CONTINUUM: Lifelong Learning in Neurology:
doi: 10.1212/01.CON.0000436153.01167.a6
Review Articles

Tremor Syndromes

Edwards, Mark J. MD, MBBS, PhD; Deuschl, Guenther MD, PhD, FAAN

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Author Information

Address correspondence to Dr Mark J. Edwards, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, m.j.edwards@ucl.ac.uk.

Relationship Disclosure: Dr Edwards has served as a speaker for the Movement Disorders Society and UCB and receives research support from The Dystonia Society UK and Parkinson’s UK. Dr Deuschl serves as a consultant for Medtronic, Inc, Novartis, and Teva Pharmaceutical Industries Ltd and receives royalties from Thieme. Dr Deuschl’s employer receives research support from Medtronic, Inc.

Unlabeled Use of Products/Investigational Use Disclosure: Dr Edwards reports no disclosure. Dr Deuschl discusses the use of currently recommended drugs for the treatment of tremors, of which only some are approved by the US Food and Drug Administration as antitremor agents.

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Abstract

Purpose of Review

The purpose of this review is to explain a practical clinical approach to the diagnosis and management of tremor.

Recent Findings

A number of rare but important causes of tremor have been delineated, which means that attention to detail in clinical assessment of patients with tremor is even more important.

Summary

Tremors are best divided into those occurring mainly at rest, mainly on posture, and mainly during action. This basic division leads directly to differential diagnosis and effective treatment.

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INTRODUCTION

Tremor might appear to be one of the simplest movement disorders to recognize; after all, it is a common, normal experience when our background physiologic (“natural”) tremor is enhanced by fear, excitement, or just too much coffee. However, this apparent simplicity hides a fair bit of difficulty in clinically separating different types of tremor. Some of these efforts at separation may seem a little academic from the outside, but they are important in efforts to make advances in understanding pathophysiology and from this to move to more effective treatment. This review sets out some simple principles of tremor recognition and classification, identifies some pitfalls along the way, and ends with some guidance on the best approach to treatment.

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THE BASICS: WHAT IS TREMOR AND HOW SHOULD WE DESCRIBE IT?

Tremor is a rhythmic oscillation of a body part. This definition is a good starting point for describing a tremor; further description can include which part or parts of the body it affects and its frequency of oscillation, usually in Hertz (1 Hz = 1 tremor oscillation or cycle per second).With some experience, the frequency of tremors can be separated into different categories: low frequency, <4 Hz; mid-frequency, 4 Hz to 7 Hz; high frequency, >7 Hz). Tremors are usually also described by the context in which they are present, as follows:

  1. Rest tremor: tremor present when the limbs are completely at rest
  2. Postural tremor: tremor present when the arms (typically) are held up by the patient
  3. Kinetic tremor: tremor present during movement; may significantly worsen toward the end of movement, as in “finger-nose” testing (this is called an intention tremor)

Postural and kinetic tremors are together called action tremor. A tremor might also be described on the basis of its amplitude: some tremors have a very small amplitude (usually called fine tremors), while others have large amplitude (usually called coarse tremors). Some tremors are variable in amplitude and frequency and may be described as jerky.

A lot of useful descriptive words are available to convey information to colleagues about the type of tremor a patient has, and, more importantly, these descriptors provide signposts toward differential diagnosis. For example, the description “A 60-year-old man with tremor” presents a long differential diagnosis list, whereas “A 60-year-old man with a coarse 3-Hz to 4-Hz tremor affecting the right hand, present at rest, re-emerging on posture after a few seconds, absent during movement” or “A 60-year-old man with a fine, 6-Hz to 8-Hz, bilateral, symmetrical, postural, and kinetic tremor affecting the arms” offer much smaller lists of possibilities, and some clear diagnoses spring to mind (Parkinson disease [PD] in the first case and essential tremor, hyperthyroidism, or drug side effects in the second).

With this in mind, the authors go into more detail below about tremor diagnosis, following the useful division of tremors as present mainly at rest, on posture, and during movement. Some causes of tremor, including some common causes, demonstrate overlap among these categories, but the categories still provide a useful rule of thumb when considering the most likely cause of tremor in an individual patient.

