Tremor

Author: Dr Daniel Tarsy Harvard Medical School 2008-07-28

Introduction

Tremor is a rhythmic movement of a portion of the body such as the arm, hand, leg, head, voice, or trunk which varies in size but has a relatively constant frequency for an individual patient. Tremor is the most common of all disorders causing involuntary movements. It also occurs from time to time in most normal individuals in the form of an exaggerated physiologic tremor.

Classification of tremors

Tremors are classified into resting, postural, action, and intention tremors. Resting tremors occur when the affected body part is completely at rest. Postural tremors occur when the arms or hands are being raised against gravity while holding on to object such as a newspaper for example. Action tremors occur during the middle of a voluntary movement. Intention tremors increase in size and severity during the course of a voluntary and goal-directed movement whereas postural and action tremors do not.

Resting tremor

Parkinson's disease (PD) and other Parkinson syndromes are the most common causes of resting tremor. The tremor is present with the affected body part fully supported and completely at rest and will temporarily disappear during voluntary activity. Resting tremors often fluctuate in their size and may come and go depending upon the degree of patient relaxation, whether the patient appears to be under observation, and other less well defined internal factors.

Resting tremors are usually less disabling than postural, action, or intention tremors because of their absence during voluntary activity. However, the tremor typically reappears when the arm or hand moves into a new position and may therefore interfere with activities of daily living such as the use of eating utensils, handwriting, and other purposeful movements. It is also usually activated while walking. In most cases, if resting tremor is a handicap or disability, it is more because of its visibility to others rather than a limiting effect on motor function.

Resting tremor associated with Parkinson’s disease (PD). Resting tremor in PD typically appears first in one hand. It may later spread to involve the leg on the same side and/or the contralateral hand. Tremor in the leg or foot is more commonly due to PD than other causes of tremor such as essential tremor (ET) (See below). The face, lips, and jaw may be involved but, unlike ET or disorders of the cerebellum, PD usually does not produce tremor of the entire head.

When the tremor is limited to muscles of the hand it may have a typical "pill-rolling" appearance, with a frequency of 4 to 6 beats/second. If it becomes more severe over time, it may become more constant, larger in size, and involve more of the arm.

Tremor dominant PD

This is a form of PD in which a low amplitude resting tremor of the hand or jaw is not accompanied by other significant signs of parkinsonism such as slowing down of movement, rigidity, or gait disturbance. It occurs by itself or with other signs of mild parkinsonism but does not progress to full blown PD. In most cases however, tremor is a first sign of PD which is eventually followed by progressive and more disabling symptoms such as slowness of movement (bradykinesia), muscle rigidity, gait disturbance, and impaired balance.

Other disorders which cause resting tremor are Wilson's disease which is a disorder of copper metabolism that affects the brain and liver; hepatocerebral degeneration which is a brain disorder that complicates cirrhosis of the liver; and various injuries of the midbrain due to stroke, trauma, or multiple sclerosis. Resting tremor may also occur in combination with severe postural and action tremors in some other chronic neurological disorders described below.

Rubral tremor. Rubral tremor is an uncommon type of tremor which occurs following midbrain injuries that are caused by head trauma, stroke, or multiple sclerosis. It is due to damage to structures of the midbrain which connect the cerebellum with other parts of the brain which regulate motor function. This tremor typically produces a mixture of resting, postural, action, and intention tremor.

Postural and action tremor

Postural and action tremors make up the largest group of tremors. During the neurological examination they are found when the patient is asked to hold his arms held straight in front of him and while carrying out goal-directed activities such as placing the index finger on the nose or drinking from a cup of water.

Physiologic tremor

Normal individuals all have a low amplitude, high frequency tremor of 10 to 12 beats/second that is not visible under ordinary circumstances. Many factors will enhance this physiologic tremor enough to make it visible. Enhanced physiologic tremor is the most common cause of postural and action tremor and is, for example, most commonly due to drugs or other medical causes rather than primary neurologic disorders

• Drugs which increase activity of the sympathetic nervous system commonly increase physiologic tremor. These include asthma drugs such as terbutaline and isoproterenol, epinephrine, amphetamines, selective serotonin reuptake inhibitor (SSRIs) and tricyclic antidepressants, levodopa, nicotine, caffeine, and theophylline.
• Situations which cause release of adrenaline all typically enhance physiologic tremor. These situations include: anxiety, excitement, fright, fatigue, low blood sugar, withdrawal from alcohol or narcotics, hyperthyroidism, fever, and pheochromocyoma (an adrenaline secreting tumor). 
• Miscellaneous drugs and toxins increase physiological tremor by uncertain means such as lithium, corticosteroids, the anti-seizure medication sodium valproate, the cardiac drug amiodarone, mercury, lead, and arsenic.

