eMedicine Specialties > Neurology > Movement and Neurodegenerative Diseases

Surgical Treatment of Tremor

Author: Michele Tagliati, MD, Division Chief of Movement Disorders, Associate Professor, Department of Neurology, Mount Sinai School of Medicine
Coauthor(s): Ron L Alterman, MD, Associate Professor of Neurosurgery, Mount Sinai School of Medicine; Consulting Surgeon, Department of Neurosurgery, Mount Sinai School of Medicine, Elmhurst Hospital, and Walter Reed Army Medical Center
Contributor Information and Disclosures

Updated: May 15, 2006

Introduction

Tremor is the most common movement disorder and can be associated with several disorders affecting the central and peripheral nervous systems. As with Parkinson disease (PD), surgical approaches to the treatment of tremor developed primarily in response to the failure of medical therapies to provide long-term relief.

Before the advent of levodopa therapy for PD, a combination of factors including the absence of effective medical therapies, introduction of human stereotaxis, the large population of patients with postencephalitic parkinsonism, and a more permissive environment promoted the development of neurosurgical approaches to tremor and related movement disorders.

With the introduction of levodopa in the late 1960s and its remarkable effectiveness against PD tremor and other parkinsonian symptoms, surgical treatments were abandoned except in rare situations when tremor was medically unresponsive. Over time, however, the waning response to levodopa and the unexpected adverse effects of long-term treatment became apparent.

The relative failure of levodopa to provide a lifelong "cure" for PD coincided with advances in stereotactic technique that resulted in a renaissance of the field of movement disorder surgery. Many factors contributed to this rebirth, including the following:

• Improved stereotactic frames adapted for use with computed tomography (CT) and magnetic resonance imaging (MRI) ushered in the era of image-guided neurosurgery.
• Computers permitted human stereotactic atlases to be digitized and overlaid onto images of the patient's brain. This mathematical "form-fitting" enhanced targeting accuracy in the early CT/MRI era.
• Advances in the understanding of basal ganglia neurophysiology and circuitry provided a stronger rationale for some surgical approaches and revealed alternative sites that may be targeted.
• Refined microelectrode recording techniques permitted more detailed physiologic "mapping" of the basal ganglia in the operating room, providing more detailed knowledge of electrode location prior to neuroablation or insertion of a permanently implanted deep brain stimulating lead.

Introduction of long-term deep brain stimulation (DBS) as an alternative to irreversible neuroablative procedures may enhance the safety of these procedures while maintaining therapeutic efficacy. Additionally, surgical targets that are lesioned at great peril may be treated effectively with DBS, broadening the surgical options for patients with PD.

Tremor

Tremor is a movement disorder defined as an involuntary rhythmic oscillation of a body part. It generally is classified according to the circumstances in which it occurs as a rest, postural, kinetic, or action tremor.

• Rest tremor - Oscillation of a part of the body that is supported in order to eliminate the need for muscle activation
• Postural tremor - Oscillation that occurs while maintaining the position of a body part against gravity
• Kinetic or action tremor - Oscillation during a voluntary contraction of skeletal muscles

Pathophysiology

Most pathophysiologic models of essential tremor (ET) hypothesize a central neural oscillator. This oscillator may be influenced by sensory stimuli that can either reset or entrain its rhythm.

Tremor activity consistently is detected in the ventrolateral (VL) thalamic nucleus of those with parkinsonian tremor or ET. Although the VL thalamic nucleus continues to be the primary surgical target for treating medically refractory tremor, whether the motor thalamus is the primary generator of tremor activity is unclear.

Animal studies suggest the presence of a tremor pacemaker in the inferior olivary nucleus, the activity of which can be pathologically enhanced by certain drugs.

Two neural circuits have been proposed to explain the pathophysiology of tremor. A basal ganglia-thalamocortical motor loop involving the globus pallidum, anterior VL thalamic nucleus, and supplementary motor area may be affected in extrapyramidal tremor diseases such as PD and ET. Another loop, involving the cerebellum, posterior VL thalamic nucleus, and motor cortex, may explain tremor of other etiologies (eg, cerebellar tremor).

Recent studies also implicate the subthalamic nucleus-globus pallidus axis in the generation of tremor in patients with PD, and both pallidotomy and subthalamic nucleus DBS are effective treatments for medically refractory tremor.

