and Peter Hedera2
(1)
Parkinson’s Clinic of Eastern Toronto, Toronto, ON, Canada
(2)
Department of Neurology Division of Movement Disorders, Vanderbilt University, Nashville, TN, USA
Abstract
Tremor is the most common abnormal movement and is defined as an involuntary, rhythmic oscillation of a body part. This chapter reviews main characteristics of tremor, such as body segments affected by tremor (arm, head vocal cords), segment position when tremor is observed (resting and action tremor), frequency and amplitude of tremor. The main emphasis is on the most common causes of tremor, essential tremor and Parkinson’s disease. We discuss main clinical features of tremor seen with these two common neurologic problems, their differential diagnosis, and main therapeutic options. Additionally, other less common causes of tremor are also briefly discussed.
Keywords
TremorTherapyEssential tremorParkinson’s diseaseDeep brain stimulation1.1 Introduction
Tremor is defined as an involuntary, rhythmic oscillation of a body part. Tremor is the most commonly seen abnormal movement among all of the movement disorders. Essential tremor is the most common movement disorder. Tremor can be of many different types as follows:
I.
Resting tremor
A resting tremor usually manifests itself when the affected body part is not voluntarily activated and is in a state of completed relaxation supported against gravity. The resting tremor either diminishes or completely disappears during the onset of voluntary activity. Some of the common causes of resting tremor are as follows:
(a)
Parkinson’s disease.
(b)
Parkinson plus syndromes.
(c)
Midbrain tremor (Holmes tremor).
(d)
Wilson’s disease.
(e)
Essential tremor, when severe, may have a resting component, and resting tremor can be seen in about 10–15 % of patients with essential tremor. Patients with essential tremor typically do not manifest resting tremor while walking, and this may be a useful feature to distinguish it from resting tremor in Parkinson’s disease, which persists during gait.
II.
Action tremor
An action tremor occurs during voluntary activity of the affected body part or when the affected body part is maintaining a steady posture against gravity and either diminishes or completely disappears at rest. This includes postural and kinetic tremors.
A postural tremor occurs when the affected body part is voluntarily maintaining a position against gravity. True postural tremor appears without any time delay, and it needs to be distinguished from a reemergent tremor, which is observed after 5–20 s and represents resting tremor.
A kinetic tremor occurs when the affected body part is performing a voluntary activity which could be goal directed or non-goal directed.
Some examples of action tremor are:
(a)
Essential tremor
(b)
Primary writing tremor
(c)
Enhanced physiological tremor:
(i)
Emotional stress or anxiety
(ii)
Endocrine: thyrotoxicosis, hypoglycemia, adrenocorticosteroids, and pheochromocytoma
(d)
Cerebellar tremor
(e)
Drug- and toxin-induced tremor such as beta agonists, lithium, neuroleptics, theophylline, valproic acid, lead, mercury, manganese, and arsenic
(f)
Peripheral neuropathy
III.
Intention tremor
An intention tremor is present if the amplitude of the tremor increases when the affected body part is approaching the target. Intention tremor is seen in cerebellar pathology.
IV.
Task-specific kinetic tremor
A task-specific kinetic tremor occurs during a specific activity, such as primary writing tremor.
1.1.1 Classification
According to Position of the Body Part Affected by Tremor
Tremor is categorized as resting tremor (if the tremor occurs while the affected body part is in complete repose), postural tremor (if the tremor occurs while the affected body part is in steady posture), or kinetic tremor (if the tremor occurs while the affected body part is exerting a movement).
According to the Regions of Body Affected
Tremor may affect different body parts including the limbs, head, tongue, jaw, vocal cords, and palate. The parts of the body that are affected by tremor depend upon the underlying neurological condition.
According to the Frequency of Tremor
1.
Low-frequency tremor, e.g., tremor of Parkinson’s disease
2.
Medium-frequency tremor, e.g., essential tremor
3.
High-frequency tremor, e.g., orthostatic tremor
According to the Amplitude of Tremor
1.
Mild amplitude
2.
Moderate amplitude
3.
Severe amplitude
According to the Etiology of Tremor
1.
Essential tremor.
2.
Enhanced physiological tremor.
3.
Drug- or toxin-induced tremor.
4.
Dystonic tremor.
5.
Cerebellar tremor.
6.
Holmes tremor (midbrain tremor).
7.
Primary orthostatic tremor.
