A Review of a Neurosurgery Effective Against Symptoms of Parkinson’s Disease

Evaluation of a Neurosurgery That Treats Symptoms of Parkinson's Disease

Tania Zeigler

Close to 1.5 million Americans over the age of fifty suffer from an incurable neurological disorder called Parkinson's disease. The majority of Parkinson's patients treat their symptoms with a drug that begins to lose its effectiveness after only a few years of use. However, a recently revived neurosurgery known as pallidotomy has been found to eliminate the major symptoms of Parkinson's disease, offering patients relief for up to ten years. This article describes pallidotomy and evaluates the procedure in relation to two alternative methods of treatment.

Introduction

At the age of fifty-six, Mary Selman, an Alabama woman who has always been described by her friends and family as "full of life" was diagnosed with Parkinson's disease [Neil and Grant, 1995]. Mary has used a cane for the past six years because the disease has undermined her ability to walk. The trembling in her hands and arms has been so severe that she has never been able to hold her two-year old granddaughter. Mary is among an estimated 1.5 million Americans suffering from this chronic and incurable neurological disorder. Each year, about 50,000 people are given diagnoses similar to Mary's based on the presence of symptoms associated with the disorder and an inability to find any other explanation for them [Brody, 1995]. What doctors do know is that Parkinson's disease results from a progressive loss of cells in the brain's motor control center, the substantia nigra . These cells produce a substance called dopamine, which is a neurotransmitter that transmits signals for normal movement. Without enough dopamine, an overactivity in another part of the brain appears in order to compensate for the dopamine-deficient chemical imbalance. As a result, patients develop symptoms such as stiff muscles, severe shaking, stooped posture, and excruciating muscle cramps. Furthermore, one out of every three patients with Parkinson's disease is eventually diagnosed with Alzheimer's disease [Levin and Katzin, 1995].

A growing number of medications and treatments have offered patients some relief, but not without severe side effects. However, there may be a new alternative that can restore hope for patients and their families: a revived neurosurgical operation called pallidotomy. The purpose of this article is to explain the pallidotomy procedure and to discuss its advantages and disadvantages. First, the article provides background about Parkinson's disease and the rationale behind the surgery. Next, the article evaluates the advantages and disadvantages of the procedure in addition to the outlook for its future. The article also compares pallidotomy with two alternative treatments based on long-term effectiveness, side effects, extent of effectiveness, and cost. Other treatments not as widely used by doctors and their patients will not be considered in this article. Included in the conclusion of the article are reasons that pallidotomy is not more widely used even though it has been in existence for over forty years. In addition, the conclusion offers an outlook for the future of pallidotomy and those patients who undergo the surgery.

Parkinson's Disease

Parkinson's disease is a progressive disease with a gradual exacerbation of three primary symptoms: tremor, muscle rigidity, and disturbances of movement due to painful muscle cramps. The tremor is a resting tremor in the limbs that disappears during sleep because of a reduced metabolic rate and reduced demand for neurotransmitter release. Muscle rigidity refers to passive movement, especially involuntary movement such as blinking; this lack of natural movement can account for the "mask-like" face seen on most patients. In addition, there is great difficulty in initiating voluntary movement because of excruciating pain in the muscles. All of these major symptoms lead to a number of minor symptoms: stooped posture, speech problems, and excessive sweating. Post-mortem examination of the brain of a Parkinson's patient shows a specific degeneration of the substantia nigra [Strange, 1992]. Although scientists do not yet know the cause for cell degeneration in the substantia nigra, they do know that Parkinson's symptoms appear when people lose 80 to 90 percent of their substantia nigra cells [McDonald, 1988]. Evidence of the loss of substantia nigra cells is provided in Figure 1.

Figure 1. The substantia nigras of a normal patient (left hand panel) and a patient with Parkinson's disease (right hand panel). A loss of pigmented substantia nigra cells is clearly seen in the Parkinson case [McDonald, 1983].

The cells in the substantia nigra, the brain's motor control center, provide most of the brain's supply of dopamine, a chemical needed to transmit nerve signals for smooth muscle movement. The degeneration of substantia nigra cells leads to a progressive depletion of dopamine and, ultimately, a severe shortage of dopamine in the nearby striatum, which is the part of the brain that controls movement, balance, and walking. The brain attempts to compensate for the dopamine-deficienct chemical imbalance by overactivating another region of the brain, the globus pallidus. The globus pallidus, the region from which pallidotomy received its name, lies deep within the middle region of the brain and releases low levels of dopamine in addition to other neurotransmitters responsible for muscle contraction. This erratic firing of neurotransmitters from the globus pallidus leads to a constant resting tremor and rigid, jerky movements. Both the loss of cells in the substantia nigra and the hyperactivity in the globus pallidus can be confirmed in living patients by a positron emission tomography (PET) scan [Strange, 1992].

