Parkinson's Disease

INTRODUCTION In 1817, a London physician, named James Parkinson, wrote the first information of Parkinson’s disease in his “Essay of the Shaking Palsy.” Little research was done throughout the years. However, researchers at the University of Vienna brought hope in 1960, that restoring low dopamine levels might effectively treat the disease. Investigators soon learned that dopamine by itself was useless; it would be metabolized before reaching the brain. So, in 1970, levodopa was approved for prescription sale and in 1975, Sinemet became available on prescription. What exactly is Parkinson’s? Are there effective treatments? Soon, we will find out the answers to these questions and many others. Not many people know what Parkinson’s disease is. Others may have misconceptions about the disease. I wrote this paper to inform the reader and to expand on my own general interest. Also, this topic is important to me because my grandmother has this disease, and I wanted to know more about it. I would like to thank the writers and publishers for writing and printing the necessary material. This paper is incomplete due to unobtainable sources, because this is an ever-changing field, and limited resources for obtaining some information. PARKINSON’S DISEASE Parkinson’s disease is a degenerative neurological disorder characterized by tremor, stiffness, and slowness of movement. Patients diagnosed with Parkinson’s disease become hunched over, tend to lose their balance, and have slurred speech (Sinha & Zang, pp. 77-81). There are many other symptoms which will be described briefly. Between one and one-and-a-half million Americans have Parkinson’s disease. It can affect men and women; men have a greater chance of getting it; living anywhere in the world. It is uncommon in people under thirty years old and eighty percent of all cases are diagnosed after the age of fifty. As with many other diseases, the risk of developing Parkinson’s disease increases with age. “Before the current best treatments, the mortality rate was three times higher than for the average person. Currently it’s one-and-a-half times as high. The saying now is that you don’t die from Parkinson’s disease; you die with it,” (Meadows, pp.117). It has been approximately 183 years since James Parkinson, who the disease is named after respectively, wrote his “Essay of the Shaking Palsy,” (www.coyotewebart.com/parkinsons_news/curve.html). Little was known then, and still, 183 years later, researchers are looking for the cure which is basically like looking for a needle in a hay stack. A daunting task, yes, but when the needle is found, all the hard work and dedication will be embellished with success. Some of the first signs or symptoms of Parkinson’s disease could be shorter strides, lack of arm swing, and possibly a tremor on one side of the body. The cause of these symptoms is from the slow degeneration of specific brain cells that make dopamine (Sinha & Zang, pp. 77-81). Dopamine is an important neurotransmitter that acts as the go signal between the brain with the rest of the body, initiating thought page 2 into motion. Primary symptoms include rigidity, tremor, Bradykinesia, poor balance, & walking problems. Rigidity is an increased tone or stiffness in the muscles which is often responsible for a mask-like expression of the face. Unless it is temporarily eased by anti-Parkinson’s medications, rigidity is always present. In some patients, rigidity leads to sensations of pain, especially in the arms and shoulders. Tremor is the symptom the public most identifies with Parkinson’s disease, but in fact, only twenty-five percent of patients experience a very slight tremor or none at all. When a tremor is present, it may be worse on one side of the body (www.pdf.org, December 2000). Bradykinesia is characterized by a delay in initiating movements. Poor balance leads to repeated falls and walking problems which include a decreased or nonexistent arm swing; short, shuffling steps; difficulty in negotiating turns; and sudden freezing spells. Everyday dilemmas patients with Parkinson’s encounter, include difficulty with fine hand movements like writing or tying shoelaces, to other movements, such as getting out of a chair or turning in bed. It is important to note that not all patients experience the full range of symptoms. In fact, most do not. People with Parkinson’s disease may also suffer from any of a long list of secondary symptoms. Depression, sleep disturbances, dizziness, dementia, and swallowing are merely a few of these. Once again, all patients experience different symptoms. The actual cause of Parkinson’s is not known. A defective gene was recently found in a few families with a high incidence of Parkinson’s disease, but most researchers believe in the vast majority of cases, genetics alone are not the cause. Instead, it is suspected that Parkinson’s usually results from the combination of a genetic predisposition and an as yet unidentified environmental trigger (www.pdf.org, December page 3 2000). For early treatments of Parkinson’s disease, extracts from the belladonna plant were found to help relax stiffened muscles and to quiet tremors and were used in therapy until after World War II, when a number of similarly acting drugs came into use. Discovery of the brain dopamine deficiency in parkinsonian patients - reported in 1960 by researchers at the University of Vienna - brought hope that restoring the dopamine level might effectively treat the disease. Investigators soon found, however, that giving dopamine by itself was completely useless: the substance did not reach the brain because it could not cross the blood-brain barrier, a protective biochemical mechanism by which the body screens agents passing from the blood into the central nervous system. Scientists then turned to levodopa, the substance that is dopamine’s metabolic precursor. Levodopa did cross the blood-brain barrier and could be quickly metabolized into dopamine. In 1970, levodopa was approved for prescription sale. It was the first major breakthrough, but side effects are severe nausea and vomiting because the drug is broken very rapidly in the body, requiring large doses if the substance is to penetrate the brain. According to the NINCDS Research Program pamphlet, some patients experienced toxic side effects from these dose levels that were so severe that the drug had to be discontinued. Researchers