Surgical Treatments for ET

Introduction

Essential tremor (ET) is one of the most common movement disorders, yet there is no cure for ET and only about 50% of patients receive satisfactory benefit from the currently available medications. For patients with disabling tremor that interferes with daily activities and is not controlled by medications, surgical treatments may be an option. Advances in the understanding of brain anatomy, more detailed imaging methods to better see the brain and improved surgical techniques allow for greater surgical accuracy and increased benefits with fewer complications. Surgical procedures for ET include thalamotomy and thalamic deep brain stimulation (DBS).

History of Surgical Treatment
Surgery for tremor disorders has been attempted for almost 100 years. Initially, surgery involved destruction of large parts of the brain, which resulted in an improvement in tremor but significant side effects such as weakness and paralysis. In 1947, stereotactic surgical techniques, which involve using electrodes to precisely locate a particular part of the brain without destroying surrounding brain areas, were first used in humans. These techniques allowed for improvement in the targeted symptoms such as tremor with fewer side effects.

In order to achieve optimal tremor control, it was necessary to determine the specific part of the brain to target for surgery. By the late 1950s, the ventralis intermedius (VIM) nucleus of the thalamus was found to be the most effective target for tremor. The thalamus is a group of cells deep in the brain involved in relaying motor and sensory signals from different portions of the brain. Creating a lesion or destroying a portion of the VIM nucleus of the thalamus is called thalamotomy.

Thalamotomy on one side of the brain (unilateral procedure) was found to be very effective in controlling the tremor of the opposite side of the body. However, thalamotomy on both sides of the brain (bilateral procedure) to improve tremor for both sides, often resulted in speech, balance and memory problems. In 1997, DBS of the thalamus was approved by the FDA as a treatment for ET. DBS was shown to have beneficial effects comparable to thalamotomy with fewer complications. In DBS, there is no destruction of the brain. Rather, a wire (electrode or lead) is placed in the VIM nucleus of the thalamus. The wire is connected under the skin to a pacemaker-like device in the chest that provides mild electrical currents to control symptoms. In ET, DBS of the VIM nucleus of the thalamus is the most commonly used procedure to control tremor.

Surgical Procedures
The patient is awake during both thalamotomy and DBS so that the effects on tremor can be observed during the procedure. Surgery most commonly begins with the neurosurgeon attaching a stereotactic frame (a halo-type device) to the patient�s head. The frame holds the patient�s head still during surgery and helps the neurosurgeon determine the exact area to target for surgery. The frame is attached to the head with four small screws. Local anesthesia is used to numb the area where" the screws are placed. Some Centers have recently adopted a frameless procedure which does not require the use of the head frame during the procedure. Instead, markers, which are small screws, are placed on the head and are used to assist in determining the exact area to target for surgery.

After the frame or frameless markers are attached, the patient undergoes a brain scan such as a CT or MRI which provides a picture of the brain. With the help of a standard brain atlas and brain scans obtained, the neurosurgeon determines the exact location of the VIM nucleus. After the scan is completed, the patient is taken to the operating room (OR). When a head frame is being used, the frame is secured to the bed so the head cannot move but the patient can move other parts of the body if needed. A small area on the top of the patient�s head is cleaned and shaved. After local anesthesia, a small hole, called a burr hole, about the size of a nickel is made in the skull.

Most neurosurgeons use a technique called microelectrode recording to help determine the precise location of the VIM nucleus. A special electrode is passed into the brain through the hole that was drilled, and the electrode sends signals that are measured to provide information to the surgeon regarding the location of the tip of the electrode in the brain.

Once the VIM nucleus is identified, for thalamotomy, a special electrode called a thermocouple electrode is placed in the brain. Electric current is passed to the tip of the electrode to assess improvement in

tremor and any abnormal sensations or movements like muscle spasms. If good tremor control is achieved and no abnormal sensations or movements occur, the tip of the electrode is heated for approximately one minute, which destroys the cells at the tip of the electrode. The electrode is then removed, the skin incision is closed, the frame/frameless markers are removed and the procedure is complete.