Essential tremor

Essential tremor (ET) is the most common neurologic disorder to cause postural or action tremor. It is estimated to be present in up to five percent of the population world-wide. The frequency of ET increases with age, although it may also affect younger individuals, especially when it runs in families. ET runs in families in approximately 50 percent of cases. The use of "benign" as a modifier for ET has been used to distinguish it from PD but this term should be omitted since the tremor may sometimes be severe and disabling.

A dominantly inherited form of ET has been tentatively linked to genes located on several different chromosomes. However, most families with ET do not appear to have these abnormal genes. Close relatives of patients with ET have an increased risk of developing the disorder, particularly when the affected individual develops the disorder at an early age.

The pathological changes in the brain responsible for ET are currently unknown but several recent studies have shown the presence of cellular inclusions called Lewy bodies in some nerve cells in the brainstem and loss of other cells in the cerebellum called Purkinje cells. The significance of these findings is uncertain and further pathological examinations will be necessary to confirm these findings.

• Clinical features of ET. ET most often affects the hands and arms and may affect one arm more than the other. It can also affect the head, voice, trunk, and legs. Tremor becomes immediately apparent in the hands when the arms are held outstretched. In many cases it increases at the very end of goal-directed movements such as drinking from a glass or finger-to-nose testing. Tremor in the legs is unusual in ET and more common in PD. 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. Some patients with ET also develop enhanced physiologic tremor due to anxiety or other adrenergic mechanisms which aggravate their underlying tremor. ET is characteristically relieved by small amounts of alcohol but unlike physiologic tremor, it is not usually aggravated by caffeine. By definition, tremor is the only neurologic abnormality which is present in patients with ET. However, in some severe cases, a mild gait disorder and signs of a cerebellar deficit may also be present. In addition, preliminary studies have recently suggest that very mild cognitive deficits with reduced performance on tests of memory and frontal lobe functions may be more common in patients with ET than age-matched controls although this finding appears to be very uncommon and remains to be confirmed.
• Differential diagnosis of ET. ET must be distinguished from PD tremor. Differentiation from the typical resting tremor of PD is usually straightforward but there is frequently some overlap of tremor types. Some patients with PD have a postural-action tremor indistinguishable from ET. Likewise, patients with severe ET may have a resting tremor in addition to their postural-action tremor. The presence of subtle motor slowing (bradykinesia) or small handwriting (micrographia) in early cases of Parkinson postural tremor helps to make the diagnosis of PD, although in some cases these additional signs may not appear until later on. Conversely, elderly patients with ET may have mild bradykinesia and limb rigidity as a nonspecific effect of aging. Head tremor is more likely to be a manifestation of ET, while tremor of the jaw or lips is more typical for PD. Head tremor is also common in another neurological movement disorder known as cervical dystonia (spasmodic torticollis) where it may be due either to the presence of both disorders occurring in a single patient or because of dystonic muscle spasm. Incoordination (ataxia), dysmetria, tremor involving the upper arm more than the hand, or a gait disorder usually suggest a disorder of the cerebellum rather than ET. However, as mentioned above, mild cerebellar signs are occasionally present in more severe familial tremors. Voice tremor rarely occurs by itelf but when it does it should be differentiated from dystonia of the muscles of the vocal cords (spasmodic dysphonia). Essential voice tremor produces a quavering voice without the hoarseness, voice strain, and voice breaks characteristic of spasmodic dysphonia.

Primary writing tremor

Many action tremors including ET are particularly severe during the act of writing. In some cases, writing becomes impossible. Tremor that occurs exclusively while writing--but not during other voluntary motor activitie--is referred to as primary writing tremor. This tremor is limited to the hand and causes relatively large amplitude tremor at a frequency of five to six beats/second. The low frequency and large amplitude of the tremor and its frequent occurrence in writer's cramp or writer's dystonia suggest a closer relationship to dystonia than to ET.

