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Surgical treatment of essential tremor

Surgical treatment of essential tremor
Literature review current through: Jan 2024.
This topic last updated: Aug 15, 2023.

INTRODUCTION — Tremor is defined as an involuntary, rhythmic, and oscillatory movement of a body part with a relatively constant frequency and variable amplitude. Tremor is the most common type of movement disorder, and essential tremor (ET) is the most common neurologic tremor disorder.

ET is a clinical syndrome characterized by an action tremor involving both upper limbs of at least three years' duration [1]. Tremor may or may not be present in other locations, such as the head or voice. The legs are usually spared. The classification, detailed clinical features, and diagnosis of ET are reviewed elsewhere. (See "Essential tremor: Clinical features and diagnosis".)

This topic will review the surgical treatment of ET. The pharmacologic treatment of ET is discussed separately. (See "Essential tremor: Treatment and prognosis".)

PATIENT SELECTION — The ideal ET surgical candidate has an upper extremity tremor that interferes with the quality of life.

Tremor characteristics — Because tremor in ET involves the upper limbs, it affects many daily activities. Common examples include eating, drinking, pouring, writing, typing, texting, doing artwork, and applying makeup. Surgical treatment significantly reduces upper extremity tremor in patients with ET, allowing them to perform such tasks more easily [2-6]. When performed unilaterally, surgical treatment typically targets the dominant hand.

By contrast, there are limited and conflicting data regarding the effectiveness of surgical approaches for head or voice tremor [7-11]. Therefore, a patient with ET whose main problem is a head or voice tremor is unlikely to be offered surgery. Botulinum toxin injections are used to treat persistently disabling head or vocal cord tremor. (See "Essential tremor: Treatment and prognosis", section on 'Botulinum toxin'.)

Failure of medical therapies — Prior to considering surgery, patients should have failed adequate trials of the two first-line medication therapies for ET, propranolol and primidone. Some surgical centers may also require an adequate trial of a second-line therapy before surgical evaluation. (See "Essential tremor: Treatment and prognosis", section on 'Second-line therapies'.)

Contraindications — Dementia or significant cognitive impairment are considered contraindications to surgical treatment for ET, as they contribute to delirium in the perioperative period and may worsen after surgery. Patients with mild cognitive impairment may be candidates for surgical therapies; most surgical centers use neuropsychological testing to screen for dementia, and this underscores the importance of the multidisciplinary evaluation. Age may increase the risk for cognitive impairment, but there is no evidence that age itself affects surgical outcomes in ET.

Prior to considering surgical treatment for ET, candidates should be screened for psychiatric illness, such as anxiety and depression. If present and active, centers may opt to delay surgery until the psychiatric symptoms are stabilized.

Significant medical comorbidities such as diabetes, heart disease, and obesity may increase general surgical risk. Although these comorbidities are not absolute contraindications, they should be carefully considered prior to offering a surgical procedure such as deep brain stimulation (DBS).

MULTIDISCIPLINARY EVALUATION — Prospective surgical candidates should undergo a multidisciplinary team evaluation at a specialized center prior to surgery [12]. The multidisciplinary team typically includes a movement disorders neurologist, a functional neurosurgeon, and a neuropsychologist. A psychiatrist, speech therapist, physical therapist, occupational therapist, nurse, and social worker may also be useful members of the team.

The goals of the multidisciplinary evaluation are to:

Confirm the diagnosis of ET (see "Essential tremor: Clinical features and diagnosis", section on 'Evaluation')

Make sure the patient has undergone adequate medication trials (see "Essential tremor: Treatment and prognosis", section on 'Treatment approach')

Assess surgical risk (see "Preoperative medical evaluation of the healthy adult patient")

Screen for cognitive impairment and dementia (see "Evaluation of cognitive impairment and dementia", section on 'Cognitive testing')

Educate the patient on realistic expectations as well as risks of the procedure

After each member of the team evaluates a potential candidate, the team convenes for a frank discussion about each candidate. If the patient is felt to be appropriate for surgery, the team would then discuss the type of surgery to perform and whether to offer unilateral or bilateral surgery before sharing the consensus opinion with the patient.

PROCEDURE SELECTION — Surgical procedures for ET typically target the ventral intermediate (VIM) nucleus of the thalamus. Although the exact origin of tremor generation in ET is not entirely clear, cellular activity in the VIM nucleus of the thalamus is highly related to the tremor itself [13].

There are two surgical options for patients with medically refractory limb tremor due to ET: thalamic VIM nucleus deep brain stimulation (DBS) and thalamotomy (conventional thalamotomy, gamma knife, or magnetic resonance imaging [MRI]-guided focused ultrasound). Among these, DBS and MRI-guided focused ultrasound thalamotomy are the only two therapies approved by the US Food and Drug Administration (FDA) for treatment of ET.

