Parkinson's Disease

Description

Alternative Names

Surgery

Surgical procedures are now available for specific patients who no longer respond to drug treatments. Advances in knowledge of the brain and new technologies, including brain "pacemakers" are making surgery a reasonable option for many patients. Patients who begin to experience dyskinesia and on-off fluctuations in spite of the optimal drug therapy might discuss surgery with their doctor. They should have good support at home and be prepared for postoperative issues. In general, deep brain stimulation is currently the option of choice.

Although surgery has produced significant improvements in symptoms, the benefits do not last. Also, not all patients are good candidates. For example, patients who did not experience any improvement to levodopa would not benefit from any of these procedures. Furthermore, the risks probably do not outweigh the benefits in patients with advanced disease.

Deep Brain Stimulation

Deep brain stimulation (also called neurostimulation) uses electric pulse generators to control symptoms. They are proving to be safe and effective alternatives to surgery. Appropriate candidates are similar to those for surgery. (Patients being given neurostimulation, however, should not have pacemakers.) Like pallidotomy and thalamotomy, neurostimulation is not a cure. On the other hand, it does not remove brain tissue and is reversible. In general, the procedure works as follows:

• The surgeon implants a tiny pulse generator near the collarbone, which is connected to four electrodes that have been implanted in the target area in the brain.
• The generator delivers programmed pulses to this area, which the patient can turn on and off using a magnet held over the skin.
• When the pulses are turned on, the symptoms are suppressed.

The generator must be replaced every three to five years.

Deep brain stimulation (DBS) has been intensively studied during the past five years, and much has been learned about how DBS affects the underpinnings of Parkinsons disease. This knowledge has enabled physicians to apply DBS to other areas of the brain and successfully treat greater numbers of patients. Two new DBS devices received FDA approval in 2003.

Neurostimulation of the Subthalamic Nucleus (STN Stimulation). Bilateral subthalamic nucleus (STN) stimulation employs double (bilateral) implants in the subthalamic nucleus, which controls symptoms of rigidity and involuntary motion.

STN stimulation is proving to improve gait, walking ability, and upper limb rigidity in some patients. Its affect on gait, however, may differ from the effects of L-dopa. One study suggested that although improvement occurred, patients did not walk as quickly nor was the stride as long as those on L-dopa. The procedure does not improve gait in patients who do not respond to L-dopa, nor does it help freezing or speech disorders. To date, candidates are generally under 70 who have motor fluctuations, drug-induced dyskinesia, and no other serious medical or psychiatric conditions. Researchers are trying to determine if more patients can be suitable candidates.

Complications. Complications occur in 2% to 4% of operations. The most serious ones are bleeding in the brain and infection. Depression is common. A 2001 study reported a moderate decrease in verbal memory and mental tasks involving visual-spatial functions. (Some other mental functions improved.) Some experts are not convinced of the safety of implanting a polyurethane device in the brain.

Neurostimulation of the Thalamus. Neurostimulation of thalamus helps patients with tremor. Studies are reporting improvement in tremor in up to 85% of patients, although only on one side of the body. Long-term effects are still unknown, although studies are indicating that it is safe and effective.

Pallidotomy and Other Procedures that Destroy Tissue

Pallidotomy is a surgical procedure that may restore normal brain activity related to voluntary movement in some patients. It is not a cure, however, and its primary benefit is to allow people to continue on medications without incurring some of the side effects. The procedure is irreversible and generally works as follows:

• The patients head is immobilized using a stereotactic frame and imaging techniques are used to visualize the injured areas.
• The neurosurgeon drills a small hole into the skull and inserts an electrode.
• The electrode generates a current and heat to destroy small amounts of tissue in the globus pallidus, a part of the brain responsible for many Parkinsons symptoms, particularly those that develop after long-term use of levodopa.
• The patient is awake during the operation, which takes about six hours.
• The hospital stay averages two days.

To date, the standard procedure involves one side of the brain (unilateral pallidotomy). Bilateral pallidotomy (surgery on both sides of the brain) is being researched but to date has higher complication rates than unilateral procedures. Patients should have the surgery performed only in centers that have experience with the procedure.