Orthostatic tremor. This is a tremor that is limited to the legs and lower trunk and occurs exclusively while standing. It is usually a much higher frequency tremor than ET. Its relationship to ET is uncertain. The tremor in the legs may be so low in amplitude that it is not easily visible and therefore often initially escapes detection. Orthostatic tremor is uniquely responsive to treatment with clonazepam, a drug which is not effective in ET.

Cerebellar tremors. Tremors due to primary disorders of the cerebellum may be postural, action, or intention in type. In severe cases, they may spill over to occur at rest. Tremor frequency is typically quite low (three to four beats/second) and is nearly always associated with incoordination of the extremities. To and fro movements of head and neck are called titubation and are commonly associated with cerebellar tremor. It is distinguished from essential head tremor by the presence of other cerebellar abnormalities.

Rubral tremor

This is caused by disturbances of pathways between the midbrain and an area called the thalamus (see description of rubral tremor under Resting Tremors). It is mainly a resting tremor which increases when maintaining a posture such as extending the arms and during voluntary activity.

Neuropathic tremor

Some disorders of the peripheral nerves, known as peripheral neuropathy, are sometimes associated with postural and intention tremor. This association is most commonly observed in hereditary neuropathies, during the recovery phase of some cases of Guillain-Barré syndrome (an immune system disorder), and in chronic inflammatory demyelinating polyneuropathy (progressive weakness and impaired sensory function in the arms and legs). A combination of muscle weakness and loss of sensation may account for the tremor.

Intention tremor

Intention tremor, also called kinetic tremor, is due to disturbances anywhere along the nerve fiber pathways leaving the cerebellum and traveling to the thalamus. The most common causes are multiple sclerosis, midbrain injury, and midbrain stroke. Hereditary degenerative diseases of the cerebellum, severe forms of ET, Wilson's disease, hepatocerebral degeneration, and mercury poisoning may also produce intention tremor.

Intention tremor typically increases in severity as the hand moves closer to its target in contrast to postural and action tremors, which either remain constant throughout the movement or abruptly increase after reaching the target such as when the patient is asked to place and keep his finger on his nose. Intention tremors are usually very large in amplitude due to involvement of the upper arm and shoulder muscles and are sometimes difficult to distinguish from cerebellar ataxia (incoordination). The frequent association with ataxia, dysmetria (undershooting or overshooting of the intended position of the hand or finger), titubation, and other typical cerebellar signs helps to determine that the tremor is due to cerebellar disease.

Psychogenic tremor

Psychogenic tremor is based on the presence of underlying and often unrecognized psychological conflicts, depression, or anxiety states. Useful criteria for the diagnosis of psychogenic tremor have been established. These are typically complicated looking mixtures of resting, postural, and action tremors with abrupt onset, a nonprogressive course, variable and changeable features, a functional disability which is out of proportion to magnitude of the tremor, and resistance to treatment. Any body part may be involved, but the fingers are often spared. Other features of psychogenic movement disorders are usually present such as inconsistent symptoms from examination to examination and clinical features that are not compatible with known tremor disorders.

Evaluation of tremor

The neurologist’s approach to evaluation of tremor involves a careful history, physical and neurological examination, and selected laboratory studies. Postural and action tremor is the most common tremor type. Within this group, ET and enhanced physiologic tremor are the most frequent causes of tremor. Patients with tremor due to other disorders such as hyperthyroidism, PD, dystonia, or Wilson's disease frequently have additional signs or symptoms that help point to the diagnosis.

History. The history concerning the onset of tremor is usually straightforward, since it is a highly visible symptom that is obvious 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 identified. A complete list of all medications the patient is taking should be reviewed to exclude the possibility of a drug-induced tremor.

Family history in ET indicates a dominant pattern of inheritance in approximately half of all patients. Parkinson tremor is usually sporadic, but a family history of PD is present in approximately 15 percent of cases

Examination

Examination begins with observation 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 more comfortable with 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 may also occur in cervical dystonia and cerebellar disorders. Localized face, jaw, and lip tremors are usually a manifestation of parkinsonism. Essential voice tremor is easily audible, but may be made more obvious by having the patient hold a prolonged vowel sound.

Tremor in the arm is observed with the affected limb fully supported at rest, with the limb elevated against gravity, and during voluntary movements such as touching the finger to the nose, drinking from a cup of water, or pouring water from one cup to another. Writing and drawing may demonstrate the large, tremulous, angulated loops of ET or the micrographia (small and cramped handwriting) of parkinsonism. Most resting tremors stop when the arms are raised or while carrying out a voluntary act but quickly reappear after getting into a new posture (called re-emergent tremor). Resting tremors are also activated by repetitive movements of the opposite hand, during walking, or if the patient is distracted by counting backwards.