Pallidotomy

Pallidotomy is a neurosurgery that was invented by two Swedish neurosurgeons in the 1950s to treat the major symptoms of Parkinson's disease. The surgery was abandoned in the early 1960s, however, because of mixed results and the discovery of effective therapy. Recently, the surgery has been revived because patients are now living long enough that their drugs are losing effectiveness after only three to four years of use. Also, advances in brain imaging, such as magnetic resonance immaging (MRI), have reduced the complication rate of the surgery. The theory of the procedure is discussed below.

Theory Behind Pallidotomy

Pallidotomies are suitable for those Parkinson's patients with severe symptoms [Alterman, 1996]. Patients are selected on the basis of a PET scan, which confirms the hyperactivity of the globus pallidus. Confirmation of hyperactivity is vital, because there exist many conditions that mimic the symptoms of Parkinson's disease but are not caused by hyperactivity of the globus pallidus. The theory of the operation is based on the knowledge that Parkinson's symptoms are caused by the loss of brain cells that release dopamine to transmit signals for smooth muscle movement. Loss of these cells leads to an overactivity in the globus pallidus, as previously discussed. The surgery involves the destruction of the cells in the globus pallidus in order to restore part of the brain's chemical balance, thus reducing or eliminating symptoms.
The procedure is quite simple. The patient is first fitted with a head frame that prevents extraneous movements of the head. The surgeon begins by making an incision in the skin on the back of the skull and peeling the layer of skin back. He then drills a hole deep into the center of the brain and inserts a probe in order to locate the globus pallidus, as shown in Figure 2. Throughout the entire surgery, the patient remains conscious. The surgeon asks the patient to move his or her limbs in order to locate the target tissue. A heatable probe is then inserted to destroy the cells. The surgeon knows to stop destroying cells when the patient's shaking ceases. At this point, the operation is complete. While prepping for the surgery takes as long as four hours, the actual procedure usually lasts about one to two hours. Since the operation eliminates the hyperactive firing of neurons in the globus pallidus, the surgery can eliminate the symptoms that result from the hyperactivity.

Figure 2. A surgeon probing deep into a Parkinson's patient's brain in order to locate the globus pallidus.

Advantages of Pallidotomy

Pallidotomies have restored the lives of hundreds of Parkinson's patients since the surgery was revived in 1990 [Kolata, 1995]. The first major benefit of the surgery is that in some cases the major symptoms of the disease are completely eliminated. In most cases, the symptomsare immediated alleviated. A man who was so stiffened by the disease that he could neither walk nor talk prior to the surgery, was shown on a January, 1996, Prime Time Live special running in a hospital corridor one hour after he received a pallidotomy. Terrie Whitling, 40, of Atlanta, who had the operation in October of 1993, is one of many patients who say the surgery restored her life. Before her surgery, Ms. Whitling said, "I was disabled; I needed a wheelchair to go beyond 30 feet. My medication was so unpredictable that I never knew from one moment to the next whether it was going to work or, if it did, to what extent" [Kolata, 1995]. After her operation, she said that she could play tennis again.

The surgery's other benefits are that, outside of prepping and probing, the procedure lasts about one hour and is completely painless, because the brain lacks pain receptors. Although these are all important advantages, researchers are mostly concerned with the surgery's potential for long term effectiveness. The surgery is still largely experimental, because it has not been performed long enough for substantial results to have been quantified. Preliminary results have been quantified by surgeons such as Dr. Robert P. Iacono of Loma Linda University Medical Center, who has performed over 500 pallidotomies. According to Dr. Iacono, about 90% of patients who have undergone the operation have experienced complete relief or at least a substantial reduction in symptoms without side effects [Kolata, 1995].

Disadvantages of Pallidotomy

Pallidotomy has dramatically improved the lives of hundreds of patients with Parkinson's disease, but, unknown to many eager and desperate Parkinson's sufferers, the operation has left others paralyzed, blind, demented, or comatose. Although most patients who have received pallidotomies have reported dramatic improvement in their symptoms, a small percentage have gone home after their surgeries, apparently feeling fine, only to develop severe side effects over the next few days. Many of these side effects are caused by brain hemhorrage after the surgery, leading to paralysis or blindness [Kolata, 1995]. However, most of the severe side effects are caused by surgical mishaps. The target tissue for the operation is tiny, making it very easy for a surgeon to destroy too many or the wrong cells in a patient's brain.