8.
Cortical tremor.
9.
Peripheral neuropathy-associated tremor.
10.
Tremor of Parkinson’s disease.
11.
Psychogenic tremor.
12.
Tremor is also seen in many other medical conditions such as thyroid disease, Wilson’s disease, hypoxia, hypotension, AIDS, and hereditary hemochromatosis.
13.
Task-specific tremor such as primary writing tremor.
14.
Posttraumatic tremor.
As previously mentioned, essential tremor is the most common movement disorder.
1.1.2 Description
The following parameters should be taken into account when describing a particular tremor:
1.
The affected body part. Also known as topography (e.g., head, limbs, chin, jaw)
2.
The frequency of the tremor
3.
The position of affected body part in which tremor is most prominent (e.g., rest, postural, activity, specific task)
4.
The amplitude of tremor
1.2 Frequencies of Various Tremor Syndromes
Different tremor syndromes have different frequencies. Approximate frequencies of various tremor syndromes are described in Table 1.1.
Table 1.1
Approximate frequencies of various tremor syndromes
Tremor syndrome | Frequency (Hz) |
|---|---|
Enhanced physiological tremor | 10–14 |
Essential tremor syndrome | 7–10 |
Primary orthostatic tremor | 14–18 |
Task-specific tremor | 4–8 |
Holmes tremor | 3–5 |
Tremor of Parkinson’s disease | 3–7 |
Cerebellar tremor | 3–5 |
Palatal tremor | 2–6 |
Dystonic tremor | 5–7 |
Alcoholic tremor | 3–4 |
Toxic- and drug-induced tremor | 5–10 |
Psychogenic tremor | Variable |
1.2.1 Investigations
In most cases of tremor, no investigations are necessary. However, when other alternative conditions are suspected, the investigations may be directed to the possible underlying cause.
Investigations including thyroid function tests and brain imaging such as CT scan or MRI of brain may be required in some cases, especially if any cerebellar or focal long tract signs are present. In patients with suspicion of Wilson’s disease, 24 h urine copper, serum ceruloplasmin, and copper as well as slit lamp examination for Kayser-Fleischer rings may be performed for initial assessment.
1.2.2 Causes
Essential tremor
Enhanced physiological tremor
Tremor of Parkinson’s disease
Dystonic tremor
Task-specific tremor such as primary writing tremor
Cerebellar tremor
Drug- or toxin-induced tremor
Holmes tremor (midbrain tremor)
Primary orthostatic tremor
Alcohol induced tremor
Cortical tremor
Peripheral neuropathy-associated tremor
Psychogenic tremor
Tremor associated with medical conditions such as thyroid disease, Wilson’s disease, hypoxia, hypotension, AIDS, and hereditary hemochromatosis
Posttraumatic tremor
1.3 Essential Tremor
Essential tremor affects 5–6 % of the patients over the age of 65. About 5–15 % of essential tremor cases occur during childhood. Essential tremor may be familial in 50–60 % of all cases and typically starts before the age of 65 years. Essential tremor is common in all races across the world.
The prevalence of essential tremor is significantly higher in individuals above the age of 40. In some studies, the prevalence of essential tremor in patients above the age of 40 has been reported to be as high as 10 %; however, the peak age of onset for essential tremor is 70–79 years. The prevalence of essential tremor is ten times greater in 70- to 79-year-old individuals as compared to 40- to 69-year-old individuals. Some studies have reported a slightly higher prevalence in men, but other studies could not find any difference between men and women.
The likelihood of patients with essential tremor having first-degree relatives with essential tremor is five times greater than the normal population. There seems to be an increase in prevalence of essential tremor with age. It is estimated that almost five million people in the USA, over the age of 40, are affected with essential tremor. Essential tremor is more common than Parkinson’s disease.
Essential tremor usually affects both sides of the body, although initially it may only be noticed on one side and up to 15 % of ET patients may have strictly unilateral tremor. It can occur at any age. Although, it may be seen in the early 20s, late onset, after the age of 55 years is more common. Essential tremor may begin in early childhood, but its prevalence and intensity increase with advancing age, and eventually, it may interfere with writing, eating, and other activities of daily life. In familial cases, the onset of essential tremor may be much earlier than sporadic cases.
Essential tremor is a slowly progressive condition in which the amplitude of tremor usually increases with time. In some cases there may be no change noted in the tremor for several years, and then in advanced age, the tremor may get worse relatively quickly. In addition, as the amplitude of tremor increases, the frequency of tremor may decrease.
