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What is Parkinson's Disease?
Common Symptoms
What Causes Parkinson's Disease?
Medications
Surgical Treatments
Role of the Patient
Caregiver Information
Additional Information

Parkinson's disease occurs when a group of cells, in an area of the brain called the substantia nigra, that produce a chemical called dopamine begin to malfunction and eventually die. Dopamine is a neurotransmitter, or chemical messenger, that transports signals to the parts of the brain that control movement initiation and coordination. When Parkinson's disease occurs, for unexplained reasons, these cells begin to die at a faster rate and the amount of dopamine produced in the brain decreases. The four primary symptoms are:

• tremor of the hands, arms, legs, jaw, and face;
• rigidity or stiffness of the limbs and trunk;
• bradykinesia or slowness of movement, and
• postural instability or impaired balance and coordination.

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Common Symptoms?
The symptoms vary from patient to patient and not every one is affected by all of them. In some people, the disease progresses quickly; in others it does not. The following are the most common primary symptoms of Parkinson's disease.

Tremor: In the early stages of the disease, about 70% of people experience a slight tremor in the hand or foot on one side of the body, or less commonly in the jaw or face. It appears as a 'beating' or oscillating movement and is regular (4-6 beats per second). Because tremor usually appears when the muscles are relaxed, it is called "resting tremor." This means that the affected body part trembles when it is at rest and not doing work and often subsides with action. The tremor often spreads to the other side of the body as the disease progresses, but remains most apparent on the original side of occurrence.

Rigidity: Rigidity or increased muscle tone means stiffness or inflexibility of the muscles. Normally muscles contract when they move, and then relax when they are at rest. In rigidity, the muscle tone of an affected limb is stiff. Rigidity can result in a decreased range of motion. For example a patient may not swing his or her arms when walking. Rigidity can also cause pain and cramps at the muscle site.

Bradykinesia: Bradykinesia is a slowing of voluntary movement. In addition to slow movements, a person with bradykinesia will likely also have incompleteness of movement, difficulty in initiating movements, and arrests of ongoing movement. Patients may begin to walk with short, shuffling steps (festination), which, combined with other symptoms such as loss of balance, increases the incidence of falls. They may also experience difficulty making turns or abrupt movements. They may go through periods of "freezing," which is when the patient is stuck and finds it difficult to stop or start walking. Bradykinesia and rigidity can occur in the facial muscles, causing a "mask-like" expression with little or no movement of the face. The slowness and incompleteness of movement can also affect speaking and swallowing.

There are many secondary symptoms of Parkinson's disease. These include stooped posture, a tendency to lean forward or backward, and speech problems, such as softness of voice or slurred speech caused by lack of muscle control. Non-motor symptoms also impact the life of a person with Parkinson's. A survey published in October 2003, "The Impact of Parkinson's Disease on Quality of Life" revealed that two of the top three most disabling symptoms for people with Parkinson's are non-motor symptoms, including loss of energy and pain. To review the results of this survey go to: http://www.amarinpharma.com/.

The following is a list of secondary symptoms of Parkinson's disease:

• Speech changes
• Loss of facial expression
• Micrographia (small, cramped handwriting)
• Difficulty swallowing
• Drooling
• Pain
• Dementia or confusion
• Sleep disturbances
• Constipation
• Skin problems
• Depression
• Fear or anxiety
• Memory difficulties and slowed thinking
• Sexual dysfunction
• Urinary problems
• Fatigue and aching
• Loss of energy

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What Causes Parkinson's Disease?
Why an individual develops Parkinson's disease remains undetermined. The causes likely include both genetic and environmental factors. A variety of mechanisms that are believed to cause accelerated cell death have also been suggested, including oxidative stress, excitotoxicity and mitochondrial dysfunction. These are described below.

• Genetics    About 15-25% of Parkinson's patients report having a relative with Parkinson's. Researchers have found a defective gene in some rare families, with a high incidence of Parkinson's disease. These rare cases have an inherited form of Parkinson's disease. Scientists have discovered several "Parkinson's genes" and there is conclusive evidence that genetics play a role in at least some patients. There appears to be a 2-3 fold increased risk of PD in first degree relatives compared to matched control populations. However, the majority of cases of PD still appear to be sporadic.
• Environmental Factors    Some scientists have suggested that Parkinson's disease may occur when a toxin selectively destroys dopaminergic neurons. Scientists have known for a number of years of several toxins that can cause Parkinson's-like symptoms, such as MPTP. Several studies have suggested a link between rural living, herbicide use and exposure to pesticides as possible factors that may contribute to a person's developing Parkinson's. Some PWP's recall a time when they were exposed to chemicals, and believe this exposure may be a possible cause. Scientists are continuing to pursue these clues to establish more concrete linkages.