Although some statistics on the side effects have been compiled, so far most of the information has been anecdotal. Dr. Ira Shoulson, a professor of neurology at the University of Rochester, said, "From my perspective, I'd clearly call [pallidotomy] experimental. We really don't have good information on its efficacy or its safety or its tolerability." [Kolata, 1995]. The Food and Drug Administration does not require that surgical procedures be proven to be effective before they go into widespread use. For this reason, only six medical facilities in the United States and Canada have been able to perform the surgery on willing patients [Alterman, 1996]. However, because the surgery is still considered experimental by most surgeons, no central registry of surgeons who perform the surgery has been developed. This complicates the problem of evaluating the effectiveness of the surgery. Furthermore, since most medical facilities consider the procedure to be experimental, most insurance agencies will not cover the cost of the surgery, which ranges from $30,000 to $40,000.

In addition to the problem of quantifying data to evaluate pallidotomy, there is the problem of the severe demand for the surgery. Even patients who are aware of the risks often decide to take the chance. One neurologist who is just beginning to do the surgery, Dr. Matthias Kurth, associate director of the movement disorders clinic at the Barrow Neurological Institute in Phoenix, said his group has been getting two to three phone calls an hour from patients requesting the surgery [Kolata, 1995]. If more and more patients undergo the surgery before adequate results can be tabulated, disaster can result. If up to 10% of one surgeon's patients end up worse off than before their operation, imagine the number of patients who could be adversely affected by surgical mishaps. Some surgeons say cases of paralysis or blindness are rare. Other medical researchers say there is no way to know how widespread the problems have been. Almost no effort has been made to scientifically evaluate the long-term effects of the operation [Kolata, 1995].

Alternative Treatments

Although it is clear that Pallidotomy has its disadvantages, the drawbacks of alternative treatments appear to be much more severe. Since scientists are certain of the reason for Parkinson's symptoms, they have been able to provide a number of treatments. Unfortunately, because the underlying cause of the disease is still mysterious, not enough is known about the long-term effectiveness of any of the treatments for Parkinson's symptoms. Pallidotomy is the only treatment that has been shown to offer long term relief (8-10 years) of the major symptoms of Parkinson's disease.

L-Dopa Drug Therapy

The most common treatment for Parkinson's symptoms is a drug called levodopa, or L-dopa. Since dopamine can not be administered directly to the brain, L-dopa, its precursor, is administered orally by the patient and is converted to dopamine within the brain. L-dopa therapy has been found to be quite effective against the major symptoms of the disease, but at best, it offers only temporary relief. After only two to five years, most patients become unresponsive to the drug or develop severe complications [McDonald, 1988]. For example, many patients have experienced irreversible dementia or wild, unpredictable jerky movements [Kolata, 1995]. One advantage associated with the use of L-dopa is that it has been approved by the Food and Drug Administration, so all insurance companies cover the cost of the therapy.

Fetal Tissue or Adrenal Medullary

To reverse the symptoms of Parkinson's disease, neuroscientists in the early 1980s were determined to find a way to replace the lost substantia nigra cells or implant dopamine-producing cells into the brain. Using this idea, researchers suggested implanting substantia nigra tissue of aborted fetuses into the brain's of Parkinson's sufferers. A less controversial alternative (one that does not use fetal cells) involves implanting cells from the patient's own adrenal medulla, the inner layer of the adrenal gland that secretes dopamine. Experiments at the Karolinska Institute in Sweden and at the National Institute of Mental Health in Rockville, Maryland, suggested that both approaches might offer some benefits [McDonald, 1988]. Results were sketchy though; all subjects saw only a reduction in symptoms, and all required supplementary medications [McDonald, 1988]. "It is clear that the patients are improved by the surgery, but it's not to a degree that eliminates their impairment," says Harold L. Klawans, head of a team at Rush Presbyterian St. Luke's Hospital in Chicago, where the technique had been used on seven patients by July of 1988.

Conclusions and Recommendations

Each year, about 50,000 people in this country--most of them over the age of fifty--are diagnosed with Parkinson's disease, a chronic neurological disorder for which the cause is still mysterious. Unfortunately, the uncertainty surrounding the cause of most neurological disorders persists. What is unique about Parkinson's disease is that its major symptoms have a clear cause--a loss of dopamine-containing cells of the substantia nigra. Treatment, therefore, is aimed at alleviating symptoms until the underlying cause of Parkinson's disease is found. There are now a growing number of drugs and experimental surgical procedures that scientists hope will reverse or at least temper some of the symptoms of the disease. This article has evaluated one such surgery, known as pallidotomy. Additionally, the article has provided background information regarding the symptoms of Parkinson's disease and mode of action of pallidotomy. Two alternative treatments have also been discussed briefly in the article.

