INTRODUCTION ? Tremor is defined as a rhythmic and oscillatory movement of a body part with a relatively constant frequency and variable amplitude. It is caused by either alternating or synchronous contractions of antagonistic muscles. Tremor is the most common of all movement disorders, occurring from time to time in most normal individuals in the form of exaggerated physiologic tremor [1].
This topic will cover the classification, clinical features, diagnostic evaluation, and treatment of tremor.
The treatment of essential tremor (ET) is discussed separately. (See "Pharmacologic treatment of essential tremor" and see "Surgical treatment of essential tremor").
CLASSIFICATION ? Tremors may be broadly classified into static and action tremors (show table 1). Static tremors are further divided into those occurring at rest (resting tremor) and those occurring with the head and limbs held in a fixed posture (postural tremor) (show table 2 and show table 3). Action tremors remain unchanged during the course of a voluntary movement, while intention tremors increase during the course of goal-directed movement.
RESTING TREMOR ? Parkinson's disease (PD) and other parkinsonian syndromes are the most common causes of resting tremor. The tremor is evident with the affected body part supported and completely at rest and temporarily dampens or disappears during voluntary activity. Resting tremors usually fluctuate in amplitude and may appear and disappear depending upon the degree of patient repose, whether the patient feels he or she is under observation, and other unknown factors.
The resting tremor is typically less disabling than postural, action, or intention tremors because of its absence during voluntary activity. However, the tremor quickly reappears as soon as the body part assumes a new resting posture and may therefore interfere with the use of eating utensils, handwriting, and other purposeful movements. It also usually is activated during walking. In most cases, if resting tremor is a handicap or disability, it is because of a cosmetic and not a functionally limiting effect.
POSTURAL AND ACTION TREMORS ? Postural and action tremors comprise the largest group of tremors. They are elicited during examination under two circumstances: with the arms suspended against gravity in a fixed posture; and during the course of goal-directed activity.
Physiologic tremor ? Normal individuals have a very low amplitude, high frequency physiologic tremor of approximately 10 to 12 Hz that is not visible under ordinary circumstances. Many factors can enhance the tremor to the point of detection, most often by increasing sympathetic activity [1].
Common drugs that increase adrenergic activity include beta-adrenergic agonists such as terbutaline, isoproterenol, epinephrine, amphetamines, selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants, levodopa, nicotine, and xanthines such as theophylline and caffeine.
Anxiety, excitement, fright, muscle fatigue, hypoglycemia, alcohol and opioid withdrawal, thyrotoxicosis, fever, and pheochromocytoma also enhance adrenergic activity.
Miscellaneous drugs and toxins that increase physiological tremor by other uncertain means include lithium, corticosteroids, sodium valproate, bromides, mercury, lead, and arsenic.
Enhancement of physiologic tremor is the most common cause of postural and action tremors. Thus, a medical rather than primary neurologic cause for postural-action tremor should be considered in most cases.
Essential tremor ? Essential tremor (ET) is the most common neurologic cause of postural or action tremor, with an estimated prevalence worldwide of up to 5 percent of the population [3-5]. The incidence of ET increases with age, although it often affects young individuals, especially when it is familial. By definition, tremor should be the only neurologic manifestation of ET; however, in some severe cases mild gait disorder and cerebellar signs may be present.
ET is referred to as familial tremor when there is a family history (approximately 50 percent of cases have an autosomal dominant pattern of inheritance) and benign essential tremor when it is sporadic. However, the use of "benign" as a modifier for ET has historically been employed only to distinguish it from PD and is best omitted, since the tremor can be severe and disabling [6].
ET appears to be genetically heterogeneous. A dominantly inherited form of ET has been genetically linked to two loci, ETM1 (on chromosome 3q13) [7] and ETM2 (on chromosome 3p24.1) [8,9]. However, other families with ET are not linked to either locus [10]. First-degree relatives of patients with ET have an increased risk of developing the disorder, particularly when the proband develops the disorder at an early age [11]. However, the lack of 100 percent concordance among monozygotic twins suggests that environmental factors may also play a role in the pathogenesis of the disease [12].
The neuropathologic basis for ET is unknown [13]. However, neuropathologic study of a single patient with severe ET and no signs of parkinsonism revealed the presence of multiple Lewy bodies in the locus coeruleus but no Lewy bodies in the substantia nigra [14]. The significance of this finding is uncertain, and further neuropathological information is needed.
The relative contribution of peripheral and central pathophysiologic mechanisms in ET is also uncertain.
Some patients with ET develop enhanced physiologic tremor due to anxiety or other adrenergic mechanisms, thereby aggravating the underlying tremor. ET is typically relieved by small amounts of alcohol. Physiologic tremor is aggravated by caffeine.
