- Parkinson's Disease Facts
- Parkinson's Disease Causes
- Parkinson's Disease Symptoms
- When to Seek Medical Care for Parkinson's Disease
- How to Test for Parkinson's Disease
- Parkinson's Disease Treatment and Self Care at Home
- Parkinson's Disease Medical Treatment
- Parkinson's Disease Medications
- Parkinson's Disease Surgery, Gene Therapy, and Other Interventions
- Parkinson's Disease Follow-up and Prognosis
- Parkinson's Disease Topic Guide
- Doctor's Notes on Parkinson's Disease (PD) Symptoms
Parkinson's Disease Facts
Parkinson's disease (PD) is an age-related progressive deterioration of certain nerve systems in the brain, which affects movement, balance, and muscle control.
- Parkinson's disease is one of the most common movement disorders, affecting about 1% of people older than 60 years. Parkinson's disease is about 1.5 times more common in men than in women, and it becomes more likely to occur in people as they age. Parkinson's disease is not a hereditary disease.
- The average age of onset is about 60 years. Onset before age 40 years is relatively uncommon, but the much-publicized diagnosis of actor Michael J. Fox shows that younger people are also vulnerable.
- In Parkinson's disease, brain cells deteriorate (or degenerate) in an area of the brain called the substantia nigra. From the substantia nigra, specific nerve cell tracts connect to another part of the brain called the corpus striatum, where the neurotransmitter (a chemical messenger in the brain) called dopamine is released. Dopamine is an important neurotransmitter and alterations in its concentration can lead to the different medical problems seen in Parkinson's disease.
- The loss of these specific brain cells and decline in dopamine concentration are key steps that lead to the signs and symptoms of Parkinson's disease as well as are the target for treatments of Parkinson's disease. However, the biological, chemical, and genetic mechanisms responsible for the brain cell loss have not been identified with certainty.
Parkinson's Disease Causes
The causes of Parkinson disease remain unclear; clinicians and researchers have clear evidence that the nerve cells that produce dopamine in the brain's region known as the substantia nigra are altered and lost (destroyed). The challenge that remains is to discover how these neurons are destroyed to cause Parkinson's disease. Advances in genetics have lead researchers to discover that about 10% of people that develop the disease are due to multiple genetic factors, but these people usually are younger than 50. The majority of researchers suggest that a combination of genetic and environmental factors cause about 90% of cases of Parkinson's disease, but how these factors interact to alter and destroy brain cells thus producing Parkinson's disease is not well understood. A few theories and risk factors are listed below that may offer additional information and clues that may help lead to a better understanding of Parkinson's disease causes.
- Environment: Studies have found that living in a rural area, drinking well water, or being exposed to pesticides, herbicides, or wood pulp mills may increase a person's risk for developing Parkinson's disease.
- Oxidation hypothesis: Free radicals, generated from dopamine's oxidation, generate cell damage and death.
- It is thought that free radicals may play a role in the development of Parkinson's disease. Free radicals are atoms or groups of atoms with unpaired electrons that can damage cells and intracellular structures. Free radicals can be created when dopamine is broken down by combining it with oxygen.
- This breakdown of dopamine by an enzyme called monoamine oxidase (MAO) leads to the formation of hydrogen peroxide.
- A protein called glutathione normally breaks down the hydrogen peroxide quickly. If the hydrogen peroxide is not broken down correctly, it may lead to the formation of these free radicals, enhanced by the presence of iron, that then can react with cell membranes to cause lipid peroxidation (when the hydrogen peroxide interacts with lipids [fat-soluble substances] in the cell membrane). This leads to cell damage and cell death.
- The association of Parkinson's disease with increased dopamine turnover, decreased mechanisms (glutathione) to protect against free radical formation, increased iron (which makes it easier to create free radicals), and increased lipid peroxidation helps support the oxidation hypothesis.
- If this hypothesis turns out to be correct, it still does not explain why or how a loss of the protective mechanism occurs. An answer to this question may not be required. If the theory is correct, drugs may be developed to stop or delay these events.