Fatigue, central nervous system stimulation, sexual arousal, emotional excitement, and temperature extremes can exacerbate the tremor. Alcohol may dampen the tremor significantly. The history of response to alcohol is helpful diagnostically. The effect of alcohol seems to be centrally mediated. Caffeine, on the other hand, seems to precipitate essential tremor. Essential tremor, like most other movement disorders, disappears in sleep.
1.3.1 Etiology and Pathogenesis
The exact cause of essential tremor is unknown. Some patients may have a family history of tremor in their parents, siblings, or close relatives. However, sporadic cases are seen quite frequently. The exact mechanism of inheritance is unclear. In a significant number of cases, essential tremor is hereditary and is transmitted in an autosomal dominant pattern. Chromosomes 3q13, 2p22–p25, and 6p23 have been suggested to be the disease loci in many reports. More recently, common sequence variants in LINGO1 have been suggested a risk factor for ET. Environmental factors may also play a role in the causation of essential tremor. This is supported by the lack of a complete concordance of essential tremor in monozygotic twins.
There is a lack of clear understanding of the pathophysiological mechanisms of essential tremor. The central nervous system pathology is supported by the observation of response of tremor to thalamotomy and centrally acting drugs. Cerebellum may play an important role in pathophysiology of essential tremor. It is believed that essential tremor may emerge from abnormal oscillations within thalamocortical and cerebello-olivary loops in the brain. This theory is supported by the findings that the lesions or injury of the cerebellar and thalamic regions reduces the intensity of essential tremor. Neuronal discharges correlated to tremor have been observed to occur in the ventrolateral thalamus, particularly in the ventralis intermedius nucleus. Contralateral limb tremor can be suppressed by the ablation or high-frequency stimulation of ventralis intermedius nucleus of the thalamus. Essential tremor may be the result of abnormal oscillations of a central nervous system pacemaker. This central oscillator could be enhanced or suppressed; however, the exact location of this oscillator is unknown. Another theory considers ET a neurodegenerative disorders with a selective degeneration of Purkinje cerebellar cells.
1.3.2 Clinical Features
Patients usually complain of their handwriting becoming sloppy, large, and irregular; trouble holding objects like a cup full of liquid; and trouble using a fork, spoon, keys, and screwdriver, pouring liquids, and shaving (Fig. 1.1). They may spill liquids and writing a check may be a challenge. In severe cases essential tremor can interfere with dressing, preparing meals, and other activities of daily living.
Figure 1.1
Spiral drawing by the examiner and a patient with essential tremor (spiral test)
The pediatric cases of essential tremor affect more males than females. Most patients with essential tremor seek attention only if they have a functional or social disability because of tremor. Essential tremor may result in social phobia due to embarrassment.
Patients with essential tremor may have mild neuropsychological deficits, including problems with visual perception, encoding, and verbal fluency as well as working memory.
Classical essential tremor is a monosymptomatic, postural, and action tremor. Essential tremor usually affects the upper extremities and the hands, but it may also involve the head, lower extremities, voice, and other body parts. In classic essential tremor, the approximate frequency of involvement of different body parts is summarized in Table 1.2.
Table 1.2
Approximate frequency of involvement of different body regions in essential tremor
Region of body | Frequency (%) |
|---|---|
Hands and arms | 90 |
Head | 30 |
Legs | 25–30 |
Voice | 10–15 |
Trunk | 5 |
Face | 5 |
Tongue | 4 |
1.3.3 Characteristics of Essential Tremor
Essential tremor is only present when the affected body part is exerting effort and not during repose. Mental tasks or stress may exacerbate the essential tremor. Essential tremor does not occur during sleep, but patients sometimes complain of an especially coarse tremor upon awakening in the morning.
Essential tremor affecting the hands causes a flexion extension movement of the hands, abduction movement of the fingers, and, only in minority of cases, supination-pronation movements of the hands or arms. The size of handwriting is usually large (macrographia) in contrast to the tremor of Parkinson’s disease, in which the size of handwriting is small (micrographia) (Fig. 1.2). The legs, tongue, voice, face, and trunk, if involved in essential tremor, are usually affected in the later stages of the disease.