ET most often affects the hands and arms and can be asymmetric. It can also affect the head, voice, chin, trunk, and legs (show table 4) [15]. Tremor becomes immediately apparent in the arms when they are held outstretched; it typically increases at the very end of goal-directed movements such as drinking from a glass or finger-to-nose testing. Cerebellar outflow tremor should be considered when the tremor oscillations increase steadily before arriving at the target rather than at the termination of goal-directed activity, although a distinction between the two is often difficult.
Tremor in the legs is unusual in ET. Head tremor may be vertical ("yes-yes") or horizontal ("no-no") and, although usually associated with hand or voice tremor, can be the predominant or only manifestation of ET in some patients.
The most common differential diagnosis is with parkinsonian tremor (show table 5). Differentiation from classical resting tremor should be straightforward; however, some patients with PD also have a postural-action tremor indistinguishable from ET [16]. Likewise, patients with severe ET may have a rest component to their tremor. The presence of subtle bradykinesia or micrographia in early cases of parkinsonian postural tremor helps make the diagnosis, although these signs may not appear until later on. Conversely, elderly patients with ET may have mild bradykinesia and limb rigidity as a nonspecific accompaniment of aging.
Head tremor is more likely to be a manifestation of ET, whereas tremor of the jaw or lips is more typically parkinsonian. However, head tremor is also common in cervical dystonia (spasmodic torticollis) where it may be due either to a coincidence of the two disorders or to a manifestation of dystonic muscle spasm.
Ataxia, dysmetria, proximal distribution of the tremor, or gait disorder usually suggests a cerebellar disorder rather than ET. However, mild cerebellar signs are present in some severe familial tremors (show table 6) [17]. Voice tremor rarely occurs in isolation; when it does, it should be differentiated from spasmodic dysphonia. Essential voice tremor produces a quavering voice unaccompanied by the hoarseness, straining, and voice breaks characteristic of spasmodic dysphonia.
Primary writing tremor ? Many action tremors are particularly severe during the act of writing. Tremor that occurs exclusively while writing and not during other voluntary motor activities is referred to as primary writing tremor [18]. This tremor is limited to the hand and causes relatively large amplitude supination-pronation movements at a frequency of 5 to 6 Hz. The low frequency and large amplitude of the tremor, its frequent occurrence in writer's cramp or writer's dystonia, its relative resistance to propranolol, and its occasional response to anticholinergic drugs suggest a closer relationship to dystonia than to ET.
Orthostatic tremor ? Orthostatic tremor is limited to the legs and trunk and occurs exclusively while standing [19]. Both high and low frequency orthostatic tremors have been described; their relationship to ET is uncertain. In cases of high frequency tremor, movements of the legs may be so low in amplitude that they initially escape clinical detection. Orthostatic tremor is uniquely, but not always, responsive to treatment with clonazepam (see "Treatment" below).
Cerebellar tremors ? Cerebellar tremors can be postural, action, or intention (kinetic). In severe cases, they can spill over to occur at rest. Tremor frequency is typically low (3 to 4 Hz) and can be associated with ataxia and dysmetria.
Rubral tremor is caused by disturbances of cerebellothalamic projections (see "Rubral tremor" above); it is usually present at rest and increases during postural fixation and voluntary activity. Titubation of the head and neck ("to and fro" movements) may be associated with cerebellar tremor; it is distinguished from essential head tremor by the presence of other cerebellar findings.
PSYCHOGENIC TREMOR ? Useful criteria for diagnosis of psychogenic tremor have been established [20,21]. These are typically complex resting, postural, and action tremors with abrupt onset, a static course, changeable features, functional disability out of proportion to tremor magnitude, and resistance to treatment. Any body part may be involved, but, remarkably, the fingers are often spared [21]. Other features of psychogenic movement disorders are usually present, such as symptoms that are inconsistent and clinical features that are incongruous with known tremors.
Examination usually shows variable tremor frequency or tremor entrainment, especially with distraction maneuvers such as repetitive tapping tasks with an uninvolved or opposite hand or foot.
EVALUATION ? The diagnostic approach to patients with tremor involves the history, physical examination, and selected laboratory studies. Action tremor is most common and, of these, essential tremor (ET) and enhanced physiologic tremor are the most frequent diagnoses [22]. Patients with tremor due to other disorders such as hyperthyroidism, Parkinson's disease (PD), dystonia, or Wilson's disease, frequently have additional signs or symptoms that help point to the diagnosis, although this is not always the case. The criteria for ET and methods for distinguishing it from other tremors are shown in the tables (show table 1, show table 2, and show table 3).
History ? The history concerning the onset of tremor is usually straightforward, since it is a highly visible symptom that is readily evident to the patient and family members. Examination of previous handwriting samples may be useful in determining the precise time of onset. Precipitating, aggravating, or relieving factors such as caffeine, alcohol, medications, exercise, fatigue, or stress should be elicited; a complete list of all medications should be reviewed to exclude the possibility of enhanced physiologic tremor (see "Physiologic tremor" above).