Tremor of the leg should be assessed with the limb at rest, while running the heel down the opposite shin, 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 often has a dramatic and exaggerated quality in patients with psychogenic tremor.

Enhanced physiologic tremor is high in frequency (10 to 12 beats/second), ET can be either low or high in frequency, and parkinsonian resting tremor is usually low in frequency (four to six beats/second). Psychogenic tremors tend to vary in frequency from moment to moment and either become more irregular or subside entirely when the patient is distracted by being asked to carry out a complex, repetitive motor task with the opposite limb.

Laboratory tests for tremor

The routine laboratory evaluation of tremor should include tests to rule out an overactive thyroid gland, tests to exclude Wilson's disease, and screening for heavy metal poisoning such as mercury or arsenic. Wilson's disease should be suspected in anyone under age 40 who has tremor or other involuntary movements or postures. Hypoglycemia and pheochromocytoma need to be ruled out in patients with markedly enhanced physiologic tremor. Brain imaging should be done in patients suspected of having a structural cause for their tremor, such as Wilson's disease, midbrain trauma, midbrain stroke, multiple sclerosis, or a brain tumor. Quantitative computerized analysis of tremor is a specialized test which is available in some medical centers but its ability to reliably distinguish between tremor types has not been well established.

Medical treatment of tremor

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 medication or toxin; diagnosis and treatment of possible endocrine disorders such as hyperthyroidism, hypoglycemia, or pheochromocytoma; and dealing with stress, anxiety, or fatigue. Single doses of the beta blocker propranolol taken in anticipation of social situations that are known by the patient to exacerbate tremor are useful in some patients.
• Rest tremor. Management of resting 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, L-dopa, and zonisamide. 
• Cerebellar tremor. There is no useful medical treatment for cerebellar tremor. The rare patient with severe tremor and little or no ataxia may be helped by deep brain stimulation (DBS) of the thalamus. 
• Orthostatic tremor. Orthostatic tremor is limited to the legs and trunk and occurs exclusively while standing and not while lying down, sitting, or walking. Orthostatic tremor is uniquely, but not always responsive to treatment with clonazepam, although little data are available and controlled trials have not been published.
• Essential tremor. The treatment of ET is discussed below.

Beta blockers

Beta blockers are the most commonly used medications for the treatment of ET. Their efficacy has been demonstrated primarily for propranalol and most studies have been limited to only relatively short-term therapy.

• Propranolol. A practice parameter on therapies for ET published by the American Academy of Neurology (AAN) in 2005 concluded that propranalol, 60 to 320 mg/day, is effective for the treatment of limb tremor associated with ET. This conclusion was supported by findings from 12 controlled clinical trials. Tremor magnitude was measured by special recording devices and rating scales improved by about 50 percent. Long-acting propranalol formulations are also effective. Propranalol is less effective for head tremor but has been of mild benefit in some studies. Single doses of propranalol taken in anticipation of social situations likely to exacerbate tremor are useful in some patients. Side effects of beta blockers may include lightheadedness due to lowering of blood pressure, slowing of heart rate, depression, fatigue, and impotence. Consultation with a cardiologist is recommended prior to starting propranolol in elderly patients or patients with cardiovascular disease.
• Other beta blockers. Selective beta blockers which have less effect on the bronchial system in the lungs but are effective for tremor such as metoprolol or atenolol, can be used instead of propranolol in patients with asthma but such selectivity may be less at higher doses. Other beta blockers which may be considered include nadalol, pindolol, and sotalol but experience with these agents for treatment of tremor is very limited. Patients who have failed to respond to propranalol at usual therapeutic doses are unlikely to respond to other beta blockers.