While the debate concerning environmental factors and genetics as causative factors in PD continues, there has been extensive investigation of the mechanisms involved in the cell death process. A number of cell death concepts have been put forward including, oxidative stress, mitochondrial dysfunction and excitotoxicity.

• Oxidative damage    This theory suggests that free radicals - unstable molecules whose toxic effects are believed to be caused by oxidation - may contribute to cell death, thereby leading to Parkinson's disease. Oxidation is thought to cause damage to tissues, including neurons. In addition, antioxidant defenses appear to be markedly reduced in PD brains. In particular, reduced levels of glutathione (an acid which plays a role in the detoxification of harmful compounds) have been discovered. The cause of the deficiency and the potential role that antioxidants like glutathione play in the development of PD remain unresolved.
• Mitochondrial dysfunction    The mitochondria are small bodies within cells that produce energy. They can be described as the 'power-house' of the cell. Scientific findings indicate a reduction in the function of mitochondria and this may play a role in PD.
• Excitotoxicity    occurs when selected neurotransmitters in the brain get out of balance leading to cell death. This mechanism has been documented in Parkinson's and scientists believe that glutamate excitotoxicity is the main culprit within this mechanism. Finding a way to correct this imbalance may prevent be neuroprotective.

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Medications for Parkinson's Disease
There are several symptomatic treatments for people with Parkinson's including medication, surgery, and physical therapy. The degree of success of each treatment varies among individuals, as does the length of time the treatment option remains effective.

Levodopa is a dopamine precursor, a substance that is converted into dopamine by an enzyme in the brain. The use of levodopa was a breakthrough in the treatment of PD. Unfortunately, patients experienced debilitating side effects, including severe nausea and vomiting. With increased dosing and prolonged use of levodopa, patients experienced other side effects including dyskinesias (spontaneous, involuntary movements) and "on-off" periods when the medication will suddenly start or stop working.

Check with a doctor before taking any of the following to avoid possible interactions: antacids, anti-seizure drugs, anti-hypertensives, anti-depressants and high protein food.

Combining Levodopa with Carbidopa (Sinemet) represented a significant improvement in the treatment of Parkinson's disease. The addition of carbidopa prevents levodopa from being metabolized in the gut, liver and other tissues, and allows more of it to get to the brain. Therefore, a smaller dose of levodopa is needed to treat symptoms. In addition, the severe nausea and vomiting often associated with levodopa treatment was greatly reduced.

Consult a doctor before taking any medications to avoid possible interactions. In particular, antacids, anti-seizure drugs, anti-hypertensives, anti-depressants and high protein food may adversely affect the function of Levodopa/carbidopa.

Stalevo (carbidopa, levodopa and entacapone) is a new (September 2003) combination tablet for patients who experience signs and symptoms of end-of-dose "wearing-off." The tablet combines carbidopa/levodopa (the most widely used agent for PD), with entacapone. While carbidopa reduces the side effects of levodopa, entacapone extends the time levodopa is active in the brain (up to 10 percent longer). The same drugs that interact with carbidopa/levodopa and entacapone interact with Stalevo.

Symmetrel (amantadine hydrochloride) is thought to work in PD because it has several actions. It activates both the release of dopamine from storage sites and possibly blocks the re-uptake of dopamine into nerve terminals. It also has a glutamate receptor blocking activity. Its dopaminergic actions result in its usefulness in reducing dyskinesia induced by levodopa. It is thus called an indirect-acting dopamine agonist, and is widely used as an early monotherapy (treatment of a condition by means of a single drug), with the more powerful Sinemet added when needed. Unfortunately, its benefit in more advanced PD is often short-lived, with patients reporting a fall-off effect.d

Symmetrel may interact with Cogentin (benztropine), Disipal (orphenadrine), Sinemet (levodopa), Artane (trihexyphenidyl), amphetamines and alcohol.

Anticholinergics (trihexyphenidyl, benztropine mesylate, procyclidine, etc.) do not act directly on the dopaminergic system. Instead they act to decrease the activity of another neurotransmitter, acetylcholine. There is a complex interaction between levels of acetylcholine in the brain and levels of dopamine. Many clinicians find that if an agonist or levodopa does not relieve tremor, then the addition of an anticholinergic drug is often effective. Adverse effects include blurred vision, dry mouth and urinary retention. These drugs may be contraindicated in older patients since they can cause confusion and hallucination.d

Check with a doctor before using anticholinergics with anti-histamines, Haldol, Thorazine, Symmetrel, Clozaril and alcohol.

Selegiline or deprenyl (Eldepryl) has been shown to delay the need for Sinemet when prescribed in the earliest stage of PD, and has also been approved for use in later stages to boost the effects of Sinemet. Eldepryl may interact with anti-depressants, narcotic pain killers and decongestants. Check with a doctor before taking any new medications.