Family history in ET reflects an autosomal dominant pattern of inheritance in approximately half of all patients. Parkinsonian tremor is usually sporadic, but a family history of PD is present in approximately 15 percent of cases; the disease affects first-degree relatives (parents, siblings or offspring) in about half of the familial cases. Autosomal PD affecting three or more generations is rare.
Examination ? Examination begins with observations of the tremor during the interview. Many patients with tremor are more symptomatic during the early part of the examination because of stress than after they become acclimated to the doctor-patient encounter. Patients should be observed while seated, lying down with the affected body part fully supported, and while walking. Horizontal or vertical head tremor is usually associated with ET, but it may also occur in cervical dystonia and midline cerebellar syndromes. Localized face, jaw, and lip tremors are more commonly a manifestation of parkinsonism. Essential voice tremor is readily audible and may be further enhanced by having the patient hold a prolonged note.
Tremor in the arm is observed with the affected limb fully supported at rest, with the limb elevated against gravity, and during goal-directed movements. Most resting tremors cease with changes in limb posture but quickly reappear following repositioning to repose. They are also activated by repetitive movements of the opposite hand, during walking, and during mental distraction such as reciting the months of the year backwards.
Postural and action tremors are best elicited with the arms held outstretched; with the shoulders abducted, elbows flexed, and index fingers held an inch apart in front of the face; during finger-to-nose maneuvers; and while drinking or pouring from a paper cup. Writing and drawing may demonstrate the large, tremulous, angulated loops of ET or the micrographia of parkinsonism.
Tremor of the leg should be assessed with the limb at rest, during heel-to-shin testing, and while standing and walking. Leg tremor is more commonly due to parkinsonism than ET.
The gait is almost always normal in patients with ET, while it is characteristically narrow-based and shuffling in PD, and is wide-based and ataxic in cerebellar disorders. The gait may have histrionic qualities in patients with psychogenic tremor.
Tremor frequency should be documented at rest and during postural and action maneuvers. Enhanced physiologic tremor is high in frequency (10 to 12 Hz), ET can be either low or high in frequency, and parkinsonian rest tremor is usually low in frequency (4 to 6 Hz). Psychogenic tremors tend to vary in frequency from moment to moment and either become more irregular or subside entirely when the patient is asked to carry out a complex, repetitive motor task with the contralateral limb. (See "Psychogenic tremor" above).
Laboratory studies ? The routine laboratory evaluation of tremor should include tests of thyroid function, diagnostic studies to exclude Wilson's disease, and screening for heavy metal poisoning such as mercury or arsenic, if an environmental cause is suspected. Wilson's disease should be suspected in anyone under age 40 who has tremor or other involuntary movement or posture [1]. (See "Diagnosis of Wilson's disease"). Hypoglycemia and pheochromocytoma may need to be ruled out in patients with enhanced physiologic tremor.
Brain imaging can be useful in patients suspected clinically of having a structural cause for tremor, such as Wilson's disease, brain trauma, stroke, or mass lesion, but it is otherwise not indicated.
Quantitative computerized analysis of tremor is available in some tertiary care facilities, but its ability to distinguish between tremor types has not been established.
TREATMENT ? The treatment of tremor depends upon the underlying cause.
Enhanced physiologic tremor ? Enhanced physiologic tremor is best managed by reduction or removal of the responsible offending medication or toxin; diagnosis and treatment of possible associated endocrine disorders; and dealing with stress, anxiety, or fatigue ( see "Physiologic tremor" above). Single doses of propranolol taken in anticipation of social situations that are likely to exacerbate tremor, as with tremor associated with public speaking, are useful in some patients.
Rest tremor ? Management of rest tremors, such as those associated with Parkinson's disease (PD) or other parkinsonian disorders, is accomplished by treatment of the underlying disorder and usually consists of anticholinergic drugs or other antiparkinson agents such as amantadine, dopamine agonists, and L-dopa. This topic is discussed separately. (See "Pharmacologic treatment of Parkinson's disease").
Cerebellar tremor ? There is no useful pharmacotherapy for cerebellar tremor. The rare patient with severe tremor and little or no ataxia can be helped by deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus. (See "Surgical treatment of essential tremor").
Orthostatic tremor ? Orthostatic tremor is limited to the legs and trunk and occurs exclusively while standing. Clinical experience suggests that orthostatic tremor is uniquely, but not always, responsive to treatment with clonazepam [23], although little data are available and no controlled trials exist.
Essential tremor ? Propranolol and primidone are the most effective and well-studied medications for the treatment of essential tremor (ET). The medical treatment of ET is discussed in detail separately. (See "Pharmacologic treatment of essential tremor").
Both DBS and unilateral thalamotomy are effective for the treatment of medically refractory ET. This topic is discussed separately. (See "Surgical treatment of essential tremor").
Discussion Zen 5 Speculation (EPYC Turin and Strix Point/Granite Ridge - Ryzen 9000)
Discussion Intel current and future Lakes & Rapids thread
Facebook
Twitter