Anticonvulsants

• Primidone. The AAN practice parameter of 2005 concluded that primidone, up to 750 mg/day, is effective for the treatment of limb tremor associated with ET. This was supported by four randomized controlled clinical trials. The size of tremor was reduced by about 50 percent which is similar to the effect of propranolol. Side effects of primidone are sometimes severe and include sedation, fatigue, nausea, vomiting, ataxia, malaise, dizziness, unsteadiness, confusion, and vertigo. The dose of primidone should be started very low and increased gradually to minimize side effects but many patients are still unable to tolerate this drug at levels required to reduce tremor. The dose should begin at 12.5 to 25 mg before sleep and be titrated slowly over several weeks. Effective doses for tremor relief are usually in the range of 250-400 mg daily. Combined administration of a beta blocker and primidone may provide additive therapeutic benefits.
• Gabapentin. Gabapentin probably reduces limb tremor associated with ET but many patients do not benefit. One randomized controlled trial found that gabapentin 1200 mg daily reduced tremor compared with placebo. Gabapentin is associated with fewer side effects than primidone. 
• Topiramate. Topiramate probably reduces limb tremor associated with ET, but in controlled trials the amount of tremor improvement was moderate at best. However, side effects such as tingling, weight loss, and speech difficulty are common causing patients to discontinue this drug. 
• Other anticonvulsants. Phenobarbital and levetiracetam have been used for treatment of ET with mixed results, but with side effects of sedation.

Other medications

• Alcohol. Alcohol has long been known to ameliorate ET. The use of small amounts of alcohol, such as a glass of wine before dinner or social events, is a reasonable practice, which is often utilized by patients. However, the use of alcohol on a daily basis to manage tremor is not recommended. Its effect is usually limited to an hour or two and it often leads to tolerance, with a need for increasingly larger amounts of alcohol to achieve the same effect. There is also the potential problem of withdrawal tremor the next morning when large amounts of alcohol are being consumed. There has been no evidence for increased incidence of alcohol addiction in patients with ET who occasionally use alcohol to control their tremor. Oral 1-octanol is an experimental alcohol which has shown promise in preliminary studies as treatment for ET. Further studies of this agent are being done to see if it will be a practical treatment for tremor.
• Benzodiazepines. Benzodiazepines are widely used because of the commonly mistaken belief on the part of both patients and physicians that tremor is due to anxiety. However, they may be helpful in patients in whom anxiety worsens tremor. Caution is advised because of the potential for dependency and the possibility of withdrawal symptoms, including worsening of tremor, if the drugs are discontinued abruptly. These problems make benzodiazepines a second-line choice for the chronic treatment of ET in selected patients in whom tremor is exacerbated by anxiety. In clinical trials, clonazepam and alprazolam have both been found to probably or possibly alleviate tremor. 
• Botulinum toxin. Botulinum toxin injections may produce modest benefit in limb tremor associated with ET but have been limited in usefulness because they usually cause hand and finger weakness in doses needed to improve tremor. As a result, there has been inconsistent improvement in functional disability. However, botulinum toxin injections are useful to reduce head tremor when injected into muscles in the back of the neck. Botulinum toxin injected into the vocal cords has been used for voice tremor but is not as effective as for spasmodic dysphonia and may be associated with side effects such as breathy voice, hoarseness, and mild swallowing difficulty. 
• Other oral drugs. A variety of other drugs have been used to treat limb tremor in ET with either limited or no effectiveness. Possibly effective are clozapine and nimodipine. Clozapine is an antipsychotic drug which is often sedating and requires weekly monitoring for possible bone marrow depression. Nimodipine is a calcium channel blocker which is possibly effective for limb tremor associated with ET. Other drugs for which clinical trials and general clinical experience have shown no convincing evidence for effectiveness include methazolamide, acetazolamide, mirtapazine, amantadine, verapamil, clonidine, glutethimide, L-tryptophan with pyridoxine, nicardipine, olanzapine, quetiapine, and theophylline. 
• Choice of therapy. Propranolol and primidone have shown similar effectiveness when compared with each other as initial treatment for ET. Acute adverse reactions with primidone and the chronic side effects of propranolol both of which are described above, may be limitations to the use of these drugs in some patients. These drugs may be used in combination to treat limb tremor and their combined use is possibly more effective than either drug alone. Both have been shown to produce benefits lasting for at least a year, although increased doses of both drugs are sometimes necessary as time goes by.

Surgical treatment of tremor

Surgery may be a treatment option for patients with severe and disabling tremor that fails to respond to medications. It has been known for many years that a very localized lesion in the thalamus will markedly improve or eliminate tremor due to a number of causes including ET or PD. This procedure is called thalamotomy. Although effective, it carries with it a significant risk of causing permanent side effects such as speech disturbance, incoordination, or weakness. For this reason, deep brain stimulation (DBS) was developed in the early 1990s as a potentially less destructive surgical procedure. Since that time it has proved to be very effective and is associated with far fewer neurological side effects.