Preoperative Evaluation And Selection Of The Proper Procedure

Good surgical outcomes begin with careful patient selection and end with attentive, detail-oriented postoperative care. The authors believe that this level of care is provided best by a multidisciplinary team composed of movement disorder neurologists, a neurosurgeon who is well versed in stereotactic technique, a neurophysiologist, and a neuropsychologist. Additional support from neuroradiology and rehabilitation medicine is essential. At the authors' movement disorders center, patients are evaluated for surgery as follows:

• First, a neurologist with expertise in movement disorders evaluates the patient, confirms the diagnosis of intractable tremor, and reviews the medication history to determine whether all reasonable medical options have been employed properly.
• Potential surgical candidates then are evaluated by the neurosurgeon, who determines whether the patient is indeed a surgical candidate and decides which procedure(s) would benefit the patient most. Close collaboration between neurologist and neurosurgeon assists in the decision-making process, minimizing patient confusion and stress.

If the neurologist and neurosurgeon agree that the patient is a good surgical candidate, further workup includes the following:

• Brain MRI to exclude comorbid conditions and assess the degree of brain atrophy; significant atrophy may increase the risk of perioperative hemorrhage
• Detailed neuropsychological testing to exclude subtle cognitive impairment, which can be worsened by the surgical procedure
• Medical evaluation to determine the patient's general fitness for surgery

Note that advanced age (>75 y) is not an absolute contraindication to this type of surgery. If a patient otherwise meets the selection criteria for a procedure and his or her quality of life is predicted to benefit substantially, surgery should be offered.

Surgical Technique

During stereotactic surgery, imaging data are correlated to 3-dimensional space, permitting the surgeon to reach a target deep within the brain blindly and with minimal trauma. Frame-based techniques depend upon the application to the skull of a reference coordinate system, permitting any point within the brain to be described with Cartesian (ie, x, y, z) coordinates.

• Ventriculography, an important method for target localization before the development of CT and MR imaging, now is used uncommonly.
• CT-guided stereotaxis provides direct imaging of brain parenchyma without image distortion; however, gray-white resolution is inferior to that of MRI, and only axial imaging is possible.
• MRI provides superior target resolution and triplanar imaging; however, some smaller targets cannot be visualized all the time, and MRI is prone to image distortion. Although usually small, these distortions can affect targeting for functional neurosurgery.

The possibility of targeting errors due to image distortion necessitates the use of some form of intraoperative neurophysiologic monitoring to confirm correct targeting during movement disorder surgery. Intraoperative physiologic monitoring can consist of any combination of the following:

• Macroelectrode (>1 mm diameter) techniques include impedance measurements and direct stimulation of the target nucleus. These techniques may be used to confirm electrode location within deep gray matter, assess the clinical effects of electrostimulation prior to permanent implantation of a DBS lead (see Deep Brain Stimulation), or estimate proximity to surrounding structures prior to lesioning.
• Semimicroelectrodes (50-150 µm) detect field potentials of neuronal groups and can be used to determine the nature of the nucleus in which the electrode is placed (ie, sensory, motor).
• Microelectrodes (1-25 µm) may be used to record individual neuronal field potentials or to stimulate discrete regions of the brain. While microelectrode techniques provide the most detailed information and the greatest targeting resolution, their routine use during movement disorder surgery is controversial. Detractors of the technique argue that the resolution provided by microelectrodes is not necessary to achieve good clinical results; the methodology is difficult to perform, time-consuming, and expensive; and speculative concern exists that the increased number of trajectories used with microelectrode techniques may increase the risk of hemorrhage.

In the authors' opinion, microelectrode techniques have provided invaluable targeting data that may have prevented aberrant targeting in as many as 12% of pallidotomy cases. Moreover, hemorrhage rates reported in series of microelectrode-guided functional neurosurgical procedures are no higher than those reported with macroelectrode techniques.

Surgical Procedures

Until recently, surgery for movement disorders predominantly involved destructive lesioning of abnormally hyperactive deep brain nuclei; however, the observation that high-frequency electrostimulation in the VL thalamus eliminates tremor in patients undergoing thalamotomy led to investigation of permanent DBS as a reversible alternative to lesioning procedures.