Candidates. In general, appropriate candidates for unilateral pallidotomy are patients with advanced disease who no longer benefit from drug treatments. Unfortunately, only about 5% to 10% of Parkinsons patients are candidates. The procedure is generally not recommended for the following:

• Patients who do not respond to levodopa.
• The very elderly.
• Patients whose primary symptom is tremor.
• Patients whose predominant symptoms are freezing and falling (especially during on-periods).
• Patients who have serious medical or mental disorders.
• Patients with parkinsonism (as opposed to idiopathic Parkinsons disease).

Benefits. The best results occur in patients with the following symptoms:

• Dyskinesia (uncontrolled movements).
• Rigidity.
• Tremor.

Significant improvements in these symptoms typically occur on the side of the body opposite to where the surgery occurred and such benefits persist in many patients for at least five years. (To a lesser degree, symptoms initially may improve on the same side of the body as the surgery but effect last for a much shorter period of time than the other side.) In one study, half of the patients went from being completely dependent to being able to perform independently, including feeding and dressing themselves. The improvement in daily functioning diminishes over time, although relief even for a few years may be worth it.

Surgery has less effect on the following symptoms:

• Balance, gait disorders, and freezing. (In one study, however, about half of patients who could stand independently before the procedure reported better stability and fewer falls. The procedure does not restore the ability to stand independently in patients who could not do so before surgery.)
• Voice volume. (Some studies have reported, however, that voice volume improved considerably after surgery in some patients with mild problems, especially when it was performed on the patients right side.)

Complications. Surgical experience is improving outcomes, but even in centers with high track records, serious and permanent complications occur in 0.41% to 23% of cases. The highest complications are in patients who have bilateral pallidotomy (both sides of the brain). The procedure can even be fatal in rare cases.

• Temporary Complications. Most complications are temporary may include facial paralysis, trouble speaking, acute confusion, and sleep attacks.
• Permanent Complications. The most common permanent complications included behavioral or personality changes, trouble speaking and swallowing, facial paralysis, and vision problems. Uncommon but very serious complications include stroke (3.9% in one study) and blindness. In one long-term study, complications were permanent in 13.8% of patients with bilateral procedures and fatality rates were 1.2%. Permanent complications occur in 6.4% in those with unilateral pallidotomy and fatality rates were 0.3%.

Stereotactic Thalamotomy. Thalamotomy uses the same techniques as in pallidotomy, but it is performed on the thalamus, which is a major brain center for relaying messages. Thalamotomy has been reported to significantly reduce or completely stop tremor in 80% to 90% of patients. It does not appear to have much effect on other symptoms. Because tremor is not as significant a disability as other Parkinsons symptoms, the value of this procedure is limited. Complications are similar to pallidotomy, except there is no danger of vision loss.

Tissue Implantation

Fetal Cell Implantation. Experimental surgery has shown promise using fetal brain cells rich in dopamine implanted in the substantia nigra. The procedure is useful only in younger adults. Of great concern were studies reporting severe dyskinesia (uncontrolled movements) in implant patients. In some cases it was severe enough to make walking impossible or require pallidotomy. This has been a major setback for this approach, although techniques that put implants only in areas where dopamine is most depleted may reduce the risk for dyskinesia. (Dyskinesia is due to excessive dopamine.)

Alternative Implant Sources. The use of fetal tissue is extremely controversial, and research is ongoing for alternatives, including the use of cells from other mammals, cells from human placentas or umbilical cords, and synthetic microspheres that deliver dopamine directly to the brain. Some researchers hope to use cloning techniques on animal fetuses as a source for dopamine-producing nerve cells. Animal and laboratory studies are also using gene therapies and other advanced treatments for transplanting dopamine-producing cells or nerve-protecting cells into the brain.

Radiosurgery and the Gamma Knife

Radiosurgery is a technique typically used for brain cancer. It employs a so-called gamma knife, which is not a knife at all, but 300 intersecting radiation beams that are directed through holes in a helmet to target precisely affected sites in the brain. The gamma knife is now being investigated as tool for both thalamotomy and pallidotomy in patients who are not candidates for standard surgery. Early studies are showing that it improves symptoms after about six to eight weeks, but it can have significant and very serious side effects. In one study, one patient out of eight patients died of complications. There were also a number of distressing side effects, including weakness and partial paralysis. In addition, the operated areas were significantly off target.

Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) employs high frequency magnetic pulses that target affected areas of the brain. It is noninvasive and is being investigated for Parkinsons disease, and one 1999 study reported symptom improvement in patients treated twice a day. Unfortunately, a 2001 study reported that symptoms actually worsened with this approach.