraction, changes with voluntary movement of contralateral limb; somatization in past history Wilson’s disease Wing-beating tremor: ascites, jaundice, signs of hepatic Liver function tests; serum ceruloplasmin; urine disease; intracorneal ring-shaped pigmentation; copper; slit-lamp examination rigidity, muscle ; mental symptoms

CBC = complete blood count; MRI = magnetic resonance imaging; PET = positron emission tomography; SPECT = single photon emission computed tomography; CT = computed tomography. Information from reference 3.

OCTOBER 15, 2003 / VOLUME 68, NUMBER 8 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1549 uneven gait (falling to one side). Multiple scle- Diagnostic Approach rosis is suspected if the tremor is associated A thorough history should explore onset, with visual disturbances and diverse neuro- exacerbating and relieving factors, medica- logic symptoms and signs. The physician tions, family history, and associated symp- should check for evidence of chronic alco- toms. It also should assess functional limita- holism, including spider angiomata, gyneco- tions including job-related disabilities, social mastia, enlarged liver, or abnormal blood test embarrassment, and difficulty with holding a results (elevated mean corpuscular volume or cup or with handwriting. -glutamyl transferase level). Observation is the initial step in the physical Postural tremor can be relatively constant examination. The physician observes the or episodic, and of acute or insidious onset. It patient sitting with hands resting in the lap or should be noted whether stress or fatigue standing with arms at the sides. When seeking increases the amplitude of the tremor. If evidence of postural tremor, the physician asks weight loss, irritability, racing heart, or the patient to extend the arms and perform the swelling is described, the patient should be finger-to-nose or finger-to-finger movement examined for thyroid enlargement, exophthal- to identify an intention tremor. It is useful to mos, brisk reflexes, and tachycardia. The thy- observe the patient drinking from a glass, writ- roid-stimulating hormone level is checked to ing, or drawing a rhythmic pattern such as a rule out . spiral. The tremor should be classified as to Tremor occurring three to four hours after body part (arms, head), activation condition eating may suggest hypoglycemia. Other signs (when the tremor is present), frequency (fast of hypoglycemia include altered sensorium, or slow), and amplitude (fine or coarse). sweating, and pallor. A blood glucose test or a In the examination of a patient with resting glucose tolerance test performed while the tremor, the physician checks for rigidity and patient is having symptoms may be appropri- bradykinesia by flexing and extending the ate. Tremor in conjunction with feelings of patient’s arms, seeking signs of cogwheel rigid- suffocation, chest tightness, and racing heart ity. Tremor and rigidity may become more may indicate . pronounced if patients perform voluntary Hand tremor, disturbance, irritability, movements with the opposite limb (e.g., the sweating, nausea, and difficulty with concen- patient draws a circle in the air with the oppo- tration may indicate benzodiazepine with- site hand). The patient is asked to stand and to drawal.5,7 The physician should ask about the walk, thus displaying evidence of difficulty ini- patient’s use of prescription or over-the- tiating movement, reduced arm swing, or counter medications that are known to cause shuffling gait. If PD is suspected, a trial of ther- tremor. Essential tremor is indicated if the apy with a dopaminergic agent such as levo- examination is normal except for postural dopa-carbidopa (Sinemet) is appropriate. tremor and a positive family history (Figure 1). Referral to a neurologist is indicated when patients fail to respond to the or Special Studies demonstrate an atypical presentation. While it is reasonable to order routine In patients with intention tremor, the physi- chemistry, hematology, and thyroid function cian asks about the onset of symptoms. If the tests in the evaluation of a patient with tremor, tremor is caused by stroke, onset is usually other testing depends on the tremor’s sus- acute, and the patient may appear ill and com- pected etiology.3 Liver function tests are help- plain of , vertigo, and difficulty with ful in young patients with non–drug-induced balance. The physician observes for nystag- tremor. In patients with Wilson’s disease, mus, difficulty with speech or swallowing, and 24-hour urine copper and serum ceruloplas-

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Evaluation of Tremor

Resting Postural Kinetic Patient taking medications Patient taking medications Task-specific (handwriting, that may cause tremor? that may cause tremor? occupational)?

Yes No Yes No Yes No

Possible drug- Other signs of Possible drug- History of Task-specific Intention induced Parkinson’s disease induced alcohol kinetic tremor parkinsonism (rigidity, bradykinesia, tremor abuse? tremor postural instability)? History of chronic Trial off drug Trial off alcoholism? Yes No medication Yes No Possible alcohol Other signs or Yes No withdrawal symptoms of Classic Possible early tremor systemic disease? Parkinson’s Parkinson’s disease disease Alcohol History of tremor lithium toxicity? Yes No Trial of Monitor dopaminergic agent Enhanced Essential Yes No physiologic tremor tremor Toxic MRI/CT of Trial of beta tremor head to Test for hyperthyroidism, blocker, rule out hypoglycemia, panic primidone stroke, attack, benzodiazepine (Mysoline) tumor, withdrawal multiple sclerosis