Thalamotomy

• Thalamotomy. This is the older operation dating from the 1950s in which a lesion is made in a portion of the thalamus which plays a role in the generation of tremor. This region is called the ventral intermediate (VIM) nucleus of the thalamus. The lesion is created by using stereotactic techniques. A frame is placed around the head and, with the assistance of brain imaging and intraoperative microrecording from brain cells, coordinates are plotted to properly guide an electrode to the VIM nucleus of the thalamus. Once the electrode is in place it is heated in order to burn a small lesion in the thalamus which removes the target from the brain circuit responsible for tremor. Unilateral (on one side) thalamotomy is effective for the long-term treatment of upper extremity tremor associated with ET. One clinical trial found that tremor was completely or almost completely suppressed in 79 percent of a mixed group of patients with tremor due to ET, Parkinson's disease, and multiple sclerosis. Bilateral thalamotomy was also carried out at one time but was largely given up because if its association with more frequent neurologic side effects such as speech disturbance, weakness, and incoordination.
• Side effects of thalamotomy. The Quality Standards Subcommittee of the American Academy of Neurology (AAN) has published a practice parameter that reviewed the efficacy and side effects associated with thalamotomy limited to one side of the brain. Adverse effects occurred in up to one-half of patients, and persistent neurologic deficits such as permanent hemiparesis (partial paralysis of one side of the body) and speech difficulty in 16 percent of patients. There were also a large incidence of temporary side effects such as speech and motor impairment, cognitive deficits, weakness, confusion, and facial weakness. Most experience with bilateral thalamotomy was in patients with tremor due to PD where serious side effects occurred in a broad range of patients across several different studies but in as high as 88% of patients. Bilateral thalamotomy is no longer performed because of its association with such a high incidence of neurologic side effects. 
• Gamma knife thalamotomy. Gamma knife thalamotomy for ET is an unproven treatment. In this procedure microelectrode recording is not done to guide electrode placement. Although favorable results have been reported in several studies involving a total of 61 patients, clinical improvement is delayed for weeks to months following the procedure and delayed neurological complications have also occurred.