The evaluation of pallidotomy in this article has shown that the revived neurosurgical procedure has both advantages and disadvantages. Pallidotomy requires very little time, lasting a total of four to five hours, including prep time. The procedure is completely painless and offers immediate relief. The treatment has also been shown to be effective for up to ten years. On the other hand, doctors do make mistakes, and it is very easy for a surgeon to destroy too many or the wrong cells in a patient's brain, causing paralysis or blindness. According to rough estimates, paralysis or blindness have resulted in approximately 5% of cases. In addition, there is no central registry of surgeons who perform pallidotomies, so results have been difficult to quantify. This is part of the reason that the surgery is still considered experimental by many surgeons. And because it is so widely considered experimental, most insurance companies will not cover the cost of the surgery, which is about $40,000.

In spite of pallidotomy's disadvantages, pallidotomy could possibly be the most successful treatment for Parkinson's disease so far. The most commonly used treatment, L-dopa, while eliminating symptoms, loses its effectiveness after only two to five years. In contrast, Pallidotomy has been effective for six to ten years in about 90% of cases. L-dopa is also unpredictable, causing wild, jerky movements. An alternative surgery that has received a great deal of attention is one in which fetal nerve cells are implanted into the brain of a Parkinson's patient in order to substitute viable cells for damaged adult cells that cannot regenerate. This controversial operation has several disadvantages. First, although the severity of symptoms is reduced, supplementary treatments are required. Another major stumbling block is that researchers know virtually nothing about the survivability of the fetal cells. If scientists don't even know the cause for the original cell loss, how can they know what will survive in the depleted region of the brain? Scientists do not have that concern with pallidotomy because the surgery deals with the destruction of cells rather than the substitution of cells.

Until researchers gain a full understanding of the cause for Parkinson's disease, the debate over which treatment is most effective will continue. This article has shown that pallidotomy has the greatest potential to restore the lives of Parkinson's patients. In order to make the surgery more accessible, a central registry of surgeons who perform the surgery must be developed. A registry will be helpful in evaluating the surgery, and it will provide a reference for those medical facilities interested in doing the surgery. Once results are tabulated, a positive evaluation in an accessible publication will certainly be grounds for nationwide approval. Although individual studies are getting underway, a cooperative effort will certainly speed the research process.

Glossary

axon: the part of a nerve fiber through which electrical signals that stimulate neurotransmitter release are sent.
dopamine: a monoamine neurotransmitter formed in the brain, primarily in the substantia nigra; essential to the normal function of the central nervous system.
globus pallidus: part of the brain located within the basal ganglia; contains and releases neurotransmitters responsible for motor function (refer to Figure G-1 for location).
neuron: any of the cells that make up the nervous system, consisting of a nucleated cell body with dendrites and a single axon.
neurotransmitter: a chemical substance, such as dopamine, that transmits nerve impulses or signals across synapses to muscle fibers.
striatum: a region of the brain that controls walking, balance, and general voluntary movements.
substantia nigra: the brain's motor control center; a group of cells that projects to the basal ganglia and is involved in the performance of willed movements (refer to Figure G-1 for location).

Figure G-1. The region of the brain affected by Parkinson's disease. The degeneration of neurons of the substantia nigra is responsible for a severe loss of dopamine, which causes symptoms of Parkinson's disease.

References

Alterman, Dr. Ron L., "Revived Neurosurgery Aids Parkinson's Patients," http:///.thonline.com/news/th0122/stories/1062.htm (NewYork: University School of Medicine, January 1996).
Kolata, Gina, "Risky Cure -- A Special Report; Parkinson's Sufferers Gamble on a Surgery With Hazards," New York Times (16 March 1995), p.1.
Levin, Bonnie E., and H. L.Katzen, Early Cognitive Changes and Nondementing Behavioral Abnormalities in Parkinson's Disease, 33136 (Miami, Florida: Dept. of Neurology, University of Miami School of Medicine, 1995)) and 33124 (Coral Gables, Florida: Dept. of Psychology, University of Miami, 1995).
Neill, Michael, "Moment of Truth," People (July 31, 1995), pp. 38-42.
Strange, Philip G., Brain Biochemistry and Brain Disorders (Oxford, New York, Tokyo: Oxford University Press, 1992).
Weiner, Dr. William J., and Dr. A.E. Lang, "Behavioral Neurology of Movement Disorders," Advances in Neurology, vol.#65 (1995) pp. 43-47.

Author's Note: Tania Zeigler is a senior in Bacteriology at the University of Wisconsin-Madison. She is also completing a certificate in technical communication. (Back to Beginning)