Neuroablative procedures

During neuroablation, a specific deep brain target is destroyed by thermocoagulation. A radiofrequency generator most commonly is used to heat the lesioning electrode tip to the prescribed temperature in a controlled fashion. The most commonly performed neuroablative procedure is thalamotomy, in which lesions are created in the VL thalamus.

VL thalamotomy was the most frequently performed movement disorder procedure in the prelevodopa era.

Physiologic rationale

VL thalamus receives afferent innervation from 2 primary sources, the globus pallidus interna via the ansa lenticularis and thalamic fasciculus and the contralateral cerebellum via the superior cerebellar peduncle. These cerebellar fibers synapse primarily in the most posterior segments of the VL thalamic nucleus, the ventral intermediate (VIM) and ventral oral posterior (VOP) nuclei. Oscillating excitatory input from the cerebellum may be responsible for the tremor observed in PD, as cellular activity synchronous with the frequency of PD tremor can be recorded in the VL thalamic nucleus. These data support the clinical observation that lesions placed within the VL thalamic nucleus (and specifically within VIM and/or VOP) arrest parkinsonian and essential tremors (see Image 1).

Indication

Thalamotomy is indicated in patients with PD who are disabled by medically refractory tremor. However, the anticipated benefit of tremor reduction or elimination must be considered carefully. Rest tremor alone is rarely disabling, and bradykinesia and rigidity can reduce dexterity irrespective of tremor. This procedure is also indicated in patients with ET, in whom the tremor worsens with action and is often disabling. Selected patients with action tremor due to multiple sclerosis are also candidates for this procedure.

Target

VIM almost unanimously is considered the best target for tremor suppression. Two types of cells can be recorded in the VIM: (1) tremor cells, with rhythmic firing pattern synchronized to electromyography; and (2) kinesthetic cells, somatotopically organized and responding to active or passive movements.

Results

Thalamotomy produces excellent short-term and long-term results in 80-90% of patients with PD and predominant tremor. In patients with ET, the reported rate of success is even higher, ranging from 80-100%.

Morbidity and mortality

The reported morbidity rate for thalamotomy ranges from 9-23%. The predominant complication is speech impairment with dysarthria and hypophonia. The risk of speech abnormalities is 30% for unilateral thalamotomy and more than 60% following bilateral procedures. Other complications include memory loss, contralateral hemiparesis, and more rarely hemineglect, dystonia, hemiballismus, athetosis, and dyspraxia. Preoperative memory and language evaluation can predict those patients at greatest risk for postoperative cognitive and language dysfunction. The mortality rate for thalamotomy is 0.5-1% in the largest series. Death results almost exclusively from intraparenchymal hemorrhage.

Deep Brain Stimulation

DBS first was used in the 1970s for the treatment of chronic pain. Mixed results and poor electrode design caused a cessation of significant activity in this field in the 1980s, but over the last 10 years DBS has reemerged as a treatment for movement disorders.

Mechanism of action

Currently, no explanation clearly describes the mechanism of action of DBS, although several hypotheses have been formulated. High-frequency stimulation may create a global hyperpolarization of the cell membrane, resulting in a loss of excitability. Alternatively, stimulation may "jam" signal flow out of an abnormally functioning structure. Antidromic and orthodromic depolarization currents may modulate neuronal activity at sites distant from the stimulation target. Finally, stimulation-induced disruption of pathological network activity has been proposed to explain deep brain stimulation effects on abnormal movement disorders (McIntyre, 2004).

Advantages

The main advantages of DBS are reversibility and adjustability. Because the DBS lead is left in place, physicians have on-going access to the target site, allowing them to adjust stimulation parameters in response to changes in the patient's condition. If stimulation induces unwanted adverse effects, the stimulator can be turned off, adjusted, or removed. In the event that DBS proves clinically ineffective, the patient has not suffered an irreversible lesion to the brain.

Disadvantages

The main disadvantage of DBS is the cost. Currently, the cost of the device is approximately $10,000 per unit. Additional disadvantages include an elevated risk of infection due to the presence of implanted hardware and the cost of maintenance (eg, repair and/or replacement of fractured wires, repeated office visits for stimulation adjustments). Currently, battery exhaustion necessitates replacement of the entire pulse generator, which is the most expensive component of the system (cost is approximately $8000), every few years.