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TREMOR PRESENT MAINLY AT REST

Parkinson Disease

PD is the most common cause of rest tremor-so common, in fact, that it is important to remember that there are other causes of rest tremor (see “Other Causes of Rest Tremor,” below). The dominant tremor of PD is typically a rest tremor,1 which will usually start on one side of the body first (as do other symptoms of PD) and over time spread to involve the other side.1 Many patients with PD are initially not aware of their tremor, and it is often noticed by a relative or friend first.

The tremor often involves the thumb and forefinger; this gives rise to the term “pill-rolling” to describe it, as it appears as if patients are rapidly rolling something back and forth between their thumb and forefinger. This does not have to be the case, and patients with PD may have a more prominent wrist flexion/extension or forearm pronation/supination tremor. Tremor is often more prominent when patients are distracted (see examination techniques below) or walking. The frequency is typically 4 Hz to 6 Hz (Case 2-1).

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Case 2–1

A 72-year-old man presented to the neurology outpatient clinic for the first time. He was previously in good health but had noticed a tremor affecting his right hand and arm over the past 3 months. His wife, who attended with him, said that she first noticed his tremor about 9 months ago. He generally noticed the tremor when his arms were relaxed, and it did not interfere with his use of his hands to eat or drink. He had noticed some difficulty with buttoning his clothes recently. On examination, the patient had a right-sided rest tremor with a pill-rolling component. The tremor was absent on posture and during action. He had a clear decrement in amplitude and progressive slowing of repetitive finger movements on the right and subtly on the left. Rigidity was evident on the right. He had reduced arm swing on the right, and the tremor was much more prominent when he was walking.

Comment. This is a classic history and examination for Parkinson disease (PD). The key point is that, while the tremor is typical for PD, it should not be relied upon solely to make the diagnosis. This patient has bradykinesia and rigidity, and in this clinical context, PD is the correct diagnosis.

Some patients with PD have a postural tremor as well, although this is only very rarely seen without a rest tremor.1 Typically, the resting tremor is suppressed when patients start to move the trembling extremity. In some patients, a tremor on posture appears after they have held their arms out in front of them for a few seconds (a re-emergent tremor). Other patients have a higher-frequency postural tremor that appears immediately on posture. Patients with PD may also have tremor outside the arms, most typically the leg and jaw. Head tremor is not a common feature of PD.1

Pitfalls. The most important pitfall is to assume that all patients with rest tremor have PD. While other causes are much less common, it is very important to keep them in mind, especially if other features in the history, treatment response, and progression of symptoms over time do not fit with PD. It is also important to note that tremor is not a cardinal feature of PD, as rigidity and bradykinesia are, and about 40% of patients with PD do not have tremor.

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Other Causes of Rest Tremor

A number of other disorders can present with rest tremor. The combination of parkinsonism and rest tremor can occur in patients treated with dopamine receptor–blocking drugs (drug-induced parkinsonism).2 These drugs are used not only as antipsychotics but also as antiemetics (metoclopramide) and antivertigo drugs (prochlorperazine). A careful review of medication is therefore of great importance when assessing patients with tremor. Rarely, some nondopamine receptor–blocking drugs (eg, calcium channel blockers, lithium, sodium valproate, amiodarone2) can cause an asymmetric rest tremor with parkinsonism. Patients with multiple system atrophy3 and some with vascular parkinsonism4or circumscribed basal ganglia lesions5 canalso have a rest tremor. Other degenerative causes of parkinsonism-forexample, spinocerebellar ataxia types 2 and 3-can also produce a rest tremor.

Rest tremor can be seen in patients with both essential and dystonic tremor (Case 2-2). In such patients, the main tremor usually occurs on posture, and certainly, for essential tremor, both the rest and the postural tremor should be symmetrical, which would not be the case for PD. Tremors associated with peripheral neuropathy and with drugs other than dopamine receptor blockers, and those due to brainstem lesions (Holmes or rubral tremor), can all have a rest component, but essential and dystonic tremors are almost never seen as an isolated rest tremor.

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Case 2–2

A 69-year-old woman described the gradual onset of tremor 7 years ago affecting her left hand. She noticed the tremor when her hand was relaxed and also when she was holding and manipulating objects. She was also aware of some very mild tremor of the right hand. Other people had commented to her that she had a head tremor, but she was not aware of this. However, she was aware of some pain in her neck and difficulty turning to the right. She received a diagnosis of Parkinson disease (PD) 5 years ago and had been receiving levodopa for this. However, she had not noticed any benefit to her tremor. On examination, she had an asymmetric tremor mainly on the right, present at rest and more markedly on posture. She had a slight head turn to the left and a “no-no” head tremor. On posture, her tremor on the right worsened, particularly when she was in a “bat’s wing” position. She demonstrated some abnormal posturing of the fingers and wrist on the left. No bradykinesia or rigidity was present.