Figure 1.2
Multiple loops drawing in a patient with essential tremor
The tremor of the hands is usually of medium frequency in the range of 7–10 Hz. It becomes more apparent with arms outstretched, extended, or straight at elbows with fingers apart, as well as with arms outstretched, flexed at elbows in front of the chest with fingers apart (wing-beating position), and during the finger-nose-finger movements.
The frequency of tremor varies with age, severity, and the location in the body. The tremor frequency usually slows down with age, at a rate of about 0.07 Hz/year. This decrease in frequency causes a gradual increase in tremor amplitude over the years. Patients with severe essential tremor may also have difficulty with tandem gait, which is tested by walking heel to toe. Neurological examination is otherwise normal. Essential tremor in the upper limbs is usually symmetric or only mildly asymmetric.
1.3.4 Diagnosis of Essential Tremor
The diagnosis of essential tremor is made by history and physical examination. The following steps are helpful in the assessment of essential tremor:
1.
Asking the patient to hold arms straight outstretched, extended at elbows with fingers spread apart.
2.
Holding arms with fingers outstretched, flexed at elbows in front of the chest (wing-beating position).
3.
While arms in the wing-beating position, asking the patients to make a fist of both hands except leaving their index finger of each hand extended pointing across each other in close proximity without touching (also known as one-to-one test). This helps to assess the subtle cases of postural tremor.
4.
Finger-nose-finger testing.
5.
Asking the patient to hold a cup full of water and to bring it to their lips and then away from their mouth a few times to see if there is any spillage of water (glass test). Pouring of liquids may also be tested.
6.
Writing a standard sentence on each visit (Fig. 1.3). The new writing sample on each visit is then compared to the writing sample from the previous visit in order to assess the therapeutic response.
Figure 1.3
Handwriting of a patient with very mild essential tremor
7.
Drawing a spiral without supporting the hand on the clipboard on each visit and comparing the drawing to the one from previous visit in order to assess the therapeutic response.
8.
Examination of voice by holding a prolonged note; head, tongue, and heel-knee-shin testing; and tandem gait are important parts of assessment of essential tremor.
In typical cases of essential tremor, no investigations are required. When considering the diagnosis of essential tremor, the primary inclusion features are as follows:
1.
Postural or kinetic tremor of both upper extremities
2.
Isolated head tremor without any dystonic features
3.
Absence of other focal findings except mild cogwheeling, especially in the elderly patients
1.3.5 Treatment of Essential Tremor
Medicinal Treatment
Sometimes patients with essential tremor may desire nothing more than to be assured that they do not have Parkinson’s disease. Any exacerbating factors, if present, should be addressed first. The avoidance of stimulants, such as caffeine, is helpful in some cases. If the tremor does not affect daily functioning, it could be observed. Milder cases of essential tremor may be helped with occupational therapy training or use of weighted wrist bracelets that are available at many sports stores.
Alcohol may transiently reduce tremor amplitude in about 50–90 % of the cases, but the rebound tremor may be worse when the effect of alcohol wears off. Alcohol intake is not recommended for treatment of essential tremor.
The most commonly used medications are propranolol, a beta-blocker, and primidone, a GABA agonist (Table 1.3).
Table 1.3
Pharmacological agents used in the treatment of essential tremor
Drug | Dose | Side effects | Comments |
|---|---|---|---|
Primidone | Starting dose is 31.25 mg HS, increased slowly up to 250 mg TID | Sedation, drowsiness, fatigue, nausea, vomiting, malaise, and dizziness | GABA agonist |
Propranolol | Starting dose is 40 mg BID, increased slowly up to 180 mg BID | Postural hypotension, bradycardia, drowsiness, impotence, fatigue, depression | B1/B2 antagonist |
Topiramate | Starting dose is 25 mg Hs, increased weekly by 50 mg/day to the maximum dose of 200 mg BID | Weight loss, tingling and paresthesias, concentration difficulties, exacerbation of glaucoma, and renal stones | Sodium channel blocker |
Gabapentin | Starting dose is 300 mg HS, increased over few days to 300–900 mg TID | Fatigue, dizziness, nervousness, lethargy | Alpha-2-delta calcium channel subunit blocker |
Nadolol | Starting dose is 40 mg once daily, maximum 240 mg/day | Dizziness | B1/B2 antagonist |
Atenolol | Starting dose is 50 mg once daily, maximum150 mg/day | Postural hypotension, lightheadedness, nausea, cough, dry mouth, sleepiness | B1 antagonist |
Clonazepam | Starting dose is 0.5 mg TID to 2 mg/day | Lethargy | Benzodiazepine |
Botulinum toxin A for head tremor | Dose ranges from 50 to 400 units depending upon muscles involved and degree of tremor | Excessive weakness of injected muscles, dysphagia, injection pain | Injected every 3–4 months |
Beta-Blockers
Among the beta-blockers, the most effective medication is propranolol. Drugs that are predominantly B–1 antagonists are less effective than those that act on B–2 receptors as well. Overall, about 25 % of patients are able to maintain their initial improvement for about 2 years. It is a nonselective beta-adrenergic receptor antagonist. Some patients may take propranolol only before social engagements, whereas others may use it on a daily basis. If propranolol is to be taken on daily basis, the dosage ranges from 60 to 260 mg/day. Propranolol is effective in treating essential tremor involving limbs, and many studies have shown that the magnitude of tremor is reduced by at least 50 % as measured by accelerometry and clinical rating scale.