- Alpha-synuclein alteration: The protein alpha-synuclein is involved in neurotransmitter release. This protein is a major component of Lewy bodies, which are found in the neurons of Parkinson's disease patients. The theory is that under certain conditions (genetic, environmental, or a combination of both) may lead to protein aggregates that develop in the Lewy bodies. During their development, some of the alpha-synuclein intermediates may be toxic to neurons. Other variations of this hypothesis suggest that lysosomes in the cells allow alpha-synuclein proteins to accumulate and then aggregate while other investigators suggest that Lewy bodies may develop like prions and may represent an autoimmune-like disease.
- Mitochondrial dysfunction: Mitochondrial activity in the cells of Parkinson's disease patients is reduced, so some investigators suggest that that whatever reduces this activity plays a causal role in Parkinson's disease. They conclude this because certain chemicals that can produce Parkinson's disease symptoms in humans cause disruption of mitochondrial functions and are effectively treated by dopamine.
- Some people have symptoms of Parkinson's disease that may have an identifiable cause. In this case, the syndrome is known as Parkinsonism or secondary Parkinson's disease. Parkinson's that is caused by drugs is probably far more common than reported and accounts for about 4% of all cases of Parkinson's. These findings give additional insight toward definition of potential Parkinson's disease causes.
- A change in the level of dopamine, whether by brain cell loss or drug use, can create the symptoms of Parkinson's disease.
- Interestingly, people who experience drug-induced Parkinson's may actually have a higher risk of developing Parkinson's disease later in life.
- A number of medications can cause Parkinson's by lowering dopamine levels. These are referred to as dopamine-receptor antagonists or blockers.
- Nearly all antipsychotic or neuroleptic medications such as chlorpromazine (Thorazine), haloperidol (Haldol), and thioridazine (Mellaril) can induce the symptoms of Parkinson's.
- The medication valproic acid (Depakote), a widely used antiseizure medication, may also cause a reversible form of Parkinson's.
- Medications such as metoclopramide (Octamide, Maxolon, Reglan), which is used to treat certain stomach disorders such as peptic ulcer disease, are capable of causing Parkinson's or making it worse.
- Antidepressants known as selective serotonin-reuptake inhibitors may cause symptoms similar to Parkinson's.
- These medications can alter the concentration of dopamine in the central nervous system.
Parkinson's Disease Symptoms
The three key signs of Parkinson's disease are tremor (shaking) at rest, rigidity, and slowness in the initiation of movement (called bradykinesia). Of these features, two are required to make the diagnosis. Postural instability is the fourth key sign, but it happens late in the disease, usually after having Parkinson's disease 8 years or more.
Tremor at Rest
- Tremor usually begins in one arm and may start and stop.
- As with most tremors, it worsens when under stress and improves during rest or sleep.
- After several months to a few years, both arms may become affected, but the initial asymmetry (one-sidedness) is often maintained.
- Parkinson's disease tremor may also involve the tongue, lips, or chin.
- The characteristic Parkinson's disease tremor is present and most prominent with the limb at rest.
- The tremor may appear as a pill-rolling motion of the hand or a simple oscillation of the hand or arm.
- Rigidity refers to an increase in resistance to someone else moving the patient's joint.
- The resistance can be either smooth ("lead-pipe") or start and stop ("cog wheeling"). (Cog wheeling is thought to be a tremor rather than rigidity.)
- Having someone else flex and extend the patient's relaxed wrists tests for rigidity.
- Rigidity can be made more obvious with voluntary movement in the opposite limb.
- Bradykinesia refers to slowness of movement but also includes a lessening of unplanned movements and decreased size of movement.
- Bradykinesia is also expressed as micrographia (small handwriting), hypomimia (decreased facial expression), decreased blink rate, and hypophonia (soft speech).
- Postural instability refers to imbalance and loss of reflexes used to keep a person upright.