Comment. This patient has a rest tremor, but her main tremor is postural, and she has an additional head tremor. Main tremor on posture and head tremor are not commonly seen in PD. In addition, she has no rigidity or bradykinesia, which one would certainly expect after 7 years of PD, and no apparent response to levodopa. She also has subtle signs of dystonia (abnormal neck and hand posture). She most likely does not have PD and instead has adult-onset dystonic tremor.

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TREMOR PRESENT MAINLY ON POSTURE

As with rest tremor, one common diagnostic possibility immediately springs to mind when seeing a patient with postural tremor: essential tremor (ET). Even more than is the case for rest tremor and PD, it is important, even essential, to keep in mind that there are many other causes of postural tremor apart from ET. ET is a common disorder, but other diagnostic possibilities are also important.

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Essential Tremor

ET is a common cause of tremor6 and presents typically when patients are in their sixties or seventies. The commonly discussed “bimodal peak” of onset, with a cluster of cases occurring with onset at approximately 20 years of age, probably does exist,6 but these younger-onset cases are rare, and careful consideration should be given to other causes of tremor in such patients.

ET is defined as a bilateral, largely symmetrical postural and kinetic tremor involving the hands and forearms (Case 2-3).7,8 Because no diagnostic test exists, and such symptoms are common to other disorders, it is important to be aware of other causes. Patients with ET should not develop other neurologic signs (eg, dystonia, significant balance disturbance, cognitive decline7), and if these symptoms are present or develop over time, they should be investigated in their own right. Most patients with ET notice a very slow progression of symptoms over years, and some patients are severely affected (hence, the change in name from “benign essential tremor” to “essential tremor”).

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Case 2–3

A 70-year-old man reported a tremor present in both arms, which he noticed mainly when holding objects or moving his hands toward objects. He had been aware of the tremor since the age of 50, and very gradually it had worsened. He described no other symptoms. He had a family history of a similar tremor in his father and brother. On examination, he had a bilateral, largely symmetrical postural and action tremor. No other clinical signs were present.

Comment. This is a good history and examination for essential tremor. The long duration of tremor without any other symptoms developing over time is typical, as is the relatively mild to moderate severity of the tremor itself. The family history is also helpful. It is still important to consider other causes of postural tremor.

A proportion of patients will report a beneficial effect of a small amount of alcohol on their tremor. This is not a diagnostic feature of ET and is seen in other causes of tremor, for example, dystonic tremor and PD. Patients with ET may have a dominant family history of tremor.

Patients with ET can have tremor outside the arms, for example, jaw and head tremor, but skepticism should prevail when considering a diagnosis of ET on the basis of isolated jaw or head tremor,9 as PD or dystonia can cause these, respectively (Table 2-1). Although the main tremor of ET is a kinetic and postural tremor, additional tremor at rest can be documented.

Table 2-1
Table 2-1
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Dystonic Tremor

Dystonia is a movement disorder that causes an abnormality of posture, which is typically mobile rather than fixed and can affect any part of the body. Many patients with dystonia also have tremor in the body part affected by dystonia (dystonic tremor). Other patients with dystonia may have tremor in a body part not obviously affected by abnormal posture; this is referred to as tremor associated with dystonia.7

Dystonic tremor is typically jerky and may be quite position specific. For example, movement disorder specialists often examine for postural tremor in different positions (eg, arms stretched out in front, arms abducted at the shoulder and bent at the elbows, arms in the same position but with the forearms pronated or supinated). If patients with dystonic tremor are examined in this manner, a significant worsening of tremor is often seen in a particular position. Sometimes dystonic tremor, like the dystonic postures themselves, can be task specific. For example, patients may only have dystonic postures and tremor of the hand during writing or playing a musical instrument but not during other tasks involving the hand.