Side effects include a drop in blood pressure, fatigue, depression, impotence, and bradycardia. Propranolol is contraindicated in patients with asthma, COPD, or heart failure. Diabetes mellitus is also a relative contraindication as propranolol can mask symptoms of hypoglycemia.
Propranolol LA may be taken only once a day as it is a long-acting preparation. Propranolol LA is also effective in improving limb tremor. In one study propranolol LA caused about 30–38 % improvement in limb tremor when measured by accelerometry. Propranolol, propranolol LA, and primidone exhibit a similar therapeutic effect for the limb tremor.
Atenolol also has a positive therapeutic effect on limb tremor. The dose is 50–150 mg/day. About 25 % mean improvement on the clinical rating scale and a 37 % improvement by accelerometry were noticed in one study. However, side effects such as lightheadedness, nausea, cough, dry mouth, and sleepiness may limit its use.
In one study, nadolol, at a dose of 120–240 mg daily, resulted in about 60–70 % improvement by accelerometry in patients who previously responded to propranolol. The side effects include dizziness.
Primidone
Primidone, conventionally used as an antiepileptic medication, provides a significant therapeutic benefit for essential tremor. It is a GABA agonist. The initial dose is one quarter of a tablet of 125 mg (31.25 mg) which is increased slowly. The average reduction in tremor is at least 50 % when measured by the clinical rating scale and accelerometry. One third of the patients may have a strong feeling of being unwell and experience side effects of drowsiness, confusion, nausea, and dizziness upon the initiation of this drug. However, these side effects may improve in 2–3 weeks time.
Combined treatment with propranolol and primidone may be more effective than monotherapy with either of these agents alone. In one study, the addition of 50–1,000 mg/day of primidone to propranolol reduced the tremor amplitude more than when propranolol was used alone. Propranolol at an average dosage of 260 mg/day (its maximum effective dosage) reduced tremor amplitude by a mean of 35 %, but the addition of primidone (50–1,000 mg/day) decreased the tremor amplitude by a mean of 60–70 %.
Propranolol and primidone alone are almost equally effective in the treatment of both postural and kinetic tremor, but the combination of these two drugs is more effective than either drug used alone. The combined treatment with primidone and propranolol can be used to treat limb tremor when monotherapy is not sufficient. The therapeutic effects of primidone and propranolol on postural and kinetic tremor last for at least several years. However, the response may decrease partially with time. The dosage of primidone and propranolol may need to be increased with time.
Other Therapies
Topiramate is a sodium channel blocker. Its common indications include epilepsy and prophylaxis of migraine. It has a mild to moderate effect in reducing essential tremor. In one study, it resulted in about a 22–37 % mean improvement in limb tremor when measured by the clinical rating scale. The initial starting dose of topiramate is 25 mg once a day, a dosage which is increased slowly to two or three times daily. Side effects include decrease in appetite, weight loss, paresthesias, concentration difficulties, exacerbation of glaucoma, and renal stone.
Gabapentin has a mild to moderate beneficial effect on essential tremor. In one study, gabapentin reduced postural and kinetic tremor when administered at a dose of 1,200 mg/day. When gabapentin was used as a monotherapy, there was about a 77 % improvement by accelerometry and a 33 % improvement on the clinical rating scale. The side effects include fatigue, dizziness, nervousness, and lethargy.