- This symptom is an important milestone, because it is not easy to treat and a common source of disability in late disease.
- People may experience freezing when starting to walk (start-hesitation), during turning, or crossing a threshold such as going through a doorway.
- Flexed postures of the neck, trunk, and limbs may occur.
- Altered mental status generally occurs late in Parkinson's disease and affects 15% to 30% of people with Parkinson's disease.
- Short-term memory and visual-spatial function may be impaired.
- The onset of Parkinson's disease is typically unilateral, with the most common initial finding being an asymmetric rest tremor in one arm. About 20% of people first experience clumsiness in one hand.
- Over time, Parkinson's disease patients will notice symptoms related to progressive bradykinesia, rigidity, and problems with walking (called gait disturbances).
- Some people experience a subtle decrease in dexterity and may notice a lack of coordination with activities such as golf, dressing, or climbing stairs.
- Some people complain of aching or tightness in the calf or shoulder region.
- The first affected arm may not swing fully when walking, and the foot on the same side may scrape the floor.
- Over time, posture becomes progressively flexed and the gait becomes shorter, leading to a shuffling gait.
- Decreased swallowing may lead to excess saliva and ultimately drooling.
- Symptoms of problems with the involuntary nervous system are common and may include constipation, sweating abnormalities, and sexual dysfunction.
- Sleep disturbances are also common.
Symptoms are usually progressive in their severity over time. However, not every symptom described may be apparent in each individual Parkinson's disease patient. However, the older the age of initial onset of Parkinson's disease, usually the more rapid development of motor and cognitive decline symptoms.
When to Seek Medical Care for Parkinson's Disease
If a person feels they are beginning to experience symptoms of Parkinson's disease, especially if they are over age 59, they should consult with their doctor.
Because Parkinson's disease is a progressive disease, people will continue to experience new and disturbing symptoms.
- These symptoms can sometimes be hard to distinguish from side effects of medications, which can be numerous in someone with Parkinson's disease.
- Thus, any change in a person's baseline health condition should prompt an evaluation to rule out other medical conditions or medication side effects.
Although the emergency department is not the setting for deciding if someone has Parkinson's disease, visits may be needed to rule out or treat other emergent medical conditions.
Specific complications associated with Parkinson's disease may need an emergency department visit. For example:
- At times, new or changing symptoms may mimic other diseases and cause the patient or their family anxiety. (For instance, people may have changes in their ability to think or be unable to move a certain body part that is worse than before, mimicking signs of a stroke.)
- With advancing Parkinson's disease, people become more likely to fall because of increasing problems with walking.
- Many people with Parkinson's disease may also develop osteoporosis (loss of calcium in bone), which in combination with walking problems of Parkinson's disease can make people more likely to have pelvic, hip, and other types of fractures.
- The involuntary nervous system problems of Parkinson's disease may cause some Parkinson's disease patients to have severe urinary retention (inability to urinate), constipation, or fecal impaction requiring medical intervention.
- The movement disorder may also affect the swallowing mechanism and esophagus causing some Parkinson's disease patients to choke or have food become impacted within the esophagus.
- Another associated complication of Parkinson's disease is aspiration (inhalation of food) of either liquids or solids, which makes people more likely to have pneumonia and possibly can cause choking.
- The medications used to treat Parkinson's disease patients are not without complications. For instance, low blood pressure may result and contribute to the sense of imbalance or increase the risk of falls or other trauma.
- In addition, people with Parkinson's disease can become immobilized by the disease, which can lead to painful muscle contractions. The muscles can become locked in spasm preventing the Parkinson's disease patient from moving the extremity. If a person with Parkinson's disease is unable to communicate effectively, this may cause a great deal of anxiety. Certain medications and physical therapy may help alleviate this problem.
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How to Test for Parkinson's Disease
No blood test exists that definitively diagnoses Parkinson's disease. Currently, a strong presumptive diagnosis of Parkinson's disease is made by a doctor's observation of the patient's symptoms, medical history and neurologic examination, and response to a treatment schedule with the combination medicine generically termed carbidopa-levodopa (Sinemet, Atamet, Parcopa).