Deep brain stimulation

• Deep brain stimulation (DBS). This technique was first introduced for the treatment of ET and tremor associated with PD in the 1990s. It was developed as an alternative to thalamotomy because of the frequent neurological side effects associated with making lesions in the brain and the inability to safely carry out bilateral operations to treat patients with tremor in both upper extremities. Deep brain electrodes are implanted in the thalamic VIM nucleus using stereotactic methods, brain imaging, and intraoperative micro-recording of brain cell activity to properly identify the brain target for electrode implantation. The patient is awake during the procedure so that the effects of test stimulation on the tremor can be directly observed during the procedure. The electrodes are connected to a pulse generator which is implanted in a pouch created under the skin below the collar bone or in the abdomen. This second phase of the operation is either done the same day as the electrode implantation or more commonly at a separate time a week later. To allow the brain to heal following the procedure, the pulse generator is turned on a week or two after its implantation to begin to stimulate the target region. The electrode configuration, voltage, pulse frequency, and pulse width are all adjustable parameters of stimulation which are programmed and adjusted over a series of postoperative visits to optimize tremor treatment. The brain electrode and pulse generator are intended to remain in place permanently unless either must be removed because of infection. The pulse generator and its battery must be replaced every three to five years but the brain electrode is left in place.
• Advantages and disadvantages of DBS. Thalamotomy is an irreversible form of therapy which doesn’t allow for adjustments once the procedure is completed. By contrast, it is possible to immediately see the effect of DBS on tremor during the operative procedure in order to help guide the stimulating electrode to its desired location within the thalamus. Once the DBS electrode(s) have been implanted several stimulation parameters such as voltage, pulse frequency, pulse width and electrode configuration may be adjusted and programmed in order to achieve maximum benefit with minimum side effects. As time goes by, further programming can easily be carried out should the tremor increase in severity. A significant advantage of thalamotomy is that it’s a one time, relatively low cost procedure. Disadvantages of thalamotomy are its irreversibility and a higher risk of persistent neurological side effects. Disadvantages of DBS are its initial higher cost and a 5-20% risk of hardware related problems such as infection, skin breakdown over the electrode, and equipment malfunction. 
• DBS for extremity tremor. DBS of the VIM nucleus of the thalamus is effective for reduction or elimination of tremor in the opposite upper extremity due to ET. Prospective trials of DBS in patients with ET found that unilateral DBS was associated with a mean tremor improvement of 60 to 90 percent. Treatment in these studies was not randomly assigned but evaluation was done in a blinded fashion. In studies reviewed by the Quality Standards Subcommittee of the American Academy of Neurology, which involved 82 patients, DBS was associated with consistent improvement of tremor in the opposite limb as assessed by observation, writing tests, pouring tests, and activities of daily living questionnaires. 
• DBS for voice and head tremor. There is limited and conflicting evidence regarding DBS for treatment of voice and head tremor associated with ET. Two small studies reported that DBS reduced voice tremor in some patients, but another open-label trial found that unilateral or bilateral DBS was not associated with significant improvement. Unilateral DBS did not improve head tremor in one study, while another study involving 38 patients found that head tremor was improved in 71 percent, was unchanged in 26 percent, and worsened in 3 percent. Another open-label study of bilateral DBS involving 10 patients with head tremor reported improvement in 90 percent. 
• Side effects associated with DBS. Several types of adverse effects may occur after DBS. Side effects directly related to brain stimulation are the most common of these but are easily reversible with reprogramming and adjustment of the stimulus settings. The most common of these include tingling sensations (paresthesias) in the face or extremities, dizziness, dysequilibrium, and dysarthria (mildly slurred speech). There is a 1-2% risk of bleeding in or above the surface of the brain during or immediately after placement of the intracerebral electrode. Hardware related problems occur at some point in approximately 5-20% of patients. These include infection in the scalp or around the pulse generator in the chest or abdomen, skin breakdown (erosions) in the scalp over the electrode, fluid collections around the pulse generator, and breakage of the connecting lead between the pulse generator and the brain electrode. Such hardware problems are manageable and only rarely require removal of the electrode from the brain. The only long-term neurologic side effect apparently due to continues stimulation has been a mild disturbance in “verbal fluency”. What is found, for example, is a reduced number of words one can name beginning with a certain letter or the number of vegetables or automobiles one can name within a minute. This word finding deficit is very mild and usually not apparent in ordinary speech. 
• Comparison of thalamotomy with thalamic DBS. Both DBS and thalamotomy effectively suppress tremor in ET but DBS is associated with fewer persistent adverse neurological side effects than thalamotomy. In a randomized, single-blind study which compared thalamotomy and thalamic DBS, both procedures were effective but thalamotomy was associated with side effects in 50 percent of patients, including cognitive deterioration, mild dysarthria, and gait or balance problems while in the DBS treated group a single patient developed mild gait and balance difficulty. The decision to use either thalamotomy or DBS for medically refractory limb tremor in ET depends on individual patient circumstances. The decision must take into consideration the risk of immediate complications after surgery, which more commonly occur with thalamotomy compared with the hardware problems associated with DBS and the practicality, feasibility and cost of ongoing stimulator monitoring and adjustments.

Summary and recommendations for surgical treatment

The following recommendations for the surgical treatment of essential tremor (ET) are based upon the available data, adapted from the 2005 practice parameter from the American Academy of Neurology (AAN), and based on this author's clinical experience.

• Unilateral thalamotomy is an effective treatment for extremity tremor in ET that is functionally disabling and resistant (refractory) to medical treatment. However, it is a one-time treatment that is inflexible and therefore unable to deal with increases or changes in tremor that may occur after the surgery has been done. Thalamotomy is associated with a relatively high risk of immediate and long lasting neurological complications such as weakness, speech impairment, and disturbances of gait and coordination. Bilateral thalamotomy is not recommended due to a much greater risk of adverse neurologic side effects.
• Thalamic DBS is effective for reduction of contralateral limb tremor in ET and is suggested for treatment of limb tremor that is functionally disabling and refractory to medical management. Adverse effects associated with DBS include a 1-2% risk of brain hemorrhage which is similar to thalamotomy and a 5-20% incidence of hardware complications such as scalp infection, skin breakdown over the electrode, and equipment malfunction or lead displacement.
• Bilateral thalamic DBS is required to suppress bilateral upper limb tremor since unilateral DBS will only suppress limb tremor in the opposite extremity. However, bilateral DBS is associated with more frequent, although reversible, adverse effects than unilateral DBS which include slurred speech and gait disturbance. Data regarding the use of DBS for head tremor and voice tremor in ET are limited and currently there is not sufficient evidence to make recommendations regarding the use of thalamic DBS for head and voice tremor.

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