The decision of whether to use either DBS or thalamotomy should be individualized and must take into consideration the risk of perioperative complications compared with the feasibility of ongoing stimulator monitoring and programming adjustments [2].

Preference for deep brain stimulation — For most patients with ET who have persistently disabling limb tremor that is refractory to medical management, DBS in the VIM nucleus of the thalamus is the more regularly chosen therapy, rather than thalamotomy. While both procedures are effective for tremor and there have been limited direct prospective comparisons, we prefer DBS for two main reasons:

The DBS procedure does not involve destruction of brain tissue, whereas thalamotomy produces a permanent lesion that cannot be reversed.

DBS can be performed bilaterally if needed, whereas bilateral thalamotomy frequently causes significant speech impairment. While bilateral VIM DBS may also cause dysarthria and other adverse effects, stimulation can typically be adjusted to relieve these side effects.

Role of unilateral thalamotomy — MRI-guided focused ultrasound is a newer technique that has become available to carry out unilateral thalamotomy. It does not require craniotomy and does not use radiation, which gives it relative advantages over other forms of thalamotomy.

As experience with focused ultrasound thalamotomy accumulates at specialized centers, it is becoming a reasonable alternative for refractory ET if DBS is not available or practical due to age, other medical issues, or poor access to DBS centers for ongoing stimulator monitoring and adjustments. More long-term outcome information for this technique is still needed, however.

Conventional unilateral thalamotomy has largely been replaced by DBS for the reasons discussed above. (See 'Preference for deep brain stimulation' above.)

DEEP BRAIN STIMULATION

Device implantation and programming — When used to treat ET, deep brain stimulation (DBS) typically involves the implantation of an electrode (or lead) with four or more contacts in the thalamic ventral intermediate (VIM) nucleus using stereotactic methods [2,14]. More limited data are available for stimulation of the posterior subthalamic area (PSA). (See 'Other stimulation targets' below.)

The implanted lead is connected via a connecting wire to a pulse generator implanted in the chest wall below the clavicle (similar to a permanent pacemaker). When turned on, the pulse generator delivers high-frequency electrical stimulation through one or more contacts in the lead.

Programming of the pulse generator to optimize the electrode configuration, voltage, pulse frequency, and pulse width is typically done by a member of the treatment team with a handheld device. The initial DBS programming visit usually occurs a few weeks after implantation. During this visit, each contact is tested for its ability to reduce tremor in the contralateral upper extremity, while observing for side effects. The effect of stimulation on tremor can be seen quickly, sometimes within seconds. The contact with the settings that provide the greatest benefit with the fewest side effects is selected for stimulation.

Since there is no universal formula for programming, each patient must participate in the transaction to inform the programmer when the best settings have been achieved. Follow-up visits to optimize the stimulator settings may initially be frequent, depending upon the clinical response. Stable settings are usually achieved after a few months of programming.

Once stable settings are achieved, regular follow-up visits for programming checks (once every 6 to 12 months) are necessary to maintain the best clinical benefit and to monitor battery life (typically three to five years) [15]. Patients who require extremely high stimulator settings to control tremor may find that the battery drains more quickly (eg, less than two years). Pulse generators with a rechargeable battery are now readily available, and their use would eliminate the need for frequent pulse generator replacements.

Ventral intermediate nucleus stimulation — Evidence-based guidelines from the American Academy of Neurology (AAN) conclude that DBS of the thalamic VIM nucleus is effective in reducing contralateral limb tremor in ET [2,3]. VIM DBS should not generally be performed for head or voice tremor in patients with ET, as the experience to date suggests that with unilateral stimulation, these tremors are not meaningfully improved by DBS in most patients. Bilateral VIM stimulation may improve head or voice tremor in some patients, but is also more likely to cause dysarthria than unilateral stimulation.

Outcomes — In short-term prospective open-label and blinded evaluation trials of VIM DBS in patients with ET, the mean relative improvement in contralateral postural and kinetic limb tremor from baseline is between 60 to 90 percent when measured within a year of implantation [4,5,10,16-18]. VIM DBS also improves disability and health-related quality of life [16-18].

Tremor improvement can even be maintained beyond 10 years, although the long-term mean contralateral limb tremor improvement may drop to approximately 50 percent [19-22]. The decrease in effectiveness of DBS over the long term has been attributed to progression of the disease but may also reflect some degree of habituation to stimulation [23].

Occasionally, patients may have unsatisfactory results from DBS. In such cases, referral to an experienced DBS center is recommended for evaluation and management. There may be several reasons for these DBS "failures," the most common of which are inadequate programming, suboptimal lead placement, and hardware-related complications. In a retrospective case series of 41 movement disorder patients (ET, Parkinson disease, and dystonia) referred to two DBS centers because of poor results from DBS, 51 percent ultimately had good outcomes after lead revision, reprogramming of the stimulator, or medication adjustments [24].