soon learned, however , that they could greatly reduce dose levels - and thus cut down on side effects - by giving levodopa in conjunction with a substance that slows its breakdown in the body. Sinemet, a combination of levodopa and the inhibiting substance carbidopa, has been available since 1975. Treatments must be fine-tuned to suit individual patients depending on their symptoms and stage of disease (Tackacs, Toronto Star). For most Parkinson’s disease patients, the levodopa/carbidopa page 4 cocktail still stands as the single , most effective therapy available. Most patients benefit from it: some moderately and some with striking relief from their symptoms - at least for several years. There are a few other drugs available that are also prescribed. Symmetrel, which was originally an anti-flu medication, is thought to block or reuptake dopamine by neurons, or it increases the release of dopamine by neurons, thereby increasing the supply of dopamine in the synapses. When its benefits seem to lessen, stopping the drug for a short time and then reintroducing it seems to provide help once again, according to some clinicians. Tremors can be controlled by prescribing anticholinergics, which act to decrease the activity of the balancing neurotransmitter, acetylcholine. Older patients may not be able to take these drugs because they tend to cause confusion and hallucination. Selegiline or deprenyl have been shown to delay the need for sinemet when prescribed in the earliest stages of Parkinson’s disease, and they have also been approved for use in later stages to boost the effects of Sinemet. COMT inhibitors such as tolcapone and entacapone, represent a new class of Parkinson’s medications. These drugs must be taken with levodopa so they prolong the duration of symptom relief by blocking the action of an enzyme which can break down levodopa before it reaches the brain. Like the symptoms of Parkinson’s disease itself, the side effects of drugs vary from patient to patient. They may include dry mouth, nausea, dizziness, confusion, hallucinations, drowsiness, insomnia, and other unwelcome symptoms. Some patients experience no side effects from a drug, while others have to discontinue its use because of them. When drugs aren’t working, there’s still surgery. The most common procedures page 5 are palliodotomys, in which the surgeon drills through the skull and destroys selected brain cells, and deep brain stimulation, in which electrodes are implanted in the thalamus and connected to a pacemaker-like device. In a palliodotomy, there is a possibility of stroke, partial loss of vision, speech and swallowing difficulties, and confusion. There aren’t many risks with deep brain stimulation. New, controversial forms of surgery, called brain tissue implants, are still in experimental , however, promising results leave researchers hopeful that this surgery will provide a long-lasting treatment for the disease. Jim Finn, a recipient of the disease, has had Parkinson’s disease for twenty years. Three years ago, at age fifty-one, doctors diagnosed him as “end stage” - they could do nothing more for him. That’s when Finn’s doctor approached him about an experimental new treatment in which surgeons would implant millions of fetal pig cells into the brains of Parkinson’s patients. Without hesitation, Finn agreed to the surgery (Sinha & Zang, pp. 77-81). Finn describes the procedure as going through a drive-thru: “Buy some burgers, get some surgery.” The whole surgery actually takes only two-and-a-half hours. Also, patients can be awake the whole time from the use of local anesthesia. The doctors inject the fetal pig cells through an injection syringe guided by a halo-shaped frame bolted to the head. Originally, surgeons used aborted human fetuses to harvest the cells which are needed, but many considered this unethical. Researchers realized these obstacles early on, and so focused on using fetal pig cells instead. The results have been amazing: Finn can now walk with out his cane, write his name, and cut his pork chops into bite-size pieces. Nowadays, he gives speeches to medical professionals and support groups about his successful surgery. “I’m a commodity now. Pork bellies, I think they call it,” he jokes. CONCLUSION In reality, Parkinson’s disease may not be such a burden as we think. The Medicine being prescribed is getting better. There are even surgeries to help out those who are at “end stage” like Finn. Many people think soon we will find the real cause for this dreadful disease, thus finding a cure. We should all care about this disease, because it could affect you or someone you know. Unfortunately, there are still only a small amount of resources available. I think this is due in part that little is known still, however more is known than the past. Lack of research funds and grants to facilities also plays a major factor. I wish I could have written more about the history of Parkinson’s, but it was very difficult finding what I have. Also, I would have liked to have written more about Jim Finn and his results from the surgery. It is truly amazing what we can do today with technology. Maybe since geneticists have mapped the human genome this past year, researcher will be able to use that information to help find a cure. Michael J. Fox, who has been in hit TV shows “Family Ties” and “Spin City”, has recently been lobbying congress to fund more money for researchers. He has been battling Parkinson’s for many years. This disease affects about one-and-a-half million Americans, but currently gets a pitiful amount of funding compared to what other causes get. We should be fighting for a cure since it affects so many people. But we must remember, there is life after Parkinson’s; patients will go one with their lives with a cure or not. It just would be nice to find that needle in the hay stack. (please e-mail me, ashley_b83@hotmail.com, to give me your opinion on my term paper. This paper recieved a 97/A+.)

Bibliography

Meadows, Bob, “War of Nerves,” People, (January 11, 1999) pp. 117-118, 120. Sinha, Gunjan and Zang, Matt, “Treating Parkinson’s: On the Road to Recovery,” Popular Science, (October 1, 1999), Vol. 255, pp. 77-81. Takacs, Marianne, “Yes, there most definitely is life after Parkinson’s,” The Toronto Star, (June 24, 2000). The NINCDS Reasearch Program, July 14, 1980, pp. 1-2, 8. , Internet, December, 2000. , Internet, December, 2000.