Dopamine agonists are drugs that activate dopamine receptors directly, and can be taken alone or in combination with Sinemet. Agonists available in the United States include bromocriptine (Parlodel), pergolide (Permax), pramipexole (Mirapex) and ropinirole (Requip).

Consult a doctor before taking any of the following to avoid possible interactions: alcohol, anti-psychotics, medications that lower blood pressure, Navane (thiothixene), Taractan (chlorprothixene), Haldol (haloperidol), Reglan (metoclopramide), phenothiazines, thiozanthenes, cimetidine, phenothiazines, butyrophenones, Cipro and benzodiazepines.

COMT inhibitors such as tolcapone (Tasmar) and entacapone (Comtan) represent a different class of Parkinson's medications. These drugs must be taken with levodopa. They prolong the duration of symptom relief by blocking the action of an enzyme which breaks down levodopa.

*** Side Effects from Medications - Like the symptoms of PD themselves, the side effects caused by Parkinson's medications 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 may have to discontinue its use because of them.

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Surgical Treatments
Surgery is an option for patients to explore after they have had experience with medications and are no longer satisfied with the results. A patient should discuss surgery thoroughly with his or her neurologist before making any decision.

Two older, and somewhat outdated, lesioning procedures that provide relief from Parkinson's symptoms are pallidotomy and thalamotomy. Pallidotomy can alleviate rigidity and bradykinesia symptoms, and thalamotomy helps to control tremors. Doctors rarely perform either procedure because both permanently destroy parts of the brain and have serious side effects. The damage could make it impossible to perform surgeries that may become available in the future, such as brain tissue transplants.

Deep brain stimulation (DBS) , a safer and more effective surgery, has replaced these methods. It is a preferred surgical option because it has the same, if not better results than pallidotomy and thalamotomy. DBS also leaves open the possibility of other therapies, should they become available in the future. As with any surgical procedure, there are risks and side effects. The main benefit of DBS surgery is to reduce motor fluctuations i.e. the ups and downs caused by a decreasing effectiveness of Sinemet.

The electrode is usually placed on one side of the brain. The DBS electrode implanted in the left side of the brain will control the symptoms on the right side of the body and vice versa. In some cases, patients will need to have stimulators on both sides of the brain.

During surgery, a device is implanted to provide an electrical impulse to a part of the brain involved in motor function. This is often the subthalamic nucleus, in a deep part of the brain called the thalamus. During the procedure, electrodes are inserted into the targeted brain region using MRI and neurophysiological mapping to ensure that they are implanted in the right place. The electrodes are connected to wires that lead to an impulse generator or IPG (similar to a pacemaker) that is placed under the collarbone and beneath the skin. Patients have a controller, which allows them to verify whether the DBS is 'on' or 'off'. They can use this device to check the battery and to turn the device 'on' or 'off'. An IPG battery lasts for about 3 to 5 years and is relatively easy to replace under local anesthesia.

Patients considering one or another surgical procedure should discuss the options first with their movement disorder specialists and then with their families and/or caregivers.

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Role of the Patient
Treating Parkinson's disease is not exclusively the doctor's job; there is much the individual can do to stay as well as possible for as long as possible. Regular exercise, being part of a support group, maintaining a healthy diet or taking part in a clinical trial are just some of the things you might consider.

Exercise: For people with Parkinson's, regular exercise and/or physical therapy are essential for maintaining and improving mobility, flexibility, balance, and a range of motion, and for warding off many of the secondary symptoms mentioned above. Exercise is as important as medication for the management of PD.

Support groups: For many people, these groups play an important role in the emotional well-being of patients and families. They provide a caring environment for asking questions about Parkinson's, for laughing and crying and sharing stories and getting advice from other sufferers, and for forging friendships with people who understand each other's problems.

Diet: There is no specific diet to prevent or slow Parkinson's but there are several suggestions to help manage the disease. A vegetable-rich diet may aid digestion and prevent constipation. Parkinson's patients should also take a balanced approach to protein intake because protein inhibits the absorption of levodopa in the gut. Avoiding high protein meals when taking levodopa helps prevent this potential problem. However, a patient should not make dietary changes without discussing this first with their doctor. Parkinson's disease nutrition author, Kathrynne Holden, offers several books, including "Eat Well, Stay Well" and "Cook Well, Stay Well" that provide beneficial eating and cooking tips. Copies can be ordered from Five Star Living, on (877) 565-2665 or at www.nutritionucanlivewith.com.