The second phase of the DBS surgery involves placing and connecting the battery(neurostimulator), which is similar to a pacemaker device. General anesthesia is used for this phase of the surgery. During this phase, an extension wire connected to the DBS electrode is connected to the battery. The extension is tunneled under the skin of the neck and another incision is made below the collar bone where the battery is placed and connected to the extension wire. Both the incisions are closed and the surgical procedure is complete. If a bilateral procedure is required, both phases are repeated on the other side of the brain. The timing of the phases may differ slightly between Centers. At some Centers the DBS electrode is placedin the brain on one day and approximately one week later the battery is placed in the chest. In other Centers the DBS electrode and battery may be placed on the same day. Similarly, for bilateral procedures, some Centers place both electrodes in the brain during the same session and other Centers place the second side approximately one month later. There are no data to support one approach over another and it is based largely on the preference of the neurosurgeon.

With DBS, once the VIM nucleus is located, the DBS electrode (lead) is placed into the brain. It is attached to the skull and remains in the brain. It is not heated and it does not destroy brain tissue as with thalamotomy. The skin incision is then closed and the frame or frameless markers are taken off. The first phase of the DBS surgery is then complete. With both procedures the patient generally spends at least one night in the hospital for observation. These procedures do not require general anesthesia because no pain is felt inside the brain. Local anesthesia is used for frame/frameless marker placement and the initial brain incision.

After DBS surgery, stimulation is usually initiated one to six weeks after surgery and is programmed in the physician�s office with a programming device placed on the skin over the battery. Parameters that can be changed include pulse width (duration of the stimulation pulse), amplitude (intensity or strength of the stimulation), stimulation frequency (number of times the stimulation pulse is delivered), and the
choice of active contacts.

The patient can turn the stimulator on or off with a handheld magnet or more commonly with an Access Review Therapy Controller which also provides information about the status of the battery and whether the device is on or off. The most commonly used stimulation parameters for ET are stimulation frequency of 135 to 185 hertz, pulse width of 60 to 120 microseconds, and amplitude of 1 to 3 volts. The patient will generally return to the surgical center periodically to adjust parameters.The battery generally lasts 3-7 years depending upon the parameter settings and use of the device. When the battery is depleted, an outpatient procedure to replace the battery is required.

Patient Selection
ET patients who do not have satisfactory tremor control with medications and have disabling tremor that affects their ability to perform activities of daily living such as eating, writing, drinking, dressing, working or enjoying their hobbies are potential candidates for these surgical procedures. Most physicians will try propranolol and primidone to control tremor before recommending surgery. Patients who have significant memory problems and patients with unstable medical conditions that would increase surgical risk are not candidates for surgery. Persons with other medical conditions requiring repeated MRI using a full body-scan may not be candidates for DBS.

Thalamotomy Outcomes
Multiple reports regarding the benefits of thalamotomy in ET have demonstrated improvement in the tremor opposite the side of the surgery in greater than 90% of patients. Typically, the improvement in hand tremor was approximately 75% while activities of daily living, such as eating, feeding, and writing, improved by 70%. The main improvement occurs in hand tremor on the opposite side of the surgery although occasionally head and voice tremor can also improve. Long term follow-up studies of thalamotomy have shown that the benefits of the procedure continue in a majority of patients. Occasionally, patients may require repeat surgery if the initial benefits are lost. One study that followed patients for approximately nine years reported that 80% of patients continued to have benefit. Bilateral thalamotomy is not recommended because of concerns about speech and balance difficulties.

Thalamotomy has largely been replaced by DBS of the VIM nucleus of the thalamus. The advantages of DBS compared to thalamotomy include the reversibility of the procedure, ability to adjust stimulation parameters to improve efficacy or reduce adverse events and the fact that there is no destruction of brain tissue. If the device is not effective or if a new treatment option becomes available, the device can be removed without having damaged the brain. In addition, bilateral procedures can be performed with fewer side effects than with thalamotomy. For patients in which the cost of DBS is prohibitive or for those that are unable to periodically return to a surgical center for programming, thalamotomy may be considered.