Procedure

Successful DBS therapy depends on the proper implementation of a series of procedures, which include accurate candidate selection, proper anatomical and electrophysiological targeting leading to accurate lead placement, proficient electrode programming, and management of side effects.

DBS implantation is performed in 2 stages. During the first stage, the DBS lead is implanted stereotactically into the target nucleus. During the second stage, the DBS lead is connected subcutaneously to an implantable pulse generator, which, like a pacemaker, is inserted into a pocket beneath the skin of the chest wall. As with most stereotactic movement disorder procedures, the first stage is performed with the patient awake in order to monitor his or her neurological status. The stereotactic head frame is applied on the morning of surgery, and a targeting MRI is performed (see Image 2).

A combination of microelectrode recording and macroelectrode stimulation is used to physiologically refine the desired target. The DBS lead is implanted and anchored to the skull with a burr hole "cap." The electrode is thin (approximately 1.3 mm in diameter) and flexible, so that it moves atraumatically with the brain (see Image 3). A brain MRI is obtained immediately postoperatively to confirm proper electrode placement and to ensure that no hemorrhage is present. If the MRI is acceptable, the patient is returned to the operating room where the remainder of the device is implanted under general anesthetic.

After approximately 2 weeks, therapeutic electrical parameters can be set using a transcutaneous programmer (see Image 4). The primary goals of DBS programming are to maximize symptom suppression and minimize adverse effects. Minimizing battery drain is a significant secondary goal. To achieve these goals, a systematic, multistep approach is recommended (Dowsey-Limousin, 2002). Stimulation can be delivered in monopolar or bipolar fashion, using any of 4 electrode contacts, alone or in combination. Thus, a great deal of therapeutic flexibility is provided, permitting customized stimulation for each patient. Moreover, stimulation parameters can be adjusted at any time if needed.

Results

Thalamic DBS initially was used contralateral to previous thalamotomies to reduce the risk associated with bilateral thalamotomy. However, the results were so encouraging that thalamic DBS has become not only an accepted alternative to thalamotomy but is currently the procedure of choice for patients who require unilateral or bilateral procedures for medically refractory tremor. A decade of experience in Europe and the United States indicates that thalamic DBS is equivalent to thalamotomy for tremor suppression.

The Multicentre European study of thalamic stimulation in parkinsonian and essential tremor reported rates of significant improvement between 85% for PD tremor and 89% for ET at 12 months (Limousin, 1999). In the latter group, head tremor was significantly reduced only at 3 months, but voice tremor was nonsignificantly reduced. In the majority of patients, the very good results with stimulation seen at 1 year were maintained after over 6 years (Sydow, 2003).

As with thalamotomy, thalamic DBS uncommonly provides significant functional improvement for patients with PD because their rest tremor is not usually a source of functional disability. In contrast, the functional benefit to patients with ET is considerable. Because the lesion is eliminated, hemorrhage rates and cognitive adverse effects may prove less frequent than with thalamotomy. Side effects related to stimulation, including paresthesia, dysarthria, and gait disorders are relatively common though reversible by setting adjustments. Device-related complications, including end of battery life, skin erosion, or infection, can be observed and resolved in most cases.

Multimedia

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Media file 1: Surgical treatment of tremor. Sagittal section through the thalamus demonstrating the ventrocaudal (green), ventral intermediate (red), ventral oral posterior (dark blue), and ventral oralis anterior (light blue) nuclei. Thalamic stimulators and thalamotomies to treat tremor are placed at the junction of the ventral intermediate and ventral oral posterior nuclei.

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Media file 2: Surgical treatment of tremor. Axial fast spin echo inversion recovery MRI at the level of the posterior commissure. The typical target for placing a thalamic stimulator is demonstrated (crosshairs).

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Media file 3: Surgical treatment of tremor. The deep brain stimulation lead is equipped with 4 electrode contacts, each of which may be employed, alone or in combination, for therapeutic stimulation.

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Media file 4: Surgical treatment of tremor. Deep brain stimulation parameters can be adjusted at any time using a transcutaneous programmer.

Keywords

deep brain stimulation, DBS, movement disorder, neurosurgery, stereotactic surgery, stereotaxis, thalamotomy, surgery for tremor, surgical treatment of tremor, Parkinson disease, PD, Parkinson's disease, parkinsonian symptoms

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