Complications — Complications of DBS may be surgery related, device related, or stimulation related.

General operative risks of brain surgery include perioperative confusion, headache, ischemia, and seizures. The risk of hemorrhage secondary to electrode implantation is approximately 1 percent in patients undergoing thalamic DBS for ET [25].

Device-related complications, such as equipment malfunction, lead breakage, infection, or lead migration, have occurred in up to 15 percent of all DBS patients depending on the series [2,26].

Stimulation-related adverse effects include dysarthria, contralateral face and/or limb paresthesias, imbalance and gait instability, and dystonia. Paresthesias in the contralateral face and limb are commonly experienced when turning the stimulator on or when increasing stimulation, but they are mostly transient, lasting a few seconds before resolving. Dysarthria, dystonia, and gait instability are less common than paresthesias and often resolve with adjustment of stimulator parameters.

Unilateral versus bilateral stimulation — Since unilateral DBS suppresses only contralateral limb tremor, bilateral thalamic DBS is needed to suppress bilateral upper limb tremor. However, bilateral thalamic stimulation is associated with a greater risk of hemorrhage and more stimulation-related side effects, in particular dysarthria and gait instability, than unilateral stimulation [2,3,5,27].

The decision as to whether to offer unilateral or bilateral thalamic DBS should be made after discussion of the relative risks and benefits between the multidisciplinary team and the patient. Some DBS centers will perform unilateral thalamic DBS for disabling tremor in the dominant hand initially and then implant a contralateral thalamic DBS lead for tremor in the other hand later if unilateral DBS does not provide sufficient improvement in quality of life.

Other stimulation targets — VIM nucleus stimulation works very well for limb tremor in ET and is the only target approved by the US Food and Drug Administration (FDA) for ET. However, occasional patients have tremor that does not respond to VIM stimulation, and other targets are being explored.

Posterior subthalamic area (PSA) stimulation is one example. A couple of crossover trials have placed DBS leads in a position that allows dorsal contacts to stimulate the VIM nucleus and ventral contacts to stimulate the PSA [28-30]. These trials have suggested that tremor control is slightly better with PSA DBS compared with VIM DBS, but a comparative trial targeting the two targets separately is needed.

UNILATERAL THALAMOTOMY — There are three types of thalamotomy procedures: conventional, gamma knife, and MRI-guided focused ultrasound. All of these procedures create a permanent lesion in the ventral intermediate (VIM) nucleus of the thalamus to treat contralateral limb tremor.

Bilateral thalamotomy is not routinely performed for ET as conventional bilateral thalamotomy was associated with an unacceptably high rate of side effects, particularly impairment of speech articulation [2]. However, there are ongoing trials of bilateral thalamotomy using MRI-guided focused ultrasound.

Conventional thalamotomy — Conventional unilateral thalamotomy is similar to DBS in that it uses stereotactic surgical and electrophysiologic techniques to locate the VIM nucleus of the thalamus. Patients are placed in an operating head frame and a burr hole is drilled in the skull. A probe is guided into the thalamus, where radiofrequency is used to create a lesion. This method has essentially been replaced by DBS, since DBS does not create a permanent lesion. (See 'Preference for deep brain stimulation' above.)

Limited data from older open-label trials suggest that unilateral thalamotomy is effective for treating contralateral limb tremor associated with ET, reducing tremor severity in 80 to 90 percent of patients, which can be maintained long term [2,31-33]. Adverse effects associated with thalamotomy occur in approximately 14 to 47 percent of patients, and persistent adverse events occur in approximately 16 percent [2].

MRI-guided focused ultrasound thalamotomy — MRI-guided focused ultrasound thalamotomy has received regulatory approval in the United States and Europe for treatment of refractory ET. As discussed above, it is a reasonable alternative to DBS in selected patients, although longer-term follow-up data are still needed (see 'Role of unilateral thalamotomy' above). The technique uses high-energy ultrasound beams to create a lesion in the VIM nucleus of the thalamus. Although MRI-guided focused ultrasound has been marketed as "noninvasive," meaning it does not require craniotomy, it should actually be considered an invasive procedure, as brain tissue is destroyed. Electrophysiologic guidance is not possible with this approach.