Pregabalin has a similar efficacy as gabapentin, and initial doses at 50 mg/day with the maximum dose of 600 mg/day reduce tremor severity at the mean dose of 286 mg/day. Side effects profile is very similar to gabapentin.
In one study, benzodiazepines, especially clonazepam, significantly reduced the kinetic tremor. There was about a 71 % mean improvement by accelerometry and a 26–57 % improvement in limb tremor on the clinical rating scale. The dose ranged from 0.5 to 6 mg/day. Side effects include drowsiness. There is a potential of abuse and possibility of withdrawal symptoms associated with clonazepam, and therefore it should be used with a great caution.
Treatment of limb tremor with atenolol, topiramate, and gabapentin is not as effective as propranolol or primidone. Therefore, atenolol, topiramate, and gabapentin are considered for treatment of postural and kinetic limb tremor if propranolol or primidone are not helpful.
Botulinum toxin may offer some improvement but may cause finger or wrist weakness. Botulinum toxin has been used to treat hand, head, and voice tremor variants of the essential tremor syndrome. About a 67 % improvement in head tremor was noticed by accelerometry in one study. The side effects include pain at the injection site and weakness. The effect of botulinum toxin on essential tremor affecting limbs is mild. About a 20 % improvement in postural tremor and a 27 % improvement in kinetic tremor were noticed in one study. It may reduce head and voice tremor, but when used to treat voice tremor, botulinum toxin may cause hoarseness of voice and swallowing difficulties. In one study, about a 22 % improvement with unilateral injections and a 30 % improvement with bilateral injections were noticed in voice tremor. The botulinum toxin injections for limb, head, and voice tremor may be considered in medically refractory cases.
Surgical Treatments
Surgical treatments are used for patients who have very advanced essential tremor which is refractory to the pharmacological management. Two types of surgical treatments are done: thalamotomy and deep brain thalamic stimulation (Table 1.4).
Table 1.4
Surgical treatments of essential tremor
Technique | Side effects | Comments |
|---|---|---|
Thalamotomy | Transient contralateral weakness, dysarthria, contralateral hemiparesis, verbal or cognitive deficits, and confusion | Marked improvement of contralateral tremor. Side effects are much more pronounced with bilateral procedure, and bilateral thalamotomy is not recommended |
Gamma knife thalamotomy | Transient contralateral arm weakness and numbness, dysarthria, dystonia of the contralateral arm and leg | Insufficient evidence. May be similar to thalamotomy and only unilateral procedure is performed |
Deep brain thalamic stimulation | Dysarthria, weakness, numbness, headache, intracranial hemorrhage, disequilibrium, and decreased verbal fluency | Marked improvement in limb tremor, insufficient evidence for voice and head tremors. Side effects less than in thalamotomy and include dysesthesia and dysarthria. Bilateral procedure is commonly performed if indicated |
Surgical procedures such as stimulation of the nucleus ventralis intermedius or ablation are used for intractable tremor, and a significant improvement in the tremor has been reported. In presurgical assessment, patients are evaluated by a multidisciplinary team, including a neurologist with expertise in movement disorders, a neurosurgeon, and a neuropsychologist. Appropriate brain imaging is also performed. The procedure may be unilateral or bilateral depending on the degree of tremor.
1.
Unilateral deep brain stimulation results in marked improvement of contralateral postural and kinetic tremor. In one study, about a 60–90 % improvement on the clinical rating scale was noticed in limb tremor. Voice tremor usually does not improve by the unilateral nucleus ventralis intermedius stimulation. Inconsistent results have been reported about the response of head tremor to unilateral or bilateral deep brain stimulation. Deep brain stimulation has shown greater improvement and fewer side effects than thalamotomy. However, these procedures are invasive, and side effects like speech and swallowing problems, sensory disturbances, and balance problems may occur. There is also a risk of infection and hemorrhage associated with these procedures. The side effects of this treatment can usually be reduced by adjusting the stimulus parameters, but this may result in reduced tremor suppression and efficacy.
2.
Unilateral thalamotomy is very effective for the treatment of contralateral limb tremor, while bilateral thalamotomy has frequent and severe side effects. In one study, about a 55–90 % improvement on the clinical rating scale was noticed. Relief of essential tremor after thalamotomy has been thought to be related to disruption of abnormal thalamocortical synchronization. The first thalamotomy for essential tremor was performed in the early 1960s.
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