A more complicated situation in terms of classification exists where patients have a jerky, position-sensitive tremor10 or a tremor only present during a particular task (eg, a tremor only present during writing, often called primary writing tremor11), but where no overt abnormal posturing would allow the clear diagnosis of dystonia. Some movement disorder specialists would be comfortable describing such tremors as dystonic, and others would not.9 Even if such tremors are not classified as dystonic, they should equally well not just be automatically labeled as ET, although they do not meet clinical criteria (as they are very asymmetric, for example).

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Other Causes of Mainly Postural Tremor

As indicated above, ET and dystonic tremor are not the only causes of postural tremor. We all have a degree of postural tremor called physiologic tremor, and, as with all physiologic phenomena, there is a normal range for this tremor. Some people therefore have naturally enhanced physiologic tremor. Anxiety and fatigue are common factors that cause enhanced physiologic tremor. Physiologic tremor is a fine postural tremor of 7 Hz to 12 Hz that is symmetrical.

Many drugs can cause postural tremor (see Table 2-2 for a list of some common causes) (Case 2-4),2 typically a 6-Hz to 8-Hz symmetrical postural arm tremor. Nonprescribed drugs (coffee, nicotine, marijuana) canalso cause postural tremor. Drug withdrawal and alcoholism are other common causes. Some toxins (eg, mercury) can also cause postural tremor.

Table 2-2
Table 2-2
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Case 2–4

A 26-year-old man described a 3-year history of postural arm tremor. The tremor was worsening and now mildly interfered with some daily tasks, for example, eating and drinking. He described no other symptoms. He had a history of epilepsy, for which he was on treatment.

Comment. Further enquiry in this man revealed treatment with sodium valproate for his epilepsy, with an increase in dose recently after a seizure. Many drugs (both prescribed and recreational) can cause tremor, and a careful drug history is an essential part of evaluation of patients with tremor.

Metabolic disturbance, especially due to hyperthyroidism, is a common cause of bilateral symmetric postural tremor. Tremor associated with peripheral neuropathy (typically inflammatory neuropathy such as immunoglobulin M paraproteinemic neuropathy,12 but also hereditary causes of neuropathy such as Charcot-Marie-Tooth disease and Kennedy syndrome)usually presents as a postural tremor.

Fragile X syndrome is a common genetic cause of mental retardation caused by a triplet repeat expansion. Males (and some females) with premutations-ie, a number of triplet repeats that is abnormal but not sufficient to cause the disease-can present in adult life with a postural and kinetic tremor, progressive ataxia, and cognitive decline.13 Affected females commonly have ovarian failure. This constellation of symptoms is now referred to as fragile X tremor-ataxia syndrome.

Rhythmic myoclonus can sometimes masquerade as tremor. Epilepsia partialis continua is a rhythmic myoclonic jerk that can affect any part of the body, but often the hand. It is typically caused by a focal motor cortical lesion. Another myoclonic syndrome, confusingly called cortical tremor, produces bilateral myoclonus of the hands/arms seen on posture that can mimic ET and other postural tremor syndromes. It is associated with epilepsy and progressive cerebellar signs.14

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TREMOR PRESENT MAINLY DURING MOVEMENT

An important distinction needs to be made between tremor that occurs during movement of the limb and a true intention tremor, which occurs only (or very clearly worsens) at the end of movement, for example, as the finger approaches the patient’s nose or the examiner’s finger in finger-nose testing. Many of the causes of postural tremor described above (eg, ET) will cause a tremor that occurs during movement, and this is best described as a kinetic tremor. The distinction from an intention tremor is important, as this term indicates that the tremor is related to cerebellar dysfunction.

Cerebellar dysfunction caused by lesions, degeneration, or toxicity (eg, chronic alcohol abuse, phenytoin) typically causes an intention tremor. The most common lesional cause is multiple sclerosis, but many causes for intention tremor exist. Usually other cerebellar signs will be present.

Intention tremors can be combined with resting and postural tremor. Some patients present with a tremor (often unilateral) that is present at rest, worse on posture, and even worse during movement, with a clear intention component. This is referred to as rubral or Holmes tremor and is related usually to an ipsilateral lesion in the brainstem. Although classical descriptions suggested a lesion in the red nucleus (hence the term “rubral tremor”), most often the lesion is in the midbrain tegmentum outside the red nucleus, especially in the superior cerebellar peduncle or posterior part of the thalamus, interrupting cerebellar outflow pathways.15

A similar tremor, often with a very severe worsening seen when the patient holds arms in front, flexed at the elbows (a bat’s wing tremor), is sometimes seen in people with Wilson disease. This inherited disorder of copper metabolism is rare but treatable and is fatal if left untreated. Often, many other neurologic, systemic, and psychiatric symptoms and signs are present, but tremor can occasionally be the dominant feature.