Definitive diagnosis of Parkinson's disease can be difficult. As stated above, there is no specific blood test or diagnostic study currently available to make the diagnosis. In fact, a brain tissue sample, though not practical in living patients, is the only way to be relatively sure of the diagnosis. This is usually done at autopsy. Studies have shown that a misdiagnosis rate in the past of 25% to 35% was not uncommon. This rate drops to about 8% when a movement disorder specialist physician (for example, a neurologist) helps make the diagnosis. Consequently, consultation with a specialist is usually recommended.
People that suspect they may be experiencing symptoms of Parkinson's disease should consult with their primary care doctor and ultimately may need a referral to a neurologist who specializes in movement disorders.
- In the past, at least two of the cardinal symptoms (tremor, rigidity, and bradykinesia) needed to be present to make the diagnosis of Parkinson's disease. These criteria alone were found to be incorrect in 25% of people diagnosed.
- Studies that look back at people with Parkinson's disease after the diagnosis is certain have found that the features or signs and symptoms that best predict Parkinson's disease are resting tremor, asymmetric presentation (symptoms on 1 side of the body), and a powerful response to a medication called carbidopa-levodopa; older literature used only levodopa. These criteria may not always provide accurate diagnosis either because of other diseases that have symptoms similar to Parkinson's disease such as Huntington's disease, essential tremors, progressive palsy, and hydrocephalus.
- In order to increase the precision of an early diagnosis, a Parkinson's disease battery has been suggested. This includes a more complete assessment including motor function, olfaction, and mood. Occasionally, other tests (CT, MRI) may be done to help confirm that the symptoms are not due to other problems.
- In the late stages of disease, the symptoms are usually unmistakable and the diagnosis can be confirmed by a simple history and complete physical exam.
- Slowness and difficulty with movement should be quite apparent in the late stages.
- Most people will have tremor at this stage, although not all, thus creating a diagnostic challenge.
- Imaging tests (such as MRI and CT scan) may be performed to rule out other possible causes.
Possible Imaging Technique Diagnosis
- It is hoped that one day a specific imaging technique will be capable of detecting early and late Parkinson's disease and provide a means to follow disease progression and the effectiveness of treatment.
- Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are imaging techniques that are both sensitive and specific for the diagnosis and separation of Parkinson's disease from other syndromes that produce similar symptoms as Parkinson's disease.
- At present, these tests are not cost-effective.
- The ultimate utility of these techniques will be in screening populations felt to be a high risk; but these tests are done very infrequently.
- A phase of Parkinson's disease occurs before patients have symptoms (called a preclinical phase). That is, patients will not have symptoms until more than about 80% of dopaminergic cells are lost.
- At this point in time, with PET, screening can be done in this phase and demonstrate dopaminergic changes before patients have symptoms.
- It cannot, however, be used to predict which people with these changes will go on to develop Parkinson's disease.
Parkinson's Disease Treatment and Self Care at Home
Treatment for Parkinson's disease may include medications, surgery, gene therapy, other therapies, or a combination of these.
Parkinson's Disease Self-Care at Home
The decision to care for a family member with Parkinson's disease is very complex.
- In the beginning, the symptoms are minimal. The person may continue carrying out the activities of daily living, for example, eating, bathing, dressing, taking medications, and toileting. In fact, the person may continue to work and excel in other areas of life.
- A time will come when the symptoms of the disease progress to the point of decline. It is, however, impossible to predict which symptoms will become most pronounced and debilitating. This makes it especially difficult in planning and arranging future care. Nevertheless, with adequate planning, providing for the person at home is feasible.
- It must be determined what level of care is required and what financial and social resources will be available to accomplish home care. There will need to be a designated caregiver, preferably someone with few other family responsibilities.
- With time, the needs of the person with Parkinson's disease will only increase. The demands on the caregiver will mount. In terms of living independence, the ability to safely cook, drive an automobile, or use public transportation will be lost. A caregiver will assume full responsibility.