A Healthy Patient/Doctor Relationship: A neurologist can most effectively help a patient manage his or her Parkinson's if the neurologist and the patient have a good working relationship. Doctors need the patient to be honest, forthright, and inquisitive in order to give the best medical attention possible. Patients should also require that a doctor treat them in the same honest, open manner, engaging them in dialogue about the patient's experiences. Doctors can provide a wealth of information and suggestions for improving quality of life.

Physical, Speech and/or Occupational Therapy: These therapies can help Parkinson's patients control their symptoms and make daily life easier. Physical therapy may increase muscle strength and flexibility and decrease the incidence of falls. Speech therapy is available to increase voice volume and assist with word pronunciation. The Lee Silverman technique is a special speech therapy that can be very beneficial to people with Parkinson's - for further information see www.lsvt.org.

Occupational therapy affords patients alternative methods of doing tasks that they can no longer perform with ease. These options may give patients a stronger sense of control when living with Parkinson's disease, which seems to take control from them. The patient should ask a physician for recommendations if he or she does not provide them. These therapies may or may not be covered by insurance.

Clinical Trials: Getting involved in a clinical trial may be a way for a patient to feel empowered and help researchers understand more about Parkinson's disease in order to improve treatment options for this disorder. Increased clinical trial participation will result in a better understanding of the disease and will also help treatments that are in the research and developmental phases reach patients more quickly. A patient should understand what the trial entails and be educated about the patient's responsibilities and obligations. To find more information on the patient's role in clinical trials, visit www.ninds.nih.gov/parkinsonsweb/clinical_trials_info.htm.

For information on Parkinson's disease clinical trials, visit:
www.clinicaltrials.gov
www.centerwatch.com

To participate in an important survey about clinical trials, please click here.

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PD Caregiver Well-Being

What can friends and family of a person with Parkinson's do?

• Stay educated about the person's condition and abilities and adapt accordingly.
• Support environment and lifestyle changes that often need to be made by a person with Parkinson's disease.
• Encourage medical consultation with a physician.
• Request a referral for occupational therapy from a family physician to promote maximal capabilities in self-care, household tasks, and valued life activities.

Physical Health
Caregiving can be physically and emotionally draining, especially when caregiving duties are demanding and constant. PD caregivers provided an average of 96 hours of care per week to their care recipients. The vast majority (73%) reported significant health problems. The most prevalent health problems reported involved arthritis (27%), self-reported depression (26%), high blood pressure (23%), and heart trouble (15%). One-third of PD caregivers reported their overall health as fair (28%) or poor (5%), while nearly half of caregivers (46%) stated their health troubles were standing in the way of assuming an expanded caregiving role. Forty-eight percent stated their current health status was worse at the time of assessment than it had been five years earlier. One in five caregivers (20%) had at least three medical exams in the last six months.

Mental Health
PD caregivers experienced high levels of depression as illustrated by an average score of 19.88 on the CES-D3. In fact, 60% of this group scored 16 or higher on the CES-D questionnaire (26% of PD caregivers self-reported depression was a current health problem). Among PD caregivers, women scored significantly higher than men (t = -2.72, p< .01). Interestingly, depression scores did not differ significantly by ethnicity, but did differ by type of relationship between the caregiver and care recipient, albeit not significantly. Mothers and daughters of care recipients scored the highest of all relationship groups on the CES-D (34.5 and 22.0, respectively). PD caregivers were significantly more likely to demonstrate higher depression scores if their care recipients needed supervision with performing personal care tasks compared with PD.

3 Score of 16 or higher on the CES-D demonstrates evidence of clinically significant depressive symptoms. caregivers reporting other functional needs. Additionally, PD caregivers who reported their loved ones were either forgetting what day it was or were being argumentative or irritable, were significantly more likely to score high on the CES-D respectively than PD caregivers whose care recipient did not report these behaviors.

PD Caregiver Strain
More than one-third (38%) of PD caregivers reported the informal help and social support they were receiving was far less than they needed. When asked how burdened they felt in caring for their relatives, 28% of PD caregivers reported feeling “quite a bit” burdened while 16% reported feeling “extremely” burdened. Another 31% of PD caregivers reported feeling “moderately” burdened.

Perception of role
Generally, PD caregivers reported feeling confident in their caregiving role, as demonstrated by an average competency score of 21.4 out of a possible 27. A relatively small percent of caregivers responded “not at all” when asked if they know where and how to request help from others (12%). A majority of caregivers felt that they “somewhat” or “very much” received the emotional support they needed (81%) and were able to develop ways to manage the stresses of caregiving (83%).

Identified PD Caregiver Problems at Assessment
CRC Family Consultants reported the most common problems for PD caregivers at assessment were the need for respite (85%), emotional support (83%), and behavior management (32%). Figure 5 presents the current problems of PD caregivers upon completion of an assessment.