One other form of tremor that may occur exclusively at rest, on posture, or during movement, but often in all three positions is a functional or psychogenic tremor (Case 2-5). Functional tremor is the most common functional movement disorder.16 As with other functional neurologic symptoms, the key is to make a positive diagnosis based on specific characteristics of the symptoms and signs. With regard to functional tremor, the main examination technique is to look for distractibility of the tremor.16,17 This is not usually demonstrated by asking patients to do self-paced tasks such as mental arithmetic. The best distraction task is to ask patients to tap with one hand in time to a rhythm set by the examiner that speeds up and slows down unpredictably. The treating physician should look for a distinct change in the tremor (eg, long pauses, shift in frequency) or “entrainment” where the tremor adopts the frequency of the tapping. Inexplicable inability to perform the tapping task correctly is another clinical sign. An additional useful maneuver is to ask patients to reach quickly to a target, such as the examiner’s finger, presented suddenly. A brief pause in the tremor is often seen.16,17

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Case 2–5

A 36-year-old woman presented with a tremor of the right arm, which began suddenly after an injury to the hand. She sustained this injury during an assault and noticed the tremor immediately afterward. The tremor was present all the time. On examination, she had a tremor at rest, on posture, and during action of the right arm. When the patient was asked to tap with her left hand in sync with a rhythm set by the examiner, the tremor stopped and started.

Comment. Sudden onset of tremor is rare and typically indicates a brain lesion (eg, from a stroke) or a functional/psychogenic cause. Here the mode of onset (after an injury to the hand) is unusual for an organic tremor. There are also few causes of a tremor present at rest, on posture, and during action except a brainstem/thalamic lesion, in which case one would expect other clinical symptoms and signs. The presence of distractibility of the tremor provides a positive diagnostic marker of functional/psychogenic tremor.

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BODY PART–SPECIFIC TREMORS

The discussion above has mainly concentrated on tremor that affects the arms, but tremor may solely or primarily affect other body parts.

Head tremor is a common feature of cerebellar disease, particularly cerebellar degenerative disease. Dystonia affecting the neck can produce a prominent head tremor, often in the absence of very significant abnormal posture. ET may also be associated with head tremor, but rarely in isolation. Of note, head tremor is very uncommon in PD.

Tremor of the chin and jaw can be seen in PD and also in dystonia. A rare childhood-onset disorder, hereditary geniospasm, can also cause tremor of the chin.18 Tremor of the palate19 is often not noticed by patients except that it can cause ear clicks due to opening and closing of the Eustachian tube. These clicks can be so loud that they can sometimes be heard by others. Palatal tremor can occur as an idiopathic phenomenon (essential palatal tremor) or as a result of brainstem lesions (secondary palatal tremor) or degenerative diseases involving the brainstem.19 In the latter category, the palatal tremor is typically associated with progressive ataxia.20 Mutations in the gene causing Alexander disease (GFAP) can be the underlying cause in such patients.21

Leg tremor commonly occurs in PD. One other important cause of leg tremor is orthostatic tremor (Case 2-6).22 This condition is characterized by a very high-frequency tremor (typically 13 Hz to 16 Hz) that occurs exclusively on standing. Because it is so high-frequency, this tremor is so fine that it can be very hard to see, and affected patients do not often report tremor. The typical concern is of poor balance when standing still, which is relieved by movement.22 These rather unusual symptoms often lead to nondiagnosis or misdiagnosis as psychogenic. Typically, symptoms worsen slowly over time. A postural arm tremor may also occur.

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Case 2–6

A 50-year-old woman reported unsteadiness and poor balance, which had been present for 5 years and was slowly worsening. She had been diagnosed elsewhere as having psychogenic/functional balance disturbance and was seeking a second opinion. She had attended a course of cognitive-behavioral therapy for this diagnosis but was no better.

She described poor balance that developed after approximately a minute of standing, particularly when she had to stand in a queue. When she walked, she felt her balance was better. She had noticed a postural arm tremor as well.