FIGURE 1. Algorithm for evaluating tremor. (MRI = magnetic resonance imaging, CT = computed tomography) min determinations are helpful. Cerebrospinal tomographic scan or an MRI is more impor- fluid examination for oligoclonal IgG bands is tant in cases of intention tremor, when , appropriate in patients suspected of having tumors, and multiple sclerosis are suspected. multiple sclerosis. PET and SPECT scanning have demon- In some PD patients, magnetic resonance strated decreased uptake in the brains of imaging (MRI) studies have shown a narrow- patients with Parkinson’s disease, mainly in ing of the high signal region between the red the posterior , and may assist in the nucleus and the . However, evaluation of rest tremor.3,15 Studies of SPECT patients with characteristic presentations and scanning as a tool for evaluating isolated pos- positive responses to anti-Parkinson medica- tural tremor are mixed, with one study4 tion do not require such imaging.3 A computed demonstrating no difference in uptake, and a

OCTOBER 15, 2003 / VOLUME 68, NUMBER 8 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1551 Tremor

review of other studies5 indicating significant 7. Cooper G, Rodnitzky R. The many forms of tremor. Precise classification guides selection of therapy. differences in uptake or activation. At this Postgrad Med 2000;108:57-8,61-4,70. time, functional imaging with PET or SPECT 8. Louis ED, Ottman R, Hauser WA. How common is scanning is not widely available and is consid- the most common adult movement disorder? Esti- mates of the prevalence of essential tremor ered to be of little clinical use in evaluating throughout the world. Mov Disord 1998;13:5-10. 3 tremor. 9. Elble RJ. Tremor in ostensibly normal elderly peo- Other evaluation tools include surface elec- ple. Mov Disord 1998;13:457-64. 10. Lou JS, Jankovic J. Essential tremor: clinical corre- tromyography, accelerometers, potentiome- lates in 350 patients. Neurology 1991;41(2 pt 1): ters, handwriting tremor analysis, and long- 234-8. term tremor records.1,3 These tools generally 11. Evidente VG. Understanding essential tremor. Dif- ferential diagnosis and options for treatment. Post- are used in research or specialty centers and grad Med 2000;108:138-40,143-6,149. are not used routinely in the office setting. 12. Uitti RJ. Tremor: how to determine if the patient has Parkinson’s disease. Geriatrics 1998;53:30-6. The author indicates that she does not have any con- 13. Young R. Update on Parkinson’s disease. Am Fam Physician 1999;59:2155-67,2169-70. flicts of interest. Sources of funding: none reported. 14. Gelb DJ, Oliver E, Gilman S. Diagnostic criteria for Parkinson disease. Arch Neurol 1999;56:33-9. REFERENCES 15. Waters CH. Diagnosis and management of Parkin- son’s disease. 2d ed. Caddo, Okla.: Professional 1. Deuschl G, Bain P, Brin M. Consensus statement of Communications, 1999:55-82. the Movement Disorder Society on Tremor. Ad Hoc 16. Jankovic J. Essential tremor: clinical characteristics. Scientific Committee. Mov Disord 1998;13(suppl Neurology 2000;54(11 suppl 4):S21-5. 3):2-23. 17. Hallett M. Classification and treatment of tremor. 2. Zesiewicz TA, Hauser RA. Phenomenology and JAMA 1991;266:1115-7. treatment of tremor disorders. Neurol Clin 2001; 18. Koller W, O’Hara R, Dorus W, Bauer J. Tremor in 19:651-80,vii. chronic alcoholism. Neurology 1985;35:1660-2. 3. Anouti A, Koller WC. Diagnostic testing in move- 19. Brown P, Thompson PD. Electrophysiological aids ment disorders. Neurol Clin 1996;14:169-82. to the diagnosis of psychogenic jerks, spasms, and 4. Lee MS, Kim YD, Im JH, Kim HJ, Rinne JO, Bhatia KP. tremor. Mov Disord 2001;16:595-9. 123I-IPT brain SPECT study in essential tremor and 20. Haslem RA. Movement disorders. In: Behrman RE, Parkinson’s disease. Neurology 1999;52:1422-6. Kliegman RM, Jenson HB, eds. Nelson Textbook of 5. Boecker H, Brooks DJ. Functional imaging of pediatrics. 16th ed. Philadelphia: Saunders, 2000: tremor. Mov Disord 1998;13(suppl 3):64-72. 1842. 6. Charles PD, Esper GJ, Davis TL, Maciunas RJ, 21. Menkes JH. Disorders of metal metabolism. In: Robertson D. Classification of tremor and update Rowland LP, ed. Merritt’s Textbook of neurology. on treatment. Am Fam Physician 1999;59:1565-72. 9th ed. Baltimore: Williams & Wilkins, 1995:584-9.

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