Unilateral lesioning – Regulatory approval was based on short-term results of a multicenter trial in which 76 patients with medically refractory ET were randomly assigned in a 3:1 ratio to focused ultrasound thalamotomy (producing unilateral thermal ablation of the thalamic VIM nucleus) or to a sham procedure [6]. At three months, the thalamotomy group had significantly greater improvement in hand tremor scores compared with the sham treatment group; the between-group difference in the mean change from baseline was 8.3 points (95% CI 5.9-10.7) and was maintained at 12 months (7.2 points, 95% CI 6.1-8.3). The thalamotomy group also had significant improvements in scores assessing disability and quality of life. Of some concern, tremor scores in the thalamotomy group increased slightly from 3 to 12 months, suggesting possible gradual loss of efficacy [34]. Adverse events at three months were more common in the thalamotomy group, including gait disturbance in 36 percent and numbness or paresthesia in 38 percent; these persisted at 12 months in 9 and 14 percent, respectively [6].

With further follow-up of the trial participants, including 19 of 20 patients in the sham group who were actively treated after the three-month blinded period, initial benefits were sustained in most patients at three and five years of follow-up, although confidence is limited by a high rate of loss to follow-up over time (eg, only 40 out of 75 treated patients completing follow-up assessments at five years) and rare crossover to other therapies (eg, deep brain stimulation [DBS] in four patients) [34-37]. Compared with preprocedure baseline scores, the improvement in postprocedure tremor scores remained stable over 60 months in patients who were available for follow-up examinations. No new adverse events emerged, and two patients with persistent paresthesias or ataxia at 12 months reported resolution of symptoms at 24 months.

Bilateral lesioning – In a phase 2 trial of 10 patients with ET who underwent bilateral MRI-guided focused ultrasound but with a smaller lesion on the second side, tremor severity and quality of life were improved at three months [38]. Only one patient reported speech difficulty, although two patients had mild dysphagia at three months. Two patients had transient gait problems that resolved by three months. These results suggest that bilateral thalamotomy (with a smaller lesion on the second side) using MRI guided-focused ultrasound is reasonably safe, but further studies are needed.

Other techniques — Stereotactic radiosurgery is a noninvasive technique in which a single high dose of radiation is delivered in a highly focused way to an MRI-defined target in the brain. In the case of ET, the target is the VIM nucleus of the thalamus. (See "Stereotactic cranial radiosurgery".)

Unilateral stereotactic radiosurgery thalamotomy delivered by gamma knife or other modalities has been reported to improve tremor in 75 to 90 percent of patients, but clinical improvement is delayed for weeks to months following the procedure [2,39-41]. Neurologic complications include transient or permanent hemiparesis, dysphagia, and transient/sustained facial sensory loss.

Radiosurgery thalamotomy has not generally been adopted for ET due to concerns about delayed radiation side effects, including risk of radiation necrosis and a theoretical risk of secondary tumor formation [2,3].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Essential tremor".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Tremor (The Basics)")

Beyond the Basics topics (see "Patient education: Tremor (Beyond the Basics)")

PATIENT PERSPECTIVE TOPICS — Patient perspectives are provided for selected disorders to help clinicians better understand the patient experience and patient concerns. These narratives may offer insights into patient values and preferences not included in other UpToDate topics. (See "Patient perspective: Essential tremor with onset in childhood" and "Patient perspective: An artist with essential tremor".)

SUMMARY AND RECOMMENDATIONS

Patient selection – Before considering surgical intervention, patients with essential tremor (ET) should have adequate trials of at least the two first-line therapies for ET, propranolol and primidone. Some surgical centers may also require failure of a second-line agent before surgical evaluation. (See 'Failure of medical therapies' above and "Essential tremor: Treatment and prognosis".)

Multidisciplinary evaluation – Prospective candidates should undergo a multidisciplinary team evaluation at a specialized center. Procedure selection is individualized and should consider the risk of perioperative complications compared with the feasibility of ongoing stimulator monitoring and adjustments. (See 'Multidisciplinary evaluation' above.)

Procedure selection – Surgical options for disabling limb tremor due to ET include deep brain stimulation (DBS) in the ventral intermediate (VIM) nucleus of the thalamus and unilateral thalamotomy with MRI-guided focused ultrasound. Botulinum toxin injections into neck muscles or vocal cords can be used to treat persistently disabling head or vocal cord tremor. (See 'Procedure selection' above.)

For most patients with ET who have persistently disabling unilateral or bilateral limb tremor that is refractory to medical management, we suggest surgical treatment with DBS over thalamotomy (Grade 2C). Compared with thalamotomy, DBS does not produce a permanent lesion, can be performed bilaterally if deemed necessary, and allows for future adjustments if these should become necessary over time. (See 'Preference for deep brain stimulation' above and 'Outcomes' above.)

Unilateral thalamotomy with MRI-guided focused ultrasound is a reasonable alternative for treating contralateral limb tremor associated with ET. This is the only form of thalamotomy approved for ET by the US Food and Drug Administration (FDA), although data on long-term durability remain limited. (See 'MRI-guided focused ultrasound thalamotomy' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Ludy Shih, MD, and Daniel Tarsy, MD, who contributed to earlier versions of this topic review.

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