On examination, she needed to hold on to the table after a few minutes of standing, as she felt she might fall (although she had never actually fallen over before). A slight quivering of her legs was noticeable when she was standing. She had a postural arm tremor.

Comment. This is a classic history for orthostatic tremor. Such patients present with concerns not of tremor but of poor balance when standing with resolution when walking. Tremor studies will reveal a high-frequency tremor (13 Hz to 18 Hz). Patients with orthostatic tremor may respond to clonazepam.

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A QUICK AIDE-MÉMOIRE TO TREMOR HISTORY TAKING AND EXAMINATION

It can be useful to have a brief set of historical details and an examination scheme in patients with tremor, as well as a list of tests that may be useful in the appropriate clinical situation.

The most useful historical details are age at onset, body part or parts affected, nature of onset (sudden, slowly progressive), drug exposure, course of the tremor (static, progressive), exacerbating factors (including task-specific worsening), relieving factors (eg, alcohol), associated neurologic symptoms, associated systemic symptoms, family history, and level of day-to-day functional impairment from the tremor.

The specific examination of tremor (in the arms) can be done as follows:

  1. Examine the patient with his or her arms relaxed, ideally on the arms of a chair or on the patient’s lap, half pronated. Ask the patient to close his or her eyes and count backward from 100-this distraction task often brings out tremor.
  2. Examine the arms on posture, stretched out in front of the patient, fingers open. Ask the patient to close his or her eyes and count backward again. Ask patient to flex his or her arms at the elbows, then slowly supinate and pronate the arms, looking for position specificity of the tremor.
  3. Examine the patient’s arms during movement by doing the finger-nose test, looking for tremor during movement (kinetic tremor) and any clear worsening at the end points (intention tremor).
  4. Ask the patient to write and copy a spiral; this is useful as a measure of tremor severity for comparison after treatment and also to look for task-specific tremor.
  5. Examine for other neurologic signs, especially parkinsonism, dystonia, and cerebellar signs.
  6. Consider systemic signs that may be relevant (eg, signs of hyperthyroidism).
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TREATMENT OF TREMOR

As with many neurologic disorders, treatment of tremor is primarily symptomatic. It is therefore important to inform the patient of this, as some patients may continue to take unhelpful medications because they believe that the underlying condition will worsen if not taken. A full history regarding the functional impairment caused by the tremor helps guide patients toward or away from taking medication.

Certain causes of tremor have specific treatments. Therefore, tremor due to PD is best treated by dopaminergic medications, although it can be a rather difficult symptom to treat in some patients. Other drugs, such as amantadine, can also reduce tremor due to PD. Tremor due to drug use or metabolic disturbance such as hyperthyroidism is best treated by withdrawal of the offending drug or treatment of the metabolic disturbance, respectively.

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Medications

For most other causes of tremor, a range of possible medication options exists. With all of these medications, it is important to counsel patients about possible side effects and to start at a low dose, slowly titrating upward to an effective dose if side effects permit. It is useful to explain this process to patients so that they understand it is impossible to completely predict the response or side effects an individual may experience, and that there will always be a process of trial and error. Some drugs have a higher likelihood to work for postural/intention tremor, while others work preferentially for resting tremors.

Postural/intention tremors. For postural/intention tremors, beta-blockers, particularly propranolol, are useful for many patients and have class A evidence.23,24 Important side effects include postural hypotension and bradycardia, and in those with a history of asthma, propranolol can trigger breathing difficulties. Hypoglycemic warning symptoms can be masked with beta-blockers. Long-acting and short-acting propranolol can be used, and there is lower-level evidence to support the use of other beta-blockers such as atenolol and sotalol. A common starting dose for long-acting propranolol could be 80 mg once daily, increasing to 80 mg 2 times per day if necessary. Short-acting propranolol can be given at a dose of 10 mg 2 to 3 times per day, and slowly increased to 20 mg to 30 mg 3 times per day.

Primidone, which is metabolized tophenobarbital, has class A23,24 evidence to support its use in tremor but is problematic, particularly in older patients, because of sedative side effects, tolerance, and occasional difficulties with withdrawal after long-term use. A normal starting dose would be about 25 mg once daily, increasing slowly to 50mg to 100 mg 3 times per day.