Deep Brain Stimulation Outcomes
Several reports have demonstrated that DBS of the thalamus has a comparable improvement in tremor compared to thalamotomy, but with fewer complications. The majority of studies have reported improvements in tremor in 90% of patients on the side opposite the side of surgery. Long-term studies have shown that the improvement in tremor is maintained in the majority of patients up to 7 years after the surgery. Multiple studies have demonstrated the immediate and long-term benefits of DBS in controlling tremor with improvements in hand tremor of approximately 90%, and improvements in functional ability and performance of activities of daily living of approximately 85%. Although all of the large studies have targeted patients with disabling hand tremor, in these studies head and voice tremor have had some improvement. The greatest improvements in head and voice tremor were seen with bilateral procedures.

Risks and Complications
The surgical risks of thalamotomy and DBS of the thalamus are similar, but have generally been shown to be less frequent with DBS. They often depend upon proper patient selection and the experience and expertise of the neurosurgeon. Surgical complications occur in fewer than 5% of patients. Risks and complications include bleeding in the brain, stroke, seizures, and infections. Most of these complications resolve within one month. However, in approximately 1-2% of patients, these complications can result in permanent neurological deficit. Death results very rarely. Other surgical complications can include confusion, headache and bleeding under the skin which are typically temporary and resolve without treatment.

DBS also carries the possibility of complications related to the device implanted in the brain and to the stimulation. Device-related complications can include repositioning of the device in the brain (electrode) if no benefit occurs after surgery, breakage of the electrode or extension wire, malfunction of the battery, and erosion of the skin. These complications generally require an additional surgical procedure to correct. In addition, the battery must be replaced every three to seven years depending on use. The side effects seen with stimulation depend upon the exact placement of the electrode and the strength of the stimulation used. Side effects include tingling, numbness, muscle spasms, speech difficulties, mood changes, balance difficulties, and pain. Adjusting the stimulation parameters can reduce most side effects. Speech and balance difficulties are generally more common with bilateral procedures.

Patients with DBS should avoid receiving diathermy, which is the use of electric currents to generate heat in tissue. It is often used during various surgeries, physical therapy for pain, and dentistry. The heat from the diathermy can be transferred to the brain through the DBS electrode resulting in brain damage and rarely death. In addition, if it is necessary to receive an MRI after the DBS system
is implanted, it is important to contact the surgical center. MRIs can lead to heating of the DBS system which can cause damage to the brain. They can generally be performed without any problems as long as the proper safety measures are followed.

Gamma Knife Thalamotomy
Gamma knife radiosurgical thalamotomy is a technique in which a thalamotomy is performed with beams of radiation rather than a surgical incision and use of electrodes. Gamma knife radiosurgical thalamotomy involves the same stereotactic localization as other procedures to identify the area in the thalamus that will be targeted for treatment. Very high resolution MRI scanning is then used to clearly identify the precise area within the thalamus that will be exposed to the radiosurgical energy of 201 highly focused beams of ionizing radiation generated by activated cobalt. The cobalt beams are directed to converge at the targeted location in the thalamus where tissue destruction occurs. The procedure takes approximately one hour and the benefit may not be apparent until three to six weeks after the procedure. This procedure is used as an attempt to reduce tremor on the side opposite of the procedure and should be restricted to patients with severe tremor who are not candidates for routine thalamotomy or DBS because of unstable medical conditions. The safety of gamma knife thalamotomy has not been fully established and further research is warranted.

Focused Ultrasound Study
Focused Ultrasound is a surgical study that takes Thalamotomy to the next level. This procedure has not been approved by the FDA for use as a treatment for essential tremor nor is it available to the public. Learn more about this study.

Excerpt from Surgical Treatments of Essential Tremor by Kelly Lyons, PhD and Rajesh Pahwa, MD, University of Kansas Medical Center, Kansas City, KS.

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