- The home should be large enough to accommodate the person's needs. Special medical equipment such as a walker, wheelchair, bedside commode, or chair lift may be required. In terms of added safety, dangerous and breakable objects will have to be removed.
- Medications should not be accessible to the patient if confusion becomes part of the symptoms.
- As with all things in life, a spectrum in the level of needs will vary from person to person. One person may need only moderate assistance. Someone else might require full-time care.
Parkinson's Disease Medical Treatment
The goal of medical management of Parkinson's disease is to control signs and symptoms as long as possible, while minimizing side effects. Medications usually provide good control for 4 to 6 years. After this time period, disability usually progresses despite medical management, and many people develop long-term motor complications including fluctuations and an inability to control their muscles called dyskinesia. Additional causes of disability in late disease include difficulty keeping one's balance and mental status changes. A doctor (often a neurologist) will choose the best treatment for the patient based on their specific symptoms.
Parkinson's Disease Medications
Some patients' treatment will include or begin with medications (called neuroprotective agents) to "protect" the neurons that make dopamine. Although "neuroprotective agents" protect cells in tissue cultures, it is not clear if they have the same effect on patients' neurons. These medications are monoamine oxidase B inhibitors (MAO-B).
- When patients are given selegiline (Emsam) or rasagiline (Azilect) alone in early Parkinson's disease, it is with the hope that the rate of degeneration of dopamine neurons and/or the breakdown of dopamine in the brain may be slowed.
- Symptomatic therapy is begun when patients have functional disability. The selection of medication depends in part on the nature and cause of the disability. Currently, with a strong presumptive diagnosis of Parkinson's disease, the most effective medication is carbidopa-levodopa; another option sometimes used is levodopa plus benserazide. If a patient's disability is due to bradykinesia, rigidity, decreased dexterity, slow speech, or shuffling gait, they have dopamine-responsive symptoms.
- Patients will be given a medication, such as carbidopa-levodopa (for example, Sinemet) that will increase the dopamine in the brain.
- These medications are started at a low dose, slowly escalated, and adjusted to control symptoms.
- Most people require this kind of treatment for bradykinesia and rigidity within 1 to 2 years after Parkinson's disease diagnosis; many will be started immediately on carbidopa-levodopa.
- An MAO-B inhibitor medication is sometimes added to carbidopa-levodopa treatments.
- If a patient's disability is due solely to tremor, a medication specific for tremors, such as amantadine (Symadine, Symmetrel), an anticholinergic agent, may be used.
- This type of medication provides good tremor relief in about 50% of people but does not improve bradykinesia or rigidity.
- Because tremor may respond to one anticholinergic medication and not another, the doctor may try a second anticholinergic if the first is not successful.
Occasionally, some doctors may prescribe amantadine for short-term treatment of early Parkinson's disease symptoms or use the medication in conjunction with carbidopa-levodopa treatment.
Patients usually will be given medications at the lowest effective dose. Over time, the various medication effects often diminish. To minimize medication side effects, (for example, side effects of memory difficulties, confusion, and hallucinations) the doctor may slowly increase dosages. Side effects involving problems with thinking are relatively common in older patients.
Parkinson's Disease Surgery, Gene Therapy, and Other Interventions
In addition to drug treatment, specific surgical options are available that may be used in patients that have severe symptoms of the disease or when medication is no longer able to give symptomatic relief. Early surgical treatments involved removal or destruction of the thalamus to reduce tremors but had little or no effect on symptoms of bradykinesia or rigidity. Pallidotomy and subthalamotomy, two surgical operations that remove parts of the brain (globus pallidus interna and subthalamus, respectively) have shown improvements in many of the symptoms of Parkinson's disease. However, these techniques often do not reduce all of the symptoms which may continue to progress and may have many different complications when the brain tissue is destroyed; in some patients, the outcomes versus the risks of these surgeries is still considered.