Clonazepam, a long-acting benzodiazepine, can also act to reduce tremor. Side effects, which include sedation, are not uncommon, and care needs to be taken in titrating the dose. Some patients find this a useful drug to use on an “as needed” basis, for example, taking it before a social engagement. Starting dose is 0.25 mg daily, increasing slowly to 0.5 mg to 1 mg 3 times per day. Withdrawal effects can be noticed with long-term use at high doses.

Tremors at rest. For parkinsonism, the regular anti-Parkinson medication should be tried first, since it has a high likelihood of improving tremor.

Trihexyphenidyl is an anticholinergic medication that has particular effectiveness for dystonic tremor and is also sometimes used to treat tremor in PD. It causes dry mouth and, in older people especially, can cause confusion. Starting dose is 1 mg daily, increasing slowly to 1 mg to 2 mg 3 times per day.

Other drugs that are sometimes tried, often unsuccessfully, to treat tremor include topiramate and gabapentin.

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Botulinum Toxin

Botulinum toxin has a long history of use in focal dystonia, and in patients who have additional tremor (eg, head tremor associated with torticollis), the tremor is often also improved by the injections. Head, jaw, and chin tremors, whatever the cause, can be helped by botulinum toxin injections.

Much less evidence exists to support the use of botulinum toxin injections in limb tremor. There have been reports of successful use in arm tremor, but data on functional benefit are limited.25

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Surgery

Patients with severe refractory tremor may benefit from brain surgery.26,27 Thalamotomy (lesioning of a specific part of the thalamus) and, more recently, deep brain stimulation of the thalamus can both produce dramatically beneficial effects on tremor. As with use of such operations in other patient groups, patient selection is paramount. Operative complications, especially hemorrhage, are more common with older age, especially over 70 years. Poor balance and speech and swallowing problems can all occur after thalamotomy, especially with bilateral surgery. However, this remains an important option for some patients when other options have failed and functional disability from the tremor is severe.

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KEY POINTS

  • Tremors can be usefully divided into those that are only or mainly present at rest, on posture, or during movement.
  • Tremors can also usefully be described according to their amplitude and regularity as fine, coarse, or jerky, and according to their frequency as low, middle, and high frequency.
  • Rest tremor is a common feature of Parkinson disease and is usually asymmetric, involves the thumb and forefinger (pill-rolling), and is worse when patients are distracted.
  • Postural tremor can occur in Parkinson disease and is usually suppressed when the extremity is actively moving. Tremor of the leg, jaw, and chin can also occur.
  • Other causes of rest tremor include drugs (typically those that also cause parkinsonism), other degenerative causes of parkinsonism (rare), tremor associated with peripheral neuropathy, and dystonic and essential tremor.
  • Essential tremor is a common cause of postural tremor and is a symmetrical postural and kinetic tremor.
  • Dystonic tremor is accompanied by dystonia in the same part of the body or another body part (tremor associated with dystonia), and is typically jerky, position specific, and sometimes task specific.
  • Many other causes of postural tremor exist apart from essential and dystonic tremors, including metabolic disturbance, drugs, and neuropathy.
  • Rhythmic myoclonus or asterixis can sometimes mimic postural tremor.
  • It is useful to distinguish between a tremor that continues during movement (kinetic tremor, seen commonly in essential tremor) and one that clearly worsens at the end of movement (intention tremor). The latter signifies cerebellar dysfunction.
  • Wilson disease, a treatable disorder of copper metabolism, can present with a postural and/or intention tremor or even with rest tremor.
  • Functional (psychogenic) tremor can be positively differentiated from other forms of tremor by its distractibility with and variability during specific examination maneuvers.
  • Head tremor is often seen in dystonia and cerebellar diseases but rarely in essential tremor. Parkinson disease does not commonly cause head tremor.
  • Orthostatic tremor is a very high-frequency tremor that occurs on standing and is relieved by walking or sitting. Patients typically report poor balance rather than tremor.
  • It is important that patients understand that tremor treatment is generally symptomatic and therefore is only necessary if functional disability is caused by the tremor.
  • The “trial and error” nature of trying different medications for tremor should be explained to patients.
  • A number of medications can be helpful for tremor, including beta-blockers, trihexyphenidyl, primidone, and clonazepam. These drugs may have differential benefits for rest and postural/intention tremors.
  • For selected patients with severe tremor, thalamic surgery-typically deep brain stimulation surgery-can be a very useful treatment.
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