The current surgical procedure of choice is termed deep brain stimulation. Electrodes are placed in the brain and connected to a battery-stimulator that stimulates tissues with an electrical current. Patients selected for such surgery are those that still have a good response to levodopa medications but have complications of dyskinesia even with medication or in whom medication doses can no longer be adequately maintained over about 12 to 16 hours. Patients and surgeons choose this option because it does not destroy brain tissue, it's reversible, it can be adjusted as the disease progresses and it can work on both sides of the brain tissue. It is mainly done on the subthalamic nucleus and the globus pallidus interna. There are only a few centers that do this type of surgery, and outcomes are not always favorable. However, for some few patients, the success of this technique encourages surgeons to further study and refine this surgical treatment for Parkinson's disease patients.
Parkinson's Disease Gene Therapy
New studies involving modified liposomes or various types of modified viruses that contain genes may offer yet another method to reduce or even eliminate the symptoms of Parkinson's disease. Briefly, these therapies involve injection of liposomes or modified viruses that are capable of delivering genes to human brain cells. The brain cells allow and facilitate the injected genes to function. The injected genes then start to produce specific compounds such as precursor chemicals that become dopamine. Some studies are being done in animal models, but a few have progressed to early clinical trials. Preliminary results seem promising, but further human trials will be needed before gene therapy techniques are approved for therapy for Parkinson's disease patients.
Parkinson's Disease Other Therapies
Some studies claim that eating velvet or fava beans help with symptoms (they contain levodopa), but these studies were not deemed conclusive. Vitamin E and coenzyme Q have been claimed by some to be neuroprotective but are not a currently recommended treatment. A high fiber diet has been recommended to reduce the constipation that usually is seen in many Parkinson's disease patients. Exercise has been suggested to help Parkinson's disease patients; studies suggest that many Parkinson's disease patients benefit from exercises that stress flexibility, leg strength, and cardiovascular conditioning.
Parkinson's Disease Follow-up and Prognosis
To manage Parkinson's disease effectively, the doctor must carefully balance the symptoms of the disease with the side effects of medications.
- No single approach to treatment of Parkinson's disease exists. Rather, every person must work in tandem with doctors and therapists throughout the course of disease to design a program for their specific and changing needs.
- Always consult with the doctor before changing or stopping a medication.
- At any point during the course of Parkinson's disease, an open discussion regarding new or changing symptoms or side effects must take place between the patient and their doctor.
Parkinson's Disease Prognosis
Parkinson's disease may reduce the length and quality of life, but it is not fatal. It is a disease that may progress from a phase without symptoms to possibly a state of complete disability, This progression varies from person to person, but may occur within 10 to 20 years. However, as with all diseases, a spectrum of possibilities exists. The course a particular person will experience cannot be predicted although certain patterns have been noted by researchers.
- Parkinson's disease has been characterized by some as either tremor predominant or with postural instability and gait disturbed (PIGD).
- Younger people usually have tremor as the main symptom, but progression of the disease is slower. They also seem to have more muscle control problems.
- By contrast, older people experience more PIGD symptoms. This can be a serious problem in this age group because of an increased fall risk.
- In addition to the physical problems with Parkinson's disease, significant emotional and mental changes may occur.
- Many people have profound depression and others may experience thinking problems throughout the disease process.
- It is estimated that about 30% of people with Parkinson's disease experience altered mental status.
- Treatments are getting better at easing symptoms and may even slow progression of the disease. With continued research and clinical trials investigating new medications, surgical procedures, and gene therapy, it is thought that one day it may be possible to either prevent most symptoms or even possibly cure Parkinson's disease.
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Denyer, Rachel, and Michael R. Douglas. "Gene Therapy for Parkinson's Disease." Parkinson's Disease 2012.
Hauser, Robert A., et al. "Parkinson Disease." Medscape. 25 Mar. 2013.
Tagliati, Michele, et al. "Sterotactic Surgery in Parkinson Disease." 14 Feb. 2012.